Shahid Akbar

Handbook of
200 Medicinal
Plants
A Comprehensive Review
of Their Traditional Medical Uses
and Scientific Justifications
Handbook of 200 Medicinal Plants
Shahid Akbar

Handbook of 200
Medicinal Plants
A Comprehensive Review of Their
Traditional Medical Uses and Scientific
Justifications

123
Shahid Akbar
Stockton, CA, USA

ISBN 978-3-030-16806-3 ISBN 978-3-030-16807-0 (eBook)

https://doi.org/10.1007/978-3-030-16807-0
© Springer Nature Switzerland AG 2020
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part
of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission
or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are exempt from
the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this
book are believed to be true and accurate at the date of publication. Neither the publisher nor the
authors or the editors give a warranty, expressed or implied, with respect to the material contained
herein or for any errors or omissions that may have been made. The publisher remains neutral with regard
to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Dedicated to the Scientists Exploring
Medicinal Plants
Preface

Medicinal plants have served humanity since its beginning. An overwhelming

majority of the rural population of the world still relies on plant-based drugs for
their healthcare needs. Earlier generations studied these plants utilizing only their
keen sense of observation, and undying dedication to humanity, uncorrupted by
financial considerations. With the wealth of inherited knowledge about these plants
coupled with modern scientific tools, we have been able to harvest the benefits of
some of these plants. However, the scientific community has barely scratched the
surface of these natural wonders. Pharmacologists in the field of natural products
have relied for references of medical uses of plants in Indian systems of medicine
on books like Indigenous Drugs of India by Sir R. N. Chopra et al., Indian
Medicinal Plants by K. R. Kirtikar and B. D. Basu, and Indian Materia Medica by
K. M. Nadkarni. These books have served as excellent references for scientists from
around the world for decades. I have also utilized these references for this book.
Interest in natural products has exponentially increased in the past few decades
and pharmacological research in natural products is expanding worldwide. With
modern daily life heavily influenced with science and technology, the use of
medicinal plants has to keep pace, and evolve with it, especially in the mode of their
utilization. Furthermore, the spiraling cost of drugs and overall healthcare is
untenable, and our sincere efforts should be directed unbiased to unlock the hidden
secrets of these natural and inexpensive resources to discover new prototype
molecules to meet the growing healthcare challenges of our time. The worth
of these plants is only realized by those who have benefitted from them, and I
would like to quote here my Prof. (Late) Marvin H. Malone, who said at the VII
Symposium on Pharmacognosy, held in Brussels in October 1980, “No person
willingly will take an inactive drug when he or she is sick, and no human will
patronize an ineffective medicine man when he or she is ill.”
Conceived more than 35 years ago in the absence of personal computers
let alone Internet, obtaining credible and comprehensive information about the
included plants, possible only by hand searches and limited to available resources,
was a painfully slow and difficult task. However, with the advent of Internet and
paid publications of the twenty-first century exploded the information available on
these plants. At the time of conception of this book, international emphasis was
being placed to exploit local customs and resources of the countries around the

vii
viii Preface

world to meet “Health for All by the Year 2000”, the goal WHO had set in 1978.
Although the self-imposed deadline passed a long time ago without achieving that
noble target, there has been a resurgence of interest in medicinal plants in the
twenty-first century but for different reasons, one being the interest in everything
“natural”, and second the exploding cost of healthcare. Undeniably, unprecedented
progress has been made in medical care over the past half a century, but at an
unaffordable high cost. In 1980, after a sudden increase in healthcare cost from the
previous year, the U.S. per capita expenditure on healthcare ballooned to $1,067
that paled in comparison to a new milestone of $10,345 reached in 2016, and still
moving upward.
Selection of plants for this book was discretionary, but largely based on the
extent of their use in the traditional systems of medicine of Indian subcontinent.
Some of these plants have been extensively studied, while others are still waiting to
be explored. The customary practice of describing medicinal properties of plants in
abstract terms leaves much to be desired. For example, statement of being anti-
cancer, anti-inflammatory or cardiotonic, does not provide enough information with
all nuances of the nature of the past work done. In this exercise, I endeavored to
provide sufficient information (where available) for each plant covered in this book,
for the inquisitive mind to chart a rewarding future course of action, including the
controversies in identification, variations in active constituents, and other reasons
for variations in observed effects, etc. I hope that it serves the purpose for which it
was conceived and worked upon.

Stockton, California, USA Shahid Akbar

November 2018
Acknowledgments

Availability of Pharmacographia Indica by Dymock et al. (1890–1893), which was

republished by the Hamdard National Foundation of Pakistan in 1972, was an
invaluable gift to me by the (Late) Hakeem Mohammed Said (May his soul rest in
Peace) of Pakistan. It provided me the information about many controversies
regarding plants’ names and their identities that existed in the nineteenth century and
still plague this field. It also served as a good reference regarding the uses of plants in
ancient Egypt, Greece, and Rome, and the Muslim era of scientific progress.
Special thanks are due to various Chairmen and staff, Department of Ilmul
Advia, Faculty of Unani Medicine, A.M.U., Aligarh, India, for providing me
facilities over the years, to consult references of old Unani books.
The author would like to express his indebtedness and gratitude to all those
scientists, researchers and academics whose works (photographs) posted on
Wikimedia have been utilized for this book.
Last but not the least, my family suffered a lot for my obsession to complete this
book during the last few years, for which I owe them a great debt of gratitude.
I am also thankful to Springer Nature and its dedicated production team for
making the publication of this book possible.
The author regrets the inclusion of one nonherbal drug, i.e., Bombyx mori.

ix
Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Abelmoschus moschatus Medik (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . 15
Abrus precatorius L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . 21
Abutilon indicum (Link) Sweet (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . 33
Acacia catechu Oliver (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . 39
Acacia nilotica (L.) Delile. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . 45
Achillea millefolium L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . 57
Achyranthes aspera L. (Amaranthaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 69
Aconitum napellus L. (Ranunculaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Acorus calamus L. (Acoraceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Adiantum venustum G. Don./Adiantun capillus-veneris L.
(Pteridaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Aegle marmelos (L.) Corrêa (Rutaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 109
Agrimonia eupatoria L. (Rosaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Alhagi maurorum Medik. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . 129
Alkanna tinctoria (L.) Tausch (Boraginaceae) . . . . . . . . . . . . . . . . . . . . . 135
Allium cepa L. (Amaryllidaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Allium sativum L. (Amaryllidaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Aloe vera (L.) Burm.f. (Asphodelaceae/Xanthorrhoeaceae) . . . . . . . . . . . 187
Alpinia galanga (L.) Willd. (Zingiberaceae) . . . . . . . . . . . . . . . . . . . . . . 207
Alpinia officinarum Hance. (Zingiberaceae) . . . . . . . . . . . . . . . . . . . . . . 217
Alstonia scholaris (L.) R.Br. (Apocynaceae) . . . . . . . . . . . . . . . . . . . . . . 225

xi
xii Contents

Althaea officinalis L. (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

Ammi majus L. and A. visnaga (L.) Lam. (Apiaceae/Umbelliferae) . . . . . 243
Anacardium occidentale L. (Anacardiaceae) . . . . . . . . . . . . . . . . . . . . . . 251
Anacyclus pyrethrum (L.) Lag (Asteraceae/Compositae) . . . . . . . . . . . . . 261
Andrographis paniculata (Burm. f.) Nees. (Acanthaceae) . . . . . . . . . . . . 267
Anethum graveolens (L.) Benth. & Hook (Apiaceae/Umbelliferae) . . . . . 285
Apium graveolens L. (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . . . . . . . 295
Argemone mexicana L. (Papaveraceae) . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Aristolochia bracteolata Lam. (Aristolochiaceae) . . . . . . . . . . . . . . . . . . . 315
Aristolochia fontanesii Boiss. & Reut. (Aristolochiaceae) . . . . . . . . . . . . 321
Aristolochia indica L. (Aristolochiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 325
Aristolochia rotunda L. (Aristolochiaceae) . . . . . . . . . . . . . . . . . . . . . . . 331
Artemisia absinthium L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . 335
Artemisia vulgaris L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . . . 345
Asparagus adscendens (Roxb.) Kunth (Asparagaceae) . . . . . . . . . . . . . . 351
Asparagus officinalis L. (Asparagaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 355
Asparagus racemosus Willd. (Asparagaceae) . . . . . . . . . . . . . . . . . . . . . . 363
Atropa belladonna L. (Solanaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Azadirachta indica A. Juss. (Meliaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 381
Bacopa monnieri (L.) Wettst. (Plantaginaceae) . . . . . . . . . . . . . . . . . . . . 401
Bauhinia tomentosa L./Bauhinia variegata L.
(Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
Berberis aristata DC. (Berberidaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
Berberis vulgaris L. (Berberidaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429
Bombyx mori L. (Bombycidae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
Borago officinalis L. (Boraginaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Boswellia serrata Roxb. ex Colebr. (Burseraceae) . . . . . . . . . . . . . . . . . . 451
Brassica nigra (L.) K. Koch. (Brassicaceae) . . . . . . . . . . . . . . . . . . . . . . 465
Butea monosperma (Lam.) Taub. (Fabaceae/Leguminosae) . . . . . . . . . . . 471
Caccinia macranthera var. glauca (Savi) Govaerts (Boraginaceae) . . . . . 479
Contents xiii

Caesalpinia bonduc (L.) Roxb. (Fabaceae/Caesalpiniaceae) . . . . . . . . . . . 483

Cannabis sativa L. (Cannabaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
Capparis spinosa L. (Capparaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
Cardiospermum halicacabum L. (Sapindaceae) . . . . . . . . . . . . . . . . . . . . 507
Carthamus tinctorius L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . 515
Carum carvi L. (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . . . . . . . . . . . 529
Cassia fistula L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . . . . . 539
Catharanthus roseus (L.) G. Don (Apocynaceae) . . . . . . . . . . . . . . . . . . 551
Celastrus paniculatus Willd. (Celastraceae) . . . . . . . . . . . . . . . . . . . . . . . 561
Centaurea behen L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . . . . 569
Centella asiatica (L.) Urban (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . 573
Chamaecrista absus (L.) H.S. Irwin & Barneby
(Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
Chamaemelum nobile (L.) All. (Asteraceae/Compositae) . . . . . . . . . . . . . 593
Cheilocostus speciosus (J. König) C.D. Specht (Costaceae) . . . . . . . . . . . 601
Cichorium intybus L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . . . 609
Cinnamomum camphora (L.) J. Presl. (Lauraceae) . . . . . . . . . . . . . . . . . 623
Cinnamomum cassia (L.) J. Presl (Lauraceae) . . . . . . . . . . . . . . . . . . . . 629
Cinnamomum verum J. Presl. (Lauraceae) . . . . . . . . . . . . . . . . . . . . . . . 645
Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) . . . . . . . . . . . . . . . . . 663
Clitoria ternatea L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . . 673
Colchicum autumnale L. (Colchicaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 681
Colchicum luteum Baker (Colchicaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 691
Commiphora gileadensis (L.) C.Chr (Burseraceae) . . . . . . . . . . . . . . . . . 695
Commiphora myrrha (Nees) Engl. (Burseraceae) . . . . . . . . . . . . . . . . . . . 701
Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks)
Engl. (Burseraceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 707
Convolvulus scammonia B.P. (Convolvulaceae) . . . . . . . . . . . . . . . . . . . . 717
Cotoneaster nummularius Fisch. & C.A.Mey. (Rosaceae) . . . . . . . . . . . . 721
Crocus sativus L. (Iridaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 725
xiv Contents

Croton tiglium L. (Euphorbiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 741

Cullen corylifolium (L.) Medicus (Fabaceae/Leguminosae) . . . . . . . . . . . 749
Cuminum cyminum L. (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . . . . . 761
Curcuma aromatica Salisb. (Zingiberaceae) . . . . . . . . . . . . . . . . . . . . . . 773
Curcuma longa L. (Zingiberaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781
Curcuma zedoaria (Christm.) Roscoe. (Zingiberaceae) . . . . . . . . . . . . . . 809
Cuscuta chinensis Lam. (or C. epithymum L.) (Convovulaceae) . . . . . . . 817
Cuscuta reflexa Roxb. (Convolvulaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 825
Cydonia oblonga Mill. (Rosaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831
Cymbopogon schoenanthus (L.) Spreng. (Poaceae/Graminae) . . . . . . . . . 839
Cyperus rotundus L. (Cyperaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 843
Datura stramonium L. (Solanaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 857
Delphinium denudatum Wall. ex Hook.f. & Thomson
(Ranunculaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 869
Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch.
(Parmeliaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 873
Doronicum pardalianches Roxb. (Asteraceae/Compositae) . . . . . . . . . . . 879
Embelia ribes Burm.f. (Primulaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
Euphorbia hirta L.; Chamaesyce hirta (L.) Mills. (Euphorbiaceae) . . . . . 889
Euphorbia resinifera O. Berg. (Euphorbiaceae) . . . . . . . . . . . . . . . . . . . 899
Ferula assa-foetida L. (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . . . . . . 905
Ficus carica L. (Moraceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
Ficus racemosa L. (Moraceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923
Foeniculum vulgare Mill. (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . . . 931
Fumaria officinalis L. (F. parviflora Lam.) (Papaveraceae) . . . . . . . . . . . 947
Gentiana lutea L. (Gentianaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 955
Glycyrrhiza glabra L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . 963
Gymnema sylvestre R. Br. (Apocynaceae) . . . . . . . . . . . . . . . . . . . . . . . . 981
Helleborus niger L. (Ranunculaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 991
Contents xv

Hemidesmus indicus (L.) R. Br. (Apocynaceae) . . . . . . . . . . . . . . . . . . . 997

Hibiscus rosa-sinensis L. (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1007
Holarrhena pubescens Wall. ex G. Don. (Apocynaceae) . . . . . . . . . . . . . 1015
Hyoscyamus niger L. (Solanaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1023
Hyssopus officinalis L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1029
Illicium verum Hook.f. (Schisandraceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1035
Iris germanica L. (Iridaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043
Juniperus communis L. (Cupressaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1049
Justicia adhatoda L. (Acanthaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1059
Lactuca sativa L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . . . . . . 1067
Lavandula stoechas L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1077
Lawsonia inermis L. (Lythraceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1085
Lepidium sativum L. (Brassicaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1095
Linum usitatissimum L. (Linaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1101
Lupinus albus L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . . . . 1123
Malva sylvestris L. (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1129
Marrubium vulgare L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1137
Matricaria chamomilla L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . 1147
Melia azedarach L. (Meliaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1161
Melilotus officinalis (L.) Pall. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . 1171
Melissa officinalis L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177
Mesua ferrea L. (Clusiaceae/Calophyllaceae) . . . . . . . . . . . . . . . . . . . . . 1189
Momordica charantia L. (Cucurbitaceae) . . . . . . . . . . . . . . . . . . . . . . . . 1195
Moringa oleifera Lam. (Moringaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1221
Myristica fragrans Houtt. (Myristicaceae) . . . . . . . . . . . . . . . . . . . . . . . . 1239
Myrtus communis L. (Myrtaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1251
Nageia nagi (Thunb.) Kuntze (Podocarpaceae) . . . . . . . . . . . . . . . . . . . . 1263
Nardostachys jatamansi (D. Don) DC (Caprifoliaceae) . . . . . . . . . . . . . . 1269
Nepeta cataria L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1279
xvi Contents

Nigella sativa L. (Ranunculaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1287

Ocimum basilicum L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1313
Ocimum gratissimum L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1327
Ocimum tenuiflorum L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1339
Operculina turpethum (L.) Silva Manso (Convolvulaceae) . . . . . . . . . . . . 1359
Paeonia officinalis L.; Paeonia emodi Royle (Paeoniaceae) . . . . . . . . . . . 1365
Pandanus odorifer (Forssk.) Kuntze (Pandanaceae) . . . . . . . . . . . . . . . . 1371
Papaver somniferum L. (Papaveraceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1377
Persicaria bistorta L. (Polygonaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1385
Phyllanthus emblica L. (Phyllanthaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1391
Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) . . . . . . . . . . . . . . . . 1409
Pimpinella anisum L. (Apiaceae/Umbelliferae) . . . . . . . . . . . . . . . . . . . . 1419
Piper cubeba L.f. (Piperaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1431
Piper nigrum L. (Piperaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1437
Pistacia lentiscus L. (Anacardiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1443
Plantago major L. (Plantaginaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1455
Plantago ovata Forssk. (Plantaginaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1465
Plumbago zeylanica L. (Plumbaginaceae) . . . . . . . . . . . . . . . . . . . . . . . . 1475
Polygonum aviculare L. (Polygonaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1485
Portulaca oleracea L. (Portulacaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . 1491
Quercus infectoria G. Olivier (Fagaceae) . . . . . . . . . . . . . . . . . . . . . . . . 1505
Rauvolfia serpentina (L.) Benth. ex Kurz (Apocynaceae) . . . . . . . . . . . . 1513
Rheum emodi Wall. ex Meisn (Polygonaceae) . . . . . . . . . . . . . . . . . . . . . 1521
Rheum officinale Baill.; R. palmatum L. (Polygonaceae) . . . . . . . . . . . . . 1527
Ricinus communis L. (Euphorbiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . 1539
Rubia cordifolia L. (Rubiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1551
Rumex vesicarius L. (Polygonaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1561
Ruta graveolens L. (Rutaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1567
Salix caprea L. (Salicaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1577
Contents xvii

Salvia officinalis L./Salvia haematodes Wall. (Lamiaceae/Labiatae) . . . . . 1581

Santalum album L. (Santalaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1601
Saussurea lappa (Falc.) Lipsch. (Asteraceae/Compositae) . . . . . . . . . . . . 1609
Semecarpus anacardium L. (Anacardiaceae) . . . . . . . . . . . . . . . . . . . . . . 1619
Senna alexandrina Mill. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . 1629
Senna occidentalis (L.) Link (Fabaceae/Leguminosae) . . . . . . . . . . . . . . 1639
Senna tora (L.) Roxb. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . 1649
Sida cordifolia L. (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1657
Smilax china L. (Smilacaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1665
Solanum americanum Mill. (Solanaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1673
Sterculia urens Roxb. (Malvaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1685
Strychnos nux-vomica L. (Loganiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1689
Swertia chirata Buck.-Ham. ex Wall. Swertia chirayita (Roxb.)
H. Karsten (Gentianaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1699
Symplocos racemosa Roxb. (Symplocaceae) . . . . . . . . . . . . . . . . . . . . . . 1709
Syzygium cumini (L.) Skeels (Myrtaceae) . . . . . . . . . . . . . . . . . . . . . . . . 1715
Tamarindus indica L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . . . . . . . . 1729
Taraxacum officinale (L.) Weber ex F.H. Wigg
(Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1743
Taxus baccata L. (Taxaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1753
Tephrosia purpurea (L.) Pers. (Fabaceae/Leguminosae) . . . . . . . . . . . . . 1763
Terminalia bellirica (Gaertn.) Roxb. (Combretaceae) . . . . . . . . . . . . . . . 1771
Terminalia chebula Retz. (Combretaceae) . . . . . . . . . . . . . . . . . . . . . . . . 1779
Thymus vulgaris L. (Lamiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1795
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms
(Menispermaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1811
Trachyspermum ammi (L.) Sprague (Apiaceae/Umbelliferae) . . . . . . . . . 1825
Tribulus terrestris L. (Zygophyllaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . 1835
Trigonella foenum-graecum L. (Fabaceae/Leguminosae) . . . . . . . . . . . . . 1851
Tussilago farfara L. (Asteraceae/Compositae) . . . . . . . . . . . . . . . . . . . . . 1873
Valeriana jatamansi Jones. (Valerianaceae) . . . . . . . . . . . . . . . . . . . . . . 1879
xviii Contents

Verbena officinalis L. (Verbenaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1887

Vernonia anthelmintica Willd. (Asteraceae/Compositae) . . . . . . . . . . . . . 1895
Vigna unguiculata (L.) Walp (Fabaceae/Leguminosae) . . . . . . . . . . . . . . 1901
Viola odorata L. (Violaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1907
Viscum album L. (Santalaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1915
Withania somnifera (L.) Dunal (Solanaceae) . . . . . . . . . . . . . . . . . . . . . . 1933
Wrightia tinctoria R. Br. (Apocynaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1951
Zingiber officinale Rosc. (Zingiberaceae) . . . . . . . . . . . . . . . . . . . . . . . . . 1957
Zingiber zerumbet (L.) Sm. (Zingiberaceae) . . . . . . . . . . . . . . . . . . . . . . 1999
Ziziphus jujuba Mill. (Rhamnaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2007

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2017
Ayurvedic Terms of Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2029
Referenced Books . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2033
Quoted Historical Scientists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2041
Index of Scientific Names . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2047
Index of Vernacular Names . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2055
Abbreviations

20-MCA 20-Methylcholanthrene
3'MeDAB 3'-Methyl-4-dimethylaminoazobenzene
5-FU 5-Fluorouracil
5-HIAA 5-Hydroxyindoleacetic acid
5-HT 5-Hydroxytryptamine (Serotonin)
5-LOX 5-Lipoxygenase
6-OHDA 6-Hydroxydopamine
A. actinomycetemcomitans Actinobacillus actinomycetemcomitans (older name)
A. actinomycetemcomitans Aggregatibacter actinomycetemcomitans
(newer name)
A. aegypti Aedes aegypti
A. baumannii Acinetobacter baumannii
A. caviae Aeromonas caviae
A. flavus Aspergillus flavus
A. fumigatus Aspergillus fumigatus
A. galli Ascaridia galli
A. hydrophila Aeromonas hydrophila
A. lumbricoides Ascaris lumbricoides
A. lwoffii Acinetobacter lwoffii
A. niger Aspergillus niger
A. ochraceus Aspergillus ochraceus
A. parasiticus Aspergillus parasiticus
A. radiobacter Agrobacterium radiobacter
A. stephensi Anopheles stephensi
A. terreus Aspergillus terreus
A. viscosus Actinomyces viscosus
AA Arachidonic Acid
AAF 2-Acetylaminofluorine
AC Adenylate Cyclase
ACE Angiotensin Converting Enzyme
AChE Acetylcholinesterase
ADH Antidiuretic Hormone
ADHD Attention-Deficit Hyperactivity Disorder

xix
xx Abbreviations

ADV Adenovirus
Al Aluminum
ALP Alkaline Phosphatase
ALT (SGPT) Alanine Aminotransferase (glutamate-pyruvate
transaminase)
AML Acute Myeloid Leukemia
AMPK AMP-activated Protein Kinase
An. culicifacies Anopheles culicifacies
An. stephensi Anopheles stephensi
ANF Atrial Natriuretic Factor
AOM Azoxymethane
APAP Acetaminophen (Paracetamol)
Apo Apolipoprotein
ASA Acetylsalicylic Acid
AST (SGOT) Aspartate Aminotransferase (glutamic oxaloacetic
transaminase)
AUC Area Under the Curve
B(a)P Benzo(a)pyrene
B. atrophaeus Bacillus atrophaeus
B. bronchiseptica Bacillus bronchiseptica
B. cereus Bacillus cereus
B. fragilis Bacteroides fragilis
B. hominis Blastocystis hominis
B. malayi Buria malayi
B. megaterium Bacillus megaterium
B. pahangi Brugia pahangi
B. pantotrophus Bacillus pantotrophus
B. pumilus Bacillus pumilus
B. subtilis Bacillus subtilis
B. thuringensis Bacillus thuringensis
BCA Bilateral Carotid Artery
BChE Butyrylcholinesterase
BDZ Benzodiazepine
BMD Bone Mineral Density
BMI Body Mass Index
BUN Blood Urea Nitrogen
C. albicans Candida albicans
C. butyricum Clostridium butyricum
C. diphtheriae Cornybacterium diphtheriae
C. dubliniensis Candida dubliniensis
C. freundii Citrobacter freundii
C. glabrata Candida glabrata
C. guilliermondii Candida guilliermondii
C. jejuni Campylobacter jejuni
C. koseri Citrobacter koseri
Abbreviations xxi

C. krusei Candida krusei

C. lunata Curvulari lunata
C. miyabeanus Cochliobolus miyabeanus (formerly Helminthospo-
rium oryzale)
C. neoformans Cryptococcus neoformans
C. parapsilosis Candida parapsilosis
C. perfringens Clostridium perfringens
C. quinquefasciatus Culex quinquefasciatus
C. ramosum Clostridium ramosum
C. stellatoida Candida stellatoida
C. tropicalis Candida tropicalis
C. xerosis Corynebacterium xerosis
Ca Calcium
CABG Coronary Artery Bypass Grafting
CAD Coronary Artery Disease
CAR Conditioned Avoidance Response
CAT Catalase
CCB Calcium Channel Blocker
CCl4 Carbon tetrachloride
Cd Cadmium
CHD Coronary Heart Disease
CK Creatine Kinase
CKD Chronic Kidney Disease
Cl Chloride
Cmax Peak Plasma Concentration
CMC Carboxymethyl Cellulose
CMV Cytomegalovirus
Co Cobalt
ConA Concanavalin A
COPD Chronic Obstructive Pulmonary Disease
COX-1 Cyclooxygenase-1
COX-2 Cyclooxygenase-2
CP Cyclophosphamide
Cr Chromium
CREB Cyclic-AMP Response Element Binding Protein
CRP C-Reactive Protein
D. pneumoniae Diplococcus pneumoniae
DA Dopamine
DEN Diethylnitrosamine
DES Diethylstilbesterol
DHEA Dehydroepiandrosterone
DHT Dihydrotestoterone
DM Diabetes Mellitus
DMBA 7,12-Dimethylbenz[a]anthracene
DMH 1,2-Dimethylhydrazine
xxii Abbreviations

DOPAC 3,4-Dihydroxyphenylacetic Acid

DSS Dextran Sulfate Sodium
E. aerogenes Enterobacter aerogenes
E. carotovora Erwinia carotovora
E. cloacae Enterobacter cloacae
E. coli Escherichia coli
E. faecalis Enterococcus faecalis
E. feacium Enterococcus feacium
E. floccosum Epidermophyton floccosum
E. histolytica Entoemeba histolytica
EAC Ehrlich Ascites Carcinoma
EE Ethinylestradiol
EG Ethylene glycol
EGFR Epidermal Growth Factor Receptor
EMF Electromagnetic Field
EO Essential Oil
Epi Epinephrine
EPS Extra Pyramidal Symptoms
ER Emergency Room
ESbetaL Extended Spectrum beta-Lactamases
ESRD End-Stage Renal Disease
ESWL Extracorporeal Shock Wave Lithotripsy
ET-1 Endotheline-1
F. moniliforme Fusarium moniliforme
F. nucleatum Fusobacterium nucleatum
F. oxysporum Fusarium oxysporum
F. solani Fusarium solani
FBG Fasting Blood Glucose
FDA Food and Drug Administration
FFA Free Fatty Acids
FSH Follicle Stimulating Hormone
G. candidum Geotrichum candidum
G. duodenalis Giardia duodenalis
G. intestinalis Giardia intestinalis
G. lamblia Giardia lamblia
G-6-Pase Glucose-6-Phosphatase
G-6-PD Glucose-6-Phosphate Dehydrogenase
GABA c-AminoButyric Acid
GAD Generalized Anxiety Disorder
GC-MS Gas Chromatography-Mass Spectrometry
GERD Gastroesophageal Reflux Disease
GIT Gastrointestinal
GlAD Glutamic Acid Decarboxylase
GLP-1 Glucagon-like Peptide 1
GLUT-4 Glucose Transporter 4
Abbreviations xxiii

GM-CSF Granulocyte-Macrophage-Colony Stimulating Factor

GPx Glutathione Peroxidase
GR Glutathione Reductase
GSH Reduced Glutathione
GST Glutathione-S-Transferase
GTT Glucose Tolerance Test
H. capsulatum Histoplasma capsulatum
H. contortus Haemonchus contortus
H. diminuta Hymenolepis diminuta
H. ducreyi Haemophilus ducreyi
H. influenzae Haemophilus influenzae,
H. nana Hymenolepis nana
H. oryzale Helminthosporium oryzale (a plant pathogen)
H. pylori Helicobacter pylori
H+ K+-ATPase Proton Pump
H2O2 Hydrogen Peroxide
Hb Hemoglobin
HBV Hepatitis B Virus
HCMV Human Cytomegalovirus
HCV Hepatitis C Virus
HDL-C HDL-cholesterol
HepG2 Human Hepatocellular Carcinoma Cells
HFD High Fat Diet
HIV-1 Human Immunodeficiency Virus-1
HMA Homeostasis Model Assessment
HMG Co-A Reductase 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase
HMPC Committee on Herbal Medicinal Products
HPIV-2 Human Parainfluenza Virus Type 2
HPV Human Papilloma Virus
HRMS High Resolution Mass Spectrometry
hs-CRP high-sensitivity C-Reactive Protein
hsp Heat Shock Protein
HSV-1 Herpes Simplex Virus-1
HSV-2 Herpes Simplex Virus-2
HUVEC Human Umbilical Vein Endothelial Cells
HVA Homovanillic Acid
Hyp Hydroxyproline
I.P. Intraperitoneal
I.V. Intravenous
I/R Ischemia/Reperfusion
IBD Inflammatory Bowel Disease
IBS Irritable Bowel Syndrome
ICV Intracerebroventricular
IDDM Insulin-Dependent Diabetes Mellitus
IFN Interferon
xxiv Abbreviations

IHD Ischemic Heart Disease

IL Interleukin
INH Isonicotinic acid Hydrazide
iNOS Inducible Nitric Oxide Synthase
INR International Normalized Ratio
IOP Intraocular Pressure
ISI Insulin Sensitivity Index
K Potassium
K. aerogenes Klebsiella aerogenes
K. oxytoca Klebsiella oxytoca
K. ozaenae Klebsiella ozaenae
K. pasteurella Klebsiella pasteurella
K. pneumoniae Klebsiella pneumoniae
L. acidophilus Lactobacillus acidophilus
L. arabinosus Lactobacillus arabinosus
L. casei Lactobacillus casei
L. chagasi Leishmania chagasi
L. donovani Leishmania donovani
L. monocytogenes Listeria monocytogenes
L. tropica Leishmania tropica
LDH Lactate Dehydrogenase
LDL-C LDL-cholesterol
LFT Liver Function Test
LH Leutinizing Hormone
LHRH Leutenizing Hormone Releasing Hormone
L-NAME N(G)-Nitro-L-Arginine Methyl Ester
LOX Lipoxygenase
LPO Lipid Peroxidation
LPS Lipopolysaccharide
LPx Lipid Peroxide
LSD Lysergic acid Diethylamide
LTs Leukotrienes
M. canis Microsporum canis
M. catarrhalis Moraxella catarrhalis
M. chelonei Mycobacterium chelonei
M. domestica Musca domestica
M. flavus Micrococcus flavus
M. furfur Malassezia furfur
M. grisea Magnaporthe grisea
M. gypseum Microsporum gypseum
M. hominis Mycoplasma hominis
M. indicus Mucor indicus
M. intracellulare Mycobacterium intracellulare
M. luteus Micrococcus luteus
M. morganii Morganella morganii
Abbreviations xxv

M. phlei Mycobacterium phlei

M. smegmatis Mycobacterium smegmatis
M. tuberculosis Mycobacterium tuberculosis
M. xenopei Mycobacterium xenopei
MABP Mean Arterial Blood Pressure
MAO Monoamine Oxidase
MAPK Mitogen Activated Protein Kinase
MBC Minimum Bactericidal Concentration
MCA Middle Cerebral Artery
MCP-1 Monocyte Chemoattractant Protein-1
MCV Mean Corpuscular Volume
MDA Malondialdehyde
MDR Multidrug Resistant
MES Maximal Electro Shock
MetS Metabolic Syndrome
Mg Magnesium
MI Myocardial Infarction
MIC Minimum Inhibitory Concentration
Mn Manganese
MNNG N-methyl-N'-nitro-N-nitrosoguanidine
MPTP 1-Methyl-4-Phenyl-1,2,3,6-TetrahydroPyridine
MRSA Methicillin-Resistant Staphylococcus aureus
MS Multiple Sclerosis
MSG MonoSodium Glutamate
MSSA Methicillin-Sensitive Staphylococcus. aureus
MTX Methotrexate
N/V Nausea/Vomiting
NA Noradrenaline
NDEA N-Nitrosodiethylamine
NDMA N-Nitrosodimethylamine
NE Norepinephrine
NF-jB Nuclear Factor kappa B
NIDDM Noninsulin Dependent Diabetes Mellitus
NMDA N-methyl-D-aspartate
NO Nitric Oxide
NSAIDs Nonsteroidal Anti-Inflammatory Drugs
NVP Pregnancy associated Nausea and Vomiting
O. volvulus Onchocerca volvulus
ODC Ornithine decarboxylase
OGTT Oral Glucose Tolerance Tests
OVA Ovalbumin
P Phosphorus
P. acnes Propionibacterium acnes
P. aeruginosa Pseudomonas aeruginosa
P. berghei Plasmodium berghei
xxvi Abbreviations

P. citrinum Penicillium citrinum

P. cochleariae Phaedon cochleariae
P. expansum Penicillium expansum
P. falciparum Plasmodium falciparum
P. fluorescens Pseudomonas fluorescens
P. funiculosum Penicillium funiculosum
P. gingivalis Porphyromonas gingivalis
P. intermedia Prevotella intermedia
P. islandicum Penicillium islandicum
P. italicum Penicillium italicum
P. melaninogenica Prevotella melaninogenica
P. mirabilis Proteus mirabilis
P. morganii Proteus morganii
P. notatum Penicillum notatum
P. posthuma Pheretima posthuma
P. pseudomallei Pseudomonas pseudomallei
P. purpurogenum Penicillium purpurogenum (a plant pathogen)
P. putida Pseudomonas putida
P. shigelloides Plesiomonas shigelloides
P. testosteroni Pseudomonas testosteroni
P. verrucosum Penicillium verrucosum
P. vulgaris Proteus vulgaris
P. yoelli nigeriensis Plasmodium yoelli nigeriensis
PAD Peripheral Artery Disease
PAF Platelet Activating Factor
PCOS Polycystic Ovary Syndrome
PCV Packed Cell Volume
PDA Photodiode Array
PDE Phosphodiesterase
PEG PolyEthylene Glycol
PEPCK Phosphoenolpyruvate Carboxykinase
PFK Phosphofructokinase
PG Prostaglandin
PGI2 Prostacyclin
P-gp P-glycoprotein
PI3 Kinase Phosphatidylinositol 3' Kinase
PK Protein Kinase
PLA2 Phospholipase A2
PMA Phorbol 12-Myristate 13-Acetate
PMNL Polymorphonuclear Leucocytes
PMS Premenstrual Syndrome
PPAR Peroxisome Proliferator-Activated Receptors
PPARc Peroxisome Proliferator Activator Receptor-c
PRA Plasma Renin Activity
PT Prothrombin Time
Abbreviations xxvii

PTSD Post-Traumatic Stress Disorder

PTZ Pentylenetetrazol
R. stolonifer Rhizopus stolonifer
RA Rheumatoid Arthritis
RBCs Red Blood Cells
RCT Randomized, Placebo Controlled Trial
RDA Recommended Dietary Allowance
RE System Reticulo-endothelial System
ROS Reactive Oxygen Species
RRT Retroviral Reverse Transcriptase
RSV Respiratory Syncytial Virus
RVLP Real Visible Light Phototherapy
S. agalactiae Streptococcus agalactiae
S. albus Staphylococcus albus
S. anginosus Streptococcus anginosus
S. aureus Staphylococcus aureus
S. bovis Streptococcus bovis
S. brevicaulis Scopulariopsis brevicaulis
S. cerevisiae Saccharomyces cerevisiae
S. cervi Setaria cervi
S. enteric Salmonella enteric
S. enteritidis Salmonella enteritidis
S. epidermidis Staphylococcus epidermidis
S. epidermis Streptococcus epidermis
S. faecalis Streptococcus faecalis
S. haematobium Schistosoma haematobium
S. haemolyticus Streptococcus haemolyticus
S. mansoni Schistosoma mansoni
S. marcescens Serratia marcescens
S. mutans Streptococcus mutans
S. paratyphi Salmonella paratyphi
S. pneumoniae Streptococcus pneumoniae
S. pyogenes Streptococcus pyogenes
S. salivarius Streptococcus salivarius
S. sanguis Streptococcus sanguis
S. schenckii Sporothrix schenckii
S. sobrinus Streptococcus sobrinus
S. stercoralis Strongyloides stercoralis
S. thermophilus Streptococcus thermophilus
S. typhi Salmonella typhi
S. typhimurium Salmonella typhimurium
S. velterans Salmonella velterans
Sh. boydii Shigella boydii
Sh. dysenteriae Shigella dysenteriae
Sh. flexneri Shigella flexneri
xxviii Abbreviations

Sh. paradysenterica Shigella paradysenterica

Sh. sonnei Shigella sonnei
SCCD Supercritical Carbon Dioxide
SHR Spontaneously Hypertensive Rats
SOD Superoxide Dismutase
T. asahii Trichosporon asahii
T. brucei rhodesiense Trypanosoma brucei rhodesiense
T. cruzi Trypanosoma cruzi
T. cutaneum Trichosporon cutaneum
T. erinacei Trichophyton erinacei
T. gondii Toxoplasma gondii
T. longifusus Trichophyton longifusus
T. mentagrophytes Trichophyton mentagrophytes
T. ovoides Trichosporon ovoides
T. rubrum Trichophyton rubrum
T. simii Trichophyton simii
T. soudanense Trichophyton soudanense
T. tonsurans Trichophyton tonsurans
T. tubifex Tubifex tubifex
T. vaginalis Trichomonas vaginalis
T. verrucosum Trichophyton verrucosum
T. violaceum Trichophyton violaceum
T1DM Type 1 Diabetes Mellitus
T2DM Type 2 Diabetes Mellitus
T3 Triiodothyronine
T4 Thyroxin
TAS Total Antioxidant Status
TBARS Thiobarbituric Acid Reactive Substances
t-BHP tert-Butyl Hydroperoxide
TC Total Cholesterol
TCM Traditional Chinese Medicine
TGF-b Transforming Growth Factor-b
TGs Triglycerides
TLC Thin Layer Chromatography
TNBSA Trinitrobenzene Sulfonic Acid
TNFa Tumor Necrosis Factor a
TPA 12, O-Tetradecanoylphorbol-13-Acetate
t-PA Tissue Plasminogen Activator
TX Thromboxane
Tx Treatment
URTI Upper Respiratory Tract Infection
UTI Urinary Tract Infection
V. cholerae Vibrio cholerae
V. mimicus Vibrio mimicus
V. parahaemolyticus Vibrio parahaemolyticus
Abbreviations xxix

VEGF Vascular Endothelial Growth Factor

VLDL Very Low-Density Lipoprotein
VZV Varicella-Zoster Virus
WBCs White Blood Cells
XDH Xanthine Dehydrogenase
XO Xanthine Oxidase
Y. enterocolitica Yersinia enterocolitica
Zn Zinc

Vernaculars Abbreviations

Indian Languages
Ben. Bengali
Guj. Gujarati
Hin. Hindi
Mal. Malayalam
Mar. Marathi
Ori. Orissa
San. Sanskrit
Tam. Tamil
Tel. Telugu
Urd. Urdu

Foreign Languages
Alb. Albanian
Alg. Algerian
Ara. Arabic
Ber. Berber
Bul. Bulgarian
Bur. Burmese
Chi. Chinese
Cro. Croatian
Cze. Czech
Dan. Danish
Dut. Dutch
E&W Ind. East and West Indies
Eng. English
Fin. Finnish
Fre. French
xxx Abbreviations

Gab. Gabon
Ger. German
Gre. Greek
Haw. Hawaiian
Hun. Hungarian
Ind. Indonesian
Ita. Italian
Jap. Japanese
Jav. Javanese
Kor. Korean
Lao. Laotian
Lat. Latin
Maly. Malay
Mex. Mexican
Mor. Moroccan
Nep. Nepalese
Nig. Nigerian
Nor. Norwegian
Per. Persian
Pol. Polish
Por. Portuguese
Rom. Roman
Rus. Russian
Sen. Senegal
Sin. Sinhalese (Sri Lanka)
Spa. Spanish
Sud. Sudanese
Swa. Swahili
Swe. Swedish
Syr. Syrian
Tag. Tagalog (The Philippines)
Tha. Thai
Tur. Turkish
Vie. Vietnamese
Zul. Zulu
Introduction

It is readily understood and realized by all and sundry that plants are an integral part
of our lives and have been so since the time immemorial, due to their omnipresence.
Plants have been the mainstay and essential for not only the survival of humankind,
but all life on this planet. Their role cannot be underestimated as they have served
mankind since its birth, providing food, shelter, healthy, beautiful and pleasing
environment, and adding colors and rhythms to the canvas of our lives. Without
plants, this planet would simply be a desolate, barren and uninhabitable piece of
rock. Plants have also been the main source of succor for human illnesses afflicting
man in one or the other form since the beginning of his existence. The number of
plant species that exists on earth can only be guesstimated; an estimate puts the
number at 400,000 plant species, though the worldwide plant list holds over one
million names under 642 plant families, of which many are considered synonyms.
Initially, man chose these plants only for one reason, that is to meet his needs,
including food, shelter and relief from physical sufferings, because of their proxi-
mity and easy accessibility. As the man evolved over the millennia, it accumulated
considerable body of experience about plants and other aspects of life including health
and diseases through repeated observations, and trial and error. However, as he
became relatively sophisticated, he also began to question his own observations and
started to explore the reasoning behind those observations, including diseases and
their treatments; simply relying on an observation as it was, no longer satisfactory.
The process of curiosity continued, observations were made, and crude hypotheses
were formulated, trials conducted, errors committed, and thus the learning process
continued for several millennia. These observations and experiences were handed
down from generations to generations. With every new generation progress was made
in understanding physiological processes about health and diseases, though not in
absolute modern terms, and effects of plants were reconciled with these processes.
Like the modern allopathic medicine which is described as evidence-based medicine,
treatment with plants was also based on evidence, though the evidence or criteria on
which justifications were arrived at were apparently different. In the absence of

© Springer Nature Switzerland AG 2020 1

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_1
2 Introduction

‘sophisticated scientific instruments’ critical observations were the only means to find
answers. Those observations might not be considered ‘scientific’ in modern lexicon,
but they utilized the human senses to the fullest, and served as the basis for the
emergence of the organized traditional folk medicines that were also intertwined with
faith, and in many cases, still are part of the cultural fabrics of many societies. It was
thought and still believed by many that there is an herb for every disease with which a
human body can be afflicted.
A place in southwest Asia called Mesopotamia (land of rivers), situated between
the two giant rivers, the Tigris and the Euphrates (modern day Iraq), is regarded as
the Cradle of Civilization. The Mesopotamians are credited for the introduction
of a writing system about 3000 B.C. on clay tablets. Babylon was the 2nd most
important civilization after Mesopotamia, which had laws for all walks of life,
including the practice of medicine. The earliest known regulations for the practice
of medicine came from the ruler of Babylon, the Hammurabi, and are known as the
Code of Hammurabi (c. 1728–1686 B.C.). The Babylonians attained great skills in
surgery and treatment of diseases, as part of their glorious intellectual advance-
ments. The Chinese medical text, Pen Tsao written about 3000 B.C., contains about
a thousand remedies utilizing plant sources. The medical Ebers Papyrus discovered
by George Moritz Ebers in Thebes dates from 1550 B.C. and contains records of
about 700 remedies of ancient Egyptian medicine. In India, the art of healing was
incorporated in the Atharvaveda (c. 1200–1000 B.C.) and Rigveda (c. 1500–1200
B.C.), which was further elaborated by the works of Charaka and Sushsruta in the
2nd century B.C. Almost 25 centuries ago, Hippocrates (460–377 B.C.), the rec-
ognized ‘Father of Medicine,’ proclaimed “Let food be thy medicine and medicine
be thy food.” He also recommended that the treatment and dosage should be
decided in accordance with the individual patients’ requirements and idiosyn-
crasies. We have now realized that the physiological effects of an agent depend on
the dose and duration of exposure of the body to it. So, we have come around a full
circle; one size does not fit all anymore.
Theophrastus, who is recognized as the ‘Father of Botany’ as well as of phar-
macognosy, and a companion of Aristotle, started documenting accurate descrip-
tions of medicinal plants in the 3rd century B.C. His books, Enquiry into Plants and
On the Causes of Plants provided invaluable information about medical uses of
plants, which were later supplemented by books like De Materia Medica, written by
Dioscorides (c. 40–90 A.D.), who as a surgeon in Nero’s armies travelled exten-
sively and gained vast knowledge and experience about medicinal plants used by
various cultures. Galen (129–199 A.D.) was also an avid traveler of far off places,
who studied plants, conducted his own observations and experimentations, and left
a wealth of knowledge in the form of an eleven volumes treatise called The Mixing
and Powers of Simple Drugs, and later, The Composition of Drugs According to
Types and The Composition of Drugs According to Sites. His place in medical
history can be judged by the fact that many of today’s formulations are still referred
to as Galenical preparations.
Introduction 3

Ellen G. White (1827–1915) wrote in the nineteenth century:

God has caused to grow out of the ground her herbs for the use of man, and if we
understand the nature of these roots and herbs, and made right use of them, people would be
in much better health than they are today. These old-fashioned, simple herbs used intelli-
gently would have recovered many sick, who have died under drug medication.

Plants remained the major sources of medicines until Paracelsus (Theophrastus

Philipus Bombastus von Hohenheim, 1493–1541), a German physician and che-
mist, who was an arrogant and self-promoting individual, first introduced and
promoted the concept in the early part of 16th century that attack on the body by
external agents, what are now known as microbes, was the real cause of diseases
and not imbalance of internal equilibrium. To denounce the internal equilibrium
theories of Galen and Avicenna he publicly burnt their books. Paracelsus recom-
mended that treatment must be directed against these external causes of diseases
with chemical agents, rather than herbs. Thus, started the era in which treatment of
every illness with chemicals was sought, adopted and vigorously promoted. Despite
the acceptance of microbial theory of Paracelsus as the cause of diseases, which is
true in many cases, the fact that more than 80% of currently marketed drugs are not
antimicrobials obviously undermines the notion of Paracelsus that all diseases are
caused by microbial agents. In fact, many of the modern diseases are now recog-
nized as psychosomatic in origin.
Despite the availability and access to modern medicine, significant number of
people from around the world still repose their trust in traditional medicines and
medicinal plants. The herbalists who specialize in medicinal plants, and branded as
quacks by the civilized world, are still a reliable source to alleviate the sufferings
of millions in Africa and other parts of the world. The reason for this faith in tradi-
tional remedies is based on the fact that patients have experienced them to be ‘ef-
fective and safe’ as these remedies are part of the cultures and have been handed down
from generations to generations. Even the unskilled herbalists from around the world,
without any knowledge of anatomy, physiology or chemistry and sometimes unlet-
tered, successfully use these herbs to prevent and cure many diseases. The World
Health Organization (WHO) defines traditional medicine as “the knowledge, skills
and practices based on the theories, beliefs and experiences indigenous to different
cultures, used in the maintenance of health and in the prevention, diagnosis,
improvement or treatment of physical and mental illness.” The WHO (2002) esti-
mated that 80% of the world’s population use medicinal plants in the treatment of
diseases, and in African countries this rate is suggested to be even higher. Even in
the U.S., more than 40% of the population report using complementary and alter-
native medicines, including botanical dietary supplements. Annual global market for
plant-derived drugs over the last decade has been estimated to be approximately US
$30.69 billion. In 2008, annual expenditures on traditional medicines in Canada, and
the United Kingdom, were reported to be US$1 billion, and US$2.3 billion,
respectively, including incorporation of herbal and other forms of traditional medici-
nes into healthcare systems and the medical training of physicians. Annual worldwide
4 Introduction

market for herbal and other forms of traditional medicines was estimated at US$60
billion a decade ago. An analysis by the National Center for Complementary and
Integrative Health (NCCIH) and the Centers for Disease Control and Prevention
(CDC), based on the 2012 National Health Interview Survey (NHIS), showed that
Americans spent $30.2 billion out-of-pocket on alternative healthcare approaches,
such as herbal supplements, meditation, chiropractic, and yoga. This amounted to
9.2% of all out-of-pocket expenses and 1.1% of the total healthcare spending.
Americans spent annually an average of $368 on natural product supplements,
totaling $12.8 billion, about one-quarter of the total out-of-pocket expenses on pre-
scription drugs. Under the Dietary Supplement Health and Education Act (DSHEA)
of 1994, herbs, botanical and natural concentrates, metabolites and constituent of
extracts, classified as dietary supplements in the United States, are presumed safe
and do not require approval from the FDA for safety and efficacy before they are
marketed.
In many countries, like India, Pakistan, China, Mexico, Russia, and others, tradi-
tional systems of medicine or phytotherapy are protected and promoted by the
governments at par with the allopathic medicine. More than 90% of general hos-
pitals in China have units for traditional medicine. In Russia, phytotherapy is
officially sanctioned and is a separate branch of medicine; the Russian Federation
still follows the 11th edition of State Pharmacopoeia of the USSR. Traditional
medicines not only include herbal medicines, acupuncture from China and Yoga
from India, but aromatherapy, massage therapy, leech therapy, cupping, venesec-
tion, and many other forms have also been part of ancient therapies. It is generally
assumed that herbal drugs are only the succor of poor African and developing
nations, though it is far from reality. Many people from European and developed
nations, especially the older generations from rural areas still place their faith in
herbal drugs. A study by Taddei-Bringas and colleagues reported that 100% health
workers of a local Family Medical Care Unit of the Mexican Institute of Social
Security (in urban area), approved and used medicinal plants, and more than 90%
patients used them. Another proof of the popularity of plant-based products is the
fact that when scientists from around the world report results of a study on a plant,
they normally associate the concerned plant belonging only to their own country, to
emphasize the importance of one of their own resources. Use of plant-based drugs
is part of the holistic approach of all traditional medicines, which puts emphasis on
the whole being, with the mind, body, and the environment in sync, and not simply
on the disease (symptoms). Generally, alternative and complementary medicines
are viewed by the public in a positive light, but held in contempt and scorn by the
scientific community or viewed with extreme suspicion and summarily regarded as
quackery. However, even in the scientific community of developing countries, there
are those who passionately, and sometimes without reservations, promote the use of
traditional medicines; and at the other end of the spectrum are those who totally
despise traditional medicines and outrightly reject them; and, then there are those
who are ambivalent about their use. None of these views can and should be regarded
as absolutely correct. Quite often ignorance about the facts leads to wrong impres-
sions and erroneous beliefs, which is likely the case about traditional medicines.
Introduction 5

The quackery of some unqualified and untrained individuals in the injudicious use
of plants adds to the ridicule by the scientific community of such practices. Nev-
ertheless, old wisdom cannot be easily discredited.
In the era of biotechnology, gene editing, and talk of future customized treat-
ments aided by computers, it is unimaginable for some to accept the use of tradi-
tional medicines as the form of treatment, with their crude and ‘unscientific’
approaches. However, we forget that initially all drugs came from natural sources
until only a few decades ago. Even now, it is estimated that one-fourth of all
prescribed pharmaceuticals in industrialized countries contain compounds that are
directly or indirectly derived from plants; and 11% of the 252 drugs considered
as basic and essential by WHO are exclusively derived from flowering plants.
Approximately half of all licensed drugs, registered worldwide in the 25-years
period prior to 2007 were natural products or their synthetic derivatives. The most
successfully used antidiabetic drug, metformin, is a synthetic analog of galegine, an
alkaloid isolated from the perennial herb, Galega officinalis. Over 60% of cancer
drugs and 66% of antimicrobial compounds on the market today (including
antibacterial, antifungal and antiviral compounds) are reported to be natural prod-
ucts or derived from them. More than 100 compounds derived from natural
resources were in clinical studies a decade ago, and 13 drugs approved in the United
States between 2005 and 2007 were of natural origin.
The WHO has listed 21,000 plants used for medicinal purposes around the
world. Among these 2,500 species are found in India, out of which 150 species are
commercially utilized on a fairly large scale. Two-thirds of medicinal plants are
collected from the wild, whereas in Europe, only approximately 10% of commer-
cially used plants are cultivated. India is the largest producer of medicinal herbs and
is called the botanical garden of the world. Two Institutes in India: Central Drug
Research Institute (CDRI) and Central Institute of Medicinal and Aromatic Plants
(CIMAP) are notable in their contributions to the exploitation of the potentials of
medicinal plants, and have developed some effective therapies for the most
prevalent diseases of our time. Most of the plants included in this book are from the
species commonly used in Indian systems of traditional medicines.
Since the time, thirty-five years ago, this book was conceptualized a lot has
changed. At the time there were very limited published data on these plants, but now
there is a glut of sometimes redundant, ‘me too’ publications on most of these plants,
some may not even be considered much reliable. Despite all efforts it was sometimes
very hard to separate grain from the chaff. Too often, results from other species of the
same genus are quoted in publications to justify and emphasize a particular activity
observed in a species, misleading the readers and perpetuating incorrect references in
future publications. A retrospective study of active plants found in the National
Cancer Institute (NCI) program concluded that the yield of active species could have
been increased 50–100% by the use of folklore information. The emphasis, focus and
purpose of scientific research on plants should be on the quality, applied use, veri-
fication or repudiation of their traditional uses in an objective manner. We are
probably lacking in discharging this noble duty. While scientific studies on certain
plants have exploded and one may find tens and hundreds of reports on some of
6 Introduction

them, many other plants of significance have remained untouched pharmacologi-

cally and clinically. A number of factors have been identified for the slow progress in
the exploitation of medicinal plants, especially not utilizing the history of their
traditional uses. One of the most important impediments in utilizing folklore is that
several plants, sometimes even dissimilar, are known by the same colloquial name or
a single plant is known by several local names, overlapping with other plants.
Although, this dilemma has been discussed in scientific community for decades, it is
still plaguing the field and is difficult to resolve. Some of these controversies about
the plants included in this compilation have been discussed.
Another important and most debated aspect is that the actions and therapeutic
effects of medicinal plants are considered to be due to the presence of a relatively
small number of constituents, generally referred to as the active principles. It has
often been argued that the use of isolated active constituents enables one to calibrate
dose levels for the precise pharmacological effects, whereas the use of crude plant
material preparations does not offer the same control. This argument is wholly
justified and valid, and isolation of the most potent analgesic at the time, morphine
from opium by Friedrich Sertürner in 1803 confirmed this view, and later isolations
of quinine from Cinchona tree bark in 1820, digoxin from foxglove (Digitalis
purpurea) in 1930, and reserpine from Indian snakeroot (Rauwolfia serpentina) in
1952 reinforced this concept. Reserpine introduced as an antihypertensive drug in
the western medicine, though, caused many patients becoming depressed, while
treatment of patients with powdered root or extract of the root of Rauwolfia ser-
pentina in Indian medicine never caused depression in any patient. Furthermore,
active principles of a number of plant drugs are still unknown, as either they have
not yet been isolated and characterized or we do not know if any one constituent is
wholly responsible for a particular activity. In the simplest case the plant should
contain only one active component, which should also be the major one, but this is
a very rare occurrence and not the case in most circumstances. Most often, a plant
drug contains several structurally related compounds with similar pharmacological
properties. There are also sometimes structurally dissimilar compounds with syn-
ergistic or antagonistic activity present in the same plant; the active principle
concept becomes tenuous when in a number of instances, a plant drug in its crude
form produces an effect but no active constituent could be isolated that would
mimic this effect. It is also not unknown or uncommon for a pure isolate to have
less therapeutic activity than a combination of various constituents. The philosophy
underlying herbal medicine is quite different from that of the modern medicine; it is
the ‘total effect’ which forms the basis of herbal medicine treatment. Health benefits
of fruits and vegetables are now ascribed to synergistic interactions among various
constituents, and not to the individual phytochemicals. The synergistic, additive, or
agonistic/antagonistic properties of various constituents present in the plant produce
the ultimate pharmacological effect. The inactive substances present in the plant,
usually considered as inert (ballast material) or useless may have a role to play, such
as being the precursors of active principles. An example has been offered of a
physiologically inactive glycoside that is converted into an active aglycone after
Introduction 7

being acted upon by some enzymes in the body. Both the glycoside isolated from
the plant and the enzyme would be inactive by themselves, although both are
essential to the activity of the whole plant. The inactive compounds may also affect
the activity of the drug for physical reasons, such as fatty acids in many alcoholic
extracts may act as co-solvents for the active principles. Ancient medical texts have
emphasized the form in which a plant should be used, or what kind of solvent
should be used, normally it is either water or alcohol, probably to preserve the
stability and activity of its constituents.
Manufacturers have often attempted to standardize the strength of many modern
phytopharmaceutical preparations to a marker compound(s). However, for a similar
product different companies use different markers, or different levels of the same
markers, or different methods of testing for the same marker compounds. For
example, some manufacturers used hypericin to standardize St. John’s wort for its
antidepressant use, while others used hyperforin or both. Hypericin is now known
not to be the ‘active constituent,’ reinforcing the concept that the major compounds
are not always responsible for a biological effect observed in crude plant prepa-
rations. A number of known/unknown constituents and their combinations could be
the possible active constituents responsible for the antidepressant activity of St.
John’s wort. Many herbalists believe that the active ingredient in a plant is the plant
itself. Therefore, when searching for answers for many of the modern health-related
problems in plants, we must not forget that a common element (active constituent)
in different plants may not be the only factor responsible for a particular therapeutic
activity. A number of studies observed that attempts to isolate active constituent(s)
do not always result in clinically useful drugs. Out of five major constituents, asiatic
acid, madecassic, madecassoside, quercetin, and isoquercetin of Centella asiatica,
only a combination of asiatic acid and madecassic demonstrated optimal synergistic
effect on neurofilaments expression in vitro, more potent than any of the single
constituents. Major components of essential oil (EO) of Ocimum gratissimum,
eugenol, 1,8-cineole and trans-caryophyllene, failed to protect animals against PTZ
and MES-induced convulsions, both in isolated forms and in combinations in the
same proportion naturally found in the plant, whereas the oil was protective against
electroshock-induced tonic episode, pointing to the role other active or inactive
constituents may play. Similarly, oleanolic acid (OA) is a major triterpenic acid of
Chios mastic (a resinous exudate of Pistacia lentiscus tree). While the mastic
powder ameliorated experimental colitis and significantly reduced inflammation
even at the mRNA level in rats, OA or other fractions of mastic failed to exert the
same effect. Sensitivity of different bacteria (E. coli, S. aureus, and B. subtilis) also
varied for the components of mastic oil: verbenone, a-terpineol, and linalool than to
the oil itself, suggesting various components working synergistically for its
antibacterial efficacy. Presence of b-pinene and b-caryophyllene in the leaf essential
oil of Syzygium cumini was credited for its anti-inflammatory activity, however,
both constituents were individually lesser effective than the oil. Ethanol extract of
seeds of Allium cepa significantly inhibits (>80%) protein tyrosine phosphatase 1B
enzyme, but none of the eight furostanol saponins, named ceparosides, showed this
activity. Antimicrobial activities of the garlic volatile oil against 22 organisms were
8 Introduction

much lower than that of aqueous-ethanol extract prepared at room temperature,

despite TLC pattern of both preparations indicating a similar composition. A study
by Brahmbhatt and colleagues about the growth-inhibiting and apoptosis-inducing
properties of ginger methanol extract and the constituent ginger biophenolics
demonstrated that binary combinations of ginger phytochemicals synergistically
inhibited proliferation of prostate cancer cells.
Two components present in an extract may also cancel each other’s effect, such as
swertiamarin antagonizes the CNS stimulant effect of mangiferin present in Swertia
chirata. A similar, but opposite situation has also been observed when two different
plants with similar effects, but with no precedent in traditional use, are combined
they may not act synergistically or additively, and may even oppose each other. As
was reported by Bhatnagar and colleagues, that individually ethanol extracts of
Centella asiatica and Withania somnifera are significantly effective as antioxidant
and relieving MPTP-induced Parkinson-like symptoms in mice, but when the two
extracts were tested in combination for the same activities, there was no additive
effect, rather they performed even worse than as individually. When Akhtar and
associates administered a combination of extracts of three well recognized antidia-
betic plants (Syzygium jambolana, Momordica charantia and Azadirachta indica),
they expected a faster and additive or synergistic effect but the combination pro-
duced a delayed and lower hypoglycemic effect than the sum of their individual
effects. A 50% methanol extract of seeds of Syzygium cumini showed maximum
percent inhibition of a-amylase activity, but the 100% methanol extract was least
active; contrarily, a 100 mg/kg dose of aqueous seed extract of Syzygium cumini did
not reduce insulin-resistance in diabetic rats but 400 mg/kg did. Another example of
toxicity and/or potential drug-herb interactions is offered by saffron and its major
constituents, crocin and safranal. While crocin significantly decreases metabolic
activity of CYP2A, CYP2B, CYP2C11, and CYP3A enzymes, safranal significantly
increases metabolic activity of CYP2B and CYP2C11 enzymes in rats, and
co-treatment of rats with lethal dose of safranal and saffron aqueous extract signif-
icantly reduced safranal-induced mortality, and increased survival. These are some
of the examples of the challenges one encounters and has to overcome when working
with herbal drugs, but these challenges have to be overcome by concerted efforts to
fully exploit plants for our own benefit.
Variations in the observed or reported pharmacological activities or the absence
thereof is an issue that many pharmacologists and clinicians encounter with medici-
nal plants. However, it is not an exclusive issue with medicinal plants, innumerable
clinical trials on synthetic drugs (single entities) conducted by multinational phar-
maceutical companies often fail at phase II stage and many at phase III trials,
despite rigorous preclinical studies, whereas plants are complex entities with a
number of inherent variables. Chemical constituents in plants vary by geographical
location, environmental conditions, cultivar type, use of fertilizers, age of the plant
and even in younger and older leaves or roots/rhizomes, season and time of the day
of collection, drying and storage, nature of extraction solvents and other processes,
etc. For these reasons, our predecessors, in the absence of chemical analysis but
based on their observations and experience, had laid down specific conditions for
Introduction 9

the collection and preservation of plant materials for medicinal use, which we
derided for long as unscientific. For example, higher concentration of EO and
eugenol levels were found in younger than in older leaves of sweet basil (Ocimum
basilicum) and older leaves predominantly had methyl-eugenol and lower levels of
linalool. Geographical location where the plant grows is as important, as the ‘active
principle(s)’ may vary in amount or may even be entirely absent if a plant has been
grown under unfavorable conditions, and in some cases if the variety of the plant
was inherently low in active constituents. In other cases, amount of active principles
could be higher than normal, and under such circumstances it would produce a
stronger action. Different processes before use can also modify effects of the herbs.
Chohan and associates observed significant increase in antioxidant capacity of
extracts of cinnamon, cloves, fennel, ginger, sage and thyme after simmering, soup
making and stewing, whilst grilling and stir frying decreased it. A number of other
unrecognized or unintended variables could also affect the outcome of an animal
experiment or a clinical trial of a plant-based drug. (1) the wrong plant was used
than the intended one described in folk medicine, due to mismatch in vernacular
names; (2) the drug was inherently ineffective for the condition(s) it was tested for,
as there was no overwhelming evidence of its use in organized traditional folk
medicines; (3) the commercially obtained plant was adulterated or collected from a
naturalized place where the active constituents were low or absent from the plant;
(4) wrong parts of the plant were tested, such as leaves or root of a plant whose
seeds or flowers are used in traditional medicines to treat a particular disease; (5) the
plant was not collected at the appropriate developmental stage, and after collection
it was not properly processed or stored or the starting material was too old; (6) it
was not used in proper dosage form, such as an extract was used instead of the
powdered plant component as traditionally recommended; (7) the extraction was
done using the wrong solvent, etc. Herbs are usually recommended to be collected
in fresh form early in the morning after the dispersal of morning dew, during
months when the species is at its fullest state of growth, usually during the spring
and summer months. Plants growing in their natural environments (not naturalized)
are said to be the most suitable for diseases of the region. Healing properties of
some herbs are associated with flowers or seeds, and these parts should be collected
during the flowering or seeding periods and properly stored. As a general rule,
properly collected and dried herbs retain their medicinal properties for at least two
years. These aspects are important and should be kept in mind when scouring for
new therapies in nature, and not ignore the nature’s way or results of keen obser-
vations of our predecessors.
Traditional medicines practiced in India include Ayurveda, Siddha and Unani
(Greco-Arab). While Ayurveda and Siddha originated in India, Unani medicine is
an extension of the medicine that originated with Hippocrates, sustained by both
Greeks and Romans, but was mainly nurtured and nourished by Arabs and Persians.
Ayurveda, Unani and Traditional Chinese Medicine (TCM) simultaneously devel-
oped and progressed independently on their own tracks. However, there are certain
concepts that look similar in these independent systems of medicine. Temperament
is a functional concept that is common to both Unani and TCM, and is recognized
10 Introduction

and practiced in many other cultures. This concept is also applied to humours, the
presumed constituent body fluids. In Latin American countries the concept of bal-
anced ‘hot and cold’ is also widely accepted for the maintenance of health, and its
imbalance as the cause of disease by local traditional medicine practitioners.
Therefore, they also categorize all foods and beverages on the basis of being ‘very
hot’ or ‘very cold’ or temperate in qualities. Similarly, in African countries the
concept of dualism in terms of ‘hot and cold’ as the forces that maintain body
equilibrium and health is widely practiced. Diseases are also classified as ‘hot’ and
‘cold’ in nature, and the treatment is directed to restore balance, the equilibrium of
the body. According to this concept, humours and all foods and drugs are func-
tionally classified into hot or cold categories. The binary qualities assigned to herbal
drugs are a combination of hot, cold, dry and moist, the former two being the active
(the primary “Drug Nature” in TCM) and the latter ones as passive qualities. None of
these qualities are considered absolute, rather they are viewed as relative to each
other. Ancient philosophers, however, emphasized that when a substance or an
element is said to be hot or cold, it does not always mean it to be literally hot or cold.
In Unani medicine, the temperament of drugs is graded into four degrees: in the first
degree (1°), the effect is almost imperceptible, whereas drugs that are classified in the
fourth degree (4°), if not used judiciously may cause serious harm, and even death.
Most of the plant drugs, including those in this book, are classified with a temper-
ament of hot and dry. Ardekani and colleagues observed that plants containing
alkaloids were found to have a temperament of hot and dry, except those containing
tropane alkaloids (such as Datura stramonium, Hyoscyamus niger, Mandragora
officinarum, and Solanum nigrum with steroidal alkaloids). Plants containing phe-
nolic compounds (benzophenones, xanthones, coumarins, flavonoids, anthraqui-
nones, lignans) were also of a temperament of hot and dry, except those having
tannins (such as Terminalia chebula, Terminalia bellerica, Acacia arabica, Punica
granatum, Quercus infectoria) as the phenolic substances. Plants containing volatile
oil (VO) generally have hot and dry temperament, if the oil does not contain alco-
hols. Alcohols containing VO from Coriandrum sativum and Santalum album are
cold and dry in temperament. Chinese scientists have devised experiments to
physically prove the temperamental qualities of herbs by an Animal Thermotropism
Behavior Surveillance System, that characterizes and quantifies the cold and hot
properties based on animal behavior. For example, after administration of Coptis
chinensis (a drug assigned cold temperament in TCM and a frequently used herb in
prescriptions to treat excessive thirst), mice stayed significantly longer on a warm
pad (40 °C), with a significant decrease in oxygen consumption and adenosine
triphosphatase (ATPase) activity, suggesting the enhancement of hot tropism. This
external behavior of hot tropism is suggested to reflect the internal cold nature of
C. chinensis.
Humoural theory originated with the Greeks (Hippocrates and Galen), and was
the dominant medical theory until Paracelsus rejected and cast doubts about it in the
early part of the 16th century. This theory espouses the existence of four humours,
i.e. blood (dam), yellow-bile (safra), black-bile (sauda) and phlegm (balgham),
based on the observation and speculation that the yellowish froth at the top of blood
Introduction 11

was yellow-bile, the white portion mixed with blood was phlegm and the darker
portion settled at the bottom was black-bile. Despite the renaissance of the 16th
century, set in motion by Paracelsus, humoural pathology as a concept remained
dominant until the year 1858 A.D., when the theory of cellular pathology was
proposed by Rudolf Virchow. Humoural theory is still the basis of Greco-Arab
(Unani) medicine. In a slightly different form, Ayurveda believes in three humours
called tridoshas, i.e. vata (air), pitta (bile) and kapha (phlegm). A humour is
regarded as the initial product of food digestion and is capable of assimilation and
complete integration into the tissues. Each humour is also assigned binary qualities
based on the assumed dominant element as their constituent. Blood is, therefore,
classified as hot and wet (air), yellow-bile as hot and dry (fire), black-bile as cold
and dry (earth), and phlegm as cold and wet (water). Each individual has a pre-
ponderance of one of these humours, ordained by nature (genetic make-up), that
defines the physical, physiological and psychological characteristics of the indi-
vidual and his/her body constitution. Admixture of humours responsible for an
individual’s body constitution in a physical sense also determines one’s tempera-
ment. In healthy persons, humours are present in equilibrium ordained by nature
that is neither in excess nor in deficiency, and this is known as eucrasia. Imbalance
in the proportions of humours results in disease and is known as dyscrasia. Quali-
tative or quantitative imbalance of humours results in abnormal temperament which
is usually restored by dietary restrictions and with the use of herbal remedies.
Herbal drugs, by themselves, are not alternative medicines but only a component
of them; like allopathic drugs cannot be described as the whole modern medicine.
However, there are fundamental differences in the use of herbal drugs and synthetic
drugs; while the former is used to treat patients based on concepts of a particular
alternative medicine, be it Ayurveda, TCM, Unani or an unorganized one, the
latter can only treat recognized individual symptoms or physical/mental abnor-
malities. It is not an uncommon observance that patients who do present to allo-
pathic physicians with ill-defined symptoms with no recognized physical/mental
abnormality are often left untreated because their symptoms do not reconcile with
any recognized disease, and some are even labeled as hypochondriac. Pharma-
ceutical industry, due to its economic and financial interests, control and set the
agenda for healthcare policies of most countries from around the world and create
and promote a narrative that suits to advance its interests and hegemony. Notwith-
standing the remarkable and unmatched successes and advancement of modern
medicine in the management of infections, acute disease conditions and surgical
procedures, certain aspects of modern medicine are not as glamorous. While the
physical part of modern medicine the ‘Science of Medicine’ has made unprece-
dented strides, largely due to advances in other sciences, such as electronics, bio-
engineering, biotechnology, biochemistry, etc., the ‘Art of Medicine’ has simul-
taneously deteriorated. Also, its accessibility and the cost involved makes it beyond
the reach of a sizable population of the world. Secondly, 30% of hospitalized
patients in the U.S., about 8.7 million have adverse drug reactions due to synthetic
or semisynthetic drugs, resulting in an estimated 140,000 American deaths annu-
ally, making it by one estimate the fourth leading cause of death in the U.S.; though,
12 Introduction

according to the CDC the fourth leading cause of death in the U.S. are accidents. Of
all hospital admissions 3–5% are estimated to be for drug reactions, and 14% of all
hospital days are devoted to the care of patients with a drug reaction. It is also
reported that eight common drugs produce one third of all adverse drug reactions,
and the most dangerous problem is the interaction of combining certain drugs. This
aspect is generally not discussed in public fora and media. However, a natural drug
not performing as expected in a clinical trial or occurrence of a certain rare adverse
reaction, toxicity or drug-interaction is disproportionately highlighted in the media.
Herbal drugs’ adverse effects or interactions with prescription drugs serve as a
magnet for detractors about the use of these drugs. Apart from the hype the reality is
much different. For example, Posadzki and colleagues conducted an overview of
the published 50 systematic reviews of adverse effects of 50 herbals. They found
that serious adverse effects including most severe, such as liver or kidney damage,
colon perforation, carcinoma, coma and death were reported only for four herbals
(one of these 4 herbs, Cassia senna is included in this book); fifteen herbs caused
moderately severe adverse effects (five of these herbs: Aloe vera, Commiphora
mukul, Medicago sativa, Taraxacum officinale and Viscum album are part of this
book), and the rest (31) produced minor adverse effects (of those Thymus vulgaris,
Boswellia serrata, Cinnamomum spp., Melissa officinalis, Trigonella foenum-
graecum, Gymnema sylvestre, and Curcuma longa are included here). Sometimes, a
plant is declared toxic or even carcinogenic based on the presence of a chemical
constituent in it that could have caused toxicity or carcinogenicity in animals or
in vitro systems in its isolated form. However, when the whole plant or its part is
used as decoction or in some other forms, a host of other chemical substances
present in it produce the ‘whole effect,’ some might be counterbalancing the
injurious effect(s) of an isolated substance, such as estragole (a potential carcino-
gen, whose levels are much higher in bitter fennel than in sweet fennel), is only one
of the 34 or so identified compounds in fennel essential oil. Out of two hundred
compounds isolated from turmeric (Curcuma longa), in vitro studies predicted 184
compounds as toxigenic, 136 as mutagenic, 153 as carcinogenic and 64 compounds
as hepatotoxic, but the whole turmeric is now commercially promoted and rec-
ommended for its beneficial effects. Plants containing phenolic compounds (fla-
vonoids, polyphenols, tannins, etc.) and the arachidonic acid analogs (alkylamides,
retinoids, etc.) are the most effective inhibitors of COX and 5-LOX enzymes.
Flavonoids are a large and diverse group of polyphenolic compounds with antioxi-
dant effects, and onion bulbs are among one of the richest sources of dietary
flavonoids. Consumption of Crucifers, like brussels sprouts, broccoli, cabbage, and
cauliflower, protects against cancer if taken prior to a carcinogen, when taken after a
carcinogen they act as promoters of carcinogenesis. This is one of the reasons why
vegetables consumption is recommended and encouraged. Crucifers also contain
allyl isothiocyanate, goitrin, and thiocyanate that are goitrogenic. Therefore, an
objective and unbiased approach is needed to unlock the secrets and establish the
norms for this inexpensive source of drugs for the benefit of the masses.
Regarding clinical trials, patients from different ethnic and cultural backgrounds
with varying genetic make-up, dietary and social habits may and do respond
Introduction 13

differently to the same drug intervention, an aspect that was ignored for long by the
modern scientific establishment. While a directive of the FDA in 1977 barred
women of child-bearing age from participation in clinical trials due to thalidomide
tragedy, a reversal of this policy soon came in the guidelines of 1985, and in 1993
FDA formally rescinded its 1977 policy; and now participation of both women and
men, and people of different races and ethnicities is required in all NIH-funded
research. Therefore, factors that might provide perspective to the results of clinical
trials have been included in this text. Moreover, plant-based products are not as
dramatic in their effects with a single dose or short-term administration as their
allopathic counterparts; hence, clinical studies that were done using single doses or
were variations of other studies not relevant in a particular treatment setting, were
generally avoided unless included for a compelling reason; the same approach was
adopted for meta-analyses. Pharmacological studies involving successive extrac-
tions and specialized studies of molecular nature were also largely avoided unless to
provide a perspective. Single dose effect on memory are not relevant, but have been
exceptionally included in some cases. Studies on isolated active chemical con-
stituents were for most part avoided or included with reservations and exceptions
when published information was scant.
This format of the book was adopted to provide sufficient information about any
controversy about the name or species of the plant, the part used, the form or extract
exhibiting the activity and other nuances to be helpful in future efforts. Also,
information about negative and inconsistent results is as important as reporting
about positive outcomes. Efforts were made to provide perspective of the phar-
macological or clinical studies. There are plants in this book that have exhaustively
been investigated (ad nauseum), while others have barely been touched. Plants that
have been extensively studied tend to show effects on almost every system in the
body, as they were some sort of panacea; some of these results should be accepted
with a grain of salt. On the other hand, plants that have been widely used in tradi-
tional medicines of many countries for long, have not shown positive results in
animal or clinical studies for these effects. Frustration of scientists due to negative
or inconsistent results about medicinal plants is understandable, the chemical
constituents of these two-hundred plants may offer an insight into the differences
not only due to geographical location or part(s) of the plant, but due to many other
factors that could theoretically affect the outcome. They may help in future efforts to
find answers for the discrepancies and learn from the mistakes that might have been
made in our interpretations of the results. One atypical example about variation in
chemical constituents to quote here would be of Pimpinella anisum, that showed
that the number of chemical constituents of essential oil increased from 27 to 45,
and phenolic compounds, especially chlorogenic acid significantly increased if Zinc
fertilizer was applied during its cultivation. Another example is the increase in Ca,
Mg, K, Fe and Zn, and a decrease in phosphorus content of Portulaca oleracea with
plant maturity, even from 15 days to 30 days old. It is expected that this aspect,
though already recognized, will attract more attention for meaningful research.
To stay within the scope of this book, references to activities and effects other
than human health-related and those that are more of a pure academic nature, such
14 Introduction

as molecular mechanisms of actions, have generally been used with reservation.

Furthermore, despite a desire to provide all relevant information about each plant,
practical limitations forced me to compromise in many instances. Many Chinese
studies published in Chinese language have been indirectly referenced from English
abstracts or other sources. Sincere efforts were made to cross-check references, and
wherever feasible, available full published articles were consulted for relevant
information. In cases, where critical information about a study was missing even
from full publication, authors of those publications were contacted, and in many
cases the queries went unanswered; therefore, results of these studies were not
included. It is one of the major challenges of research on medicinal plants that
inaccurate references are perpetuated without corroboration. Not only relying on
cross references was a challenge, sometimes even data from the abstract of an
original research turned out to be inaccurate. For example, while reporting the
major constituents of an essential oil, one report did not come even close to other
reports. Further review of the full paper revealed that the authors in reporting the
results in their abstract reversed the contents of two essential oils they analyzed.
Such errors are very unlikely but this example proves that it can occur. Since the
collection of literature on these plants started few decades ago, interspersed with
long periods of inactivity, details and in some cases complete references might have
been lost, for which I am regretfully responsible. Each plant reviewed is presented
with its complete list of references; however, to avoid repeat listings of books
referred, they have been collated at the end, and references to them are indicated in
Roman numerals in the text. Quite often, actions and uses described in different
references are deliberately repeated to emphasize similar uses in different cultures
and countries; and older references have been included to highlight the past history
and trail of research. I have deliberately used both the present and past tenses to
describe actions and effects of the plants.
Current assignment of nomenclature of Families to plants has been adopted,
along with the traditional classification, especially for Compositae, Leguminosae
and Umbelliferae families. All plant names, their authorities and the synonyms were
checked against the list of plants at Kew Botanical Garden, Missouri Botanical
Garden, Global Compositae Checklist, and Royal Botanical Garden, Edinburgh, on
Sept. 16, 2016. Synonyms with confidence level of *** and sometimes with **
were adopted, but not those that were still under review. In addition to the published
sources, European and Mediterranean Plant Protection Organization (EPPO) Global
Database and Encyclopedia of Life (EOL) were utilized for names in local lan-
guages of other countries.
Abelmoschus moschatus Medik
(Malvaceae)

(Syn.: Hibiscus abelmoschus L.)

Abstract
The seeds of an annual plant, named musk-mallow because on bruising they emit
an aromatic odor resembling to musk due to the presence of nitrogen-containing
pyrazines and pyridines derivatives and thiazoles. In Arabia, seeds were regarded
stimulant, carminative, stomachic, cooling and demulcent, given in gonorrhea,
catarrh of the bladder, and as inhalation for hoarseness of voice, and dryness of
mouth. In the Unani medicine, seeds are used for the treatment of gonorrhea
and nocturnal emissions, and also used in hysteria, nervous debility, and other
nervous disorders. In Hawaiian Islands, leaves and flower buds are largely used
for softening contents of stomach and bowel in cases of constipation. In the
Philippines, seeds decoction was used as tonic, antihysteric, diuretic and carmi-
native, and the mucilaginous decoction of roots and leaves was used for the
treatment of gonorrhea. In Trinidad and Tobago, it is used for the treatment of
menstrual pain and unspecified female complaints, childbirth and infertility.
Aqueous and hydroalcohol extracts of seeds and leaves showed the presence of
polyphenols and flavonoids. Seed extract demonstrated significant antimicrobial
activity and prevented natural degradation of fibroblast growth factor, helping in
reducing wrinkles. Aerial parts extract also significantly reduced insulin resistance
in rats; presence of myrcetin is credited for blood glucose-lowering activity.

Keywords





Ambrette Anber çiç Dalupang Gandapura Jangli-bhenda Mushkdana






Muskateller-bisameibisch Musk-mallow Musk-okra Ryûkyû tororo aoi

Vernaculars: Urd.: Mushkdana; Hin.: Jangli bhenda, Kasturi bhendi, Mish-bhendi-

ke-bij, Mushk-dana; San.: Gandapura, Latakasturikam, Zatakasaturika; Ben.:
Kalkasturi, Kasturi-dana, Latakasturi, Mushkdana; Mal.: Katta-kasturi, Latha-
kasthuri; Mar.: Kasturi-bhenda-che-bij, Van bhendi; Tam.: Kasturivendaik-kayvirai,
Kattuk-kasturi, Vattilai-kasturi; Tel.: Karpuri-benda, Kasturi-benda-vittulu; Ara.:
© Springer Nature Switzerland AG 2020 15
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_2
16 Abelmoschus moschatus Medik

Anbar bûl, Habbul mishk, Habb-ul-mushk, Kababul-mishk; Chi.: 野棉花, Huang

kui, Shan you ma, Ye you ma; E&W Ind.: Bandiki, Gombo, Ochro; Eng.:
Musk-mallow, Musk-okra, Musk seeds, Okra; Fre.: Almizcle vegetal, Ambrette,
Gombo musqué, Graine de musc, Ketmia ambrette, Ketmie des marais, Ketmie
musquée; Ger.: Ambramalve, Bisamstrauch, Muskateller-bisameibisch, Muska-
teller-eibisch; Haw.: Kokio, Puaaloalo; Ind.: Kasturi; Ita.: Abelmosco, Ambretta,
Fior muschiato, Ibisco muschiato; Jap.: Ryûkyû tororo aoi; Maly.: Gandapura, Kapas
hutan; Per.: Makstan, Mushkdana; Rus.: Abelʹmosh muskatnyj, Gibiskus muskus-
nyj; Tag.: Dalupang, Kastiokastiogan, Kastuli; Tha.: Chamot ton, Mahakadaeng,
Som chaba; Tur.: Anber çiç; Vie.: Búp vàng, Cây bông vàng, Vông vang.

Description: An annual, erect, branched herb, up to 1 m high, covered with very

long hairs, and is found in tropical countries. Leaves are orbicular-ovate to ovate,
6–15 cm long, variously angled or lobed, usually broad or heart-shaped at the
base, pointed at the tip, and toothed in the margins. Flowers are about 10 cm in
diameter, with yellow petals that are purple at the base inside. The capsules are
oblong-ovoid, 5 to 7 cm long and covered with long hairs, and contain numerous
musky seeds. Seeds are brown in color, irregularly kidney-shaped, the surface marked

Fig. 1 Abelmoschus moschatus, Illustration, Francisco Manuel Blanco (O.S.A.), Flora de Filip-
inas […] Gran edicion […] [Atlas II] [1], WikimediaCommons, https://commons.wikimedia.
org/wiki/File:Abelmoschus_moschatus_Blanco2.245.png
Abelmoschus moschatus Medik 17

Fig. 2 Abelmoschus moschatus, Seeds, Maša Sinreih in Valentina Vivod, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Abelmoschi1.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

with concentric rings, pointed at one end. The name musk-mallow is due to the fact
that the seeds possess an aromatic odor resembling to that of musk; the odor is not
perceptible unless seeds are well bruised (Figs. 1 and 2).CXVII
Actions and Uses: In Arabia, seeds were regarded stimulant, carminative, stom-
achic, cooling and demulcent, given in gonorrhea, catarrh of the bladder, and as
inhalation for hoarseness of voice, and dryness of mouth. Mixed with coffee, seeds
are used in fevers, and powdered seeds steeped in alcohol as an application for
serpents’ bites.LXIII,LXXXI,CV In Unani medicine, seeds (temperament, hot 2° and dry
2°) are regarded stimulant, stomachic, carminative, astringent, analgesic and anti-
spasmodic and tonic for eyes, and used for the treatment of gonorrhea and nocturnal
emissions.LXXVII Leaves and stems are also useful for gonorrhea and semen fluid-
ity.L Seeds are also described as cardiac tonic, aphrodisiac, and diuretic. Powdered
seeds in lukewarm milk are recommended for treatment of constipation, dyspepsia
and gonorrhea. Leaf decoction is effective against intestinal complaints, and for
vomiting [7]. In Ayurveda, seeds are cooling, tonic and carminative, and used in
hysteria, nervous debility, and other nervous disorders, and the mucilage from roots
and leaves is used for the treatment of gonorrhea.XXI,LXXXIV,CV In Hawaiian Islands,
leaves and flower buds are largely used for softening contents of stomach and bowel
in cases of constipation.LXXVI In the Philippines, seeds decoction was used as tonic,
antihysteric, diuretic and carminative, and the mucilaginous decoction of roots and
leaves was used for the treatment of gonorrhea.LVI,CXVII In Trinidad and Tobago, it
is used for the treatment of menstrual pain and unspecified female complaints,
childbirth and infertility [5].
18 Abelmoschus moschatus Medik

Phytoconstituents: Aqueous and hydroalcohol extracts of seeds and leaves

showed presence of polyphenols and flavonoids [4]. Gum, albumin, fixed oil, a
solid crystalline matter, odorous principles and resin have also been isolated. Fixed
oil is greenish-yellow fluid, which solidifies on exposure to the air. The solid
crystalline matter is white, pearly, of a pleasant taste and is soluble in ether. The
odorous matter is a light green fluid of strong smell of musk and is not volatile.
Fifty-eight nitrogen-containing compounds, including 27 pyrazine derivatives and
12 pyridines, and 7 thiazoles have been isolated. The characteristic smell is due to
the presence of these nitrogen-containing pyrazines and pyridines derivatives and
thiazoles [2]. Four trypsin inhibitors, AMTI-I, AMTI-II, AMTI-III, and AMTI-IV,
were isolated from seeds [1], and myrcetin has been reported from aerial parts [7].

Pharmacology: Seed extract prevents natural degradation of fibroblast growth

factor (FGF-2), which maintains its bioavailability for the growth of skin fibrob-
lasts, helping in reducing wrinkles [11]. An aerial parts extract with high levels of
polyphenolic flavonoids reduced insulin resistance in rats induced by a 60% fruc-
tose containing diet for six weeks [9]. Bolus i.v. injection of myricetin, isolated
from aerial parts, decreased plasma glucose concentrations, stimulated glucose
uptake by isolated soleus muscles from diabetic rats, and significantly attenuated
increase in plasma glucose in normal rats, after intravenous glucose challenge [7].
Repeated i.v. injection of myricetin to obese Zucker rats, thrice daily for one week
reduced insulin resistance [8]. Aqueous leaves extract shows higher antioxidant
activity than the seed extract, but the superoxide radical scavenging activity is
higher in seed extract [4]. Aqueous seed extract also showed significant in vitro
antimicrobial activity against B. subtilis, S. aureus and P. aeruginosa; whereas
hydroalcohol leaf extract was active against P. vulgaris and C. albicans [4].
Aqueous root extract was larvicidal against An. culicifacies, An. stephensi, and C.
quinquefasciatus [3]. Chloroform and methanol extracts significantly improved
glomerular filtration rate, and significantly reduced deposition of calculi around
implanted zinc disc in the urinary bladders of rats [10].
Mechanism of Action: Glucose lowering effect of myricetin is mediated through
activation of opioid mu-receptors of peripheral tissues in response to increased
b-endorphin secretion [6].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: No studies have been carried out or reported on its use in gonor-
rhea, nervous and seminal debility, which find repeated mention in traditional uses.
There are also no clinical studies reported in the mainstream English publications
listed on PubMed.
Abelmoschus moschatus Medik 19

References
1. Dokka MK, Seva L, Davuluri SP. Isolation and purification of trypsin
inhibitors from the seeds of Abelmoschus moschatus L. Appl Biochem
Biotechnol. 2015;175:3750–62.
2. Du Z, Clery RA, Hammond CJ. Volatile organic nitrogen-containing
constituents in ambrette seed Abelmoschus moschatus Medik (Malvaceae).
J Agric Food Chem. 2008;56:7388–92.
3. Dua VK, Pandey AC, Alam ME, Dash AP. Larvicidal activity of Hibiscus
abelmoschus Linn. (Malvaceae) against mosquitoes. J Am Mosq Control
Assoc. 2006;22:155–7.
4. Gul MZ, Bhakshu LM, Ahmad F, et al. Evaluation of Abelmoschus
moschatus extracts for antioxidant, free radical scavenging, antimicrobial and
antiproliferative activities using in vitro assays. BMC Complement Altern
Med. 2011;11:64.
5. Lans C. Ethnomedicines used in Trinidad and Tobago for reproductive
problems. J Ethnobiol Ethnomed. 2007;3:13.
6. Liu IM, Liou SS, Cheng JT. Mediation of beta-endorphin by myricetin to
lower plasma glucose in streptozotocin-induced diabetic rats. J Ethnophar-
macol. 2006;104:199–206.
7. Liu IM, Liou SS, Lan TW, Hsu FL, Cheng JT. Myricetin as the active prin-
ciple of Abelmoschus moschatus to lower plasma glucose in streptozotocin-
induced diabetic rats. Planta Med. 2005;71:617–21.
8. Liu IM, Tzeng TF, Liou SS, Lan TW. Myricetin, a naturally occurring
flavonol, ameliorates insulin resistance induced by a high-fructose diet in
rats. Life Sci. 2007;81:1479–88.
9. Liu IM, Tzeng TF, Liou SS. Abelmoschus moschatus (Malvaceae), an
aromatic plant, suitable for medical or food uses to improve insulin sensitivity.
Phytother Res. 2010;24:233–9.
10. Pawar AT, Vyawahare NS. Antiurolithiatic activity of Abelmoschus moscha-
tus seed extracts against zinc disc implantation-induced urolithiasis in rats.
J Basic Clin Pharm. 2016;7:32–8.
11. Rival D, Bonnet S, Sohm B, Perrier E. A Hibiscus abelmoschus seed extract
as a protective active ingredient to favour FGF-2 activity in skin. Int J
Cosmet Sci. 2009;31:419–26.
Abrus precatorius L.
(Fabaceae/Leguminosae)

Abstract
It is a woody climber, found throughout the plains of India, Sri Lanka, and other
hot countries, and also along the Himalayas. The leaves are used to relieve
hoarseness of voice and as a cure for aphthous ulcers of mouth, and topically in
skin diseases, such as leucoderma and eczema, and also recommended as a cure
for baldness. Zulus use leaves decoction as a remedy for pain in the chest, and in
Sri Lanka, the juice is taken as a blood purifier. Seeds are poisonous and their
internal use is attended with extreme danger but are used in a purified form in
affections of the nervous system. In Ayurveda, detoxified or purified seeds are
used for the treatment of alopecia, edema, helminths, skin diseases, itching, and
urinary disorders. Black seeds are never used medicinally. Internal use of seeds
by women is toxic, disturbs uterine functions, prevents conception, and induces
abortion. Powdered seeds (ca 200 mg) are used as oral contraceptive in Central
Africa; a single dose remains effective for 13 menstrual cycles; and are also taken
as snuff to relieve violent headaches arising from cold. Abrins, very similar in
action to ricin, are the major poisonous phytotoxins of the seeds. One seed is
reported to contain enough abrin (*5 mg) to kill an adult human. A paste made
of powdered seeds is used to poison darts and arrows to kill animals. The
antifertility effects of seed extracts have been inconsistent in animals. Methanol
leaf extract has demonstrated significant blood glucose lowering and insulino-
tropic effects in diabetic rats. The leaf extract and abrin have exhibited significant
in vivo antitumor and in vitro cytotoxic effects. Poisoning of humans due to seeds
results in acute demyelinating encephalitis, increased intracranial pressure and
papilledema, which may result in death.

Keywords




Abrus Arbre a chapelet Ayn-ed-dik Chochito de indio Crab’s eyes






Ghungchi Guñjā Jequirity seeds Paternostererbse Xian si zi

© Springer Nature Switzerland AG 2020 21

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_3
22 Abrus precatorius L.

Vernaculars: Urd.: Ghungchi; Hin.: Ghungchi, Gunch-rutti, Guñjā, Rati; San.:

Gunja; Ben.: Chun hali, Gunjachi, Kunch, Kunchgula; Mal.: Gundumani, Kunni,
Kunni kuru (seeds), Kunnikkuru; Mar.: Gunj; Tam.: Gundumani, Kunthamani; Tel.:
Guruginia, Guruvenda; Ara.: Ayn-ed-dik (Egypt), Batrah hindi, Habb-e-shoush,
Qulqul; Bur.: Ywe gale, Ywe nge; Chi.: 相思子, Ji mu zhu, Xian si zi, Xiang xi dou,
Xian xi teng; Cze.: Sotorek obecný, Sotorek růžencový; Eng.: Abrus, Buckbead,
Chicken eyes, Circassian-bean, Coquelicot, Crab’s eyes, Indian liquorice, Jequirity,
Jequirity seeds, Jumbie-bead, Jumble beads, Liquorice bush, Love pea, Prayer beads,
Precatory bean, Red bead vine, Red bean, Rosary pea, Sandal bead tree, Weather plant,
Wild liquorice; Fre.: Arbre a chapelet, Graines d’eglise, Herbe a beau-pere, Liane a
reglisse, Reglisse d’Amerique, Reglisse sauvage; Gab.: Liane reglisse, Odepou, pois
de Bedeau; Ger.: Paternostererbse, Paternosterkraut; Ita.: Liquirizia, Regolizia,
Regolizia d’America; Jap.: Tou azuki; Kor.: Hong du; Maly.: Kenderi, Piling-piling,
Pokok saga; Nep.: Laalgedii; Mex.: Tzompaquahitl; Per.: Ain-ud-dik (Cock’s eye),
Chashme-kharosh, Gunchi; Por.: Jequiriti, Olho de pombo; Rus.: Abrus molitvennyj,
Chétochnik; Spa.: Bejuco de chochos, Bejuco de pionia, Chochito de indio, Chochos,
Chochos de pinta negra, Colorines, Coral, Coralin, Coralillo, Guairuros, Ojos de
cangrejos, Orosus orozus, Peronia, Peronias, Peronilas, Peronilla, Pionia, Regaliz,
Regaliza; Sin.: Olinda; Sud.: Fadougale, Ido zakara, Ido zakari; Swa.: Mongaluchi,
Mtipitipi, Muturituri; Tag.: Saga; Tha.: Cha em thet, Ma khaam tao, Ma khaek, Ma
klam daeng, Ma klam khru; Tur.: Amerika kaya sarmaşığı; Vie.: Cam thảo dây, Cườm
thảo, Dây chi chi, Dây cườm cườm
Description: It is a beautiful woody climber, found throughout the plains of India,
Sri Lanka, and other hot countries, and also along the Himalayas, ascending to an
altitude of 3,000 ft. It flowers in August and September and the pods ripen by the
end of the cold season. Leaves are 5–7.5 cm long, abruptly pinnated; leaflets 8 to 20
pairs, linear oval, obtuse at both ends, glabrous or slightly hairy, membranous,
deciduous 1–1.6 cm long and 0.4–0.5 cm broad, taste sweet like that of liquorice.
Seeds are bright scarlet with a black spot at one end; the white variety of seeds is
polished, smaller than a pea in size but larger than the red variety; average weight of
scarlet variety 114 mg, black variety 115 mg and white variety 128 mg. Roots
long, woody, hard and much branched, seldom more than 0.6 cm in diameter.
Cortical layer very thin, reddish brown; wood yellowish white; odor and taste acrid,
hardly at all sweet (Figs. 1 and 2).XL
Actions and Uses: Fresh leaves of the white seeded variety have a sweet taste and
are chewed to relieve hoarseness of voice and with cubeb and sugar as a cure for
aphthous ulcers of mouth.XXI,XL,LXXXI In spermatorrhea with bloody discharge,
equal parts of the juice of white abrus leaves and henna leaves (Lawsonia inermis)
are rubbed with the root of Holostemma rheedii, cumin and sugar and administered
orally.XL,LXXXI Seeds are purgative, emetic, tonic, antiphlogistic, and aphrodisiac.
Fresh leaves juice mixed with some bland oil is applied to painful swellings.CV The
seeds’ paste (temperament, hot 3° and dry 3°) being resolvent is mainly used
externally for the treatment of leucoderma, eczema and freckles.LXXVII Leaves paste
mixed with bland oils is also applied in skin diseases, such as leucoderma and
Abrus precatorius L. 23

Fig. 1 Abrus precatorius, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Abrus_precatorius_-_Köhler–s_Medizinal-
Pflanzen-002.jpg

Fig. 2 Abrus precatorius, Plant and Seeds, Forest and Kim Starr, USGS Plants of Hawaii,
WikimediaCommons, https://commons.wikimedia.org/wiki/File:Abrus_precatorius_pods.jpg

eczema, and to painful swellings,LXXVII,LXXXI and is also recommended as a cure

for baldness.LXXXI In Ayurveda, detoxified or purified seeds are used for the
treatment of alopecia, edema, helminths, skin diseases, itching, and urinary disor-
ders [50]. GhaniL mentioned that according to Ayurvedic practitioners it is bitter,
24 Abrus precatorius L.

hot, emetic, and increases semen production. The root and leaves are reported to
possess diuretic, emetic, and tonic properties, and are used for the treatment of
gonorrhea, jaundice and hemoglobinuric bile [19]. Black seeds are never used
medicinally.LXXXI The Tharu tribe of Gonda and Baharaich districts (India) insert
into the vagina the seed paste of Gumachi on a cotton pad to induce abortion [55].
Seeds are poisonous, are reported emmenagogue [33], and used internally in
affections of the nervous system but their use is attended with extreme danger [12,
25],XXX,XXXV and externally applied in skin diseases, ulcers and to fistulas to excite
inflammatory reaction. They are reported to have been used for centuries in Brazil
as a popular remedy for granular eyelids and pannus.XL Internal use of seeds by
women is toxic, disturbs uterine functions, prevents conception,LXXXIV and induces
abortion [51].XXI Powdered seeds (ca 200 mg) are used as oral contraceptive in
Central Africa; a single dose remains effective for 13 menstrual cycles;XXXVIII and
are also taken as snuff to relieve violent headaches arising from cold.LXXXIV Seeds
have also been used in India to commit murders,CXXXIII,CXXXXVI and as aphro-
disiac.LXXXIV Khory and Katrak described seeds as harmless when eaten but poi-
sonous when their paste is applied to open wounds.LXXXI Seeds’ paste is used as
rubefacient in sciatica, stiff shoulder and paralysis, and the seed oil is used in
removing scurf of the scalp, in prurigo, exuberant granulations and proliferating cell
growths.LXXVII,LXXXI Residents of Andaman Islands of India eat boiled seeds; the
seed proteins are rich in most essential amino acids, except for cystine and threonine
[44]. Roots are described as emetic, and used as a substitute of liquorice, and are
often sold in Indian bazaar as liquorice because when dried they resemble exactly like
liquorice. However, it bears little resemblance in qualities to liquorice.XXI,XL
Zulus use leaves decoction as a remedy for pain in the chest,XXX,CXXXV,CXXXXIX
and in Sri Lanka, the juice is taken as a blood purifier.XCIII Water extract of the root
is used to relieve obstinate cough,XXXV,LXXXIV and in Java, the root is considered
demulcent and antidiarrhetic.XXXVI A paste made of powdered seeds is used to
poison darts and arrows to kill animals. Wounds afflicted by such arrows are
generally fatal within 24 h. Seeds, seed hulls, and decorticated seeds have been
used for epitheliomas of the face, hand, mucosa, vagina and vulva and for warts on
the eyelids [20]. Chinese use seeds for dropsy, fever, headache, malaria, and
worms. Indo-Chinese use the plant for conjunctivitis, diarrhea, dysentery and
malaria. Malayans chew or drink leaves or roots decoctions for colics, colds or
cough. Indonesians use leaves for hoarseness and sore throat and sprue. West
Africans use leaves as CNS sedative, for conjunctivitis, constipation, cough, con-
vulsions, cancer, enteritis, hoarseness of voice, freckles, leucoderma, stomatitis,
spermatorrhea and syphilis; the root for chest complaints, gonorrhea, hookworm,
jaundice, pleurisy, rheumatism, sore throat and snakebite. West Indians use leaves
in teas for chest cold, cough, fever and flu, and the seeds for conjunctivitis and
worms.XI Tanzanian traditional healers use the plant to successfully treat cases of
epilepsy [36]. In Zimbabwe, the traditional healers use the plant to treat urinary
schistosomiasis, and a government research laboratory found the plant lethal to
adult schistosomes [35, 38]. Leaves are also used as a substitute for licorice for
Abrus precatorius L. 25

throat ailments in Dutch East Indies (Indonesia) and seeds are used for eye ailments
[24]. In East Africa, whole plant except the seeds, which are considered somewhat
toxic, is used. A decoction of leaves and roots is used as a remedy for gonorrhea; a
piece of uncooked root is chewed and at the same time the leaf decoction is
swallowed. Leaves relieve stomach troubles including dysentery, and the roots are
chewed as a remedy for snakebite and as aphrodisiac.LXXXV East Africans use seed
for gonorrhea and other venereal diseases.XXXVIII In Livingstone, a southern Pro-
vince of Zambia, the plant was utilized to treat HIV/AIDS-related infections during
the epidemic [10].
Phytoconstituents: Abrin, a glycoside, abraline and a small quantity of fatty oil
from seeds were isolated, and monoglycosidic anthraquinone was identified as
the coloring matter of the seed coat. Abrin A, B and C are major toxic proteins of
the seeds [32, 64]. Abrin contains two fractions—a globulin, and an albumose—the
former being a very powerful irritant that produces edema and echymosis at the site
of inoculation. Abrin A and abrin C are closely related and may have the same
mechanisms of toxic action [23]. Actions of abrin are very similar to those of ricin.
However, abrin, while less toxic than ricin, is much more severe irritant to the
conjunctiva than ricin. Seeds also contain abraline, abrine, abrussic acid, campe-
strol, 5b-cholanic acid, squalene, cycloartenol, precatorine, trigonelline, gallic acid
and hepaphorine.XC A biologically active flavonol glycoside was isolated from
seeds [66]. Root and leaves contain glycyrrhizin; no alkaloids were detected [5].
Five isoflavanquinones were isolated from the roots, and designated as abru-
quinones A, B, D, E and F [30], and Zore et al. reported four antibacterial com-
pounds from the roots, one showing a maximum 56% growth inhibition of S.
aureus A, as compared to ampicillin [67]. Two triterpenoid saponins isolated from
aerial parts are reported to possess anti-inflammatory activity [4]. Xiao et al. iso-
lated triterpinoid saponin, 3-O-b-D-glucopyranosyl-(1 ! 2)-b-D-glucopyranosyl
subprogenin D [65], and Hata et al. also isolated six triterpenoids: subprogenin D,
abrusgenic acid, triptotriterpenic acid B, abruslactone A, abrusogenin and abru-
soside C [22]. Isoflavanquinones, abruquinone G [31], and abruquinones J, K, and
L [21] were reported from aerial parts. Ghosh and Maiti [17] isolated an abrus
aglutinin from seeds, that showed immunomodulator and immunoadjuvant activity
both in native and heat denatured states. Four sweet-tasting (30–100 sweeter than
sucrose) triterpene glycosides, derivatives of abrusogenin were isolated by Choi
et al. [11].
Pharmacology: Oral administration of the petroleum ether, ether and water extracts
of the leaves in mice and rats did not show any antifertility activity; petroleum ether
seed extract showed antifertility activity but with significant toxicity [7]. Khanna et al.
also reported no significant inhibition of implantation in rats following administra-
tion of petroleum ether, alcohol, and water extracts of the plant [28]. However, the
petroleum ether and ether extracts of the root in rats prevented nidation; the ether
extract also showed antiestrogenic activity [3]. Desai and Rupawala [13] reported
100% antifertility activity when the petroleum ether extract (oil) of the seeds
(150 mg/rat) was administered orally for 20 days before mating, and a single oral
26 Abrus precatorius L.

dose of the steroidal oil in the postcoital period produced 80% sterility in rats. The oil
obtained from the white and red varieties of seeds orally administered in the dose of
1 g/kg for four days resulted in 94% and 84% fertility control, respectively [13].
Munshi et al. [37] reported absence of any antifertility activity in female rats at a daily
dose of up to 300 mg; however, it was one of the six shortlisted plants by the Central
Drug Research Institute of India with potentials for further study as antifertility agent
[26]. Bukhari et al. [8] reported that administration of one decorticated seed of white
variety daily for two days to Wistar rats of proven fertility resulted in 86% fertility
control; while the red seed in the same dose produced 63% fertility control. Sinha
observed oral administration of 50% ethanol seed extract (250 mg/kg) to albino rats
for 30 and 60 days induced a reversible absolute infertility in males, with sperm
motility suppression in the cauda epididymis as the most pronounced effect, but with
normal histologic and histocytometric findings in testes and parareproductive tissues
[56]. Similar results were obtained by Rao [47] who treated rats with alcohol seed
extract in a dose of 100 mg/kg body weight/day/rat for 60 days. Observations under
scanning electron microscope showed decapitation, acrosomal damage and forma-
tion of bulges on midpiece region of sperms from treated rats. Also, average number
of implantation sites in female rats significantly declined when mated with treated
rats. However, an apparent paradoxical increase in serum testosterone levels was
observed in treated rats. Methanol seed extract produced irreversible inhibition of
motility of washed human spermatozoa in a concentration-dependent manner.
Highest concentration (20 mg/ml) produced almost instant immotility and impaired
functional integrity of the plasma membrane and viability of spermatozoa [48]. Sinha
and Mathur reported degenerative changes in testicular weight, sperm count, latter
stages of spermatogenesis and Leydig cells in testes of rats treated with steroidal
fraction of the seeds [57]. The extract and seed oil are also reported to be uterotonic
[40, 41].
Aqueous raw seed extract exerts antibacterial effect on both Gram-positive and
Gram-negative bacteria, but the purified (detoxified) seeds are devoid of any bacte-
ricidal effect. However, chloroform extract of purified seeds exhibits variable
antibacterial effects [50]. Adelowotan et al. [2] reported S. aureus being the most
sensitive to leaf extract (MIC 8 ug/ml), while extract of the stem and seed oil are active
against S. aureus, S. epidermidis, B. subtilis, Cornybacterium spp. and C. albicans
but not against S. anginosus, E. faecalis and Gram-negative bacteria (E. coli,
K. pneumoniae, P. mirabilis, P. aeruginosa). Isoflavanquinone exhibited antituber-
cular, antiplasmodial and cytotoxic activities, while abruquinone G showed mild
antiviral and cytotoxic activities [31]. Extracts of stem and root are also reported lethal
to S. mansoni in very low concentrations [35], and orally administered crude extract of
aerial parts to hamsters infected with S. haematobium, was lethal to adult schisto-
somes [38]. Methanol seed extract also exhibits trypanocidal activity in mice [39], and
a methyl chloride/methanol extract of aerial parts produced strong antiprotozoal
activity against P. falciparum (98%), T. brucei rhodesiense (100%), and L. donovani
(76%) at a concentration of 10 µg/ml [22].
Reddy and Sirsi [49] first reported antitumor activity of a seed protein extract on
Yoshida sarcoma in rats and a fibrosarcoma in mice, due to its direct cytotoxic
Abrus precatorius L. 27

effect on tumor cells. The leaf extract exhibited a growth inhibitory effect by induc-
tion of apoptosis in MDA-MB-231 cells and reduced ROS formation [54]. Hexane,
ethyl acetate, ethanol and water extracts of leaves also showed strong antioxidant
activity and antiproliferative activity against various human cancer cell lines [18].
Abrin-A induces apoptosis in human cultured cell lines derived from acute lym-
phoblastic leukemia [42], and the abrus agglutinin (AAG) inhibits growth of
Dalton’s lymphoma ascites cells. Treatment of mice bearing Dalton’s lymphoma,
with both native and denatured AAG decreased tumor cell number and significantly
increased median survival time [16, 17]. Also, both intralesion and intraperitoneal
administration of abrin, in a sublethal dose of 7.5 µg/kg every alternate day for
10 days, reduced tumor mass development in mice induced by Dalton’s Lymphoma
Ascites and Ehrlich’s Ascites Carcinoma (EAC) cells. However, prophylactic admin-
istration of abrin was not effective [45]. An even smaller dose of 1.25 µg/kg for five
days to normal mice produced significant immunostimulation [46]. However, water
seed extract inhibited delayed hypersensitivity reaction in mice and increased
phagocytic index [60]. Simultaneous injection of sublethal doses of both abrin-A and
abrin-B, with EAC cells to mice inhibited tumor growth [32].
Three isoflavanquinones, abruquinones A, B and D isolated from the root, sig-
nificantly inhibited AA- and collagen-induced platelet aggregation. Abruquinones A,
B, D and F also showed significant anti-inflammatory and antiallergic effects [30], and
abruquinone A supressed polymyxin B-induced edema in both normal and adrenalec-
tomized mice, and histamine-, serotonin- and substance P-induced plasma extrava-
sation [63]. Methanol leaf extract significantly restored body weight, blood glucose,
and insulin levels of diabetic rats [61]. A curare-like effect is produced by the
ethanol extract of the leaves that reversibly inhibits ACh-induced contractions of toad
rectus abdominis and rat phrenic nerve-diaphragm muscle. The inhibitory effect on
rat phrenic nerve diaphragm is potentiated by reduced calcium or potassium and
increased magnesium ions. Similar effect was not duplicated with petroleum ether and
water extracts [62].
Mechanism of Action: Upregulation of p21 and p53 is suggested to be the likely
molecular mechanism of apoptosis by the leaf extract [54]. The cytotoxic agent,
abrin, is thought to be responsible for the antifertility activity.
Human A/Es, Allergy and Toxicity/Poisoning: Seeds cause dermatitis of unproven
type,CXXXV the juice irritates mucous membranes, and necklaces made of the pierced
seeds may induce contact dermatitis [34]. Abrin is an exceedingly poisonous phy-
totoxin, a potent lymphocyte mitogen [27] that can cause death depending on the
amount of seeds, thoroughly chewed and ingested. Symptoms of toxicity are at first
gastrointestinal, with hemorrhagic gastroenteritis, hemolysis, acute renal damage,
hepatotoxicity and temperature fluctuations, followed by incoordination and paraly-
sis. Many different tissues are found damaged during postmortum examination.
Livestock and humans are equally vulnerable.LXXXVIII Abrin causes endothelial cell
damage leading to increased capillary permeability with consequent fluid and protein
leakage and tissue edema [14].
28 Abrus precatorius L.

In August 1979, a case of poisoning due to jequirity bean was treated at the Cardial
Glennon Memorial Hospital for Children in St. Louis, Missouri [29], and another
poisoning with pulmonary edema and hypertension was reported from Sri Lanka
[15]. In an unusual poisoning incident, two patients presented with raised ICP and
papilledema, and one of them expired before effective treatment could be adminis-
tered, while the other recovered completely after conservative management to lower
ICP [58]. Another case of a 30-year-old previously healthy female was reported by
Sahni et al. [52], who presented with bloody diarrhea and in deep coma after eating
3–4 seeds. Brain MRI Scan showed evidence of acute demyelinating encephalitis
which led to patient’s death in three days. In a similar case, a 19-years old man, after
ingesting crushed seeds developed vomiting, abdominal pain and bloody diarrhea,
followed by convulsions and altered sensorium. Brain MRI Scan showed demyeli-
nation in bilateral medial temporal lobes. After supportive care and intravenous
methylprednisolone, the patient recovered completely without any residual effects
[53]. Demyelination is immune-mediated, and abrin is a known immunomodulator,
thus a possible immunologic pathogenic mechanism is involved. Another middle-
aged person survived after ingesting white seed variety, without any long-term
sequelae but after a long hospitalization [43]. An infusion of bruised seeds, when
applied to conjunctiva may cause a fatal poisoning due to absorption of abrin from
conjunctiva. A watery extract of bruised seeds, when dropped into the eyes produces
inflammation of the conjunctiva, edema of lids and ulceration of cornea; the face and
neck become swollen, and the maxillary glands enlarged.LXXXI,CXVII
Human Lethal Dose: Seeds are very toxic; less than one seed contains enough abrin
to kill an adult human. One chewed seed or 5 mg abrin may be fatal.C According to
another estimate human fatal dose of abrin is 0.1–1 µg/kg [14].
Animal Toxicity: Various doses of aqueous leaves extract administered to rats for
18-days decreased levels of PCV, Hb concentration, RBC and WBC counts, MCV,
and MC Hb, and increased levels of total serum protein, albumin, ALT, AST, ALP
and total bilirubin. Histologically, testicular degeneration was characterized by
decreased numbers of lining cells of the epithelium, as well as reduction in sperm
cells [1]. Intraperitoneal LD50 of ethanol leaves extract in mice was estimated as
more than 1,300 mg/kg body weight [59], and i.p. LD50 of purified abrin in mice
was 0.91 lg/kg [9]. Lethal doses of abrin-A and abrin-B causing death of mice
within 48 h are 10 and 25 µg/kg body weight, respectively. Abrin-A also agglu-
tinates human O-type erythrocytes at 0.8 µg/ml concentration, while abrin-B does
not show such activity [32].
Detoxification: In Ayurveda, seeds are used after a specific detoxification process,
called shodhana. For shodhana powdered seeds are tied in a muslin cloth, immersed
in cow’s milk and boiled for 6 h, cleaned, and the husk is removed. Barve and Ojha
[6] compared normal seed extract (chloroform:water; 5:95) and the detoxified seed
extract for chemical contents by TLC, and their relative efficacy and safety. Seeds
Abrus precatorius L. 29

detoxified with shodhana process lacked one spot on TLC compared to normal seed
extract and the processed seeds could be used up to a dose of 2 g/kg without toxicity.
However, both extracts were comparably effective for their hair growth activity.
Commentary: There are no clinical studies reported in English publications listed
on PubMed.

References
1. Adedapo AA, Omoloye OA, Ohore OG. Studies on the toxicity of an
aqueous extract of the leaves of Abrus precatorius in rats. Onderstepoort J
Vet Res. 2007;74:31–6.
2. Adelowotan O, Aibinu I, Adenipekun E, et al. The in-vitro antimicrobial
activity of Abrus precatorius (L) fabaceae extract on some clinical pathogens.
Niger Postgrad Med J. 2008;15:32–7.
3. Agarwal SS, Ghatak N Arora RB, et al. Antifertility activity of the roots of
Abrus precatorius, Linn. Pharmacol Res Commun. 1970;2:159–63.
4. Anam EM. Anti-inflammatory activity of compounds isolated from the
aerial parts of Abrus precatorius (Fabaceae). Phytomedicine. 2001;8:24–7.
5. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies on medicinal
plants of Sri Lanka. Part 14. Toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–35.
6. Barve KH, Ojha N. Effective detoxification of Abrus precatorius Linn.
seeds by Shodhana. J Ayurveda Integr Med. 2013;4:82–5.
7. Bhaduri H, Ghose CR, Bose AN, Moza BK, Basu UP. Antifertility activity
of some medicinal plants. Indian J Exp Biol. 1968;6:252–3.
8. Bukhari AQS, Shahnaz Ahmad, Qureshi S. Antifertility activity in medicinal
herbs. Pakistan J Pharmacol. 1986;3:13–9.
9. Chaturvedi K, Jadhav SE, Bhutia YD, et al. Purification and dose-dependent
toxicity study of abrin in swiss albino male mice. Cell Mol Biol (Noisy-
le-grand). 2015;61:36–44.
10. Chinsembu KC. Ethnobotanical study of plants used in the management of
HIV/AIDS-related diseases in Livingstone, Southern Province, Zambia.
Evid Based Complement Alternat Med. 2016;2016:4238625.
11. Choi YH, Hussain RA, Pezzuto JM, et al. Abrusosides A-D, four novel
sweet-tasting triterpene glycosides from the leaves of Abrus precatorius.
J Nat Prod. 1989;52:1118–27.
12. Crevost CH, Petelot A. Catalogue des Produits de L’Indo-chine. (Plantas
Medicinales). Bull Econ d L’Indo-Chine. 1934;37:340.
13. Desai RV, Rupawala EN. Antifertility activity of the steroidal oil of the seed
of Abrus precatorius Linn. Indian J Pharm. 1967;29:235.
14. Dickers KJ, Bradberry SM, Rice P, et al. Abrin poisoning. Toxicol Rev.
2003;22:137–42.
15. Fernando C. Poisoning due to Abrus precatorius (jequirity bean). Anesthe-
sia. 2001;56:1178–80.
30 Abrus precatorius L.

16. Ghosh D, Bhutia SK, Mallick SK, et al. Stimulation of murine B and T
lymphocytes by native and heat-denatured Abrus agglutinin. Immunobiol-
ogy. 2009;214:227–34.
17. Ghosh D, Maiti TK. Immunomodulatory and antitumor activities of native
and heat denatured Abrus agglutinin. Immunobiology. 2007;212:589–99.
18. Gul MZ, Ahmad F, Kondapi AK, et al. Antioxidant and antiproliferative
activities of Abrus precatorius leaf extracts—an in vitro study. BMC Com-
plement Altern Med. 2013;13:53.
19. Gupta AK, Tandon N (editors). Reviews on Indian medicinal plants, vol. 1.
New Delhi: ICMR; 2004. p. 18–25.
20. Hartwell JL. Plants used against cancer. A Survey. Lloydia. 1967–71;30.
21. Hata Y, Ebrahimi SN, De Mieri M, et al. Antitrypanosomal isoflavan
quinones from Abrus precatorius. Fitoterapia. 2013;93C:81–7.
22. Hata Y, Raith M, Ebrahimi SN, et al. Antiprotozoal isoflavan quinones from
Abrus precatorius ssp. africanus. Planta Med. 2013;79:492–8.
23. Herrmann MS, Behnke WD. A characterization of abrin A from the seeds of
the Abrus precatorius plant. Biochem Biophys Acta. 1981;667:397–410.
24. Hirschhorn HH. Constructing a phototherapeutic concordance based upon
Tropical American and Indonesian examples. J Ethnopharmacol. 1983;7:
157–67.
25. Holland JH. The useful plants of Nigeria. Kew Bull Add Ser. 1911;9:1–342.
26. Kamboj VP, Dhawan BN. Research on plants for fertility regulation in
India. J Ethnopharmacol. 1982;6:191–226.
27. Kaufman SJ, McPherson A. Abrin and hurin: two new lymphocyte mitogens.
Cell. 1975;4:263–8.
28. Khanna U, Garg SK, Vohra SB, et al. Antifertility screening of plants. II.
Effect of six indigenous plants on early pregnancy in albino rats. Indian J
Med Res. 1969;57:237–44.
29. Kinamore PA, Jaeger RW, de Castro FJ. Abrus and ricinus ingestion:
management of three cases. Clin Toxicol. 1980;17:401–5.
30. Kuo SC, Chen SC, Chen LH, et al. Potent antiplatelet, anti-inflammatory and
antiallergic isoflavanquinones from the roots of Abrus precatorius. Planta
Med. 1995;61:307–12.
31. Limmatvapirat C, Sirisopanaporn S, Kittakoop P. Antitubercular and antiplas-
modial constituents of Abrus precatorius. Planta Med. 2004;70:276–8.
32. Lin JY, Lee TC, Tung TC. Isolation of antitumor proteins abrin-A and
abrin-B from Abrus precatorius. Int J Pept Protein Res. 1978;12:311–7.
33. Malhi BS, Trivedi VP. Vagetable antifertility drugs of India. Quart J Crude
Drug Res. 1972;12:1922.
34. Mitchell JC, Rook AJ. Diagnosis of contact dermatitis from plants. Int J
Dermatol. 1977;16:257–66.
35. Mølgaard P, Nielsen SB, Rasmussen DE, et al. Anthelmintic screening of
Zimbabwean plants traditionally used against schistosomiasis. J Ethnophar-
macol. 2001;74:257–64.
Abrus precatorius L. 31

36. Moshi MJ, Kagashe GA, Mbwambo ZH. Plants used to treat epilepsy by
Tanzanian traditional healers. J Ethnopharmacol. 2005;97:327–36.
37. Munshi SR, Shetye TA, Nair RK. Antifertility activity of three indigenous
plant preparations. Planta Med. 1977;31:73–5.
38. Ndamba J, Nyazema N, Makaza N, et al. Traditional herbal remedies used
for the treatment of urinary schistosomiasis in Zimbabwe. J Ethnopharmacol.
1994;42:125–32.
39. Nwodo NJ, Nwodo OF. Antitrypanosomal potentials of the extract and
fractions of Abrus precatorius seeds. Asian Pac J Trop Med. 2012;5:857–61.
40. Nwodo OF, Botting JH. Uterotonic activity of extracts of the seeds of Abrus
precatorius. Planta Med. 1983;47:230–3.
41. Nwodo OF. Studies on Abrus precatorius seeds. I: Uterotonic activity of
seed oil. J Ethnopharmacol. 1991;31:391–4.
42. Ohba H, Moriwaki S, Bakalova R, et al. Plant-derived abrin-A induces apop-
tosis in cultured leukemic cell lines by different mechanisms. Toxicol Appl
Pharmacol. 2004;195:182–93.
43. Pillay VV, Bhagyanathan PV, Krishnaprasad R, et al. Poisoning due to white
seed variety of Abrus precatorius. J Assoc Physicians India. 2005;53:317–9.
44. Rajaram N, Janardhanan K. The chemical composition and nutritional
potential of the tribal pulse, Abrus precatorius L. Plant Foods Hum Nutr.
1992;42:285–90.
45. Ramnath V, Kuttan G, Kuttan R. Antitumour effect of abrin on transplanted
tumours in mice. Indian J Physiol Pharmacol. 2002;46:69–77.
46. Ramnath V, Kuttan G, Kuttan R. Immunopotentiating activity of abrin, a
lectin from Abrus precatorius Linn. Indian J Exp Biol. 2002;40:910–3.
47. Rao MV. Antifertility effect of alcoholic seed extract of Abrus precatorius
in male albino rats. Acta Europ Fertil. 1987;18:217–20.
48. Ratnasooriya WD, Amarasekera AS, Perera NS, Premakumara GA. Sperm
antimotility properties of a seed extract of Abrus precatorius. J Ethnophar-
macol. 1991;33:85–90.
49. Reddy VV, Sirsi M. Effect of Abrus precatorius L. on experimental tumors.
Can Res. 1969;29:1447–51.
50. Roy S, Acharya R, Mandal NC, et al. A comparative antibacterial evaluation
of raw and processed Guñjā (Abrus precatorius Linn.) seeds. Anc Sci Life.
2012;32:20–3.
51. Saha JC, Kasinathan S. Ecbolic properties of Indian medicinal plants. II.
Indian J Med Res. 1961;49:1094–8.
52. Sahni V, Agarwal SK, Singh NP, Sikdar S. Acute demyelinating encephalitis
after jequirity pea ingestion (Abrus precatorius). Clin Toxicol (Phila). 2007;
45:77–9.
53. Sahoo R, Hamide A, Amalnath SD, Narayana BS. Acute demyelinating
encephalitis due to Abrus precatorius poisoning—complete recovery after
steroid therapy. Clin Toxicol (Phila). 2008;46:1071–3.
32 Abrus precatorius L.

54. Shafi Sofi M, Sateesh MK, Bashir M, et al. Cytotoxic and proapoptotic
effects of Abrus precatorius L. on human metastatic breast cancer cell line,
MDA-MB-231. Cytotechnology. 2013;65:407–17.
55. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
56. Sinha R. Post-testicular antifertility effects of Abrus precatorius seed extract
in albino rats. J Ethnopharmacol. 1990;28:173–81.
57. Sinha S, Mathur RS. Effect of steroidal fraction of seeds of Abrus precatorius
Linn. on rat testes. Indian J Exp Biol. 1990;28:752–6.
58. Subrahmanyan D, Mathew J, Raj M. An unusual manifestation of Abrus
precatorius poisoning: a report of two cases. Clin Toxicol (Phila). 2008;46:
173–5.
59. Taur DJ, Patil RY. Mast cell stabilizing and antiallergic activity of Abrus
precatorius in the management of asthma. Asian Pac J Trop Med. 2011;4:
46–9.
60. Tilwari A, Shukla NP, Pathirissery UD. Immunomodulatory activity of the
aqueous extract of seeds of Abrus precatorius Linn (Jequirity) in mice.
Iran J Immunol. 2011;8:96–103.
61. Umamahesh B, Veeresham C. Antihyperglycemic and insulin secretagogue
activities of Abrus precatorius leaf extract. Pharmacognosy Res. 2016;8:
303–8.
62. Wambebe C, Amosun SL. Some neuromuscular effects of the crude extracts
of the leaves of Abrus precatorius. J Ethnopharmacol. 1984;11:49–58.
63. Wang JP, Hsu MF, Chang LC, et al. Inhibition of plasma extravasation by
abruquinone A, a natural isoflavanquinone isolated from Abrus precatorius.
Eur J Pharmacol. 1995;273:73–81.
64. Wei CH, Hartman FC, Pfuderer P, Yang WK. Purification and character-
ization of two major toxic proteins from seeds of Abrus precatorius. J Biol
Chem. 1974;249:3061–7.
65. Xiao ZH, Wang FZ, Sun AJ, et al. A new triterpenoid saponin from Abrus
precatorius Linn. Molecules. 2011;17:295–302.
66. Yadava RN, Reddy VM. A new biologically active flavonol glycoside from
the seeds of Abrus precatorius Linn. J Asian Nat Prod Res. 2002;4:103–7.
67. Zore GB, Awad V, Thakre AD, et al. Activity-directed-fractionation and
isolation of four antibacterial compounds from Abrus precatorius L. roots.
Nat Prod Res. 2007;21:838–45.
Abutilon indicum (Link) Sweet
(Malvaceae)

(Syns.: Sida asiatica L.; S. indica L.; S. populifolia Lam.)

Abstract
A plant of the tropics and subtropical regions, with fruits dentate like a comb. Juice
of its leaves and flowers is used in the treatment of bleeding, hematuria, bloody
piles, and to soothe dysuria in gonorrhoea, and is reputed in Ayurveda with Vata
dosha pacifying qualities that helps to treat diabetic neuropathy. Decoction of
leaves is used as gargle in toothache, diphtheria, tonsillitis and pharyngitis. In the
Philippines, leaves decoction is used for cleansing wounds and ulcers, and
for enemas or vaginal douche or lotions. Aqueous extract contains alkaloids,
flavonoids, tannins, glycosides, and saponins. Aqueous leaf extract has demon-
strated significant hypoglycemic effect in normal and moderately diabetic rats, and
offered protection against hepatotoxic agents in rats. Antidiabetic activity is
reported due to decreased absorption of glucose from intestines, increased insulin
secretion and activation of glucose transporter 1 (GLUT1) promoter activity.
Decoction of the plant alleviated symptoms of diabetic neuropathy in a randomized
controlled clinical trial.

Keywords





Abutilão Abutilone Atibalaa Darakht-e-shanah Fausse guimauve satinée





Indian marshmallow Indische schönmalve Kanghi Mo pan cao Takasago

ichibi

Vernaculars: Urd.: Kanghi; Hin.: Anter-vela, Kali kanghi, Kanghi, Kanghani; San.:
Atibalaa, Kankatika; Ben.: Balbij, Gungi-potari, Jhumka, Potari; Mal.: Ooram,
Petaka-putti, Uram, Velluram; Mar.: Madmi chakra-bhenda, Petaari; Tam.: Payrun-
tuthi, Thuththi, Thuthi, Tutti; Tel.: Duvvena benda, Duvvena kayalu, Nagu-benda,
Tutiri-chettu, Tutti, Tutturu-benda; Ara.: Khatmi hindi, Masht-el-ghoul; Chi.: 磨盘草,
Mo pan cao; Eng.: Indian abutilon, Indian marshmallow, Chinese bell flower, Country
mallow; Fre.: Fausse guimauve satinée, Guimauve, Herbe de douze heures, Mauve du
pays; Ger.: Indische schönmalve; Gre.: Avutilon to indikon; Ita.: Abutilone, Fiore di
© Springer Nature Switzerland AG 2020 33
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_4
34 Abutilon indicum (Link) Sweet

dodici ore; Jap.: Takasago ichibi; Per.: Darakht-e-shanah; Por.: Abutilão (Brazil),
Abutilo; Rus.: Kanatnik indijskij; Spa.: Botón de oro, Malva amarilla; Tag.:
Giling-giliñgan, Kuakuakohan, Málbas, Mális, Márbas, Málbas-kastila, Mélbas,
Tabing; Tha.: Khrop chak krawaan; Vie.: Cây cối xay, Cối xay.
Description: A plant found in the tropics and subtropical regions of India and Sri
Lanka, is up to one m high with oval leaves serrated like that of cotton plant, with
yellow flowers, and the fruits dentate like a comb [5]. The bark is described as thin,
tough, striped and fibrous, cinnamon-colored externally, and covered with silky,
hoary tomentum, with bitter and astringent taste. Seeds are dull brown, reniform,
resembling cardamom seeds, and mucilaginous (Figs. 1 and 2).LXXXI
Actions and Uses: The plant leaves (temperament, hot 2° and dry 2°) are regarded
in Unani medicine to possess astringent, styptic, diuretic, antiseptic, analgesic and
resolvent properties. Juice of the leaves and flowers is used in the treatment of
bleeding, hematuria, bloody piles, and to soothe dysuria in gonorrhea, and the
decoction of leaves as gargle in toothache, diphtheria, tonsillitis and pharyngi-
tis.LXXVII Leaves have also been described as demulcent, aphrodisiac, laxative,
diuretic, and sedative; the root as diuretic,CV and the bark as astringent, diur-
etic,LXXXI,CV cooling, and used in the treatment of gonorrhea and strangury.LXXXI
In Ayurveda, the diabetic neuropathy symptoms like paraesthesiae, pain and tin-
gling sensation are indicative of Vata and Pitta dosha involvement, and the plant,
Atibala, is reputed with Vata dosha pacifying qualities [9]. It is used in traditional
medicine of Pakistan for its analgesic, anthelmintic, hepatoprotective, and hypo-
glycemic properties [17]. Traditional Siddha medical practitioners in Tamil Nadu
State of India use it for the treatment of hemorrhoids [3, 8]. In the Philippines,
leaves decoction is used for cleansing wounds and ulcers, and for enemas or vaginal
douche or lotions.CXVII Guerrero (1921)LVI says an emollient decoction of the
leaves is used by Filipinos as a diuretic, sedative and aphrodisiac. The plant is also

Fig. 1 Abutilon indicum, Flower, B.navez, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Abutilon_indicum_flower.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Abutilon indicum (Link) Sweet 35

Fig. 2 Abutilon indicum, Fruits, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:ABUTILON_INDICUM.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

reported to accumulate cadmium from the soil and is suggested as a prospective

means for phytoremediation of heavy metal-contaminated soils [16].
Phytoconstituents: Aqueous extract contains alkaloids, flavonoids, tannins, gly-
cosides, and saponins [5]. Abutilin A and (R)-N-(1′-methoxy-carbonyl-2′-pheny-
lethyl)-4-hydroxy-benzamide were isolated from the whole plant [6], and the
petroleum ether extract exhibited mosquito larvicidal effect, leading to identification
of b-sitosterol as the active agent [1]. Seven flavonoids: luteolin, chrysoeriol, luteolin
7-O-b-glucopyranoside, chrysoeriol 7-O-b-glucopyranoside, apigenin 7-O-b-gluco-
pyranoside, quercetin 3-O-b-glucopyranoside, and quercetin 3-O-a-rhamnopyran-
osyl (1 ! 6)-b-glucopyranoside were isolated from flowers [7].
Pharmacology: Both alcohol and aqueous leaves extracts show significant hypo-
glycemic effect in normal rats [13], and the aqueous extract of the whole plant also
significantly reduced plasma glucose in moderately diabetic rats, and at a faster rate
than glibenclamide [5]. Aqueous extract was protective against CCl4- and parac-
etamol (APAP)-induced hepatotoxicity in rats [11, 12]. Ethanol extract of the whole
plant produced significant anti-inflammatory activity, comparable to ibuprofen [15],
and Ahmed et al. [2] identified eugenol [4-allyl-2-methoxyphenol] as the active
principle for its significant analgesic activity. Various extracts of aerial parts and
roots exhibited significant antioxidant/radical scavenging activity [17]. Antioxidant
activities of various extracts were not significantly correlated with the total phenol
and flavonol contents, rather to the type of phenolic compound present, and ethyl
acetate extract showed the maximum free radical scavenging activity [14]. Aqueous
leaves extract is devoid of any antibacterial activity; however, the ethanol extract
36 Abutilon indicum (Link) Sweet

was significantly effective against B. subtilis, S. aureus, K. pneumoniae, P. aerug-

inosa, E. coli and S. typhi, and the chloroform extract showed weaker activity [10].
Clinical Studies: In an RCT, a decoction of 10 g plant twice daily for 30 days to
patients with diabetic neuropathy diminished sensory perception and significantly
reduced the neuropathy symptoms like paraesthesiae, pain and tingling sensation [9].
Mechanism of Action: Aqueous extract reduced glucose absorption from intesti-
nes, increased insulin secretion from isolated pancreatic b-cells [5], and activated
glucose transporter 1 (GLUT1) promoter activity [4].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: LD50 of the aqueous extract is reported to be more than 4,000
mg/kg body weight [12].
Commentary: Clinical study reporting improvement in diabetic neuropathy
symptoms by the decoction deserves further corroborating studies, in addition to its
antidiabetic potentials.

References
1. Abdul Rahuman A, Gopalakrishnan G, Venkatesan P, Geetha K. Isolation
and identification of mosquito larvicidal compound from Abutilon indicum
(Linn.) Sweet. Parasitol Res. 2008;102:981–8.
2. Ahmed M, Amin S, Islam M, Takahashi M. Analgesic principle from Abutilon
indicum. Pharmazie. 2000;55:314–6.
3. Chellappandian M, Mutheeswaran S, Pandikumar P, Duraipandiyan V,
Ignacimuthu S. Quantitative ethnobotany of traditional Siddha medical
practitioners from Radhapuram taluk of Tirunelveli District, Tamil Nadu,
India. J Ethnopharmacol. 2012;143:540–7.
4. Krisanapun C, Lee SH, Peungvicha P, Temsiririrkkul R, Baek SJ. Antidia-
betic activities of Abutilon indicum (L.) sweet are mediated by enhancement
of adipocyte differentiation and activation of the GLUT1 promoter. Evid
Based Complement Alternat Med. 2011;167684.
5. Krisanapun C, Peungvicha P, Temsiririrkkul R, Wongkrajang Y. Aqueous
extract of Abutilon indicum Sweet inhibits glucose absorption and stimulates
insulin secretion in rodents. Nutr Res. 2009;29:579–87.
6. Kuo PC, Yang ML, Wu PL, et al. Chemical constituents from Abutilon
indicum. J Asian Nat Prod Res. 2008;10:699–703.
7. Matławska I, Sikorska M. Flavonoid compounds in the flowers of Abutilon
indicum (L.) Sweet (Malvaceae). Acta Pol Pharm. 2002;59:227–9.
8. Pandikumar P, Chellappandian M, Mutheeswaran S, Ignacimuthu S. Consen-
sus of local knowledge on medicinal plants among traditional healers in
Mayiladumparai block of Theni District, Tamil Nadu, India. J Ethnopharma-
col. 2011;134:354–62.
Abutilon indicum (Link) Sweet 37

9. Patel K, Patel M, Gupta SN. Effect of Atibalamula and Bhumyamalaki on

thirty-three patients of diabetic neuropathy. Ayu. 2011;32:353–6.
10. Poonkothai M. Antibacterial activity of leaf extract of Abutilon indicum.
Anc Sci Life. 2006;26:39–41.
11. Porchezhian E, Ansari SH. Effect of liquid extract from fresh Abutilon indicum
leaves and Allium cepa bulbs on paracetamol and carbon tetrachloride induced
hepatotoxicity. Pharmazie. 2000;55:702–3.
12. Porchezhian E, Ansari SH. Hepatoprotective activity of Abutilon indicum on
experimental liver damage in rats. Phytomedicine. 2005;12:62–4.
13. Seetharam YN, Chalageri G, Setty SR. Bheemachar: hypoglycemic activity
of Abutilon indicum leaf extracts in rats. Fitoterapia. 2002;73:156–9.
14. Srividya AR, Dhanabal SP, Jeevitha S, Varthan VJ, Kumar RR. Relation-
ship between antioxidant properties and chemical composition of Abutilon
indicum Linn. Indian J Pharm Sci. 2012;74:163–7.
15. Tripathi P, Chauhan NS, Patel JR. Anti-inflammatory activity of Abutilon
indicum extract. Nat Prod Res. 2012;26:1659–61.
16. Varun M, Jaggi D, D’Souza R, Paul MS, Kumar B. Abutilon indicum L.: a
prospective weed for phytoremediation. Environ Monit Assess. 2015;187:527.
17. Yasmin S, Kashmiri MA, Asghar MN, Ahmad M, Mohy-ud-Din A. Antioxi-
dant potential and radical scavenging effects of various extracts from
Abutilon indicum and Abutilon muticum. Pharm Biol. 2010;48:282–9.
Acacia catechu Oliver
(Fabaceae/Leguminosae)

(Syns.: A. sundra (Roxb.) Bedd.; A. wallichiana DC. Mimosa catechuoides Roxb.)

Abstract
The tree is native to India, Sri Lanka, Malabar and Singapore. Kattha is prepared by
boiling the wood in water and then evaporating the brew; the resultant hard material
is powdered and chewed with betel leaves and lime with or without tobacco by a
large number of the people of Indian subcontinent as an addictive psychostimu-
lating and euphoria-inducing formulation. It is a powerful astringent used to treat
loosened teeth, as a gargle in sore throat and hoarseness of voice, and in stomatitis
and diarrhea, and its powder is sprinkled on wounds and injuries. It also kills
intestinal worms, and is beneficial in intestinal ulcers, colic, diarrhea, and prevents
spermatorrhea. In Ayurveda, the dried heartwood is used in kustha, vrana, śotha,
and prameha. It is a rich source of catechin and epicatechin (gallic acid derivatives),
and small amounts of flavonoids. It is reported to possess antibacterial, antifungal,
anti-inflammatory, tissue protectant, antihyperglycemic, antineoplastic, antidiar-
rheal, analgesic, and antipyretic activities. Its aqueous extract significantly increases
phagocytic index, and protects against CP-induced neutropenia and increases serum
immunoglobulin levels. Significant hypoglycemic effect of methanol extract
against glucose-induced hyperglycemia and antinociceptive activity against acetic
acid-induced gastric pain in mice have been reported. Methanol extract is also
protective against iron overload-induced liver damage. The hypotensive effect of
the aqueous extract is suggested to be bradykinin-related.

Keywords



Acacia catecú Bālapatra Cachoutier Catechu

Dantadhāvana
Erh-cha





Katechu-akazie Kattha Khair Sunt kāshū

Vernaculars: Urd.: Kattha; Hin.: Kattha, Kera-sara, Khair, Dant-dhavan, Gayatrin,

Kagli, Madan; San.: Bālapatra, Dantadhāvana, Gāyatri, Khadira-sara, Pathi drum,
Payor, Raktasarā; Ben.: Khair, Khayar, Khayer (khaẏer), Khera, Khoyer, Kuth; Mal.:

© Springer Nature Switzerland AG 2020 39

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_5
40 Acacia catechu Oliver

Gambia, Kachu, Kadaram, Khadiram; Mar.: Kaderi, Khaderi, Khadir, Khair, Yaj-
navrksa; Tam.: Baga, Cenkarungali, Kacukkatti, Kadiram, Kalu, Kamugu,
Karan-galli, Kashketti, Kasku-kutta, Voadalam, Wodalai, Wothalay; Tel.: Chandra,
Kanchu, Kaviricandra, Khadiramu, Mallasandra, Podalimanu, Pogamu, Sandra, Sun-
dra; Ara.: Sunt kāshū; Bur.: Mung-ting, Nya; Chi.: 儿茶, Erh-cha, He xian yao
(Taiwan); Dan.: Katechu akacie; Dut.: Cachou, Cachouboom; Eng.: Black catechu,
Black cutch, Catechu, Cutch tree; Fre.: Acacia à cachou, Cachoutier; Ger.: Gerber-
akazie, Katechu-akazie, Katechubaum; Ita.: Acacia catecu; Jap.: Peguasenyaku, Pegu
no ki; Maly.: Pinang; Nep.: Khayar; Per.: Kaat; Por.: Seringueira; Rus.: Akatsiia
katexinskaia, Akatsiia katexu; Sin.: Katu andara, Ratkihiri; Spa.: Acacia catecú; Swe.:
Katechuakacia; Tha.: Gra thin thaeht, Sa jaeh, See siiat gaen, Seesiat nua.
Description: The tree is native to India, Sri Lanka, Malabar and Singapore. Tree
bark rough, externally of a dark-brown color, smooth and reddish within. In some
specimens, the bark is smooth, of a yellowish color; external surface here and there
denuded of its epidermis, tastes highly astringent. Catechu is a chocolate-colored
extract prepared by making a decoction of heartwood, straining and finally evap-
orating to the consistency of jaggary and pouring into clay moulds. Similar product
is obtained by boiling water from the unripe pods and twigs (Figs. 1 and 2).LXXXI

Fig. 1 Acacia catechu, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wikime-
diaCommons, https://commons.wikimedia.org/wiki/File:Acacia_catechu_-_K%C3%B6hler%E2%
80%93s_Medizinal-Pflanzen-003.jpg
Acacia catechu Oliver 41

Fig. 2 Acacia catechu, Plant with Flowers, J.M. Garg, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Khair_(Acacia_catechu)_
flowers_at_Hyderabad,_AP_W_IMG_7261.jpg; https://creativecommons.org/licenses/by-sa/3.0/
deed.en

Actions and Uses: Kattha, known as ‘Khoyer’ in Bangladesh, is prepared by boiling

the wood in water, and then evaporating the brew. The resultant hard material is
powdered and chewed with betel leaves and lime with or without tobacco by a large
number of the people of Indian subcontinent as an addictive psychostimulating and
euphoria-inducing formulation [15]. Unani physicians assign the temperament of cold
2° and dry 2° to it; Chinese also regard it cold in property.CLV It is a powerful astringent
used as treatment for loosened teeth, as a gargle in sore throat and hoarseness of voice;
its powder is used in stomatitis and diarrhea, and also on wounds and injuries.LXXVII
GhaniL adds that it kills intestinal worms, and is beneficial in intestinal ulcers, colic,
and diarrhea, and prevents spermatorrhea. It is used in diarrhea alone or in combination
with cinnamon or opium;CV in ulceration of the gums, sore throat and toothache; it also
possesses antiseptic properties and is used in passive hemorrhage [2]. In Ayurveda, the
dried heartwood is used in kustha, vrana, śotha, and prameha.LIX Powerful astringent
to the mucous membranes, stronger than kino, antiperiodic and digestive; this action is
due to the tannic acid it contains. It is used in the treatment of dyspepsia attended with
pyrosis; and also, in diarrhea in children, in dysentery, intermittent fever and scurvy;
locally, as a dusting powder to hypertrophied relaxed tonsils, in ulcerated and spongy
gums as a gargle, and as an injection in leucorrhea. The ointment is used in chancers,
sores or cracked nipples, eczematous eruptions on the skin, and also on leprous
indurated ulcers. Its powder is used as snuff in epistaxis.LXXXI
Phytoconstituents: Aqueous extract of heartwood is a rich source of catechin and
epicatechin (gallic acid derivatives), and smaller amounts of flavonoids [20]. Phenolic
compounds, 5-hydroxy-2-[2-(4-hydroxyphenyl) acetyl]-3-methylbenzoic acid,
(2S,3S)-3,7,8,3′,4′-pentahydroxyflavane, rhamnetin, 4-hydroxyphenyl ethanol, 3,3′,
5,5′,7-pentahydroxyflavane, and fisetinidol have been reported [9]. Li et al. [8]
42 Acacia catechu Oliver

reported the presence of 4-hydroxybenzoic acid, kaempferol, quercetin, 3,4′,7-

trihydroxyl-3′,5-dimethoxyflavone, catechin, epicatechin, epiafzelechin, afzelechin,
mesquitol, ophioglonin, aromadendrin and phenol. Bark contains astrin, catechin,
catechuannic acid, and tannin; wood contains DL-catechins and l-epicatachin.XXI
Pharmacology: It is reported as antibacterial, antifungal, anticancer and hypogly-
cemic [2]. Animal studies and cell culture systems have shown anti-inflammatory,
tissue protectant, antineoplastic, antihyperglycemic, antidiarrheal, analgesic, and
antipyretic activities [20]. Its hypoglycemic activity in normal rats was first reported
by Singh et al. [19]. Recently, significant hypoglycemic effect of methanol extract
against glucose-induced hyperglycemia and antinociceptive activity against acetic
acid-induced gastric pain in mice have been reported [15]. Methanol extract also
caused significant cytotoxicity to human breast adenocarcinoma cells (MCF-7) by
inducing apoptosis [3]. (+)-Catechin-rich aqueous extract significantly decreased
tumor burden of DMBA-induced mammary carcinoma in Balb/c mice, and signifi-
cantly reversed tumor markers and antioxidant system [12], produced growth inhi-
bition of human epithelial carcinoma cell line and significantly decreased DMBA/
TPA-induced skin carcinoma in Balb/c mice to 30% compared to 100% in untreated
control mice [13], and protected against DMBA-induced hepatocellular carcinoma in
Balb/c mice. Tumor incidence in extract-treated mice was 37.5%, compared to 100%
in untreated control mice with reduced liver injury and restored tumor markers levels
[11]. Ethyl acetate extract fraction also reversed DMBA-induced hepatotoxicity by
modulating phase I, II and antioxidative enzymes [7]. Aqueous extract exhibits sig-
nificant effects on both cell-mediated and humoral immunity, as it increases phago-
cytic index, and protects against CP-induced neutropenia and increases serum
immunoglobulin levels [6]. Methanol extract was also protective against iron
overload-induced liver damage [5], and ethyl acetate fraction of methanol extract
exhibited highest antioxidant property [4]. Methanol bark extract also protected
against B(a)P-induced lung toxicity in mice, and improved activities of detoxifying
enzymes [17].
Intravenous injection of aqueous extract produced hypotensive effect in both
dogs and rats, not antagonized by histamine, a- and b-adrenoceptor and cholinergic
receptor blockers, and captopril significantly potentiated the duration of hypoten-
sive effect. The extract was more effective in relaxing vasopressin preconstricted rat
tail arteries than the methoxamine preconstricted ones. Thus, the hypotensive effect
of the extract could be bradykinin-related [18]. Methanol extract showed antimi-
crobial activity against B. subtilis, S. aureus, S. typhi, E. coli, P. aeruginosa and
C. albicans; with activity decreasing during purification [14], and moderate activity
against MDR S. typhi [16]. Ethanol extract was active against enterohemorrhagic
E. coli strains, including E. coli O157:H7 [21], and Micucci et al. [10] reported it
active against C. jejuni, E. coli, and Salmonella spp.
Mechanism of Action: Increased Bax/Bcl-2 ratio results in the activation of
caspase-cascade leading to apoptosis of MCF-7 cells [3].
Acacia catechu Oliver 43

Human A/Es, Allergy and Toxicity: It decreases libido and may cause kidney
stones.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential Drug-Herb Interactions: Pretreatment of rabbits with
kattha (A. catechu) for seven days increased the maximum blood concentration of
theophylline, possibly due to inhibition of CYP1A and P-glycoprotein activity [1].
Commentary: Despite being extensively used as a psychostimulant in the Indian
subcontinent, there are no clinical studies reported in the mainstream English
publications listed on PubMed. It should also be a good candidate for further
anticancer and hepatoprotective studies.

References
1. Al-Mohizea AM, Raish M, Ahad A, Al-Jenoobi FI, Alam MA. Pharma-
cokinetic interaction of Acacia catechu with CYP1A substrate theophylline
in rabbits. J Tradit Chin Med. 2015;35:588–93.
2. Dhar ML, Dhar MM, Dhawan BN, et al. Screening of Indian plants for
biological activity: I. Indian J Exp Biol. 1968;6:232–47.
3. Ghate NB, Hazra B, Sarkar R, et al. Heartwood extract of Acacia catechu
induces apoptosis in human breast carcinoma by altering bax/bcl-2 ratio.
Pharmacogn Mag. 2014;10:27–33.
4. Guleria S, Tiku AK, Singh G, et al. Antioxidant activity and protective
effect against plasmid DNA strand scission of leaf, bark, and heartwood
extracts from Acacia catechu. J Food Sci. 2011;76:C959–64.
5. Hazra B, Sarkar R, Ghate NB, et al. Study of the protective effects of Katha
(heartwood extract of Acacia catechu) in liver damage induced by iron
overload. J Environ Pathol Toxicol Oncol. 2013;32:229–40.
6. Ismail S, Asad M. Immunomodulatory activity of Acacia catechu. Indian J
Physiol Pharmacol. 2009;53:25–33.
7. Kumar R, Kaur R, Singh AP, et al. Diminution of hepatic response to 7,
12-dimethylbenz (a)anthracene by ethyl acetate fraction of Acacia catechu
Willd. through modulation of xenobiotic and antioxidative enzymes in rats.
PLoS One. 2014;9:e90083.
8. Li X, Wang H, Liu C, Chen R. Chemical constituents of Acacia catechu.
Zhongguo Zhong Yao Za Zhi. 2010;35:1425–7 (Article in Chinese).
9. Li XC, Liu C, Yang LX, et al. Phenolic compounds from the aqueous
extract of Acacia catechu. J Asian Nat Prod Res. 2011;13:826–30.
10. Micucci M, Gotti R, Corazza I, et al. Newer insights into the antidiarrheal
effects of Acacia catechu Willd. extract in guinea pig. J Med Food.
2017;20:592–600.
44 Acacia catechu Oliver

11. Monga J, Chauhan CS, Sharma M. Chemopreventive efficacy of (+)-

catechin-rich aqueous extract of Acacia catechu Willd. heartwood against
7,12-dimethylbenz[a]anthracene-induced hepatocarcinoma in Balb/c mice.
J Environ Pathol Toxicol Oncol. 2012;31:313–23.
12. Monga J, Chauhan CS, Sharma M. Human breast adenocarcinoma cytotox-
icity and modulation of 7,12-dimethylbenz[a]anthracene-induced mammary
carcinoma in Balb/c mice by Acacia catechu (L.f.) Wild. heartwood. Integr
Cancer Ther. 2013;12:347–62.
13. Monga J, Chauhan CS, Sharma M. Human epithelial carcinoma cytotoxicity
and inhibition of DMBA/TPA induced squamous cell carcinoma in Balb/c
mice by Acacia catechu heartwood. J Pharm Pharmacol. 2011;63:1470–82.
14. Negi BS, Dave BP. In vitro antimicrobial activity of Acacia catechu and its
phytochemical analysis. Indian J Microbiol. 2010;50:369–74.
15. Rahmatullah M, Hossain M, Mahmud A, et al. Antihyperglycemic and
antinociceptive activity evaluation of ‘khoyer’ prepared from boiling the
wood of Acacia catechu in water. Afr J Tradit Complement Altern Med.
2013;10:1–5.
16. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi. Phy-
tother Res. 2004;18:670–3.
17. Shahid A, Ali R, Ali N, et al. Methanolic bark extract of Acacia catechu
ameliorates benzo(a)pyrene induced lung toxicity by abrogation of oxidative
stress, inflammation, and apoptosis in mice. Environ Toxicol. 2017;32:
1566–77.
18. Sham JSK, Chiu KW, Pang PKT. Hypotensive action of Acacia catechu.
Planta Med. 1984;177–80.
19. Singh KN, Mittal RK, Barthwal KC. Hypoglycaemic activity of Acacia
catechu, Acacia suma, and Albizzia odoratissima seed diets in normal albino
rats. Indian J Med Res. 1976;64:754–7.
20. Stohs SJ, Bagchi D. Antioxidant, anti-inflammatory, and chemoprotective
properties of Acacia catechu heartwood extracts. Phytother Res. 2015;29:
818–24.
21. Voravuthikunchai SP, Limsuwan S. Medicinal plant extracts as anti-
Escherichia coli O157:H7 agents and their effects on bacterial cell aggregation.
J Food Prot. 2006;69:2336–41.
Acacia nilotica (L.) Delile.
(Fabaceae/Leguminosae)

(Syns.: A. arabica (Lam.) Willd.; A. vera Willd.; A. scorpioides W. Wight; Mimosa

arabica Lam.; M. nilotica L.; M. scorpioides L.; Vachellia nilotica (L.) P.J.H. Hurter
& Mabb.)

Abstract
The translucent gum of a tropical shrub, found throughout tropical Africa, India,
Iraq, and West Indies, is chiefly composed of calcium, magnesium and potassium
salts of polysaccharides. It has been used for centuries in traditional medicines, by
Egyptians and other Arab physicians. British Pharmacopoeia describes gum
acacia as a source of useful medicaments. Gum Arabica is very brittle, nearly
scentless and bland in taste; soluble in water and insoluble in alcohol, ether and
oils. The gum is ascribed astringent, demulcent, emollient, antiseptic, tonic and
nutritive properties, and is used for irritated conditions of mucous membranes,
such as cough, sore throat, chronic bronchitis, diarrhea, dysentery, leucorrhea,
cystitis, urethritis, gonorrhea, burns, sore nipples, inflammations and nodular
leprosy. It is primarily indigestible in humans, and extensively used as food
additive. Chief use of the gum in pharmacy is as an emulsifying agent to suspend
insoluble powders in aqueous mixtures, and as a binding agent to make pills and
tablets specially cough drops and lozenges. It is commonly employed as a
demulcent in preparations designed to treat diarrhea, dysentery, coughs, sore
throat and fevers. A paste of the gum with egg white is applied in conjunctivitis,
and is also reported to be useful as food for diabetic patients. Pounded tender
leaves into a pulp are also administered in dysentery and diarrhea; the leaves
decoction used as gargle is useful in spongy gums and relaxed sore throat, and to
wash hemorrhagic ulcers and wounds. Decoction of leaves and pods is dried and
made into tablets, and is known as Aqaqia. Gentamicin-induced nephrotoxicity in
rats was significantly ameliorated by pretreatment and concomitant treatment
with gum Arabic, in part, due to reduced oxidative stress. Gum Arabic is reported
clinically useful in cases of chronic renal disease, especially the End-Stage Renal
Disease (ESRD) requiring renal dialysis; and, administration of gum Arabic is
also reported to decrease TC and LDL-C in mild hypercholesterolemia.

© Springer Nature Switzerland AG 2020 45

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_6
46 Acacia nilotica (L.) Delile.

Keywords





Acacia du Sénégal Ägyptische akazie Aqaqia Babool Bablah Gum Arabica






Jiao shu Kinkirāta Samagh-e-Arabi Umm-e-gheelan

Vernaculars: Urd.: Aqaqia, Babool, Samagh-e-Arabi; Hin.: Babool, Keekar, Kikar;

San.: Babbūla, Barbūra, Kala-babal, Kinkirāta, Mālāphala, Pitapuspa, Sūksmapatra,
Vabbula, Yugmakanta; Ben.: Babala, Babla (Bāblā), Babool; Mal.: Babola, Babul,
Kalababli, Karivelam, Karuvelum; Mar.: Babhul, Babli, Tamra-gond, Vedibabul;
Tam.: Karu-vael, Karuve (karuvē), Karuvel, Karuvelam, Karuvelamaram; Tel.: Bar-
baramu, Barburamu, Nalla-umona, Nallatumma, Thumma chettu, Tumma, Tumma
bamka; Ara.: Akasia alnil, Al samgh al’ arabi (gum), Aqaqia (extract), Mughilan,
Sunt, Umm-e-gheelan; Chi.: 阿拉伯金合欢, A la bo jin he huan, Jiao shu, Tsung;
Dut.: Babul, Echte acacia, Gom-acacia; Eng.: Acacia gum, Gum Arabica, Gum
Senegal; Fre.: Acacia à gomme, Acacia du Nil, Acacia du Sénégal, Acacia nilotique,
Gommier rouge; Ger.: Ägyptische Akazie, Ägyptischer Schotendorn, Arabische Gum-
miakazie; Gre.: Akakia i arabiki; Ita.: Acacia arabica; Jap.: Arabia akashia, Arabia
gomu modoki; Per.: Kharo, Kare-mughilan, Mugheelan; Por.: Acácia-egípcia; Rus.:
Akatsiia arabiiskaia, Akatsiia nilotika, Akatsiia nil’skaia; Sen.: Red gum; Sin.: Baab-
ulu, Katu kihiri; Spa.: Acacia arábiga, Acacia de Egipto, Acacia gomifera, Espino
egipcio Swe.: Bablah, Gummiakacia; Tag.: Sibuyas.
Description: A tropical shrub or flat-topped tree, found throughout tropical Africa,
India, Iraq, and West Indies; up to 9 m high but usually less than 4.5 m with short
trunk, and pale, fissured and flaking bark. A translucent gum accumulates in the
cambium and exudes from cracks or wounds in the bark. The flexuous branches bear
sharp thorns 7 mm long, grouped in 3s on the enlarged nodes; the central thorn being
slightly recurved. Leaves are deciduous, bi-pinnately compound. Flower buds and
flowers are bright golden-yellow in color, solitary or in 2s or 3s, usually emerging
before the new leaves, that are ivory white in dense spikes. Fruit is a flat, papery seed
pod, brown, pubescent, oblong, 20 to 25 mm wide and 4 to 12.5 mm long, con-
taining 1 to 6 greenish-brown, disk-like seeds. Pods do not split open. The tree is said
to produce seeds at five years intervals.III,XXIX,XXXII,XLI
Gum exudate from the bark hardens on exposure to air into globular or angular
‘tears’, up to 4 cm wide, white, yellowish or pinkish in color. Gum from wild trees is
usually darker than that from cultivated trees. It is very brittle, nearly scentless and
bland in taste; soluble in water and insoluble in alcohol,IV,C ether and oils.CXI Gum
Arabica is a branched chain complex polysaccharide, primarily indigestible in
humans, and extensively used as food additive [7, 42]. Most of the gum Arabica used
commercially comes from A. senegal and various pharmacological studies reported
here were carried out on gum Arabica obtained from this source (Figs. 1, 2 and 3).
Acacia nilotica (L.) Delile. 47

Fig. 1 Acacia nilotica, Tree in Bloom, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Babool_(Acacia_nilotica)_flowers_at_
Hodal_W_IMG_1248.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Acacia nilotica, Flowers, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA 3.0, https://commons.wikimedia.org/wiki/Category:Acacia_nilotica#/media/File:Babool_
(Acacia_nilotica)_flowers_at_Hodal_W_IMG_1163.jpg; https://creativecommons.org/licenses/
bysa/ 3.0/deed.en

Actions and Uses: Gum acacia has been used for centuries in traditional medicines.
Egyptians and other Arab physicians used it extensively to treat a wide variety of
ailments and therefore it is also known as Samagh-e-Arabi. It is still an important
constituent of many pharmaceutical products of the traditional medicines of various
developing countries. However, the modern uses of gum acacia in pharmaceutical
industry are confined to as a demulcent in cough mixtures and as stabilizer in
emulsions. The bark of this and several other Acacia species is used in India to
48 Acacia nilotica (L.) Delile.

Fig. 3 Acacia nilotica, Gum, Prof. Akbar, Original

prepare spirit from sugar and palm juice by precipitating the albuminous substances
in the liquor and facilitating fermentation.XL Ibn al-BaitarLXIX mentioned that this
tree is mainly found in Hijaz region of Arabia, and referring to Avicenna says, it is
beneficial in bleeding. In Unani medicine, the leaves, flowers, legumes, and bark are
regarded cold 2° and dry 2° in temperament, while the gum is considered moderate;
the gum is ascribed astringent, demulcent, emollient, antiseptic, tonic and nutritive
properties, and is used for irritated conditions of mucous membranes, such as cough,
sore throat, chronic bronchitis, diarrhea, dysentery, leucorrhea, cystitis, urethritis,
gonorrhea, burns, sore nipples, inflammations and nodular leprosy.L Pounded tender
leaves into a pulp are administered in dysentery and diarrhea; the leaves decoction
used as gargle is useful in spongy gums and relaxed sore throat, and to wash
hemorrhagic ulcers and wounds.CV Decoction of leaves and pods is dried and made
into tablets, and is known as Aqaqia. It is astringent and styptic, and is used for
leucorrhea, menorrhagia, and to stop bleeding from any organ.LXXVII A paste of the
gum with egg white is applied in conjunctivitis. It is also reported to be useful as
food for diabetic patients.LXXXI The bark is astringent, demulcent, refrigerant and
antiseptic,XXI,LXXVII and its decoction is used as gargle and mouth wash in sore
throat, foul aphthous stomatitis, cancerous and syphilitic affections, for copious
salivation,XXI,LXXXI,CV as a douche in leucorrhea and vaginal discharges, as an
enema in piles and prolapse of rectum,XXI and to wash ulcers.LXXXI The burnt wood
is used as antacid, and the gum increases viscosity of seminal fluid; however, it is
said to sclerose blood vessels.CXXXXVII British Pharmacopoeia describes gum acacia
as a source of useful medicaments. It is believed to be of value in treating gingivitis
and reducing plaque [28]. Several species of acacia are also used as chewing sticks
and are credited with antibacterial effect on oral bacteria. In East Africa, the bark
decoction is used to treat diarrhea and stomach disorders, while the root decoction is
mildly purgative and is given in cases of constipation, stomachache and for the
Acacia nilotica (L.) Delile. 49

treatment of gonorrhea. Powdered bark with ginger oil is used externally for
cancerous afflictions. Pods are used in cough; leaves are local stimulant and poultices
of bruised tender leaves are applied to wounds with foul discharges.LXXXV In Liv-
ingstone, a southern Province of Zambia, the plant was utilized to treat HIV/AIDS-
related infections during the epidemic [21].
Chief use of the gum in pharmacy is as an emulsifying agent to suspend insoluble
powders in aqueous mixtures, and as a binding agent to make pills and tablets specially
cough drops and lozenges. It is commonly employed as a demulcent in preparations
designed to treat diarrhea, dysentery, coughs, sore throat and fevers.CLIV
Phytoconstituents: The gum is chiefly composed of calcium, magnesium and
potassium salts of polysaccharides, and is built upon a backbone of D-galactose
units with side chains of D-glucuronic acid with L-rhamnose or L-arabinose as
terminal units. On hydrolysis with dilute acid, it yields 1-arabinose, 1-rhamnose
and 3-D-galactoside-1-arabinose. The residue consists of galactose and uronic acid
[14, 16],XXIV When hydrolyzed with dilute sulphuric acid, it yields 1-rhamnopyranose,
D-galactopyranose, 1-arabofuranose and aldobionic acid 6-D-glucuronosido-D-
galactose.C,CXXXXI It possesses an oxidase-type enzyme which is destroyed by heating
at 100 °C, and 12–15% of water.XXIV Presence of cardiac glycosides and flavonoids
has been reported in Acacia arabica leaves [50].
Pharmacology: Gentamicin-induced nephrotoxicity in rats was significantly ame-
liorated by pretreatment and concomitant treatment with gum Arabic, in part, due to
reduced oxidative stress [10]. However, Ali et al. [5] reported a modest protection
against gentamicin-nephrotoxicity. Administration of gum Arabic to healthy rats for
eight days also did not significantly affect the levels of free radical scavengers, such
as GSH, ascorbic acid, and SOD in kidneys and the liver [8]. Ali et al. [4] also
reported that gum Arabic treatment of rats for 5-weeks, following a two-stage sur-
gical nephrectomy to induce chronic renal failure (CRF), slightly and insignificantly
reduced the CRF-induced increases in urea and creatinine concentrations. Also, gum
Arabic co-treatment with cisplatin did not prevent cisplatin-nephrotoxicity, though
the cisplatin-induced LPO was significantly reduced by gum Arabic treatment [9].
Gum Arabic treatment significantly but incompletely reversed adenine-induced
increase in plasma creatinine, urea, and urinary protein; and increased SOD activity
and GSH concentration in renal homogenate [6]. Gum Arabic administration to
normal mice significantly increased creatinine renal clearance and antidiuretic hor-
mone, and decreased daily sodium and urinary output [38]. Pretreatment of mice
with gum Arabic significantly protected against APAP-hepatotoxicity without
affecting APAP-induced glutathione depletion but significantly reducing LPO and
NO formation [27]. Doxorubicin-cardiotoxicity is also significantly prevented by
treatment with gum Arabic [1].
50 Acacia nilotica (L.) Delile.

Wadood et al. [55] reported significant hypoglycemic effect of powdered seeds

in normal rabbits, but no significant effect on blood glucose of alloxan-diabetic
rabbits. Chloroform extract of Acacia bark significantly decreased blood glucose of
alloxan-diabetic rats and reversed values of TC, LDL-C, HDL-C and TGs [41].
Similar results of chloroform bark extract in alloxan-diabetic rats were reported
after 21-days of treatment. There were significant decreases in serum levels of
glucose, TC, LDL-C, TGs and MDA, while serum insulin and HDL-C were sig-
nificantly increased, compared to control diabetic animals [30]. Gum Arabic,
however, did not lower serum cholesterol in rats [53], it decreased cholesterol
absorption and increased its biosynthesis in cholesterol-fed rats [32]. Inhibition of
LDL-C oxidation [17], and uncoupling of oxidative phosphorylation in liver and
heart mitochondria, and partial inhibition of mixed function oxidases of liver
endoplasmic reticulum by gum Arabica have also been reported [19]. Addition of
gum Arabic to oral rehydrating solution increases water and electrolytes absorption
in normal and chronic osmosecretory diarrhea model in rats [23, 56], enhances
recovery from diarrhea [52], reduces cholera toxin-induced sodium excretion [54],
and decreases nitrite and nitrate formation in jejunum [45]. Sethi et al. [49] reported
an insignificant (11%) abortifacient activity of aqueous flowers extract in rats, that
also caused a 50 and 7.5% decrease in fetal body weight and length, respectively.
However, the same administered orally to rats for 10-days after insemination was
found ineffective as abortifacient [39].
Whole gum fine aqueous suspension inhibited growth of fresh isolates and
reference strains of P. gingivalis and P. intermedia cultures; while a soluble fraction
of aqueous suspension showed no similar activity [22]. Methanol leaf extract is
moderately active against S. aureus, S. typhi, S. paratyphi, and S. flexineri [50].
Antibacterial activity of water extract of chewing sticks against S. fecalis was
reported by Almas [11]. Gum Arabic has also been reported to enhance reminer-
alization of caries-like enamel lesions of teeth in vitro, similar to sodium fluoride,
suggesting a preventing effect against caries [40].
Clinical Studies: Gum Arabic is reported useful in cases of chronic renal disease,
especially the End-Stage Renal Disease (ESRD) requiring renal replacement therapy
(dialysis). Two out of three children with ESRD treated with gum acacia (1 g/kg/day
in divided doses) as complementary to low-protein diet reported improvement in
well-being and reduction in serum creatinine and urea levels not achieved previously
without dialysis [12]. An 11-years old girl with ESRD, who required peritoneal
dialysis to control uremic symptoms despite conservative measures, was treated with
gum acacia along with other conservative measures, after the parents refused further
dialysis treatment. The patient continuously improved over time and never experi-
enced acidotic or significant uremic symptoms over a four-year dialysis-free period
[13]. Another case of ESRD treated with gum Arabic remained dialysis-free for
six-years with improved well-being and without uremia [2]. Beneficial effects of
gum Arabic on serum creatinine, urea and uric acid were also observed in 36 chronic
renal failure patients who required regular hemodialysis, and in 10 normal healthy
subjects. Supplementation of low protein diet with gum Arabic in a dose of 50 g/day
Acacia nilotica (L.) Delile. 51

for 3 months significantly reduced serum urea levels by 31%, and the decrease was
even greater (44%) in patients who were also given ferrous sulfate (200 mg/day) and
folic acid (5 mg/day), compared to their baseline values. Serum creatinine was
decreased by 9.9 and 12.6% in these groups, respectively, and by 11.7% in normal
volunteers, compared to patients that were treated with only iron and folic acid [3].
An 8-weeks study in seven normal healthy volunteers, administered 25 g/day of
gum acacia, showed increased serum butyrate levels by two-fold. Exposure of renal
epithelial cells to increased levels of butyrate suppressed both basal and stimulated
generation of the profibrotic cytokine transforming growth factor-beta1 [36].
Ross [46] reported no significant effect of 3-weeks administration of gum Arabic
on glucose tolerance in healthy men, but serum cholesterol was decreased. Since no
gum was recovered from the stools, it was suggested that it was metabolized in the
colon. Mee and Gee [37] also reported a decrease in TC and LDL-C in men with
mild hypercholesterolemia. However, administration of water-soluble dietary fiber
from gum acacia (15 g/d) for 4 to 12-weeks to hypercholesterolemic men and
women failed to lower TC, LDL-C, VLDL-C and TGs or to increase HDL-C in
double-blind controlled studies [29, 31]. Calame et al. [20] found gum Arabic
producing prebiotic effect, increasing the useful Bifidobacteria and Lactobacilli in
healthy human volunteers, with 10 g being the optimal daily dose. Gazi [28]
reported antiplaque activity of Acacia gum compared to sugar-free gum in two
blind crossover clinical trials. RCTs have also indicated usefulness of commercially
available gel [43, 44] and toothpastes [51] containing A. arabica in patients with
gingivitis, comparable to chlorhexidine.
Human A/Es, Allergy and Toxicity/Safety: Sensitization to gum Arabic carbo-
hydrates has been reported in atopic patients with pollen sensitization without
obvious exposure to it [47]. An unusual case of a teenager with plasma cell gin-
givitis due to antigenic reaction to toothpaste containing A. arabica was reported
[35]. International Food Safety authorities put no limitation on the use of gum
Arabic as a food additive, if it is used with established criteria of identity and purity
[15]. A report also concluded that extensive safety test data support the safety of A.
senegal gum and gum extract, and these two ingredients are safe as used in cos-
metic formulations. According to industry data only material from A. senegal are in
current use in concentrations ranging from 9% in mascara to 0.0001% in tonics,
dressings and other hair grooming aids [18]. In Unani medicine, it is considered
harmful for GIT.LXXVII
Animal Toxicity: No dose-related changes in maternal findings, number of fetuses,
fetal viability or external, visceral or skeletal abnormalities were noted when gum
acacia was given up to 15% in diet ad lib to male and female rats during pre-mating,
mating and throughout gestation [24]. A toxicity study (subchronic toxicity) of gum
Arabic (from A. senegal) administered orally in diet to F344 rats at doses up to 5%
produced no clinical changes, survival, body weight, food and water consumption,
changes in urine, hematology or blood chemistry at the end of 90-days treatment
[25]. Flowers of A. arabica are also devoid of any teratogenicity [39]. Even modified
52 Acacia nilotica (L.) Delile.

gum acacia showed no mutagenic potential, and the LD50 in Sprague Dawley rats
was determined to be >2,000 mg/kg, while subacute toxicity studies of 13-weeks
administration showed no untoward effects or histological findings [48].
Potential Drug-Herb Interactions: Acacia gum may reduce the effectiveness of
preservative methyl-p-hydroxybenzoate against P. aeruginosa by its physical barrier
protection of microbial cells from the action of the agent [33]. Administration of gum
Arabic concurrently or 2 h before amoxicillin is reported to significantly decrease
the Cmax of amoxicillin [26], and it can also antagonize phenobarbital-induced
demethylation of aminopyrine [34]. Due to the presence of enzymes, it should not be
used for preparations with readily oxidizable ingredients e.g. vitamin A, and is also
incompatible with drugs containing morphine, apomorphine, eugenol, phenol, thy-
mol, guiacol, cresols, epinephrine, aminopyrine, vanillin, creosol, eserine, isobar-
baloin, gallic acid, and tannins; also with strong alcoholic liquids, solutions of ferric
chloride and lead subacetate and strong solution of sodium borate.CXI
Commentary: Although dramatic beneficial effects of gum Arabic in ESRD have
been reported, they have been reported only from one source, that need to be
verified in other patient populations and in RCTs.

References
1. Abd-Allah AR, Al-Majed AA, Mostafa AM, et al. Protective effect of Arabic
gum against cardiotoxicity induced by doxorubicin in mice: a possible
mechanism of protection. J Biochem Mol Toxicol. 2002;16:254–9.
2. Al Mosawi AJ. Six-year dialysis freedom in end-stage renal disease. Clin
Exp Nephrol. 2009;13:494–500.
3. Ali AA, Ali KE, Fadlalla AE, Khalid KE. The effects of gum Arabic oral
treatment on the metabolic profile of chronic renal failure patients under
regular hemodialysis in Central Sudan. Nat Prod Res. 2008;22:12–21.
4. Ali BH, Al-Qarawi AA, Ahmed IH. Does treatment with gum Arabic affect
experimental chronic renal failure in rats? Fundam Clin Pharmacol. 2004;
18:327–9.
5. Ali BH, Al-Qarawi AA, Haroun EM, Mousa HM. The effect of treatment
with gum Arabic on gentamicin-induced nephrotoxicity in rats: a prelim-
inary study. Ren Fail. 2003;25:15–20.
6. Ali BH, Al-Salam S, Al Za’abi M, et al. New model for adenine-induced
chronic renal failure in mice, and the effect of gum acacia treatment thereon:
comparison with rats. J Pharmacol Toxicol Methods. 2013;68:384–93.
7. Ali BH, Ziada A, Blunden G. Biological effects of gum Arabic: a review of
some recent research. Food Chem Toxicol. 2009;47:1–8.
8. Ali BH. Does gum Arabic have an antioxidant action in rat kidney? Ren
Fail. 2004;26:1–3.
Acacia nilotica (L.) Delile. 53

9. Al-Majed AA, Abd-Allah AR, Al-Rikabi AC, Al-Shabanah OA, Mostafa AM.
Effect of oral administration of Arabic gum on cisplatin-induced nephrotox-
icity in rats. J Biochem Mol Toxicol. 2003;17:146–53.
10. Al-Majed AA, Mostafa AM, Al-Rikabi AC, Al-Shabanah OA. Protective
effects of oral gum administration on gentamicin-induced nephrotoxicity in
rats. Pharmacol Res. 2002;46:445–51.
11. Almas K. The antimicrobial effects of seven different types of Asian
chewing sticks. Odontostomatol Trop. 2001;24:17–20.
12. Al-Mosawi AJ. Acacia gum supplementation of a low-protein diet in
children with end-stage renal disease. Pediatr Nephrol. 2004;19:1156–9.
13. Al-Mosawi AJ. The use of acacia gum in end-stage renal failure. J Trop
Pediatr. 2007;53:362–5.
14. Anderson DM, Millar JR, Weiping W. Gum Arabic (Acacia senegal):
Unambiguous identification by 13C-NMR spectroscopy as an adjunct to the
Revised JECFA Specification, and the application of 13C-NMR spectra for
regulatory/legislative purposes. Food Addit Contam. 1991;8:405–21.
15. Anderson DM. Evidence for the safety of gum Arabic (Acacia senegal (L.)
Willd.) as a food additive—a brief review. Food Addit Contam. 1986;3:
225–30.
16. Anderson DMW, Dea ICM, Daramalla KA, Smith JF. Studies on uronic acid
materials: XXIV. An analytical study of different forms of the gum from
Acacia senegal Willd. Carbohyd Res. 1968;6:97 (Biol. Abstr. 50:15973).
17. Andrikopoulos NK, Kaliora AC, Assimopoulou AN, Papapeorgiou VP. Bio-
logical activity of some naturally occurring resins, gums and pigments
against in vitro LDL oxidation. Phytother Res. 2003;17:501–7.
18. Anonymous. Final report of the safety assessment of Acacia catechu gum,
Acacia concinna fruit extract, Acacia dealbata leaf extract, Acacia dealbata leaf
wax, Acacia decurrens extract, Acacia farnesiana extract, Acacia farnesiana
flower wax, Acacia farnesiana gum, Acacia senegal extract, Acacia senegal
gum, and Acacia senegal gum extract. Int J Toxicol. 2005;24 Suppl 3:75–118.
19. Bachmann E, Weber E, Post M, et al. Biochemical effects of gum Arabic,
gum tragacanth, methylcellulose and carboxymethylcellulose-Na in rat heart
and liver. Pharmacology. 1978;17:39–49.
20. Calame W, Weseler AR, Viebke C, et al. Gum Arabic establishes prebiotic
functionality in healthy human volunteers in a dose-dependent manner. Br J
Nutr. 2008;100:1269–75.
21. Chinsembu KC. Ethnobotanical study of plants used in the management of
HIV/AIDS-related diseases in Livingstone, Southern Province, Zambia.
Evid Based Complement Alternat Med. 2016;2016:4238625.
22. Clark DT, Gazi MI, Cox SW, Eley BM, Tinsley GF. The effects of Acacia
arabica gum on the in vitro growth and protease activities of periodonto-
pathic bacteria. J Clin Periodontol. 1993;20:238.
54 Acacia nilotica (L.) Delile.

23. Codipilly CN, Teichberg S, Wapnir RA. Enhancement of absorption by

gum Arabic in a model of gastrointestinal dysfunction. J Am Coll Nutr.
2006;25:307–12.
24. Collins TF, Welsh JJ, Black TN, Graham SL, Brown LH. Study of the
teratogenic potential of gum Arabic. Food Chem Toxicol. 1987;25:815–21.
25. Doi Y, Ichihara T, Hagiwara A, et al. A ninety-day oral toxicity study of a
new type of processed gum Arabic, from Acacia tree (Acacia senegal)
exudates, in F344 rats. Food Chem Toxicol. 2006;44:560–6.
26. Eltayeb IB, Awad AI, Elderbi MA, Shadad SA. Effect of gum Arabic on the
absorption of a single oral dose of amoxicillin in healthy Sudanese volun-
teers. J Antimicrob Chemother. 2004;54:577–8.
27. Gamal el-din AM, Mostafa AM, Al-Shabanah OA, Al-Bekairi AM,
Nagi MN. Protective effect of Arabic gum against APAP-induced hepato-
toxicity in mice. Pharmacol Res. 2003;48:631–35.
28. Gazi MI. The finding of antiplaque features in Acacia Arabica type of
chewing gum. J Clin Periodontol. 1991;18:75.
29. Haskell WL, Spiller GA, Jensen CD, et al. Role of water-soluble dietary
fiber in the management of elevated plasma cholesterol in healthy subjects.
Am J Cardiol. 1992;69:433.
30. Hegazy GA, Alnoury AM, Gad HG. The role of Acacia arabica extract as an
antidiabetic, antihyperlipidemic, and antioxidant in streptozotocin-induced
diabetic rats. Saudi Med J. 2013;34:727–33.
31. Jensen CD, Spiller GA, Gates JE, Miller AF, Whittam JH. The effect of
acacia gum and a water-soluble dietary fiber mixture on blood lipids in
humans. J Am Coll Nutrit. 1993;12:147.
32. Kelley JJ, Tsai AC. Effect of pectin, gum Arabic and agar on cholesterol
absorption, synthesis, and turnover in rats. J Nutr. 1978;108:630–9.
33. Kurup TR, Wan LS, Chan LW. Interaction of preservatives with macro-
molecules: Part 1-natural hydrocolloids. Pharm Acta Helv. 1992;67:301.
34. Lutz WK, Brändle E, Zbinden G. Effect of gum Arabic on aminopyrine
demethylation in rats. Experientia. 1978;34:1609–10.
35. Makkar A, Tewari S, Kishor K, et al. An unusual clinical presentation of plasma
cell gingivitis related to “Acacia” containing herbal toothpaste. J Indian Soc
Periodontol. 2013;17:527–30.
36. Matsumoto N, Riley S, Fraser D, et al. Butyrate modulates TGF-beta1
generation and function: potential renal benefit for Acacia (sen) SUPERGUM
(gum Arabic)? Kidney Int. 2006;69:257–65.
37. Mee KA, Gee DL. Apple fiber and gum Arabic lowers total and low-density
lipoprotein cholesterol levels in men with mild hypercholesterolemia. J Am
Diet Assoc. 1997;97:422–4.
Acacia nilotica (L.) Delile. 55

38. Nasir O, Artunc F, Saeed A, et al. Effects of gum Arabic (Acacia senegal) on
water and electrolyte balance in healthy mice. J Ren Nutr. 2008;18:230–8.
39. Nath D, Sethi N, Singh RK, Jain AK. Commonly used Indian abortifacient
plants with special reference to their teratologic effects in rats. J Ethnophar-
macol. 1992;36:147.
40. Onishi T, Umemura S, Yanagawa M, et al. Remineralization effects of gum
Arabic on caries-like enamel lesions. Arch Oral Biol. 2008;53:257–60.
41. Patil RN, Patil RY, Ahirwar B, et al. Evaluation of antidiabetic and related
actions of some Indian medicinal plants in diabetic rats. Asian Pac J Trop
Med. 2011;4:20–3.
42. Phillips GO. Acacia gum (Gum Arabic): a nutritional fibre; metabolism and
calorific value. Food Addit Contam. 1998;15:251–64.
43. Pradeep AR, Agarwal E, Bajaj P, et al. Clinical and microbiologic effects of
commercially available gel and powder containing Acacia arabica on
gingivitis. Aust Dent J. 2012;57:312–8.
44. Pradeep AR, Happy D, Garg G. Short-term clinical effects of commercially
available gel containing Acacia arabica: a randomized controlled clinical
trial. Aust Dent J. 2010;55:65–9.
45. Rehman KU, Codipilly CN, Wapnir RA. Modulation of small intestinal nitric
oxide synthase by gum Arabic. Exp Biol Med (Maywood). 2004;229:
895–901.
46. Ross AH, Eastwood MA, Brydon WG, et al. A study of the effects of dietary
gum Arabic in humans. Am J Clin Nutr. 1983;37:368–75.
47. Sander I, Raulf-Heimsoth M, Wiemer K, et al. Sensitization due to gum
Arabic (Acacia senegal): the cause of occupational allergic asthma or cross
reaction to carbohydrates? Int Arch Allergy Immunol. 2006;141:51–6.
48. Schmitt D, Tran N, Riefler S, et al. Toxicologic evaluation of modified gum
acacia: mutagenicity, acute and subchronic toxicity. Food Chem Toxicol.
2008;46:1048–54.
49. Sethi N, Nath D, Singh RK. Teratological evaluation of some commonly used
indigenous antifertility plants in rats. Int J Crude Drug Res. 1989;27:118.
50. Tambekar DH, Khante BS, Chandak BR, et al. Screening of antibacterial
potentials of some medicinal plants from Melghat forest in India. Afr J
Tradit Complement Altern Med. 2009;6:228–32.
51. Tangade PS, Mathur A, Tirth A, et al. Antigingivitis effects of Acacia
arabica-containing toothpaste. Chin J Dent Res. 2012;15:49–53.
52. Teichberg S, Wingertzahn MA, Moyse J, et al. Effect of gum Arabic in an
oral rehydration solution on recovery from diarrhea in rats. J Pediatr
Gastroenterol Nutr. 1999;29:411–7.
53. Tsai AC, Elias J, Kelley JJ, et al. Influence of certain dietary fibers on serum
and tissue cholesterol levels in rats. J Nutr. 1976;106:118–23.
56 Acacia nilotica (L.) Delile.

54. Turvill JL, Wapnir RA, Wingertzahn MA, et al. Cholera toxin-induced
secretion in rats is reduced by a soluble fiber, gum Arabic. Dig Dis Sci.
2000;45:946–51.
55. Wadood A, Wadood N, Shah SA. Effects of Acacia arabica and Caralluma
edulis on blood glucose levels of normal and alloxan diabetic rabbits.
J Pakistan Med Assoc. 1989;39:208.
56. Wapnir RA, Wingertzahn MA, Moyse J, Teichberg S. Gum Arabic
promotes rat jejunal sodium and water absorption from oral rehydration
solutions in two models of diarrhea. Gastroenterology. 1997;112:1979–85.
Achillea millefolium L.
(Asteraceae/Compositae)

Abstract
An herb that grows in Asia, North America and Europe, with a long history behind
its clinical use. It is said to have been used since Trojan War (C. 1200 B.C.);
one legend credits Chiron, the Roman Centaur, telling Achilles how to make an
ointment from it to heal the bleeding wounds of the soldiers, hence the name
Achillea. Dioscorides and Galen recommended its use after surgery to prevent
inflammation, and to promote healing. In the Northern hemisphere, its traditional
uses include digestive problems, liver and gall-bladder conditions, menstrual
irregularities, cramps, fever and wound healing. An ointment made of the fresh
plant by the Scottish Highlanders is good for piles, and a decoction of the whole
herb is used for bleeding piles, and for kidney disorders. A poultice of the whole
herb is applied to sprains, muscular strains, rheumatism and stiff neck. The native
Indians used it extensively for various medicinal purposes. The Cherokee tribe
used a tea made from yarrow to aid sleep and to relieve fever; the Pawnee tribe
used the stalk for pain relief. The Navajo tribe held it in highest esteem and called
it ‘life medicine’ and chewed it to relieve toothache and dropped its infusion into
the ear for earache; and the Chippewa inhaled steam of the plant to relieve
headache. Aqueous extract of aerial parts and flowering tops increased gastric acid
and mucous production, exerted a direct spasmogenic effect in vitro and prokinetic
effect in vivo, protected gastric mucosa against ethanol and indomethacin-induced
acute gastric lesions, against toxic chemical hepatic damage, and reduced
mortality in mice. The European Commission E approved it for internal use for
loss of appetite and dyspeptic disorders, and externally in the form of sitz-bath or
as a compress for skin inflammation, slow-healing wounds, bacterial or fungal
infections. Dried herb contains protein, carbohydrates, fat, fibers, calcium,
phosphorus, phenolic compounds, such as flavonoids and phenol carbonic acid.

© Springer Nature Switzerland AG 2020 57

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_7
58 Achillea millefolium L.

Clinical trial also demonstrated that administration of powdered flowers to chronic

kidney disease patients significantly decreased plasma nitrite and nitrate
concentrations.

Keywords





Achillée millefeuille Almindelig røllike Aquiléia Biranjasif Biranjasipha





Bloodwort Ju cao Qaisum jabali Rojmari Schafgarbe

Vernaculars: Urd.: Biranjasif1,2; Hin.: Bhut kesi, Gandrain, Puthkanda, Rojmari or

Rojamari; San.: Biranjasipha, Gandana; Mar.: Rojmaari; Tam.: Achchilliya; Ara.:
Om alf waraka (Egypt), Qaisum jabali; Chi.: 蓍, Ju cao, Shi cao, Ou shi, Qian ye shi;
Dan.: Almindelig røllike, Finbladet røllike, Røllike; Dut.: Duizendblad; Eng.:
Bloodwort, Devil’s nettle, Knight’s milfoil, Nosebleed, Soldier’s woundwort, Thou-
sandweed, Yarrow; Fin.: Aivastusjuuri, Akantupakki, Siankärsämö; Fre.: Achillée
des monts Sudètes, Achillée millefeuille, Achillée tomenteuse; Ger.: Gemeine
schafgarbe, Gotteshand, Schafgarbe, Wiesen-schafgarbe; Ita.: Achillea millefoglie,
Millefoglio; Jap.: Seiyou no kogirisou; Nor.: Ryllik, Vanlig ryllik; Per.: Bui-e-
madarân; Por.: Aquiléia, Espuma-do-mar, Milefólio; Rus.: Tysjačelistnik obyknoven-
nyj; Spa.: Alcanfor, Ciento en rama (Mexico), Milenrama, Mil hojas (Argentina);
Swe.: Röllika; Tag.: Milfoil; Tur.: Civanperçemi.
Description: An erect, perennial herb that grows in Asia, North America and Europe;
up to 50–90 cm in height, with a slender creeping root-stock, giving off numerous
filiform roots and several long subterranean, reddish stolons with a blunt succulent scale
at each node. Leaves are without stalks, and are 1- to 2-pinnately parted into linear-
toothed segments. Flowers are white, red or purplish with five rays, grow in level topped
corymbs, heads numerous, with the involucre oblong. Florets several, perfect, tubular
with the margin whitish and the tube greenish. The plant has a feeble aromatic somewhat
chamomile-like odor and a bitterish, rather saline taste (Figs. 1, 2 and 3).CXVII
Actions and Uses: Dioscorides and Galen mentioned it as an astringent, and rec-
ommended it to use after surgery to prevent inflammation, and to promote healing.LXIX
In the Northern hemisphere, its traditional uses include digestive problems, liver and
gall-bladder conditions, menstrual irregularities, cramps, fever and wound healing. Its
chief local action is in piles, and in relaxation of sphincter ani with mucous or blood
discharge; and is also applied to sore nipples. It is said to have been used since Trojan
War (C. 1200 B.C.). One legend credits Chiron, the Roman Centaur, telling Achilles
how to make an ointment from it to heal the bleeding wounds of the soldiers, hence the
name Achillea.LXXIX The temperament ascribed to the herb is hot 1° and dry 2°, with
attributes such as rubefacient, deobstruent, resolvent, emollient, powerful diuretic,
antipyretic, and lithotriptic; and is particularly used for the treatment of inflammation

1
Anthemis nobilis and Matricaria chamomile are also referred to as Biranjasif in Unani Medicine.
2
Hakeem S. Safiuddin Ali mentions Artemisia vulgaris L. as Biranjasif. The same has been
translated as Brinjasif in Ibn-e-Baitar’s Jame-ul-Mufradat-al-Advia wal Aghzia.
Achillea millefolium L. 59

Fig. 1 Achillea millefolium, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Achillea_millefolium_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-149.jpg

Fig. 2 Achillea millefolium, Whole Plant, O. Pichard, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Achillea_millefolium_vallee-
de-grace-amiens_80_22062007_1.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
60 Achillea millefolium L.

Fig. 3 Achillea millefolium, Flowers, Walter Siegmund, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Achillea_millefolium_7981.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

of internal organs.LXXVII Ibn al-RushdLXX described it as resolvent and deobstruent, and

application of the ash of its aerial parts useful for indurated ulcers. With honey, its
flowers act as anti-inflammatory, emmenagogue, oxytocic, and expel placenta.L An
ointment made of the fresh plant by the Scottish Highlanders is good for piles, and a
decoction of the whole herb is used for bleeding piles, and for kidney disorders. Modern
literature mentions the plant use as hair rinse and shampoo to prevent baldness; and is
also reported to have been used for cancers, indurations or tumors of breast, feet, liver,
penis, spleen, and uterus, condylomata, warts and wens [31]. TylerCXXXXII describes the
whole flowering herb as efficacious and safe carminative, antispasmodic, antiinfective,
and anti-inflammatory. Chandler et al. [17] added abortive, analgesic, anthelmintic,
antiviral, contraceptive, diaphoretic, febrifuge, diuretic, emmenagogue, laxative, stimu-
lant and tonic properties. Its uses also include epilepsy, hysteria, melancholy, ner-
vousness, hemorrhage, leucorrhea, menorrhagia, hypertension, rheumatism, influenza,
pneumonia, small pox, tuberculosis, sore throat, ulcers, rashes, measles and urinary
incontinence. LucasXCII mentioned that a tea made from the leaves is used to reduce
fever, gout and headache. A poultice of the whole herb is applied to sprains, muscular
strains, rheumatism and stiff neck. In Norway, a liniment made from yarrow is a favorite
remedy for muscular aches and pains. Fresh leaves are chewed to relieve toothache in
Eastern North America. The native Indians used it extensively for various medicinal
purposes. For example, the Cherokee tribe used a tea made from yarrow to aid sleep and
to relieve fever; the Pawnee tribe used the stalk for pain relief. The Navajo tribe held it in
highest esteem and called it ‘life medicine’ and chewed it to relieve toothache and
dropped its infusion into the ear for earache; and the Chippewa inhaled steam of the
plant to relieve headache. In Canada, farmers use it to treat mastitis in their livestock
[35]. The Micmacs Indians used it as a sweet herb to cure colds, after boiling for one
hour and taking it in warm milk. To brighten, stimulate and strengthen blonde hair, a
rinse made from equal parts of chamomile and yarrow is said to be most effec-
tive.LXXXVIII It is used in the treatment of gastrointestinal disorders, hepatobiliary
Achillea millefolium L. 61

complaints and inflammation in traditional European medicines [9], also used as

emmenagogue in Italy [33], and France [13]. The herb is most useful in colds, inade-
quate perspiration, and fevers; it opens pores and purifies blood, and is also useful in
hysteria, flatulence and heartburn, colic and epilepsy. In England, it was widely used
topically as a vulnerary, and internally to suppress hemorrhages and profuse mucous
discharges, in intermittent fevers, as an antispasmodic in flatulent colic, and in nervous
affections [13]. The European Commission E approved it for internal use for loss of
appetite and dyspeptic disorders, and externally in the form of sitz bath or as a compress
for skin inflammation, slow-healing wounds, bacterial or fungal infections [43]. In
Australia, it is used for the treatment of diarrhea, as a urinary antiseptic, hypotensive, and
diuretic; and has also traditionally been used as abortifacient, emmenagogue, contra-
ceptive and uterine stimulant and thus contraindicated for use during pregnancy [12].
Like other stimulant tonics, it is given during convalescence after fevers, and is capable
to promote appetite and digestion in atonic gastric disorders. It has a specific relation to
the pelvic organs, and is used in conditions of atony in the female reproductive organs
associated with amenorrhea, dysmenorrhea, menorrhagia and leucorrhea.XL,LXXXI Hot
infusion of leaves is a powerful emmenagogue.CV In Brazilian folk medicine, it is used
to treat inflammations, hemorrhage, gastrointestinal disorders, pain, and wounds [16]. It
is also reported beneficial as gargle in relaxed and otherwise inert conditions of the
throat. Recent findings have confirmed several traditional uses, such as analgesic,
antiulcer, choleretic, hepatoprotective and wound healing activities. The largest data
available for it are for antioxidant and anti-inflammatory effects.LIX The herb was
official in the Austrian, Belgian, Danish, French, Finnish, Greek, Mexican, Romanian,
Spanish, Swedish, Swiss and the United States Pharmacopeias.CXVII In the last decades,
pharmacological studies became intensive, although human clinical investigations are
still rare. It is reportedly still used in 65 cosmetic products as a “biological additive” in
concentrations of 0.5–10%, though its safety data is not comprehensive to support its
use in cosmetics [4].
Phytoconstituents: Dried herb contains 71–72% carbohydrates, 12–14% protein,
1.8–3.9% fat, 20–23% fibers, 1.33 mg calcium and 360 mg phosphorus.XXXVIII
Pharmacologically important phytoconstituents present in the plant are phenolic com-
pounds, such as flavonoids and phenol carbonic acid. Total amount of the identified
phenolics in yarrow flowers from different populations vary from 13.29 to 27.94 mg/g
[10]. b-sitosterol is the major sterol, along with stigmasterol, campesterol and choles-
terol. Major triterpenes are a-amyrin, with b-amyrin, taraxasterol and pseudo-
taraxasterol being the other triterpenes present [18]. Alkaloids present are achiceine,
achilletin, betaine, betonicine, homostachydrine, choline, moschatine, stachydrine and
trigonelline, while flavonoids include apigenin, apigenin glycosides, artemetin,
isorhamnetin, casticin, luteolin, luteolin glucosides, 5-hydroxy-3,6,7,4′-tetramethoxy-
flavone, rutin (quercetin rhamnoglucoside) and quercetin glycoside [47]. Dias et al. [23]
found only quantitative differences in the chemical profile of wild and commercial
samples, and in methanol extract, infusion and decoction of the plant. They found higher
62 Achillea millefolium L.

contents offat and saturated fatty acids, protein, ash, energy value, sugars and flavonoids
in commercial variety; whereas, the wild variety had higher levels of carbohydrates,
unsaturated fatty acids, organic acids, tocopherols and phenolic acids.
Average quantity of EO in the Millefollii herba samples is reported to be 0.24%;
yield varies between 0.35% (from samples collected from altitudes up to 1,100 m) and
0.18% (from samples of higher altitudes). Variations in EO contents in samples from
different altitudes of Himalayan regions of India reported major components to be
b-pinene, 1,8-cineole, borneol and b-caryophyllene [1]. Samples gathered in June
were of the best quality. The yellow flower kind contained an average of 0.20% of EO,
and none of the analyzed samples contained any azulene [34]. However, Oswiecimska
[45] reported autumn-harvested herb not inferior to the raw stufffrom summer harvest.
The content of EO and azulenes did not change after 2.5 years storage. The richest
content of oil and azulenes was found in the inflorescence, followed by the leaves, and
the smallest in the stalks. Small buds have the highest percent content of azulenes and
oil; during growth of the flowerhead the content diminishes proportionately. Cap-
pelletti et al. [15] reported the herb to yield volatile oil containing azulene and
achilleine, a glycoalkaloid, gum, tannin, resin, phosphates, maleates, chloride of
calcium, potassium and lime. Apigenin, luteolin, centaureidin, b-sitosterol, b-hydroxy-
11a,13-dihydrocostunolide, desacetylmatricarin, leucodin, achillin, 8a-angeloxy-
leucodin and 8a-angeloxyachillin were reported from flowerheads of Hungarian A.
millefolium [28].
Recent estimates of EO yield from samples growing in different European coun-
tries range between 0.09 and 0.95%, with 102 identified components. Most important
components being sabinene, b-pinene, 1,8-cineole, artemisia ketone, linalool, a-
thujone, b-thujone, camphor, borneol, fenchyl acetate, germacrene D, bornyl acetate,
b-bisabolol, d-cadinol, (E)-b-caryophyllene, caryophyllene oxide, and chamazulene.
Samples from Estonia, Germany, Greece, Hungary, Latvia, Lithuania and Moldova
showed higher contents of monoterpenes and chamazulene; while samples from
Armenia, Belgium, France, Italy, Russia and Spain were rich in oxygenated monoter-
penes and lesser amounts of chamazulene [44]. Also, the EO contents differ greatly
between the vegetative stages (0.13%) and the stage of full bloom (0.34%), with
increasing amounts of monoterpenes, such as a- and b-pinene and a-thujone and
decreasing levels of sabinene, borneol, and bornyl acetate [48]. Wildly growing
Achillea on Sardinia Island, Italy, and on the Atlantic coast (Portugal-Serra de Mon-
temuro), showed the Italian volatile extracts predominantly composed of a-asarone
(25.6–33.3%), b-bisabolene (27.3–16.6%) and a-pinene (10.0–17.0%); whereas the
main components of the Portuguese extracts were trans-thujone (31.4–29.0%),
trans-crhysanthenyl acetate (19.8–15.8%) and b-pinene (1.2–11.1%) [25].
Major components of flower samples collected from several provinces of Iran were
2-methyl butanal, a-pinene, a-thujene, camphene, hexanal, b-pinene and 1,8-cineole;
whereas, aerial parts contained a-pinene, camphene, DL-limonene, and 1,8-cineole
[24]. Eight phenolic compounds were isolated from flowerheads, including chloro-
genic acid and seven flavonoids, vicenin-2, luteolin-3′,7-di-O-glucoside, luteolin-7-O-
glucoside, rutin, apigenin-7-O-glucoside, luteolin and apigenin [10]. A glycosylne-
olignan, dihydrodehydrodiconiferyl alcohol 9-O-b-D-glucopyranoside was reported
Achillea millefolium L. 63

from aerial parts [33]. Achillinin A (2b,3b-epoxy-1a,4b,10a-trihydroxyguai-11(13)-

en-12,6a-olide, 1), a new guaianolide was isolated from flowers [37]. Three antitumor
sesquiterpenoids, achimillic acids A, B and C, active in vivo against mouse P-388
leukemia cells [51], and three flavones, 5-hydroxy-3,6,7,4′-tetramethoxyflavone,
artemitin and casticin, have also been reported from flowering heads [26]. Two gua-
ianolides, a-peroxyachifolid and b-peroxyisoachifolid were isolated by Rucker et al.
[49] from flowering heads, the former was identified to be responsible for the allergic
contact dermatitis caused by yarrow [32].
Pharmacology: Hydroalcohol extract reduces intestinal contractility [5, 46]; the
aglycone fractions, quercetin, luteolin and apogenin exhibiting the highest antispas-
modic activity [36]. In isolated intestinal preparations, the extract relaxed both
spontaneous and potassium-induced contractions and exhibited verapamil-like effect
on calcium concentration response curve [53], and exhibited muscarinic receptors
inhibitory activity in isolated tracheal smooth muscle [27]. The extract also increased
urinary volume and the excretion of sodium and potassium in rats, that depends on
both the activation of bradykinin B2 receptors and the activity of cyclooxygenases
[22]. Aqueous extract of aerial parts and flowering tops increased gastric acid and
mucous production [3], exerted a direct spasmogenic effect in vitro and prokinetic
effect in vivo [11], protected gastric mucosa against ethanol and indomethacin-induced
acute gastric lesions [16], against toxic chemical hepatic damage, and reduced mor-
tality in mice [41, 50, 53], The choleretic effect was attributed to dicaffeoylquinic acids
[7, 8]. Methanol extract moderately inhibited growth of several strains of H. pylori
[38], and the EO demonstrated antimicrobial activity against C. albicans, C. krusei, S.
pneumoniae, M. smegmatis, C. perfringens and A. lwoffii [14].
Hydroalcohol extract exerted anxiolytic effects in mice, similar to diazepam, at
doses that did not alter locomotor activity [6], and did not show analgesic activity in
hot-plate or formaline tests [46]. However, it showed topical anti-inflammatory
activity in a gel-formulation, comparable to diclofenac gel [40], and this activity
was attributed partly to inhibitory effect of dicaffeoylquinic acid on neutrophil
elastase [9]. Ethanol extract of aerial parts also produced 29% inhibition of
carrageenin-induced edema of rat paw [39]. Presence of matricin or achillin azuelen
were responsible for the anti-inflammatory activity [29]. Almustafa and Thunibat
[2] reported weak antioxidant activity of methanol extract, but the EO exhibited
strong antioxidant activity and inhibited nonenzymatic LPO of rat liver homogenate
[14]. The plant was, however, reported to significantly inhibit generation of ROS
from H. pylori-infected gastric epithelial cells [54]. Chloroform extract exhibited
antiproliferation activity against HeLa and MCF-7 cells; centaureidin being the
most effective, but casticin and paulitin also highly effective for this activity [20].
Casticin inhibited cell growth in G2/M phase, induced p21, down regulated cyclin
A, and its effect was maintained in p53 mutant or null cell lines [30]. The alkaloid
achilletin is reported to reduce coagulation time in canines.XXXVIII
64 Achillea millefolium L.

Clinical Studies: Administration of 1.5 g powdered flowers 3 days a week for

2 months to chronic kidney disease patients significantly decreased plasma nitrite
and nitrate concentrations [52].
Mechanism of Action: Antispasmodic activity of hydroalcohol extract is mediated
via calcium channel blockade by the aglycone fractions [36].
Human A/Es, Allergy and Toxicity: It is a photosensitizer when crushed on
skin.CXXXV a-peroxyachifolid was identified as the main sensitizer by Hausen et al.
[32], whereas both a- peroxyachifolid and b-peroxy-isoachifolid were identified by
Rucker et al. [49] as the sensitizers. Kabeeruddin LXXVII mentioned it harmful for
the kidneys, and it may also cause occupational bronchial asthma [19].
Animal Toxicity: Administration of water extract to male and female Wistar rats
for up to 90 days did not show any significant toxicity [16]. However, aqueous,
ethanol and hydroalcohol extracts administration to male rats for up to 90-days is
also reported to cause sperm abnormalities [21, 42], and administration of ethanol
preparation in a dose 56 times of human dose to female rats during pregnancy
produced a reduction in fetal weight and increase in placental weight [12].
Commentary: Except one study on powdered flowers in chronic kidney disease
patients, there are no other clinical studies reported in the mainstream English
publications listed on PubMed.

References
1. Agnihotri VK, Lattoo SK, Thappa RK, et al. Chemical variability in the essen-
tial oil components of Achillea millefolium agg. from different Himalayan
habitats (India). Planta Med. 2005;71:280–3.
2. Al-Mustafa AH, Al-Thunibat OY. Antioxidant activity of some Jordanian
medicinal plants used traditionally for treatment of diabetes. Pak J Biol Sci.
2008;11:351–8.
3. Anonymous. Experimental study of the effect of the phytomixture made of
leaves of Plantago major L. and Achillea millenfolium L. on the secretion
activity of the stomach in dogs. Eksp Klin Gastroenterol. 2005;73–6:113
(Russian).
4. Anonymous. Final report on the safety assessment of yarrow (Achillea
millefolium) extract. Int J Toxicol. 2001;20 Suppl 2:79–84.
5. Babaei M, Abarghoei ME, Akhavan MM, et al. Antimotility effect of
hydroalcoholic extract of yarrow (Achillea millefolium) on the guinea-pig
ileum. Pak J Biol Sci. 2007;10:3673–7.
6. Baretta IP, Felizardo RA, Bimbato VF, et al. Anxiolytic-like effects of acute
and chronic treatment with Achillea millefolium L. extract. J Ethnopharma-
col. 2012;140:46–54.
7. Benedek B, Geisz N, Jäger W, et al. Choleretic effects of yarrow (Achillea
millefolium s.l.) in the isolated perfused rat liver. Phytomedicine. 2006;13:
702–6.
Achillea millefolium L. 65

8. Benedek B, Kopp B, Melzig MF. Achillea millefolium L. s.l.—Is the

anti-inflammatory activity mediated by protease inhibition? J Ethnophar-
macol. 2007;113:312–7.
9. Benedek B, Kopp B. Achillea millefolium L. s.l. revisited: recent findings
confirm the traditional use. Wien Med Wochenschr. 2007;157:312–4.
10. Benetis R, Radusiene J, Janulis V. Variability of phenolic compounds in
flowers of Achillea millefolium wild populations in Lithuania. Medicina
(Kaunas). 2008;44:775–81.
11. Borrelli F, Romano B, Fasolino I, et al. Prokinetic effect of a standardized
yarrow (Achillea millefolium) extract and its constituent choline: studies in
the mouse and human stomach. Neurogastroenterol Motil. 2012;24:164–71.
12. Boswell-Ruys CL, Ritchie HE, Brown-Woodman PD. Preliminary screen-
ing study of reproductive outcomes after exposure to yarrow in the pregnant
rat. Birth Defects Res B Dev Reprod Toxicol. 2003;68:416–20.
13. Caius JF. The medicinal and poisonous composites of India. J Bombay Nat
Hist Soc. 1940;41:607.
14. Candan F, Unlu M, Tepe B, et al. Antioxidant and antimicrobial activity of
the essential oil and methanol extracts of Achillea millefolium subsp. mille-
folium Afan. (Asteraceae). J Ethnopharmacol. 2003;87:215–20.
15. Cappelletti EM, Trevisan R, Caniato R. External antirheumatic and antineu-
ralgic herbal remedies in the traditional medicine of North Eastern Italy.
J Ethnopharmacol. 1982;6:161–90.
16. Cavalcanti AM, Baggio CH, Freitas CS, et al. Safety and antiulcer efficacy
studies of Achillea millefolium L. after chronic treatment in Wistar rats.
J Ethnopharmacol. 2006;107:277–84.
17. Chandler RF, Hooper SN, Harvey MJ. Ethnobotany and phytochemistry of
Yarrow. Achillea millefolium, Compositae. Econ Bot. 1982;36:203.
18. Chandler RF, Hooper SN, Hooper DL, et al. Herbal remedies of the Maritime
Indians: sterols and triterpenes of Achillea millefolium L. (Yarrow). J Phar-
maceut Sci. 1982;71:690–3.
19. Compes E, Bartolomé B, Fernández-Nieto M, et al. Occupational asthma from
dried flowers of Carthamus tinctorious (safflower) and Achillea millefolium
(yarrow). Allergy. 2006;61:1239–40.
20. Csupor-Löffler B, Hajdú Z, Zupkó I, et al. Antiproliferative effect of
flavonoids and sesquiterpenoids from Achillea millefolium s.l. on cultured
human tumour cell lines. Phytother Res. 2009;23:672–6.
21. Dalsenter PR, Cavalcanti AM, Andrade AJ, et al. Reproductive evaluation
of aqueous crude extract of Achillea millefolium L. (Asteraceae) in Wistar
rats. Reprod Toxicol. 2004;18:819–23.
22. de Souza P, Crestani S, da Silva Rde C, et al. Involvement of bradykinin and
prostaglandins in the diuretic effects of Achillea millefolium L. (Asteraceae).
J Ethnopharmacol. 2013;149:157–61.
23. Dias MI, Barros L, Dueñas M, et al. Chemical composition of wild and
commercial Achillea millefolium L. and bioactivity of the methanolic
extract, infusion and decoction. Food Chem. 2013;141:4152–60.
66 Achillea millefolium L.

24. Dokhani S, Cottrell T, Khajeddin J, Mazza G. Analysis of aroma and

phenolic components of selected Achillea species. Plant Foods Hum Nutr.
2005;60:55–62.
25. Falconieri D, Piras A, Porcedda S, et al. Chemical composition and
biological activity of the volatile extracts of Achillea millefolium. Nat Prod
Commun. 2011;6:1527–30.
26. Falk AJ, Smolenski SJ, Bauer L, Bell CL. Isolation and identification of three
new flavones from Achillea millefolium L. J Pharmaceut Sci. 1975;64:1838–42.
27. Feizpour A, Boskabady MH, Byrami G, Golamnezhad Z, Shafei MN. The effect
of hydroethanolic extract of Achillea millefolium on muscarinic receptors of
guinea pig tracheal smooth muscle. Indian J Pharmacol. 2013;45:13–7.
28. Glasl S, Mucaji P, Werner I, et al. Sesquiterpenes and flavonoid aglycones
from a Hungarian taxon of the Achillea millefolium group. Z Naturforsch.
2002;57:976–82.
29. Goldberg AS, Mueller EC, Eigen F, Desalra SJ. Isolation of the anti-
inflammatory principles from Achillea millefolium (Compositae). J Pharm
Sci. 1969;58:938–41.
30. Haïdara K, Zamir L, Shi QW, Batist G. The flavonoid Casticin has multiple
mechanisms of tumor cytotoxicity action. Cancer Lett. 2006;242:180–90.
31. Hartwell JL. Plants used against cancer. A survey. Lloydia. 30:1967–71.
32. Hausen BM, Breuer J, Weglewski J, Rucker G. alpha-Peroxyachifolid and
other new sensitizing sesquiterpene lactones from yarrow (Achillea mille-
folium L., Compositae). Contact Dermatitis. 1991;24:274–80.
33. Innocenti G, Vegeto E, Dall’Acqua S, et al. In vitro estrogenic activity of
Achillea millefolium L. Phytomedicine. 2007;14:147–52.
34. Janackovic B, Kilibarda R. Contribution to the pharmacognostic study of
the genus Achillea in southwest Macedonia. Acta Pharmaceut Jugoslav.
1960;10:103–10.
35. Lans C, Turner N, Khan T, et al. Ethnoveterinary medicines used for
ruminants in British Columbia, Canada. J Ethnobiol Ethnomed. 2007;3:11.
36. Lemmens-Gruber R, Marchart E, Rawnduzi P, et al. Investigation of the
spasmolytic activity of the flavonoid fraction of Achillea millefolium s.l. on
isolated guinea-pig ilea. Arzneimittel-forschung. 2006;56:582–8.
37. Li Y, Zhang ML, Cong B, et al. Achillinin A, a cytotoxic guaianolide from
the flower of Yarrow, Achillea millefolium. Biosci Biotechnol Biochem.
2011;75:1554–6.
38. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of
Helicobacter pylori to botanical extracts used traditionally for the treatment
of gastrointestinal disorders. Phytother Res. 2005;19:988–91.
39. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal
plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
40. Maswadeh HM, Semreen MH, Naddaf AR. Anti-inflammatory activity of
Achillea and Ruscus topical gel on carrageenan-induced paw edema in rats.
Acta Pol Pharm. 2006;63:277–80.
Achillea millefolium L. 67

41. Middleton E, Drzewiecki G. Flavonoid inhibition of human basophil histamine

release stimulated by various agents. Biochem Pharmacol. 1984;33:3333–8.
42. Montanari T, de Carvalho JE, Dolder H. Antispermatogenic effect of
Achillea millefolium L. in mice. Contraception. 1998;58:309–13.
43. Nemeth E, Bernath J. Biological activities of yarrow species (Achillea spp.).
Curr Pharm Des. 2008;14:3151–67 (Review).
44. Orav A, Arak E, Raal A. Phytochemical analysis of the essential oil of
Achillea millefolium L. from various European Countries. Nat Prod Res.
2006;20:1082–8.
45. Oswiecimska M. Variable content of volatile oil and azulenes in herbs of
milfoil (Achillea millefolium). I. Variability independent of habitat. Dissert
Pharmaceut. 1962;14:539–45.
46. Pires JM, Mendes FR, Negri G, et al. Antinociceptive peripheral effect of
Achillea millefolium L. and Artemisia vulgaris L.: both plants known
popularly by brand names of analgesic drugs. Phytother Res. 2009;23:212–9.
47. Plowman T, Chamairo. Mussatia hyacinthia—an admixture to coca from
Amazonian Peru and Bolivia. Bot Mus Leafl. 1980;28:253.
48. Rohloff J, Skagen EB, Steen AH, Iversen TH. Production of yarrow
(Achillea millefolium L.) in Norway: essential oil content and quality.
J Agric Food Chem. 2000;48:6205–9.
49. Rucker G, Manns D, Breuer J. Peroxides as plant constituents. 8. Guaianolide-
peroxides from yarrow, Achillea millefolium L., a soluble component causing
yarrow dermatitis. Archiv der Pharmazie. 1991;324:979–81 (German).
50. Sama SK, Krishnamurthy L, Ramachnadran K, Lal K. Efficacy of an indige-
nous compound preparation (Liv-52) in acute viral hepatitis—a double blind
study. Indian J Med Res. 1976;64:738–42.
51. Tozyo T, Yoshimura Y, Sakurai K, et al. Novel antitumor sesquiterpenoids
in Achillea millefolium. Chem Pharm Bull (Tokyo). 1994;42:1096–100.
52. Vahid S, Dashti-Khavidaki S, Ahmadi F, Amini M, Salehi Surmaghi MH.
Effect of herbal medicine Achillea millefolium on plasma nitrite and nitrate
levels in patients with chronic kidney disease: a preliminary study. Iran J
Kidney Dis. 2012;6:350–4.
53. Yaeesh S, Jamal Q, Khan AU, Gilani AH. Studies on hepatoprotective,
antispasmodic and calcium antagonist activities of the aqueous-methanol
extract of Achillea millefolium. Phytother Res. 2006;20:546–51.
54. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and
cytoprotective effects of selected Pakistani medicinal plants in Helicobacter
pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
Achyranthes aspera L.
(Amaranthaceae)

Abstract
An herbaceous plant, found throughout India as a weed, in Baluchistan and
East Africa. The plant is considered carminative, diuretic, gastric tonic, anti-
inflammatory, expectorant, blood purifier and antidote for snake and scorpion
bites. Decoction of the whole plant is used in gastritis, gaseous distention, ascites,
eczema, skin eruptions and boils, and the leaves juice sometimes applied to
relieve toothache. Whole plant ash is used in gaseous distention, gastritis, cough,
asthma and urinary bladder stones in traditional medicines; the ash with honey is
also used to relieve cough. In China, the root, known as Niuxi, is considered
blood-stimulant, stasis-deobstruent, emmenagogue, liver and kidney-tonifying,
fortifying to muscles, tendons and bones, “heat-purgative”, anti-inflammatory,
and detoxicant. The herb is mainly prescribed in amenorrhea due to hemostasis,
dysmenorrhea, irregular menstruation, injuries due to impact, fractures, contu-
sions and strains, hematemesis, epistaxis, hematuria due to gonorrhea, gingivitis,
laryngitis, and carbuncle. In Ethiopian folk medicine, it is one of the plants used
for contraception, and the leaves are traditionally used for the treatment of
wounds. In the Philippines, a decoction of leaves and roots is used as a diuretic,
and the sap of the plant is useful in dissipating the corneal opacity. Seeds are used
in folk medicine of Fiji as expectorant, while the Sri Lankans use seeds as
astringent, diuretic, and for hydrophobia. It contains carbohydrates, proteins,
alkaloids, flavonoids, glycosides, saponins and tannins. Antifertility activity of
various parts has been reported by several investigators. Ethanol extract also
reduced sperm count and serum testosterone levels, and a protein isolated from
the roots exhibited irreversible spermicidal effect. Other pharmacological activi-
ties observed in animals include antioxidant, hypoglycemic, anxiolytic, antiepilep-
tic, and hypocholesterolemic. Aqueous and ethanol extracts exhibit significant
anti-inflammatory effect, which is comparable to diclofenac at higher dose of the
aqueous extract. Supplementation of DDS treatment with A. aspera of subacute
and mild leprosy patients hastened the rate of improvement and reduced chances
of reaction.
© Springer Nature Switzerland AG 2020 69
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_8
70 Achyranthes aspera L.

Keywords




Achyranth a feuilles rudes Adhoghanta Apāmarga Chile de perro Chirchita






Kafbloem Khar-e-vazhgunah Prickly chaff Spreublume Tu niu xi

Vernaculars: Urd.: Chirchita; Hin.: Apamarg, Chirchita, Khar, Latjira, Unga;

San.: Adhahśalya, Adhoghanta, Aghata, Apāmarga, Dharmargava, Khara-manjari,
Kini, Kinihi, Mayūraka, Śikhari; Ben.: Apang; Guj.: Sufed-aghado; Mal.: Kadal-
adi, Katalati; Mar.: Aghada, Pandhara-aghada; Tam.: Naayuruvi, Shiru-kadaladi;
Tel.: Antisha, Apamargamu, Uttaraeni; Ara.: Atkumah; Chi.: 土牛膝, Cu mao niu
xi, Niuxi, Tu niu xi; Dut.: Kafbloem; Eng.: Chaff flower, Devil’s horsewhip,
Prickly chaff; Fre.: Achyranth a feuilles rudes, Cadelari, Herbe d’Inde, Herbe
sergent, Queue de rat; Ger.: Spreublume; Ita.: Scimitro; Mex.: Abrojo; Per.:
Khar-e-vazhgunah; Sin.: Karalhaba; Spa.: Anamú, Chile de perro, Cola de zorro,
Mosotillo; Tag.: Dokot-dokot, Hangod, Hangor, Hangot, Libai; Vie.: Cây cỏ xước.

Fig. 1 Achyranthes aspera, Plant, Krish Dulal, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Achyranthes_aspera_NP_01.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Achyranthes aspera L. 71

Fig. 2 Achyranthes aspera, Flowers, Frank Vincentz, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Achyranthes_aspera_(Puntallana)_03_ies.
jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Description: It is an herbaceous, erect plant, found throughout India as a weed, up

to altitudes of 3,000 ft, in Baluchistan, and East Africa; leaves opposite and obovate
6–15 cm long, margins wavy, surface covered with whitish hairs; spikes terminal,
long and generally curved about the middle; flowers small and of a reddish color;
bracts green, old bracts tough, rigid, prickly and adhere to clothes; fruit conical,
covered with sharp pointed bracts and containing numerous seeds; seeds oblong
and of a shining pale-brown color. Root angular and longitudinally furrowed,
greenish or reddish in color (Figs. 1 and 2).CXVII
Actions and Uses: Unani physicians of India consider the plant (temperament, hot
2° & dry 2°) carminative, diuretic, gastric tonic, anti-inflammatory, expectorant,
blood purifier and a good antidote for snake and scorpion bites. Decoction of the
whole plant is used in gastritis, gaseous distention, ascites, eczema, skin eruptions
and boils. Leaves decoction, along with black pepper, is given in bleeding piles, and
used externally for fomentation. Whole plant ash is also used in gaseous distention,
gastritis, cough, asthma and urinary bladder stones. Its salt is used in cough as
expectorant and as treatment for asthma, and gastritis, and particularly in ascites
with camel milk.L,LXXVII NadkarniCV described it as astringent, diuretic, alterative,
antiperiodic and purgative; and topical application of a paste of grounded flowering
spikes or the seeds for bites of poisonous snakes and reptiles. Dymock et al.XL
mentioned the whole plant as pungent, purgative, digestive, diuretic, and a remedy
for phlegm, flatulence, inflammation of internal organs, piles, itch, abdominal
enlargement, and enlarged cervical glands; the ash with honey is used to relieve
cough; and the leaves juice sometimes applied to relieve toothache. The root in a
dose of 10 g was used at bedtime for night blindness, and also rubbed with water
into a paste and used as eye salve in corneal opacities. Its diuretic effect was well
known to the European physicians, and its value in dropsical affections was agreed
72 Achyranthes aspera L.

upon by many; one ounce (30 g) of the plant boiled in 300 ml of water for 15 min,
and 30–60 ml of the decoction was given 3 times a day. In the sub-Himalayan
region of Uttarakhand (India), it is one of the most preferred plants of the Tharu
community [53] and the tribes of the Chittoor district of Andhra Pradesh to tradi-
tionally treat epilepsy patients [38]. The Boxa tribe of Nainital district (India)
applies leaf paste on prolapsed uterus; and infertile women wear a piece of the root
on the neck to conceive, and also tie over the thigh during parturition for easy
delivery [55]. The root is mentioned as astringent and alterative, and used in
menorrhagia, diarrhea and dysentery; and a medicated oil is dropped in ear for
deafness and tinnitus.LXXXI In Ayurveda, the dried plant is used in śula, udararoga,
apacī, arśa, kandu, and medoroga, and the dried root is used in chardi, ādhmana,
kandu, śula, granthi, apacī, bhagandara, hrdaroga, jwara, świtra, vādhirya,
udararoga, yakrtroga, dantaroga, and raktavikāra [24].
In China, root of A. aspera is also known as Niuxi (though mainly the root of A.
bidentata is used as Niuxi), is sweetish with a bitter and sour after-taste, and a “mild”
property. Its actions are considered to be blood-stimulant, stasis-deobstruent, emme-
nagogue, liver and kidney-tonifying, fortifying to muscles, tendons and bones,
“heat-purgative,” anti-inflammatory, and detoxicant. The herb is mainly prescribed in
amenorrhea due to hemostasis, dysmenorrhea, irregular menstruation, injuries due to
impact, fractures, contusions and strains, lumber and knee atrophy, contracture of
limbs, hematemesis, epistaxis, hematuria due to gonorrhea, gingivitis, laryngitis, and
carbuncle.XVIII In the Philippines, a decoction of leaves and roots is used as a diuretic,
and the sap of the plant is useful in dissipating the corneal opacity.CXVII In Ethiopia, it
is one of the plants used for contraception in folk medicine [54], and the leaves are
traditionally used in various parts of Ethiopia for the treatment of wounds [18]. Seeds
are used in folk medicine of Fiji as expectorant [56], while the Sri Lankans use seeds
as astringent, diuretic, and for hydrophobia [6]. Leaf tea is used for colic, cough,
nausea, chest pain, flu and fever; while roots have hypotensive, cardiac depressant,
vasodilating, diuretic and purgative activity. The leaf juice has also been reported as
abortifacient, ecbolic and oxytocic [16]. In East Africa, it is used for headache,
constipation, general venereal diseases, abscesses, boils and wounds, broken and
sprained body parts, and in psychosomatic diseases. Different parts of the plant are
also used in treating wounds and ringworm [42]. Leaves dried by a fire and ground up
into a powder are applied on cuts made with a razor blade in cases of ankle sprains,
and as a medicine for headache; and the ash of the burned leaves is applied on boils.
Chewed roots are applied on cuts to stop bleeding. A decoction made from the roots
is used as a remedy for constipation in children, and to cure stitch, and pounded root
steeped in hot water is drunk cold as a cure for venereal diseases.LXXXV In Living-
stone, the plant was utilized to treat HIV/AIDS-related infections during peak of the
disease [13]. Patamona tribe of Guyana uses the plant decoction as antipyretic,
antiseptic, anti-influenza, and for the treatment of back pain.XXXIV
Phytoconstituents: Ethanol extract of leaves, collected from Bhopal, India,
showed the presence of flavonoids, saponins and tannins [14]; whereas aqueous
extract of leaves, collected near the foothills of Tirumala, Andhra Pradesh, showed
Achyranthes aspera L. 73

the presence of carbohydrates, proteins, alkaloids, flavonoids, glycosides, tannins

and saponins [38]. Methanol leaves extract also showed presence of steroids,
alkaloids and triterpene [8]. A. aspera from Pakistan was reported to contain pro-
teins 20.5%, fats 0.9%, ash 20.2%, and carbohydrates 54.2%, along with vitamin
B1, B2, B3, B6 and B9 [17]. Variation in the levels of phenolic compounds of
leaves has been reported; with rutin, chlorogenic acid and genistein present in the
extracts of plant collected from Ciaat (Eritrea), but not present in samples collected
from Ukulinga (South Africa) [42]. A water-soluble alkaloid achyranthine, betaine
and traces of other basic substances were reported in the whole plant [30, 31].
However, Arseculeratne et al. [6], reported negative tests for alkaloid. A saponin
containing oleanolic acid, glucose, galactose, rhamnose and xylose was reported
from the seeds [22, 23, 34], and later two more saponins called Achyranthus
saponins A and B were identified [27]. The root contains potassium chloride and the
alkaloid achyranthine, and ecdysterone that has strong protein anabolic action [5].
Pharmacology: Antifertility activity of A. aspera has been reported by various
investigators. Anti-implantation and abortifacient activities of benzene extract in
mice and rabbits, but not in rats [47, 48]; anti-implantation activity of methanol and
acetone extracts [49], and anti-implantation and abortifacient activities of ethanol
extract of the root [62], and methanol extract of aerial parts were reported in rats
[54]. An earlier finding by Jamwal and Anand [28] was a mild oxytocic activity of
the 50% ethanol extract on isolated guinea pig uterus; whereas the alkaloidal
fraction of root bark inhibited contractile response of isolated rat uterus to oxytocin,
but the response to serotonin and acetylcholine in rat uterus and to histamine in
guinea pig uterus was not inhibited by the fraction [25]. Pakrashi and Bhattacharya
[47] reported no estrogenic, antiestrogenic or androgenic effects of benzene extract
in mice, but potent estrogenic activity of n-butanol [65], and methanol extracts of
aerial parts [54], and ethanol root extract was observed in ovariectomized immature
female rats [62]. Ethanol extract is also reported to reduce sperm count and serum
testosterone levels [52]. A 58-kDa protein isolated from the roots exhibited irre-
versible spermicidal effect [3, 4].
Methanol leaf extract produced anxiolytic effect [7], and increased seizure
threshold, and significantly enhanced GABA levels in hippocampus and cortex of
mice [20, 64]. Seed saponins produced spasmogenic and/or parasympathomimetic
effect on CNS and caused hypotension [46]. Whole plant ethanol extract produced
hypoglycemic activity in albino rats [15], and the aqueous and methanol extracts
lowered blood glucose level in both normal and alloxan-diabetic rabbits [2]. Single
oral dose of stem and leaves ethanol extract to normal mice significantly lowered
serum glucose, and daily treatment of diabetic mice for three weeks significantly
increased antioxidant activity, and lowered glucose to normal levels [60]. Contrary
to ethanol and methanol extracts, the aqueous extract is reported to increase serum
glucose level, thyroid hormone, body weight and hepatic protein content; and
decrease hepatic LPO, without affecting the activities of SOD and CAT [59]. Single
dose of ethanol extract also significantly decreased serum TC, TGs, phospholipids,
and total lipids in Triton-induced hyperlipidemic rats, and also significantly reduced
74 Achyranthes aspera L.

the same in normal rats after 30-days dosing. Observed marked increase in the fecal
excretion of bile acids (cholic acid and deoxycholic acid) may be responsible for its
hypocholesterolemic effect [33]. Six-weeks administration of defatted ethanol seed
extract to high fat diet-induced obese mice significantly lowered serum TC, LDL-C
and TGs, and increased HDL-C, without affecting serum glucose levels [51].
Aqueous extract treatment decreased serum urea and serum creatinine levels,
reduced renal tissue architecture changes, and also decreased the crystals size of
ethylene glycol and ammonium chloride-induced nephrolithiasis in rats [1]. Aqu-
eous seed extract also reverted toward normal serum TC, TGs, phospholipids, and
FFA in liver, heart and kidney tissues of the sesame oil-induced hypercholes-
terolemic rats, and increased HDL levels [37], and significantly decreased LPO
[50]. Ethanol leaf extract was also protective against pylorus ligated gastric ulcers in
rats [14]. Sequential plant extracts with hexane, ethyl acetate, and methanol showed
significant in vitro antioxidant activity in cancer cell lines and a normal cell line
[10].
Oral ethanol extract significantly inhibited inflammation in mice and rats [21,
63], while aqueous extract at a higher dose produced significant anti-inflammatory
effect in mice, comparable to diclofenac [11]. Methanol leaves extract showed
significant anti-inflammatory effects in rats [35], also exerted significant antinoci-
ceptive effect, and potentiated the effect of morphine [8], and exhibited a pro-
nounced anticarcinogenic effect in mouse skin carcinoma model, whereas the non-
alkaloid fraction containing mainly nonpolar compounds showed most activity in
in vitro model [12]. Pancreatic cancer cells were significantly more sensitive to
in vitro cytotoxicity of methanol leaves extract than colon, breast, lung and prostate
cancer cells [57]. Oral treatment with polyphenolic extract (a mixture of quinic acid,
chlorogenic acid, kaempferol, quercetin, chrysin, and other unknown components)
to urethane primed lung cancerous mice for thirty-days significantly enhanced
antioxidant enzymes activities and downregulated expression of proinflammatory
cytokines [41]. Methanol extract to athymic mice harboring human pancreatic
tumor subcutaneous xenograft, significantly reduced both tumor weight and volume
[58], and ethanol extract for four-weeks to rats with established NDEA- and CCl4-
induced hepatocarcinogenesis, significantly decreased serum levels of ALT, AST,
ALP, bilirubin, and LPO, and significantly increased body weight and levels of
antioxidant enzymes [32].
Ethanol extracts of the roots and aerial parts were moderately but equally active
against B. subtilis, B. pumilus, P. vulgaris, C. neoformans, and A. flavus [39]. While
aqueous stem and root extracts were active against S. mutans [66]; the ethyl acetate,
ethanol and methanol extracts exhibited growth inhibitory activity against both
S. mutans and C. albicans [29]. Chloroform and butanol leaf extracts showed consid-
erable antibacterial activity against S. flexneri and E. coli; while the ethyl acetate extract
had highest activity against S. typhi [36]. Aqueous and acetone leaf extracts of samples
collected from Ciaat (Eriteria) exhibited good activity against S. aureus, B. subtilis,
K. pneumoniae and C. albicans, but moderate to weak activity by extracts of samples
collected from Ukulinga (South Africa) [42]. Methanol extract of the plant possesses
weak antiherpes virus activity, but one of its components, oleanolic acid exhibited
Achyranthes aspera L. 75

potent antiherpes virus activity against both HSV-1 and HSV-2 [40]. Topical applica-
tion of methanol leaf extract in ointment form significantly enhanced wound healing in
rats [9, 18].
Aqueous and ethanol extracts produced a sharp but transient fall in BP, and in higher
doses a slight depression of respiration of anesthetized dogs, increased the tone and
amplitude of contractions of gravid and non-gravid uteri of albino rats, guinea pigs and
rabbits, and significantly increased urinary output in rabbits [19]. They also increased
diuretic response of ethanol, and decreased the antidiuretic response of adrenaline in
albino rats [61]. Achyranthine caused a fall in BP, cardiac depression, vasodilatation and
an increase in the rate and amplitude of respiration of anesthetized dogs. However, a
mixture containing two alkaloids obtained from the whole plant increased BP, stimu-
lated respiration and increased cardiac contractility of anesthetized dogs [30]. Diuretic
and purgative effects were also observed in albino rats [43].
Clinical Studies: When twelve leprosy patients, particularly in subacute and mild
types, were treated with diamino-diphenyl-sulphone (DDS) along with A. aspera,
the rate of improvement was faster and chances of reaction were reduced [45].
Further studies on 36 treatment naïve patients with advanced, infiltrated and nodular
types of lepromatous leprosy, treated with DDS and the whole plant decoction 1 oz
twice daily, showed significant encouraging results [44].
Mechanism of Action: Anxiolytic and increased seizure threshold effects of
methanol leaf extract are mediated via significantly enhanced GABA levels in
hippocampus and cortex [20, 64].
Human A/Es, Allergy and Toxicity: A 57-years old Taiwanese man suffered from
hypotension, bradycardia and unconsciousness after consuming one liter of A. aspera
decoction but recovered fully after four days of supportive care [26].
Animal Toxicity: Acute and chronic toxicity studies, including teratogenic study,
showed the drug to be nontoxic and nonteratogenic in rats [47]. Oral aqueous [11],
and ethanol (50%) leaves extracts were nontoxic and nonlethal to mice up to a dose
of 2,000 mg/kg [32]. A 7-days toxicity study in rabbits was also unremarkable, up
to a dose of 8,000 mg/kg body weight [2].
Commentary: Its beneficial effects in leprosy patients should be revisited and
firmly established by further corroborating studies in larger patient populations. The
plant is also a good candidate for clinical investigation for its contraceptive, diuretic
and anticholesterolemic activities.

References
1. Aggarwal A, Singla SK, Gandhi M, Tandon C. Preventive and curative
effects of Achyranthes aspera Linn. extract in experimentally induced
nephrolithiasis. Indian J Exp Biol. 2012;50:201–8.
76 Achyranthes aspera L.

2. Akhtar MS, Iqbal J. Evaluation of the hypoglycaemic effect of Achyranthes

aspera in normal and alloxan-diabetic rabbits. J Ethnopharmacol. 1991;31:
49–57.
3. Anuja MM, Nithya RS, Swathy SS, Rajamanickam C, Indira M. Spermi-
cidal action of a protein isolated from ethanolic root extracts of Achyranthes
aspera: an in vitro study. Phytomedicine. 2011;18:776–82.
4. Anuja MN, Nithya RN, Rajamanickam C, Madambath I. Spermatotoxicity
of a protein isolated from the root of Achyranthes aspera: a comparative
study with gossypol. Contraception. 2010;82:385–90.
5. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Medicinal plants of East
and Southeast Asia, Attributed properties and uses. Massachusetts: MIT
Press; 1980.
6. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies on medicinal
plants of Sri Lanka. Part 14. Toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–35.
7. Barua CC, Talukdar A, Begum SA, Borah P, Lahkar M. Anxiolytic activity of
methanol leaf extract of Achyranthes aspera Linn in mice using experimental
models of anxiety. Indian J Pharmacol. 2012;44:63–7.
8. Barua CC, Talukdar A, Begum SA, et al. Antinociceptive activity of
methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae)
in animal models of nociception. Indian J Exp Biol. 2010;48:817–21.
9. Barua CC, Talukdar A, Begum SA, et al. In vivo wound-healing efficacy
and antioxidant activity of Achyranthes aspera in experimental burns.
Pharm Biol. 2012;50:892–9.
10. Baskar AA, Al Numair KS, Alsaif MA, Ignacimuthu S. In vitro antioxidant
and antiproliferative potential of medicinal plants used in traditional Indian
medicine to treat cancer. Redox Rep. 2012;17:145–56.
11. Bhosale UA, Yegnanarayan R, Pophale P, Somani R. Effect of aqueous
extracts of Achyranthes aspera Linn. on experimental animal model for
inflammation. Anc Sci Life. 2012;31:202–6.
12. Chakraborty A, Brantner A, Mukainaka T, et al. Cancer chemopreventive
activity of Achyranthes aspera leaves on Epstein-Barr virus activation and
two-stage mouse skin carcinogenesis. Cancer Lett. 2002;177:1–5.
13. Chinsembu KC. Ethnobotanical study of plants used in the management of
HIV/AIDS-related diseases in Livingstone, Southern Province, Zambia.
Evid Based Complement Alternat Med. 2016;2016:4238625.
14. Das AK, Bigoniya P, Verma NK, Rana AC. Gastroprotective effect of
Achyranthes aspera Linn. leaf on rats. Asian Pac J Trop Med. 2012;5:197–201.
15. Dhar ML, Dhar MM, Dhawan BN, Mehrotra BN, Ray C. Screening of Indian
plants for biological activity. Part I. Indian J Exp Biol. 1968;6:232–47.
16. Farnsworth NR, Bingal AS, Cordell GA, Crane FA, Fong HHS. Potential
value of plants as sources of new antifertility agents. J Pharmaceut Sci.
1975;64:535–98.
Achyranthes aspera L. 77

17. Fatima N, Dar NG, Imran H, et al. Evaluation of nutritional and subacute
toxicological study of plant based supplement of Achyranthes aspera. Pak J
Pharm Sci. 2014;27:1199–202.
18. Fikru A, Makonnen E, Eguale T, Debella A, Abie Mekonnen G. Evaluation
of in vivo wound healing activity of methanol extract of Achyranthes aspera
L. J Ethnopharmacol. 2012;143:469–74.
19. Gambhir SS, Sanyal AK, Chowdhury NK. Pharmacological study of Achyran-
thus aspera Linn.—A preliminary report. Indian J Physiol Pharmacol. 1965;9:
185–8.
20. Gawande DY, Druzhilovsky D, Gupta RC, Poroikov V, Goel RK.
Anticonvulsant activity and acute neurotoxic profile of Achyranthes aspera
Linn. J Ethnopharmacol. 2017;202:97–102.
21. Gokhale AB, Damre AS, Kulkami KR, Saraf MN. Preliminary evaluation
of anti-inflammatory and antiarthritic activity of S. lappa, A. speciosa and
A. aspera. Phytomedicine. 2002;9:433–7.
22. Gopalachari R, Dhar ML. Chemical examination of the seeds of Achyran-
thus aspera Linn. J Sci Indus Res. 1952;11B:209.
23. Gopalachari R, Dhar ML. Studies in the constitution of the saponin from the
seeds of Achyranthus aspera. Part I: Identification of the sapogenin. J Sci
Indus Res. 1958;17B:276.
24. Gupta AK, Tandon N (Editor.). Reviews on Indian medicinal plants, vol. 1.
New Delhi: ICMR; 2004. p. 140.
25. Gupta SS, Khanijo I. Antagonistic effect of Achyranthus aspera on uterine
contractility induced by oxytocin. Indian J Physiol Pharmacol. 1970;14:63.
26. Han ST, Un CC. Cardiac toxicity caused by Achyranthes aspera. Vet Hum
Toxicol. 2003;45:212–3.
27. Hariharan V, Rangaswami S. Structure of saponins A and B from the seeds
of Achyranthus aspera Linn. Phytochemistry. 1970;9:409.
28. Jamwal KS, Anand KK. Preliminary screening of some reputed abortifa-
cient indigenous plants. Indian J Pharm. 1962;24:218–20.
29. Jebashree HS, Kingsley SJ, Sathish ES, Devapriya D. Antimicrobial activity of
few medicinal plants against clinically isolated human cariogenic pathogens—
an in vitro study. ISRN Dent. 2011;2011:541421.
30. Kapoor VK, Singh H. Investigations of Achyranthus aspera Linn. Indian J
Pharm. 1967;29:285.
31. Kapoor VK, Singh H. Isolation of betaine from Achyranthus aspera Linn.
Indian J Chem. 1966;4:461.
32. Kartik R, Rao ChV, Trivedi SP, Pushpangadan P, Reddy GD. Amelioration
effects against N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogen-
esis in Swiss albino rats by whole plant extract of Achyranthes aspera. Indian J
Pharmacol. 2010;42:370–5.
78 Achyranthes aspera L.

33. Khanna AK, Chander R, Singh C, Srivastava AK, Kapoor NK. Hypolipi-
demic activity of Achyranthus aspera Linn in normal and triton-induced
hyperlipemic rats. Indian J Exp Biol. 1992;30:128–30.
34. Khastgir HN, Sengupta SK, Sengupta P. Sapogenin from seeds of
Achyranthus aspera. J Indian Chem Soc. 1958;35:693.
35. Khuda F, Iqbal Z, Khan A, et al. Anti-inflammatory activity of the topical
preparation of Valeriana wallichii and Achyranthes aspera leaves. Pak J
Pharm Sci. 2013;26:451–4.
36. Khuda F, Iqbal Z, Khan A, et al. Report: antibacterial and antifungal activities
of leaf extract of Achyranthes aspera (Amaranthaceae) from Pakistan. Pak J
Pharm Sci. 2015;28:1797–800.
37. Krishnakumari S, Priya K. Hypolipidemic efficacy of Achyranthes aspera
on lipid profile in sesame oil fed rats. Anc Sci Life. 2006;25:49–56.
38. Krishnaveni A, Thaakur SR. Pharmacognostical and preliminary phyto-
chemical studies of Achyranthes aspera linn. Anc Sci Life. 2006;26:1–5.
39. Kumar SS, Perumal P, Boopathy D, Mukherjee PK, Suresh B. Comparative
microbiological activities of ethanolic extracts of roots and aerial parts of
Achyranthes aspera Linn. Anc Sci Life. 2003;22:140–5.
40. Mukherjee H, Ojha D, Bag P, et al. Antiherpes virus activities of Achyranthes
aspera: An Indian ethnomedicine, and its triterpene acid. Microbiol Res.
2013;168:238–44.
41. Narayan C, Kumar A. Antineoplastic and immunomodulatory effect of polyphe-
nolic components of Achyranthes aspera (PCA) extract on urethane induced
lung cancer in vivo. Mol Biol Rep. 2014;41:179–91.
42. Ndhlala AR, Ghebrehiwot HM, Ncube B, et al. Antimicrobial, anthelmintic
activities and characterisation of functional phenolic acids of Achyranthes
aspera Linn.: A medicinal plant used for the treatment of wounds and
ringworm in East Africa. Front Pharmacol. 2015;6:274.
43. Neogi NC, Garg RD, Rathor RS. Preliminary pharmacological studies on
achyranthine. Indian J Pharm. 1970;32:43.
44. Ojha D, Singh G. Apamarga (Achyranthus aspera) in the treatment of
lepromatous leprosy. Lep Rev. 1968;39:23.
45. Ojha D, Tripathi SN, Singh G. Role of an indigenous drug (Achyranthus
aspera) in the management of reactions of leprosy—Preliminary observa-
tions. Lep Rev. 1966;37:115–20.
46. Oliver-Bever B. Medicinal plants in tropical West Africa II. Plants acting on
nervous system. J Ethnopharmacol. 1983;7:1–93.
47. Pakrashi A, Bhattacharya N. Abortifacient principle of Achyranthus aspera
Linn. Indian J Exp Biol. 1977;15:856–8.
48. Pakrashi A, Mookerji N, Basak B. Effect of chromatographic fractions of
the plant Achyranthus aspera L. on fertility in female albino mice. J Reprod
Fert. 1975;43:127–8.
49. Prakash AO. Potentialities of some indigenous plants for antifertility
activity. Int J Crude Drug Res. 1986;24:19–24.
Achyranthes aspera L. 79

50. Priya K, Krishnakumari S. Phytochemical analysis of Achyranthes aspera

and its activity on sesame oil induced lipid peroxidation. Anc Sci Life.
2007;27:6–10.
51. Rani N, Sharma SK, Vasudeva N. Assessment of antiobesity potential of
Achyranthes aspera Linn. seed. Evid Based Complement Alternat Med.
2012;715912.
52. Sandhyakumary K, Boby RG, Indira M. Impact of feeding ethanolic extracts
of Achyranthes aspera Linn. on reproductive functions in male rats. Indian J
Exp Biol. 2002;40:1307–9.
53. Sharma J, Gairola S, Gaur RD, Painuli RM, Siddiqi TO. Ethnomedicinal plants
used for treating epilepsy by indigenous communities of sub-Himalayan region
of Uttarakhand, India. J Ethnopharmacol. 2013;150:353–70.
54. Shibeshi W, Makonnen E, Zerihun L, Debella A. Effect of Achyranthes
aspera L. on fetal abortion, uterine and pituitary weights, serum lipids and
hormones. Afr Health Sci. 2006;6:108–12.
55. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
56. Singh YN. Traditional medicine in Fiji; Some herbal folk cures used by Fiji
Indians. J Ethnopharmacol. 1986;15:57–88.
57. Subbarayan PR, Sarkar M, Impellizzeri S, et al. Antiproliferative and anticancer
properties of Achyranthes aspera: specific inhibitory activity against pancreatic
cancer cells. J Ethnopharmacol. 2010;131:78–82.
58. Subbarayan PR, Sarkar M, Nagaraja Rao S, et al. Achyranthes aspera
(Apamarg) leaf extract inhibits human pancreatic tumor growth in athymic
mice by apoptosis. J Ethnopharmacol. 2012;142:523–30.
59. Tahiliani P, Kar A. Achyranthes aspera elevates thyroid hormone levels and
decreases hepatic lipid peroxidation in male rats. J Ethnopharmacol. 2000;
71:527–32.
60. Talukder FZ, Khan KA, Uddin R, Jahan N, Alam MA. In vitro free radical
scavenging and antihyperglycemic activities of Achyranthes aspera extract
in alloxan-induced diabetic mice. Drug Discov Ther. 2012;6:298–305.
61. Tripathi RM, Gupta SS, Sharma RK. Effect of saponin of Achyranthus
aspera (Apomarga) against adrenaline-induced antidiuresis in rats. J Assoc
Physiol Pharmacol India. 1970;15.
62. Vasudeva N, Sharma SK. Postcoital antifertility activity of Achyranthes
aspera Linn. root. J Ethnopharmacol. 2006;107:179–81.
63. Vetrichelvan T, Jegadeesan M. Effect of alcohol extract of Achyranthes aspera
Linn. on acute and subacute inflammation. Phytother Res. 2003;17:77–9.
64. Viswanatha GL, Venkataranganna MV, Prasad NBL, Godavarthi A. Achyran-
thes aspera attenuates epilepsy in experimental animals: possible involvement
of GABAergic mechanism. Metab Brain Dis. 2017;32:867–79.
80 Achyranthes aspera L.

65. Wadhwa V, Singh MM, Gupta DN, Singh C, Kamboj VP. Contraceptive
and hormonal properties of Achyranthus aspera in rats and hamsters. Planta
Med. 1986;3:231–3.
66. Yadav R, Rai R, Yadav A, et al. Evaluation of antibacterial activity of Achyran-
thes aspera extract against Streptococcus mutans: An in vitro study. J Adv
Pharm Technol Res. 2016;7:149–52.
Aconitum napellus L.
(Ranunculaceae)

Abstract
An herbaceous flowering perennial plant, was used in ancient times on spears and
arrows for hunting and battle, as it contains several poisonous alkaloids, including
cardiac poison, and during ancient Roman period was also often used to eliminate
criminals and enemies. Aconitum grows upon steep rocks, hence the name;
napellus means little turnip, the shape of the root. The root is regarded by Unani
physicians beneficial for black bile and phlegmatic diseases, nerve tonic, anesthetic
and antifebrile; and used in diseases like pneumonia, pleurisy, and topically used
for sciatica and migraine headaches. Aconitum was classified by Charaka in
Charakasamhita as lekhaneyagana, which means it reduces excess fat, and the
subterranean part is used for the treatment of nervous system disorders, fever,
diarrhea, and obesity. Aconitum species have also been used in traditional Chinese
medicine for 2000 years for weak constitution, poor metabolism, dysuria, cardiac
weakness, gout, rheumatism in the limbs, neuralgia and chills, for analgesia, as
antirheumatic and for neurological indications. It contains highly toxic alkaloids
which are structurally classified as C18-, C19-, and C20-diterpenoid alkaloids.
Among the C19-diterpenoid alkaloids, aconitine, jesaconitine, mesaconitine, and
hypaconitine are highly toxic. These diester diterpene alkaloids are mainly
responsible for the toxicity of Aconitum species, which mainly affect the CNS,
muscle tissues and heart with malignant ventricular arrhythmias. Aconitine is
a potent neurotoxin that opens tetrodotoxin-sensitive sodium channels, and
increases sodium influx through these channels and delays repolarization. It is
always used internally after a purification (detoxification) process. All Indian and
Chinese detoxification procedures convert toxic diester diterpenoid alkaloids to
relatively safer monoester diterpenoid alkaloids. Pharmacologically, Aconitum
species are reported to possess antifungal, anti-inflammatory, and immunostim-
ulant properties.

© Springer Nature Switzerland AG 2020 81

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_9
82 Aconitum napellus L.

Keywords





Aconite Aconit napel Bachchnag Beesh Blauer eisenhut Blauwe





monnikskap Monk’s hood Taj-ul-malook Vatsanábha Zhichuanwu

Vernaculars: Urd.: Beesh; Hin.: Bachchnag, Batsnab-bish, Dudhia bikha, Kota

bikha, Meetha, Metha teelea; San.: Vatsanábha, Visha; Ben.: Bisha, Dudhia bikha,
Katbish; Mal.: Vatsanabhi; Mar.: Bachnag punjabi; Tam.: Vashanavi; Tel.:
Vesanabhi; Ara.: Khaniq al-namr, Khaniq et-zeib; Chi.: 舟形乌头, Zhicaowu,
Zhichuanwu; Dut.: Blauwe monnikskap, Gewone akoniet; Eng.: Aconite, Blue
rocket, Devil’s helmet, Monk’s hood, Wolf’s bane; Fre.: Aconit napel, Capuce de
moine, Gueule de loup; Ger.: Blauer eisenhut, Blauer sturmhut; Ita.: Aconito
napello, Erba luparia; Per.: Taj-ul-malook; Spa.: Aconite, Anapelo, Stormhatt;
Vie.: Cây phu tử.
Description: An herbaceous flowering perennial plant growing in temperate
sub-alpine Himalayas, from Sikkim to Garhwal (India) [11], up to a height of 1 m,
with hairless stems and leaves. The leaves in segments, wedge-shaped and deeply
cut; flowers are dark purple to bluish-purple, narrow, oblong, helmet-shaped, 1–
2 cm long. The conical tuberous roots, brown in color, irregular and roughly
wrinkled, 5–7 cm long and 2 cm thick at the crown, the lower portion tapered and
marked with few scars and fragments of rootlets, is devoid of any marked odor.
Chewing leaves and roots leaves a long-lasting tingling sensation on the tongue.
Aconitum grows upon steep rocks, hence the name; napellus means little turnip, the
shape of the root (Figs. 1 and 2).LXXXI
Actions and Uses: Aconite was the name given to Apollo, the god who averts evil,
and used by the ancients to destroy wild beasts.XL In ancient times, it was used on
spears and arrows for hunting and battle as it contains several poisonous alkaloids,
including a cardiac poison. During the ancient Roman period, it was also often used to
eliminate criminals and enemies. Unani physicians consider the root (temperament,
hot 4° and dry 4°) beneficial for black bile and phlegmatic diseases, nerve tonic,
anesthetic and antifebrile; and use it as analgesic, local anesthetic, diuretic, and
emmenagogue, and as antipyretic in diseases like pneumonia, pleurisy, and topically
used for sciatica and migraine headaches.LXXVII It is described as a powerful sedative,
anodyne, antiphlogistic and antipyretic,CV and always used internally after purifica-
tion (detoxification) of the drug with cow’s urine or cow’s milk [30]; by suspending 20
g of beesh in 2 L milk and heated at low heat until the whole milk is evaporated, then it
is washed with hot water and used. Without purification, it is a strong poison and kills
within a short time. The poisoning symptoms start with a loss of sensation in the mouth
and pharynx, burning sensation in the stomach, vomiting, the body skin becomes
sticky or extreme sweating with creeping sensation, irregular pulse, dilated pupils,
asphyxiation, muscular weakness, convulsions, followed by coma and death. Ibn
al-BaitarLXIX quoted Avicenna that its topical application cures leucoderma, and also
mentioned that one of its kinds grows only in the Chinese city of ‘Hala-Hal’ near a
place called ‘Sind’ where dried beesh is used as a diet without any toxicity, but
anywhere outside the city it will be fatal. Also, Ibn al-Baitar quoted Hubaish that other
than humans, it is not poisonous to animals, and a bird called Salomi feeds on it and rats
Aconitum napellus L. 83

Fig. 1 Aconitum napellus, Flowers, Jerzy Opioła, WikimediaCommons, https://commons.wiki

media.org/wiki/File:Aconitum_napellus_a1.jpg

become obese eating it. In modern literature also, Aconitum species are recorded as
food plant of the caterpillars of several moth. A. heterophyllum is described as Atis in
Unani medicine and regarded nontoxic, is considered astringent, styptic and anti-
pyretic, and is used in the treatment of nosebleed, dysentery and periodic fevers.LXXVII
However, Prasad et al. [27] mentioned traditional uses of A. heterophyllum in hysteria,
throat infection, dyspepsia, abdominal pain and diabetes, and consider it a valuable
febrifuge, and nervine tonic especially to combat debility after malaria, and in
hemiplegia. In Ayurveda, A. heterophyllum is a good aphrodisiac and effective
diuretic, a potent anthelmintic against guinea-worms, lowers BP, and prescribed
for cough irritations and bronchitis, malarial fevers, noninsulin dependent diabetes,
and as a bitter remedy against gastroenteric fevers in infants and children. Four forms
of A. heterophyllum (White, Yellow, Black and Red) have been identified; the white
variety tuberous roots of a pale-yellow color are considered the best. The roots contain
two intensely bitter diterpene alkaloid atisine and atidine [34]. Aconitum is classified
by Charaka in Charakasamhita as lekhaneyagana, which means it reduces excess fat,
and the subterranean part is used for the treatment of nervous system disorders, fever,
84 Aconitum napellus L.

Fig. 2 Aconitum napellus, Flower (Close up), H. Zell, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Aconitum_napellus_010.JPG;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

diarrhea, and obesity [33]. Khory and KatrakLXXXI described it as sedative, anodyne,
mydriatic and poisonous, that depresses circulation and respiration, and as a powerful
antiphlogistic, if used early it is very useful in the early stages of acute catarrhal or
asthenic fevers, acute catarrhal inflammation and vascular excitement, acute pleurisy,
pericarditis, orchitis, acute peritonitis, and in acute rheumatism. However, it should
not be used in asthenic patients, in weak, fatty or dilated heart, in continued fevers, in
gastrointestinal irritation and pulmonary inflammation. Ultra high dilutions of
aconitum are also used in the homeopathic medicine [2]. Aconitum is recorded in the
earliest Chinese herb classic, The Herbal by Shen Nung, and aconitum species have
been used in TCM for 2000 years for weak constitution, poor metabolism, dysuria,
cardiac weakness, gout, rheumatism in the limbs, neuralgia and chills,LXVI for anal-
gesia, as antirheumatic and neurological indications [3] in a herbal medicine called
Bushi [36] after a detoxification process called Paozhi [23, 31]. All Indian and Chinese
detoxification procedures convert toxic diester diterpenoid alkaloids to relatively safer
monoester diterpenoid alkaloids [19]. Detoxified roots of A. carmichaelii Debx.
(Zhichuanwu) and A. kusnezoffii (Zhicaowu) are the only sanctioned species of
Aconitum for clinical use in China for the treatment of rheumatalgia, rheumatic
arthritis, cold, and pain, and are listed in the Chinese Pharmacopoeia [4]. In Mexican
traditional medicine, it is used topically to relieve pain, itching and inflammation, and
internally to reduce febrile states [10]. In Italy, the roots and seeds of A. napellus are
freely sold at the herb market for treating musculoskeletal pain [17].
Aconitum napellus L. 85

Phytoconstituents: Aconitum species are rich in diterpene alkaloids, flavonoids,

tannins, saponins, and sugars [26, 37]. The highly toxic alkaloids are structurally
classified as C18-, C19-, and C20-diterpenoid alkaloids. Among the C19-diterpenoid
alkaloids, aconitine, jesaconitine, mesaconitine, and hypaconitine are highly toxic,
while the C20-diterpenoid alkaloids, lucidusculine, kobusine, pseudokobusine, and
atisine are much less toxic [36]. A number of diterpenoid alkaloids, including aco-
nitine, N-deethylaconitine [9] and norditerpenoid alkaloids from ssp. Neomontanum
[22], kobusine and pseudokobusine [35], neoline, napelline, isotalatizidine, karako-
line, senbusine A, senbusine C, aconitine and taurenine from ssp. Firmum [20],
heterophyllinine-A, heterophyllinine-B, dihydroatisine and lycoctonine [25], ben-
zoylmesaconine, mesaconitine, aconitine, hypaconitine and deoxyaconitine [37], and
6-dehydroacetylsepaconitine, 13-hydroxylappaconitine, lycoctonine, delphatine and
lappaconitine from the roots of A. heterophyllum [1], and flavonol glycosides from
different subspecies [7, 12, 13] have been isolated. Jaiswal et al. [18] analyzed three
species, being used in TCM and Ayurveda, namely: A. carmichaelii, A. kusnezoffii and
A. heterophyllum, for their diterpene alkaloid contents. Aconitine, mesaconitine and
hypaconitine were exclusively found in A. carmichaelii and A. kusnezoffii, the two
officially approved species in China, and most toxic components were found in the
large A. carmichaelii roots.
Pharmacology: Aconitum species are reported to possess antifungal [5], anti-
inflammatory [29], and immunostimulant properties [6]. Oral administration of
methanol root extract of A. heterophyllum to obese rats substantially lowered TC,
TGs and apolipoprotein B concentrations, increased HDL-C and apolipoprotein A1
concentrations, and lowered HMG-CoA reductase activity [33], while the ethanol
root extract, with aconitine content of 0.0833% w/w, to rats significantly reduced
castor oil-induced diarrhea, small intestinal transit, and fluid accumulation [27].
Ikram et al. [16] reported significant antipyretic activity of hexane and chloroform
extracts of A. napellus, but no antipyretic activity in A. heterophyllum root extracts.
Mechanism of Action: Aconitine is a potent neurotoxin that opens tetrodotoxin
sensitive sodium channels, and increases sodium influx through these channels and
delays repolarization, thus increasing excitability and promoting ventricular dys-
rhythmias. Modulation of neurotransmitter release and related receptors, promotion
of LPO and induction of cell apoptosis in heart, liver or other organs are other
suggested mechanisms [14].
Human A/Es, Allergy and Toxicity/Poisoning: Diester diterpene alkaloids inclu-
ding aconitine (AC), mesaconitine and hypaconitine are mainly responsible for the
toxicity of Aconitum species; the alkaloids mainly affect the CNS, muscle tissues
and heart with malignant ventricular arrhythmias [17]. Cases of intoxication,
intentional and unintentional, with A. napellus (Monk’s hood) roots and seeds are
regularly reported in the literature, including a rare poisoning of a 20 month old
child [11]. Adults show up in ERs with gastrointestinal (nausea, violent vomiting
and diarrhea), neurological (burning, tingling, and numbness in the mouth and face
paresthesia, vertigo, dyschromatopsia, unconsciousness, syncope), and cardiovas-
cular (hypotension and arrhythmias) symptoms [8, 17, 21, 24], who recover after
86 Aconitum napellus L.

supportive treatment, but some with lethal outcome, usually due to malignant
ventricular arrhythmias [15, 28, 32]. Aconitine is the most toxic alkaloid; its human
lethal dose in adults is 3–6 mg [15]. All toxicities reported here are only for
A. napellus and not for any other Aconitum species.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Potential Drug-Herb Interactions: Aconitine, benzoylaconine, and aconine in-
crease expression of p-glycoprotein (p-gp) in vitro in LS174T and Caco-2 cells, and
AC significantly upregulates the p-gp protein levels in the jejunum, ileum, and
colon of FVB mice, and protects them against acute AC toxicity. AC also decreases
the cellular toxicity of vincristine and doxorubicin [38].
Commentary: There are no clinical studies, probably due to its toxic nature,
reported in the mainstream English publications listed on PubMed.

References
1. Ahmad M, Ahmad W, Ahmad M, et al. Norditerpenoid alkaloids from the
roots of Aconitum heterophyllum Wall with antibacterial activity. J Enzyme
Inhib Med Chem. 2008;23:1018–22.
2. Ahmad S, Rehman T, Abbasi WM. Effects of homoeopathic ultrahigh
dilutions of Aconitum napellus on Baker’s yeast-induced fever in rabbits.
J Integr Med. 2017;15:209–13.
3. Ameri A. The effects of Aconitum alkaloids on the central nervous system.
Prog Neurobiol. 1998;56:211–35.
4. Anonymous. Chinese Pharmacopoeia Commission: The Pharmacopoeia of
the People’s Republic of China (English edition). Beijing, China: China
Medical Science Press; 2010.
5. Anwar S, Ahmad B, Sultan M, Gul W, Islam N. Biological and pharmaco-
logical properties of Aconitum chasmanthum. J Biol Sci. 2003;3:989–93.
6. Atal CK, Sharma ML, Koul A, Khajuria A. Immunomodulating agents of
plant origin. I: Preliminary screening. J Ethnopharmacol. 1986;18:133–41.
7. Braca A, Fico G, Morelli I, et al. Antioxidant and free radical scavenging
activity of flavonol glycosides from different Aconitum species. J Ethnophar-
macol. 2003;86:63–7.
8. Chan TY. Incidence and causes of aconitum alkaloid poisoning in Hong
Kong from 1989 to 2010. Phytother Res. 2015;29:1107–11.
9. Colombo ML, Bravin M, Tome F. A study of the diterpene alkaloids of
Aconitum napellus ssp. neomontanum during its onthogenetic cycle. Phar-
macol Res Commun. 1988;20 Suppl 5:123–8.
10. de la Peña SS, Sothern RB, López FS, et al. Circadian aspects of hyper-
thermia in mice induced by Aconitum napellus. Pharmacogn Mag. 2011;7:
234–42.
Aconitum napellus L. 87

11. Feldkamp A, Köster B, Weber HP. Fatal poisoning caused by aconite

monk’s hood (Aconitum napellus). Monatsschr Kinderheilkd. 1991;139:366–
7 (Article in German).
12. Fico G, Braca A, Bilia AR, Tomè F, Morelli I. New flavonol glycosides
from the flowers of Aconitum napellus ssp. tauricum. Planta Med. 2001;67:
287–90.
13. Fico G, Braca A, De Tommasi N, Tomè F, Morelli I. Flavonoids from
Aconitum napellus subsp. neomontanum. Phytochemistry. 2001;57:543–6.
14. Fu M, Wu M, Qiao Y, Wang Z. Toxicological mechanisms of Aconitum
alkaloids. Pharmazie. 2006;61:735–41.
15. German Jørgensen JR, Andersen AE. Fatal exposure to Aconitum napellus.
Ugeskr Laeger. 2013;175:1707–8 (Article in Danish).
16. Ikram M, Khattak SG, Gilani SN. Antipyretic studies on some indigenous
Pakistani medicinal plants: II. J Ethnopharmacol. 1987;19:185–92.
17. Imazio M, Belli R, Pomari F, et al. Malignant ventricular arrhythmias due to
Aconitum napellus seeds. Circulation. 2000;102:2907–8.
18. Jaiswal Y, Liang Z, Ho A, et al. Distribution of toxic alkaloids in tissues
from three herbal medicine Aconitum species using laser micro-dissection,
UHPLC-QTOF MS and LC-MS/MS techniques. Phytochemistry. 2014;107:
155–74.
19. Jaiswal Y, Liang Z, Yong P, Chen H, Zhao Z. A comparative study on the
traditional Indian Shodhana and Chinese processing methods for aconite
roots by characterization and determination of the major components. Chem
Cent J. 2013;7:169.
20. Kiss T, Orvos P, Bánsághi S, et al. Identification of diterpene alkaloids from
Aconitum napellus subsp. firmum and GIRK channel activities of some
Aconitum alkaloids. Fitoterapia. 2013;90:85–93.
21. Kunz A, Marty H, Nohl F, Schmitt W, Schiemann U. Mixed intoxication
with Aconitu nappellans (Monk’s hood) and Digitalis grandiflora (large
yellow foxglove). Med Sci Monit. 2010;16:CS103–5.
22. Liu H, Katz A. Norditerpenoid alkaloids from Aconitum napellus ssp. neomon-
tanum. Planta Med. 1996;62:190–1.
23. Liu S, Li F, Li Y, et al. A review of traditional and current methods used to
potentially reduce toxicity of Aconitum roots in Traditional Chinese
Medicine. J Ethnopharmacol. 2017;207:237–50.
24. Moritz F, Compagnon P, Kaliszczak IG, et al. Severe acute poisoning with
homemade Aconitum napellus capsules: toxicokinetic and clinical data. Clin
Toxicol (Phila). 2005;43:873–6.
25. Nisar M, Ahmad M, Wadood N, et al. New diterpenoid alkaloids from
Aconitum heterophyllum Wall: selective butyrylcholinestrase inhibitors.
J Enzyme Inhib Med Chem. 2009;24:47–51.
26. Pelletier SW, Aneja R. The diterpene alkaloids. Three new diterpene lactone
alkaloids from Aconitum heterophyllum Wall. Tetrahedron Lett. 1967;6:
557–62.
88 Aconitum napellus L.

27. Prasad SK, Jain D, Patel DK, Sahu AN, Hemalatha S. Antisecretory and
antimotility activity of Aconitum heterophyllum and its significance in
treatment of diarrhea. Indian J Pharmacol. 2014;46:82–7.
28. Pullela R, Young L, Gallagher B, Avis SP, Randell EW. A case of fatal
aconitine poisoning by Monk’s hood ingestion. J Forensic Sci. 2008;53:
491–4.
29. Santosh V, Shreesh O, Mohammad R. Anti-inflammatory activity of Aconitum
heterophyllum on cotton pellet-induced granuloma in rats. J Med Plants Res.
2010;4:1566–9.
30. Shah RK, Kenjale RD, Shah DP, Sathaye S, Kaur H. Evaluation of
cardiotoxicity of shodhit and ashodhit samples of aconite root. Int J
Pharmacol Biol Sci. 2010;4:65–8.
31. Singhuber J, Zhu M, Prinz S, Kopp B. Aconitum in traditional Chinese
medicine: a valuable drug or an unpredictable risk? J Ethnopharmacol.
2009;126:18–30.
32. Sørensen B. Poisoning with Aconitum napellus (Monk’s hood). Ugeskr
Laeger. 2003;165:2109–10 (Danish).
33. Subash AK, Augustine A. Hypolipidemic effect of methanol fraction of Aconi-
tum heterophyllum Wall ex Royle and the mechanism of action in diet-induced
obese rats. J Adv Pharm Technol Res. 2012;3:224–8.
34. Ukani MD, Mehta NK, Nanavati DD. Aconitum heterophyllum (ativisha) in
ayurveda. Anc Sci Life. 1996;16:166–71.
35. Wada K, Ishizuki S, Mori T, Fujihira E, Kawahara N. Effects of Aconitum
alkaloid kobusine and pseudokobusine derivatives on cutaneous blood flow
in mice. Biol Pharm Bull. 1998;21:140–6.
36. Wada K, Ohkoshi E, Zhao Y, et al. Evaluation of Aconitum diterpenoid
alkaloids as antiproliferative agents. Bioorg Med Chem Lett. 2015;25:
1525–31.
37. Wang Z, Wen J, Xing J, He Y. Quantitative determination of diterpenoid
alkaloids in four species of Aconitum by HPLC. J Pharm Biomed Anal.
2006;40:1031–4.
38. Wu J, Lin N, Li F, et al. Induction of p-glycoprotein expression and activity
by Aconitum alkaloids: implication for clinical drug-drug interactions. Sci
Rep. 2016;6:25343.
Acorus calamus L.
(Acoraceae)

(Syns.: A. angustatus Raf.; A. belangeri Schott; A. casia Bertol.; A. elatus Salisb.;

A. flexuosus Raf.; A. odoratus Lam.)

Abstract
A semiaquatic perennial plant, found in damp marshy places especially at the banks of
lakes and streams in India, Myanmar, Iran, South China, Europe, and North America.
Arabian physicians identify it as Acoron of the Greeks. Avicenna described the drug
under the name of Waj and quoted Galen with regard to its properties, and all the
Arabian and Persian physicians reproduced what Dioscorides had written about it.
Arabian physicians also agree in identifying it as the Acoron of the Greeks. The
rhizomes are considered deobstruent, carminative, brain and nerve tonic, and
purgative of phlegmatic humours which are supposed to be the causes of paralysis,
dropsy and many other diseases; hence used in cases of convulsions, paralysis,
insomnia and numbness. It is also used as an infusion in dyspepsia, flatulence,
anorexia, and in atonic and choleric diarrhea of children. It is one of the three most
frequently cited drugs in the Chinese classical medical literature over the past
1800 years for the treatment of forgetfulness. Chinese consider it analeptic,
expectorant, anti-inflammatory, detoxicant, and anthelmintic, and use it to treat
manic-depressive psychosis, epilepsy induced by fear, convulsions, coma due to
phlegm, rheumatism, loss of appetite due to fulminant dysentery, and to promote
wound healing. The Potawatomis native Indians sniffed the powdered root to treat
catarrh; other American natives chewed the root to stop coughs, drank a decoction or
inhaled smoke to relieve cold symptoms. Acorin and acoretin are the two bitter
principles of the root. Asarone (chemically like muscaline), and b-asarone
(chemically like myristicin and Kava alkaloids) are said to be the active
hallucinogenic principles. A volatile oil, due to its major constituent b-asarone, is
responsible for the drug’s characteristic odor and taste; the exact composition of the
oil varies somewhat with the geographical origin of the plant. Ethanol rhizome extract
exhibits analgesic, sedative, anticonvulsive, moderately hypotensive and respiratory
depressant properties, and demonstrated significant antidepressant effects in animal
models. Its hypnosis-potentiating and hypotensive activities reside in the volatile oil.

© Springer Nature Switzerland AG 2020 89

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_10
90 Acorus calamus L.

Keywords





Acoro aromatico Agar-e-Turki Arzneikalmus Bacch Cálamo acuático







Jatila Calamus Eğir out Myrtle grass Shôbu Shui Ch’ang-p’u Sweet-flag

Vernaculars: Urd.: Bacch, Waj Turki; Hin.: Bacch, GherBacch, Gora-bach; San.:
Bhadra, Jatila, Sadgrantha, Śataparvika, Shadgranthagolomi, Shad-grandtra, Ugra-
gandhā, Vachā, Vacha-golomi, Vayambur; Ben.: Sweet-bach; Mal.: Vashambu,
Vashampa, Vayambu; Mar.: Bal-vekhand, Vekhand; Tam.: Vasambu, Vashambu;
Tel.: Vadaja, Vasa, Vudya; Ara.: Ighir, Ikaroon, Oodul-waj, Oodul-zanj, Qasabul
zareera, Zanjabeel-al-ajam; Bur.: Linhe, Chi.: Chāng pu, Pai ch’ang-p’u, Shui
ch’ang-p’u; Dut.: Echte kalmus, Kalmoes; Eng.: Acorus roseau, Belle angélique
(Canada), Calamus, Flag root, Grass myrtle, Myrtle flag, Myrtle grass, Sweet cala-
mus, Sweet-flag, Sweetroot; Fre.: Acore aromatique, Acore calame, Acore odorant,
Acore vrai, Canne aromatique, Jonc odorant, Lis des marais, Roseau odorant; Ger.:
Arzneikalmus, Deutscher Ingwer, Kalmus; Ind.: Dlingo; Ita.: Acoro aromatico,
Acoro vero, Calamo aromatico; Jap.: Shôbu; Kor.: Changpo; Nep.: Bojho,
Shyuedaa; Per.: Agar, Agar-e-Turki, Waj; Por.: Calamo-aromatico; Spa.: Acoro,
Calamís, Cálamo acuático, Cálamo aromático; Sin.: Wadakaha; Tag.: Lubigan;
Thai.: Hang khao pha, Som chuen, Wan nam, Wan nam lek; Tur.: Eğir otu.
Description: It is a semiaquatic perennial plant, found in damp marshy places
especially at the banks of lakes and streams in India (Manipur, Naga Hills), Myanmar,
Iran, south China, Europe, and North America. It has indefinitely branched rhizomes,

Fig. 1 Acorus calamus, Plant, J.F. Gaffard, Autoreille, France, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Acorus_calamus1.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Acorus calamus L. 91

Fig. 2 Acorus calamus, Illustration. Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://commons.
wikimedia.org/wiki/File:Illustration_Acorus_calamus0.jpg

which are cylindrical up to 20 cm long and 2 cm in diameter, longitudinally furrowed

on the upper surface and with conspicuous root scars on the lower surface, varying in
color from dark brown to orange-brown. They break easily with a short corky fracture,
and exhibit a whitish spongy interior. The odor is aromatic and agreeable; the taste
bitterish and pungent. The Persian variety is darker in color when fractured, and has a
more powerful odor (Figs. 1 and 2).LIX
Actions and Uses: Avicenna described the drug under the name of Waj and quoted
Galen with regard to its properties, and all the Arabian and Persian physicians
reproduced what Dioscorides had written about it. Arabian physicians also agree in
identifying it with the Acoron, a plant of the Greeks. The authors of Pharma-
cographia Indica remarked—“The description of Acoron, a plant of Colchis,
Galatia, Pontus, and Crete, given by Dioscorides and Pliny, certainly refer to this
drug.”XL In Unani medicine, the rhizomes (temperament, hot 2° and dry 2°) are
considered deobstruent, carminative, brain and nerve tonic, and purgative of
phlegmatic humours which are supposed to be the causes of paralysis, dropsy and
many other diseases; hence used in cases of convulsions, paralysis, insomnia and
92 Acorus calamus L.

numbness. It is also reputed as an emmenagogue, diuretic, and aphrodisiac. As

poultice, it is applied to paralyzed limbs and rheumatic swellings; internally, it is
also given as gastric tonic, carminative, and for calculous afflictions.XL,L,LXIX,
LXXVII,LXXXI
It is used as an infusion in dyspepsia, flatulence, anorexia, and also in
atonic and choleric diarrhea of children; also a nervine sedative, beneficial in
hysteria and neuralgia, and in large doses, nauseant and emetic.CV Chopra et al.XXI
described it as emetic, nauseant, carminative, antispasmodic and expectorant; and
used as a remedy for asthma, chronic diarrhea, snake and scorpion bites. According
to Macmillan,XCIII it is used in bowel complaints of children.
This plant bears the Sanskrit names of Vacha (talking), Shadgrantha (six-knotted),
Ugragandha (strong-smelling), and Jatila (having entangled hair), and is described in
the Niganthas as hot, pungent, bitter, stomachic and emetic; useful for clearing the
voice by removing phlegm, and in colic. In Ayurveda, dried rhizomes are used in the
treatment of apasmāra, unmāda, vibandha, śūla, ādhmāna, karna srāva, kāsa, śwāsa,
smrti daurbalya,LIX insomnia, melancholia, neurosis, hysteria, and remittent
fevers.LXXXIV A pessary composed of acorus, saffron and mare’s milk is used to
facilitate delivery; a hip bath of the decoction is also effective for this purpose.XL The
rhizomes are stimulant and tonic, and used for ague and tonic dyspepsia.XIII,XXXI,LIV,
LXXXIV,CXXXXVIII
In Garhwal region of India, pieces of rhizomes are hung around
neck of children for hastening the teething process, and the rhizome powder is used for
epileptic fits [76]. The Boxa tribe of Nainital district (India) tie a dried piece of root
‘Bach’ on the neck of both mother and child to protect them from the evil spirits, while
traveling on foot [82].
The Potawatomis native Americans sniffed the powdered root to treat catarrh; other
native Americans chewed the root to stop coughs, drank a decoction or inhaled smoke
to relieve cold symptoms. In Tehran, the rhizome is considered to be an excellent
remedy for rheumatism.LXIV It is used for coughs, colds, bronchial, throat and
stomach troubles in China, Japan, Africa, North America and Mexico; and used as
intoxicating snuff ritual in the western hemisphere [26]. It is known as Wadakaha in
Sri Lanka, and the rhizomes are used for rheumatism. The Surinam Javans use the
roots for stomachache and dysentery.XXXIV In China, the rhizome is called Shui-
changpu; with a bitter, acrid taste and “warm” property, and considered analeptic,
expectorant, detoxicant, anti-inflammatory, and anthelmintic, and used to treat manic-
depressive psychosis, epilepsy induced by fear, convulsions, coma due to phlegm,
rheumatism, loss of appetite due to fulminant dysentery, carbuncle, furuncle, tinea,
and scabies,XIX and also used to promote wound healing [77]. It is one of the three
most frequently cited drugs in the Chinese classical medical literature over the past
1800 years for the treatment of forgetfulness [56]. It is also used in traditional Korean
medicine for improvement of memory and cognition in old age [64], and to treat
allergic symptoms, including asthma and bronchitis [42].
Many modern writers recommend an infusion of the rhizome for fevers and dys-
pepsia; chewing the rhizome to ease digestion and to clear voice, and using the
powdered material as a sachet and toilet powders. Dried rhizome is chewed ad libitum
to relieve dyspepsia, specifically for the heartburn accompanied with sour eructations.
For prompt relief a few small pieces of the cut root are chewed and the juice (only)
Acorus calamus L. 93

swallowed for five to ten minutes. In chronic conditions, the root may be chewed for
several times a day until the stomach is back in good healthy working order.
HonigbergerLXIII said that the Hakims use the rhizome in hemorrhages and intestinal
ulcerations, and also for treatment of suppression of urine (oliguria or anuria), and
menstrual evacuations. Powdered rhizome is also useful as insecticide.XLV,LXIV The
root prepared in various manners is a folk remedy for indurations of the liver, spleen
and stomach, hard swellings and tumors of the testicles, uterus and vagina [33], are
aromatic bitters, and used as stomachic and tonic [12]. The oil has expectorant action,
and is used for asthma. Chopra quoted Evers, who had tried the oil effectively in
chronic dysentery. The oil is used for scenting and snuff, and in preparation of aro-
matic cordials and liquors, for flavoring beer, and also in making perfumes. In the
Philippines, it is used as a masticatory for toothache, as a stimulant and carminative,
and antirheumatic when used as a liniment.CXVII
Phytoconstituents: Following constituents have been identified in calamus: aco-
lamone, acoric acid, acorine, acorone, acoroxide, acoragermacrone, asaraldehyde,
asaronaldehyde, asarone, b-asarone, azulene, calamene, calameone, calamenol,
calamenone, calamendiol, isocalamendiol, calamol, camphene, camphor, choline,
cineole, dextrin, dextrose, dimethylamine, eugenol, n-heptylic acid, isoacalamone,
isoacorone, linalol, methylamine, methyleugenol, palmitic acid, parasarone, pinene
and trymethylamine [88]. Acorin and acoretin are the two bitter principles reported.
Mucilage, resin and tannins are also present; calamol is a colorless, mobile liquid
with a strong characteristic and rather pleasant aromatic odor.XXXVIII Ethanol root
extract showed the presence of glycosides, tannins, flavonoids and saponins [41].
GrieveLV reported that the rhizome also contains an alkaloid, mainly choline, soft
resin, gum, starch and the bitter glucoside acorin, which is amorphous, semifluid,
resinous, of neutral reaction, aromatic odor and bitter aromatic taste. A novel
tropoloisoquinoline alkaloid, neotatarine, has been isolated from the ethanol rhi-
zome extract [46]. Asarone (chemically like muscaline), and b-asarone (chemically
like myristicin and Kava alkaloids) are said to be the active hallucinogenic prin-
ciples.LXXXVIII A potent mitogenic lectin from rhizomes significantly inhibited
growth of murine macrophage cancer cell-line [7]. Various sesquiterpenes, neoa-
corane A, acoric acid, calamusin D, 1b, 4b, 7a-trihydroxyeudesmane, bullatantriol,
teuclatriol, threo-1′,2′-dihydroxyasarone, erythro-1′,2′-dihydroxyasarone, (+)-de-4′-
O-methyleudesmin, (+)-de-4′-O-methylmagnolin, (+)-eudesmin, (+)-magnolin and
b-sitosterol, have been isolated from the roots/rhizomes [29, 30, 32, 47, 70].
The volatile oil yield, a yellowish-brown fluid responsible for the drug’s charac-
teristic odor and taste, ranges from 1.5% to more than 3.5%. Although the exact
composition of the oil varies somewhat with the geographical origin of the plant, its
major constituent (75%) is invariably b-asarone. The oil contains palmitic and heptoic
acids, ester of palmitic acid together with some pinene, camphene, asaraldehyde,
eugenol, asarone, calamene, calamerol and calameon.XLIX The month of June is
described the best for harvesting the plant for volatile oil [48]. Main components of
rhizomes EO have been identified as acorenone, isoacorone, (Z)-sesquilavandulol,
94 Acorus calamus L.

dehydroxyisocalamendiol and b-asarone; the contents of isoacorone and cryptoa-

corone differed in the EOs from the same starting material by hydrodistillation, and by
steam distillation [55]. Essential oil obtained from rhizomes collected from various
northwest Himalayan regions of Uttarakhand in India differed in composition, both
qualitatively and quantitatively, but b-asarone was the main component of all sam-
ples, which showed potent anthelmintic activity against A. galli [44]. Bisht et al. [10]
reported fifteen constituents, accounting for 97.8% of EO, obtained from roots (col-
lected from Uttarakhand State) by hydrodistillation; major constituents included (Z)-
asarone (81.1–92.4%), (Z)-methyl isoeugenol, (Z)-isoelemicin, (E)-asarone, (E)-
methyl isoeugenol, (Z)-b-ocimene, elemicin, linalool and kessane. Joshi [38] reported
forty constituents in the hydrodistilled EO from rhizomes, accounting for 98.3%, with
b-asarone being the major constituent. Essential oils obtained by hydrodistillation of
leaves and rhizomes collected from various parts of Nepal were dominated by (Z)-
asarone; also contained (E)-asarone and small amounts of c-asarone, (Z)-methyl
isoeugenol, and linalool [75]. Methyl isoeugenol and cyclohexanone were identified
as the major constituents of the EO from Korean Acorus [43].
Pharmacology: Ethanol rhizome extract possesses analgesic activity [41], sedative,
moderately hypotensive and respiratory depressant properties [2], and exhibits signif-
icant antidepressant effects in animal models, without postsynaptic 5-HT1A receptors
sensitization [84]. Its hypnosis-potentiating and hypotensive activities reside in the
volatile oil [15, 16, 24]. Ethanol rhizome extract potentiated pentobarbitone-induced
sleeping, caused a significant inhibition of CAR and exhibited hypothermic effect in
albino rats. A single injection reduced aggressive behavior and attack response, and
provided marked protection against PTZ-induced convulsions in mice [86]. Water-
soluble dried powder of alcohol extract was not protective against strychnine-induced
convulsions in frogs and exhibited negative inotropic and chronotropic effects in frog
heart. Nevertheless, the extract produced sedative and tranquilizing effects and antag-
onized spontaneous motor activity and amphetamine-induced hyperactivity in mice
[65]. Pretreatment with both raw and classically processed (detoxified according to
Ayurveda) powder suspended in water exhibited anticonvulsant activity, decreasing
duration of tonic extensor phase, and duration of convulsion and stupor phases of
MES-induced seizures [8]. Pretreatment of rats with oral extract for two-weeks
decreased wet-dog-shake behavior and spike wave discharges induced by topical
application of ferric chloride to sensorimotor cortex, and significantly decreased SOD
activity and LPO in cerebral cortex [34]. Hydroalcohol extract prevented acrylamide-
induced neurotoxicity (hind limb paralysis), and increased GSH content and GST
activity in the corpus striatum of rats [80], and significantly improved neurobehavioral
performance of rats with MCA occlusion-induced ischemia, and increased GSH levels
and SOD activity in the cortex [79]. Coadministration of the rhizome extract prevented
restraint-induced cognitive impairment [74], and ethyl acetate extract and a-asarone
prevented noise stress-induced memory impairment in rats [83]. Methanol and
hydroalcohol extracts, EO, b-asarone and a-asarone have shown in vitro AChE inhi-
bitory activity; with b-asarone followed by EO being the most potent [60, 64]. Acetone
and methanol leaf extracts also show AChE inhibitory activity [85].
The EO produced sedative-tranquillizing effects in rats, mice, cats, dogs, and on
forced motor activities in mice; inhibited MAO in high doses [27], and antagonized
Acorus calamus L. 95

dextroamphetamine-induced agitational symptoms in rats [9]. Pretreatment of mice

with LSD prevented potentiation of barbiturate-induced hypnosis by the oil [22,
52]. In vitro studies revealed that the oil inhibited oxygen uptake of brain tissue to
varying degrees, which was antagonized by LSD-25, while 5HT potentiated it [28].
The EO protected rats against MES seizures, comparable to diphenylhydantoin
[51], and coadministration of hydroalcohol rhizome extract with subanticonvulsant
doses of sodium valproate and carbamazepine offered greater protection against
PTZ-induced convulsions in rats, as compared to either drug used alone [39].
Asarone exhibits pharmacological actions similar to reserpine and chlorpromazine
in equivalent doses. However, unlike chlorpromazine, asarone promotes vomiting,
and unlike reserpine asarone does not cause depression [23]. Pretreatment with
asarone did not block effect of reserpine on spontaneous motor activity and ptosis in
mice, as well as CAR of trained rats. In animals with depleted brain noradrenaline,
effects of asarone viz. hypothermia, potentiation of barbiturate hypnosis and
specific blockade of CAR were markedly enhanced [57]. a-asarone and b-asarone
prolonged pentobarbital, hexabarbital and ethanol-induced hypnosis in mice;
however, b-asarone facilitated MES seizures, while a-asarone was slightly pro-
tective [21, 58]. In small doses, both the oil and asarones potentiated effects of
reserpine and chlorpromazine [18], and asarone also decreased spontaneous motor
activity and caused amelioration of anxiety without affecting perception in rats, and
without affecting brain content of 5-HT [17, 20]. Asarone antagonized mescaline-
induced hyperactivity and hallucinogenic effects in rats, and showed protection to
aggregated mice treated with dextroamphetamine [19]. In experimentally induced
conflict neurosis in rats, an i.p. dose increased the number of shocks accepted by the
animals [13]. Essential oil and asarone produced a smooth muscle relaxant effect, as
well as antispasmodic effect against various spasmogens, similar to papaverine [25].
The oil and the crude alcohol and water roots extracts also produced depression in
dogs, inhibited rhythmicity of frog and dog heart and relaxed isolated intestine of
guinea pigs and rabbits, and the isolated rat uterus [11]. b-asarone-free oil was more
active as spasmolytic [40], but the antidiarrheal activity against castor oil-induced
diarrhea was more marked with methanol extract [78].
Ethanol extract produced diuretic effect in rats, increasing urine volume and
excretion of Na+ and K+, and protecting against ethylene glycol induced urolithiasis
[31]. Pretreatment of rats with methanol extract significantly reduced ethanol-
hepatotoxicity [35]. Ethyl acetate fraction markedly reduced serum glucose, TGs,
FFA, potentiated the TC lowering effect of rosiglitazone, and increased adiponectin
levels in genetically obese diabetic C57BL/Ks db/db mice [87], suppressed the
increase of blood glucose levels after glucose loading in normal mice [81], and
significantly lowered FBG in db/db diabetic mice [50]. Both aqueous and ethanol
extracts, and saponins showed significant hypolipidemic activity [66]. Antioxidant
activity in different oxidative-stress models has been reported of various extracts [1,
54, 69], and a-asarone [53], and the methanol extract exhibited strong antimutagenic
activity [6]. Ethanol and methanol rhizome extracts, and the EO also inhibit in vitro
growth of human gastric cancer cells [71]. Hydroalcohol extract prevented
vincristine-induced, and chronic sciatic nerve constriction injury-induced neuropathic
96 Acorus calamus L.

pain in rats [61, 62]. Topical application of aqueous extracts of fresh roots and rhi-
zomes [77], and ethanol leaf extract [36, 67] promoted wound-healing, enhancing
wound contraction, and decreasing epithelialisation time.
Ethanol rhizome extract inhibited growth of extended spectrum b-lactamases
producing MDR E. coli and Shigella, and MRSA. The extract activity was syner-
gistic with various antibiotics against E. coli and MRSA and was mainly confined to
acetone and ethyl acetate fractions of the extract [3–5]. Essential oil from Korean
Acorus with methyl isoeugenol as the major constituent, was also active against
P. acnes [43]. Essential oil also inhibited growth of human, bovine and avine types
of M. tuberculae, inhibited streptomycin-resistant strains, and also inhibited growth
of Gram-negative organisms in high concentrations [14]. Jain et al. [37] reported
growth inhibition of S. albus, Pneumococcus, a-hemolytic Streptococcus, S. typhi,
C. diphtheriae, S. faecalis, and B. pantotrophus by the oil. Rhizome oil also showed
cytotoxicity against MCF-7 cells, and antifungal activity against A. niger [75], A.
flavus [10], A. fumigatus and bactericidal to M. luteus [38]. b-asarone inhibited
growth of C. albicans that is suggested to be through inhibition of ergosterol
biosynthesis [72]. The asarones (a and b) exhibit synergistic anticandidal activities
with antifungal drugs (fluconazole, clotrimazole, and amphotericin B) [45].
Methanol extract and b-asarone also exhibited anthelmintic effect against H.
diminuta-infected rats, comparable to praziquantel [63]. Hot water extract signifi-
cantly suppressed b-hexosaminidase secretion and IL-4 production from
IgE-sensitized rat basophilic leukemia cells, and anaphylaxis reaction in mice [42].
Prakash [68] reported ethanol root extract devoid of anti-implantation activity in rats.
Mechanism of Action: Ethanol extract is reported to activate human peroxisome
proliferator-activated receptors (PPARa and PPARc) [73]. b-asarone is reported to
suppress growth of colon cancer cells by inducing senescence [49], and induces
apoptosis, possibly mediated through mitochondria/caspase pathways [89].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Oral LD50 of ethanol root extract in mice was reported to be
865 mg/kg body weight [41]. LD50 (i.p.) of the oil in guinea pigs, rats, mice and
guinea pigs are reported to be 0.275 ml/kg, 221 mg/kg and 177 mg/kg [24], and
0.6275 ml/100 g body weight, respectively [14]. Oil of calamus is reported car-
cinogenic [59], probably due to its asarone or safrole content.
Commentary: Despite being an important and widely used drug in traditional
medicines, there are no clinical studies reported in the mainstream English publi-
cations listed on PubMed.

References
1. Acuña UM, Atha DE, Ma J, et al. Antioxidant capacities of ten edible North
American plants. Phytother Res. 2002;16:63–5.
2. Agarwal SL, Dandiya PC, Singh KP, Arora RB. A note on the preliminary
studies of certain pharmacological actions of Acorus calamus. J Am
Pharmacol Assoc. 1956;45:655–6 (Scientific Ed.).
Acorus calamus L. 97

3. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal plants

against ESbetaL-producing multidrug-resistant enteric bacteria. Microbiol
Res. 2007;162:264–75.
4. Aqil F, Ahmad I, Owais M. Evaluation of antimethicillin-resistant Staphy-
lococcus aureus (MRSA) activity and synergy of some bioactive plant
extracts. Biotechnol J. 2006;1:1093–102.
5. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian
medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
6. Aqil F, Zahin M, Ahmad I. Antimutagenic activity of methanolic extracts of
four ayurvedic medicinal plants. Indian J Exp Biol. 2008;46:668–72.
7. Bains JS, Dhuna V, Singh J, et al. Novel lectins from rhizomes of two
Acorus species with mitogenic activity and inhibitory potential towards
murine cancer cell lines. Int Immunopharmacol. 2005;5:1470–8.
8. Bhat SD, Ashok BK, Acharya RN, Ravishankar B. Anticonvulsant activity
of raw and classically processed Vacha (Acorus calamus Linn.) rhizomes.
Ayu. 2012;33:119–22.
9. Bhattacharya IC. Effect of Acorus (Vacha) oil on the amphetamine induced
agitation, hexobarbital sleeping time and on instrumental avoidance
conditioning in rats. J Res Indian Med. 1968;2:195.
10. Bisht D, Pal A, Chanotiya CS, Mishra D, Pandey KN. Terpenoid composition
and antifungal activity of three commercially important essential oils against
Aspergillus flavus and Aspergillus niger. Nat Prod Res. 2011;25:1993–8.
11. Bose BC, Vijyavargiya R, Saifi AQ, Sharma SK. Some aspects of chemical
and pharmacological studies of Acorus calamus Linn. J Am Pharm Assoc.
1960;49:32–4.
12. Casey RC. 298 alleged antifertility plants of India. Indian J Med Sci. 1960;
14:590–600.
13. Chak IM, Sharma JN. Effect of asarone on experimentally-induced conflict
neurosis in rats. Indian J Exp Biol. 1965;3:252.
14. Chopra IC, Khajuria BN, Chopra CL. Antibacterial properties of volatile
principles from Alpinia galanga and Acorus calamus. Antibiot Chemother.
1957;7:378.
15. Dandiya PC, Baxter RM, Cullumbine H. Studies on Acorus calamus. I: a
phytochemical investigation. Can Pharm J. 1958;91:607–10.
16. Dandiya PC, Cullumbine H. Studies on Acorus calamus. III: some
pharmacological properties of the volatile oil. J Pharmacol Exp Ther. 1959;
125:353–9.
17. Dandiya PC, Menon MK. Actions of asarone on behaviour, stress and
hyperpyrexia and its interaction with central stimulants. J Pharmacol Exp
Ther. 1964;145:42.
18. Dandiya PC, Menon MK. Effects of asarone and a-asarone on conditioned
responses, fighting behaviour and convulsions. Br J Pharmacol. 1963;20:436–42.
19. Dandiya PC, Menon MK. Interaction of asarone with mescaline, ampheta-
mine and tremonine. Life Sci. 1965;4:1635.
20. Dandiya PC, Menon MK. Some more pharmacological actions of asarone, the
active principle of Acorus calamus. Indian J Physiol Pharmacol. 1964;8:44.
98 Acorus calamus L.

21. Dandiya PC, Sharma JD. Studies on Acorus calamus Part I. Pharmacolog-
ical actions of asarone and b-asarone on central nervous system. Indian J
Med Res. 1962;50:46–60.
22. Dandiya PC. Acorus calamus (A pharmacological study). Univ Rajasthan
Stud Med. 1960;5:7.
23. Dandiya PC. Psychopharmacological agents: receptors and mechanisms. Sir
Ram Nath Chopra Oration, Indian Pharmacological Society, Bangalore. Institute
of History of Medicine and Medical Research, New Delhi; 1987. p. 1–18.
24. Dandiya PC, Cullumbine H, Sellers EA. Studies on Acorus calamus. IV.
Investigations on mechanism of action in mice. J Pharmacol Exp Ther.
1959;126:334–7.
25. Das PK, Malhotra CL, Dhalla NS. Spasmolitic activity of asarone and essential
oil of Acorus calamus Linn. Arch Int Pharmacodyn. 1962;135:167–77.
26. de Smet PA. A multidisciplinary overview of intoxicating snuff rituals in the
Western hemisphere. J Ethnopharmacol. 1985;13:3–49 (Review).
27. Dhalla NS, Bhattacharya IS. Further studies on neuropharmacological
actions of Acorus oil. Arch Int Pharmacodyn. 1968;172:356.
28. Dhalla NS, Malhotra CL, Sastry MS. Effect of Acorus oil in vitro on the
respiration of rat brain. J Pharm Sci. 1961;50:580.
29. Dong W, Li M, Yang D, Lu R. Two new sesquiterpenes from Acorus
calamus. Planta Med. 2010;76:1742–5.
30. Dong W, Yang D, Lu R. Chemical constituents from the rhizome of Acorus
calamus L. Planta Med. 2010;76:454–7.
31. Ghelani H, Chapala M, Jadav P. Diuretic and antiurolithiatic activities of an
ethanolic extract of Acorus calamus L. rhizome in experimental animal
models. J Tradit Complement Med. 2016;6:431–6.
32. Hao ZY, Liang D, Luo H, et al. Bioactive sesquiterpenoids from the
rhizomes of Acorus calamus. J Nat Prod. 2012;75:1083–9.
33. Hartwell JL. Plants used against cancer. A survey. Lloydia. 1969–1971;32–33.
34. Hazra R, Ray K, Guha D. Inhibitory role of Acorus calamus in ferric
chloride-induced epileptogenesis in rat. Hum Exp Toxicol. 2007;26:947–53.
35. Ilaiyaraja N, Khanum F. Amelioration of alcohol-induced hepatotoxicity and
oxidative stress in rats by Acorus calamus. J Diet Suppl. 2011;8:331–45.
36. Jain N, Jain R, Jain A, Jain DK, Chandel HS. Evaluation of wound-healing
activity of Acorus calamus Linn. Nat Prod Res. 2010;24:534–41.
37. Jain SR, Jain PR, Jain MR. Antibacterial evaluation of some indigenous
volatile oils. Planta Med. 1974;26:196–9.
38. Joshi RK. Acorus calamus Linn.: phytoconstituents and bactericidal
property. World J Microbiol Biotechnol. 2016;32:164.
39. Katyal J, Sarangal V, Gupta YK. Interaction of hydroalcoholic extract of
Acorus calamus Linn. with sodium valproate and carbamazepine. Indian J
Exp Biol. 2012;50:51–5.
40. Keller K, Odenthal KP, Leng-Peschlow E. Spasmolytische wirkung des
isoasaronfreien kalmus1. Planta Med. 1985;51:6–9.
Acorus calamus L. 99

41. Khan MA, Islam MT. Analgesic and cytotoxic activity of Acorus calamus L.,
Kigelia pinnata L., Mangifera indica L. and Tabernaemontana divaricata L.
J Pharm Bioallied Sci. 2012;4:149–54.
42. Kim DY, Lee SH, Kim WJ, et al. Inhibitory effects of Acorus calamus
extracts on mast cell-dependent anaphylactic reactions using mast cell and
mouse model. J Ethnopharmacol. 2012;141:526–9.
43. Kim WJ, Hwang KH, Park DG, et al. Major constituents and antimicrobial
activity of Korean herb Acorus calamus. Nat Prod Res. 2011;25:1278–81.
44. Kumar R, Prakash O, Pan AK, et al. Compositional variations and anthelmentic
activity of essential oils from rhizomes of different wild populations of Acorus
calamus L. and its major component, beta-asarone. Nat Prod Commun.
2009;4:275–8.
45. Kumar SN, Aravind SR, Sreelekha TT, Jacob J, Kumar BS. Asarones from
Acorus calamus in combination with azoles and amphotericin B: a novel
synergistic combination to compete against human pathogenic Candida
species in vitro. Appl Biochem Biotechnol. 2015;175:3683–95.
46. Li J, Li ZX, Zhao J, et al. A novel tropoloisoquinoline alkaloid, neotatarine,
from Acorus calamus L. Chem Biodivers. 2017;14.
47. Li J, Zhao J, Wang W, et al. New acorane-type sesquiterpene from Acorus
calamus L. Molecules. 2017;22. pii: E529.
48. Li MX, Jiang ZR. Variations of the essential oils in Acorua calamus L. and
their major compositions. Zhongguo Zhong Yao Za Zhi. 1994;19:274–6, 319
(Chinese).
49. Liu L, Wang J, Shi L, et al. b-Asarone induces senescence in colorectal cancer
cells by inducing lamin B1 expression. Phytomedicine. 2013;20:512–20.
50. Liu YX, Si MM, Lu W, et al. Effects and molecular mechanisms of the
antidiabetic fraction of Acorus calamus L. on GLP-1 expression and
secretion in vivo and in vitro. J Ethnopharmacol. 2015;166:168–75.
51. Madan BR, Arora RB, Kanti K. Anticonvulsant, anti-veratrinic and
antiarrhythmic actions of Acorus calamus Linn.—An Indian indigenous
drug. Arch Int Pharmacodyn. 1960;124:201–11.
52. Malhotra CL, Das PK, Dhalla NS. Investigations on the mechanism of
potentiation of barbiturate hypnosis by hersaponin, acorus oil, reserpine and
chlorpromazine. Arch Int Pharmacodyn Ther. 1962;138:537–47.
53. Manikandan S, Devi RS. Antioxidant property of alpha-asarone against
noise-stress-induced changes in different regions of rat brain. Pharmacol
Res. 2005;52:467–74.
54. Manikandan S, Srikumar R, Jeya Parthasarathy N, Sheela Devi R.
Protective effect of Acorus calamus Linn. on free radical scavengers and
lipid peroxidation in discrete regions of brain against noise stress exposed
rat. Biol Pharm Bull. 2005;28:2327–30.
55. Marongiu B, Piras A, Porcedda S, Scorciapino A. Chemical composition of
the essential oil and supercritical CO2 extract of Commiphora myrrha (Nees)
Engl. and of Acorus calamus L. J Agric Food Chem. 2005;53:7939–43.
56. May BH, Lu C, Lu Y, Zhang AL, Xue CC. Chinese herbs for memory
disorders: a review and systematic analysis of classical herbal literature.
J Acupunct Meridian Stud. 2013;6:2–11.
100 Acorus calamus L.

57. Menon MK, Dandiya PC. The mechanism of the tranquillizing action of
asarone from Acorus calamus Linn. J Pharm Pharmacol. 1967;19:170–5.
58. Menon MK, Dandiya PC. Tranquillizing properties of asarone and a-asarone,
active constituents of A. calamus. Indian J Physiol Pharmacol. 1963;7:14.
59. Morton ID. Toxic substances in foods. J Hum Nutr. 1977;31:53–60.
60. Mukherjee PK, Kumar V, Mal M, Houghton PJ. In vitro acetylcholinesterase
inhibitory activity of the essential oil from Acorus calamus and its main
constituents. Planta Med. 2007;73:283–5.
61. Muthuraman A, Singh N. Attenuating effect of Acorus calamus extract in
chronic constriction injury induced neuropathic pain in rats: an evidence of
antioxidative, anti-inflammatory, neuroprotective and calcium inhibitory
effects. BMC Complement Altern Med. 2011;11:24.
62. Muthuraman A, Singh N. Attenuating effect of hydroalcoholic extract of
Acorus calamus in vincristine-induced painful neuropathy in rats. J Nat
Med. 2011;65:480–7.
63. Nath P, Yadav AK. Anthelmintic activity of a standardized extract from the
rhizomes of Acorus calamus Linn. (Acoraceae) against experimentally
induced cestodiasis in rats. J Intercult Ethnopharmacol. 2016;5:390–5.
64. Oh MH, Houghton PJ, Whang WK, Cho JH. Screening of Korean herbal
medicines used to improve cognitive function for anticholinesterase activity.
Phytomedicine. 2004;11:544–8.
65. Panchal GM, Venkatakrishna-Bhatt H, Doctor RB, Vajpayee S. Pharma-
cology of Acorus calamus L. Indian J Exp Biol. 1989;27:561–7.
66. Parab RS, Mengi SA. Hypolipidemic activity of Acorus calamus L. in rats.
Fitoterapia. 2002;73:451–5.
67. Ponrasu T, Madhukumar KN, Ganeshkumar M, et al. Efficacy of Acorus
calamus on collagen maturation on full thickness cutaneous wounds in rats.
Pharmacogn Mag. 2014;10 Suppl 2:S299–305.
68. Prakash AO. Potentialities of some indigenous plants for antifertility
activity. Int J Crude Drug Res. 1986;24:19–24.
69. Prasad L, Khan TH, Jahangir T, Sultana S. Acorus calamus extracts and
nickel chloride: prevention of oxidative damage and hyperproliferation
response in rat kidney. Biol Trace Elem Res. 2006;113:77–92.
70. Qiao D, Gan LS, Mo JX, Zhou CX. Chemical constituents of Acorus
calamus. Zhongguo Zhong Yao Za Zhi. 2012;37:3430–3 (Chinese).
71. Rahamooz Haghighi S, Asadi MH, Akrami H, Baghizadeh A. Anti-
carcinogenic and antiangiogenic properties of the extracts of Acorus calamus
on gastric cancer cells. Avicenna J Phytomed. 2017;7:145–56.
72. Rajput SB, Karuppayil SM. b-Asarone, an active principle of Acorus
calamus rhizome, inhibits morphogenesis, biofilm formation and ergosterol
biosynthesis in Candida albicans. Phytomedicine. 2013;20:139–42.
73. Rau O, Wurglics M, Dingermann T, et al. Screening of herbal extracts for
activation of the human peroxisome proliferator-activated receptor. Phar-
mazie. 2006;61:952–6.
74. Reddy S, Rao G, Shetty B, Hn G. Effects of Acorus calamus rhizome extract
on the neuromodulatory system in restraint stress male rats. Turk Neurosurg.
2015;25:425–31.
Acorus calamus L. 101

75. Satyal P, Paudel P, Poudel A, et al. Chemical compositions, phytotoxicity,

and biological activities of Acorus calamus essential oils from Nepal. Nat
Prod Commun. 2013;8:1179–81.
76. Shah NC. Herbal folk medicines in Northern India. J Ethnopharmacol.
1982;6:293–301.
77. Shi GB, Wang B, Wu Q, et al. Evaluation of the wound-healing activity and
anti-inflammatory activity of aqueous extracts from Acorus calamus L.
Pak J Pharm Sci. 2014;27:91–5.
78. Shoba FG, Thomas M. Study of antidiarrhoeal activity of four medicinal
plants in castor-oil induced diarrhoea. J Ethnopharmacol. 2001;76:73–6.
79. Shukla PK, Khanna VK, Ali MM, et al. Neuroprotective effect of Acorus
calamus against middle cerebral artery occlusion-induced ischaemia in rat.
Hum Exp Toxicol. 2006;25:187–94.
80. Shukla PK, Khanna VK, Ali MM, et al. Protective effect of Acorus calamus
against acrylamide induced neurotoxicity. Phytother Res. 2002;16:256–60.
81. Si MM, Lou JS, Zhou CX, et al. Insulin releasing and alpha-glucosidase
inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and
in vivo. J Ethnopharmacol. 2010;128:154–9.
82. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
83. Sundaramahalingam M, Ramasundaram S, Rathinasamy SD, Natarajan RP,
Somasundaram T. Role of Acorus calamus and alpha-asarone on hippocampal
dependent memory in noise stress exposed rats. Pak J Biol Sci. 2013;16:770–8.
84. Tripathi AK, Singh RH. Experimental evaluation of antidepressant effect of
Vacha (Acorus calamus) in animal models of depression. Ayu. 2010;31:153–8.
85. Vijayapandi P, Annabathina V, SivaNagaSrikanth B, et al. In vitro
anticholinergic and antihistaminic activities of Acorus calamus Linn. leaves
extracts. Afr J Tradit Complement Altern Med. 2012;10:95–101.
86. Vohora SB, Shah SA, Dandiya PC. Central nervous system studies on an ethanol
extract of Acorus calamus rhizomes. J Ethnopharmacol. 1990;28:53–62.
87. Wu HS, Zhu DF, Zhou CX, et al. Insulin sensitizing activity of ethyl acetate
fraction of Acorus calamus L. in vitro and in vivo. J Ethnopharmacol. 2009;
123:288–92.
88. Wu LJ, Sun LL, Li M, et al. Studies on the constituents of the roots of
Acorus calamus L. Yakugaku Zasshi. 1994;114:182–5 (Japanese).
89. Zou X, Liu SL, Zhou JY, et al. Beta-asarone induces LoVo colon cancer cell
apoptosis by upregulation of caspases through a mitochondrial pathway
in vitro and in vivo. Asian Pac J Cancer Prev. 2012;13:5291–8.
Adiantum venustum G. Don./Adiantun capillus-veneris L.
(Pteridaceae)

Abstract
Adiantum venustum is a fern that is native to China and Himalayas; but also
grows in Persia, Indo-China, Africa, Mexico, Latin America, and Australia.
Adiantun capillus-veneris is native to North America, Central America, Europe
and Africa. Phenolic contents of both species are almost equal, which might
produce similar clinical effects, and thus the two species are used interchange-
ably. Dioscorides described the decoction of the drug as beneficial in oliguria,
spleen pain, pleurisy, kidney stones, jaundice, and ringworm infection of the
scalp. Galen reinforced the observations of Dioscorides and added that the drug
is astringent, resolvent and demulcent, resolves lymph nodes inflammation and
boils, disintegrates renal stones, and expels pus from pulmonary alveoli. Used as
plaster, it is considered to be discutient, and is applied to chronic tumors of
various kinds. The ashes of the plant mixed with olive oil and vinegar are used to
make the hair grow on the bald patches produced by ringworm of the scalp. The
expressed juice with pepper is a favorite remedy in all kinds of fevers; syrup
prepared from leaves is useful in chronic cough. In Ayurveda, it is used in cold,
tumors of spleen, liver and other viscera, skin diseases, bronchitis and
inflammatory diseases and is also considered a tonic and diuretic. Adiantu-
lanostene ether, a lanostane triterpenic ether, was isolated from aerial parts of A.
venustum. Three other terpenes, 30-normethyl lupane-20-one, 30-normethyl
olean-3-one-30b-ol and lanost-20(22)-ene-30-ol have also been reported. The
leaves, stem and roots of A. capillus-veneris all show the presence of flavonoids,
alkaloids, tannins, saponins, cardiac glycosides, terpenoids, steroids, and
reducing sugars. Hydroalcohol extract of A. capillus-veneris protected rats
against ethylene glycol and ammonium chloride-induced urolithiasis.

Keywords





Adianto Capelvenere commune Cheveux de vénus Fairies Frauenhaarfarn





Godhāvatī Hansraj Persiawushan Shaa’r-ul-Jinn Venushår

© Springer Nature Switzerland AG 2020 103
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_11
104 Adiantum venustum G. Don./Adiantun capillus-veneris L.

Vernaculars: Urd.: Persiawushan; Hin.: Galmarium, Hansraj, Hansraja or Raja

hansa, Mubaraka; San.: Godhāvatī, Hansapadi; Ben.: Kalijhant; Mal.: Paravan;
Mar.: Mhar; Tam.: Mayirsikki, Paraiyan, Paraiyar, Paraiyadi kiravan; Ara.:
Kazbarat-el-bir (coriander of the well), Nasif-el-aswad (black veil), Saq-el-aswad
(black stem), Shaa’r-ul-jinn (fairies hair), Shaa’r-ul-jibal, Shaa’r-ul-khinazeer; Chi.:
细叶铁线蕨; Dan.: Ægte venushår, Venushår; Dut.: Europees venushaar; Eng.:
Evergreen maidenhair, Fairies, Himalayan maidenhair; Fin.: Venuksenhiussani-
ainen; Fre.: Capillaire cheveux-de-Vénus, Capillaire de Montpellier, Cheveux de
Vénus; Ger.: Frauenhaarfarn, Venushaar-farn; Ita.: Capelvenere comune; Per.:
Persiavashan, Sir sia-peshane; Spa.: Adianto, Capilera, Culantrillo de pozo.
Description: Adiantum venustum is a fern that is native to China and Himalayas;
but also grows in Persia, Indo-China, Africa, Mexico, Latin America, and Australia.
Adiantun capillus-veneris is native to North America, Central America, Europe and
Africa, and both species are used interchangeably. The genus name is derived from
the Greek, meaning “not wetting” due to the fronds’ ability to shed water without
becoming wet. It grows under shade in moist areas near ponds and wells. Its leaves
resemble coriander leaves, but are smaller. Both leaves and stem are used medic-
inally; its potency weakens in six months and is completely lost in a year.LXXVII
The stems are very slender, black and highly polished as if varnished, one or more
chanelled; channels more deep, irregular and on one side. Leaves small, reniform,
rogous and marked with fan-like veins, serrated at the top like coriander, of a
brownish dark color; taste faintly astringent; odor rather disagreeable (Fig. 1).LXXXI
Actions and Uses: Dioscorides is quoted by Ibn al-BaitarLXIX that the decoction of
the drug is beneficial in oliguria, spleen pain, pneumonia (Raboo), kidney stones,

Fig. 1 Adiantum venustum, Plant, Botanischer Garten München-Nymphenburg, Munich, Germany,

Daderot, WikimediaCommons, https://commons.wikimedia.org/wiki/File:Adiantum_venustum_-_
Botanischer_Garten_M%C3%BCnchen-Nymphenburg_-_DSC07765.JPG
Adiantum venustum G. Don./Adiantun capillus-veneris L. 105

jaundice, and ringworm infection of the scalp. Rhazes and Basri reiterated the hair
growth property after application of ashes of the plant, and Galen reinforced the
observations of Dioscorides and added that the drug is astringent, resolvent and
demulcent, resolves lymph nodes inflammation and boils, disintegrates renal stones,
and expels pus from pulmonary alveoli. Dymock et al.XL described it as deob-
struent, demulcent and resolvent, also pectoral expectorant, emmenagogue, diuretic
and alexipharmic; useful for clearing the bile, adust bile and phlegmatic humours.
Used as plaster, it is considered to be discutient, and is applied to chronic tumors of
various kinds. The ashes of the plant mixed with olive oil and vinegar are used to
make the hair grow on the bald patches produced by ringworm of the scalp. The
expressed juice with pepper is a favorite remedy in all kinds of fevers; syrup
prepared from leaves is useful in chronic cough.XXI,CV Unani physicians of Indian
subcontinent regard its temperament as moderate towards heat, while Rhazes
considered it hot 1° and dry 1°. It is resolvent, emollient, deobstruent, detergent,
diuretic, emmenagogue, and cleans phlegmatic humors, and used in pulmonary
catarrh, pneumonia, common cold, cough and asthma, and fevers due to morbid or
impure phlegm. The powder is used for oral sores in children, and the decoction is
used as emmenagogue, in puerperium and for the expulsion of placenta. Also used
in boils, stomatitis, skin eruptions, snakebites, foxbite and dogbite. Particularly used
as a purgative of black bile, yellow bile and phlegm; it cures common cold.LXXVII
Washing hair with it clears dandruff and strengthens hair. Khory and KatrakLXXXI
described it as stimulant, tonic and demulcent; and used in pulmonary catarrh,
asthma and as a flavoring agent in expectorant mixtures. In Ayurveda, it is used in
cold, tumors of spleen, liver and other viscera, skin diseases, bronchitis and
inflammatory diseases and is also considered a tonic and diuretic [11]. A. capillus-
veneris is used for the treatment of inflammatory diseases in traditional folk
medicine of south China [14]. In the Philippines, fronds are used for chest diseases
and as emmenagogue; whereas in Iraq and Iran the rhizomes are believed to have
expectorant properties, and are used to relieve symptoms of whooping cough.CXVII
Phytoconstituents: Adiantulanostene ether, a lanostane triterpenic ether, was
isolated from aerial parts of A. venustum [3]. Three other terpenes, 30-normethyl
lupane-20-one, 30-normethyl olean-3-one-30b-ol and lanost-20(22)-ene-30-ol have
also been reported [2]. Phenolic contents of A. venustum and A. capillus-veneris are
almost equal, 0.81% and 0.83%, respectively [11], which might produce similar
clinical effects, and thus the two species are used interchangeably. The leaves, stem
and roots of A. capillus-veneris all show the presence of flavonoids, alkaloids,
tannins, saponins, cardiac glycosides, terpenoids, steroids, and reducing sugars [6].
Thirteen compounds, namely 4-hydroxybenzoic acid, chlorogenic acid, caftaric
acid, kaempferol glycosides, p-coumaric acid, rosmarinic acid, 5-caffeoylquinic
acid, quercetin glycosides, kaempferol-3-sophorotrioside, chlorogenic acid, 5-O-
caffeoylquinic acid, coumaric acid, and its derivative were isolated in high amounts
from the leaves of A. capillus-veneris [15]. A number of triterpenoids have been
isolated from A. capillus-veneris, collected from Japan, China and Egypt [8].
b-sitosterol, stigmasterol and capesterol were identified in the sterol fraction of
106 Adiantum venustum G. Don./Adiantun capillus-veneris L.

A. capillus veneris [7]. One triterpenoid, 4-a-hydroxyfilican-3-one, showed sig-

nificant analgesic and anti-inflammatory activities [5].
Pharmacology: Methanol extract of A. venustum showed significant antifungal
activity against A. terreus, which is implied to be due to high phenolic contents [11];
whereas ethanol extract exhibited significant anticancer activity against Ehrlic
ascites carcinoma, and reduced LPO [12]. Ethanol extract of A. capillus-veneris and
its ethyl acetate fraction exhibited significant anti-inflammatory and analgesic effects
[4]. Hydroalcohol extract of A. capillus-veneris was protective against ethylene
glycol and ammonium chloride-induced urolithiasis in rats [1], and aqueous fraction
of methanol extract of A. capillus-veneris promoted significant angiogenesis in vitro
[9]. An A. capillus-veneris extract protected rats from bisphenol A-induced testicular
toxicity [13]. Topical application of ethanol extract solution on the back of mice
significantly reduced testosterone-induced hair loss, and increased hair follicle
density [10].
Human A/Es, Allergy and Toxicity: It is harmful in the presence of splenic
diseases.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported on this plant, with a long
history of medicinal use, in the mainstream English publications listed on PubMed.

References
1. Ahmed A, Wadud A, Jahan N, Bilal A, Hajera S. Efficacy of Adiantum
capillus veneris Linn in chemically induced urolithiasis in rats. J Ethnophar-
macol. 2013;146:411–6.
2. Alam MS, Chopra N, Ali M, Niwa M. Normethyl pentacyclic and lanostane-type
triterpenes from Adiantum venustum. Phytochem. 2000;54:215–20.
3. Chopra N, Alam MS, Ali M, Niwa M. A new lanostane triterpenic ether
from Adiantum venustum. Pharmazie. 2000;55:538–9.
4. Haider S, Nazreen S, Alam MM, et al. Anti-inflammatory and antinociceptive
activities of ethanolic extract and its various fractions from Adiantum capillus
veneris Linn. J Ethnopharmacol. 2011;138:741–7.
5. Haider S, Kharbanda C, Alam MS, et al. Anti-inflammatory and antinoci-
ceptive activities of two new triterpenoids from Adiantum capillus-veneris
Linn. Nat Prod Res. 2013;27:2304–10.
6. Ishaq MS, Hussain MM, Afridi MS, et al. In vitro phytochemical, antibacterial,
and antifungal activities of leaf, stem, and root extracts of Adiantum capillus
veneris. ScientificWorldJournal. 2014;2014:269793.
7. Marino A, Elberti MG, Cataldo A. Phytochemical investigation of Adiantum
capillus veneris. Boll Soc Ital Biol Sper. 1989;65:461–3 (Italian).
8. Nakane T, Maeda Y, Ebihara H, et al. Fern constituents: triterpenoids from
Adiantum capillus-veneris. Chem Pharm Bull (Tokyo). 2002;50:1273–5.
Adiantum venustum G. Don./Adiantun capillus-veneris L. 107

9. Nilforoushzadeh MA, Javanmard SH, Ghanadian M, et al. The effects of

Adiantum capillus-veneris on wound healing: an experimental in vitro
evaluation. Int J Prev Med. 2014;5:1261–8.
10. Noubarani M, Rostamkhani H, Erfan M, et al. Effect of Adiantum capillus
veneris Linn on an animal model of testosterone-induced hair loss. Iran J
Pharm Res. 2014;13(Suppl):113–8.
11. Singh M, Singh N, Khare PB, Rawat AK. Antimicrobial activity of some
important Adiantum species used traditionally in indigenous systems of
medicine. J Ethnopharmacol. 2008;115:327–9.
12. Viral D, Shivanand P, Jivani N. Anticancer evaluation of Adiantum
venustum Don. J Young Pharm. 2011;3:48–54.
13. Yousaf B, Amina, Liu G, et al. Bisphenol A exposure and healing effects of
Adiantum capillus-veneris L. plant extract (APE) in bisphenol A-induced
reproductive toxicity in albino rats. Environ Sci Pollut Res Int. 2016;23:
11645–57.
14. Yuan Q, Zhang X, Liu Z, et al. Ethanol extract of Adiantum capillus-veneris
L. suppresses the production of inflammatory mediators by inhibiting
NF-jB activation. J Ethnopharmacol. 2013;147:603–11.
15. Zeb A, Ullah F. Reversed Phase HPLC-DAD Profiling of carotenoids,
chlorophylls and phenolic compounds in Adiantum capillus-veneris leaves.
Front Chem. 2017;5:29.
Aegle marmelos (L.) Corrêa
(Rutaceae)

Abstract
The tree grows in dry forests of India, Bangladesh, Myanmar, Nepal and Sri
Lanka; and is sacred to the goddess of riches, is considered auspicious and
grown in Hindu gardens, and the leaves are used in the worship of Shiva. The
ripe fruit pulp is sweet, nutritious, delicious, aromatic, alterative and laxative,
hemostatic, a tonic for stomach, and is useful for chronic diarrhea, dysentery and
ulcerative colitis, and beneficial for all kinds of bleeding, such as bloody
diarrhea, and menorrhagia. Dried fruit pulp is called Vilva peshika in Sanskrit
and in Ayurveda, the unripe or half-ripe fruit is regarded as astringent, digestive
and stomachic, and prescribed for diarrhea and dysentery. In the 19th century,
the plant was part of official Indian Pharmacopoeia for the treatment of atonic
diarrhea, dysentery, irregularity of bowels, and habitual constipation. Fruit pulp
contains mucilage, pectin, sugar, tannin, a volatile oil, and a bitter principle, and
also contains umbelliferone, a natural antioxidant benzopyrone. Aqueous fruit
extract protected against aspirin-induced gastroduodenal ulceration, while unripe
fruit extract was protective against inflammation of ulcerative colitis, and
enterocolitis in rats, and produced antioxidant and mast cell stabilizing effects.
Aqueous fruit extract also lowered FBG and improved glucose tolerance of
normal rats, and reversed STZ-induced hyperglycemia, increased plasma insulin
and liver glycogen, and decreased HbA1c level, and improved pancreatic b-cells
histology better than glibenclamide (glyburide) treatment. Methanol extract is
suggested to produce hypoglycemic effect by increasing glucose utilization, as it
upregulates GLUT-4, PPAR-c and PI3 kinase.

Keywords
Bael
Belbaum

Berunoki

Cotogno d’India

Oranger de Malabar





Safarjal-e-hindi Shivaphala Shriphal Slijmappelboom Ying pi ju

© Springer Nature Switzerland AG 2020 109

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_12
110 Aegle marmelos (L.) Corrêa

Vernaculars: Urd.: Bel, Bael; Hin.: Bel, Bela, Shivadume, Shriphal; San.: Bilva,
Bilvam, Bilva-phalam, Mahura, Shivaphala, Sriphal; Ben.: Bael, Bela, Shriphal;
Guj.: Bel; Mal.: Baela koovalam, Kuvalam, Maaredy, Vilvam; Mar.: Bela; Tam.:
Bilva, Kuuviram, Villuvam, Vilvam, Vilvama, Vilva-maram, Vilva-pazham; Tel.:
Bilva, Bilvamu, Bilva-pandu, Maradu-pandu, Malu-remu-chettu; Ara.: Safarjal-
e-hindi, Shul; Bur.: Ohshit, Opesheet; Chi.: 木橘, Mu ju, Yin du gou qi, Ying pi ju;
Dut.: Slijmappelboom; Eng.: Bael, Bengal quince; Fre.: Bel indien, Cognassier du
Bengal, Coing de l’Inde, Oranger de Malabar, Oranger du Malabar; Ger.: Belbaum,
Bengalische quitte, Indische quitte, Schleimapfelbaum; Ita.: Cotogno del Bengala,
Cotogno d’India; Jap.: Berunoki, Igure marumerozu; Lao.: Toum; Maly.: Bel,
Bila, Bilak, Maja, Maja batuh, Maja pahit; Nep.: Belapatra, Belpatra; Per.: Bah
hindi, Safarjal-e-hindi, Shull; Sin.: Be li; Spa.: Bela, Milva; Tag.: Bael; Tha.:
Mapin, Matum; Tur.: Hind ayva agh; Vie.: Bau nau, Tráimam.
Description: The tree grows in dry forests of India, Bangladesh, Myanmar, Nepal
and Sri Lanka; and is sacred to the goddess of riches, is considered auspicious
(anti-mangalya) and grown in Hindu gardens, and the leaves are used in the worship
of Shiva.XL Leaves are green or dark green in color, smooth, shining and thick with
an aromatic smell and taste; pinnate or ternate; leaflets oblong, broad, lanceolate
and crenulate. Fruits vary in shapes and sizes, which has a very hard rind, becoming
stony when dry, nearly smooth and of a lightish-yellow, cherry-red or brown color.
The pulp is brownish-red in color, firm and having 12 or more stony carpels, which
contain hairy seeds, one or more in each carpel. In the cavities between the carpels
and surrounding the seeds, is a reddish-brown color, tenacious, transparent gluten-
like or gummy resinous substance, which becomes hard on drying. The pulp tastes
sweet, astringent with an agreeable aromatic odor (Figs. 1 and 2).LXXXI
Actions and Uses: In Unani medicine, the ripe fruit pulp is hot 1° and dry 1°,
while the unripe fruit is cold 2° and dry 2°, and half-ripe fruit is considered cold 1°
and dry 2° in temperament. The fruit pulp is astringent, hemostatic, a tonic for
stomach, and is useful for chronic diarrhea, dysentery and ulcerative colitis, and
beneficial for all kinds of bleeding, such as bloody diarrhea, and menorrha-
gia.LXXVII The ripe fruit is sweet, nutritious, delicious, aromatic, alterative and
laxative, and is used to prevent and treat constipation. GhaniL said that the pulp of
the ripe fruit strengthens heart, liver and stomach, cures chronic diarrhea, relieves
constipation and improves appetite but produces gases. A decoction of unripe or
half-ripe fruit, or unripe fruit baked for 6 h is astringent, digestive and stomachic,
and is used to treat diarrhea and dysentery. The root bark is refrigerant, and is used
in fevers, asthma with palpitation of the heart. A poultice of the leaves is applied to
the head in delirium of fever, and to the chest in acute bronchitis; leaves decoction
is also used in asthma.XXI,LXXXI Fruit having mucilage and pectin is useful against
chronic diarrhea and dysentery.LXXXVIII NadkarniCV also described ripe fruit pulp
cooling, stimulant, antipyretic, and antiscorbutic, with laxative property; whereas
the unripe fruit is astringent, digestive, stomachic, and a little constipative. Dried
fruit pulp is called Vilva peshika in Sanskrit and in Ayurveda, the unripe or half-ripe
fruit is regarded as astringent, digestive and stomachic, and prescribed for diarrhea
Aegle marmelos (L.) Corrêa 111

Fig. 1 Aegle marmelos, Tree, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported CC BY-
SA 3.0, https://commons.wikimedia.org/wiki/File:Bael_(Aegle_marmelos)_tree_at_Narendrapur_W_
IMG_4116.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Aegle marmelos, Ripe Fruit, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Bael_(Aegle_marmelos)_fruit_at_Naren
drapur_W_IMG_4099.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
112 Aegle marmelos (L.) Corrêa

and dysentery; whereas the root bark is used as a remedy for hypochondriasis,
melancholia and heart palpitation. Fruit pulp is used in the treatment of pravāhikā,
agnimāndya, grahaniroga, and the dried root is used in vātavyādhi, śotha, śūla,
agnimandya, chardi, mūtrakrcchra, and āmavāta.LIX In 1869, the plant was made
part of official Indian Pharmacopoeia for the treatment of atonic diarrhea, dysentery,
irregularity of bowels, and in habitual constipation [33]. Leaf extract is used for the
treatment of diabetes [50, 53, 86]. In Bangladesh, a decoction of the leaves is the
most commonly used form for gastrointestinal problems [45].
Phytoconstituents: Fruit pulp contains mucilage, pectin, sugar, tannin, a volatile oil,
and a bitter principle,LXXXI and also contains umbelliferone, a natural antioxidant
benzopyrone [81, 82]. From the acetone extract of green fruits 1-5,marmesiline, 6-
(4-acetoxy-3-methyl-2-butenyl)-7-hydroxycoumarin, 6-(2-hydroxy-3-hydroxyme
thyl-3-butenyl)-7-hydroxycoumarin, 8-hydroxysmyrindiol and marmelonine have
been isolated [22]. Leaves contain alkaloids, tannin, saponins, flavonoid, cardiac
glycosides, terpenoid, steroid and phlobatannins [30]; praealtin D, trans-cinnamic
acid, valencic acid, betulinic acid, 4-methoxybenzoic acid, N-p-cis- and trans-
coumaroyl-tyramine, montanine, rutaretin, and a 7-geranyloxy-coumarin, named
marmenol [8]. A 7-hydroxy-6-methoxy coumarin, named scopoletin with antithyroid,
antioxidative and antihyperglycemic activities [72], an antihyperglycemic alkaloidal-
amide, aegeline-2, that also lowers FFAs, TGs, and TC, and increases HDL-C in
dyslipidemic animal model [66], and phenylethyl cinnamides, anhydromarmeline,
aegelinoside A and B have also been identified in the leaves [74], that also contain trace
amounts of copper, nickel, zinc, potassium and sodium, and marginal levels of iron,
chromium and vanadium [68]. Seeds contain antifungal compounds, 2-isopropenyl-
4-methyl-1-oxa-cyclopenta[b]anthracene-5,10-dione and (+)-4-(2′-hydroxy-3′-
methylbut-3′-enyloxy)-8H-[1,3] dioxolo[4,5-h]chromen-8-one, in addition to
imperatorin, b-sitosterol, b-sitosterol glucoside, plumbagin, stigmasterol, vanillin,
salicin, and 1-methyl-2-(3′-methyl-but-2′-enyloxy)-anthraquinone; the anthraqui-
none being significantly active against pathogenic Aspergillus species and C. albicans
[64, 65]. Skimmiarepin A and C, with insecticidal activity against P. cochleariae and
M. domestica, have been isolated from the stem bark [91], and three neutral and two
acidic oligosaccharides and a monosaccharide were reported from bael gum [85].
Pharmacology: Unripe fruit extract protects against ethanol-induced gastric
lesions in rats, but not those produced by cold restraint stress or indomethacin,
reduces castor oil-induced increase in intestinal fluids and the transit, and antago-
nizes contractility of isolated ileum produced by various agents [31]. Aqueous
leaves extract significantly reduced number of gastric ulcer lesions, volume of
gastric juice and acidity, and caused an increase in gastric pH [38]. Aqueous fruit
extract was also protective against aspirin-induced gastroduodenal ulceration, and
significantly reversed aspirin-induced increase in serum AST, ALT and ALP
activities [29]. Unripe fruit extract is also protective against inflammation of acetic
acid-induced ulcerative colitis, and indomethacin-induced enterocolitis in rats, and
produces antioxidant, and mast cell stabilizing effects [16, 33]. Aqueous extract of
the dried unripe fruit pulp showed limited antimicrobial activity, but showed
Aegle marmelos (L.) Corrêa 113

antigiardial and antirotaviral activities, and affected bacterial colonization to gut

epithelium, and production and action of E. coli heat labile toxin and cholera toxin
[21]. Methanol extract of unripe fruits was more protective than aqueous extract
against castor oil-induced diarrhea [96]. A lectin isolated from fruit pulp signifi-
cantly inhibits hemagglutination activity of Shigella [79]. Arul et al. [12] attributed
the smooth muscle relaxing effect of the alcohol leaves extract to antagonism of
H1-histamine receptors in the ileum and tracheal smooth muscles. Aegeline, the
main alkaloid of the leaves also inhibits histamine release from mast cells, probably
through alteration of the signaling pathway related to intracellular Ca2+ pool [70].
Another compound, marmin, from the plant antagonizes contractions of isolated
guinea pig trachea, induced by histamine and the compound 48/80, an inducer of
histamine release, effectively producing an antihistaminic effect [69].
Aqueous fruit extract lowered FBG and improved glucose tolerance of normal rats
[52], and reversed STZ-induced hyperglycemia, increased plasma insulin and liver
glycogen, and decreased HbA1c level, and improved pancreatic b-cells histology better
than glibenclamide (glyburide) treatment [46–48]; the hypoglycemic effect was not due
to decrease in serum cortisol concentration [35]. Aqueous fruit extract also produced
significant antilipid peroxidative activity in heart and pancreas of STZ-diabetic rats [49],
and prevented inflammatory changes and b-cell damage, along with a reduction in
mitochondrial and endoplasmic reticulum swelling in high fat diet-fed STZ-induced
diabetic rats [95]. Aqueous leaf extract pretreatment maintained blood glucose, urea,
serum cholesterol and liver glycogen to the control levels in alloxan-diabetic rats [75],
and reversed microscopic changes in pancreatic b-cells and acinar cells, liver and the
kidney [28], the malate dehydrogenase enzyme of STZ-diabetic rats [93], lowered
HbA1c, increased liver glycogen, Hb, insulin, C-peptide levels, and activities of car-
bohydrate metabolizing enzymes [67]. Ethanol leaf extract pretreatment also lowered
glucose-induced hyperglycemia in rats, increased glucose utilization, either by stimu-
lation of cellular glucose uptake or increased insulin secretion [87], produced antihy-
perglycemic effect [50], decreased levels of FBG, TC, TBARS, LDH and CK, and
increased levels of GSH, CAT and SOD, and ameliorated diabetic nephropathy in rats
[18, 19], and significantly attenuated elevated serum TC and TGs levels in hyperlipi-
demic rats, with an increase in HDL-C [101]. Chloroform leaf extract also produced
antidiabetic, antiglycating and antioxidant activity, effectively preventing kidney dam-
age and establishment of cataracts in rats [71]. Aqueous and methanol leaf extracts also
inhibit pancreatic a-amylase activity that might be effective in lowering postprandial
hyperglycemia [89]. Muscarinic receptor binding in cerebral cortex is significantly
reduced in diabetic rats; pretreatment with aqueous leaf extract for 14-days post STZ
injection reverses binding parameters to their control level [36]. Leaf extract regulates
insulin synthesis and release, normalizes diabetes related oxidative stress and neurode-
generation affecting motor ability, through hippocampal serotonergic function [1, 2].
Ethyl acetate leaf extract also inhibits aldose reductase enzyme of rat lens and delays
cataract progression [92]. Bark methanol extract containing aegelin and lupeol, signifi-
cantly reduced blood glucose and increased insulin level in STZ-diabetic rats [32].
Repeated administrations of methanol and water extracts to diabetic rats lowered blood
glucose by more than 50%, and significantly decreased oxidative stress [86, 98].
114 Aegle marmelos (L.) Corrêa

Aqueous seed extract also lowered blood glucose of normal and diabetic rats, but more in
severe diabetic rats, and significantly decreased TC, LDL-C, and TGs, and increased
HDL-C by 33% [53]. Aqueous leaf and fruit extracts reversed the decrease in Na+/K+/
ATPase and increase in Ca2+/ATPase activity in heart and aorta of isoprenaline-induced
MI in rats, and decreased levels of TC and TGs, and also significantly modified activities
of other marker enzymes [59, 78, 80]. Umbelliferone, a natural antioxidant and a cou-
marin derivative from the fruits, restores plasma insulin and glucose levels, reverses
insulin, glucose and LPO markers, and diabetes-induced alterations in the activities of
membrane bound erythrocytes and tissue ATPases of diabetic rats [82]. It also reverses
the decrease in prothrombin, clotting and bleeding time in diabetic rats [81].
Methanol leaf extract produced a significant anxiolytic and antidepressant effect
in mice, and potentiated antidepressant activity of imipramine and fluoxetine.
Pretreatment with prazosin, haloperidol and baclofen significantly decreased the
antidepressant activity of the extract [56]. Leaves extract protected against PTZ and
MES-induced convulsions, comparable to phenytoin, and significantly ameliorated
the postseizure depression on chronic administration [20], and the ethanol leaves
extract was also effective in chronic fatigue syndrome in rats, and significantly
increased activities of CAT and SOD enzymes [60]. Leaves extracts exhibit
significant analgesic, antipyretic and anti-inflammatory activities [13, 94]. Aqueous
root bark extract also produces anti-inflammatory activity [17].
Essential oil and various leaf extracts demonstrated antibacterial and antifungal
activities [27, 73, 83], whereas extracts of leaves, stem, stem-bark, fruit, root,
root-bark, and the pure compound marmelide have shown significant antiviral
activity against coxsackieviruses B1-B6, with marmelide being the most effective
virucidal against coxsackievirus B3 [14]. Methanol extracts of leaves, bark and
fruits exhibit significant activity against B. subtilis, S. aureus, K. pneumoniae,
P. mirabilis, E. coli, S. paratyphi A and B [76], and methanol leaf extract also
showed strong activity against MDR S. typhi [84], while the petroleum ether extract
had highest antifungal efficacy [57]. Aqueous and ethanol leaf extracts also inhibit
growth of dermatophytes, T. mentagrophytes, M. canis, and E. floccosum [15].
Chloroform root extract was active against pathogenic diarrhea causing strains of
V. cholerae, E. coli and Shigella spp., comparable to in vitro activity of cipro-
floxacin [63]. Methanol extract also exhibits antifilarial activity against B. malayi
microfilariae, with complete loss of motility after 48 h of incubation [90].
Administration of ethanol (50%) leaf extract to male albino rats for 60-days
produced reversible infertility, with full recovery after 120-days of withdrawal [23,
25]. Aqueous leaf extract also produced identical effects but the complete reversible
infertility was achieved at twice the dose of ethanol extract [24]. However, aqueous
extract treatment for 60-days produced no significant effect on fertility of female
rats or the fetal development [88]. Methanol bark extract contains marmin and
fagarine, compounds known for reducing male fertility, also produced infertility in
male rats, but the restoration of fertility was faster after only 30-days of stopping the
treatment [7]. Leaf extract decreased T3 concentration by 62% of male mice,
decreased hepatic LPO and increased activities of SOD and CAT enzymes [51].
Aegle marmelos (L.) Corrêa 115

Scopoletin from the leaves, decreased levels of serum thyroid hormones, glucose, as
wells as hepatic G6P activity in levothyroxin-induced hyperthyroid rats [72].
Various extracts produced in vitro cell growth inhibition of human tumor cell lines
[61, 62]. Hydroalcohol dried fruit pulp extract significantly reduced tumor burden and
yield of DMBA-induced skin papillomas in mice [6], and significantly increased liver
and skin CAT activity, GSH and total proteins, and decreased level of LPO [4, 5].
A methanol extract also markedly reduced DENA-induced hepatocarcinogenesis in
rats [55]. Hydroalcohol leaf extract also produced remission of the tumor, and sig-
nificantly lengthened mean and average survival time of EAC-bearing mice [40],
significantly increased mean survival time of Dalton’s lymphoma ascites-bearing
mice, and increased activities of antioxidant enzymes [26], and significantly
decreased IL-1b, IL-6, Bcl-2 and c-jun expressions and upregulated the expression of
p53 and IL-4 in Balb mice with hepatocarcinoma [100]. Hydroalcohol extracts of leaf
and fruits protected mice from radiation-induced sickness, prolonged survival, limited
LPO, and increased GSH levels [41, 43]. Leaf and fruit extracts possess significant NO
scavenging activity [39, 54], though the fruits have lower phenol contents but strong
antiradical power [77]. Topical application of aqueous fruit extract to the eye sig-
nificantly lowered IOP in rabbits, with normal and experimentally-induced high IOP
[3]. An ointment made from methanol root extract significantly enhanced dermal
wound healing in rats, comparable to nitrofurazone [44].
Clinical Studies: Sixteen patients suffering from acute shigellosis and treated with
dried unripe fruit powder in a double-blind RCT did not show any clinical
improvement or bacteriological cure as compared to ampicillin [37]. However, in
another randomized double-blind trial, a compound Ayurvedic preparation con-
taining A. marmelos and Bacopa monniere, was effective in 65% cases of IBS with
diarrhea, as compared to therapy with clidinium, chlordiazepoxide and isaphagulla
being effective in 78% cases [102].
Mechanism of Action: Methanol extract is suggested to produce hypoglycemic
effect by increasing glucose utilization, as it upregulates GLUT-4, PPAR-c and PI3
kinase [9]. The antidiabetic effect also involves preservation of b-cell function, and
insulin-sensitivity through increased PPARc expression [95]. Analgesic effect of
methanol leaves extract is suggested to be mediated through both opioid and
monoaminergic pain pathways [58]. Xanthorrhizol and marmelosin are suggested
responsible for the immunoprophylactic and antitumor effects in transplantable
tumor models [34].
Human A/Es, Allergy and Toxicity: It may cause hemorrhoids and produces
thrombosis.LXXVII
Animal Toxicity: Eight-weeks treatment with aqueous extract was nontoxic on
male rat reproduction and progeny outcome, such as number of implantation sites,
number of viable fetuses and number of dead fetuses in females mated with
plant extract-treated males [10]. Also, i.p. administration of aqueous, ethanol and
methanol extracts of leaves, up to a dose of 100 mg/kg for 14-days, did not produce
any toxicity [99]. However, Arseculeratne et al. [11] reported hepatic lesions, though
it lacks the presence of pyrrolizidine alkaloids. Hydroalcohol leaf extract was
116 Aegle marmelos (L.) Corrêa

nontoxic up to a dose of 1,750 mg/kg body weight in acute toxicity study.

Intraperitoneal LD10 and LD50 were 2,000 and 2,250 mg/kg [40], and hydroalcohol
fruit extract was nontoxic up to the highest administered dose of 6,000 mg/kg [42].
CYP450 and Potential for Drug-Herb Interactions: Hydroalcohol leaf extract
administration to mice for 14-days produced bifunctional induction of hepatic and
extrahepatic metabolizing enzymes, as it induced both phase I and phase II enzymes;
thus, it has the potential for drug-drug interactions on chronic simultaneous use [97].
Commentary: Despite its well-recognized beneficial effects on gastrointestinal
functions and widespread use in traditional medicines, there are no RCTs conducted
or reported except one in acute shigellosis, in the mainstream English publications
listed on PubMed.

References
1. Abraham PM, Kuruvilla KP, Mathew J, et al. Alterations in hippocampal
serotonergic and INSR function in streptozotocin induced diabetic rats
exposed to stress: neuroprotective role of pyridoxine and Aegle maremelos.
J Biomed Sci. 2010;17:78.
2. Abraham PM, Paul J, Paulose CS. Down regulation of cerebellar
serotonergic receptors in streptozotocin induced diabetic rats: effect of
pyridoxine and Aegle maremelos. Brain Res Bull. 2010;82:87–94.
3. Agarwal R, Gupta SK, Srivastava S, et al. Intraocular pressure-lowering
activity of topical application of Aegle marmelos fruit extract in experi-
mental animal models. Ophthalmic Res. 2009;42:112–6.
4. Agrawal A, Jahan S, Goyal PK. Chemically induced skin carcinogenesis in
mice and its prevention by Aegle marmelos (an Indian medicinal plant)
fruit extract. J Environ Pathol Toxicol Oncol. 2011;30:251–9.
5. Agrawal A, Jahan S, Soyal D, et al. Amelioration of chemical-induced skin
carcinogenesis by Aegle marmelos, an Indian medicinal plant, fruit extract.
Integr Cancer Ther. 2012;11:257–66.
6. Agrawal A, Verma P, Goyal PK. Chemomodulatory effects of Aegle
marmelos against DMBA-induced skin tumorigenesis in Swiss albino
mice. Asian Pac J Cancer Prev. 2010;11:1311–4.
7. Agrawal SS, Kumar A, Gullaiya S, et al. Antifertility activity of methanolic
bark extract of Aegle marmelos (l.) in male wistar rats. Daru. 2012;20:94.
8. Ali MS, Pervez MK. Marmenol: a 7-geranyloxycoumarin from the leaves
of Aegle marmelos Corr. Nat Prod Res. 2004;18:141–6.
9. Anandharajan R, Jaiganesh S, Shankernarayanan NP, et al. In vitro glucose
uptake activity of Aegles marmelos and Syzygium cumini by activation of
Glut-4, PI3 kinase and PPARgamma in L6 myotubes. Phytomedicine.
2006;13:434–41.
10. Aritajat S, Kaweewat K, Manosroi J, Manosroi A. Dominant lethal test in
rats treated with some plant extracts. Southeast Asian J Trop Med Public
Health. 2000;31 Suppl 1:171–3.
Aegle marmelos (L.) Corrêa 117

11. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies of medicinal

plants of Sri Lanka. Part 14: toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–5.
12. Arul V, Miyazaki S, Dhananjayan R. Mechanisms of the contractile effect
of the alcoholic extract of Aegle marmelos Corr. on isolated guinea pig
ileum and tracheal chain. Phytomedicine. 2004;11:679–83.
13. Arul V, Miyazaki S, Dhananjayan R. Studies on the anti-inflammatory,
antipyretic and analgesic properties of the leaves of Aegle marmelos Corr.
J Ethnopharmacol. 2005;96:159–63.
14. Badam L, Bedekar SS, Sonawane KB, Joshi SP. In vitro antiviral activity
of bael (Aegle marmelos Corr) upon human coxsackieviruses B1-B6.
J Commun Dis. 2002;34:88–99.
15. Balakumar S, Rajan S, Thirunalasundari T, Jeeva S. Antifungal activity of
Aegle marmelos (L.) Correa (Rutaceae) leaf extract on dermatophytes.
Asian Pac J Trop Biomed. 2011;1:309–12.
16. Behera JP, Mohanty B, Ramani YR, et al. Effect of aqueous extract of
Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J
Pharmacol. 2012;44:614–8.
17. Benni JM, Jayanthi MK, Suresha RN. Evaluation of the anti-inflammatory
activity of Aegle marmelos (Bilwa) root. Indian J Pharmacol. 2011;43:393–7.
18. Bhatti R, Sharma S, Singh J, Ishar MP. Ameliorative effect of Aegle
marmelos leaf extract on early stage alloxan-induced diabetic cardio-
myopathy in rats. Pharm Biol. 2011;49:1137–43.
19. Bhatti R, Sharma S, Singh J, et al. Effect of Aegle marmelos (L.) Correa on
alloxan induced early stage diabetic nephropathy in rats. Indian J Exp Biol.
2013;51:464–9.
20. Bhatti R, Singh J, Nepali K, Ishar MP. Possible involvement of PPAR-c in
the anticonvulsant effect of Aegle marmelos (L.) Correa. Neurochem Res.
2013;38:1624–31.
21. Brijesh S, Daswani P, Tetali P, Antia N, Birdi T. Studies on the
antidiarrhoeal activity of Aegle marmelos unripe fruit: validating its
traditional usage. BMC Complement Altern Med. 2009;9:47.
22. Chakthong S, Weaaryee P, Puangphet P, et al. Alkaloid and coumarins
from the green fruits of Aegle marmelos. Phytochemistry. 2012;75:108–13.
23. Chauhan A, Agarwal M, Kushwaha S, Mutreja A. Suppression of fertility
in male albino rats following the administration of 50% ethanolic extract of
Aegle marmelos. Contraception. 2007;76:474–81.
24. Chauhan A, Agarwal M. Assessment of the contraceptive efficacy of the
aqueous extract of Aegle marmelos Corr. leaves in male albino rats. Hum
Fertil (Camb). 2009;12:107–18.
25. Chauhan A, Agarwal M. Reversible changes in the antifertility induced by
Aegle marmelos in male albino rats. Syst Biol Reprod Med. 2008;54:240–6.
26. Chockalingam V, Kadali SS, Gnanasambantham P. Antiproliferative and
antioxidant activity of Aegle marmelos (Linn.) leaves in Dalton’s
Lymphoma Ascites transplanted mice. Indian J Pharmacol. 2012;44:225–9.
118 Aegle marmelos (L.) Corrêa

27. Dabur R, Gupta A, Mandal TK, et al. Antimicrobial activity of some Indian
medicinal plants. Afr J Tradit Complement Altern Med. 2007;4:313–8.
28. Das AV, Padayatti PS, Paulose CS. Effect of leaf extract of Aegle marmelose
(L.) Correa ex Roxb. on histological and ultrastructural changes in tissues of
streptozotocin induced diabetic rats. Indian J Exp Biol. 1996;34:341–5.
29. Das SK, Roy C. The protective role of Aegle marmelos on aspirin-induced
gastroduodenal ulceration in albino rat model: a possible involvement of
antioxidants. Saudi J Gastroenterol. 2012;18:188–94.
30. Dhandapani R, Sabna B. Phytochemical constituents of some Indian
medicinal plants. Anc Sci Life. 2008;27:1–8.
31. Dhuley JN. Investigation on the gastroprotective and antidiarrhoeal properties
of Aegle marmelos unripe fruit extract. Hindustan Antibiot Bull. 2004;45–
6:41–6.
32. Gandhi GR, Ignacimuthu S, Paulraj MG. Hypoglycemic and b-cells regener-
ative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-
induced diabetic rats. Food Chem Toxicol. 2012;50:1667–74.
33. Gautam MK, Ghatule RR, Singh A, et al. Healing effects of Aegle marmelos (L.)
Correa fruit extract on experimental colitis. Indian J Exp Biol. 2013;51:157–64.
34. George SK, Radhakrishnan R, Sunil Kumar S, et al. Chemopreventive
efficacy of Aegle marmelos on murine transplantable tumors. Integr Cancer
Ther. 2014;13:68–78.
35. Gholap S, Kar A. Hypoglycaemic effects of some plant extracts are possibly
mediated through inhibition in corticosteroid concentration. Pharmazie.
2004;59:876–8.
36. Gireesh G, Reas SK, Jobin M, Paulose CS. Decreased muscarinic M1
receptor gene expression in the cerebral cortex of streptozotocin-induced
diabetic rats and Aegle marmelose leaf extract’s therapeutic function.
J Ethnopharmacol. 2008;116:296–304.
37. Haider R, Khan AK, Aziz KM, et al. Evaluation of indigenous plants in the
treatment of acute shigellosis. Trop Geog Med. 1991;43:266–70.
38. Ilavarasan JR, Monideen S, Vijayalakshmi M. Antiulcer activity of Aegle
marmelos Linn. Anc Sci Life. 2002;21:256–9.
39. Jagetia GC, Baliga MS. The evaluation of nitric oxide scavenging activity
of certain Indian medicinal plants in vitro: a preliminary study. J Med
Food. 2004;7:343–8.
40. Jagetia GC, Venkatesh P, Baliga MS. Aegle marmelos (L.) Correa inhibits
the proliferation of transplanted Ehrlich ascites carcinoma in mice. Biol
Pharm Bull. 2005;28:58–64.
41. Jagetia GC, Venkatesh P, Baliga MS. Evaluation of the radioprotective
effect of bael leaf (Aegle marmelos) extract in mice. Int J Radiat Biol.
2004;80:281–90.
42. Jagetia GC, Venkatesh P, Baliga MS. Fruit extract of Aegle marmelos
protects mice against radiation-induced lethality. Integr Cancer Ther. 2004;
3:323–32.
Aegle marmelos (L.) Corrêa 119

43. Jagetia GC, Venkatesh P. Radioprotection by oral administration of Aegle

marmelos (L.) Correa in vitro. J Environ Pathol Toxicol Oncol. 2005;24:
315–32.
44. Jaswanth A, Sathya S, Ramu S, et al. Effect of root extract of Aegle
marmelos on dermal wound healing in rats. Anc Sci Life. 2001;20:111–4.
45. Kadir MF, Bin Sayeed MS, Mia MM. Ethnopharmacological survey of
medicinal plants used by indigenous and tribal people in Rangamati,
Bangladesh. J Ethnopharmacol. 2012;144:627–37.
46. Kamalakkanan N, Rajadurai M, Prince PS. Effect of Aegle marmelos fruits
on normal and streptozotocin-diabetic Wistar rats. J Med Food. 2003;6:93–8.
47. Kamalakkannan N, Prince PS. Hypoglycaemic effect of water extracts of
Aegle marmelos fruits in streptozotocin diabetic rats. J Ethnopharmacol.
2003;87:207–10.
48. Kamalakkannan N, Prince PS. The effect of Aegle marmelos fruit extract in
streptozotocin diabetes: a histopathological study. J Herb Pharmacother.
2005;5:87–96.
49. Kamalakkannan N, Stanely Mainzen Prince P. Effect of Aegle marmelos
Correa. (Bael) fruit extract on tissue antioxidants in streptozotocin diabetic
rats. Indian J Exp Biol. 2003;41:1285–8.
50. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
51. Kar A, Panda S, Bharti S. Relative efficacy of three medicinal plant extracts
in the alteration of thyroid hormone concentrations in male mice.
J Ethnopharmacol. 2002;81:281–5.
52. Karunanayake EH, Welihinda J, Sirimanne SR, Sinnadorai G. Oral
hypoglycaemic activity of some medicinal plants of Sri Lanka. J Ethnophar-
macol. 1984;11:223–31.
53. Kesari AN, Gupta RK, Singh SK, et al. Hypoglycemic and antihyper-
glycemic activity of Aegle marmelos seed extract in normal and diabetic
rats. J Ethnopharmacol. 2006;107:374–9.
54. Khan TH, Sultana S. Antioxidant and hepatoprotective potential of Aegle
marmelos Correa. against CCl4-induced oxidative stress and early tumor
events. J Enzyme Inhib Med Chem. 2009;24:320–7.
55. Khan TH, Sultana S. Effect of Aegle marmelos on DEN initiated and
2-AAF promoted hepatocarcinogenesis: a chemopreventive study. Toxicol
Mech Methods. 2011;21:453–62.
56. Kothari S, Minda M, Tonpay SD. Anxiolytic and antidepressant activities
of methanol extract of Aegle marmelos leaves in mice. Indian J Physiol
Pharmacol. 2010;54:318–28.
57. Kothari S, Mishra V, Bharat S, Tonpay SD. Antimicrobial activity and
phytochemical screening of serial extracts from leaves of Aegle marmelos
(Linn.). Acta Pol Pharm. 2011;68:687–92.
120 Aegle marmelos (L.) Corrêa

58. Kothari S, Kushwah A, Kothari D. Involvement of opioid and monoamin-

ergic pain pathways in Aegle marmelos induced analgesia in mice. Indian J
Pharmacol. 2013;45:371–5.
59. Krushna GS, Kareem MA, Reddy VD, et al. Aegle marmelos fruit extract
attenuates isoproterenol-induced oxidative stress in rats. J Clin Biochem
Nutr. 2012;50:199–204.
60. Lalremruta V, Prasanna GS. Evaluation of protective effect of Aegle
marmelos Corr. in an animal model of chronic fatigue syndrome. Indian J
Pharmacol. 2012;44:351–6.
61. Lambertini E, Piva R, Khan MT, et al. Effects of extracts from Bangladeshi
medicinal plants on in vitro proliferation of human breast cancer cell lines and
expression of estrogen receptor alpha gene. Int J Oncol. 2004;24:419–23.
62. Lampronti I, Martello D, Bianchi N, et al. In vitro antiproliferative effects
on human tumor cell lines of extracts from the Bangladeshi medicinal plant
Aegle marmelos Correa. Phytomedicine. 2003;10:300–8.
63. Mazumder R, Bhattacharya S, Mazumder A, et al. Antidiarrhoeal evaluation
of Aegle marmelos (Correa) Linn. root extract. Phytother Res. 2006;20:82–4.
64. Mishra BB, Kishore N, Tiwari VK, et al. A novel antifungal anthraquinone
from seeds of Aegle marmelos Correa (family Rutaceae). Fitoterapia. 2010;
81:104–7.
65. Mishra BB, Singh DD, Kishore N, et al. Antifungal constituents isolated
from the seeds of Aegle marmelos. Phytochemistry. 2010;71:230–4.
66. Narender T, Shweta S, Tiwari P, et al. Antihyperglycemic and antidyslipi-
demic agent from Aegle marmelos. Bioorg Med Chem Lett. 2007;17:1808–11.
67. Narendhirakannan RT, Subramanian S, Kandaswamy M. Biochemical
evaluation of antidiabetogenic properties of some commonly used Indian
plants on streptozotocin-induced diabetes in experimental rats. Clin Exp
Pharmacol Physiol. 2006;33:1150–7.
68. Narendhirakannan RT, Subramanian S, Kandaswamy M. Mineral content
of some medicinal plants used in the treatment of diabetes mellitus. Biol
Trace Elem Res. 2005;103:109–15.
69. Nugroho AE, Anas Y, Arsito PN, et al. Effects of marmin, a compound
isolated from Aegle marmelos Correa, on contraction of the guinea
pig-isolated trachea. Pak J Pharm Sci. 2011;24:427–33.
70. Nugroho AE, Riyanto S, Sukari MA, Maeyama K. Effects of aegeline, a
main alkaloid of Aegle marmelos Correa leaves, on the histamine release
from mast cells. Pak J Pharm Sci. 2011;24:359–67.
71. Panaskar SN, Joglekar MM, Taklikar SS, et al. Aegle marmelos Correa leaf
extract prevents secondary complications in streptozotocin-induced dia-
betic rats and demonstration of limonene as a potent antiglycating agent.
J Pharm Pharmacol. 2013;65:884–94.
72. Panda S, Kar A. Evaluation of the antithyroid, antioxidative and antihyper-
glycemic activity of scopoletin from Aegle marmelos leaves in hyperthy-
roid rats. Phytother Res. 2006;20:1103–5.
Aegle marmelos (L.) Corrêa 121

73. Pattnaik S, Subramanyam VR, Kole C. Antibacterial and antifungal

activity of ten essential oils in vitro. Microbios. 1996;86:237–46.
74. Phuwapraisirisan P, Puksasook T, Jong-Aramruang J, Kokpol U. Pheny-
lethyl cinnamides: a new series of alpha-glucosidase inhibitors from the
leaves of Aegle marmelos. Bioorg Med Chem Lett. 2008;18:4956–8.
75. Ponnachan PT, Paulose CS, Panikkar KR. Effect of leaf extract of Aegle
marmelos in diabetic rats. Indian J Exp Biol. 1993;31:345–7.
76. Poonkothai M, Saravanan M. Antibacterial activity of Aegle marmelos
against leaf, bark and fruit extracts. Anc Sci Life. 2008;27:15–8.
77. Prakash D, Upadhyay G, Pushpangadan P, Gupta C. Antioxidant and free
radical scavenging activities of some fruits. J Complement Integr Med.
2011. https://doi.org/10.2202/1553-3840.1513.
78. Prince PS, Rajadurai M. Preventive effect of Aegle marmelos leaf extract on
isoprenaline-induced myocardial infarction in rats: biochemical evidence.
J Pharm Pharmacol. 2005;57:1353–7.
79. Raja SB, Murali MR, Kumar NK, Devaraj SN. Isolation and partial
characterisation of a novel lectin from Aegle marmelos fruit and its effect on
adherence and invasion of Shigellae to HT29 cells. PLoS ONE. 2011;6:e16231.
80. Rajadurai M, Prince PS. Comparative effects of Aegle marmelos extract
and alpha-tocopherol on serum lipids, lipid peroxides and cardiac enzyme
levels in rats with isoproterenol-induced myocardial infarction. Singapore
Med J. 2005;46:78–81.
81. Ramesh B, Pugalendi KV. Effect of umbelliferone on tail tendon collagen
and haemostatic function in streptozotocin-diabetic rats. Basic Clin
Pharmacol Toxicol. 2007;101:73–7.
82. Ramesh B, Pugalendi KV. Influence of umbelliferone on membrane-bound
ATPases in streptozotocin-induced diabetic rats. Pharmacol Rep. 2007;59:
339–48.
83. Rana BK, Singh UP, Taneja V. Antifungal activity and kinetics of inhibition
by essential oil isolated from leaves of Aegle marmelos. J Ethnopharmacol.
1997;57:29–34.
84. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
85. Roy A, Mukherjee AK, Rao CV. Graded-hydrolysis studies on bael (Aegle
marmelos) gum. Carbohydr Res. 1975;41:219–26.
86. Sabu MC, Kuttan R. Antidiabetic activity of Aegle marmelos and its
relationship with its antioxidant properties. Indian J Physiol Pharmacol.
2004;48:81–8.
87. Sachdewa A, Raina D, Srivastava AK, Khemani LD. Effect of Aegle marmelos
and Hibiscus rosa sinensis leaf extract on glucose tolerance in glucose induced
hyperglycemic rats (Charles Foster). J Environ Biol. 2001;22:53–7.
88. Saenphet K, Aritajat S, Saenphet S, et al. Safety evaluation of aqueous extracts
from Aegle marmelos and Stevia rebaudiana on reproduction of female rats.
Southeast Asian J Trop Med Public Health. 2006;37 Suppl 3:203–5.
122 Aegle marmelos (L.) Corrêa

89. Saha S, Verma R. Inhibitory potential of traditional herbs on a-amylase

activity. Pharm Biol. 2012;50:326–31.
90. Sahare KN, Anandhraman V, Meshram VG, et al. Antimicrofilarial activity
of methanolic extract of Vitex negundo and Aegle marmelos and their
phytochemical analysis. Indian J Exp Biol. 2008;46:128–31.
91. Samarasekera JK, Khambay BP, Hemalal KP. A new insecticidal
protolimonoid from Aegle marmelos. Nat Prod Res. 2004;18:117–22.
92. Sankeshi V, Kumar PA, Naik RR, et al. Inhibition of aldose reductase by
Aegle marmelos and its protective role in diabetic cataract. J Ethnopharma-
col. 2013;149:215–21.
93. Seema PV, Sudha B, Padayatti PS, et al. Kinetic studies of purified malate
dehydrogenase in liver of streptozotocin-diabetic rats and the effect of leaf
extract of Aegle marmelose (L.) Correa ex Roxb. Indian J Exp Biol. 1996;
34:600–2.
94. Shankarananth V, Balakrishnan N, Suresh D, et al. Analgesic activity of
methanol extract of Aegle marmelos leaves. Fitoterapia. 2007;78:258–9.
95. Sharma AK, Bharti S, Goyal S, et al. Upregulation of PPARc by Aegle
marmelos ameliorates insulin resistance and b-cell dysfunction in high fat
diet fed-streptozotocin induced type 2 diabetic rats. Phytother Res. 2011;
25:1457–65.
96. Shoba FG, Thomas M. Study of antidiarrhoeal activity of four medicinal
plants in castor oil-induced diarrhoea. J Ethnopharmacol. 2001;76:73–6.
97. Singh RP, Banerjee S, Rao AR. Effect of Aegle marmelos on biotrans-
formation enzyme systems and protection against free-radical-mediated
damage in mice. J Pharm Pharmacol. 2000;52:991–1000.
98. Upadhya S, Shanbhag KK, Suneetha G, et al. A study of hypoglycemic
and antioxidant activity of Aegle marmelos in alloxan induced diabetic
rats. Indian J Physiol Pharmacol. 2004;48:476–80.
99. Veerappan A, Miyazaki S, Kadarkaraisamy M, Ranganathan D. Acute and
subacute toxicity studies of Aegle marmelos Corr., an Indian medicinal
plant. Phytomedicine. 2007;14:209–15.
100. Verma S, Bahorun T, Singh RK, et al. Effect of Aegle marmelos leaf
extract on N-methyl N-nitrosourea-induced hepatocarcinogensis in Balb/c
mice. Pharm Biol. 2013;51:1272–81.
101. Vijaya C, Ramanathan M, Suresh B. Lipid lowering activity of ethanolic
extract of leaves of Aegle marmelos (Linn.) in hyperlipidaemic models of
Wistar albino rats. Indian J Exp Biol. 2009;47:182–5.
102. Yadav SK, Jain AK, Tripathi SN, Gupta JP. Irritable bowel syndrome:
therapeutic evaluation of indigenous drugs. Indian J Med Res Section A-Infect
Dis. 1989;90:496–503.
Agrimonia eupatoria L.
(Rosaceae)

(Syn.: Agrimonia officinalis Lamarck)

Abstract
Both Dioscorides and Pliny described this plant as having inverted fruits, so
rough and bristly that they adhere to clothes when ripe. The name Agrimonia
may have its origin in the Greek ‘agremone’ which refers to plants that
supposedly healed cataracts of the eye. It is a folk remedy for asthma, bronchitis,
dermatitis, enterorrhagia, enuresis, gastrorrhagia, hematuria, hepatosis, metror-
rhagia, neuralgia, neuritis, pharyngitis, rheumatism, tuberculosis and warts. The
herb was used by singers and speakers in gargles to clear and improve their
voice, and is said to induce sleep if placed under one’s pillow. Unani physicians
describe aerial parts, especially flowers, with demulcent, detergent, purgative of
dried humours, vasodilator, blood purifier, deobstruent of liver and spleen,
diuretic, emmenagogue, galactagogue, and stomachic properties; and use it for
the treatment of liver, stomach and pancreatic inflammations, and chronic fevers.
In Europe, it is widely used as a mild astringent, both externally and internally,
for inflammation of the throat, gastroenteritis, and stomach flu. In Bulgarian
phytomedicine, it is used for the treatment of respiratory, gastrointestinal and
other inflammatory disorders, and the Anglo-Saxon medical texts from the 10th
century mention the plant to treat bacterial infections and wounds. Fifty-two
volatile components have been identified in the leaves and roots of the herb.
Leaves decoction or dried leaves in diet did not affect plasma glucose and insulin
levels in normal mice, but, hyperglycemia and its associated polydipsia and body
weight loss were reduced in diabetic mice. One-month consumption of agrimony
tea by healthy volunteers significantly elevated plasma total antioxidant capacity,
and improved lipid profile, increased HDL-C and HDL-C correlation with
adiponectin levels.

Keywords





Agrimony Amoricos Erva-agrimónia Eupatoria Fıtıkotu Gewöhnlicher





odermennig Ghafis Gul kalli Shajaratul-baraghees Xian he cao

© Springer Nature Switzerland AG 2020 123
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_13
124 Agrimonia eupatoria L.

Vernaculars: Urd.: Ghafis; Ara.: Ghafith, Hashishatul-ghafis, Khafil, Shajaratul-

baraghees, Shaukat-el-muntineh, Terfaq; Chi.: Xian he cao; Dut.: Gewone agri-
monie; Eng.: Agrimony, Church steeples, Cocklebur, Liverwort, Sticklewort; Fre.:
Agrimoine, Aigremoine eupatoire, Francormier, Gariot, Herbe de Saint Guillaume,
Herbe de Sainte Madeleine, Soubeirette, Thé des bois, Thé du nord, Toute-bonne,
Véteresque; Ger.: Duft-odermennig, Gemeiner odermennig, Gewöhnlicher oder-
mennig, Kleiner odermennig; Ita.: Agrimonia, Agrimonia comune, Eupatoria; Per.:
Gul kalli, Khila; Por.: Agrimónia, amoricos, Erva-agrimónia, Erva-eupatória,
Erva-hepática, Eupatório-dos-gregos; Spa.: Agrimonia, Agrimonia común, Algafil,
Amores pequeños, Amoricos, Cabsidiella, Gafetí, Hierba bacera, Hierba de San
Guillermo, Hierba del podador, Mermasangre, Serverola; Tur.: Fıtıkotu.
Description: An herb which Dioscorides described as having inverted fruits, so rough
and bristly that they adhere to clothes when ripe. Pliny mentioned the plant to be in royal
patronage (Eupator Mithridates, king of Pontus).XL A perennial herb, common in
grasslands throughout Europe, found in temperate Himalayas of India, China, Japan,
Korea, Taiwan, and widely distributed in Northern Hemisphere, United States and
Canada. It grows to 30–60 cm high, vilous, reddish, the basal leaves are alternate,
glabrous and pinnatified; segments oval-lanceolate, deeply dentate, irregular, underside
villous white and without glands. Flowers (September–October) are small, yellow and
star-shaped and grow at the top of the stem in a long terminal spike. The name Agri-
monia may have its origin in the Greek ‘agremone’ which refers to plants that sup-
posedly healed cataracts of the eye.XL However, GhaniL and KabeeruddinLXXVII
described it as a thorny plant with broad hairy leaves with bright blue flowers, and a very
bitter taste. Khory and KatrakLXXXI mentioned the stem ligneous, hairy and swarthy,
and leaves indented at their edges, downy and swarthy; fruits as rough and bristly,
generally inverted when ripe, and adhering to clothes (Figs. 1, 2 and 3).
Actions and Uses: Agrimony is a folk remedy for asthma, bronchitis, dermatitis,
enterorrhagia, enuresis, gastrorrhagia, hematuria, hepatosis, metrorrhagia, neuralgia,
neuritis, pharyngitis, rheumatism, tuberculosis and warts.XC Persian peasants use it to
treat ringworm of the scalp in children.XL Aromatic, astringent, diuretic and taeni-
cide,LXXXI,CV and used in dyspepsia and taken hot to induce perspiration in fever, and
also used as an antiscorbutic. The seeds with wine are used in dysentary.LXXXI The herb
is used by singers and speakers in gargles to clear and improve their voice,XC and is said
to induce sleep if placed under one’s pillow.LV Hartwell [7] reported the herb to alleviate
condylomata, sclerosis of the spleen and liver, tumors of the internal organs, mesenteric
region, scrotum, and stomach, as well as corns and warts, and cancer of the breast, face,
mouth and stomach. It is also described as cardiotonic, coagulant, depurative, litholytic,
sedative, tonic, vermifuge and vulnerary. Unani physicians describe aerial parts,
especially flowers, (temperament, hot 2° and dry 2°) with demulcent, detergent,
purgative of dried humours, vasodilator, blood purifier, deobstruent of liver and spleen,
diuretic, emmenagogue, galactagogue, and stomachic properties; and use it for the
treatment of liver, stomach and pancreatic inflammations, and chronic fevers.L,LXXVII
The tonic effect of the herbal infusion is suggested to be due to high thiamine contents
(2.36 lg/g) [5]. In Europe, it is widely used as a mild astringent, both externally and
internally, for inflammation of the throat, gastroenteritis, and stomach flu. The extract is
Agrimonia eupatoria L. 125

Fig. 1 Agrimonia eupatoria, Illustration, Kurt Stueber, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Illustration_Agrimonia_eupatoria0.jpg

a constituent of stomach and bowel remedies and urological products. In Bulgarian

phytomedicine, it is used for the treatment of respiratory, gastrointestinal and other
inflammatory disorders [8], and the Anglo-Saxon medical texts from the 10th century
mention the plant to treat bacterial infections and wounds [15].
Phytoconstituents: Fifty-two volatile components have been identified in the
leaves and roots of the herb [5]. Zang and Chen [17] isolated nine compounds from
the plant, apigenin-7-O-3-D-glucopyranoside, catechin, quercetin, rutin, kaempferol-
3-O-a-L-rhamnoside, Kampferol-3-O-b-D-glucopyranoside, lutcolin-7-O-b-D-glu-
copyranosidc, 19a,24-dihydroxy ursolic acid, and 3,3′-di-O-mcthyl ellagic acid
4-O-b-D-glucopyranoside with blood sugar lowering activity. Fresh herb contains a
glucoside alkaloid, a nicotinic acid amide, traces of essential oil and organic acids,
Vit. B, Vit. K, ascorbic acid, 1.5% triterpene and a derivative of a-amyrin.
Fresh drug also contains agrimonolide, palmitic acid, stearic acid, ceryl alcohol and
phytosterols.XC In methanol extract, eight phenolic substances, rutin, quercetin,
elagic acid, chlorogenic acid, caffeic acid were identified; and a hydroalcohol extract
showed high concentration of flavan-3-ols, flavonols, flavones and phenolic acids
[3]. In alcohol extract the free sugars are saccharose, glucose and fructose, and the
126 Agrimonia eupatoria L.

Fig. 2 Agrimonia eupatoria, Flowers, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Agrimonia_eupatoria_002.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

bound sugars were identified as galactose, glucose and arabinose. Aqueous extract
contained saccharose, glucose and fructose as free sugars and galactose, glucose,
arabinose and rhamnose as bound sugars [1]. Aerial parts contain 4–10% condensed
tannins, small amounts of ellagitannins and traces of gallotannins. Seeds contain
35% oil, which contain oleic, linoleic and linolenic acids.
Pharmacology: Administration of leaves decoction or dried leaves in diet did not
affect food and water intake, body weight, plasma glucose and insulin levels in
normal mice, but, the hyperglycemia and its associated polydipsia and body weight
loss were reduced in diabetic mice [13]. Ethanol extract of aerial parts significantly
protected rats from cisplatin-induced neuropathic pain [11]. The plant exhib-
ited significant antioxidant activity [8], and radical scavenging properties [14].
Hydroalcohol extract and a polyphenol-enriched fraction that contains flavan-3-ols,
flavonols, flavones and phenolic acids, exhibited strong radical scavenger activity
and potential antioxidant capacity against reactive species formed during inflam-
mation [3]. The plant is reported to have diuretic and uricosuric activities [6], and
the aqueous extract was protective against chronic ethanol consumption-induced
hepatotoxicity in rats [16]. Hydroalcohol extract demonstrated strong growth
inhibiting activity against H. pylori [4], and the aqueous extract of aerial parts
showed maximum inhibition of HBsAg release against hepatitis B virus; plant
collected in mid-July produced the strongest effect [10]. Antibacterial and radical
scavenging activities have also been reported in n-hexane, dichloromethane and
methanol extracts of the seeds [2]. Methanol stems extract also significantly
attenuated glutamate-induced oxidative stress in HT22 hippocampal cells [12].
Agrimonia eupatoria L. 127

Fig. 3 Agrimonia eupatoria, Fruits, Pethan, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Agrimonia_eupatoria02.jpg, https://creative
commons.org/licenses/by-sa/3.0/deed.en

Clinical Studies: One-month consumption of agrimony tea by healthy volunteers

significantly elevated plasma total antioxidant capacity, and significantly lowered
IL-6 levels at the end of the intervention, indicating its potential to improve markers
of lipid metabolism, oxidative status and inflammation in healthy adults. Lipid
profile showed improvement by increased HDL-C level and HDL-C correlation
with adiponectin levels [9].
Human A/Es, Allergy and Toxicity: It is reported to produce photodermatitis.XXXVIII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It has shown significantly improving antioxidant status and HDL-C
levels in healthy individuals but there are no studies in disease states, and some of
the other recognized clinical effects.

References
1. Buckova A, Eisenreichova E, Leifertova I, Licha K. Pharmacobotanical
study of the genus Agrimonia. III. Phanolic substances and saccharides in
Agrimonia eupatoria subspecies eupatoria and Agrimonia procera. Cesk
Farm. 1972;21:244–8.
2. Copland A, Nahar L, Tomlinson CT, et al. Antibacterial and free radical
scavenging activity of the seeds of Agrimonia eupatoria. Fitoterapia. 2003;
74:133–5.
128 Agrimonia eupatoria L.

3. Correia HS, Batista MT, Dinis TC. The activity of an extract and fraction of
Agrimonia eupatoria L. against reactive species. Biofactors. 2007;29:91–104.
4. Cwikla C, Schmidt K, Matthias A, et al. Investigations into the antibacterial
activities of phytotherapeutics against Helicobacter pylori and Campy-
lobacter jejuni. Phytother Res. 2010;24:649–56.
5. Feng XL, He YB, Liang YZ, et al. Comparative analysis of the volatile compo-
nents of Agrimonia eupatoria from leaves and roots by gas chromatography-
mass spectrometry and multivariate curve resolution. J Anal Methods Chem.
2013;2013:246986.
6. Giachetti D, Taddei E, Taddei I. Diuretic and uricosuric activity of
Agrimonia eupatoria L. Boll Soc Ital Biol Sper. 1986;62:705–11.
7. Hartwell JL. Plants used against cancer. A survey. Lloydia. 1969–1971;
32–34.
8. Ivanova D, Gerova D, Chervenkov T, Yankova T. Polyphenols and antioxidant
capacity of Bulgarian medicinal plants. J Ethnopharmacol. 2005;96:145–50.
9. Ivanova D, Vankova D, Nashar M. Agrimonia eupatoria tea consumption in
relation to markers of inflammation, oxidative status and lipid metabolism in
healthy subjects. Arch Physiol Biochem. 2013;119:32–7.
10. Kwon DH, Kwon HY, Kim HJ, et al. Inhibition of hepatitis B virus by an
aqueous extract of Agrimonia eupatoria L. Phytother Res. 2005;19:355–8.
11. Lee KH, Rhee KH. Antinociceptive effect of Agrimonia eupatoria extract
on a cisplatin-induced neuropathic model. Afr J Tradit Complement Altern
Med. 2016;13:139–44.
12. Lee KY, Hwang L, Jeong EJ, et al. Effect of neuroprotective flavonoids of
Agrimonia eupatoria on glutamate-induced oxidative injury to HT22
hippocampal cells. Biosci Biotechnol Biochem. 2010;74:1704–6.
13. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatments
for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetolo-
gia. 1990;33:462–4.
14. Venskutonis PR, Skemaite M, Ragazinskiene O. Radical scavenging capacity
of Agrimonia eupatoria and Agrimonia procera. Fitoterapia. 2007;78:166–8.
15. Watkins F, Pendry B, Sanchez-Medina A, Corcoran O. Antimicrobial assays
of three native British plants used in Anglo-Saxon medicine for wound healing
formulations in 10th century England. J Ethnopharmacol. 2012;144:408–15.
16. Yoon SJ, Koh EJ, Kim CS, et al. Agrimonia eupatoria protects against chronic
ethanol-induced liver injury in rats. Food Chem Toxicol. 2012;50:2335–41.
17. Zhang JH, Chen YS. Studies on the lowering blood sugar substances from
agrimony. Zhong Yao Cai. 2009;32:1537–9 (Chinese).
Alhagi maurorum Medik.
(Fabaceae/Leguminosae)

(Syns.: A. camelorum DC; A. pseudalhagi (M.Bieb.) Fisch; Hedysarum alhagi L.)

Abstract
A perennial plant growing in the deserts of Persia, Syria, Egypt, Pakistan and
India, but found from the Mediterranean to Russia. Camel thorn is a favorite food of
camels. It is regarded emollient, bile purgative, expectorant, aphrodisiac and
fattening by Unani physicians; it also improves memory. Whole plant is laxative,
diuretic, and expectorant; the leaf oil is used for rheumatism, and the flowers are
used for piles. A poultice or fumigation is recommended to cure piles; the
expressed juice is applied to corneal opacities and is directed to be snuffed up the
nose as a remedy for migraine. In Ayurveda, dried plant is used in trsnā, chardi,
kāsa, jvara, vātarakta, raktapitta, and visarpa. In the Concan region of India, the
plant is smoked along with black datura, tobacco and ajwan seeds as a remedy for
asthma. In the Arabian and Persian traditional medicines, it is used for the
prevention and treatment of liver ailments, such as jaundice, lack of appetite,
nausea, vomiting, and other gastrointestinal disorders, Aqueous root extract is used
to dilate ureter to pass kidney stones, and the methanol extract is used as an
antidiarrheal, and as herbal cough syrup. Major phytoconstituents reported are
b-sitosterol, cinnamic acid, coumaric acid, and hydroxybenzoic acid. Ethanol
extract produced significant antioxidant and gastric antiulcer activities. Aqueous
and ethanol extracts exhibited significant anti-inflammatory activity, and the
ethanol extract produced centrally-mediated analgesic activity. Aqueous and
ethanol extracts of aerial parts also significantly lowered FBG, TGs, TC, LDL-C,
and VLDL-C, and increased HDL-C concentration in diabetic rats. It is also
reported to protect rats from cisplatin-nephrotoxicity.

Keywords




Alghoul Alhagi des chameaux Camel’s thorn Juvansa Khar-e-shutar






Lupinella alhagi Manna di Persia Mannakameldorn Turanjbeen Tz’u mi

© Springer Nature Switzerland AG 2020 129

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_14
130 Alhagi maurorum Medik.

Vernaculars: Urd.: Alghoul, Shonkul-jamal, Turanjbeen; Hin.: Bharbharra,

Dulal-labah, Juvansa, Shakar jawasa; San.: Duhsparśā, Dura-labha, Yāsa, Yavāsa
(manna); Ben.: Dullal-abha, Javasha; Mal.: Kappathumba, Kodithuva; Mar.:
Javaasa, Jawaso, Kas; Tam.: Tellanginiyo; Tel.: Giri-karmika, Tellaginiya chettu;
Ara.: Aaqhul, Alghoul, Asalulhawa, Asalussamawi, Nadas-sama, Qaisoom; Chi.:
Tz’u mi; Eng.: Camel’s thorn, Manna of the desert, Persian mannaplant; Fre.:
Alhagi des chameaux, Alhagi des maures, Manne de Perse, Sainfoin agul, Sainfoin
des chameaux; Ger.: Mannakameldorn, Mannastrauch, Orientalischer kameldorn;
Ita.: Lupinella alhagi, Manna di Persia, Sanofieno di levante; Per.: Khare-buz, Khar
shotor, Khar-e-shutar.
Description: A perennial plant growing in the deserts of Persia (Khorasan and
Hamadan), Syria, Egypt, Pakistan (Sind, Baluchistan) and India (Gujarat, Punjab,
U.P., Rajasthan, Konkan), but found from the Mediterranean to Russia. Camel
thorn or aqool is a favorite food of camels [17, 23]. It is a low shrub armed with
copious subpatent hard pungent spines 1.3–2.5 cm long; leaves simple, drooping
from the base of the spines or branches, oblong, obtuse, rigidly coriaceous, glab-
rous; flowers 1–6 from a spine or on short pedicles; calyx glabrous 0.2–0.4 cm;
corolla reddish, three times the length of the calyx; pods 2.5 cm long or less, falcate
or straight, constricted between the seeds; seeds kidney-shaped, greenish-grey, very
hard. Turanjbeen occurs in white grains or small agglutinated masses, mixed more
or less with the thorns, pods and leaves. It has hardly any odor; the taste is sac-
charine, and afterward slightly acrid; white is fresh and better (Fig. 1).L
Actions and Uses: Whole plant is laxative, diuretic, and expectorant;XXI,CV the
leaves oil is used for rheumatism, and the flowers are used for piles.XXI It is

Fig. 1 Alhagi maurorum, Flowers, F. Eitan, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Camel_Thorn_flower.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Alhagi maurorum Medik. 131

regarded emollient, bile purgative, expectorant, aphrodisiac and fattening, of a

moderate temperament by Unani physicians. It specifically purges bile from the
body, and improves memory. Due to its sweet taste, it is useful as a laxative in
children and delicate persons.LXIX,LXXVII In Mashhad, traditional healers of Iranian
medicine use the decoction for the treatment of jaundice [3], and in the Arabian and
Persian traditional medicines, it is used for the prevention and treatment of liver
ailments, such as jaundice, lack of appetite, nausea, vomiting, and other gastroin-
testinal disorders [14, 20], such as gastric ulcers, intestinal tract infections, and as a
purgative [4]. Dymock et al.,XL in their Pharmacographia Indica described the
plant as: “the Hindus use fresh juice as diuretic, generally in combination with
laxatives and aromatics. In Mohammadan works, it is considered aperient, attenuant
and alexipharmic (antidote). A poultice or fumigation is recommended to cure piles;
the expressed juice is applied to corneal opacities and is directed to be snuffed up
the nose as a remedy for migraine. An oil is prepared with the leaves as an external
application in rheumatism. The flowers are applied to remove piles. Mir Moham-
mad Hussain described it as aperient and cholagogue, more digestible than shir-
khisht, expectorant, a good blood purifier of corrupt and adust humours when given
in diet drink such as barley water; and with milk, fattening and aphrodisiac. In the
Concan, the plant is smoked along with black datura, tobacco and ajwan seeds as a
remedy for asthma.” Khory and KatrakLXXXI describe it laxative, diuretic, chola-
gogue, aphrodisiac, demulcent and expectorant, and used in cough. Aqueous root
extract is used to dilate ureter to pass kidney stones, and the methanol extract is
used as an antidiarrheal [6], and as herbal cough syrup [16]. In Ayurveda, dried
plant is used in trsnā, chardi, kāsa, jvara, vātarakta, raktapitta, and visarpa.LIX
Phytoconstituents: b-sitosterol, cinnamic acid, coumaric acid, and hydroxyben-
zoic acid are reported as major phytoconstituents [12]. Six flavonoid glycosides,
isolated from the ethanol extract were identified as kaempferol, chrysoeriol,
isorhamnetin, chrysoeriol-7-O-xylosoid, kaempferol-3-galactorhamnoside, and
isorhamnetin3-O-b-D-apio-furanosyl(1-2)b-D-galactopyranoside [7]. Three flavo-
noids, isorhamnetin-3-O-[-a-1-rhamnopyranosyl-(1 > 3)]-b-D-glucopyranoside, 3′-
O-methylorobol, and quercetin 3-O-b-d-glucopyranoside are also reported [1].
Pharmacology: Methanol extract produced significant analgesic effect in mice [5],
and demonstrated antidiarrheal effect against castor oil-induced diarrhea. However,
lower concentrations of the extract increased contractions of the isolated duodenal
smooth muscle of rabbit, while higher concentrations produced a rapid depressant
effect due to calcium channel blockade [6]. Ethanol extract produced significant
antioxidant and gastric antiulcer activities [7, 22], and two flavonoid glycosides also
showed significant gastric antiulcer activity [7]. Aqueous and ethanol extracts
exhibited significant antioxidant and anti-inflammatory activities [8, 21], and the
ethanol extract also produced centrally-mediated analgesic activity [2]. Antioxidant
activity of leaves is higher, with higher phenolic contents than those of the flowers
[15]. Aqueous and ethanol extracts of aerial parts significantly lowered levels of
132 Alhagi maurorum Medik.

FBG, TGs, TC, LDL-C, and VLDL-C, and increased HDL-C concentration in
diabetic rats [23]. It is also reported to protect rats from cisplatin-nephrotoxicity
[11]. Hossein et al. [13] reported an increase in force of contraction and cardiac
output of toad heart, and a slight fall in dogs’ BP. Ethanol root extract possesses
spasmolytic and ureter relaxing activity [18], and aqueous acetic acid root extract
exhibited litholytic effect [19]. Methanol extract exhibited modest antibacterial
activity against two strains of E. coli [10], while butanol extract of aerial parts was
reported to exhibit significant antibacterial and antifungal activity against B. atro-
phaeus, B. subtilis, S. aureus, E. coli, K. pneumonia, S. typhi, and C. albicans [9].
Human A/Es, Allergy and Toxicity: It should not be used or used with caution in
patients with hot temperament and those suffering from smallpox.LXXVII
Animal Toxicity: Methanol extract was orally nontoxic to mice up to a dose of
2,000 mg/kg [5].
Commentary: It is one of the inadequately investigated plants in this book. There
are no RCTs on any of its clinical effects reported in the mainstream English
publications listed on PubMed.

References
1. Ahmad S, Riaz N, Saleem M, et al. Antioxidant flavonoids from Alhagi
maurorum. J Asian Nat Prod Res. 2010;12:138–43.
2. Almeida R, Navarro D, Barbosa-Filho J. Plants with central analgesic
activity. Phytomed. 2001;8:310–22.
3. Amiri MS, Joharchi MR, Taghavizadehyazdi ME. Ethnomedicinal plants
used to cure jaundice by traditional healers of Mashhad, Iran. Iran J Pharm
Res. 2014;13:157–62.
4. Asghari MH, Fallah M, Moloudizargari M, et al. A systematic and
mechanistic review on the phytopharmacological properties of Alhagi
Species. Anc Sci Life. 2016;36:65–71.
5. Atta AH, El-Sooud KA. The antinociceptive effect of some Egyptian
medicinal plant extracts. J Ethnopharmacol. 2004;95:235–8.
6. Atta AH, Mouneir SM. Antidiarrhoeal activity of some Egyptian medicinal
plant extracts. J Ethnopharmacol. 2004;92:303–9.
7. Awaad Amani A, Maitland D, Soliman G. Antiulcerogenic activity of
Alhagi maurorum. Pharm Biol. 2006;44:292–6.
8. Awaad AS, El-Meligy R, Qenawy S, Atta A, Soliman GA. Anti-inflammatory,
antinociceptive and antipyretic effects of some desert plants. J Saudi Chem
Soc. 2011;15:367–73.
9. Bakht J, Naqash G, Shafi M. Report: In vitro antibacterial and antifungal
activity of different solvent extracted samples of Alhagi maurorum. Pak J
Pharm Sci. 2014;27:1953–9.
10. Bonjar GS. Screening for antibacterial properties of some Iranian plants
against two strains of Escherichia coli. Asian J Plant Sci. 2004;3:310–4.
Alhagi maurorum Medik. 133

11. Changizi-Ashtiyani S, Alizadeh M, Najafi H, et al. Physalis alkekengi and

Alhagi maurorum ameliorate the side effect of cisplatin-induced nephro-
toxicity. Cancer Gene Ther. 2016;23:235–40.
12. Hameed M, Ashraf M, Al-Quriany F, et al. Medicinal flora of the Cholistan
desert: a review. Pak J Bot. 2011;43:39–50.
13. Hossein AM, Fahim I, Hassan AAH. The toxicity and activity of Alhagi
maurorum. Proc Pharm Soc Egypt Sci Ed. 1955;37:107–12.
14. Hudaib M, Mohammad M, Bustanji Y, et al. Ethnopharmacological survey
of medicinal plants in Jordan, Mujib nature reserve and surrounding area.
J Ethnopharmacol. 2008;120:63–71.
15. Laghari AH, Ali Memon A, Memon S, et al. Determination of free phenolic
acids and antioxidant capacity of methanolic extracts obtained from leaves and
flowers of camel thorn (Alhagi maurorum). Nat Prod Res. 2012;26:173–6.
16. Laghari AH, Ali Memon A, Nelofar A, et al. A new flavanenol with urease-
inhibition activity isolated from roots of manna plant camelthorn (Alhagi
maurorum). J Mol Struct. 2010;965:65–7.
17. Loizzo MR, Rashed K, Said A, et al. Antiproliferative and antioxidant
properties of Alhagi maurorum Boiss (Leguminosae) aerial parts. Indust
Crops Prod. 2014;53:289–95.
18. Marashdah M, Al-Hazimi H. Pharmacological activity of ethanolic extract
of Alhagi maurorum roots. Arabian J Chem. 2010;3:39–42.
19. Marashdah M, Farraj A. Pharmacological activity of 2% aqueous acetic acid
extract of Alhagi maurorum roots. J Saudi Chem Soc. 2010;14:247–50.
20. Mirdeilami SZ, Barani H, Mazandarani M, Heshmati GA. Ethnopharma-
cological survey of medicinal plants in Maraveh Tappe region, North of
Iran. Iran J Plant Physiol. 2011;2:327–38.
21. Neamah NF. A pharmacological evaluation of aqueous extract of Alhagi
maurorum. Glob J Pharmacol. 2012;6:41–6.
22. Shaker E, Mahmoud H, Mnaa S. Anti-inflammatory and antiulcer activity of
the extract from Alhagi maurorum (camelthorn). Food Chem Toxicol.
2010;48:2785–90.
23. Sheweita SA, Mashaly S, Newairy AA, Abdou HM, Eweda SM. Changes in
oxidative stress and antioxidant enzyme activities in streptozotocin-induced
diabetes mellitus in rats: role of Alhagi maurorum extracts. Oxid Med Cell
Longev. 2016;2016:5264064.
Alkanna tinctoria (L.) Tausch
(Boraginaceae)

(Syns.: A. tuberculata (Forsskål) Meikle; Anchusa tinctoria L.)

Abstract
The plant is native to the Mediterranean region, and the dark red root of the plant,
blackish in appearance externally but blue-red inside with a whitish core, provides
the fine red coloring material that has been used as a dye in the Mediterranean
region since antiquity. The plant was known to Greeks and Romans for the dye as it
is mentioned by Theophratus, Dioscorides and Pliny. Unani physicians in India
describe roots as astringent, emollient, emmenagogue and lithotriptic. Externally it
is used in ointments for the treatment of weeping ulcers; grounded in vinegar it is
applied to vitiligo and leucoderma. Application of the burnt root mixed with oil to
alopecia is claimed to cure it within two weeks. Naphthoquinones, alkannin,
acetylalkannin, angelylalkannin, 5-methoxyangenylalkannin, dimethylacryl alkan-
nin, arnebifuranone, alkandiol, and alkanfuranol have been isolated from the roots.
Alkannin has been identified to be the coloring agent in the root, and one of the
wound healing agents along with shikonin. Aqueous, chloroform, ethanol and
hexane leaf extracts have shown significant growth inhibitory activity against MDR
S. aureus, and the aqueous extract being most active against A. baumannii,
P. aeruginosa, and S. aureus, compared to imipenem. Dressing of wounds of skin
graft donors with a root powder-based ointment (20%) significantly improved
healing and closure of wound.

Keywords




Alkanna Alkanet Arganetta Dyers’ buglos
Färberalkanna
Harjuya




Onoquiles Orcanette Ratanjot Shinjār

Vernaculars: Urd.: Ratanjot; Hin.: Ratanjot; San.: Ratanjot; Ara.: Hawa` jwānī,
Shinjār; Chi.: 朱草根; Dut.: Alkanna; Eng.: Alkanet or Dyers’ buglos, Orchanet,
Puccoon, Languedoc bugloss or Spanish bugloss; Fre.: Alkanna, Orcanette; Ger.:

© Springer Nature Switzerland AG 2020 135

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_15
136 Alkanna tinctoria (L.) Tausch

Alkanne, Färberalkanna, Färberochsenzunge, Schminkwurz; Ita.: Alcanna spuria,

Arganetta; Per.: Harjuya; Spa.: Onoquiles, Orcaneta roja, Palomilla de tintes; Tur.:
Havaciva out, Sığırdili.
Description: The plant is native to the Mediterranean region, and the dark red root
of the plant, blackish in appearance externally but blue-red inside with a whitish
core, provides the fine red coloring material that has been used as a dye in the
Mediterranean region since antiquity. The plant has elongated hairy leaves and
bell-shaped bright blue flowers. In India, the dye is called Ratanjot and is tradi-
tionally used to impart red color to certain curry dishes, such as Roghanjosh
(Fig. 1).
Actions and Uses: The plant was known to Greeks and Romans for the dye
derived from it as it is mentioned by Theophratus, Dioscorides and Pliny; Avicenna
called it anjusa [2]. It is used in Greek folk medicine for its wound healing and
anti-inflammatory activities [4]. Its roots yield a water-insoluble red dye that is
used to color fat, oil, perfume, wood, marble, and pharmaceutical products. In
Unani medicine, roots (temperament, hot 2° and dry 2°) are described as astringent,
emollient, emmenagogue and lithotriptic. Externally it is used in ointments for
treatment of weeping ulcers; grounded in vinegar it is applied to vitiligo and leu-
coderma and is also employed for alopecia. Internally used, though less frequently,
for jaundice, gout, renal colic, renal stones, amenorrhea, and chronic fevers.LXXVII
Ghani [3] says that the root burnt and mixed with oil is applied to alopecia, which it
cures within two weeks; and the same dropped into the nose during epileptic attack
would relieve it.

Fig. 1 Alkanna tinctoria, Flowers, prise à Torreilles, WikimeidaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Alkanna_tinctoria2.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Alkanna tinctoria (L.) Tausch 137

Phytoconstituents: Eight naphthoquinones, alkannin, acetylalkannin, angely-

lalkannin, 5-methoxyangenylalkannin, dimethylacryl alkannin, arnebifuranone,
alkanfuranol, and alkandiol were isolated from the roots [12, 13]. Alkannin/shikonin
were identified as the wound healing agents [6]; their contents in the hexane extract of
Alkanna roots varied in wildly growing samples collected from various Greek regions
[11]. The coloring agent in the root has been identified to be alkannin. Naph-
thaquinones from the root are reported to possess antimicrobial activity [8]. The
predominating fatty acids in the root lipids are stearic, palmitic, oleic, linoleic and
c-linolenic acids [7].
Pharmacology: Alkannin and angelylalkannin exihibit antiproliferative activity
against human colon cancer cells HCT-116 and SW-480, by arresting the cell cycle
in G1 phase and causing apoptosis; whereas 5-methoxyangenylalkannin arrest cell
cycle in the S and G2/M phases [12, 13]. Aqueous, chloroform, ethanol and hexane
leaf extracts showed significant growth inhibitory activity against MDR S. aureus,
and the aqueous extract was most active against A. baumannii, P. aeruginosa, and
S. aureus, compared to imipenem [2], whereas methanol extract of aerial parts
showed highly significant antioxidant activity and antimicrobial activity against 9
out of 32 microorganisms tested [10]. Significant antioxidant and anti-inflammatory
activities have been reported of the root extracts and its main constituents,
hydroxynaphthaquinones [1, 4]. A 16% solution in olive oil, topically applied twice
daily by gently rubbing against the burn area, completely healed the partial
thickness and olive oil burn wounds in rabbits, with well formed dermal-epidermal
junctions; though, not benefitting severely burned wounds [5].
Clinical Studies: Dressing of wounds of skin graft donors with a root powder-based
ointment (20%) significantly improved healing and closure of wound [3]. The root
alkannin esteric pigments, b-dimethylacrylic acid, b-acetoxy-isovaleric acid, isova-
leric acid, and angelic acid were also reported to show excellent wound healing in a
clinical study on 72 patients with leg ulcers [9].
Human A/Es, Allergy and Toxicity: It causes headaches.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: The root powder-based ointments have shown significant wound-
healing effects, that could be further explored.
138 Alkanna tinctoria (L.) Tausch

References
1. Assimopoulou AN, Papageorgiou VP. Radical scavenging activity of
Alkanna tinctoria root extracts and their main constituents, hydroxynaph-
thoquinones. Phytother Res. 2005;19:141–7.
2. Khan UA, Rahman H, Qasim M, et al. Alkanna tinctoria leaves extracts: a
prospective remedy against multidrug resistant human pathogenic bacteria.
BMC Complement Altern Med. 2015;15:127.
3. Kheiri A, Amini S, Javidan AN, Saghafi MM, Khorasani G. The effects of
Alkanna tinctoria Tausch on split-thickness skin graft donor site manage-
ment: a randomized, blinded placebo-controlled trial. BMC Complement
Altern Med. 2017;17:253.
4. Kourounakis AP, Assimopoulou AN, Papageorgiou VP, et al. Alkannin and
shikonin: effect on free radical processes and on inflammation—a prelim-
inary pharmacochemical investigation. Arch Pharm (Weinheim). 2002;335:
262–6.
5. Ogurtan Z, Hatipoglu F, Ceylan C. The effect of Alkanna tinctoria Tausch on
burn wound healing in rabbits. Dtsch Tierarztl Wochenschr. 2002;109:481–5.
6. Papageorgiou VP, Assimopoulou AN, Ballis AC. Alkannins and shikonins:
a new class of wound healing agents. Curr Med Chem. 2008;15:3248–67.
7. Papageorgiou VP, Assimopoulou AN. Lipids of the hexane extract from the
roots of medicinal boraginaceous species. Phytochem Anal. 2003;14:251–8.
8. Papageorgiou VP, Winkler A, Sagredos AN, Digenis GA. Studies on the
relationship of structure to antimicrobial properties of naphthaquinones and
other constituents of Alkanna tinctoria. Planta Med. 1979;35:56–60.
9. Papageorgiou VP. Wound healing properties of naphthaquinone pigments
from Alkanna tinctoria. Experientia. 1978;34:1499–501.
10. Sengul M, Yildiz H, Gungor N, et al. Total phenolic content, antioxidant
and antimicrobial activities of some medicinal plants. Pak J Pharm Sci.
2009;22:102–6.
11. Tappeiner J, Vasiliou A, Ganzera M, et al. Quantitative determination of
alkannins and shikonins in endemic Mediterranean Alkanna species. Biomed
Chromatogr. 2014;28:923–33.
12. Tung NH, Du GJ, Wang CZ, et al. Naphthoquinone components from
Alkanna tinctoria (L.) Tausch show significant antiproliferative effects on
human colorectal cancer cells. Phytother Res. 2013;27:66–70.
13. Tung NH, Du GJ, Yuan CS, et al. Isolation and chemopreventive evaluation of
novel naphthoquinone compounds from Alkanna tinctoria. Anticancer Drugs.
2013;24:1058–68.
Allium cepa L.
(Amaryllidaceae)

Abstract
This common vegetable is used in cooking throughout the world. Galen said that its
application on ringworm of the scalp causes hair to grow and its use with sesame oil
followed by exposure to sunlight is beneficial for albunism. Use of onion juice in eyes
for cataract due to thick humours is beneficial. Dioscorides described onion as
irritant, gas-forming, appetizer, polydipsic, emetic, laxative, and emmenagogue, and
used it for dimness of vision, ringworm, piles, tinnitus and ear infections with pus
discharge. It has also been mentioned by many to thin the thick humours and acts as
antobstruent. Its use with vinegar has been recommended by various authors to
decrease its intensity and make it useful for stomach, to increase appetite, prevent
nausea due to bile and phlegm, and relieve bronchial irritation. On Hawaiian Islands,
onions are used in compound remedies to treat tuberculosis, cold and venereal
diseases. In the Philippines, onion bulbs cooked and mixed with coconut oil are
applied as ointment to the abdomen to provoke diuresis. Onion use positively affects
risk factors in normal subjects and in patients with atherosclerotic disease.
Epidemiological studies have also suggested inverse relationships between frequency
of onion intake and various cancers. Analysis of the National Health and Nutrition
Examination Survey 2003–2004 showed that onion consumption has beneficial
effect on bone density in perimenopausal and postmenopausal non-Hispanic white
women 50 years and older. Flavonols are the predominant pigments of onions. Onion
bulbs are among the richest sources of dietary flavonoids and contribute to the overall
dietary intake of flavonoids. Red onions contain the highest amount of flavonols per
Kg of fresh weight, whereas white onions contain the least amount of flavonols.
Sulphur-containing compounds in onion are responsible for enhancement of blood
fibrinolysis, without depressing fibrinogen content in humans.

Keywords


Aschlauch Basal Kanda

Onion
Oignon
Piyaz
Platandu
Sjalotten



Skalotteløg Yáng cōng

© Springer Nature Switzerland AG 2020 139

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_16
140 Allium cepa L.

Vernaculars: Urd.: Piyaz; Hin.: Duk, Kanda, Piyaz; San.: Durgandha, Platandu;
Ben.: Gundhun, Palandu, Piyaj, Piyang, Pulantic, Pulantu; Mal.: Bawang, Cheriya
ulli, Chuvanna ulli, Eerulli, Ira-venyayam; Mar.: Kanda, Kande; Tam.:
Ira-vengayam, Irulli, Ulli, Ullegaddi, Vengayam; Tel.: Neermulli, Nirulli, Vulli-
gaddalu, Yerragadda, Yerra-vulli, Vellulli; Ara.: Basal; Chi.: 火葱, Cong tou, Huo
cong, Tsung, Yáng cōng, Yuan cong; Cze.: Šalotka; Dan.: Skalotteløg; Dut.:
Sjalotten, Ui; Eng.: Onion; Fin.: Šalottisipuli, Shalottisipuli; Fre.: Ail oignon,
Ciboule, Echalote, Oignon, Oignon des jardins, Oignon patate; Ger.: Aschlauch,
Bolle, Gewöhnliche, Hauszwiebel, Kartoffelzwiebel, Klöben, Küchenzwiebel,
Sommerzwiebel, Zwiebel; Gre.: Askalonio; Haw.: Akaakai, Kikania; Ita.: Cipolla,
Cipollina, Scalogna, Scalogno; Jap.: Sharotto, Tamanegi, Wakegi; Kor.: Eonieon,
Onieon, Yangpa; Maly.: Brambang (Java); Nep.: Chyaapii; Nor.: Sjalott-løk; Per.:
Goondina, Mousir, Piazcheh; Por.: Cebola miúda, Cebolha roxa, Cebolinha branca;
Rus.: Shalot; Spa.: Ascalonia, Cebolla, Chalota, Escalma, Escalona; Tag.: Sibuyas;
Tha.: Dton hom bua; Tur.: Soğan; Vie.: Hành, Hành tăm, Hành tím.
Description: Onion is a common vegetable used in cooking throughout the world.
Bulbs may vary in size from a walnut to a large orange; color varies according to
the variety, white, yellow and red. Its taste is very acrid and pungent; on cutting the
oil volatilizes causing irritation of eyes and tearing (Figs. 1 and 2).
Actions and Uses: The Ebers papyrus mentions a remedy for diarrhea: “Spring
onions…oil, honey, wax, and water; boil together and drink for four days.” Ibn
al-BaitarLXIX quoted various Greco-Arab physicians for the medical uses of onion,
such as: Galen says that its application on balkhora (ringworm of the scalp)
causes hair to grow and its use with sesame oil followed by exposure to sunlight is
beneficial for albunism. Onion juice is very strong, and its use in eyes for cataract
due to thick humours is beneficial. Dioscorides described onion as irritant,

Fig. 1 Allium cepa, Yellow and Red Onions, Prof. Akbar, Original
Allium cepa L. 141

Fig. 2 Allium cepa, White Onions, Prof. Akbar, Original

gas-forming, appetizer, polydipsic, emetic, laxative, emmenagogue, and to be used

for dimness of vision, ringworm, piles, tinnitus and ear infections with pus dis-
charge. Ibn-e-Masawaiyh says that boiled onion is aphrodisiac; its excess use
produces abnormal humors in the stomach. Avicenna described it in Canon of
Medicine as pyretic, emmenagogue, antiepileptic, emetic, antidiabetic, expectorant/
bronchodilator, antiobstructive and irritant. He also mentioned it as beneficial for
jaundice and as a preventive to the spread of poison in the body. It is also men-
tioned by many others to thin the thick humours and acts as antobstruent. Its use
with vinegar has been recommended by various authors to decrease its intensity and
make it useful for stomach, to increase appetite, prevent nausea due to bile and
phlegm, and relieve bronchial irritation. It is also used for hemorrhoids and anal
prolapse. The seeds are used as a traditional herbal medicine to treat diarrhea and
promote blood flow by the Uygur Muslim community in China [98]. Onions are an
essential component of Mediterranean diet [85]. In Unani medicine (onion tem-
perament, hot 3° and dry 1°; some authors mention it hot 4° and dry 4°; seeds are
hot 2° and dry 2°), it is deobstruent, appetizer, digestive, diuretic, aphrodisiac,
emmenagogue, laxative, carminative, lithotriptic, and relieves bilious nausea.L,
LXXVII
NadkarniCV recommended it as useful in fever, dropsy, catarrh and chronic
bronchitis; the oil as stimulant, diuretic and expectorant; the juice mixed with
honey, ginger-juice and ghee as aphrodisiac, stimulant and expectorant. Onion bulb
is emmenagogue, externally stimulant and rubefacient, and after roasting, it acts as
a demulcent, both externally and internally. Using its juice as ear drops improves
hearing and relieves ringing in the ear. Roasted or otherwise onions are applied as a
poultice to indolent boils, bruises, wounds, etc., and applied to naval in dysentery
and body heat. Onions are eaten to mitigate cough in phthisis; mixed with vinegar
are used for sore throat, jaundice, spleen enlargement and dyspepsia. Its juice is
used like smelling salts in faintness of infantile convulsions, headache, epileptic and
hysterical fits. It is inhaled in epistaxis, dropped warm into the ear to relieve earache
142 Allium cepa L.

and applied to the eyes in dimness of vision.XXI Juice is a good application for
rheumatic pains and other inflammatory swellings when applied mixed with equal
proportions of mustard oil. A decoction of onions is very useful in cases of strangury
and extreme heaty sensations.CV In Ayurveda, the bulbs are used in jirnajawara,
krmiroga, gulma, kustha, arśa, kãsa, śwãsa, pinasa, śūla, karnaśūla, vãtavyãdhi,
hikkã, medoroga, yonivyãpata, visucikã, plihãvrddhi, ksaya, visamajawara, apas-
mãra, unmãda, śosa, śopha, hrdroga, vātśūla, trikaśūla and vranakrmi.LIX Khory
and KatrakLXXXI mention seeds to be demulcent and used in gonorrhea. In Mexico,
the onion bulb is considered diuretic and vermifuge.XCVI According to Sanyal and
Ghose,CXXII onion bulbs increase intestinal peristalsis and are thus prescribed for
obstruction. In the Philippines, QuisumbingCXVII quotes Guerrero [59], that onion
bulbs cooked and mixed with coconut oil are applied as ointment to the abdomen to
provoke diuresis. The bulb and juice are reported emmenagogue and have shown
uterine stimulant activity [123]. In Guyana, onion boiled with bread and milk are
applied to swellings of Guinea worm, and the patient drinks a decoction of garlic,
black pepper, flowers of sulfur and a quart of rum thrice daily.XXXIV
Onion use positively affects risk factors in normal subjects and in patients with
atherosclerotic disease [88]. Epidemiological studies have suggested inverse rela-
tionships between frequency of onion intake and various cancers, such as stomach
cancer [129, 164], localized prostate cancer in men [33, 68], squamous cell carci-
noma of lung [96], and breast cancer in women [30], and intake of quercetin is
inversely related to cardiovascular diseases [80, 94]. In areas of China where
stomach cancer is more prevalent, individuals consuming more allium vegetables
have only 40% risk of gastric cancer compared to those not using these vegetables
[163]. A hospital-based, multicenter, case-control study in Poland involving 741
stomach-cancer cases (520 males and 221 females), and the same number of
controls showed a strong decrease in risk associated with consumption of radishes
and onions [20]. According to Hertog et al. [65] only a high intake of flavonoids
from vegetables and fruits is inversely associated with risk of cancer of the ali-
mentary and respiratory tracts in the elderly. However, an epidemiological study in
Japan involving 93 cases of stomach cancer, 93 cases with colorectal cancer, and
186 controls, revealed that relatively frequent intakes (4 times/week) of some
vegetables, including onions, showed high relative risks for both stomach and colon
cancers which is contrary to the findings of earlier epidemiological studies [144].
Dorant et al. [37] also found no association between the consumption of onions or
leeks, or garlic supplement use and the incidence of female breast carcinoma in
Netherlands Cohort Study that followed 120,852 Dutch men and women, aged 55–
69 years, for 3.3 years. However, the Netherlands Cohort Study provided evidence
for a strong inverse association between onion consumption and stomach carcinoma
incidence [35], but did not support an inverse association between the consumption
of onions and the incidence of male and female colon and rectum carcinoma [36].
An onion-enriched diet could also counteract ovariectomy-induced bone loss and
deterioration of biomechanical properties [69]. Analysis of the U.S. National Health
and Nutrition Examination Survey 2003–2004 showed that onion consumption has
beneficial effect on bone density in perimenopausal and postmenopausal
Allium cepa L. 143

non-Hispanic white women 50 years and older. Also, older women who consume
onions most frequently may decrease their risk of hip fracture by more than 20%
versus those who never consume onions [105]. On Hawaiian Islands, onions are
used in compound remedies to treat tuberculosis, cold and venereal diseases.LXXVI
Onions, however, could be a potent and long-lasting refluxogenic agent in heart-
burn patients [4].
Some authors have reported interesting effects of onion use. Levick et al. [97]
reported about a family “counter-ritual” practiced in Iran. A case of a family of a
schizophrenic patient is described in which onion peeling is done to induce tearing.
The intervention addressed the family’s inappropriate laughter and denial of sad-
ness, and seemed to lead to therapeutic gain for the patient and the family.
Phytoconstituents: Onion bulbs are among the richest sources of dietary flavo-
noids and contribute to the overall dietary intake of flavonoids [66]. Most important
sources of flavonoids are tea (48% of total intake), onions (29%), and apples (7%).
Yellow onions contain 270–1,187 mg of flavonols (flavonoids) per Kg of fresh
weight (FW), whereas red onions contain 415–1,917 mg of flavonols per Kg of
FW. Flavonols are the predominant pigments of onions [136]; peel is also rich in
flavonol contents which are 103 ± 7.90 µg/g dry weight (red variety) and
17.3 ± 0.69 µg/g dry weight (white variety) [16]. Western yellow onion variety
exhibits the highest total flavonoid content, and the Western white variety with the
lowest flavonoid content; total phenolic and flavonoid contents are strongly cor-
related with total antioxidant activity [162]. Red onions contain significant amount
of quercetin, the polyphenolic flavonoid credited for its 5-LOX inhibitory activity
[120]. However, Yamada et al. [159] found no correlation between quercetin content
and antithrombotic activity of onion, and suggested that onion can be classified
into varieties with or without antithrombotic and thrombolytic effects. Sulphur-
containing compounds in onion are responsible to enhance blood fibrinolysis,
without depressing fibrinogen content in human volunteers; one sulphur-containing
but nearly odorless compound possesses indirect fibrinolytic potentials [9].
Organosulfur compounds in onion extracts are formed following the lysis of the
S-alk(en)yl-L-cysteine sulfoxides by alliinase [118]. Prostaglandins A2, B1, E1 and
F1 have also been identified in green onions [5]. Three saponins named ceposide A,
ceposide B, and ceposide C with antifungal activity, were isolated from white onions
[93]. Thiosulfinates were identified as the active antiallergic and antiasthmatic
compounds in onion [154]. Essential oil contains mainly allyl-propyl disulphide and
diallyl disulphide. Ethanol extract of the seeds of red onion caused more than 80%
inhibition of protein tyrosine phosphatase 1B (PTP1B) enzyme, but none of the eight
furostanol saponins isolated from it inhibited PTP1B enzyme [98].
Pharmacology: Incorporation of 5% onion to the diet of rats ameliorated their
butter-fat- or beef fat-induced increase in serum and tissue lipids, LPO and enzymes
activities [8]. Blanching of onions for 90 seconds fully preserves the bioactive
compounds and antioxidant potentials, and prevents the rise in plasma lipid levels
and the decrease in plasma antioxidant activity of cholesterol-fed rats [58]. Essential
oil of onion was more effective than clofibrate in preventing rise in serum TC and
144 Allium cepa L.

blood coagulability, following 3-months of cholesterol feeding to rabbits. The oil

(equivalent to 1 g/kg/day of raw bulb) increased fibrinolytic activity even above the
normal control levels, and normalized the lipid content of aorta [21]. EO decreased
serum TC and TGs levels, enhanced fibrinolytic activity, and prevented increase in
beta/alpha lipoproteins ratio, and reduced aortic atheroma formation by half in
hypercholesterolemic rabbits [23, 124]. Aqueous extract also significantly reduced
serum, liver and aorta TGs, and serum and liver proteins in sucrose-fed rabbits [128,
150]. Lata et al. [95] also reported significant preventive effect of petroleum ether
extract on serum TC and TGs levels, and atherosclerosis caused by atherogenic diet
to albino rats. Fresh whole onion extract to rabbits for six-months along with
cholesterol (0.5%) significantly lowered total lipids, cholesterol and phospholipids
levels in the eye [153], and prevented change in shape of erythrocytes, and their
increased tendency to aggregate [1, 151]. Kendler [88] suggested that use of certain
formulations of garlic and/or onion has favorable effects on risk factors both in
normal subjects and in patients with atherosclerotic disease.
Onion extract possesses inhibitory activity on platelet aggregation [100, 102,
158]. Nagda et al. [114] reported in vitro anticoagulant and fibrinolytic activity of
the aqueous extract. Aqueous and oily extracts reduced formation of TX and LPO
products in platelets from exogenous AA, but did not inhibit incorporation of
AA into platelet phospholipids [138, 140, 141]. The least polar fraction of oily
chloroform extract exhibited most inhibitory activity on ADP or AA-induced pla-
telet aggregation; almost completely suppressed TXB2 synthesis [103]. Aqueous
extract significantly inhibited collagen-, thrombin-, AA-induced aggregations, and
collagen-induced TXA2 formation in rat and human platelets [111], and onion
treatment for 4-weeks significantly inhibited collagen- or AA-induced TXB2 for-
mation and platelet aggregation, more in platelets of diabetic than normal rats [83].
Single i.v. infusion of aqueous extract did not elicit any inhibitory effect on TXB2
synthesis in the serum of rabbit [147]; however, i.v. injection of onion juice and
intragastric administration of onion homogenate in dogs with damaged and ste-
nosed coronary arteries, abolished flow reduction due to platelet thrombus forma-
tion and embolization [27]. Treatment of rats with high dose of aqueous extract
lowered serum levels of TXB2, but boiled onion extract had very little effect on
TXB2 synthesis [3, 24]; steaming of onion also abolished the antiplatelet activity
[62]. Extensively cooked onions may stimulate, rather than inhibit platelet aggre-
gation [29]. Fresh whole onion extract administration to cholesterol-fed animals
prevents increases in activities of alkaline phosphatase, acid phosphatase, amino
transferases and LDH [152]. Adenosine, allicin and paraffinic polysulfides were
identified as the main antiplatelet constituents; however, antiplatelet effects of onion
ingestion in vivo are suggested to be due mainly to adenosine, than to allicin and
paraffinic polysulphide constituents [101]. Onions with mild flavor and low sulfur
content exhibit significantly lower antiplatelet activity than those containing high
levels of sulfur-containing compounds [56]. Raw onion also lowers BP in
L-NAME-induced hypertension and in SHR, but the activity is lost after boiling the
onion [87]. Antioxidative activity of onion increases NO level due to higher NOS
Allium cepa L. 145

activity, lowering BP in SHR [125]. Hydroethanol peel extract also lowered BP in

fructose-induced hypertension in rats without affecting HR [115].
Organosulfur compounds, including S-methylcysteine and flavonoids, such as
quercetin are also responsible for the hypoglycemic activity of onions. S-methylcysteine
and flavonoids decrease levels of blood glucose, serum lipids, oxidative stress, and LPO,
and increase activities of antioxidant enzymes, and insulin secretion [2]. Brahmachari
and Augusti [25, 26] observed a favorable effect of onion on alloxan diabetic animals but
no effect in pancreatized animals; Mathew and Augusti [106] reported a hypoglycemic
fraction that lowered FBG and improved glucose tolerance of diabetic rabbits.
Diphenylamine was identified as the antihyperglycemic constituent, whose concen-
tration is highest in mature onion bulbs, and cooking decreases its contents [86]. Onion
solution (0.4 g A. cepa/rat) increased fasting serum HDL-C levels and alleviated
hyperglycemia in STZ-diabetic rats [28]. Onion powder supplemented diet to diabetic
rats decreased blood glucose levels, the total serum lipid, TGs, and atherogenic index,
and increased HDL-C/TC ratio [13]. Both ethanol onion peel extract and quercetin
significantly and equally reduce blood glucose spike after sucrose loading in rats [91,
122], and significantly improve glucose tolerance, and increase expression of insulin
receptor and GLUT4 in muscle tissues of diabetic rats [82]. Quercetin-rich onion peel
extract downregulates the PPARc mRNA levels in high-fat fed rats [112]. Several other
studies reported no significant effect of onions on blood glucose of diabetic animals [81],
and unlike positive effect reported by Babu and Srivastava [11], showed worsening
effect on both blood glucose and lipids in high fat-diet and diabetic rats [78].
Crude ethanol extract pretreatment of guinea pigs, sensitized to ovalbumin,
markedly reduced the asthmatic response to ovalbumin inhalation challenge [44].
Dorsch et al. [38] found both chloroform and ethanol extracts protective against
ovalbumin challenge to sensitized guinea pigs. Benzyl isothiocyanate was suggested
to be responsible for the antiasthmatic effects. Later, Dorsch et al. [39] reported
onion oils as counteracting PAF inhalation caused bronchial obstruction and iden-
tified thiosulfinates and capaenes as the active antiasthmatic compounds [40, 42, 43,
155], that also inhibit 5-LOX and COX in vitro [154]. Anti-inflammtory properties
of onion extracts are suggested to be due, in part, to the inhibition of inflammatory
cell influx by thiosulfinates and capaenes [41].
Crude onion juice, aqueous extract and volatile contents showed positive activity
against Gram-positive bacteria and yeast, but no effect on Gram-negative bacteria
[34, 48]. Onion extracts were bactericidal to S. mutans and S. sobrinus, the causal
bacteria for dental caries, and P. gingivalis and P. intermedia that cause adult
periodontitis; however, the activity was lost after boiling the onion [90]. Aqueous
extract is also active against M. furfur (25 strains), C. albicans (18 strains), other
Candida sp. (12 strains) and 35 strains of various dermatophyte species [130], and
five strains of Leishmania [127]. S. aureus was the most susceptible Gram-positive
bacteria and P. aeurginosa and S. typhi were the most resistant Gram-negative
bacteria to various extracts of dried onion bulb [12]. Onion extract also inhibits
production of aflatoxin (60%) by A. flavus [19]. Quercetin inhibits in vitro growth
of periodontal bacteria A. actinomycetemcomitans and P. gingivalis [53, 54], while
the EO inhibits growth of T. rubrum, T. erinacei, and T. soudanense, and exhibits
146 Allium cepa L.

significant synergistic antifungal activity when combined with ketoconazole [121].

Fresh juice significantly prevented and treated harmful effects on kidneys of Tox-
oplasma gondii-infected rats [55], and decreased levels of IgG, IgM, IL-2, IL-6,
TNF-a and CAT enzyme, and increased GPx and SOD of S. mansoni-infected mice
[104].
Suplementation of rats’ diet with onion oil for 21-days increased resistance to
nicotine-induced LPO, equivalent to a-tocopherol [63, 64], and also reduced
exercise-induced oxidative stress in rats, without altering the plasma cholesterol
profile [31]. Both hydroalcohol and aqueous extracts of fresh onion bulbs show
antioxidant properties, significantly influenced by their chemical composition [145].
Park et al. [119] reported antioxidant activity correlated to total polyphenols and
quercetin, as they were greatest in onion peel ethanol extract, followed by onion peel
powder, onion flesh ethanol extract, and onion flesh powder. Myricetin was iden-
tified as the most bio-accessible flavonoid in both red and yellow onions, and the
antioxidant activity stronger in the outer layer than in the inner layer [132]. Fer-
mented aqueous extract, that lacks flavonoids, shows most antibacterial, antigeno-
toxic, and antiproliferative activities [109]. Fermentation raises quercetin content,
and consequently increases antioxidative and neuroprotective activities [161].
Onion oil, applied three times per week, inhibited the yield and incidence of
phorbol-myristate-acetate promoted skin tumors [15], and organosulfur compounds,
allyl methyl trisulfide, allyl methyl disulfide, diallyl trisulfide and diallyl sulfide,
inhibited BP-induced forestomach tumors in mice, and induced GST activity in the
forestomach [137]. Topical application of diallyl sulfide and diallyl disulfide also
significantly inhibited DMBA-induced and TPA-promoted skin papilloma from the
9th week of promotion and significantly increased the survival of mice [45]. Diallyl
disulfide was the most potent in reducing, by more than 90%, NDEA-induced
forestomach tumor in female mice when the test compounds were administered
orally 96 and 48 h prior to NDEA. Pulmonary adenoma formation was also
inhibited but to a considerably lesser extent [157]. Red onion peel methanol extract
was also protective against atypical prostatic hyperplasia in rats, due potentially to
anti-inflammatory and immunomodulatory effects [47].
Supplementation with hydroethanol onion extract significantly improved muscle
coordination and memory deficits, reduced oxidative stress, brain AChE level, and
decreased abnormal aluminium deposition in brains of aluminium exposed mice for
60-days [135], and showed highly ameliorative effect on memory impairment in
senescence-accelerated mice [116]. Hwang et al. [72] reported neuroprotective
effects of repeated treatment with onion extract and its major component, quercetin
for 15-days before ischemic damage in the pyramidal neurons of gerbil hip-
pocampus; and prevented brain edema, BBB hyperpermeability, and tight junction
proteins disruption in MCA occlusion-induced ischemia in mice [74]. Methanol
extract of the outer scales also significantly improved hyperalgesia due to diabetic
neuropathy [17], and markedly reduced cerebral infarct size and attenuated
impairment in short-term memory and motor coordination of bilateral cerebral
Allium cepa L. 147

arteries-occluded ischemic mice [133]. Pretreatment of rats with onion powder

exhibited antidepressant-like activity, independent of the hypothalamic-pituitary-
adrenal axis [126].
Fresh onion juice administered to rats for 20 consecutive days significantly
increased serum total testosterone and LH levels, without affecting FSH, and sig-
nificantly increased sperm viability and motility [89]. Pretreatment of rats with
aqueous extract protected against Cd-induced [77, 117], and aluminum chloride-
induced [76] testicular oxidative damage and spermiotoxicity. Onion extract was
also protective against Cd-induced nephrotoxicity [142], and dyslipidemia and
oxidative stress [75], doxorubicin- and Cd-cardiotoxicity [6, 7], and fresh onion
juice protected against doxorubicin-hepatotoxicity in rats [108], via reduction in
LPO and enhanced antioxidant defense. Aqueous extract shows immune boosting
capabilities in rats [110]. Onions reduce serum uric acid levels in hyperuricemic
rats, with no significant effects in normal animals, and significantly inhibit XDH
and XO enzymes activities. Hypouricemic effect in experimental animals, though,
does not parallel changes in XDH and XO activities, implying other mechanisms
may be involved in the hypouricemic effect [60, 61].
Clinical studies: Italian and Swiss case-control studies suggested that consumption
of allium vegetables, especially onion and garlic, was inversely related to incidence
of cancer of the oral cavity and pharynx, esophageal, colorectal, laryngeal, breast,
ovarian, prostate and renal cell cancer [49]. However, a prospective cohort study of
more than 3 years duration, involving 120,852 men and women in The Netherlands,
found no significant relationship between the consumption of onion and the risk of
colorectal carcinoma [36]. In a European Prospective Investigation into Cancer and
Nutrition study of 299,649 women for 9-years, a statistically nonsignificant inverse
relationship was found for leafy vegetables, root vegetables, garlic and onions for
invasive squamous cervical cancer [57]. However, a multicenter case-control study
of 1,369 patients with BPH and 1,451 controls, admitted to the same hospitals in
Italy between 1991 and 2002, showed an inverse association between allium (onion
and garlic) vegetable consumption and BPH [50].
In humans, the total average intake of quercetin and kaempferol is estimated at
20 mg/day and consumption of quercetin from onions was inversely correlated with
lung cancer risk [71]. Quercetin levels peaked 2 h after ingestion of fried onions by
healthy volunteers, with an increase in plsma total antioxidant activity, but no sig-
nificant change in susceptibility to oxidation of isolated LDL [107]. However,
another study with quercetin in diet of healthy volunteers did not show any substantial
effect on oxidative DNA damage in leucocytes [14]. In a randomized crossover study
with each treatment period lasting 2-weeks, 18 healthy volunteers fed 220 g
onions/day providing 114 mg quercetin/day, or a placebo for 7-days each, raised
mean plasma quercetin concentrations but no significant effect on platelet aggrega-
tion, TXB2 production, factor VII, or other hemostatic variables [80]. In Danish
volunteer women, after eating 70 g raw onion/day for seven days, a wide variation in
TXB2 levels as compared to their pretreatment values was observed [139].
148 Allium cepa L.

Random administration of freshly extracted juice of 50 g onion or an equivalent

amount of ether-extracted essential oil to 10 healthy subjects produced a significant
equally effective protective action against fat-induced increases in serum cholesterol,
plasma fibrinogen and blood coagulability and decrease in fibrinolytic activity [22].
In an RCT double-blind, crossover phase-I study, an onion-olive-oil maceration
capsule administered to apparently healthy subjects caused a decrease in arterial BP,
a significant reduction in plasma viscosity and haematocrit, and reduced platelets
aggregation; the effects were stronger in subjects with reduced blood fluidity com-
pared to those with normal rheological parameters [85]. Quercetin supplementation
also reduced BP in hypertensive subjects, with no quercetin-evoked reduction in
systemic markers of oxidative stress [46]. Ingestion of quercetin or onion soup with
high contents of quercetin reduces ex vivo platelet aggregation [70].
Four hours after ingestion of 100 g crude red onion by type 1 diabetic patients,
FBG levels were lowered by 89 mg/dl compared to 145 mg/dl by insulin, and a
reduction of 40 mg/dl in FBG compared to 81 mg/dl by glibenclamide in type 2
diabetic patients [143]. In a crossover, comparative study on 20 diabetic outpatients
in Indonesia, half of the patients were assigned to a special diet plus 3  20 g fresh
onion per day for one week and the special diet only in the second week; the order
was reversed for the other half patients. There was a significant decrease in blood
sugar level in onion treated group [148]. Onion EO significantly lowered blood
glucose levels and increased insulin levels in six healthy volunteers [10], and juice
expressed residue of onion fed to diabetic patients with food effectively controlled
the hyperglycemia [106].
Application of crude onion juice to alopecia areata, a patchy, non-scarring hair
loss condition, in 48 patients significantly increased hair regrowth after six weeks in
20 patients (86.9%) and was significantly higher among male (93.7%) than female
patients (71.4%) [131]. Clinical studies on onion extract based topical gel for
improving postsurgical scars showed the gel did not improve scar cosmesis or
symptomatology when compared with a petrolatum-based ointment [32, 79].
However, the Contractubex®, an onion extract based proprietary gel was signifi-
cantly effective in scar prevention in Chinese patients having laser removal of
tattoos than the control group [67]. Also, intralesional injection of triamcinolone
acetonide (TAC) with onion extract in keloidal and hypertrophic scars was more
effective than TAC alone in reducing pain-sensitivity, itching and elevation, but not
in erythema and induration [92].
Mechanism of Action: The exact mechanisms of the cancer-preventive effects are
not clear. Organosulfur compounds modulate activity of several metabolizing
enzymes that activate CYP450s, or detoxify (glutathione S-transferases) carcino-
gens, and inhibit formation of DNA adducts in several target tissues. Decrease in
CYP2E1, and increase in phase II enzymes activity by onion consumption due to
the presence of alk(en)yl polysulphides and/or glycosides of flavonols can afford
protection against some carcinogens [146]. Dipropenyl sulfide has been suggested
Allium cepa L. 149

to exert the beneficial drug metabolizing action of onions [113]. Antiproliferative

activity is possibly mediated by induction of apoptosis and alterations of the cell
cycle [18]. Ethyl acetate extract of onion shows potent inhibitory effects on animal
fatty acid synthase (FAS), and induces apoptosis in FAS overexpressing human
breast cancer MDA-MB-231 cells; the extract also suppresses lipid accumulation
during the differentiation of 3T3-L1 adipocytes due to its inhibition of intracellular
FAS activity [156].
Ethanol extract stimulates glucose uptake by increased synthesis and translo-
cation of glucose transporter GLUT4 protein from the cytoplasm to the plasma
membrane, and also enhances tyrosine phosphorylation of the insulin receptor-b,
insulin receptor substrate-1, and the serine phosphorylation of Akt [52]. However,
Kadan et al. [84] disputed that the antidiabetic property is mediated through
GLUT4 translocation to the plasma membrane. Increased NO caused by the greater
NOS activity, and the increased saving of NO by the antioxidative activity was
suggested as one of the mechanisms of the antihypertensive effect of onion in SHR
[125]. However, hydroethanol peel extract was suggested to reduce aortic con-
tractions possibly via inhibition of calcium influx, but without the involvement of
NO, cGMP, endothelium and prostaglandins [115].
Human A/Es, Allergy and Toxicity: In a Japanese case-control study, frequent
use of pickled onion increased relative risk of both stomach and colon cancers
[144]. In a comparative study of sixteen normal subjects and 16 heartburn patients,
ingestion of onions significantly increased number of reflux episodes, heartburn
episodes and belches, concluding onions as a potent and long-lasting refluxogenic
agent in heartburn patients [4]. Consumption of Spanish pickled onions with high
levels of SO2 is reported to have caused asthma outbreaks in several patients [51].
Fungal corneal ulcers in onion harvesters in southern Taiwan have been reported
during harvest period [99], and air-suspended onion particles were found respon-
sible for corneal ulceration [73]. Occupational eczema is also reported in onion
harvesters [149].
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interaction: Coadministration of onion
significantly decreased the Cmax of cyclosporin by 60% and reduced the AUC0-t
by 68%. In conclusion, onion markedly decreases the oral bioavailability of
cyclosporin [160]. Flavonoids have effects on CYP450 activity, and flavonols are
inhibitors of CYP2C9 [134].
Commentary: The results of epidemiological, and clinical studies of onions as
anticancer, antiplatelet, antihyperglycemic, and antidyslipidemic have generally
been positive but inconsistent, so the jury is still out for its final verdict.
150 Allium cepa L.

References
1. Ahluwalia P, Mohindroo A. Effect of oral ingestion of different fractions of
Allium cepa on the blood and erythrocyte membrane lipids and certain
membrane-bound enzymes in rats. J Nutr Sci Vitaminol. 1989;35:155–61.
2. Akash MS, Rehman K, Chen S. Spice plant Allium cepa: dietary
supplement for treatment of type 2 diabetes mellitus. Nutrition. 2014;30:
1128–37.
3. Ali M, Bordia T, Mustafa T. Effect of raw versus boiled aqueous extract of
garlic and onion on platelet aggregation. Prostaglandins Leukot Essent
Fatty Acids. 1999;60:43–7.
4. Allen ML, Mellow MH, Robinson MG, Orr WC. The effect of raw onions
on acid reflux and reflux symptoms. Am J Gastroenterol. 1990;85:377–80.
5. Al-Nagdy SA, Abdel Rahman MO, Heiba HI. Extraction and identification
of different prostaglandins in Allium cepa. Compar Biochem Physiol C:
Compar Pharmacol Toxicol. 1986;85:163–6.
6. Alpsoy S, Aktas C, Uygur R, et al. Antioxidant and antiapoptotic effects of
onion (Allium cepa) extract on doxorubicin-induced cardiotoxicity in rats.
J Appl Toxicol. 2013;33:202–8.
7. Alpsoy S, Kanter M, Aktas C, et al. Protective effects of onion extract on
cadmium-induced oxidative stress, histological damage, and apoptosis in
rat heart. Biol Trace Elem Res. 2014;159:297–303.
8. Augusti KT, Arathy SL, Asha R, et al. A comparative study on the
beneficial effects of garlic (Allium sativum Linn), amla (Emblica Officinalis
Gaertn) and onion (Allium cepa Linn) on the hyperlipidemia induced by
butter fat and beef fat in rats. Indian J Exp Biol. 2001;39:760–6.
9. Augusti KT, Benaim ME, Dewar HA, Virden R. Partial identification of
the fibrinolytic activators in onion. Atherosclerosis. 1975;21:409–16.
10. Augusti KT, Benaim ME. Effect of essential oil of onion (allyl propyl
disulphide) on blood glucose, free fatty acid and insulin levels of normal
subjects. Clin Chim Acta. 1975;60:121–3.
11. Babu PS, Srinivasan K. Influence of dietary capsaicin and onion on the
metabolic abnormalities associated with streptozotocin induced diabetes
mellitus. Mol Cell Biochem. 1997;175:49–57.
12. Bakht J, Khan S, Shafi M. In vitro antimicrobial activity of Allium cepa
(dry bulbs) against Gram-positive and Gram-negative bacteria and fungi.
Pak J Pharm Sci. 2014;27:139–45.
13. Bang MA, Kim HA, Cho YJ. Alterations in the blood glucose, serum lipids
and renal oxidative stress in diabetic rats by supplementation of onion
(Allium cepa Linn). Nutr Res Pract. 2009;3:242–6.
14. Beatty ER, O’Reilly JD, England TG, et al. Effect of dietary quercetin on
oxidative DNA damage in healthy human subjects. Br J Nutr. 2000;84:
919–25.
15. Belman S. Onion and garlic oils inhibit tumor promotion. Carcinogenesis.
1983;4:1063–5.
Allium cepa L. 151

16. Benmalek Y, Yahia OA, Belkebir A, Fardeau ML. Antimicrobial and

antioxidant activities of Illicium verum, Crataegus oxyacantha ssp
monogyna and Allium cepa red and white varieties. Bioengineered. 2013;
4:244–8.
17. Bhanot A, Shri R. A comparative profile of methanol extracts of Allium
cepa and Allium sativum in diabetic neuropathy in mice. Pharmacognosy
Res. 2010;2:374–84.
18. Bianchini F, Vainio H. Allium vegetables and organosulfur compounds:
do they help prevent cancer? Environ Health Perspect. 2001;109:893–902.
19. Bilgrami KS, Sinha KK, Sinha AK. Inhibition of aflatoxin production and
growth of Aspergillus flavus by eugenol, and onion and garlic extracts.
Indian J Med Res Section A-Infectious Diseases. 1992;96:171–5.
20. Boeing H, Jedrychowski W, Wahrendorf J, et al. Dietary risk factors in
intestinal and diffuse types of stomach cancer: a multicenter case-control
study in Poland. Cancer Causes Control. 1991;2:227–33.
21. Bordia A, Arora SK, Kothari LK, et al. The protective action of essential oils
of onion and garlic in cholesterol-fed rabbits. Atherosclerosis. 1975;22:
103–9.
22. Bordia A, Bansal HC, Arora SK, Singh SV. Effect of the essential oils of
garlic and onion on alimentary hyperlipemia. Atherosclerosis. 1975;21:
15–9.
23. Bordia A, Verma SK, Vyas AK, et al. Effect of essential oil of onion and
garlic on experimental atherosclerosis in rabbits. Atherosclerosis. 1977;26:
379–86.
24. Bordia T, Mohammed N, Thomson M, Ali M. An evaluation of garlic and
onion as antithrombotic agents. Prostaglandins Leukot Essent Fatty Acids.
1996;54:183–6.
25. Brahmachari HD, Augusti KT. Effect of orally effective hypoglycemic
agents from plants on alloxan diabetes. J Pharm Pharmacol. 1962;14:617.
26. Brahmachari HD, Augusti KT. Hypoglycemic agents from onions.
J Pharm Pharmacol. 1961;13:128.
27. Briggs WH, Folts JD, Osman HE, Goldman IL. Administration of raw
onion inhibits platelet-mediated thrombosis in dogs. J Nutr. 2001;131:
2619–22.
28. Campos KE, Diniz YS, Cataneo AC, et al. Hypoglycaemic and antioxidant
effects of onion, Allium cepa: dietary onion addition, antioxidant activity
and hypoglycaemic effects on diabetic rats. Int J Food Sci Nutr. 2003;
54:241–6.
29. Cavagnaro PF, Galmarini CR. Effect of processing and cooking conditions
on onion (Allium cepa L.) induced antiplatelet activity and thiosulfinate
content. J Agric Food Chem. 2012;60:8731–7.
30. Challier B, Perarnau JM, Viel JF. Garlic, onion and cereal fibre as
protective factors for breast cancer: a French case-control study. Eur J
Epidemiol. 1998;14:737–47.
152 Allium cepa L.

31. Choi EY, Cho YO. Allium vegetable diet can reduce the exercise-induced
oxidative stress but does not alter plasma cholesterol profile in rats. Ann
Nutr Metab. 2006;50:132–8.
32. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus
petrolatum emollient on new surgical scars: prospective double-blinded
study. Dermatol Surg. 2006;32:193–7.
33. Colli JL, Amling CL. Chemoprevention of prostate cancer: what can be
recommended to patients? Curr Urol Rep. 2009;10:165–71.
34. Dankert J, Tromp TF, De Vries H, Klasen HJ. Antimicrobial activity of
crude juices of Allium Ascalonicum, Allium cepa and Allium sativum.
Zentralbl Bakteriol Orig A. 1979;245:229–39.
35. Dorant E, van den Brandt PA, Goldbohm RA, Sturmans F. Consumption
of onions and a reduced risk of stomach carcinoma. Gastroenterology.
1996;110:12–20.
36. Dorant E, van den Brandt PA, Goldbohm RA. A prospective cohort study
on the relationship between onion and leek consumption, garlic supplement
use and the risk of colorectal carcinoma in The Netherlands. Carcinogen-
esis. 1996;17:477–84.
37. Dorant E, van den Brandt PA, Goldbohm RA. Allium vegetable
consumption, garlic supplement intake, and female breast carcinoma
incidence. Breast Cancer Res Treat. 1995;33:163–70.
38. Dorsch W, Adam O, Weber J, Ziegeltrum T. Antiasthmatic effects of onion
extracts—detection of benzyl- and other isothiocyanates (mustard oils) as
antiasthmatic compounds of plant origin. Eur J Pharmacol. 1984;107:17–24.
39. Dorsch W, Ettl M, Hein G, et al. Antiasthmatic effects of onions. Inhibition
of platelet-activating factor-induced bronchial obstruction by onion oils.
Int Arch Allergy Appl Immunol. 1987;82:535–6.
40. Dorsch W, Scharff J, Bayer T, Wagner H. Antiasthmatic effects of onions.
Prevention of platelet-activating factor induced bronchial hyperreactivity
to histamine in guinea pigs by diphenylthiosulfinate. Int Arch Allergy Appl
Immunol. 1989;88:228–30.
41. Dorsch W, Schneider E, Bayer T, et al. Anti-inflammatory effects of
onions: inhibition of chemotaxis of human polymorphonuclear leukocytes
by thiosulfinates and cepaenes. Int Arch Allergy Appl Immunol. 1990;
92:39–42.
42. Dorsch W, Wagner H, Bayer T, et al. Antiasthmatic effects of onions. Alk
(en)yl sulfinothioic acid alk(en)yl-esters inhibit histamine release,
leukotriene and thromboxane biosynthesis in vitro and counteract PAF
and allergen-induced bronchial obstruction in vivo. Biochem Pharmacol.
1988;37:4479–86.
43. Dorsch W, Wagner H. New antiasthmatic drugs from traditional medicine?
Int Arch Allergy Appl Immunol. 1991;94:262–5.
44. Dorsch W, Weber J. Prevention of allergen-induced bronchial obstruction
in sensitized guinea pigs by crude alcoholic onion extract. Agents Actions.
1984;14:626–9.
Allium cepa L. 153

45. Dwivedi C, Rohlfs S, Jarvis D, Engineer FN. Chemoprevention of

chemically-induced skin tumor development by diallyl sulfide and diallyl
disulfide. Pharm Res. 1992;9:1668–70.
46. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in
hypertensive subjects. J Nutr. 2007;137:2405–11.
47. Elberry AA, Mufti S, Al-Maghrabi J, et al. Immunomodulatory effect of
red onion (Allium cepa Linn) scale extract on experimentally induced
atypical prostatic hyperplasia in Wistar rats. Mediators Inflamm.
2014;2014:640746.
48. El-Nima EI, Ahmad SA, Mekkawi AG, Mossa JS. The antimicrobial
activity of garlic and onion extracts. Pharmazie. 1983;38:747–8.
49. Galeone C, Pelucchi C, Levi F, et al. Onion and garlic use and human
cancer. Am J Clin Nutr. 2006;84:1027–32.
50. Galeone C, Pelucchi C, Talamini R, et al. Onion and garlic intake and the
odds of benign prostatic hyperplasia. Urology. 2007;70:672–6.
51. Gastaminza G, Quirce S, Torres M, et al. Pickled onion-induced asthma: a
model of sulfite-sensitive asthma? Clin Exp Allergy. 1995;25:698–703.
52. Gautam S, Pal S, Maurya R, Srivastava AK. Ethanolic extract of Allium
cepa stimulates glucose transporter type 4-mediated glucose uptake by the
activation of insulin signaling. Planta Med. 2015;81:208–14.
53. Geoghegan F, Wong RW, Rabie AB. Inhibitory effect of quercetin on
periodontal pathogens in vitro. Phytother Res. 2010;24:817–20.
54. Geoghegan F, Tsui VW, Wong RW, Rabie AB. Inhibitory effect of quercetin
on periodontal pathogens. Ann R Australas Coll Dent Surg. 2008;19:157–8.
55. Gharadaghi Y, Shojaee S, Khaki A, et al. Modulating effect of Allium cepa
on kidney apoptosis caused by Toxoplasma gondii. Adv Pharm Bull. 2012;
2:1–6.
56. Goldman IL, Kopelberg M, Debaene JE, Schwartz BS. Antiplatelet
activity in onion (Allium cepa) is sulfur dependent. Thromb Haemost.
1996;76:450–2.
57. González CA, Travier N, Luján-Barroso L, et al. Dietary factors and in situ
and invasive cervical cancer risk in the European prospective investigation
into cancer and nutrition study. Int J Cancer. 2011;129:449–59.
58. Gorinstein S, Leontowicz H, Leontowicz M, et al. The influence of raw
and processed garlic and onions on plasma classical and nonclassical
atherosclerosis indices: investigations in vitro and in vivo. Phytother Res.
2010;24:706–14.
59. Guerrero LM. Minor products of philippine forests. Bur Forest Manila
Bull. 1921;22:222.
60. Haidari F, Rashidi MR, Eshraghian MR, et al. Hypouricemic and
antioxidant activities of Allium cepa Lilliaceae and quercetin in normal
and hyperuricemic rats. Saudi Med J. 2008;29:1573–9.
61. Haidari F, Rashidi MR, Keshavarz SA, et al. Effects of onion on serum uric
acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities
in hyperuricemic rats. Pak J Biol Sci. 2008;11:1779–84.
154 Allium cepa L.

62. Hansen EA, Folts JD, Goldman IL. Steam-cooking rapidly destroys and
reverses onion-induced antiplatelet activity. Nutr J. 2012;11:76.
63. Helen A, Krishnakumar K, Vijayammal PL, Augusti KT. Antioxidant
effect of onion oil (Allium cepa Linn) on the damages induced by nicotine
in rats as compared to alpha-tocopherol. Toxicol Lett. 2000;116:61–8.
64. Helen A, Rajasree CR, Krishnakumar K, et al. Antioxidant role of oils
isolated from garlic (Allium sativum Linn) and onion (Allium cepa Linn)
on nicotine-induced lipid peroxidation. Vet Hum Toxicol. 1999;41:316–9.
65. Hertog MG, Feskens EJ, Hollman PC, et al. Dietary flavonoids and cancer
risk in the Zutphen Elderly Study. Nutr Cancer. 1994;22:175–84.
66. Hertog MG, Hollman PC, Katan MB, Kromhout D. Intake of potentially
anticarcinogenic flavonoids and their determinants in adults in The
Netherlands. Nutr Cancer. 1993;20:21–9.
67. Ho WS, Ying SY, Chan PC, Chan HH. Use of onion extract, heparin,
allantoin gel in prevention of scarring in chinese patients having laser
removal of tattoos: a prospective randomized controlled trial. Dermatol
Surg. 2006;32:891–6.
68. Hsing AW, Chokkalingam AP, Gao YT, et al. Allium vegetables and risk
of prostate cancer: a population-based study. J Natl Cancer Inst. 2002;
94:1648–51.
69. Huang TH, Mühlbauer RC, Tang CH, et al. Onion decreases the ovariectomy-
induced osteopenia in young adult rats. Bone. 2008;42:1154–63.
70. Hubbard GP, Wolffram S, de Vos R, et al. Ingestion of onion soup high in
quercetin inhibits platelet aggregation and essential components of the
collagen-stimulated platelet activation pathway in man: a pilot study. Br J
Nutr. 2006;96:482–8.
71. Hung H. Dietary quercetin inhibits proliferation of lung carcinoma cells.
Forum Nutr. 2007;60:146–57.
72. Hwang IK, Lee CH, Yoo KY, et al. Neuroprotective effects of onion
extract and quercetin against ischemic neuronal damage in the gerbil
hippocampus. J Med Food. 2009;12:990–5.
73. Hwang YH, Chou EJ, Chang CW, et al. Suspended onion particles and
potential corneal injury in onion harvesters. Arch Environ Health. 2002;
57:78–84.
74. Hyun SW, Jang M, Park SW, Kim EJ, Jung YS. Onion (Allium cepa)
extract attenuates brain edema. Nutrition. 2013;29:244–9.
75. Ige SF, Akhigbe RE. Common onion (Allium cepa) extract reverses
cadmium-induced organ toxicity and dyslipidaemia via redox alteration in
rats. Pathophysiology. 2013;20:269–74.
76. Ige SF, Akhigbe RE. The role of Allium cepa on aluminum-induced
reproductive dysfunction in experimental male rat models. J Hum Reprod
Sci. 2012;5:200–5.
77. Ige SF, Olaleye SB, Akhigbe RE, et al. Testicular toxicity and sperm
quality following cadmium exposure in rats: Ameliorative potentials of
Allium cepa. J Hum Reprod Sci. 2012;5:37–42.
Allium cepa L. 155

78. Islam MS, Choi H, du Loots T. Effects of dietary onion (Allium cepa L.) in
a high-fat diet streptozotocin-induced diabetes rodent model. Ann Nutr
Metab. 2008;53:6–12.
79. Jackson BA, Shelton AJ. Pilot study evaluating topical onion extract as
treatment for postsurgical scars. Dermatol Surg. 1999;25:267–9.
80. Janssen K, Mensink RP, Cox FJ, et al. Effects of the flavonoids quercetin
and apigenin on hemostasis in healthy volunteers: results from an in vitro
and a dietary supplement study. Am J Clin Nutr. 1998;67:255–62.
81. Jelodar GA, Maleki M, Motadayen MH, Sirus S. Effect of fenugreek,
onion and garlic on blood glucose and histopathology of pancreas of
alloxan-induced diabetic rats. Indian J Med Sci. 2005;59:64–9.
82. Jung JY, Lim Y, Moon MS, Kim JY, Kwon O. Onion peel extracts amelio-
rate hyperglycemia and insulin resistance in high fat diet/streptozotocin-
induced diabetic rats. Nutr Metab (Lond). 2011;8:18.
83. Jung YS, Kim MH, Lee SH, et al. Antithrombotic effect of onion in
streptozotocin-induced diabetic rat. Prostaglandins Leukot Essent Fatty
Acids. 2002;66:453–8.
84. Kadan S, Saad B, Sasson Y, Zaid H. In vitro evaluations of cytotoxicity of
eight antidiabetic medicinal plants and their effect on GLUT4 transloca-
tion. Evid Based Complement Alternat Med. 2013;2013:549345.
85. Kalus U, Pindur G, Jung F, et al. Influence of the onion as an essential
ingredient of the Mediterranean diet on arterial blood pressure and blood
fluidity. Arzneimittelforschung. 2000;50:795–801.
86. Karawya MS, Abdel Wahab SM, El-Olemy MM, Farrag NM. Dipheny-
lamine, an antihyperglycemic agent from onion and tea. J Nat Prod. 1984;
47:775–80.
87. Kawamoto E, Sakai Y, Okamura Y, Yamamoto Y. Effects of boiling on
the antihypertensive and antioxidant activities of onion. J Nutr Sci
Vitaminol (Tokyo). 2004;50:171–6.
88. Kendler BS. Garlic (Allium sativum) and onion (Allium cepa): a review of
their relationship to cardiovascular disease. Prev Med. 1987;16:670–85.
89. Khaki A, Fathiazad F, Nouri M, et al. Evaluation of androgenic activity of
Allium cepa on spermatogenesis in the rat. Folia Morphol (Warsz). 2009;
68:45–51.
90. Kim JH. Antibacterial action of onion (Allium cepa L.) extracts against oral
pathogenic bacteria. J Nihon Univ Sch Dent. 1997;39:136–41.
91. Kim SH, Jo SH, Kwon YI, Hwang JK. Effects of onion (Allium cepa L.)
extract administration on intestinal a-glucosidases activities and spikes in
postprandial blood glucose levels in SD rats model. Int J Mol Sci.
2011;12:3757–69.
92. Koc E, Arca E, Surucu B, Kurumlu Z. An open, randomized, controlled,
comparative study of the combined effect of intralesional triamcinolone
acetonide and onion extract gel and intralesional triamcinolone acetonide
alone in the treatment of hypertrophic scars and keloids. Dermatol Surg.
2008;34:1507–14.
156 Allium cepa L.

93. Lanzotti V, Romano A, Lanzuise S, Bonanomi G, Scala F. Antifungal

saponins from bulbs of white onion. Allium cepa L. Phytochemistry.
2012;74:133–9.
94. Larson AJ, Symons JD, Jalili T. Therapeutic potential of quercetin to
decrease blood pressure: review of efficacy and mechanisms. Adv Nutr.
2012;3:39–46.
95. Lata S, Saxena KK, Bhasin V, et al. Beneficial effects of Allium sativum,
Allium cepa and Commiphora mukul on experimental hyperlipidemia and
atherosclerosis—a comparative evaluation. J Postgrad Med. 1991;37:132–5.
96. Le Marchand L, Murphy SP, Hankin JH, et al. Intake of flavonoids and
lung cancer. J Natl Cancer Inst. 2000;92:154–60.
97. Levick SE, Jalali B, Strauss JS. With onions and tears: a multidimensional
analysis of a counter-ritual. Fam Process. 1981;20:77–83.
98. Li CJ, Yuan L, Ji TF, et al. Furostanol saponins from the seeds of Allium
cepa L. Fitoterapia. 2014;99C:56–63.
99. Lin SH, Lin CP, Wang HZ, et al. Fungal corneal ulcers of onion harvesters
in southern Taiwan. Occup Environ Med. 1999;56:423–5.
100. Makheja AN, Vanderhoek JY, Bailey JM. Inhibition of platelet aggrega-
tion and thromboxane synthesis by onion and garlic [letter]. Lancet. 1979;
1:781.
101. Makheja AN, Bailey JM. Antiplatelet constituents of garlic and onion.
Agents Actions. 1990;29:360–3.
102. Makheja AN, Vanderhoe JY, Bailey JM. Effect of onion (Allium cepa)
extract on platelet aggregation and thromboxane synthesis. Prostagland
Med. 1979;2:413–24.
103. Makheja AN, Vanderhoek JY, Bailey JM. Properties of an inhibitor of
platelet aggregation and thromboxane synthesis isolated from onion and
garlic. Thromb Haemost. 1979;42.
104. Mantawy MM, Ali HF, Rizk MZ. Therapeutic effects of Allium sativum
and Allium cepa in Schistosoma mansoni experimental infection. Rev Inst
Med Trop Sao Paulo. 2011;53:155–63.
105. Matheson EM, Mainous AG 3rd, Carnemolla MA. The association between
onion consumption and bone density in perimenopausal and post-
menopausal non-Hispanic white women 50 years and older. Menopause.
2009;16:756–9.
106. Mathew PT, Augusti KT. Hypoglycaemic effects of onion, Allium cepa Linn.
on diabetes mellitus—a preliminary report. Indian J Physiol Pharmacol.
1975;19:213–7.
107. McAnlis GT, McEneny J, Pearce J, Young IS. Absorption and antioxidant
effects of quercetin from onions, in man. Eur J Clin Nutr. 1999;53:92–6.
108. Mete R, Oran M, Topcu B, et al. Protective effects of onion (Allium cepa)
extract against doxorubicin-induced hepatotoxicity in rats. Toxicol Ind
Health. 2016;32:551–7.
Allium cepa L. 157

109. Millet A, Lamy E, Jonas D, et al. Fermentation enhances the biological

activity of Allium cepa bulb extracts. J Agric Food Chem. 2012;60:
2148–56.
110. Mirabeau TY, Samson ES. Effect of Allium cepa and Allium sativum on
some immunological cells in rats. Afr J Tradit Complement Altern Med.
2012;9:374–9.
111. Moon CH, Jung YS, Kim MH, et al. Mechanism for antiplatelet effect of
onion: AA release inhibition, thromboxane A(2)synthase inhibition and
TXA(2)/PGH(2) receptor blockade. Prostaglandins Leukot Essent Fatty
Acids. 2000;62:277–83.
112. Moon J, Do HJ, Kim OY, Shin MJ. Antiobesity effects of quercetin-rich
onion peel extract on the differentiation of 3T3-L1 preadipocytes and the
adipogenesis in high fat-fed rats. Food Chem Toxicol. 2013;58:347–54.
113. Munday R, Munday CM. Relative activities of organosulfur compounds
derived from onions and garlic in increasing tissue activities of quinone
reductase and glutathione transferase in rat tissues. Nutr Cancer. 2001;
40:205–10.
114. Nagda KK, Ganeriwal SK, Nagda KC, Diwan AM. Effect of onion and
garlic on blood coagulation and fibrinolysis in vitro. Indian J Physiol
Pharmacol. 1983;27:141–5.
115. Naseri MK, Arabian M, Badavi M, Ahangarpour A. Vasorelaxant and
hypotensive effects of Allium cepa peel hydroalcoholic extract in rat. Pak J
Biol Sci. 2008;11:1569–75.
116. Nishimura H, Higuchi O, Tateshita K, et al. Antioxidative activity and
ameliorative effects of memory impairment of sulfur-containing com-
pounds in Allium species. BioFactors. 2006;26:135–46.
117. Ola-Mudathir KF, Suru SM, Fafunso MA, et al. Protective roles of onion
and garlic extracts on cadmium-induced changes in sperm characteristics
and testicular oxidative damage in rats. Food Chem Toxicol. 2008;
46:3604–11.
118. Osmont KS, Arnt CR, Goldman IL. Temporal aspects of onion-induced
antiplatelet activity. Plant Foods Hum Nutr. 2003;58:27–40.
119. Park J, Kim J, Kim MK. Onion flesh and onion peel enhance antioxidant
status in aged rats. J Nutr Sci Vitaminol (Tokyo). 2007;53:21–9.
120. Prasad NS, Raghavendra R, Lokesh BR, Naidu KA. Spice phenolics
inhibit human PMNL 5-lipoxygenase. Prostaglandins Leukot Essent Fatty
Acids. 2004;70:521–8.
121. Pyun MS, Shin S. Antifungal effects of the volatile oils from Allium plants
against Trichophyton species and synergism of the oils with ketoconazole.
Phytomedicine. 2006;13:394–400.
122. Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Antihyper-
glycemic effect of some edible plants. J Ethnopharmacol. 1995;48:25–32.
123. Saha JC, Kasinathan S. Ecbolic properties of Indian medicinal plants.
Indian J Med Res. 1961;49:1094–8.
158 Allium cepa L.

124. Sainani GS, Desai DB, Natu MN, et al. Onion, garlic, and experimental
atherosclerosis. Jap Heart J. 1979;20:351–7.
125. Sakai Y, Murakami T, Yamamoto Y. Antihypertensive effects of onion on
NO synthase inhibitor-induced hypertensive rats and spontaneously
hypertensive rats. Biosci Biotechnol Biochem. 2003;67:1305–11.
126. Sakakibara H, Yoshino S, Kawai Y, Terao J. Antidepressant-like effect of
onion (Allium cepa L.) powder in a rat behavioral model of depression.
Biosci Biotechnol Biochem. 2008;72:94–100.
127. Saleheen D, Ali SA, Yasinzai MM. Antileishmanial activity of aqueous
onion extract in vitro. Fitoterapia. 2004;75:9–13.
128. Sebastian KL, Zacharias NT, Philip B, Augusti KT. The hypolipedemic
effect of onion (Allium cepa Linn.) in sucrose fed rabbits. Indian J Physiol
Pharmacol. 1979;23:27–30.
129. Setiawan VW, Yu GP, Lu QY, et al. Allium vegetables and stomach
cancer risk in China. Asian Pac J Cancer Prev. 2005;6:387–95.
130. Shams-Ghahfarokhi M, Shokoohamiri MR, Amirrajab N, et al. In vitro
antifungal activities of Allium cepa, Allium sativum and ketoconazole
against some pathogenic yeasts and dermatophytes. Fitoterapia. 2006;77:
321–3.
131. Sharquie KE, Al-Obaidi HK. Onion juice (Allium cepa L.), a new topical
treatment for alopecia areata. J Dermatol. 2002;29:343–6.
132. Shim SM, Yi HL, Kim YS. Bioaccessibility of flavonoids and total
phenolic content in onions and its relationship with antioxidant activity.
Int J Food Sci Nutr. 2011;62:835–8.
133. Shri R, Singh Bora K. Neuroprotective effect of methanolic extracts of
Allium cepa on ischemia and reperfusion-induced cerebral injury. Fitoter-
apia. 2008;79:86–96.
134. Si D, Wang Y, Zhou YH, et al. Mechanism of CYP2C9 inhibition by
flavones and flavonols. Drug Metab Dispos. 2009;37:629–34.
135. Singh T, Goel RK. Neuroprotective effect of Allium cepa L. in aluminium
chloride induced neurotoxicity. Neurotoxicology. 2015;49:1–7.
136. Slimestad R, Fossen T, Vågen IM. Onions: a source of unique dietary
flavonoids. J Agric Food Chem. 2007;55:10067–80.
137. Sparnins VL, Barany G, Wattenberg LW. Effects of organosulfur
compounds from garlic and onions on benzo[a]pyrene-induced neoplasia
and glutathione S-transferase activity in the mouse. Carcinogenesis.
1988;9:131–4.
138. Srivastava KC. Aqueous extracts of onion, garlic and ginger inhibit platelet
aggregation and alter arachidonic acid metabolism. Biomed Biochem Acta.
1984;43:S335–46.
139. Srivastava KC. Effect of onion and ginger consumption on platelet
thromboxane production in humans. Prostagland Leukotr Essent Fatty
Acids. 1989;35:183–5.
Allium cepa L. 159

140. Srivastava KC. Effects of aqueous extracts of onion, garlic and ginger on
platelet aggregation and metabolism of arachidonic acid in the blood
vascular system: in vitro study. Prostagland Leukotr Med. 1984;13:227–35.
141. Srivastava KC. Onion exerts antiaggregatory effects by altering arachi-
donic acid metabolism in platelets. Prostagland Leukotr Med. 1986;24:
43–50.
142. Suru SM. Onion and garlic extracts lessen cadmium-induced nephrotox-
icity in rats. Biometals. 2008;21:623–33.
143. Taj Eldin IM, Ahmed EM, Elwahab HMA. Preliminary study of the
clinical hypoglycemic effects of Allium cepa (red onion) in type 1 and type
2 diabetic patients. Environ Health Insights. 2010;4:71–7.
144. Tajima K, Tominaga S. Dietary habits and gastrointestinal cancers: a
comparative case-control study of stomach and large intestinal cancers in
Nagoya, Japan. Jap J Cancer Res. 1985;76:705–16.
145. Tătărîngă G, Miron A, Păduraru I, et al. Characterization of some
extractive fractions isolated from raw Allium cepa L. bulbs. Rev Med Chir
Soc Med Nat Iasi. 2008;113:522–4.
146. Teyssier C, Amiot MJ, Mondy N, et al. Effect of onion consumption by
rats on hepatic drug-metabolizing enzymes. Food Chem Toxicol. 2001;39:
981–7.
147. Thomson M, Mustafa T, Ali M. Thromboxane-B(2) levels in serum of
rabbits receiving a single intravenous dose of aqueous extract of garlic and
onion. Prostaglandins Leukot Essent Fatty Acids. 2000;63:217–21.
148. Tjokroprawiro A, Pikir BS, Budhiarta AA, et al. Metabolic effects of onion
and green beans on diabetic patients. Tohoku J Exp Med. 1983;141
(Suppl):671–6.
149. van Ketel WG, de Haan P. Occupational eczema from garlic and onion.
Contact Dermat. 1978;4:53–4.
150. Vatsala TM, Singh M, Murugesan RG. Effects of onion in induced
atherosclerosis in rabbits: I. Reduction of arterial lesions and lipid levels.
Artery. 1980;7:519–30.
151. Vatsala TM, Singh M. Changes in shape of erythrocytes in rabbits on
atherogenic diet and onion extracts. Atherosclerosis. 1980;36:39–45.
152. Vatsala TM, Singh M. Effects of onion in atherosclerosis in rabbits: IV.
Maintenance of normal activity of aortic enzymes. Curr Sci. 1982;51:
276–8.
153. Vatsala TM, Singh M. Effects of onion in induced atherosclerosis in
rabbits: II. Reduction of lipid levels in the eye. Curr Sci. 1982;51:230–2.
154. Wagner H, Dorsch W, Bayer T, et al. Antiasthmatic effects of onions:
inhibition of 5-lipoxygenase and cyclooxygenase in vitro by thiosulfinates
and “Cepaenes”. Prostaglandins Leukot Essent Fatty Acids. 1990;39:
59–62.
155. Wagner H. Search for new plant constituents with potential antiphlogistic
and antiallergic activity. Planta Med. 1989;55:235–41 (Review).
160 Allium cepa L.

156. Wang Y, Tian WX, Ma XF. Inhibitory effects of onion (Allium cepa L.)
extract on proliferation of cancer cells and adipocytes via inhibiting fatty
acid synthase. Asian Pac J Cancer Prev. 2012;13:5573–9.
157. Wattenberg LW, Sparnins VL, Barany G. Inhibition of N-nitrosodiethyl-
amine carcinogenesis in mice by naturally occurring organosulfur com-
pounds and monoterpenes. Cancer Res. 1989;49:2689–92.
158. Weisenberger H, Grube H, Konig E, Pelzer H. Isolation and identification
of the platelet aggregation inhibitor present in the onion. Allium cepa.
FEBS Letters. 1972;26:105–8.
159. Yamada K, Naemura A, Sawashita N, et al. An onion variety has natural
antithrombotic effect as assessed by thrombosis/thrombolysis models in
rodents. Thromb Res. 2004;114:213–20.
160. Yang CY, Chao PD, Hou YC, et al. Marked decrease of cyclosporin
bioavailability caused by coadministration of ginkgo and onion in rats.
Food Chem Toxicol. 2006;44:1572–8.
161. Yang EJ, Kim SI, Park SY, et al. Fermentation enhances the in vitro
antioxidative effect of onion (Allium cepa) via an increase in quercetin
content. Food Chem Toxicol. 2012;50:2042–8.
162. Yang J, Meyers KJ, van der Heide J, Liu RH. Varietal differences in
phenolic content and antioxidant and antiproliferative activities of onions.
J Agric Food Chem. 2004;52:6787–93.
163. You WC, Blot WJ, Chang YS, et al. Allium vegetables and reduced risk of
stomach cancer. J Natl Cancer Inst. 1989;81:162–4.
164. Zhou Y, Zhuang W, Hu W, et al. Consumption of large amounts of Allium
vegetables reduces risk for gastric cancer in a meta-analysis. Gastroen-
terology. 2011;141:80–9.
Allium sativum L.
(Amaryllidaceae)

Abstract
The Ebers papyrus mentions external application of garlic for indurations.
Hippocrates prescribed eating garlic as treatment for uterine tumors, and
Dioscorides as official physician of the Roman army specified garlic for
intestinal and lung disorders occurring among Roman troops in Asia.
A preparation of garlic and vinegar known as the Four Thieves was credited
with protecting citizens of Marseilles when plague struck in 1722. Louis Pasteur
reported antibacterial activity of garlic in 1858. The Hindus consider it to be
tonic, hot, digestive, aperients, cholagogue, and alterative; useful in cough, and
phlegmatic affections, fever, swellings, gonorrhea, piles, leprosy, colic,
rheumatism and worms. In the Raja Nirgantha it is described under the name
of Rasona, and bears many synonyms indicative of its properties, such as Ugra-
gandha (strong smelling), Mahanshadha (panacea), and Bhuta-ghna (destroying
demons), and Lasuna. Epidemiological studies indicate that consumption of
garlic is inversely associated with cancer risk. In Chinese medicine, garlic,
known as Dasuan, is credited as vital-energy-stimulant, spleen- and stomach-
warming, digestant, anti-inflammatory, detoxicant, and anthelmintic. Sulfur-
containing compounds, the odoriferous substances in garlic are principally made
of diallyl disulphide, together with smaller quantities of diallyl trisulphide and
diallyl polysulphide. Allin serves as the precursor of alliin, allicin, diallylsul-
phide and ajoene. When garlic bulb is crushed, alliin present in fresh garlic is
converted by the enzyme alliin lyase or alliinase into allicin. Allicin and diallyl
disulphide combine to form ajoene, the diallyl disulphide being formed from
allicin by heat. Allicin, a water-soluble substance, is responsible for the strong
characteristic odor of garlic, is the major potent platelet antiaggregator, and is
active against Gram-positive and Gram-negative bacteria, as well as against acid
fast organisms. Garlic extracts have shown anticancer, antiatherogenic, antibac-
terial, blood cholesterol lowering, fibrinolytic, and platelet antiaggregation
activities. Garlic oil inhibits human platelet aggregation by interfering with

© Springer Nature Switzerland AG 2020 161

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_17
162 Allium sativum L.

TXB2 synthesis. Meta-analyses of clinical studies agree that garlic supplemen-

tation, especially aged garlic, reduces both SBP and DBP in hypertensive
patients, reduces TC and LDL-C, decreases platelet aggregation, prevents LPO
of oxidized erythrocytes and LDL, increases antioxidant status, stimulates
immune system, and exhibits anticancer activity.

Keywords






Ail blanc Duk Garlic Hvidløg Knoblauch Knoflook Lehsun Rasona





Suàn Thome

Vernaculars: Urd.: Lehsun; Hin.: Duk; San.: Bhutaghna, Lasuna, Mahausudha,

Mlecha-gandha, Rasona, Rasonam, Ugra-gandha, Yavanesta; Ben.: Lashuna,
Rasun; Mal.: Vallaipundu, Vellulli, Veluthaulli; Mar.: Duk, Lasuun; Tam.: Ulli-
poondu, Vellai-pundu; Tel.: Tella-gidda, Velluli, Velluli tella-gadda; Ara.: Fum,
Thome, Thoum; Bur.: Chyet thon phew; Chi.: 蒜, Dà suàn, Hsiao suan, Suàn, Syun
tàuh; Dan.: Hvidløg; Dut.: Knoflook; Eng.: Garlic; Fin.: Valkosipuli; Fre.: Ail, Ail
blanc, Ail commun, Ail cultivé, Thériaque des pauvres; Ger.: Gemeiner knoblauch,
Gewöhnlicher knoblauch, Knoblauch; Gre.: Skordo; Ita.: Aglio; Jap.: Gaarikku,
Ninniku; Kor.: Kallik, Ma nul; Nep.: Lasun; Nor.: Hvitløk; Per.: Sir or Seer; Por.:
Alho, Alho-ordinário; Rus.: Luk chesnok, Luk posevnoi; Spa.: Ajo; Swe.: Hvitlök,
Vitlök; Tag.: Bauang, Bawang; Tha.: Gratiem, Kathiam, Krathiam; Tur.: Sar-
ımsak; Vie.: Cây tỏi, Tỏi.
Historical Perspective: The Ebers papyrus mentions external application of garlic
for indurations. Hippocrates prescribed eating garlic as treatment for uterine tumors.
Dioscorides, as official physician of the Roman army specified garlic for intestinal
and lung disorders occurring among Roman troops in Asia. A preparation of garlic
and vinegar known as the Four Thieves was credited with protecting citizens of
Marseilles when plague struck in 1722. Ibn al-BaitarLXIX quoted Dioscorides, that it
is carminative, causes heartburn, is diuretic and expels intestinal worms, and
application of it mixed with olive oil and salt cures boils; quoting Galen he said it is
useful in winter, and very beneficial in pulmonary ulcers. Louis Pasteur reported
antibacterial activity of garlic in 1858 [29]. Dymock et al.XL mentioned that in the
Raja Nirgantha it is described under the name of Rasona, and bears many syn-
onyms indicative of its properties, such as Ugra-gandha (strong smelling),
Mahanshadha (panacea), Bhuta-ghna (destroying demons), and Lasuna. etc. Hin-
dus consider it to be tonic, hot, digestive, aperients, cholagogue, and alterative;
useful in cough, and phlegmatic affections, fever, swellings, gonorrhea, piles,
leprosy, colic, rheumatism and worms. A decoction of garlic in milk is given in
small doses in hysteria, flatulence, sciatica, and heart disease. Hartwell [97]
reported that cancer incidence in France is supposedly lowest where garlic con-
sumption is greatest; garlic eaters in Bulgaria do not have cancer, and that a
physician in Victoria, British Columbia, claimed that he has successfully treated
malignancies by prescribing garlic eating. Italy was one of the European countries
Allium sativum L. 163

Fig. 1 Allium sativum, Garlic, Prof. Akbar, Original

with the highest mortality rates for gastric cancer (males 17.3 and females 8.7 X
100,000 in 1987) which was the third cause of death due to cancers, accounting for
over 14,000 deaths per year. Epidemiological studies showed that consumption of
traditional soups, meat, salted and dried fish, cold cuts and seasoned cheeses, as
well as the intake of animal proteins and nitrites were related to an increased gastric
cancer risk; whereas, higher consumption of garlic, olive oil and spices was
associated with reduced gastric cancer risk [45, 62]. An epidemiological prospec-
tive cohort study monitored 41,837 women, aged 55–69 years, for cancer incidence
for 5 years. Consumption of garlic was inversely associated with risk, with an age-
and energy-adjusted relative risk of 0.68 [205]. Wang et al. [224] also reported that
consumption of garlic and onion was associated with a decreased risk of nodular
disease of thyroid in women residing in areas of China where continuous low-dose
radiation exposure is a cause of nodular thyroid disease (Fig. 1).
Actions and Uses: Garlic (temperament, hot 3° and dry 3°) is described externally
as detergent and anti-inflammatory,LXXVII and internally blood thinner, stomachic,
digestive, emmenagogue, diuretic and diaphoretic,L,LXXVII aphrodisiac,LXXVII clears
voice, and is beneficial in the treatment of hemorrhoids, leprosy, paralysis, facial
palsy, tremors and epilepsy; also useful as a paste in vinegar or honey for alopecia
due to ringworm, and vitiligo;L a gastric stimulant, expectorant, carminative,
increases semen, and beneficial in forgetfulness, colicky pains, internal ulcers of the
lungs, and chronic fevers; in large doses, an irritant and produces flatulence, head-
ache, nausea, vomiting, and diarrhea.LXXXI NadkarniCV also described it hot, anti-
rheumatic, anthelmintic, and alterative; and the seed oil as stimulant. In Chinese
medicine, garlic is known as Dasuan and has a “warm” property, and is credited as
vital-energy-stimulant, spleen- and stomach-warming, digestant, anti-inflammatory,
detoxicant, and anthelmintic; and is used for indigestion, edema, diarrhea, dysen-
tery, whooping cough, furuncle, carbuncle, tinea capitis, snakebites, and insect
164 Allium sativum L.

stings.XVIII In the Philippines, the bulbs are prescribed for high blood pressure, eaten
fresh or burned for cough in children, as diuretic, and also to mitigate pain caused by
bites of insects, scorpions, and centipedes. A poultice applied to temples relieves
headache.CXVII In Surabaya province of Indonesia, garlic is part of the special diet to
treat allergic bronchial asthma in children [96]. Garlic is also considered hot in
Mexican folk medicine, and used for the treatment of whooping cough and applied
topically to treat bites and stings. In Surinam, the bulbs are used to improve poor
blood circulation to heart, and in Guyana, raw bulbs are consumed to strengthen
lungs, and the boiled ones are eaten to relieve flatulence.XXXIV It is used as
emmenagogue, abortifacient and oxytocic in Trinidad, Jamaica, Mexico, Yucatán
and other areas.XI,C
Phytoconstituents: Wertheim [227] established that the odoriferous substance in
garlic is made principally of diallyl disulphide, together with smaller quantities of
diallyl trisulphide and diallyl polysulphide. Rundquist [184] was the first to isolate
the precursor of diallyl disulphide and named it ‘allin,’ and identified the carbo-
hydrate as sinistrin. Four closely related constituents, derived from allin are alliin,
allicin, diallylsulphide and ajoene. When garlic bulb is crushed, alliin present in
fresh garlic is converted by the enzyme alliin lyase or alliinase into allicin. Allicin
and diallyl disulphide combine to form ajoene, the diallyl disulphide being formed
from allicin by heat. Diallyl disulphide is also converted into various sulphides
which give garlic its characteristic odor [146]. Mohammad and Woodward [152]
identified allicin as the major potent platelet antiaggregator; whereas Makheja and
Bailey [138] credited adenosine, allicin and paraffinic polysulfides as the main
antiplatelet constituents. Adenosine and allicin, both inhibit platelet aggregation
without affecting COX and LOX metabolites of AA. The trisulfides inhibit platelet
aggregation as well as TX synthesis along with induction of new LOX metabolites.
Allicin, a water-soluble substance is irritating to the skin, is responsible for the
strong characteristic odor of garlic, and is active against Gram-positive and Gram-
negative bacteria, as well as against acid fast organisms [50, 51]; allicin loses its
antibacterial activity during storage in aqueous extract. One mg of allicin is
equivalent to 15 Oxford units of penicillin. Alliin, the precursor of allicin, is more
stable than allicin but possesses no antibacterial activity [202]. Alliin contents in
garlic vary by the species, the cultivation mode, and the area or geography of
production [216]. Garlic bulbs from various parts of Yugoslavia contained 0.192 to
0.245% volatile oil. Antimicrobial activities of the volatile oil against 22 organisms
were much lower than that of aqueous ethanol extract prepared at room tempera-
ture, despite TLC pattern of both preparations indicating a similar composition. The
extract is more stable both at room temperature and at 4 °C; antioxidants protect
active components from rapid decay [167].
Pharmacology: Various authors have reviewed garlic for its medicinal properties,
described in traditional literatures, and also those based on scientific evaluations [3,
4, 27, 69, 77, 80, 82, 84, 85, 101, 214, 221]. Garlic extracts have shown anticancer,
antiatherogenic, antibacterial, blood cholesterol lowering, secondary vascular
changes reducing, fibrinolytic, and platelet antiaggregation activities [68, 81].
Allium sativum L. 165

Garlic supplemented diet significantly suppressed cholesterol content of plasma,

aorta and liver, and increased plasma fibrinolytic activity in hypercholesterolemic
rabbits [121, 150, 151]. Dietary garlic decreased hyperphagia and polydipsia, but
no significant effect on hyperglycemia or hypoinsulinemia in STZ-diabetic mice
[209], but aqueous maceration significantly lowered FBG, reduced oxidative stress
and increased levels of GSH and SOD of diabetic rats [53, 136]. Freeze-dried garlic
powder in an atherogenic diet of rats lowered serum cholesterol and partly reversed
increased levels of LDL and LDL-C [57, 112]. Garlic powder decreased mean
values of TC, TGs and phospholipids for forty-eight hours in dogs [76], and
improved peroxide detoxification in hypercholesterolemic rats [56, 98]. Garlic
powder suspension also significantly alleviated metabolic syndrome, and elevated
atherogenic indices, increased insulin level, enhanced antioxidant defense system
and decreased LPO of diabetic rats [134]. However, Islam and Choi [102] reported
no influence on body weight, FBG, HbA1c, liver weight, liver glycogen levels, and
serum lipid profile, after adding freeze-dried garlic powder to high-fat diet of
diabetic rats for four-weeks. Garlic oil prevented cholesterol-induced hyperlipi-
demia [54], almost completely reversed increase in lipid levels of ethanol and
high-fat diet-induced hyperlipidemic rats [194], was more effective in lowering
cholesterol than clofibrate in hypercholesterolemic rabbits [30, 31, 34, 35, 39],
lowered aortic and liver cholesterol [107, 108], markedly prevented increase in
beta/alpha ratio, reduced established aortic atheromas to about half [34, 36, 105],
and also reduced aortic lipid content by 72% [142]. Water-soluble extract of garlic
powder significantly reduces HMG-CoA reductase activity and reduces cholesterol
biosynthesis (20–25%) in cultured rat hepatocytes, compared to 90% inhibition by
mevastatin [89]. Inhibition of cholesterol synthesis by chloroform and acetone/
chloroform extracts was 44–52%; while ajoene, methylajoene, allicin, 2-vinyl-
4H-1,3-dithiin and diallylsulfide inhibited synthesis by 37–72% [191]. Petroleum
ether extract also significantly prevented atherogenic diet-induced increase of serum
TC and TGs in rats [122]. Sodimu et al. [199] observed that garlic oil almost
nullified the serum albumin-decreasing effect of a high-fat/high-cholesterol diet
in rats.
Garlic oil inhibits human platelet aggregation [11, 38, 188] by interfering with
TXB2 synthesis [139, 219]. Rabbits administered garlic oil for nine-months had
85–100% increase in fibrinolytic activity [32]. Methyl allyl trisulphide, a minor
component in natural garlic oil, also inhibits platelet aggregation [11]. Aqueous
extract is a weak inhibitor of platelet aggregation and TXB2 synthesis [203, 204].
However, pretreatment with aqueous garlic extract reduces TXB2 synthesis, and
protects rabbits from thrombocytopenia and hypotension, and toxic symptoms of
thrombogenic agents [6, 7]. Allicin and adenosine both inhibit platelet aggregation
without affecting COX and LOX metabolites of AA. The trisulfides inhibit platelet
aggregation as well as TX synthesis, with induction of new LOX metabolites [138,
145]. Garlic also exerted hypotensive activity in normotensive rats and dogs [141],
and a ‘normalizing’ effect on elevated BP [183]. Garlic extracts injection produced
small reductions in both SBP and DBP [41, 173, 195]; and atropine pretreatment
166 Allium sativum L.

did not affect the hypotensive effects of the aqueous extract [159]. Garlic homo-
genate with hydrochlorothiazide and captopril was synergistically cardioprotective
and antihypertensive against fructose- and isoproterenol-induced toxicities in rats
[16, 17]. Aged garlic extract lowers BP in SHR more safely than the raw garlic [94].
Garlic aqueous extract protected rabbits against lethal dose of collagen and
arachidonic acid [7]. Coadministration of garlic extract to mice reduced level of
LPO in the liver, and protected against lethal dose of CP, with increased life span of
more than 70% [218], and inhibited enhanced LPO in CCl4-induced liver injury in
mice [111]. Garlic also ameliorates copper deficiency associated signs without
affecting hepatic lipogenesis in rats [87]. Garlic and its organosulfur compounds
exert protective effects against chemically-induced carcinogenesis in several organs
[25, 26, 59, 67, 128, 148, 157, 158, 165, 172, 210, 211, 217], inhibit metabolism of
DES, prevent DNA adducts formations [9, 91, 127], increase apoptotic index in
DMBA-induced nonmalignant and malignant skin tumors in mice [12], and cause
apoptosis of cancer cells [22, 75]. Garlic supplementation for two-weeks prior and
four-weeks after the insertion of carcinogen-bearing thread into the uterine cervix of
Swiss mice significantly reduced cervical carcinoma incidence in mice (23 vs. 73%)
[100], and delayed onset of tumors and reduced final mammary tumors in rats
[128]. Selenium-enriched garlic powder treated rats developed fewest DMBA-
induced mammary tumors compared to regular garlic-treated rats [101], and i.
p. administration of garlic oil prevented formation of postoperative peritoneal
adhesions in rats [185]. Garlic powder possesses antioxidant activity and alliin is a
very good hydroxyl radical scavenger [120].
Sharma et al. [192] reported garlic extract effective against Salmonella, E. coli,
Proteus, Enterobacteria and Klebsiella species. Five Gram-negative, three
Gram-positive bacterial species, and two yeast species were reported susceptible to
crude garlic juice [66], and a 10% water extract completely inhibited growth of
B. cereus [187]. Aqueous extract has shown in vitro activity against drug resistant
E. coli, P. aeruginosa, B. subtilis, S. aureus, S. epidermidis, K. pneumoniae, Sh.
sonnei, and S. typhi [93], S. pneumoniae, S. pyogenes, H. influenzae, Proteus spp.,
Candida spp. [74, 103], V. parahaemolyticus, M. phlei, S. faecalis, B. cereus, and
M. luteus [55]. Fresh garlic extract than garlic powder extract [125] and ajoene
[230] have greater efficacy against C. albicans. Aqueous extract also inhibits
growth of H. pylori [52], and shows a synergistic effect with omeprazole against H.
pylori [110]. Chowdhury et al. [58] found aqueous garlic extract and allicin effi-
cacious against Sh. flexneri Y-induced shigellosis, fully curing infected rabbits
within 3 days; while 4 of the 5 rabbits in the control group died within 48 h.
Aqueous extract also significantly enhanced growth of one strain of probiotic
bacteria (Lactobacillus reuteri), and inhibited growth of pathogenic strains of
E. coli [208]. Aqueous extract and allicin also showed significant antibacterial
activity against isolates of MDR Sh. dysenteriae, Sh. flexneri Y, Sh. sonnei and
enterotoxigenic E. coli. However, garlic was ineffective in experimental crypto-
coccosis in mice [129]. Shashikanth et al. [193] reported raw garlic extract being
more potent antibacterial agent than tetracycline on caecal microflora. Abdel-Nasser
et al. [2] also found ether extract of garlic tops to possess significant antibacterial
Allium sativum L. 167

activity against a variety of Gram-positive organisms. Garlic extracts rich in allicin

show appreciable antimycobacterial activity [1, 71], and garlic oil is significantly
effective against MRSA [64, 222], P. aeruginosa, E. coli [49], and fungi of the
genus Aspergillus [161]. Fresh garlic extract exhibits antimicrobial activity against
C. albicans and MRSA, and synergistically acts with fluconazole and itraconazole
on C. albicans, and with cefotaxime and ceftriaxone on P. aeruginosa [126].
Ethanol extract shows highly significant inhibition of P. aeruginosa [114]. Aged
garlic extract, garlic powder and the garlic-derived compounds, S-allylcysteine,
diallyl sulfide and diallyl disulfide enhance antimicrobial activity of gentamicin
against E. coli and ameliorate gentamicin-induced nephrotoxicity in rats [140, 190].
A single dose of ajoene on the day of malarial infection, suppressed development of
parasitemia, and combined with chloroquine completely prevented development of
parasitemia in mice [166]. The shelf life of meat was increased up to 50-days as
against 21-days at low temperature by using garlic. Addition of aqueous extract to
hamburgers significantly inhibited growth of S. aureus [153]; both fungi and
bacteria were inhibited in this process. Broad-spectrum antimicrobial activity of
crushed garlic is credited to the formation of allicin; other antibacterial factors
known to be present in garlic are allistatin-I, allistatin-II, scrodinine and heat-stable
factors developed during storage of garlic extract at elevated temperature [201].
Fresh garlic extract and its constituents were also virucidal against HSV-1, HSV-2,
parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human
rhinovirus type 2; the order for virucidal activity was: ajoene > allicin > allyl
methyl thiosulfinate > methyl allyl thiosulfinate [226]. Ajoene was found in
oil-macerates of garlic but not in fresh extracts.
Clinical Studies: Meta-analyses of clinical studies agree that garlic supplementa-
tion, especially aged garlic, reduces both SBP and DBP in hypertensive patients
[23, 44, 175, 179, 220, 228], reduces TC and LDL-C [5, 168, 178, 196, 231],
decreases platelet aggregation, prevents LPO of oxidized erythrocytes and LDL,
increases antioxidant status [40, 171], stimulates immune system [179, 189], and
exhibits anticancer activity [60, 170, 215]. One review of garlic treatment in
peripheral arterial occlusive disease revealed no significant difference from the
placebo in change of SBP or DBP, HR, ankle and brachial pressures [109].
A meta-analysis by Warshafsky et al. [225] concluded that garlic, in an amount
approximately one half to one clove per day decreased serum TC levels by about
9% in the patients studied, and Brosche and Platt [43] reported that in seven out of
eight studies, including 500 patients, a daily dose of 0.6–0.9 g garlic powder
reduced TC and TGs levels by 5–20%.
Administration of garlic (5 g/day) to six male healthy Indian subjects signifi-
cantly lowered serum TGs and increased fibrinolytic activity by the end of second
and third weeks [106], and random administration of freshly extracted garlic (50 g)
juice or an equivalent amount of ether-extracted EO to 10 healthy Indian volunteers
significantly protected against alimentary hyperlipemia and decreased coagulation
time and fibrinolytic activity [31]. Ten gram of raw garlic daily to healthy
168 Allium sativum L.

volunteers for two-months significantly decreased serum cholesterol [28, 88], and
increased clotting time and fibrinolytic activity [88]. One-half to one clove of garlic
per day by U.S. adults reduced cholesterol levels by approximately 9% [90].
Coadministration of 40 g garlic with fat-rich diet for seven-days to healthy
Pakistani individuals, significantly prevented increase in serum TC, TGs and total
lipids [21]. Twenty healthy volunteers, given garlic oil (equivalent to 30 g fresh
garlic) for six-months, reduced serum TGs, TC and LDLs, and increased HDLs,
giving a favorable HDL/LDL ratio; the effect persisted for two months after garlic
discontinuation; sixty-two Indian patients with CHD and elevated serum cholesterol
had similar results after garlic administration, reaching statistically significant levels
at the end of 8-months and persisting for the next 2-months of follow-up [37].
A double-blind RCT of 42 healthy U.S. adults (52 ± 12 years) with a serum TC
level of greater than or equal to 220 mg/dL, given standardized garlic powder
900 mg a day, had significant reduction in serum TC, with LDL-C reduced by 11%
by 12-weeks, with no changes in HDL-C, TGs, serum glucose and BP [104].
A significant decrease (10%) in serum cholesterol, fibrinogen and fibrinopeptide A
in German patients with hyperlipoproteinemia after intake of dried garlic was
reported by Harenberg et al. [95]. A large multicenter double-blind RCT, involving
261 patients and 30 general practitioners in West Germany, also reported a mean
drop of 12% in serum TC and 17% in TGs of hyperlipidemic patients, mostly
hyperlipoproteinemia type IIa/IIb, after treatment with 800 mg garlic powder for
16-weeks; best cholesterol lowering effects were evident in patients with initial
cholesterol values between 250 and 300 mg/dl [133]. Vorberg and Schneider [223]
used a garlic powder preparation (900 mg powder/day) in a double-blinded RCT on
40 hypercholesterolemic outpatients, and reported significant reduction in TC, TGs
and BP, compared to the placebo group; garlic group also reported greater feeling
of ‘well-being.’ Garlic exhibited clofibrate-like effect on coagulation time and
checked postprandial fall in blood fibrinolytic activity in both normal subjects and
in IHD patients [14]. Holzgartner et al. [99] reported comparatively similar effects
of highly significant reduction in TC, LDL-C and TGs, and an increase in HDL-C,
after treatment with standardized 900 mg garlic powder per day or 600 mg ben-
zafibrate for 12-weeks of 98 German patients with primary hyperlipoproteinemia.
After three-months treatment with 600 mg of garlic powder, German volunteers
aged 70 years and over with initial normal plasma cholesterol levels (<200 mg/dl),
showed no significant changes; however, volunteers with initial high cholesterol
levels (>200 mg/dl) had their plasma TC reduced by 7.7%, TGs by 15.9%, and
choline phospholipids by 4.6% [42]. In a double-blind RCT, twenty-four healthy
volunteers with plasma concentrations of HDL2-C less than 10 mg/dL (men) and
15 mg/dL (women) treated with a daily dose of 900 mg garlic powder (Kwai®)
over a period of 6-weeks, postprandial increase of TGs was significantly reduced in
the test group compared to the placebo group [182]. Luley et al. [131], though,
reported no significant effect of dried garlic (3X198 or 3X450 mg/day for
six-weeks) on TC, HDL-C and LDL-C, TGs, apolipoproteins A and B, PT, whole
blood coagulation time, euglobulin lysis time, and fibrinogen levels in 85 hyper-
lipidemic patients after two double-blind clinical trials. The study was criticized for
Allium sativum L. 169

using a batch of garlic with exceptionally low biological activity. Continuous use of
high dose garlic powder over four years significantly reduced increase in carotid
and femoral arteriosclerotic plaques in elderly German patients [119], and addition
of aged garlic 1,200 mg daily with statins reduced progression of coronary artery
calcification to 7.5%, compared to 22.2% in statins only treated U.S. patients [44].
Dry garlic powder tablet to Iranian patients with CAD for three-months also sig-
nificantly prevented increase of carotid intima-media thickness [135]. Peripheral
arterial occlusive disease patients treated with 800 mg of garlic powder daily for
twelve-weeks significantly improved walking distance with a significant decrease in
DBP, spontaneous platelet aggregation, plasma viscosity and cholesterol concen-
tration [116].
Twenty volunteers receiving high-fat diet plus garlic oil had fibrinolysis
increased by 36% and platelet adhesion reduced, compared to fibrinolytic activity
reduced by 22% and the platelet adhesion increased in 40 Indian volunteers given
fat enriched diet without garlic for 3-weeks [33]. In a clinical trial of ten high risk
patients, who had experienced MI, garlic oil increased fibrinolytic activity 80%
above that of the control group of ten healthy subjects. However, the fibrinolytic
activity fell after the cessation of garlic oil administration [186]. In ten other MI
patients, garlic oil treatment was begun within 24 h of the coronary episode, along
with conventional treatment, while another ten patients treated identically but
without garlic served as controls. Fibrinolytic activity was increased by 95% in the
garlic group by 20-days, compared to only 24% increase in the control
group. However, discontinuation of garlic resulted in decrease of fibrinolytic
activity [32]. Fibrinolytic activity increased by 72 and 63% within 6 h of admin-
istration of raw or fried garlic, respectively, in twenty IHD patients; four weeks
administration resulted in sustained increase, rising to 84 and 72% on 28th day in
raw and fried group, respectively [61]. In a double-blind, placebo-controlled study
in sixty subjects with cerebrovascular risk factors and constantly increased platelet
aggregation, daily ingestion of 800 mg of powdered garlic coated tablets over
4-weeks led to a significant decrease in spontaneous platelet aggregation by 56.3%
during the garlic phase; after a 4-weeks wash-out period, the values increased back
to the initial values [115, 118]. In another double-blind RCT, Kiesewetter et al.
[117] reported improvement of blood fluidity and simultaneous increase in fibri-
nolytic activity, leading to enhanced capillary perfusion and ‘purification’ of the
microcirculation. Legnani et al. [124] reported significantly higher t-PA activity
after two-weeks treatment with a daily dose of 900 mg of dried garlic powder, after
a double-blind, crossover RCT in 12 healthy subjects, but not significantly different
from placebo. Garlic therapy for 12-weeks did not cause any appreciable changes in
serum TGs, b-lipoprotein, plasma fibrinogen levels or coagulation time in either
IHD patients or control subjects. Peak blood fibrinolytic activity (BFA) achieved at
the 4th week of garlic therapy was not sustained despite its continuation and
returned to pregarlic use values at the 12th week [13].
Dried garlic powder (Kwai® tablets), 600 mg/day produced an average of *9%
decrease in BP [95, 113], and significant fall in both sitting and erect DBP after a
single dose of Kwai tablets (2,400 mg) in nine patients with severe primary
170 Allium sativum L.

hypertension [147]. Other studies also reported similar results [24, 92, 143, 144]. In
a double-blind RCT of forty-seven German outpatients with mild hypertension
treated with garlic powder by 11 general practitioners had their DBP significantly
reduced from 102 to 89 mmHg after 12-weeks of treatment [20]. Patients attending
a general Pakistani hospital with lower readings of SBP were found to consume
more garlic, an average of 134 g per month [169]. A time-released garlic powder
tablet was found more effective than the regular garlic supplements for the treat-
ment of mild to moderate hypertension [198]. Garlic addition to standard therapy
for 30-days to patients with primary hypertension significantly lowered lipid levels
and LPO, but failed to significantly affect BP [78]; however, in patients with
uncontrolled hypertension on standard therapy, addition of aged garlic for 12-weeks
significantly improved BP fall in patients with higher than 140 mmHg SBP [176,
177]. Treatment of patients with mild hypertension with garlic tablets for 24-weeks
lowered SBP and DBP, and significantly better to both placebo and atenolol [19].
A traditional Japanese garlic homogenate-based supplementary diet produced
clinically relevant fall in SBP and DBP of prehypertensive and mildly hypertensive
patients after 12-weeks [156]. Garlic supplementation also counteracts oxidative
stress and prevents oxidative DNA damage in primary hypertension [73].
A meta-analysis of clinical trials of patients with SBP of more than 140 mmHg
showed that garlic lowered SBP by about 16.3 mmHg and DBP by 9.3 mmHg
[174, 180]. Some questioned these meta-analyses due to inadequate study designs,
methodological deficiencies, and with too little information about BP measurement
of the included trials [197].
Aged garlic in patients with confirmed colorectal adenomas, significantly
reduced progression of adenomas after 6–12 months of treatment [212]. Oral
supplementation with garlic extract and oil for 7.3 years to patients prone to gastric
cancer in Shandong Province of China resulted in an insignificant reduction in
incidence and mortality [132]. Intragastric infusion of uncooked and cooked garlic
caused a significant increase in DNA content of gastric aspirate in volunteers [72].
Topical application of ajoene to tumors of 21 patients with either nodular or
superficial basal cell carcinoma reduced tumor size in 17 patients [213]. Caldwell
et al. [46] reported a patient with severe hepatopulmonary syndrome, unresponsive
to somatostatin therapy, who refused liver transplantation, experienced a partial
palliation of symptoms and some objective signs of improvement over 18-months
of continuous self medication with large daily doses of powdered garlic. Garlic
ingestion by nursing mothers consistently perceived increased intensity of milk
odor, peaking in strength 2 h after ingestion; this enhanced odor was detected by
the infants, who were attached to breast for longer period and sucked more when
the milk smelled like garlic [149].
Approximately 40% of allogenic bone marrow transplant recipients develop
HCMV pneumonia with a mortality of *80 to 90% [10], HCMV infection is also
one of the major causes of morbidity and mortality in AIDS patients [63]. Intra-
venous use of garlic extract or garlic ingredients prevented fungal and viral
infections in 47 patients of allogenic bone marrow transplant at Beijing Medical
University. Out of thirteen other patients, who did not receive garlic treatment, five
Allium sativum L. 171

(38.5%) developed interstitial pneumonitis, resulting in death of two patients, and

recovery in three after garlic treatment [130]. Inhibitory effect of garlic extract on
HCMV is stronger if the monolayers are pretreated with garlic extract and con-
tinuous application shows strongest antiviral effect [154]. Orally administered fresh
garlic extract is of limited value in therapy of human fungal infections [48],
however, i.v. injection of a commercial garlic extract in two patients with crypto-
coccal meningitis and three patients with other types of meningitis resulted in a
twofold increase in plasma titers of anti-Cryptococcus neoformans activity over
preinfusion titers [70]. Campos et al. [47] reported no effect of garlic infusion in A.
lumbricoides-infected children. However, Soffar and Mukhtar [200] found it effi-
cient and safe in the treatment of ten children infected with H. nana and twenty-six
infected with G. lamblia. A mouth wash containing 10% garlic in quarter Ringer
solution drastically reduced number of oral bacteria [79].
Mechanism of Action: Sulfur-containing compounds such as alliin and com-
pounds produced enzymatically from alliin (e.g. allicin) synergistically influence
each other and can have different effects. Aged garlic extract that lacks allicin, still
exhibits significant clinical effects, such as on BP, blood fluidity, immune system,
cancer, liver, etc. Chemical complexity and the various processes used to obtain
different formulations result in varying degrees of efficacy and safety [137]. In
primary hepatocyte cultures, the hypocholesterolemic effect was suggested to be
due, in part, to decreased hepatic cholesterol synthesis, whereas the triacylglycerol-
lowering effect was due to inhibition of fatty acid synthesis [229]. The antihyper-
tensive effect may be partly mediated through NO pathway [8]. Suppression of
CYP2E1 by garlic might influence the metabolic activation of chemical procar-
cinogens and prevent carcinogenesis [164], and stimulation of glutathione
S-transferase activity by water-soluble organosulfur compounds is believed to
detoxify carcinogens and help in chemoprevention [207].
Human A/Es, Allergy and Toxicity: Contact dermatitis usually occurs in
housewives sensitive to garlic, in the form of pulpitis, typically affecting the thumbs
and fingers [86]. Eight Chinese patients are reported to have developed contact
dermatitis after rubbing the cut end of a fresh garlic bulb onto skin to treat fungal
and other infections in groin, neck, lower limb, hand or face [123]. A child
developed partial thickness skin burns as a result of a garlic-petroleum jelly plaster
[163]. Diallyl disulfide and allicin have been identified as the allergenic substances
[162]. Rose et al. [181] reported a case of spontaneous spinal epidural hematoma
causing paraplegia secondary to a qualitative platelet disorder, allegedly due to
excessive garlic ingestion. Topically, the garlic oil is irritating.LXXXVIII
Animal Toxicity: LD50 values by PO, IP and SC routes were estimated over
30 ml/kg of garlic extract in male and female of both rats and mice [155], and garlic
extract up to a dose of 2,000 mg/kg five times a week for 6-months was nontoxic to
rats [206]. LD50 values of the aqueous extract and allicin in mice are reported as
172 Allium sativum L.

173.78 ml/kg and 204.17 lL/kg body weight, respectively [58]. Rats fed diet
containing 4% garlic had a decrease in daily food intake, weight gain, and
digestibility, and a significant decrease in PCV, Hb, RBCs, and WBCs [160]. Fehri
et al. [83] also reported doses of 300 and 600 mg/kg/24 h of a garlic aqueous
extract for 21-days affected weight growth, biologic parameters and histologic
structures.
CYP450 and Potential for Drug-Herb Interaction: Single dose of garlic oil
significantly depressed hepatic CYP450 of Sprague-Dawley rats; however, daily
administration of garlic oil for 5-days significantly increased CYP450 activity [65].
Garlic increased bioavailability and half-life, decreased clearance and elimination
rate of hydrochlorothiazide, and caused substantial decrease in potassium excretion
in rats [18]; the bioavailability and half life of propranolol were also significantly
enhanced by 2- and 3-folds, respectively, in rats [15].
Commentary: The fibrinolytic, antidyslipidemic, antihypertensive and antibacte-
rial effects of garlic are mostly supported by the clinical studies. Any inconsis-
tencies in results might be due to variations in chemical constituents.

References
1. Abbruzzese MR, Delaha EC, Garagusi VF. Absence of antimycobacterial
synergism between garlic extract and antituberculosis drugs. Diagn
Microbiol Infect Dis. 1987;8:79–85.
2. Abdel-Nasser M, Safwat MS, Ali MZ. Detection of antibacterial substances
in some plant residues and their effect on certain microorganisms.
Zentralblatt fur Mikribiologie. 1983;138:63–9.
3. Adetumbi MA, Lau BH. Allium sativum (garlic)—a natural antibiotic. Med
Hypotheses 1983;12:227–37 (Review).
4. Akbar S. Garlic: the stinking majic herb. Victoria, BC, Canada: Trafford
Publishing; 2006.
5. Alder R, Lookinland S, Berry JA, Williams M. A systematic review of the
effectiveness of garlic as an antihyperlipidemic agent. J Am Acad Nurse
Pract. 2003;15:120–9.
6. Ali M, Thomson M, Al-Naqeeb MA, et al. Antithrombotic activity of
garlic: its inhibition of the synthesis of thromboxane-B2 during infusion of
arachidonic acid and collagen in rabbits. Prostagland Leukot Essent Fatty
Acids. 1990;41:95–9.
7. Al-Naqeeb MA, Ali M, Thomson M, et al. Histopathological evidence of
protective action of garlic against collagen and arachidonic acid toxicity in
rabbits. Prostagland Leukot Essent Fatty Acids. 1992;46:301–6.
8. Al-Qattan KK, Thomson M, Al-Mutawa’a S, et al. Nitric oxide mediates
the blood-pressure lowering effect of garlic in the rat two-kidney, one-clip
model of hypertension. J Nutr. 2006;136(3 Suppl):774S–6S.
Allium sativum L. 173

9. Amagase H, Milner JA. Impact of various sources of garlic and their

constituents on 7,12-dimethylbenz(a)anthracene binding to mammary cell
DNA. Carcinogenesis. 1993;14:1627–31.
10. Apperley JF, Goldman JM. Cytomegalovirus: biology, clinical features
and methods for diagnosis. Bone Marrow Transplant. 1988;3:253–64.
11. Ariga T, Oshiba S, Tamada T. Platelet aggregation inhibitor in garlic.
Lancet. 1981;1:150–1 (Letter).
12. Arora A, Shukla Y. Induction of apoptosis by diallyl sulfide in DMBA-
induced mouse skin tumors. Nutr Cancer. 2002;44:89–94.
13. Arora RC, Arora S, Gupta RK. The long-term use of garlic in ischaemic
heart disease—an appraisal. Atherosclerosis (Ireland). 1981;40:175–9.
14. Arora RC, Arora S. Comparative effect of clofibrate, garlic and onion on
alimentary hyperlipemia. Atherosclerosis. 1981;39:447–52.
15. Asdaq SM, Inamdar MN. Pharmacodynamic and pharmacokinetic inter-
actions of propranolol with garlic (Allium sativum) in rats. Evid Based
Complement Alternat Med. 2011;2011:824042.
16. Asdaq SM, Inamdar MN. Potential of garlic and its active constituent,
S-allyl cysteine, as antihypertensive and cardioprotective in presence of
captopril. Phytomedicine. 2010;17:1016–26.
17. Asdaq SM, Inamdar MN. The potential benefits of a garlic and
hydrochlorothiazide combination as antihypertensive and cardioprotective
in rats. J Nat Med. 2011;65:81–8.
18. Asdaq SM, Inamdar MN. The potential for interaction of hydrochloro-
thiazide with garlic in rats. Chem Biol Interact. 2009;181:472–9.
19. Ashraf R, Khan RA, Ashraf I, Qureshi AA. Effects of Allium sativum
(garlic) on systolic and diastolic blood pressure in patients with essential
hypertension. Pak J Pharm Sci. 2013;26:859–63.
20. Auer W, Eiber A, Hertkorn E, et al. Hypertension and hyperlipaedemia:
garlic helps in mild cases. Br J Clin Prac Symp Suppl. 1990;69:3–7.
21. Bakhsh R, Chughtai MI. Influence of garlic on serum cholesterol, serum
triglycerides, serum total lipids and serum glucose in human subjects.
Nahrung. 1984;28:159–63.
22. Balasenthil S, Rao KS, Nagini S. Garlic induces apoptosis during 7,12-
dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.
Oral Oncol. 2002;38:431–6.
23. Banerjee SK, Maulik SK. Effect of garlic on cardiovascular disorders: a
review. Nutr J. 2002;1:4.
24. Barrie SA, Wright JV, Pizzarno JE. Effects of garlic oil on platelet
aggregation, serum lipids, and blood pressure in humans. J Orthomol Med.
1987;2:15–21.
25. Belman S, Sellakumar A, Bosland MC, Savarese K, Estensen RD. Papilloma
and carcinoma production in DMBA-initiated, onion oil-promoted mouse
skin. Nutr Cancer. 1990;14:141–8.
26. Belman S. Onion and garlic oils inhibit tumor promotion. Carcinogenesis.
1983;4:1063–5.
174 Allium sativum L.

27. Beretz A, Cazenave JP. Old and new natural products as the source of
modern antithrombotic drugs. Planta Med. 1991;57:S68–72 (Review).
28. Bhushan S, Sharma SP, Singh SP, et al. Effect of garlic on normal blood
cholesterol level. Indian J Physiol Pharmacol. 1979;23:211–4.
29. Block E. The chemistry of garlic and onions. Scien Am. 1985;252:114–9.
30. Bordia A, Arora SK, Kothari LK, et al. The protective action of essential
oils of onion and garlic in cholesterol-fed rabbits. Atherosclerosis.
1975;22:103–9.
31. Bordia A, Bansal HC, Arora SK, Singh SV. Effect of the essential oils of
garlic and onion on alimentary hyperlipemia. Atherosclerosis. 1975;21:
15–9.
32. Bordia A, Joshi HK, Shanadhya YK, Bhu N. Effect of essential oil of
garlic on serum fibrinolytic activity in patients with coronary artery
disease. Atherosclerosis. 1977;28:155–9.
33. Bordia A, Sharma KD, Parmar YK, Verma SK. Protective effect of garlic
oil on the changes produced by 3 weeks of fatty diet on serum cholesterol,
serum triglycerides, fibrinolytic activity and platelet adhesiveness in man.
Indian Heart J. 1982;34:86–8.
34. Bordia A, Verma SK, Khabia BL, et al. The effective of active principle of
garlic and onion on blood lipids and experimental atherosclerosis in rabbits
and their comparison with clofibrate. J Assoc Physicians India. 1977;25:
509–16.
35. Bordia A, Verma SK. Effect of garlic feeding on regression of experi-
mental atherosclerosis in rabbits. Atherosclerosis. 1978;7:428–37.
36. Bordia A, Verma SK. Effect of garlic feeding on regression of
experimental atherosclerosis in rabbits. Artery. 1980;7:428–37.
37. Bordia A. Effect of garlic on blood lipids in patients with coronary heart
disease. Am J Clin Nutr. 1981;34:2100–3.
38. Bordia A. Effect of garlic on human platelet aggregation in vitro. Athero-
sclerosis. 1978;30:355–60.
39. Bordia AK, Verma SK. Garlic on the reversibility of experimental athero-
sclerosis. Indian Heart J. 1978;30:47–50.
40. Borek C. Garlic reduces dementia and heart-disease risk. J Nutr. 2006;136
(3 Suppl):810S–2S.
41. Brankovic S, Radenkovic M, Kitic D, et al. Comparison of the hypotensive
and bradycardic activity of ginkgo, garlic, and onion extracts. Clin Exp
Hypertens. 2011;33:95–9.
42. Brosche T, Platt D, Dorner H. The effect of a garlic preparation on the
composition of plasma lipoproteins and erythrocyte membranes in geriatric
subjects. Br J Clin Prac 44 Symp. Suppl 1990;69:12–9.
43. Brosche T, Platt D. Garlic as phytogenic antilipemic agent. Recent studies
with a standardized dry garlic powder substance. Fortschritte der
ZZMedizin. 1990;108:703–6 (Review).
44. Budoff M. Aged garlic extract retards progression of coronary artery
calcification. J Nutr. 2006;136(3 Suppl):741S–4S.
Allium sativum L. 175

45. Buiatti E, Palli D, Decarli A, et al. A case-control study of gastric cancer

and diet in Italy. Int J Cancer. 1989;44:611–6.
46. Caldwell SH, Jeffers LJ, Narula OS, et al. Ancient remedies revisited: does
Allium sativum (garlic) palliate the hepatopulmonary syndrome? J Clin
Gastroenterol. 1992;15:248–50.
47. Campos R, Amato Neto V, Castanho RE, Moreira AA, Pinto PL.
Treatment of ascardiasis with garlic (Allium sativum). Revesta do Hospital
das Clinicas; Faculdade de Medicina Da Universidade de Sao Paulo
1990;45:213–5 (Portuguese).
48. Caporaso N, Smith SM, Eng RH. Antifungal activity in human urine and
serum after ingestion of garlic (Allium sativum). Antimicrob Agents
Chemotherap. 1983;23:700–2.
49. Casella S, Leonardi M, Melai B, Fratini F, Pistelli L. The role of diallyl
sulfides and dipropyl sulfides in the in vitro antimicrobial activity of the
essential oil of garlic, Allium sativum L., and leek, Allium porrum L.
Phytother Res. 2013;27:380–3.
50. Cavallito CJ, Bailey JH. Allicin the antibacterial principle of Allium
sativum. I Isolation, physical properties and antibacterial action. J Am
Chem Soc. 1944.66:1950–1.
51. Cavallitto CJ, Buck JS, Suter CM. Allicin the antibacterial principle of
Allium sativum. II. Determination of chemical structure. J Am Chem Soc.
1944;66:1952–4.
52. Cellini L, Di Campli E, Masulli M, Di Bartolomeo S, Allocati N.
Inhibition of Helicobacter pylori by garlic extract (Allium sativum). FEMS
Immunol Med Microbiol. 1996;13:273–7.
53. Chandra A, Mahdi AA, Singh RK, et al. Effect of Indian herbal
hypoglycemic agents on antioxidant capacity and trace elements content
in diabetic rats. J Med Food. 2008;11:506–12.
54. Chaudhuri BN, Mukherjee SK, Mongia SS, Chakravarty SK. Hypolipi-
demic effect of garlic and thyroid function. Biomed Biochem Acta.
1984;43:1045–7.
55. Chen HC, Chang MD, Chang TJ. Antibacterial properties of some spice
plants before and after heat treatment. Zhonghua Min Guo Wei Sheng Wu
Ji Mian Yi Xue Za Zhi. 1985;18:190–5 (Chinese).
56. Chetty KN, Calahan L, Harris KC, et al. Garlic attenuates hypercholes-
terolemic risk factors in olive oil fed rats and high cholesterol fed rats.
Pathophysiology. 2003;9:127–32.
57. Chi MS. Effects of garlic products on lipid metabolism in cholesterol-fed
rats. Proc Soc Exp Biol Med. 1982;171:174–8.
58. Chowdhury AK, Ahsan M, Islam SN, Ahmad ZU. Efficacy of aqueous
extract of garlic and allicin in experimental shigellosis in rabbits. Indian J
Med Res Section A-Infectious Diseases. 1991;93:33–6.
59. Choy YM, Kwok TT, Fung KP, Lee CY. Effect of garlic, Chinese
medicinal drugs and amino acids on growth of Erlich ascites tumor cells in
mice. Am J Chin Med. 1983;11:69–73.
176 Allium sativum L.

60. Chu YL, Raghu R, Lu KH, et al. Autophagy therapeutic potential

of garlic in human cancer therapy. J Tradit Complement Med. 2013;3:
159–62.
61. Chutani SK, Bordia A. The effect of fried versus raw garlic on fibrinolytic
activity in man. Atherosclerosis. 1981;38:417–21.
62. Cipriani F, Buiatti E, Palli D. Gastric cancer in Italy. Ital J Gastroenter.
1991;23:429–35.
63. Collaborative DHPG Treatment Study Group. Treatment of serious
cytomegalovirus infections with 9-(1,3-Dihydrox-2-Propoxymethyl) gua-
nine in patients with AIDS and other immunodeficiencies. New Eng J
Med. 1986;31:801.
64. Cutler RR, Wilson P. Antibacterial activity of a new, stable, aqueous
extract of allicin against methicillin-resistant Staphylococcus aureus. Br J
Biomed Sci. 2004;61:71–4.
65. Dalvi RR. Alterations in hepatic phase I and phase II biotransformation
enzymes by garlic oil in rats. Toxicol Lett. 1992;60:299–305.
66. Dankert J, Tromp TF, de Vries H, Klasen HJ. Antimicrobial activity of
crude juices of Allium ascalonic, Allium cepa and Allium sativum.
Zentralbl Bakteriol (Orig A). 1979;245:229–39.
67. Das S. Garlic—a natural source of cancer preventive compounds. Asian
Pac J Cancer Prev. 2002;3:305–11.
68. Dausch JG, Nixon DW. Garlic: a review of its relationship to malignant
disease. Prev Med. 1990;19:346–61.
69. Davis DL. Natural anticarcinogens, carcinogens, and changing patterns in
cancer: some speculation. Environmen Res. 1989;50:322–40 (Review).
70. Davis LE, Shen J, Cai Y. Antifungal activity in human cerebrospinal fluid
and plasma after intravenous administration of Allium sativum. Antimicrob
Agent Chemother. 1990;34:651–3.
71. Delaha EC, Garagusi VF. Inhibition of mycobacteria by garlic extract
(Allium sativum). Antimicrob Agents Chemother. 1985;27:485–6.
72. Desai HG, Kalro RH, Choksi AP. Effect of ginger and garlic on DNA
content of gastric aspitrate. Indian J Med Res Section A-Infectious
Diseases. 1990;92:139–41.
73. Dhawan V, Jain S. Garlic supplementation prevents oxidative DNA
damage in essential hypertension. Mol Cell Biochem. 2005;275:85–94.
74. Dikasso D, Lemma H, Urga K, et al. Investigation on the antibacterial
properties of garlic (Allium sativum) on pneumonia causing bacteria.
Ethiop Med J. 2002;40:241–9.
75. Dirsch VM, Antlsperger DS, Hentze H, Vollmar AM. Ajoene, an
experimental antileukemic drug: mechanism of cell death. Leukemia.
2002;16:74–83.
76. Dixit VP, Joshi S, Sinha R, Bhargava SK, Varma M. Hypolipidemic
activity of guggal resin (Commiphora mukul) and garlic (Allium sativum)
in dogs (Canis familiaris) and monkeys (Presbytis entellus entellus
Dufresne). Biochem Exp Biol. 1980;16:421–4.
Allium sativum L. 177

77. Dubick MA. Historical perspective on the use of herbal preparations to

promote health. J Nutr. 1986;116:1348–54.
78. Duda G, Suliburska J, Pupek-Musialik D. Effects of short-term garlic
supplementation on lipid metabolism and antioxidant status in hypertensive
adults. Pharmacol Rep. 2008;60:163–70.
79. Elnima EI, Ahmad SA, Mekkawi AG, Mossa JS. The antimicrobial
activity of garlic and onion extracts. Pharmazie. 1983;38:747–8.
80. Ernst E. Cardiovascular effects of garlic (Allium sativum): a review.
Pharmatherap. 1987;5:83–9.
81. Ernst E. Garlic therapy? Theories of a folk remedy. Munchener Medizinis-
che Wochenschrift 1981;123:1537–8 (German).
82. Esanu V. Recent advances in the chemotherapy of herpes virus infections.
Virologie 1981;32:57–77 (Review).
83. Fehri B, Aiache JM, Korbi S, et al. Toxic effects induced by the repeat
administration of Allium sativum L. J Pharmacie Belgique. 1991;46:363–
74 (French).
84. Fenwick GR, Hanley AB. The genus Allium—Part 1. Critical Rev Food
Sci Nutr. 1985;22:199–271 (Review).
85. Fenwick GR, Hanley AB. The genus Allium—Part 3. Critical Rev Food
Sci Nutr. 1985;23:1–73 (Review).
86. Fernandez de Corres L, Leanizbarrutia I, Munoz D, Corrales JL. Allergic
contact dermatitis caused by garlic, Primula, Frullania and Compositae.
Allergologia et Immunopathologia 1985;13:291–9 (Spanish).
87. Fields M, Lewis CG, Lure MD. Garlic oil extract ameliorates the severity
of copper deficiency. J Am Coll Nutr. 1992;11:334–9.
88. Gadkari JV, Joshi VD. Effect of ingestion of raw garlic on serum
cholesterol level, clotting time and fibrinolytic activity in normal subjects.
J Postgrad Med. 1991;37:128–31.
89. Gebhardt R. Inhibition of cholesterol biosynthesis by a water-soluble garlic
extract in primary cultures of rat hepatocytes. Arzneimittelforschung.
1991;41:800–4.
90. Gore JM, Dalen JE. Cardiovascular disease. JAMA. 1994;271:1660–1.
91. Green M, Thomas R, Gued L, Sadrud-Din S. Inhibition of DES-induced
DNA adducts by diallyl sulfide: implications in liver cancer prevention.
Oncol Rep. 2003;10:767–71.
92. Grunwald J. Garlic and cardiovascular risk factors. Br J Clin Pharmacol.
1990;29:582–3 (Letter).
93. Gull I, Saeed M, Shaukat H, et al. Inhibitory effect of Allium sativum
and Zingiber officinale extracts on clinically important drug resistant
pathogenic bacteria. Ann Clin Microbiol Antimicrob. 2012;11:8.
94. Harauma A, Moriguchi T. Aged garlic extract improves blood pressure in
spontaneously hypertensive rats more safely than raw garlic. J Nutr.
2006;136(3 Suppl):769S–73S.
178 Allium sativum L.

95. Harenberg J, Giese C, Zimmermann R. Effect of dried garlic on blood

coagulation, fibrinolysis, platelet aggregation, and serum cholesterol levels
in patients with hyperlipoproteinemia. Atherosclerosis. 1988;74:247–9.
96. Harsono A, Partana JS, Partana L. The allergy management of bronchial
asthma in children in Surabaya. Paed Indonesiana. 1990;30:266–9 (Review).
97. Hartwell JL. Plants used against cancer. A Survey. Lloydia. 1969;32:78–
107.
98. Heinle H, Betz E. Effects of dietary garlic supplementation in a rat model
of atherosclerosis. Arzneimittelforschung. 1994;44:614–7.
99. Holzgartner H, Schmidt U, Kuhn U. Comparison of the efficacy and
tolerance of a garlic preparation versus bezafibrate. Arzneimittelforschung.
1992;42:1473–7.
100. Hussain SP, Jannu LN, Rao AR. Chemopreventive action of garlic on
MCA-induced carcinogenesis in the uterine cervix of mice. Cancer Lett.
1990;49:175–80.
101. Ip C, Lisk DJ, Stoewsand GS. Mammary cancer prevention by regular
garlic and selenium-enriched garlic. Nutr Cancer. 1992;17:279–86.
102. Islam MS, Choi H. Comparative effects of dietary ginger (Zingiber
officinale) and garlic (Allium sativum) investigated in a type 2 diabetes
model of rats. J Med Food. 2008;11:152–9.
103. Iwalokun BA, Ogunledun A, Ogbolu DO, Bamiro SB, Jimi-Omojola J. In
vitro antimicrobial properties of aqueous garlic extract against multidrug-
resistant bacteria and Candida species from Nigeria. J Med Food. 2004;
7:327–33.
104. Jain AK, Vargas R, Gotzkowsky S, McMahon FG. Can garlic reduce
levels of serum lipids? A controlled clinical study. Am J Med. 1993;
94:632–5.
105. Jain RC, Konar DB. Effect of garlic oil in experimental cholesterol
atherosclerosis. Atherosclerosis. 1978;29:125–9.
106. Jain RC. Effect of garlic on serum lipids, coagulability and fibrinolytic
activity of blood. Am J Clin Nutr. 1977;30:1380–1.
107. Jain RC. Onion and garlic in cholesterol atherosclerosis. Lancet.
1975;1:1240.
108. Jain RC. Onion and garlic in experimental cholesterol atherosclerosis in
rabbits. I. Effect on serum lipids and development of atherosclerosis.
Artery 1975;1:115–25.
109. Jepson RG, Kleijnen J, Leng GC. Garlic for peripheral arterial occlusive
disease. Cochrane Database Syst Rev. 2013;4:CD000095.
110. Jonkers D, van den Broek E, van Dooren I, et al. Antibacterial effect of
garlic and omeprazole on Helicobacter pylori. J Antimicrob Chemother.
1999;43:837–9.
111. Kagawa K, Matsutaka H, Yamaguchi Y, Fukuhama C. Garlic extract
inhibits the enhanced peroxidation and production of lipids in carbon
tetrachloride-induced liver injury. Jap J Pharmacol. 1986;42:19–26.
Allium sativum L. 179

112. Kamanna VS, Chandrasekhara N. Effect of Garlic (Allium sativum) on

serum lipoproteins and lipoprotein cholesterol levels in albino rats
rendered hypercholesterolemic by feeding cholesterol. Lipids. 1982;17:
483–7.
113. Kandziora J. Antihypertensive effectiveness and tolerance of a garlic
medication. Arztliche Forschung. 1988;1:1–8.
114. Karuppiah P, Rajaram S. Antibacterial effect of Allium sativum cloves and
Zingiber officinale rhizomes against multiple-drug resistant clinical
pathogens. Asian Pac J Trop Biomed. 2012;2:597–601.
115. Kiesewetter H, Jung F, Jung EM, et al. Effect of garlic on platelet
aggregation in patients with increased risk of juvenile ischaemic attack.
Eur J Clin Pharmacol. 1993;45:333–6.
116. Kiesewetter H, Jung F, Jung EM, et al. Effects of garlic coated tablets in
peripheral arterial occlusive disease. Clin Investig. 1993;71:383–6.
117. Kiesewetter H, Jung F, Mrowietz C, et al. Effects of garlic on blood fluidity
and fibrinolytic activity: a randomized, placebo-controlled, double-blind
study. Br J Clin Pract Symp Suppl. 1990;69:24–9.
118. Kiesewetter H, Jung F, Pindur G, et al. Effect of garlic on thrombocyte
aggregation, microcirculation, and other risk factors. Int J Clin Pharmacol
Ther Toxicol. 1991;29:151–5.
119. Koscielny J, Klussendorf D, Latza R, et al. The antiatherosclerotic effect of
Allium sativum. Atherosclerosis. 1999;144:237–49.
120. Kourounakis PN, Rekka EA. Effect on active oxygen species of alliin and
Allium sativum (garlic) powder. Res Commun Chem Pathol Pharmacol.
1991;74:249–52.
121. Kwon MJ, Song YS, Choi MS, et al. Cholesteryl ester transfer protein
activity and atherogenic parameters in rabbits supplemented with choles-
terol and garlic powder. Life Sci. 2003;72:2953–64.
122. Lata S, Saxena KK, Bhasin V, et al. Beneficial effects of Allium sativum,
Allium cepa and Commiphora mukul on experimental hyperlipidemia and
atherosclerosis—a comparative evaluation. J Postgrad Med. 1991;37:
132–5.
123. Lee TY, Lam TH. Contact dermatitis due to topical treatment with garlic in
Hong Kong. Cont Derm. 1991;24:193–6.
124. Legnani C, Frascaro M, Guazzaloca G, et al. Effects of a dried garlic
preparation on fibrinolysis and platelet aggregation in healthy subjects.
Arzneimittelforschung. 1993;43:119–22.
125. Lemar KM, Turner MP, Lloyd D. Garlic (Allium sativum) as an
anti-Candida agent: a comparison of the efficacy of fresh garlic and
freeze-dried extracts. J Appl Microbiol. 2002;93:398–405.
126. Li G, Ma X, Deng L, et al. Fresh garlic extract enhances the antimicrobial
activities of antibiotics on resistant strains in vitro. Jundishapur J
Microbiol. 2015;8:e14814.
127. Lin XY, Liu JZ, Milner JA. Dietary garlic suppresses DNA adducts caused
by N-nitroso compounds. Carcinogenesis. 1994;15:349–52.
180 Allium sativum L.

128. Liu J, Lin RI, Milner JA. Inhibition of 7,12-dimethylbenz(a)anthracene-

induced mammary tumors and DNA adducts by garlic powder. Carcino-
genesis. 1992;13:1847–51.
129. Louria DB, Lavenhar M, Kaminski T, Eng RHK. Garlic (Allium sativum)
in the treatment of experimental cryptococcosis. J Med Vet Mycol.
1989;27:253–6.
130. Lu DP, Guo NL, Jin NR, et al. Allogenic bone marrow transplantation for
the treatment of leukemia. Chin Med J. 1990;103:125–30.
131. Luley C, Lehmann-Leo W, Moller B, Martin T, Schwartzkopff W. Lack of
efficacy of dried garlic in patients with hyperlipoproteinemia. Arzneimit-
telforschung. 1986;36:766–8.
132. Ma JL, Zhang L, Brown LM, et al. Fifteen-year effects of Helicobacter
pylori, garlic, and vitamin treatments on gastric cancer incidence and
mortality. J Natl Cancer Inst. 2012;104:488–92.
133. Mader FH. Treatment of hyperlipidemia with garlic powder tablets.
Evidence from the German Association of General Practitioners’ multi-
centric placebo-controlled double-blind study. Arzneimittel-Forschung.
1990;40:1111–6.
134. Madkor HR, Mansour SW, Ramadan G. Modulatory effects of garlic,
ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and
oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr.
2011;105:1210–7.
135. Mahdavi-Roshan M, Zahedmehr A, Mohammad-Zadeh A, et al. Effect of
garlic powder tablet on carotid intima-media thickness in patients with
coronary artery disease: a preliminary randomized controlled trial. Nutr
Health. 2013;22:143–55.
136. Mahdi AA, Chandra A, Singh RK, et al. Effect of herbal hypoglycemic
agents on oxidative stress and antioxidant status in diabetic rats. Indian J
Clin Biochem. 2003;18:8–15.
137. Majewski M. Allium sativum: facts and myths regarding human health.
Rocz Panstw Zakl Hig. 2014;65:1–8.
138. Makheja AN, Bailey JM. Antiplatelet constituents of garlic and onion.
Agents Actions. 1990;29:360–3.
139. Makheja AN, Vanderhoek JY, Bailey JM. Inhibition of platelet aggrega-
tion and thromboxane synthesis by onion and garlic. Lancet. 1979;1:781.
140. Maldonado PD, Chanez-Cardenas ME, Pedraza-Chaverri J. Aged garlic
extract, garlic powder extract, S-allylcysteine, diallyl sulfide and diallyl
disulfide do not interfere with the antibiotic activity of gentamicin.
Phytother Res. 2005;19:252–4.
141. Malik ZA, Siddiqui S. Hypotensive effect of freeze-dried garlic (Allium
sativum) sap in dog. J Pak Med Assoc. 1981;31:12–3.
142. Mand JK, Gupta PP, Soni GL, Singh R. Effect of garlic on experimental
atherosclerosis in rabbits. Indian Heart J. 1985;37:183–8.
143. Mansell P, Reckless JP. Garlic [editorial]. Br Med J. 1991;303:379–80.
Allium sativum L. 181

144. Mansell P, Reckless JP. Garlic: effects on serum lipids, blood pressure,
coagulation, platelet aggregation, and vasodilatation. Br Med J. 1991;
303:379–80.
145. Mayeux PR, Agrawal KC, Tou JSH. The pharmacological effects of
allicin, a constituent of garlic oil. Agents Actions. 1988;25:182–90.
146. McElnay JC, Li Wan Po A. Garlic (Dietary supplements). Pharmaceut J.
1991;324–6.
147. McMahon FG, Vargas R. Can garlic lower blood pressure? A pilot study.
Pharmacother. 1993;13:406–7.
148. Meng CL, Shyu KW. Inhibition of experimental carcinogenesis by
painting with garlic extract. Nutr Cancer. 1990;14:207–17.
149. Mennella JA, Beauchamp GK. Maternal diet alters the sensory qualities of
human milk and the nursling’s behavior. Pediat. 1991;88:737–44.
150. Mirhadi SA, Singh S, Gupta PP. Effect of garlic supplementation to
atherogenic diet on collagen biosynthesis in various tissues of rabbits.
Indian Heart J. 1990;42:99–104.
151. Mirhadi SA, Singh S, Gupta PP. Effect of garlic supplementation to
cholesterol-rich diet on development of atherosclerosis in rabbits. Indian J
Exp Biol. 1991;29:162–8.
152. Mohammed SF, Woodward SC. Characterization of a potent inhibitor of
platelet aggregation and release reaction isolated from Allium sativum
(garlic). Thromb Res. 1986;44:793–806.
153. Mozaffari Nejad AS, Shabani S, Bayat M, Hosseini SE. Antibacterial effect
of garlic aqueous extract on Staphylococcus aureus in hamburger.
Jundishapur J Microbiol. 2014;7:e13134.
154. Nai-lan G, Dao-pei L, Woods GL, et al. Demonstration of the antiviral
activity of garlic extract against human cytomegalovirus in vitro. Chinese
Med J. 1993;106:93–6.
155. Nakagawa S, Masamoto K, Sumiyoshi H, Hirada H. Acute toxicity test of
garlic extract. J Toxicol Sci. 1984;9:57–60 (Japanese).
156. Nakasone Y, Nakamura Y, Yamamoto T, Yamaguchi H. Effect of a
traditional Japanese garlic preparation on blood pressure in prehyperten-
sive and mildly hypertensive adults. Exp Ther Med. 2013;5:399–405.
157. Nishikawa T, Yamada N, Hattori A, Fukuda H, Fujino T. Inhibition by
ajoene of skin-tumor promotion in mice. Biosci Biotechnol Biochem.
2002;66:2221–3.
158. Nishino H, Iwashima A, Itakura Y, Matsuura H, Fuwa T. Antitumor-
promoting activity of garlic extracts. Oncology. 1989;46:277–80.
159. Nwokocha CR, Ozolua RI, Owu DU, Nwokocha MI, Ugwu AC.
Antihypertensive properties of Allium sativum (garlic) on normotensive
and two kidney one clip hypertensive rats. Niger J Physiol Sci. 2011;
26:213–8.
160. Oboh G. Prevention of garlic-induced hemolytic anemia using some
tropical green leafy vegetables. J Med Food. 2004;7:498–501.
182 Allium sativum L.

161. Pai ST, Platt MW. Antifungal effects of Allium sativum (garlic) extract
against the Aspergillus species involved in otomycosis. Lett Appl
Microbiol. 1995;20:14–8.
162. Papageorgiou C, Corbet, JP, Menezes-Brandao F, et al. Allergic contact
dermatitis to garlic (Allium sativum L.) identification of the allergens: the
role of mono-, di- and trisulfides present in garlic. Arch Dermatol Res.
1983;275:229–34.
163. Parish RA, McIntire S, Heimbach DM. Garlic burns: a naturopathic
remedy gone awry. Pediatr Emerg Care. 1987;3:258–60.
164. Park KA, Kweon S, Choi H. Anticarcinogenic effect and modification of
cytochrome P450 2E1 by dietary garlic powder in diethylnitrosamine-
initiated rat hepatocarcinogenesis. J Biochem Mol Biol. 2002;35:615–22.
165. Perchellet JP, Perchellet EM, Belman S. Inhibition of DMBA-induced
mouse skin tumorigenesis by garlic oil and inhibition of two tumor-
promotion stages by garlic and onion oils. Nutr Cancer. 1990;14:183–93.
166. Perez HA, De la Rosa M, Apitz R. In vivo activity of ajoene against rodent
malaria. Antimicrob Agents Chemother. 1994;38:337–9.
167. Petricic J, Lulic B, Kupinic M. Antimicrobial efficiencies and stabilities of
active components of garlic (Allium sativum L.). Acta Pharm Jugosl
1977;27:35–41.
168. Qidwai W, Ashfaq T. Role of garlic usage in cardiovascular disease
prevention: an evidence-based approach. Evid Based Complement Alternat
Med. 2013;2013:125649.
169. Qidwai W, Qureshi R, Hasan SN, Azam SI. Effect of dietary garlic (Allium
sativum) on the blood pressure in humans—a pilot study. J Pak Med Assoc.
2000;50:204–7.
170. Raghu R, Lu KH, Sheen LY. Recent research progress on garlic (dà suàn)
as a potential anticarcinogenic agent against major digestive cancers.
J Tradit Complement Med. 2012;2:192–201.
171. Rahman K, Lowe GM. Garlic and cardiovascular disease: a critical review.
J Nutr. 2006;136(3 Suppl):736S–40S.
172. Rao AR, Sadhana AS, Goel HC. Inhibition of skin tumors in
DMBA-induced complete carcinogenesis system in mice by garlic (Allium
sativum). Indian J Exp Biol. 1990;28:405–8.
173. Rashid A, Khan HH. The mechanism of hypotensive effect of garlic
extract. J Pak Med Assoc. 1985;35:357–62.
174. Reinhart KM, Coleman CI, Teevan C, Vachhani P, White CM. Effects
of garlic on blood pressure in patients with and without systolic hyper-
tension: a meta-analysis. Ann Pharmacother. 2008;42:1766–71.
175. Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high
blood pressure: mechanisms of action and clinical relevance. Integr Blood
Press Control. 2014;7:71–82.
176. Ried K, Frank OR, Stocks NP. Aged garlic extract lowers blood pressure
in patients with treated but uncontrolled hypertension: a randomised
controlled trial. Maturitas. 2010;67:144–50.
Allium sativum L. 183

177. Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure
in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013;67:64–70.
178. Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated
meta-analysis. Nutr Rev. 2013;71:282–99.
179. Ried K. Garlic lowers blood pressure in hypertensive individuals, regulates
serum cholesterol, and stimulates immunity: an updated meta-analysis
and review. J Nutr. 2016;146:389S–96S.
180. Rohner A, Ried K, Sobenin IA, Bucher HC, Nordmann AJ. A systematic
review and meta-analysis on the effects of garlic preparations on blood
pressure in individuals with hypertension. Am J Hypertens. 2015;28:
414–23.
181. Rose KD, Croissant PD, Parliament CF, Levin MB. Spontaneous spinal
epidural hematoma with associated platelet dysfunction from excessive
garlic ingestion: a case report. Neurosurgery. 1990;26:880–2.
182. Rotzsch W, Richter V, Rassoul F, Walper A. Postprandial lipemia under
treatment with Allium sativum. Controlled double-blind study of subjects
with reduced HDL2-cholesterol. Arzneim-Forschung 1992;42:1223–7
(German).
183. Ruffin J, Hunter SA. An evaluation of the side effects of garlic as an
antihypertensive agent. Cytobios. 1983;37:85–9.
184. Rundquist C. cited in Stoll A & Seebeck AE. Adv Enzymol. 1951;11:377.
185. Sahbaz A, Isik H, Aynioglu O, Gungorduk K, Gun BD. Effect of
intraabdominal administration of Allium sativum (garlic) oil on postoper-
ative peritoneal adhesion. Eur J Obstet Gynecol Reprod Biol. 2014;177:
44–7.
186. Sainani GS, Desai DB, Gorhe NH, et al. Effect of garlic and onion on
important lipid and coagulation parameters in alimentary hyperlipaemia.
J Assoc Phys India. 1979;27:57–64.
187. Saleem ZM, Al-Delaimy KS. Inhibition of Bacillus cereus by garlic
extracts. J Food Prot. 1982;45:1007–9.
188. Samson RR. Effects of dietary garlic and temporal drift on platelet
aggregation. Atherosclerosis. 1982;44:119–20.
189. Schäfer G, Kaschula CH. The immunomodulation and anti-inflammatory
effects of garlic organosulfur compounds in cancer chemoprevention.
Anticancer Agents Med Chem. 2014;14:233–40.
190. Seckiner I, Bayrak O, Can M, Mungan AG, Mungan NA. Garlic supple-
mented diet attenuates gentamicin nephrotoxicity in rats. Int Braz J Urol.
2014;40:562–7.
191. Sendl A, Schliack M, Loser R, et al. Inhibition of cholesterol synthesis
in vitro by extracts and isolated compounds prepared from garlic and wild
garlic. Atherosclerosis. 1992;94:79–85.
192. Sharma VD, Sethi MS, Kumar A, Rarotra JR. Antibacterial property of
Allium sativum Linn.: In vivo & in vitro studies. Indian J Exp Biol.
1977;15:466–8.
184 Allium sativum L.

193. Shashikanth KN, Basappa SC, Sreenivasa Murthy V. A comparative study

of raw garlic extract and tetracycline on caecal microflora and serum
proteins of albino rats. Folia Microbiol (Praha). 1984;29:348–52.
194. Shoetan A, Augusti KT, Joseph PK. Hypolipidemic effects of garlic oil in
rats fed ethanol and a high lipid diet. Experientia. 1984;40:261–3.
195. Sial AY, Ahmad SI. Study of the hypotensive action of garlic extract in
experimental animals. J Pak Med Assoc. 1982;32:237–9.
196. Silagy C, Neil A. Garlic as a lipid lowering agent—a meta-analysis. J R
Coll Physicians Lond. 1994;28:39–45.
197. Simons S, Wollersheim H, Thien T. A systematic review on the influence
of trial quality on the effect of garlic on blood pressure. Neth J Med.
2009;67:212–9.
198. Sobenin IA, Andrianova IV, Fomchenkov IV, Gorchakova TV,
Orekhov AN. Time-released garlic powder tablets lower systolic and
diastolic blood pressure in men with mild and moderate arterial hyperten-
sion. Hypertens Res. 2009;32:433–7.
199. Sodimu O, Joseph PK, Augusti KT. Certain biochemical effects of garlic
oil on rats maintained on high fat-high cholesterol diet. Experientia.
1984;40:78–80.
200. Soffar SA, Mokhtar GM. Evaluation of the antiparasitic effect of aqueous
garlic (Allium sativum) extract in hymenolepiasis nana and giardiasis.
J Egypt Soc Parasitol. 1991;21:497–502.
201. Sreenivasa Murthy V, Shashikanth KN, Basappa SC. Antimicrobial action
and therapeutics of garlic. J Sci Indus Res. 1983;42:410–4.
202. Sreenivasa Murthy V, Sreekantiah KR, Johar DS. Studies on the stability
of allicin & alliin present in garlic. J Sci Indus Res. 1961;20C:292–5.
203. Srivastava KC. Aqueous extracts of onion, garlic and ginger inhibit platelet
aggregation and alter arachidonic acid metabolism. Biomed Biochim Acta.
1984;43:S335–46.
204. Srivastava KC. Effects of aqueous extracts of onion, garlic and ginger on
platelet aggregation and metabolism of arachidonic acid in blood vascular
system: in vitro study. Prostagland Leukot Med. 1984;13:227–35.
205. Steinmetz KA, Kushi LH, Bostick RM, et al. Vegetables, fruits, and colon
cancer in the Iowa Women’s Health Study. Am J Epidemiol. 1994;139:1–
15.
206. Sumiyoshi H, Kanezawa A, Masamoto K, et al. Chronic toxicity test of
garlic extract in rats. J Toxicol Sci. 1984;9:61–75 (Japanese).
207. Sumiyoshi H, Wargovich MJ. Chemoprevention of 1,2-dimethylhydrazine-
induced colon cancer in mice by naturally occurring organosulfur com-
pounds. Cancer Res. 1990;50:5084–7.
208. Sutherland J, Miles M, Hedderley D, et al. In vitro effects of food extracts
on selected probiotic and pathogenic bacteria. Int J Food Sci Nutr. 2009;
60:717–27.
Allium sativum L. 185

209. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatment
for diabetes. Studies in normal and streptozotocin diabetic mice.
Diabetologia. 1990;33:462–4.
210. Takada N, Kitano M, Chen T, et al. Enhancing effects of organosulfur
compounds from garlic and onions on hepatocarcinogenesis in rats:
association with increased cell proliferation and elevated ornithine
decarboxylase activity. Jpn J Cancer Res. 1994;85:1067–72.
211. Takahashi S, Hakoi K, Yada H, et al. Enhancing effects of diallyl sulfide
on hepatocarcinogenesis and inhibitory actions of the related diallyl
disulfide on colon and renal carcinogenesis in rats. Carcinogenesis. 1992;
13:1513–8.
212. Tanaka S, Haruma K, Kunihiro M, et al. Effects of aged garlic extract
(AGE) on colorectal adenomas: a double-blinded study. Hiroshima J Med
Sci. 2004;53:39–45.
213. Tilli CM, Stavast-Kooy AJ, Vuerstaek JD, et al. The garlic-derived
organosulfur component ajoene decreases basal cell carcinoma tumor size
by inducing apoptosis. Arch Dermatol Res. 2003;295:117–23.
214. Tonstad S. Dietary supplementation in the treatment of hyperlipidemia.
Tidsskrift for Den Norske Laegeforening. 1991;111:3398–400 (Review,
Norwegian).
215. Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K. Anticancer
effects of garlic and garlic-derived compounds for breast cancer control.
Anticancer Agents Med Chem. 2011;11:249–53.
216. Uchida Y, Takahashi T, Sato N. The characteristics of the antibacterial
activity of garlic. Jap J Antibiot. 1975;28:638–42 (Japanese).
217. Unnikrishnan MC, Kuttan R. Tumor reducing and anticarcinogenic
activity of selected spices. Cancer Lett. 1990;51:85–9.
218. Unnikrishnan MC, Soudamini KK, Kuttan R. Chemoprotection of garlic
extract toward cyclophosphamide toxicity in mice. Nutr Cancer. 1990;
13:201–7.
219. Vanderhoek JY, Makheja AN, Bailey JM. Inhibition of fatty acid
oxygenase by onion and garlic oils: Evidence for the mechanism by
which these oils inhibit platelet aggregation. Biochem Pharmacol. 1980;29:
3169–73.
220. Varshney R, Budoff MJ. Garlic and heart disease. J Nutr. 2016;146:
416S–21S.
221. Vialettes B. Mediterranean nutrition: a model for the world? Archives des
Maladies du Coeur et des Vaisseaux. 1992;85 Spec No. 2, 135–8 (Review,
French).
222. Viswanathan V, Phadatare AG, Mukne A. Antimycobacterial and
antibacterial activity of Allium sativum bulbs. Indian J Pharm Sci. 2014;
76:256–61.
223. Vorberg G, Schneider B. Therapy with garlic: results of a placebo-
controlled, double-blind study. Br J Clin Prac. 1990;44(Symp. Suppl 69):
7–11.
186 Allium sativum L.

224. Wang ZY, Boice JD Jr, Wei LX, et al. Thyroid nodularity and
chromosome aberration among women in areas of high background
radiation in China. J Nat Cancer Inst. 1990;82:478–85.
225. Warshafsky S, Kamer RS, Sivak SL. Effect of garlic on total serum
cholesterol. A meta-analysis. Ann Int Med. 1993;119:599–605.
226. Weber ND, Andersen DO, North JA, et al. In vitro virucidal effects of
Allium sativum (garlic) extract and compounds. Planta Med. 1992;58:
417–23.
227. Wertheim T. Cited in Stoll A. & Seebeck AE; Adv Enzymol. 1951;
11:377.
228. Xiong XJ, Wang PQ, Li SJ, et al. Garlic for hypertension: A systematic
review and meta-analysis of randomized controlled trials. Phytomedicine.
2015;22:352–61.
229. Yeh YY, Yeh SM. Garlic reduces plasma lipids by inhibiting hepatic
cholesterol and triacylglycerol synthesis. Lipids. 1994;29:189–93.
230. Yoshida S, Kasuga S, Hayashi N, et al. Antifungal activity of ajoene
derived from garlic. Appl Environ Microbiol. 1987;53:615–7.
231. Zeng T, Zhang CL, Zhao XL, Xie KQ. The roles of garlic on the lipid
parameters: a systematic review of the literature. Crit Rev Food Sci Nutr.
2013;53:215–30.
Aloe vera (L.) Burm.f.
(Asphodelaceae/Xanthorrhoeaceae)

(Syns.: A. barbadensis Mill.; A. chinensis Steud. ex Baker; A. elongata Murray;

A. vulgaris Lam.)

Abstract
The name aloe is derived from the Arabic which means ‘bitter and shiny
substance.’ The plant was widely used by the Egyptians, Assyrians and
Mediterranean civilizations and in biblical times. Dried leaf exudate was the
main product used; though the gel was also used. Dioscorides used Aloe as a
purge and to treat wounds, mouth infections, to soothe itching, and to cure sores.
It was called the “Plant of Immortality,” and was a traditional funerary gift for
the Pharaohs of Egypt. The mucilaginous gel from the parenchymatous cells in
the leaf pulp should be distinguished from the bitter yellow exudate (aloe)
originating from the bundle sheath cells, which is used for its purgative effects.
In China, A. vera has been an important medicine for centuries, and is still a
common household remedy. Aloe is strongly aromatic, very bitter and pungent
in taste due to the presence of anthraquinone derivatives, especially aloins (18–
25%), which yields emodin upon cleavage in the intestine. Over a hundred
medical disorders have at times been treated with A. vera, such as arthritis, gout,
acne, cuts, dermatitis, headache, high blood pressure, indigestion, hair loss,
rheumatism, peptic ulcers, mouth diseases, pruritis, psoriasis, and burns. Fresh
leaf juice promotes wound healing on external application, but has also been
used internally for a variety of maladies. Polysaccharides contained in the leaf
gel possess biological activities that include promotion of wound healing,
antifungal activity, hypoglycemic or antidiabetic effects, anti-inflammatory,
anticancer, immunomodulatory and gastroprotective properties. Aloe vera gel
(AVG) powder significantly reduced TC, LDL-C, glucose, HbA1c, and
fructosamine levels of prediabetic and diabetic patients in randomized clinical
trials. Topical treatment with fresh AVG drastically decreased growth of bacteria
in cases with leg ulcers infected with MDR organisms. However, there are also
reports of delayed healing after AVG application in women who had wound
healing complications after cesarean delivery or laparotomy.

© Springer Nature Switzerland AG 2020 187

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_18
188 Aloe vera (L.) Burm.f.

Keywords


Aloë Azebre-vegetal
Echte alö
Elva
Gharita kumari
Gheekawar



Lääkeaaloe Lægealoe
Lu hui
Sibr

Vernaculars: Urd.: Elva (dried latex), Gheekawar; Hin.: Elva, Ghee-kanwar,

Kumar-kuvara; San.: Gharita kumari; Ben.: Ghrita-kumari, Musabbar; Mal.:
Katru-vazha, Kattavala; Mar.: Kora-kanda, Pivalaboel; Tam.: Bhottu-katrozhae,
Chirukattalai, Kattalai, Shotu-katraz-lai; Tel.: Kalabanda; Ara.: Sabbar, Sabr, Sibr,
Subeer; Chi.: Lu hui; Dan.: Lægealoe; Dut.: Aloë; Eng.: Aloe, Barbados aloe;
Fin.: Lääkeaaloe; Fre.: Aloès officinal, Aloès vrai, Aloès vulgaire; Ger.: Echte alö;
Ita.: Aloe vera; Jap.: Aroe, Aroe vera; Maly.: Pohon gaharu; Nep.: Ghiu kumari;
Per.: Darakhte sibr, Sabr-e-zard; Por.: Aloe-dos-barbados, Azebre-vegetal, Babosa,
Cacto-dos-aflitos, Cura-câncros, Erva-azebra, Erva-babosa, Erva-que-arde, Planta-
dos-milagres, Planta-mistério, Planta-que-cura; Rus.: Aloe nastojaščee; Spa.: Ací-
bar, Apabila, Babosa, Gamonita, Hierba babosa, Pita perfoliada, Pita zabila, Sábila,
Zabila (Mexico), Zadiva, Zambana; Swe.: Barbados aloe; Tag.: Sábila-piñá; Tha.:
Hang ta khe; Tur.: Sarısabır; Vie.: Cây aloe vera, Cây lô hội, Cây nha đam.
Description: Aloes are mostly stemless succulent plants with a whorl of elongated,
pointed leaves, with over 360 accepted species [61]; some put the number at 400
species [45]. The name aloe is derived from the Arabic, which means ‘bitter and
shiny substance.’ Some species are tree-like with long stems, while others are small
with thin leaves at ground level. It is a perennial plant, growing wild throughout
most of Africa, southern Arabia and Madagasker, and cultivated in the Mediter-
ranean, Japan, North America, and throughout India. It grows best in a dry chalky
soil, or in a sandy loam as the plant needs warm semi-tropical conditions, but it
cannot tolerate overexposure to the sun. It also requires good drainage to prevent
root rot. It takes about 3 years to reach maturity and continues to produce leaves for
7 or 8 more years. The mucilaginous gel from the parenchymatous cells in the leaf
pulp should be distinguished from the bitter yellow exudate originating from the
bundle sheath cells, which is used for its purgative effects [56]. The fleshy leaves
arise in a rosette from a short stem; in young plants the leaves appear at ground
level, but the stem can grow up to 25 cm long in older plants. There may be 15–30
leaves per plant, the young leaves are more or less erect, and the older, lower ones
more spreading. Leaves are up to 50 cm long and 8–10 cm across at the base,
tapering to a point with saw-like teeth along their margins. In young plants and in
the suckers, which arise from the plant base, leaves are bright green color with
irregular whitish spots on both sides; but the successive leaves have fewer spots and
the fully mature leaves are spotless glaucous grey-green color. A bitter yellow sap
exudes when the leaves are cut, that hardens on exposure to air, and sold as
irregular solidified pieces of waxy texture (2 cm  3 cm). It is this dried exudate
that is mostly used medicinally and is known as aloe. The surface is dull, color
Aloe vera (L.) Burm.f. 189

Fig. 1 Aloe vera, Plant, Prof. Akbar, Original

varying from orange-brown to blackish-brown. The odor is strongly aromatic, taste

very bitter and pungent (Fig. 1).LXXIX
Historical Perspective: The plant was widely used by the Egyptians, Assyrians and
Mediterranean civilizations and in biblical times. Dried leaf exudate was the main
product used; though it seems that the gel was also used. Dioscorides used aloe as a
purge and to treat wounds, mouth infections, to soothe itching, and to cure sores.LVII
It was called the “Plant of Immortality,” and was a traditional funerary gift for the
Pharaohs of Egypt. The dried juice of various species of aloe has been used in medicine
for at least 18 centuries, but before that time its history is somewhat obscured by the use
of the same name to describe the fragrant wood of another plant which was used as
incense.XCI In China, A. vera has been an important medicine for centuries, and is still a
common household remedy [22, 128]. According to Harding [61], its probable origin
was in North America, or the Canary, Madeira and Cape Verde islands. However,
Brandham [16] thinks this is unlikely, and suggests its origin in the upper Nile area in
Sudan or possibly the Arabian Peninsula, where many species of Aloe are native.
Actions and Uses: Aloe is strongly aromatic, very bitter and pungent in taste due
to the presence of anthraquinone derivatives, especially aloins (18–25%), which
yields emodin upon cleavage in the intestine. It is a bitter stomachic in 10–30 mg
dose, laxative in 60–200 mg dose and causes purgation in doses of 300–1,000 mg.
It is moderately irritating, and has a tendency to cause griping, but it does not lose
its efficacy on continued use, and is especially useful in correcting constipating
action of iron medications.LXXIX Ibn al Baitar,LXIX quoting Dioscorides, describes it
as astringent, hypnotic and drying; using 7 g with milk or cold water purges the
intestines of yellow bile, and stops any bleeding. KabeeruddinLXXVII described
leaves pulp as purgative, blood purifier, anti-inflammatory, and moderator of
phlegmatic humours, and the latex (aloe) as laxative/purgative, stomachic, liver
190 Aloe vera (L.) Burm.f.

tonic, emmenagogue, anthelmintic, and promoter of wound healing. Both the pulp
and aloe are assigned a temperament of hot 2° and dry 2°. NadkarniCV described it
stomachic-tonic in small doses, and purgative in large doses, and indirectly
emmenagogue and anthelmintic, and a favorite remedy for intestinal worms in
children. A sweet confection prepared from the pulp is used in piles; and dried latex
dissolved in spirit is used as a hair dye to stimulate hair growth. Over a hundred
medical disorders have at times been treated with A. vera, such as arthritis, gout,
acne, cuts, dermatitis, headache, high blood pressure, indigestion, hair loss,
rheumatism, peptic ulcers, mouth diseases, pruritis, psoriasis, and burns. Some of
the unusual applications include bee stings [90], and jelly-fish sting [15]. There is a
vast folk literature indicating that the fresh juice promotes wound healing on
external application, but has also been taken internally for a variety of maladies
[21]. GhaniL described it as digestive, appetizer, aphrodisiac, and mentions its uses
in Unani medicine to expel bilious humor via loose stools, in abdominal colic, and
combined with other drugs used for the treatment of inflammations, red eye,
chronic fevers, and diabetes. In Ayurveda, dried juice is used in udararoga,
kastãrtava, jvara, and yakrtvikãra.LIX
Aloe ferox is used in southern Africa in commercial products for the treatment of
infections and internal parasites, digestive ailments and injuries [55]. In Trinidad
and Tobago, it is used to treat hypertension by traditional healers [76], while in
Erzurum, eastern Turkey, 52% of the parents of children with Type 1 diabetes use
complementary alternative medicine therapies, especially oral herbal preparations,
including Aloe vera [7]. In the Australian state of Victoria, A. vera is one of the
most popular herbs, others being garlic and green tea [142]. Aloe juice is described
as cleanser, anesthetic, antiseptic, antipyretic, antipruritic, nutrient, moisturizer, and
vasodilator, and also possesses anti-inflammatory properties. Internal usage ranges
from treatment of coughs to constipation, and externally it is used for burns, for
conditioning the skin and even for headaches.CXXXXIII Topical application can be
effective for genital herpes, psoriasis, HPV, seborrheic dermatitis, aphthous stom-
atitis, xerosis, lichen planus, frostbite, burns, wound healing and inflammation [45].
In the Philippines, the juice of fleshy leaves is mixed with wine and applied to scalp
to preserve hair.CXVII In Mexico, leaves are used to treat burns, bruises, skin irri-
tations and even leprosy [40]. In Guyana, whole plant juice mixed with raw cow’s
milk is used to treat asthma, pneumonia, biliousness, and cold. Juice mixed with
grated cassava and fresh fat is applied to treat ringworm and acute dermatitis. Leaf
juice is used to stop bleeding from cuts, as hair-wash, and as laxative, antimalarial,
for stomach pain and dysmenorrhea.XXXIV Anthraquinone derivatives of the leaves
cause irritation and inflammation of pelvic organs at high doses and may possibly
be at the origin of its oxytocic and abortive properties [43].
Phytoconstituents: Phytochemicals identified in the lyophilized leaf gel include
various phenolic acids/polyphenols, phytosterols, fatty acids, indoles, alkanes,
pyrimidines, alkaloids, organic acids, aldehydes, dicarboxylic acids, ketones, and
alcohols [89]. The dried exudate is rich in anthraquinone glycosides, accounting for
its use as cathartic.CXXXXII Fresh juice also contains lesser concentrations of these
Aloe vera (L.) Burm.f. 191

active principles along with other common constituents, such as sugars, polysac-
charides, amino acids, inorganic salts, low concentrations of vitamins and water.
Aloe vera gel (AVG) is devoid of anthraquinone glycosides, which are responsible
for the strong laxative effects of aloes, but it contains polysaccharide glucomannan,
which is believed to be responsible for its emollient effect.
Pharmacology: Polysaccharides contained in the leaf gel possess biological
activities that include promotion of wound healing, antifungal activity, hypo-
glycemic or antidiabetic effects, anticancer, anti-inflammatory, immunomodulatory
and gastroprotective properties [60]. Topical application of AVG enhanced healing
of surgical wounds in rats [92], and 2nd degree burns in guinea pigs, produced
significantly higher contraction and granulation of the wounds than 1% silver
sulfadiazine cream [71]. Rodriguez-Bigas et al. [108] reported significant reduction
in the average healing time of full thickness burn wounds in guinea pigs to 30-days
in AVG extract-treated animals, from 50-days in the control group; aloe-emodin
was also effective in improving burn wound healing in mice [79]. Davis et al. [30]
reported both oral and topical application improved wound healing in mice; oral
being a little more effective; while topical application of AVG to surgical incisions
significantly improved re-epithelialization and angiogenesis, compared to applica-
tion of thyroid hormone cream and silver sulfadiazine in rats [86, 127], and an
ointment increased concentration of hydroxyproline in partially transected calcaneal
tendons [6]. Topical application of the supernatant fraction of 50% ethanol extract
decreased croton oil-induced ear-swelling by 29% [33], and the precipitate fraction
decreased the wound diameter by an average of 47%, but the supernatant had
little or no wound healing activity [32]. A. vera cream application combats local
vasoconstrictive effects of thromboxane in frostbite, and improves tissue survival
[84, 141]. Robson et al. [107] reported antibacterial and antiprostaglandin effects
with preserved vascular supply to the dermis in experimentally burned animals;
Cera et al. [19] also successfully used a commercial A. vera cream (Dermaide Aloe
Cream®) to treat severe accidental thermal burns in dogs, which prevented dermal
ischemia and infection by P. aeruginosa. Two of the writers of this report were
professors of plastic surgery, who performed biopsies to test for Pseudomonas
infection and to determine PGs and TXs. Cera et al. [18] reported extensive
re-epithelialization by 7th day and complete recovery in 30-days, after topical
application of A. vera cream to a Rhesus monkey with full-thickness burns over
70% of his body after accidental scalding.
Lushbaugh and Hale [82], of the U.S. Atomic Energy Commission, exposed 20
albino rabbits to b-radiation, and applied different treatments to quadrants, and
visually observed them for 58-days. Improvement in healing in A. vera treated
quadrant with accelerated ulceration, followed by rapid epithelialization and com-
plete healing, without scabbing and telangiectasis occurred at the end of two
months treatment; healing did not occur even after four months in the control areas.
However, Ashley et al. [9], of the U.S. Army, after extensive clinical and laboratory
studies suggested that the plant does not have any useful curative properties. Other
192 Aloe vera (L.) Burm.f.

studies, though, involving the use of rabbits [109] and mice [53] reported signifi-
cant positive results in healing of thermal burns and wounds.
AVG inhibited (79%) in vitro growth of E. faecalis [12], and preadministration
to BALB/c mice eliminated E. coli from the peritoneal cavity in the early stage of
the infection [125], markedly enhanced bacterial clearance, ameliorated multiple
organ dysfunction syndrome, attenuated increases in the levels of TNF-a, IL-1b,
and IL-6, and reversed the lethality induced by cecal ligation and puncture [140].
Lorenzetti et al. [80] found the fresh ‘juice’ from cut leaves inhibiting S. aureus, but
the activity was unstable unless the extract was refrigerated, or heated and then
freeze-dried; freeze-dried extract inhibited some species of Staphylococcus,
Corynebacterium, Streptococcus and Salmonella, but the exudate components, such
as aloe-emodin, emodin and chrysophanic acid did not inhibit S. aureus. Robson
et al. [106] reported that P. aeruginosa was inhibited by the gel at concentrations of
60–70%. Grindlay and Reynolds [56], and Klein and Penneys [74] presented
published reports supporting A. vera for its antibacterial and antifungal properties,
and its effectiveness in the treatment of radiation ulcers and stasis ulcers in man and
burn and frostbite injuries in animals. AVG also significantly inhibited HSV-1
growth in Vero cell line [104]. Both aqueous and ethanol extracts of dried leaves
were ineffective against C. albicans and A. niger [116].
A. vera with honey can modulate tumor growth by reducing cell proliferation
and increasing apoptosis susceptibility, and may reduce tumor mass and metastasis
rates [129]. A processed AVG (devoid of anthraquinones) significantly reduced
AOM-initiated mouse colon carcinogenesis by inhibiting inflammation and cell
cycle progression [67]. Oral, topical and a combination of topical and oral treatment
of mice significantly reduced the incidence, cumulative number, tumor yields and
tumor burden of DMBA-induced skin papillomas [20, 114]. The leaf extract
administered to Swiss mice for 15-days, followed by full body irradiation, signif-
icantly increased CAT and SOD in the skin, and GSH levels in the liver and blood,
compared to untreated control animals [54]. AVG synergistically inhibited human
breast (MCF-7) and cervical (HeLa) cancer cells viability, in combination with
cisplatin [66]. Aloe-emodin (an anthraquinone) given to mice in which tumor cells
had been injected, inhibited growth of malignant tumors. Other animal data also
suggest that components of aloe inhibit tumor growth and improve survival.
In a carrageenan-inflamed synovial pouch model of inflammation, a 10% A. vera
treatment of synovial pouches reduced vascularity by 50% and the number of mast
cells in synovial fluid by 48%. There were an increased number of fibroblasts,
suggesting that A. vera stimulated fibroblasts for growth and repair of the synovial
pouch [35]. Applied topically, administered intraperitoneally or in combination also
modulates the inflammatory response to Salmonella mediated inflammation; sug-
gestive of the potential of A. vera to decrease peroxidative damage via a decrease in
the levels of monokines (TNF-a, IL-1 and IL-6), and an increase in the level of SOD
[105]. However, aloin and aloe-emodin, two anthraquinones present in the exudate,
are proposed to cause anti-inflammatory effect by inhibiting iNOS, and COX-2
expression [96]. AVG produced an insignificant decrease in pain response in the
tail-flick test, but significantly decreased the second phase of formalin-induced pain,
Aloe vera (L.) Burm.f. 193

suggesting a peripheral rather than a central mechanism of action [103]. Ethanol

leaves extract also increased threshold for nociception in thermal hyperalgesia,
chemical hyperalgesia, and in sciatic nerve ligation-induced neuropathic pain [70].
Dried AVG powder for 90-days caused a modest decrease in body weight but a
significant reduction in subcutaneous, visceral and body fat, and serum lipids of
HFD-induced obese rats [87], and significantly decreased TC and CRP, and pre-
vented fatty streaks formation in the aorta [28]. Supplementation of HFD-fed rats
with AVG in combination with Lactobacillus rhamnosus decreased serum TC,
VLDL-C, LDL-C, and triacylglycerol by more than 30%, and increased HDL-C by
12% [75]. Pretreatment with AVG extract for one week significantly suppressed
ethanol-induced accumulation of liver TGs level [115]. Oral administration of AVG
[100], and processed AVG reduced FBG in diet-induced obesity in C57BL/6J mice,
with a significant decrease in plasma insulin, and lowered TGs levels in liver and
plasma [73]. Administration of an AVG formulation for 30-days to female rats with
letrozole-induced PCOS-like state, significantly reduced plasma TGs and LDL-C
with an increase in HDL-C, and caused reversion of abnormal estrous cyclicity,
glucose intolerance and lipid metabolizing enzymes to normal [37]. Supplementation
with the polysaccharide exerts a potent hepatoprotective effect against chronic
alcohol-induced liver injury [26], and attenuates APAP-hepatitis by decreasing
oxidative stress and restoring hepatic GSH [132]. Aqueous leaf extract produced
sedative and hypnotic effects in rats [1], significantly enhanced learning and memory,
and alleviated depression in mice [59], and also markedly attenuated withdrawal
syndrome in morphine-dependent female rats [118]. Processed AVG was an effective
immunomodulator and prevented CP toxicity in mice [68]. Coadministration of an
extract prevented indomethacin gastropathy in rats, including gastric ulcers, reduced
MDA, TNF-a, and IL-18 levels [133].
Clinical Studies: In an RCT of prediabetic metabolic syndrome patients, two
standardized preparations of AVG were tested. AVG powder (AC952) caused
significant reduction in TC, LDL-C, glucose, and fructosamine levels; whereas the
AVG powder standardized with 2% aloesin group (UP780), significantly reduced
HbA1c, fructosamine, FBG, insulin, and HMA [38]. Eight-weeks intake of AVG
significantly improved FBG, HbA1c, and lipid profile of prediabetic Iranian volun-
teers [4]. A meta-analysis of clinical trials showed that A. vera significantly
decreased FBG and HbA1c in prediabetic and diabetic patients [39]. One table-
spoonful of A. vera juice twice daily for at least 2-weeks, significantly lowered FBG
and TGs levels in treatment-naïve [139], as well as an adjunct to antidiabetic
therapy [17] of Thai diabetic patients. Addition of the ‘Husk of Isabgol’ and Aloe
vera to the diet of five thousand Indian patients with atheromatous heart disease
significantly reduced TC, TGs, total lipids, fasting, and post prandial blood sugar
level in diabetic patients, increased HDL-C, and reduced frequency of anginal
attacks over a five-years follow-up; most benefitted patients were the diabetics,
without addition of any antidiabetic drug [2]. In an RCT, a commercial extract
(AVH200®) reduced overall gastrointestinal symptoms severity in Swedish IBS
194 Aloe vera (L.) Burm.f.

patients [122], and a syrup reduced symptoms in Iranian patients with GERD, but
with a higher frequency of belching [94]. Vogler and Ernst [131], after reviewing
clinical studies, concluded that it is useful as an adjunct for lowering blood glucose
in diabetic patients, and to reduce lipid levels in patients with hyperlipidemia;
topical application, however, is not an effective prevention for radiation-induced
injuries, but might be effective for genital herpes and psoriasis.
El-Zawahry et al. [42] applied fresh AVG on chronic leg ulcers of 5–15 years
standing, with apparently successful results; and encouraging results in treating hair
loss due to seborrhea and control of acne vulgaris in three women patients. Growth
of bacteria in thirty cases with leg ulcers infected with MDR organisms, topically
treated with fresh AVG, decreased from 100% (30 cases) to 6.7% (2 cases) by day
11; whereas, 30 age and sex-matched controls treated with topical antibiotics did
not show any decrease in the bacterial growth [11]. AVG dressing significantly
reduced dressing pain intensity in superficial 2nd degree burn wounds [130], and
enhanced epithelialization and granulation tissue [69]. AVG application healed
chronic wounds in 28 (93%) elderly patients after three-months treatment compared
to 14 (47%) of conventionally treated patients [10]. Healing score of cesarean
operation wound was significantly better after 24 h in patients with A. vera dressing
than the controls, but insignificant after eight days [88]. Schmidt and Greenspoon
[117] reported delayed healing after using AVG in women who had wound healing
complications after cesarean delivery or laparotomy. Topical application of AVG
on labia minora for 8-weeks in female patients with erosive (83%) and ulcerative
(17%) vulval lichen planus lesions, clinically improved by at least 50% in fourteen
(82%) out of 17 patients, compared to one in 17 placebo-treated patients [102].
AVG was also as effective as benzyl benzoate in the treatment of scabies in 30
patients [93]. Topical application of A. vera extract 0.5% in a hydrophilic cream for
sixteen-weeks cured twenty-five out of thirty patients of slight to moderate chronic
plaque-type psoriasis [123]. Prophylactic use of A. vera lotion in cancer patients
undergoing radiation therapy reduced the intensity of radiation-induced dermatitis
[58], but Ahmadloo et al. [3] reported no such benefits; and Williams et al. [134],
after two Phase III trials had also reported that AVG did not protect against radi-
ation therapy-induced dermatitis in women receiving breast or chest wall irradia-
tion. However, breast cancer patients in the U.S. undergoing radiotherapy are
routinely provided A. vera gel to be locally applied after the radiotherapy sessions.
Oral A. vera juice with topical AVG application, and intralesional injection of
hydrocortisone and hyaluronidase for 6-weeks with antioxidant supplements, for
3 months were equally effective in patients with oral submucous fibrosis [5].
Application of A. vera 3% ointment significantly benefitted patients with radiation
proctitis [113]. Combination therapy with tretinoin and AVG was significantly
more effective in reducing noninflammatory, inflammatory, and total lesion scores
in an 8-week prospective RCT of 60 Iranian subjects with mild to moderate acne
vulgaris [112]. In an RCT of 30-day period in patients with plaque and gingivitis,
there was no statistically significant difference among those using dentifrice con-
taining A. vera compared to the fluoridated dentifrice, though both significantly
reduced plaque and gingivitis [36].
Aloe vera (L.) Burm.f. 195

Collins and Collins [23] had for the first time treated roentgen dermatitis on the
forehead of a woman with A. vera that had worsened with various treatments. She
had to wear gloves at night to prevent scratching of the wound due to pain and
itching. Application of macerated gel, bound in place with wax paper and a ban-
dage, completely subsided burning sensation and itching within 24 h, and by
5-weeks a complete regeneration of skin without a scar. Later, Wright [136]
reported good results in two cases of long-standing X-ray ulceration, including
almost complete healing of accidental acute radiation dermatitis on a doctor’s hand
after 3-weeks of treatment. Similar results on radiation ulcers with rapid epithe-
lialization and relief in pain and discomfort were reported by Loveman [81], and
Fine and Brown [46]. Crewe [25] used pulp to treat eczema with some success, and
also obtained promising results treating ulcers on amputation stumps. Mandeville
[83] observed a definite and rapid relief of pain while treating 5 cases of radiation
ulcers. One case of ulceration of the mouth due to radium and X-rays reportedly
healed with the gel, and the patient survived 2 more years without ever having any
problem. In this case the patient held the gel in mouth for an average 7 h a day for
8 weeks. Singh et al. [120] reported improvement in burning sensation, mouth
opening, tongue protrusion and cheek flexibility in patients with oral submucous
fibrosis after three-months treatment with AVG and physiotherapy than with
antioxidants.
All these case reports were critisized for being isolated cases and lacking con-
trols in the studies and thus started the era of experimental studies. Rowe [111], in
an attempt to substantiate these reports investigated the effects of fresh A. vera gel
on 3rd degree radiation burns in rats under laboratory conditions. His results
revealed 50% lesions treated with the gel showed increased healing rate and 36%
showed virtually complete healing, twice the number showing improvement with
saline. However, another group showed opposite results, better with saline than
with the gel. Rowe et al. [110] in further experiments in rats observed 64% of rats
showing increased healing rate, 9.5 times the number in the control group. They
also observed that if beneficial effect did not appear within two weeks, then further
treatment was unlikely to be of any benefit. Another interesting observation was
improvement by partially decomposed leaves pulp in 87.5% of the rats tested. They
also obtained 100% complete healing in 8 rats within 6 days by fresh rind from one
of their shipments, but the rind from two other shipments gave negative results.
A qualified dentist Bovik [15] experimented on himself; after a complete gin-
givectomy, he treated one side with A. vera juice and observed cessation of pain
and a rapid healing compared to the conventional periodontal pack applied to the
other side. Later, Payne [98] reported accelerated healing in five patients of peri-
odontal flap surgery treated with AVG, without the patient knowing which part had
been treated with the gel; patients reported less pain and swelling from those
quadrants. Application of AVG after scaling and root planing in patients with type 2
DM and chronic periodontitis, was significantly more effective in clinical attach-
ment and other parameters [101]. Nimma et al. [91] reported enhanced healing by
A. vera of post dental extraction sockets. Fulton [52] used polyethylene oxide
(PEO) gel wound dressing on one side of the face, and the other half was treated
196 Aloe vera (L.) Burm.f.

with a PEO gel dressing saturated with stabilized aloe vera (Vigilon®), after
full-face dermabrasion. Overall, wound healing was approximately 72 h faster on
the aloe-treated side; accelerated wound healing reduced bacterial contamination,
subsequent keloid formation, and/or pigmentary changes. Fulton [51] also reported
good results using Vigilon® after dermabrasion-Loo-punch-excision of acne-
induced osteoma cutis.
Mechanisms of Action: Various mechanisms have been proposed for the healing
properties of A. vera. Since no single definitive active ingredient has been identi-
fied, a synergistic effect between various components and the polysaccharide base is
suggested [63, 77, 78]. A common belief is that the action is due to its moisturizing
and emolient effects [44, 85, 119, 121]. Juice possesses some activity in its fresh
state, but there is considerable doubt whether this activity is retained during storage.
Commercial processors claim that a ‘stabilized’ product is incorporated in a wide
variety of preparations including juices, gels, ointments, creams, lotions and
shampoos [47]; however, tests failed to verify any beneficial effects of a ‘stabilized’
AVG on human cells [135]. Fluid from fresh leaf significantly promotes attachment
and growth of normal human cells grown in artificial culture and enhances healing
of wounded monolayers of such cells. However, the ‘stabilized’ commercial pro-
duct not only failed to induce such effects but actually proved toxic to such cultured
cells. Aloe vera contains several active ingredients, including a carboxypeptidase
that inactivates bradykinin in vitro, salicylates, and a substance that inhibits TX
formation in vivo [74].
Aloe vera is also suggested to possess anti-inflammatory ingredients, and a number
of Japanese workers have found anti-inflammatory compounds in Aloe species other
than A. vera. Yagi et al. [137] observed antibradykinin activity in A. saponaria, while
Fujita et al. [49, 50] showed bradykinase and carboxypeptidase activity in
A. arborescens. Although, such compounds have not been observed in A. vera, but it is
presumed by some that such compounds may also be responsible for A. vera activity.
Robson et al. [106] reported the presence of salicylate, lactate and magnesium in
A. vera and suggested that the anesthetic property could either be due to an aspirin-like
effect or the high magnesium content, or possibly both acting synergistically. The
antiprostaglandin activity is suggested as the basis for anti-inflammatory effect, and
Penneys [99] described inhibition of AA oxidation in vitro by a number of vehicle
components used as carrier bases for the active drugs. The percent inhibition,
however, increased with the increased concentration of aloe. Robson et al. [106]
reported improved perfusion of capillaries and reduction in TXB2 and PGF2 by AVG,
similar to methylprednisolone and methimazole effect in thermal burns. Heggers
and Robson [62] suggested the presence of sufficient quantities of anthraquinone
and related compounds, such as barbaloin and aloe-emodin, may act as false sub-
strate inhibitors blocking prostanoid synthesis due to similarity in their chemical
structure to prostaglandin substrates. Davis et al. [29] confirmed that broad-spectrum
anti-inflammatory activity was dependent on the presence of anthraquinones. Con-
trarily, Davis and colleagues [34] also found that the decolorized Aloe (without
anthraquinones) was more effective topically in croton oil-induced edema than the
Aloe vera (L.) Burm.f. 197

colorized Aloe, an indication that Aloe’s anti-inflammatory activity via oral and
topical routes may involve different mechanisms. Davis and Maro [31] also suggested
that the anti-inflammatory potential may be due to the presence of gibberellin or a
gibberellin-like substance, because they both produced anti-inflammatory activity by
inhibiting PMNL infiltration into a site of gelatin-induced inflammation in diabetic
mice. Low molecular constituents of an aqueous gel-extract also inhibit release of
ROS by PMA-stimulated human PMNL [124], and ethanol extract exhibited signif-
icant in vitro inhibitory activity against AChE, BChE and LOX enzymes [72].
Increased LDL receptors expression, and decreased cholesterol 7a-hydroxylase
mRNA expression levels may be responsible for its hypocholesterolemic effect [75].
Human A/Es, Allergy and Toxicity: Diarrhea, hypokalemia, pseudomelanosis
coli, kidney failure, as well as phototoxicity and hypersensitive reactions are
reported as adverse effects of aloe ingestion [57]. Hunter and Frumkin [65] reported
severe burning sensation in three women and one man (aged 41–65 years), after
application of A. vera or vitamin E preparations to the skin, following chemical peel
or dermabrasion. The dermatitis resolved slowly over a period of three months or
more. Contact dermatitis was also the only adverse effect of AVG in women
receiving breast or chest wall irradiation [134]. A Spanish man, who had been
drinking A. vera tea for 2–4 weeks, developed severe acute hepatitis and liver
failure, which resolved after stopping the tea [27]. An MS patient developed toxic
hepatitis after concomitant treatment with interferon-b and A. vera [64]. Similar
cases of hepatitis have been reported from elsewhere [13, 97]. In 2002, the FDA
declared aloe extract and aloe flower extract in stimulant laxative ingredients, as not
generally recognized safe and effective [48].
Animal Toxicity: Administration of A. vera whole-leaf extract (not the pulp or
dried aloe), to F344/N rats and B6C3F1 mice for 2-years in drinking water,
decreased survival of female rats in the 1.5% dose group. Incidences of adenomas
and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending
and transverse colon were also significantly higher than in control male and female
rats in the 1 and 1.5% dose groups, an indication that the whole-leaf extract could act
as an intestinal irritant and a carcinogen of the large intestine [14]. A dose-dependent
increase in large intestinal tumors in F344 rats chronically exposed to non-
decolorized whole leaf extract in drinking water was also reported [95]. Ethanol leaf
gel extract significantly reduced testes weight, serum testosterone, sperm count, and
fertility of rats [8]. The International Agency for Research on Cancer has classified
A. vera as a possible human carcinogen (Group 2B) [57]. Nevertheless, according to
the Cosmetic Ingredient Review Expert Panel Report of 2007 [24] aloin (an
anthraquinone) did not produce tumors when included in the diet of mice for
20-weeks, nor did aloin increase incidence of DMH-induced colorectal tumors.
CYP450 and Potential for Drug-Herb Interactions: Yang et al. [138] reported
that systemic exposure of cyclosporine (CSP) to A. vera leaf juice significantly
decreased blood concentration of CSP in rats by activating p-glycoprotein. Major
metabolites of the leaf juice, aloe-emodin glucuronides and rhein sulfates/
glucuronides, in vitro activated CYP3A4. However, rhein, in vitro inhibited
198 Aloe vera (L.) Burm.f.

CYP2E1, CYP3A and CYP2C9, and to some extent CYP1A2 and CYP2D6,
prospecting drug interactions with other drugs on systemic use [126]. Two com-
mercially available A. vera juice products are also reported to inhibit CYP3A4 and
CYP2D6 [41].
Commentary: The wound healing, emollient, anti-inflammatory, and beneficial
effects on lipids, glucose and blood pressure are generally supported by pharma-
cological and clinical studies. However, there are some studies casting doubts on
these observations, and these inconsistencies must be resolved for a consensus
verdict of its benefits.

References
1. Abdollahnejad F, Mosaddegh M, Nasoohi S, et al. Study of sedative-
hypnotic effects of Aloe vera L. aqueous extract through behavioral
evaluations and EEG recording in rats. Iran J Pharm Res. 2016;15:293–300.
2. Agarwal OP. Prevention of atheromatous heart disease. Angiology. 1985;
36:485–92.
3. Ahmadloo N, Kadkhodaei B, Omidvari S, et al. Lack of prophylactic
effects of Aloe vera gel on radiation induced dermatitis in breast cancer
patients. Asian Pac J Cancer Prev. 2017;18:1139–43.
4. Alinejad-Mofrad S, Foadoddini M, Saadatjoo SA, Shayesteh M. Improve-
ment of glucose and lipid profile status with Aloe vera in prediabetic subjects:
a randomized controlled-trial. J Diabetes Metab Disord. 2015;14:22.
5. Anuradha A, Patil B, Asha VR. Evaluation of efficacy of Aloe vera in the
treatment of oral submucous fibrosis—a clinical study. J Oral Pathol Med.
2017;46:50–5.
6. Aro AA, Nishan U, Perez MO, et al. Structural and biochemical alterations
during the healing process of tendons treated with Aloe vera. Life Sci.
2012;91:885–93.
7. Arýkan D, Sívríkaya SK, Olgun N. Complementary alternative medicine
use in children with type 1 diabetes mellitus in Erzurum, Turkey. J Clin
Nurs. 2009;18:2136–44.
8. Asgharzade S, Rafieian-Kopaei M, Mirzaeian A, Reiisi S, Salimzadeh L.
Aloe vera toxic effects: expression of inducible nitric oxide synthase
(iNOS) in testis of Wistar rat. Iran J Basic Med Sci. 2015;18:967–73.
9. Ashley FL, O’Loughlin BJ, Peterson R, et al. The use of Aloe vera in the
treatment of thermal and irradiation burns in laboratory animals and
humans. Plastic Reconst Surg. 1957;20:383–96.
10. Avijgan M, Kamran A, Abedini A. Effectiveness of Aloe vera gel in
chronic ulcers in comparison with conventional treatments. Iran J Med Sci.
2016;41:S30.
11. Banu A, Sathyanarayana B, Chattannavar G. Efficacy of fresh Aloe vera
gel against multidrug resistant bacteria in infected leg ulcers. Australas
Med J. 2012;5:305–9.
Aloe vera (L.) Burm.f. 199

12. Bhardwaj A, Ballal S, Velmurugan N. Comparative evaluation of the

antimicrobial activity of natural extracts of Morinda citrifolia, papain and
Aloe vera (all in gel formulation), 2% chlorhexidine gel and calcium
hydroxide, against Enterococcus faecalis: an in vitro study. J Conserv
Dent. 2012;15:293–7.
13. Bottenberg MM, Wall GC, Harvey RL, Habib S. Oral Aloe vera-induced
hepatitis. Ann Pharmacother. 2007;41:1740–3.
14. Boudreau MD, Mellick PW, Olson GR, et al. Clear evidence of carcinogenic
activity by a whole-leaf extract of Aloe barbadensis Miller (Aloe vera) in
F344/N rats. Toxicol Sci. 2013;131:26–39.
15. Bovik EG. Aloe vera. Panacea or old wives’ tales? Texas Dental J. 1966;84:
13–6.
16. Brandham PE. Jodrell Laboratory, Royal Botanic Gardens, Kew, Surrey,
U.K., quoted by Grindlay D and Reynolds T in J Ethnopharmacol. 1986;16:
117–51.
17. Bunyapraphatsara N, Yongchaiyudha S, Rungpitarangsi V, Chokechaijaroen-
porn O. Antidiabetic activity of Aloe vera L. juice II. Clinical trial in diabetes
mellitus patients in combination with glibenclamide. Phytomedicine. 1996;3:
245–8.
18. Cera LM, Heggers JP, Hagstroms WJ, Robson MC. Therapeutic prortocol of
Aloe vera for thermally injured animals and its successful use in an extensively
burned Rhesus monkey. J Am Anim Hosp Assoc. 1982;18:633–8.
19. Cera LM, Heggers JP, Robson MC, Hagstrom WJ. The therapeutic efficacy
of Aloe vera cream (Dermaide Aloe, Reg.Trademark) in thermal injuries:
two case reports. J Am Anim Hosp Assoc. 1980;16:768–72.
20. Chaudhary G, Saini MR, Goyal PK. Chemopreventive potential of Aloe
vera against 7,12-dimethylbenz(a) anthracene induced skin papillomage-
nesis in mice. Integr Cancer Ther. 2007;6:405–12.
21. Cheney RH. Aloe drug in human therapy. Quat J Crude Drug Res. 1970;10:
1523–30.
22. Cole HN, Chen KK. Aloe vera in oriental dermatology. Arch Dermatol
Syphilology. 1943;47:250.
23. Collins CE, Collins C. Roentgen dermatitis treated with fresh whole leaf of
Aloe vera. Am J Roentg. 1935;33:396–7.
24. Cosmetic Ingredient Review Expert Panel. Final report on the safety
assessment of Aloe andongensis extract, Aloe andongensis leaf juice, Aloe
arborescens leaf extract, Aloe arborescens leaf juice, Aloe arborescens
leaf protoplasts, Aloe barbadensis flower extract, Aloe barbadensis Leaf,
Aloe barbadensis leaf extract, Aloe barbadensis leaf juice, Aloe bar-
badensis Leaf Polysaccharides, Aloe barbadensis leaf water, Aloe ferox
leaf extract, Aloe ferox leaf Juice, and Aloe ferox leaf juice extract. Int J
Toxicol. 2007;26 Suppl 2:1–50.
25. Crewe JE. The external use of Aloes. Minnesota Med. 1937;20:670–3.
200 Aloe vera (L.) Burm.f.

26. Cui Y, Ye Q, Wang H, et al. Hepatoprotective potential of Aloe vera

polysaccharides against chronic alcohol-induced hepatotoxicity in mice.
J Sci Food Agric. 2014;94:1764–71.
27. Curciarello J, De Ortúzar S, Borzi S, Bosia D. Severe acute hepatitis associated
with intake of Aloe vera tea. Gastroenterol Hepatol. 2008;31:436–8.
28. Dana N, Javanmard SH, Asgary S, Asnaashari H, Abdian N. The effect
of Aloe vera leaf gel on fatty streak formation in hypercholesterolemic
rabbits. J Res Med Sci. 2012;17:439–42.
29. Davis RH, Leitner MG, Russo JM, Byrne ME. Anti-inflammatory activity
of Aloe vera against a spectrum of irritants. J Am Podiat Med Assoc. 1989;
79:263–76.
30. Davis RH, Leitner MG, Russo JM, Byrne ME. Wound healing. Oral and
topical activity of Aloe vera. J Am Podiat Med Assoc. 1989;79:559–62.
31. Davis RH, Maro NP. Aloe vera and gibberellin. Anti-inflammatory activity
in diabetes. J Am Podiat Med Assoc. 1989;79:24–6.
32. Davis RH, Parker WL, Samson RT, Murdoch DP. Isolation of a stimulatory
system in an Aloe extract. J Am Podiat Med Assoc. 1991;81:473–8.
33. Davis RH, Parker WL, Samson RT, Murdoch DP. The isolation of an
active inhibitory system from an extract of Aloe vera. J Am Podiat Med
Assoc. 1991;81:258–61.
34. Davis RH, Rosenthal KY, Cesario LR, Rouw GA. Processed Aloe vera
administered topically inhibits inflammation. J Am Podiat Med Assoc.
1989;79:395–7.
35. Davis RH, Stewart GJ, Bregman PJ. Aloe vera and the inflamed synovial
pouch model. J Am Podiat Med Assoc. 1992;82:140–8.
36. de Oliveira SM, Torres TC, Pereira SL, Mota OM, Carlos MX. Effect of a
dentifrice containing Aloe vera on plaque and gingivitis control. A double-
blind clinical study in humans. J Appl Oral Sci. 2008;16:293–6.
37. Desai BN, Maharjan RH, Nampoothiri LP. Aloe barbadensis Mill.
formulation restores lipid profile to normal in a letrozole-induced polycystic
ovarian syndrome rat model. Pharmacognosy Res. 2012;4:109–15.
38. Devaraj S, Yimam M, Brownell LA, et al. Effects of Aloe vera supplemen-
tation in subjects with prediabetes/metabolic syndrome. Metab Syndr Relat
Disord. 2013;11:35–40.
39. Dick WR, Fletcher EA, Shah SA. Reduction of fasting blood glucose and
hemoglobin A1c using oral Aloe vera: a meta-analysis. J Altern Comple-
ment Med. 2016;22:450–7.
40. Diez-Martinez SD. La Zabila. Communicado No. 46 sobre recursos
bioticos potenciales del pais INIREB, Mexico, 1981.
41. Djuv A, Nilsen OG. Aloe vera juice: IC50 and dual mechanistic inhibition
of CYP3A4 and CYP2D6. Phytother Res. 2012;26:445–51.
42. El-Zawahry M, Hegazy MR, Helal M. Use of Aloe in treating leg ulcers
and dermatoses. Int J Dermatol. 1973;12:68–73.
Aloe vera (L.) Burm.f. 201

43. Farnsworth NR, Bingel AS, Cordell GA, et al. Potential value of plants as
a source of new antifertility agents. I. J Pharmaceut Sci. 1975;64:535–98.
44. Feil C. Aloe cosmetics. Bestways (USA) August 1980, p. 108.
45. Feily A, Namazi MR. Aloe vera in dermatology: a brief review. G Ital
Dermatol Venereol. 2009;144:85–91.
46. Fine AF, Brown S. Cultivation and clinical application of Aloe vera leaf.
Radiology. 1938;31:735–6.
47. Flagg J. Am Perfumer Aromatics. 1959;74:27–8.
48. Food and Drug Administration. HHS: status of certain additional
over-the-counter drug category II and III active ingredients. Final rule.
Fed Regist. 2002;67:25–7.
49. Fujita K, Ito S, Teradaira R, Beppu H. Properties of a carboxypeptidase
from aloe. Biochem Pharmacol. 1979;28:1261–2.
50. Fujita K, Teradaira R, Nagatsu T. Bradykinase activity of aloe extract.
Biochem Pharmacol. 1976;25:205.
51. Fulton JE Jr. Dermabrasion-Loo-punch-excision technique for the treatment
of acne-induced osteoma cutis. J Dermat Surg Oncol. 1987;13:655–9.
52. Fulton JE Jr. The stimulation of postdermabrasion wound healing with
stabilized Aloe vera gel-polyethylene oxide dressing. J Dermat Surg Oncol.
1990;16:460–7.
53. Goff S, Levenstein I. Measuring the effects of topical preparations upon the
healing of skin wounds. J Soc Cosmetic Chemists. 1964;15:509–18.
54. Goyal PK, Gehlot P. Radioprotective effects of Aloe vera leaf extract on
Swiss albino mice against whole-body gamma irradiation. J Environ Pathol
Toxicol Oncol. 2009;28:53–61.
55. Grace OM, Simmonds MS, Smith GF, van Wyk AE. Therapeutic uses of
Aloe L. (Asphodelaceae) in southern Africa. J Ethnopharmacol. 2008;119:
604–14.
56. Grindlay D, Reynolds T. The Aloe vera phenomenon: a review of the
properties and modern uses of the leaf parenchyma gel. J Ethnopharmacol.
1986;16:117–51 (Review).
57. Guo X, Mei N. Aloe vera: a review of toxicity and adverse clinical effects.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2016;34:77–96.
58. Haddad P, Amouzgar-Hashemi F, Samsami S, Chinichian S, Oghabian MA.
Aloe vera for prevention of radiation-induced dermatitis: a self-controlled
clinical trial. Curr Oncol. 2013;20:e345–8.
59. Halder S, Mehta AK, Mediratta PK. Aloe vera improves memory and
reduces depression in mice. Nutr Neurosci. 2013;16:250–4.
60. Hamman JH. Composition and applications of Aloe vera leaf gel. Molecules.
2008;13:1599–616.
61. Harding TBC. Aloes of the world: a checklist, index and code. Excelsa. 1979;
9:57–94.
62. Heggers JP, Robson MC. Prostaglandins and thromboxanes. In: Ninne-
mann JL, editor. Traumatic Injury. Infection and other immunological
sequelae. Baltimore: University Park Press; 1983. p. 79–102.
202 Aloe vera (L.) Burm.f.

63. Henry R. An updated review of Aloe vera. Cosmet Toil. 1979;94:42–50.

64. Hervás-García JV, Montané E, Serrado-Iglesias A, Ramo-Tello C. Toxic
hepatitis after concomitant interferon beta and Aloe vera treatment in a
patient with multiple sclerosis: a case report. Neurologia. 2017;32:546–7.
65. Hunter D, Frumkin A. Adverse reactions to vitamin E and Aloe vera
preparations after dermabrasion and chemical peel. Cutis. 1991;47:193–6.
66. Hussain A, Sharma C, Khan S, Shah K, Haque S. Aloe vera inhibits
proliferation of human breast and cervical cancer cells and acts synergis-
tically with cisplatin. Asian Pac J Cancer Prev. 2015;16:2939–46.
67. Im SA, Kim JW, Kim HS, et al. Prevention of azoxymethane/dextran
sodium sulfate-induced mouse colon carcinogenesis by processed Aloe
vera gel. Int Immunopharmacol. 2016;40:428–35.
68. Im SA, Kim KH, Kim HS, et al. Processed Aloe vera gel ameliorates
cyclophosphamide-induced immunotoxicity. Int J Mol Sci. 2014;15:
19342–54.
69. Irani PS, Varaie S. Comparison of the effect of Aloe vera gel and nitrofurazone
2% on epithelialization and granulation tissue formation regarding superficial
second-degree burns. Iran J Med Sci. 2016;41(3 Suppl):S3.
70. Kanyadhara S, Dodoala S, Sampathi S, Punuru P, Chinta G. Ethanolic
extract of Aloe vera ameliorates sciatic nerve ligation induced neuropathic
pain. Anc Sci Life. 2014;33:208–15.
71. Kaufman T, Kalderon N, Ullmann Y, Berger J. Aloe vera gel hindered
wound healing of experimental second-degree burns: a quantitative
controlled study. J Burn Care Rehab. 1988;9:156–9.
72. Khattak S, Saeed-Ur-Rehman, Shah HU, et al. In vitro enzyme inhibition
activities of crude ethanolic extracts derived from medicinal plants of
Pakistan. Nat Prod Res. 2005;19:567–71.
73. Kim K, Kim H, Kwon J, et al. Hypoglycemic and hypolipidemic effects of
processed Aloe vera gel in a mouse model of noninsulin-dependent
diabetes mellitus. Phytomedicine. 2009;16:856–63.
74. Klein AD, Penneys NS. Aloe vera [published erratum appears in J Am Acad
Dermatol 1988;19 (1 Pt 1):82]. J Am Acad Dermatol. 1988;18(4 Pt 1):
714–20 (Review).
75. Kumar M, Rakesh S, Nagpal R, et al. Probiotic Lactobacillus rhamnosus
GG and Aloe vera gel improve lipid profiles in hypercholesterolemic rats.
Nutrition. 2013;29:574–9.
76. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary
problems and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2:45.
77. Leung AY. Aloe vera in cosmetics. Drugs Cosmet Indust. 1977;120:34–
35/154–5.
78. Leung AY. Aloe vera in cosmetics. Excelsa. 1978;8:65–8.
79. Lin LX, Wang P, Wang YT, et al. Aloe vera and Vitis vinifera improve
wound healing in an in vivo rat burn wound model. Mol Med Rep. 2016;13:
1070–6.
Aloe vera (L.) Burm.f. 203

80. Lorenzetti LJ, Salisbury R, Beal JL, Baldwin JN. Bacteriostatic property of
Aloe vera. J Pharm Sci. 1964;53:1287.
81. Loveman AB. Leaf of Aloe vera in treatment of Roentgen ray ulcers. Arch
Dermatol Syphilology. 1937;36:838–43.
82. Lushbaugh CC, Hale DB. Experimental acute radiodermatitis following
beta radiation. V. Histopathological study of the mode of action of therapy
with Aloe vera. Cancer. 1953;6:690–8.
83. Mandeville FB. Aloe vera in the treatment of radiation ulcers of mucous
membranes. Radiology. 1939;32:598–9.
84. McCauley RL, Heggers JP, Robson MC. Frostbite. Methods to minimize
tissue loss. Postgrad Med. 1990;88:67–8, 73–7.
85. Meadows TP. Aloe as a humectant in new skin preparations. Cosmet
Toiletr. 1980;95:51–6.
86. Mendonça FA, Passarini Junior JR, Esquisatto MA, et al. Effects of the
application of Aloe vera (L.) and microcurrent on the healing of wounds
surgically induced in Wistar rats. Acta Cir Bras. 2009;24:150–5.
87. Misawa E, Tanaka M, Nabeshima K, et al. Administration of dried Aloe
vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.
J Nutr Sci Vitaminol (Tokyo). 2012;58:195–201.
88. Molazem Z, Mohseni F, Younesi M, Keshavarzi S. Aloe vera gel and
cesarean wound healing; a randomized controlled clinical trial. Glob J
Health Sci. 2014;7:203–9.
89. Nejatzadeh-Barandozi F. Antibacterial activities and antioxidant capacity
of Aloe vera. Org Med Chem Lett. 2013;3:5.
90. Nieberding JF. Ancients knew value of Aloe for bee stings. Am Bee J. 1974;
114:15.
91. Nimma VL, Talla HV, Bairi JK, et al. Holistic healing through herbs:
effectiveness of Aloe vera on post extraction socket healing. J Clin Diagn
Res. 2017;11:ZC83–6.
92. Oryan A, Mohammadalipour A, Moshiri A, Tabandeh MR. Topical
application of Aloe vera accelerated wound healing, modeling, and
remodeling: an experimental study. Ann Plast Surg. 2016;77:37–46.
93. Oyelami OA, Onayemi A, Oyedeji OA, Adeyemi LA. Preliminary study of
effectiveness of Aloe vera in scabies treatment. Phytother Res. 2009;23:
1482–4.
94. Panahi Y, Khedmat H, Valizadegan G, Mohtashami R, Sahebkar A.
Efficacy and safety of Aloe vera syrup for the treatment of gastroe-
sophageal reflux disease: a pilot randomized positive-controlled trial.
J Tradit Chin Med. 2015;35:632–6.
95. Pandiri AR, Sills RC, Hoenerhoff MJ, et al. Aloe vera nondecolorized
whole leaf extract-induced large intestinal tumors in F344 rats share similar
molecular pathways with human sporadic colorectal tumors. Toxicol
Pathol. 2011;39:1065–74.
96. Park MY, Kwon HJ, Sung MK. Evaluation of aloin and aloe-emodin as
anti-inflammatory agents in aloe by using murine macrophages. Biosci
Biotechnol Biochem. 2009;73:828–32.
204 Aloe vera (L.) Burm.f.

97. Parlati L, Voican CS, Perlemuter K, Perlemuter G. Aloe vera-induced acute

liver injury: a case report and literature review. Clin Res Hepatol Gastroenterol.
2017;41:e39–42.
98. Payne JM. Tissue response to Aloe vera gel following periodontal surgery.
Thesis submitted to Faculty of Baylor University in partial fulfilment of the
requirements for the Degree of Master of Science; 1970.
99. Penneys NS. Inhibition of arachidonic acid oxidation in vitro by vehicle
components. Acta Dermatovener (Stockholm). 1982;62:59–61.
100. Pothuraju R, Sharma RK, Rather SA, Singh S. Comparative evaluation of
antiobesity effect of Aloe vera and Gymnema sylvestre supplementation in
high-fat diet fed C57BL/6J mice. J Intercult Ethnopharmacol. 2016;5:403–7.
101. Pradeep AR, Garg V, Raju A, Singh P. Adjunctive local delivery of Aloe
vera gel in patients with type 2 diabetes and chronic periodontitis: a
randomized, controlled clinical trial. J Periodontol. 2016;87:268–74.
102. Rajar UD, Majeed R, Parveen N, Sheikh I, Sushel C. Efficacy of Aloe vera
gel in the treatment of vulval lichen planus. J Coll Physicians Surg Pak.
2008;18:612–4.
103. Rathor N, Mehta AK, Sharma AK, Mediratta PK, Sharma KK. Acute effect
of Aloe vera gel extract on experimental models of pain. Inflammation.
2012;35:1900–3.
104. Rezazadeh F, Moshaverinia M, Motamedifar M, Alyaseri M. Assessment
of anti HSV-1 activity of Aloe vera gel extract: an in vitro study. J Dent
(Shiraz). 2016;17:49–54.
105. Rishi P, Rampuria A, Tewari R, Koul A. Phytomodulatory potentials of
Aloe vera against Salmonella OmpR-mediated inflammation. Phytother
Res. 2008;22:1075–82.
106. Robson MC, Heggers JP, Hegstrom WJ Jr.: Myth, magic, witchcraft, or
fact? Aloe vera revisited. J Burn Care Rehabilit (U.S.A.). 1982;3:157–63.
107. Robson MC, Heggers JP, Pineless GR. Myth, magic, witchcraft, or fact?
Aloe vera revisited. Am Burn Assoc Abstracts. 1979;31:65–6.
108. Rodriguez-Bigas M, Cruz NI, Suarez A. Comparative evaluation of Aloe
vera in the management of burn wounds in guinea pigs. Plast Reconst
Surg. 1988;81:386–9.
109. Rovatti B, Brennan RJ. Experimental thermal burns. Indust Med Surg.
1959;28:364–8.
110. Rowe TD, Lovell BK, Parks LM. Further observations on the use of Aloe
vera leaf in the treatment of third-degree X-ray reactions. J Am
Pharmaceut Assoc. 1941;30:266–9.
111. Rowe TD. Effect of fresh Aloe vera jell in the treatment of third-degree
Roentgen reactions on white rats. J Am Pharmaceut Assoc. 1940;29:348–50.
112. Saeedi M, Hajheydari Z, Morteza-Semnani K, Soltani A. Effect of Aloe
vera topical gel combined with tretinoin in treatment of mild and moderate
acne vulgaris: a randomized, double-blind, prospective trial. J Dermatolog
Treat. 2014;25:123–9.
Aloe vera (L.) Burm.f. 205

113. Sahebnasagh A, Ghasemi A, Akbari J, et al. Successful treatment of acute

radiation proctitis with Aloe vera: a preliminary randomized controlled
clinical trial. J Altern Complement Med. 2017;23:858–65.
114. Saini M, Goyal PK, Chaudhary G. Antitumor activity of Aloe vera against
DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice.
J Environ Pathol Toxicol Oncol. 2010;29:127–35.
115. Saito M, Tanaka M, Misawa E, et al. Aloe vera gel extract attenuates
ethanol-induced hepatic lipid accumulation by suppressing the expression
of lipogenic genes in mice. Biosci Biotechnol Biochem. 2012;76:2049–54.
116. Saniasiaya J, Salim R, Mohamad I, Harun A. Antifungal effect of Malaysian
Aloe vera leaf extract on selected fungal species of pathogenic otomycosis
species in in vitro culture medium. Oman Med J. 2017;32:41–6.
117. Schmidt JM, Greenspoon JS. Aloe vera dermal wound gel is associated
with a delay in wound healing. Obstet Gynecol. 1991;78:115–7.
118. Shahraki MR, Mirshekari H, Sabri A. Aloe vera aqueous extract effect on
morphine withdrawal syndrome in morphine-dependent female rats. Int J
High Risk Behav Addict. 2014;3:e11358.
119. Ship AG. Is topical Aloe vera plant mucus helpful in burn traetment?
JAMA. 1977;94:42.
120. Singh N, Hebbale M, Mhapuskar A, et al. Effectiveness of Aloe vera and
antioxidant along with physiotherapy in the management of oral submu-
cous fibrosis. J Contemp Dent Pract. 2016;17:78–84.
121. Spoerke DG, Ekins BR. Aloe vera—fact or quackery. Vet Hum Toxicol.
1980;22:418–24.
122. Størsrud S, Pontén I, Simrén M. A pilot study of the effect of Aloe
barbadensis Mill. extract (AVH200®) in patients with irritable bowel
syndrome: a randomized, double-blind, placebo-controlled study. J Gas-
trointestin Liver Dis. 2015;24:275–80.
123. Syed TA, Ahmad SA, Holt AH, et al. Management of psoriasis with Aloe
vera extract in a hydrophilic cream: a placebo-controlled, double-blind
study. Trop Med Int Health. 1996;1:505–9.
124. ‘t Hart LA, Nibbering PH, van den Barselaar MT, et al. Effects of low
molecular constituents from Aloe vera gel on oxidative metabolism and
cytotoxic and bactericidal activities of human neutrophils. Int J
Immunopharmacol. 1990;12:427–34.
125. Tamura N, Yoshida T, Miyaji K, Sugita-Konishi Y, Hattori M. Inhibition
of infectious diseases by components from Aloe vera. Biosci Biotechnol
Biochem. 2009;73:950–3.
126. Tang JC, Yang H, Song XY, et al. Inhibition of cytochrome P450 enzymes
by rhein in rat liver microsomes. Phytother Res. 2009;23:159–64.
127. Tarameshloo M, Norouzian M, Zarein-Dolab S, et al. Aloe vera gel and
thyroid hormone cream may improve wound healing in Wistar rats. Anat
Cell Biol. 2012;45:170–7.
128. Tchou MT. Aloe vera (jelly leeks). Arch Dermatol Syphilology. 1943;47:
249.
206 Aloe vera (L.) Burm.f.

129. Tomasin R, Gomes-Marcondes MC. Oral administration of Aloe vera and

honey reduces Walker tumour growth by decreasing cell proliferation and
increasing apoptosis in tumour tissue. Phytother Res. 2011;25:619–23.
130. Varaei S, Mohaddes Ardabili F, Sabaghzadeh Irani P, Ranjbar H. The
effect of Aloe vera gel and nitrofurazone on dressing related pain of
superficial burn wounds. World J Plast Surg. 2017;6:254–6.
131. Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical
effectiveness. Br J Gen Pract. 1999;49:823–8 (Review).
132. Werawatganon D, Linlawan S, Thanapirom K, et al. Aloe vera attenuated
liver injury in mice with APAP-induced hepatitis. BMC Complement
Altern Med. 2014;14:229.
133. Werawatganon D, Rakananurak N, Sallapant S, et al. Aloe vera attenuated
gastric injury on indomethacin-induced gastropathy in rats. World J
Gastroenterol. 2014;20:18330–7.
134. Williams MS, Burk M, Loprinzi CL, et al. Phase III double-blind
evaluation of an Aloe vera gel as a prophylactic agent for radiation-induced
skin toxicity. Int J Radiat Oncol Biol Phys. 1996;36:345–9.
135. Winters WD, Benavides R, Clouse WJ. Effects of Aloe (Aloe vera) extracts
on human normal and tumour cells in vitro. Econ Bot. 1981;35:89–95.
136. Wright CS. Aloe vera in the treatment of Roentgen ulcers and telangiec-
tasis. JAMA. 1936;106:1363–4.
137. Yagi A, Harada N, Yamada H, et al. Antibradykinin active material in Aloe
saponaria. J Pharmaceut Sci. 1982;71:1172–4.
138. Yang MS, Yu CP, Huang CY, et al. Aloe activated p-glycoprotein and
CYP 3A: a study on the serum kinetics of aloe and its interaction with
cyclosporine in rats. Food Funct. 2017;8:315–22.
139. Yongchaiyudha S, Rungpitarangsi V, Bunyapraphatsara N, Chokechai-
jaroenporn O. Antidiabetic activity of Aloe vera L. juice. I. Clinical trial
in new cases of diabetes mellitus. Phytomedicine. 1996;3:241–3.
140. Yun N, Lee CH, Lee SM. Protective effect of Aloe vera on polymicrobial
sepsis in mice. Food Chem Toxicol. 2009;47:1341–8.
141. Zachary LS, Smith DJ Jr, Heggers JP, et al. The role of thromboxane in
experimental inadvertent intra-arterial drug injections. J Hand Surg Am.
1987;12:240–5.
142. Zhang AL, Story DF, Lin V, Vitetta L, Xue CC. A population survey on
the use of 24 common medicinal herbs in Australia. Pharmacoepidemiol
Drug Saf. 2008;17:1006–13.
Alpinia galanga (L.) Willd.
(Zingiberaceae)

(Syns.: A. alba (Retz.) Roscoe; A. bifida Warb.; A. carnea Griff.; Zingiber galanga (L.)
Stokes)

Abstract
A ginger-like perennial herb is native to Indonesia, India, Sri Lanka, China,
Vietnam, Java, and Sumatra. It is known in China by the same names as the lesser
Galangal, and also Greeks, Arabs and Persian do not distinguish it from the latter.
The rhizomes are aromatic, refrigerant, mouth-freshener, detergent, stomachic
and carminative, and are considered cardiac, liver and gastric tonic, used in
dyspepsia, gastralgia, as a fragrant adjunct to cough and digestive mixtures,
useful in rheumatism, catarrhal affections, diabetes insipidus, and as aphrodisiac.
Its slight irritant action on the gastric mucosa may produce a reflex increase in
bronchial secretions, and due to the excretion of the oil through lungs it acts as an
expectorant, and thus its use in various pulmonary ailments. Use of A. galanga in
honey lessened the paroxysm of whooping cough in children, and relieved the
distressing symptoms in young children suffering from bronchitis. Application on
the face of a paste made by rubbing the rhizome with oil or water is claimed to
remove freckles. Rhizomes contain tannins, coumarins, flavonoids, sterols, and
glycosides. Leaf and flower essential oils mainly contain 1,8-cineole, a-terpineol,
(E)-methyl cinnamate, terpinen-4-ol, camphor, and a- and b- pinenes. Methanol
rhizome extract administration to male rats daily for eight-weeks significantly
increased serum testosterone, sperm count, sperm viability and motility, whereas
ethanol extract daily for 90-days significantly increased RBC counts, sex organs
weight, sperm count and motility in male mice. The rhizome EO shows strong
and rapid bactericidal activity against a number of Gram-negative and
Gram-positive food-borne bacteria, yeast and a number of dermatophytes.

Keywords





Galanga major Galgantalpinie Galigaan Gengibre do laos Hung-dau-kau





Khulanjan Khurduwara Langkauás Stor galangal Sugandhavacha

© Springer Nature Switzerland AG 2020 207

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_19
208 Alpinia galanga (L.) Willd.

Vernaculars: Urd.: Khulanjan; Hin.: Bara khulanjan, Khulanjan, Sapheda-

pana-ki-jhad; San.: Dharnula tikshra mula, Dhumpa-rastma, Kulanjana, Mahab-
hara vacha, Sugandhavacha; Ben.: Barakulanjar, Bomb, Kulanjan, Sugandhavacha;
Mal.: Arattha, Chitta-ratta, Kol-inji, Pera-ratta; Mar.: Kosht-kolanjan, Malabari-
kolanjan, Motha-kolanjan; Tam.: Perarattai, Peria-reta; Tel.: Pedda-dhumpa, Pedda-
dumparash-trakan, Rash-trakam; Ara.: Khulanjan-e-kabir, Khulanjan-e-qasbi; Chi.:
Da guo liang jiang, Hung-dau-kau; Cze.: Galgán obecný, Galgán veliký, Galgán
větší; Dan.: Stor galanga; Dut.: Galigaan, Grote galanga, Lengoewas; Eng.:
Galanga major, Great galangal, Java galangal; Fre.: Galanga, Galanga d’Inde,
Souchet long, Souchet odorant; Ger.: Galanga, Galgant, Galgantalpinie, Großer
galgant, Siam-ingwer; Ind.; Laos; Ita.: Galanga maggiore; Maly.: Lawas and
Langkuweh (Sumatra), Lengkuas (Indonesia); Per.: Khurduwara, Khusravedurue-
kalan; Por.: Gengibre do Laos, Gengibre tailandés; Rus.: Al’piniia galanga; Spa.:
Calanga, Garengal; Tag.: Langkauás, Lannkauás; Tha.: Dok kha, Ginza, Khaa;
Vie.: Cao khương hương, Một loại gừng, Riềng ấm, Riềng nếp, Sơn nại.
Description: The herb is native to Indonesia, India (Bengal, south India), Sri
Lanka, China, Vietnam, Java, and Sumatra. It is known in China by the same names
as the lesser Galangal, and also Greeks, Arabs and Persian do not distinguish it
from the latter. The distinction between the two was made by Garcia D’Orta in
1563, who described the smaller-sized, brought from China to India, with more
potent virtues than the thicker less aromatic rhizome produced in Java. Hindus
regard the plant as a native of Malabar (lies between the Western Ghats and
the Arabian Sea) of western India.XL It is a ginger-like perennial, leafy-stemmed
herb, 0.7–1.2 m tall. Rhizomes creeping 12–18 mm in diameter, reddish-brown,
glabrous, covered with fibrous scales which leave irregular rings; leaves carti-
lagenous, glabrous, lanceolate, 29–40 cm long and 24 mm wide, sheath scariose.
The rhizomes as available in Indian market appear as long transverse pieces
11.5 cm long by 2 cm in diameter, ramificate, dark reddish or cinnamon-brown
externally with yellowish-white interior, fibrous, surface annulate with yellowish,
wavy leaf bases. The odor is aromatic and the taste is aromatic and pungent
(Figs. 1, 2 and 3).XL
Actions and Uses: The rhizomes (temperament, hot 2° and dry 2°) are aromatic,
refrigerant and mouth freshener,LXXVII,LXXXI detergent, stomachic and carminative,
used in dyspepsia and gastralgia,XXI,LXXVII,LXXXI,CV as a fragrant adjunct to cough
and digestive mixtures,XXI useful in rheumatism and catarrhal affections,XXI,LXXVII
and are considered cardiac, liver and gastric tonic, useful in diabetes insipidus, and
as aphrodisiac.LXXVII Application on the face of a paste made by rubbing the
rhizome with oil or water is claimed to remove freckles.LXXXI Other uses reported
are for the treatment of bronchitis, heart diseases, chronic enteritis, renal calculus,
diabetes, rheumatism and kidney disorders [17]. Its slight irritant action on the
gastric mucosa may produce a reflex increase in bronchial secretions, and due to the
excretion of the oil through lungs it acts as an expectorant, and thus its use in
various pulmonary ailments.XXI,CV Use of A. galanga in honey lessened the
paroxysm of whooping cough in children, relieved the distressing symptoms in
Alpinia galanga (L.) Willd. 209

Fig. 1 Alpinia galanga, Plant, Raffi Kojian, Queen Sirikit Botanic Garden, Thailand. Wikime-
diaCommons, https://commons.wikimedia.org/wiki/File:Gardenology.org-IMG_7562_qsbg11mar.
jpg

young children suffering from bronchitis, and also had a favorable effect on body
temperature of the patients. The antispasmodic action could also be beneficial in
conditions like asthma.XXI It is reported to be good for impotence, and also stim-
ulates respiration.LXXXVIII In the Philippines, the juice of the rhizomes is applied to
anan or paño blanco, a kind of skin disease.CXVII
Phytoconstituents: Rhizomes contain tannins, coumarins, flavonoids, sterols, and
glycosides [13]. Three hydroxy-1,8-cineole glucopyranosides [42], three neolignans,
galanganal, galanganols A and B, and a sesquineolignan, galanganol [27], and three
novel chalcones, galanganones A-C [49], have been isolated from the rhizomes. The
rhizomes also contain the oil, acrid resin, galangol, 0.5–5% EO, a sesquiterpene and
dioxyflavonol. Rhizome EO contains 1,8-cineole (28.4%), a-fenchyl acetate
(18.4%), camphor (7.7%), (E)-methyl cinnamate (4.2%) and guaiol (3.3%), whereas
the root EO contains a-fenchyl acetate (40.9%), 1,8-cineole (9.4%), borneol (6.3%),
bornyl acetate (5.4%), and elemol (3.1%) [16]. Leaf and flower EOs mainly contain
1,8-cineole, a-terpineol, (E)-methyl cinnamate, terpinen-4-ol, camphor, and a- and
b-pinenes [29]. Actions of galangol and the EO are that of an aromatic stimulant,
with effect similar to those of ginger. The pungent principal in galangal rhizomes is
identified as 1′-acetoxychavicol acetate (ACA, galangal acetate), which is not stable
in aqueous solutions, is less pungent than capsaicin and can be used as an alcohol
enhancer, or an alcohol replacer in alcohol and alcohol-free beverages [50].
210 Alpinia galanga (L.) Willd.

Fig. 2 Alpinia galanga, Illustration, Kurt Stüber, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Maranta_galanga_Ypey51.jpg

However, dihydrogalangal acetate, present in quantity approximately 0.0005%

of fresh roots and in about 0.004% of dried roots, has a taste sensation similar to
galangal acetate, is more stable in food and beverage applications, and provides
advantages as a flavor ingredient for alcohol enhancement and taste modification
[51]. Following flavonoids, (2R, 3S)-pinobaksin-3-cinnamate, (2R, 3R)-pinobaksin-
3-cinnamate, pinocembrin, pinobaksin, 3-O-acetylpinobaksin, galangin-3-methyl-
ether, kumatakenin, galangin, 3-methylkaempferol and (2R, 3R)-3, 5-dihydroxy-
7-methoxy-flavanone, were reported from ethanol extract of seeds [5]. Pharma-
cognostical characteristics for the identification of the rhizome have been descri-
bed [6, 48].
Pharmacology: Powdered rhizomes, aqueous and methanol extracts significantly
lowered blood glucose of normal rabbits, but did not affect glucose level in
alloxan-diabetic rabbits [2]; however, methanol extract of defatted aerial parts
normalized serum glucose in STZ-diabetic rats after three-weeks treatment, and
Alpinia galanga (L.) Willd. 211

Fig. 3 Alpinia galanga, Roots, McLeod, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Alpinia_galanga.jpg; https://creativecom
mons.org/licenses/by-sa/3.0/deed.en

significantly lowered TC, LDL-C, and TGs, and increased HDL-C [46]. Ethanol
extract also significantly lowered serum TC, LDL-C, and TGs, and increased
HDL-C of Triton-induced hyperlipidemic rats [13], and STZ-diabetic rats [18].
Methanol and ethyl acetate extracts caused CNS stimulation in mice [36]. Ethanol
extract also showed significant analgesic effects, probably through both central and
peripheral actions [1], and preteatment with ethanol extract improved cognitive
function of oxidative stress-induced Alzheimer’s type amnesia in mice, and
attenuated the elevated levels of AChE and MAO enzymes [10]; 1′d-1′-acetox-
yeugenol acetate was identified as the neuroprotective agent [9]. Ethanol extract
decreased cell viability, induced apoptosis in cultured human breast carcinoma
(MCF-7) cells [37], while ACA exhibited potent antioxidant activity and potenti-
ated cell apoptosis and decreased cytokine production by T helper cells. Hydrox-
ychavicol acetate has neither antioxidant activity, nor proapoptotic function, but
increased IL-2 production and attenuated IFNc expression in T helper cells [26].
ACA protected against OVA-induced asthma in mice [41]. Methanol extract is a
significant inhibitor of PAF [15], and the aqueous extract and ACA have significant
cytotoxic effect against several human normal and cancer cell lines [22, 28].
Methanol rhizome extract administration to male rats daily for eight-weeks sig-
nificantly increased serum testosterone, sperm count, sperm viability and motility
[25], whereas ethanol extract daily for 90-days significantly increased RBC counts,
sex organs weight, sperm count and motility in male mice [32].
Methanol extract showed significant antibacterial activity against B. subtilis,
E. aerogene, E. cloacae, E. faecalis, E. coli, K. pneumoniae, P. aeruginosa,
S. typhimurium, S. aureus and S. epidermis [35], and also strongly inhibited HIV-1
protease, and to a lesser degree hepatitis C virus and HCV proteases [43]. Chlo-
roform extract showed antiamebic activity against E. histolytica, and G. intestinalis
212 Alpinia galanga (L.) Willd.

[38, 39], antifungal activity against opportunistic fungal pathogens associated with
AIDS patients, such as C. neoformans, and M. gypseum [30], and the ethanol
extract against T. longifusus [20], and other human pathogenic fungi strains,
including those resistant to antifungals, ketoconazole and amphotericin B [7]. The
colorless oil from rhizome showed activity against S. aureus, P. aeruginosa,
S. bovis, and C. albicans [45]. ACA inhibits HIV-1 replication and acts synergis-
tically with didanosine to inhibit HIV-1 replication [52], is a potent inhibitor of
influenza virus replication [47], and inhibitor of IFN-b production in LPS-activated
mouse peritoneal macrophages [4, 23], and also shows gastric cytoprotective effect
against ethanol-induced gastric lesions in rats [24]. An antimicrobial diterpene
synergistically enhanced antifungal activity of quercetin and chalcone against
C. albicans [11]. The rhizome EO shows strong and rapid bactericidal activity
against a number of Gram-negative and Gram-positive food-borne bacteria [31],
yeast and a number of dermatophytes, and ACA was identified as the active con-
stituent [14, 40]. Crude acetone extract exhibits activity against S. typhi and E. coli,
with an efficiency of 92% and 82% respectively; principal compound responsible
for the activity, ACA, showed the ability to prevent plasmid encoded antibiotic
resistance in various MDR bacterial strains of clinical isolates, such as E. faecalis,
S. typhi, P. aeruginosa, and E. coli with efficiency of 66%, 75%, 70%, and 32%,
respectively [21]. Alcohol extract of the rhizomes also showed good in vitro
anthelmintic activity against human A. lumbricoides [33, 34].
Clinical Studies: In a double-blind, multicenter, parallel-group, 6-weeks RCT of
261 patients with osteoarthritis of the knee, patients who received a highly purified
and standardized extract of Zingiber officinale and A. galanga had significant
reduction in symptoms of osteoarthritis, such as reduction in knee pain on standing,
reduction in knee pain after walking 50 feet, and reduction in the Western Ontario
and McMaster Universities osteoarthritis composite index [3].
Mechanism of Action: Ethanol extract in vitro inhibits AChE, BChE and LOX
enzymes [19], LPS, cytokine, and amyloid Ab peptide-induced expression of the
proinflammatory genes TNF-a, IL-1b, and COX-2 [8]. Inhibition of expression of
Th2 cytokines, IL-4 and IL-13, and Th1 cytokines, IL-12a and IFN-c by ACA may
be responsible for its antiasthmatic effect in OVA-induced asthma in mice [41].
Human A/Es, Allergy and Toxicity: In human, the drug causes a decrease in
urine formation (oliguria).LXXVII A case of localized contact dermatitis leading to
generalized erythema multiforme-like eruptions after topical application of a herbal
remedy containing A. galanga was reported [12].
Animal Toxicity: Ethanol rhizomes extract, with doses up to 3,000 mg/kg body
weight, was nontoxic and nonlethal to mice, during acute (24 h) toxicity studies
[32]; methanol extract of defatted aerial parts was also nontoxic to mice up to an
oral dose of 1,600 mg/kg [46].
CYP450 and Potential for Drug-Herb Interaction: Methanol extract is reported
to cause more than 30% inhibition of CYP2D6 [44].
Alpinia galanga (L.) Willd. 213

Commentary: There are no clinical studies reported on the rhizome or its oil by
itself in the mainstream English publications listed on PubMed, except one in
combination with Zingiber officinale on osteoarthritis.

References
1. Acharya SD, Ullal SD, Padiyar S, et al. Analgesic effect of extracts of
Alpinia galanga rhizome in mice. Zhong Xi Yi Jie He Xue Bao. 2011;
9:100–4.
2. Akhtar MS, Khan MA, Malik MT. Hypoglycaemic activity of Alpinia
galanga rhizome and its extracts in rabbits. Fitoterapia. 2002;73:623–8.
3. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in
patients with osteoarthritis. Arthritis Rheum. 2001;44:2531–8.
4. Ando S, Matsuda H, Morikawa T, Yoshikawa M. 1′S-1′-acetoxychavicol
acetate as a new type inhibitor of interferon-beta production in lipopolysac-
charide-activated mouse peritoneal macrophages. Bioorg Med Chem.
2005;13:3289–94.
5. Bian MQ, Wang HQ, Kang J, et al. Flavonoids from the seeds of Alpinia
galanga Willd. Yao Xue Xue Bao. 2014;49:359–62 (Chinese).
6. Chitra M, Thoppil JE. A pharmacognostical report on the rhizome of
Alpinia galanga Linn. (Willd). Anc Sci Life. 2008;27:9–21.
7. Ficker CE, Smith ML, Susiarti S, et al. Inhibition of human pathogenic
fungi by members of Zingiberaceae used by the Kenyah (Indonesian
Borneo). J Ethnopharmacol. 2003;85:289–93.
8. Grzanna R, Phan P, Polotsky A, et al. Ginger extract inhibits beta-amyloid
peptide-induced cytokine and chemokine expression in cultured THP-1
monocytes. J Altern Complement Med. 2004;10:1009–13.
9. Hanish Singh JC, Alagarsamy V, Diwan PV, et al. Neuroprotective effect of
Alpinia galanga (L.) fractions on Ab(25–35) induced amnesia in mice.
J Ethnopharmacol. 2011;138:85–91.
10. Hanish Singh JC, Alagarsamy V, Sathesh Kumar S, Narsimha Reddy Y.
Neurotransmitter metabolic enzymes and antioxidant status on Alzheimer’s
disease induced mice treated with Alpinia galanga (L.) Willd. Phytother
Res. 2011;25:1061–7.
11. Haraguchi H, Kuwata Y, Inada K, et al. Antifungal activity from Alpinia
galanga and the competition for incorporation of unsaturated fatty acids in
cell growth. Planta Med. 1996;62:308–13.
12. Hong SJ, Chang CH. Erythema multiforme-like generalized allergic contact
dermatitis caused by Alpinia galanga. Contact Dermatitis. 2006;54:118–20.
13. Iyer D, Sharma BK, Patil UK. Isolation of bioactive phytoconstituent from
Alpinia galanga L. with antihyperlipidemic activity. J Diet Suppl. 2013;10:
309–17.
14. Janssen AM, Scheffer JJ. Acetoxychavicol acetate, an antifungal component
of Alpinia galanga. Planta Med. 1985;51:507–11.
214 Alpinia galanga (L.) Willd.

15. Jantan I, Rafi IA, Jalil J. Platelet-activating factor (PAF) receptor-binding

antagonist activity of Malaysian medicinal plants. Phytomedicine. 2005;12:
88–92.
16. Jirovetz L, Buchbauer G, Shafi MP, Leela NK. Analysis of the essential oils
of the leaves, stems, rhizomes and roots of the medicinal plant Alpinia
galanga from southern India. Acta Pharm. 2003;53:73–81.
17. Kaushik D, Yadav J, Kaushik P, et al. Current pharmacological and
phytochemical studies of the plant Alpinia galanga. Zhong Xi Yi Jie He
Xue Bao. 2011;9:1061–5.
18. Kaushik P, Kaushik D, Yadav J, Pahwa P. Protective effect of Alpinia galanga
in STZ induced diabetic nephropathy. Pak J Biol Sci. 2013;16:804–11.
19. Khattak S, Saeed-Ur-Rehman, Shah HU, et al. In vitro enzyme inhibition
activities of crude ethanolic extracts derived from medicinal plants of
Pakistan. Nat Prod Res. 2005;19:567–71.
20. Khattak S, Saeed-ur-Rehman, Ullah Shah H, et al. Biological effects of
indigenous medicinal plants Curcuma longa and Alpinia galanga. Fitoter-
apia. 2005;76:254–7.
21. Latha C, Shriram VD, Jahagirdar SS, et al. Antiplasmid activity of 1′-
acetoxychavicol acetate from Alpinia galanga against multidrug resistant
bacteria. J Ethnopharmacol. 2009;123:522–5.
22. Lee CC, Houghton P. Cytotoxicity of plants from Malaysia and Thailand
used traditionally to treat cancer. J Ethnopharmacol. 2005;100:237–43.
23. Matsuda H, Ando S, Morikawa T, et al. Structure-activity relationships of 1′
S-1′-acetoxychavicol acetate for inhibitory effect on NO production in
lipopolysaccharide-activated mouse peritoneal macrophages. Bioorg Med
Chem Lett. 2005;15:1949–53.
24. Matsuda H, Pongpiriyadacha Y, Morikawa T, et al. Gastroprotective effects
of phenylpropanoids from the rhizomes of Alpinia galanga in rats: structural
requirements and mode of action. Eur J Pharmacol. 2003;471:59–67.
25. Mazaheri M, Shahdadi V, Nazari Boron A. Molecullar and biochemical
effect of alcohlic extract of Alpinia galanga on rat spermatogenesis process.
Iran J Reprod Med. 2014;12:765–70.
26. Min HJ, Nam JW, Yu ES, et al. Effect of naturally occurring hydroxychavicol
acetate on the cytokine production in T helper cells. Int Immunopharmacol.
2009;9:448–54.
27. Morikawa T, Ando S, Matsuda H, et al. Inhibitors of nitric oxide production
from the rhizomes of Alpinia galanga: structures of new 8–9′ linked neo-
lignans and sesquineolignan. Chem Pharm Bull (Tokyo). 2005;53:625–30.
28. Muangnoi P, Lu M, Lee J, et al. Cytotoxicity, apoptosis and DNA damage
induced by Alpinia galanga rhizome extract. Planta Med. 2007;73:748–54.
29. Padalia RC, Verma RS, Sundaresan V, Chanotiya CS. Chemical diversity in
the genus Alpinia (Zingiberaceae): comparative composition of four Alpinia
species grown in Northern India. Chem Biodivers. 2010;7:2076–87.
Alpinia galanga (L.) Willd. 215

30. Phongpaichit S, Subhadhirasakul S, Wattanapiromsakul C. Antifungal

activities of extracts from Thai medicinal plants against opportunistic fungal
pathogens associated with AIDS patients. Mycoses. 2005;48:333–8.
31. Prakatthagomol W, Klayraung S, Okonogi S. Bactericidal action of Alpinia
galanga essential oil on food-borne bacteria. Drug Discov Ther. 2011;5:84–9.
32. Qureshi S, Shah AH, Ageel AM. Toxicity studies on Alpinia galanga and
Curcuma longa. Planta Med. 1992;58:124–7.
33. Raj RK. Screening of indigenous plants for anthelmintic action against human
Ascaris lumbricoides—part I. Indian J Physiol Pharmacol. 1975;19:47–9.
34. Raj RK. Screening of indigenous plants for anthelmintic action against human
Ascaris lumbricoides: part-II. Indian J Physiol Pharmacol. 1975;19.
35. Rao K, Ch B, Narasu LM, Giri A. Antibacterial activity of Alpinia galanga
(L.) Willd crude extracts. Appl Biochem Biotechnol. 2010;162:871–84.
36. Saha S, Banerjee S. Central nervous system stimulant actions of Alpinia
galanga (L.) rhizome: a preliminary study. Indian J Exp Biol. 2013;51:828–32.
37. Samarghandian S, Hadjzadeh MA, Afshari JT, Hosseini M. Antiprolifer-
ative activity and induction of apoptotic by ethanolic extract of Alpinia
galanga rhizhome in human breast carcinoma cell line. BMC Complement
Altern Med. 2014;14:192.
38. Sawangjaroen N, Phongpaichit S, Subhadhirasakul S, et al. The antiamoebic
activity of some medicinal plants used by AIDS patients in southern
Thailand. Parasitol Res. 2006;98:588–92.
39. Sawangjaroen N, Subhadhirasakul S, Phongpaichit S, et al. The in vitro
antigiardial activity of extracts from plants that are used for self-medication
by AIDS patients in southern Thailand. Parasitol Res. 2005;95:17–21.
40. Scheffer JJC, Baerheim Svendsen A, Gani A. Antifungal activity of Alpinia
galanga. Planta Med (West Ger). 1981;42:140–1.
41. Seo JW, Cho SC, Park SJ, et al. 1′-Acetoxychavicol acetate isolated
from Alpinia galanga ameliorates ovalbumin-induced asthma in mice.
PLoS ONE. 2013;8:e56447.
42. Someya Y, Kobayashi A, Kubota K. Isolation and identification of trans-2-
and trans-3-hydroxy-1,8-cineole glucosides from Alpinia galanga. Biosci
Biotechnol Biochem. 2001;65:950–3.
43. Sookkongwaree K, Geitmann M, Roengsumran S, et al. Inhibition of viral
proteases by Zingiberaceae extracts and flavones isolated from Kaempferia
parviflora. Pharmazie. 2006;61:717–21.
44. Subehan, Usia T, Iwata H, et al. Mechanism-based inhibition of CYP3A4
and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 2006;105:
449–55.
45. Tadtong S, Watthanachaiyingcharoen R, Kamkaen N. Antimicrobial
constituents and synergism effect of the essential oils from Cymbopogon
citratus and Alpinia galanga. Nat Prod Commun. 2014;9:277–80.
46. Verma RK, Mishra G, Singh P, Jha KK, Khosa RL. Antidiabetic activity of
methanolic extract of Alpinia galanga Linn. aerial parts in streptozotocin
induced diabetic rats. Ayu. 2015;36:91–5.
216 Alpinia galanga (L.) Willd.

47. Watanabe K, Takatsuki H, Sonoda M, et al. Anti-influenza viral effects of

novel nuclear export inhibitors from Valerianae radix and Alpinia galanga.
Drug Discov Ther. 2011;5:26–31.
48. Wijayasiriwardena C, Premakumara S. Comparative powder microscopy of
Alpinia calcarata Roscoe and Alpinia galanga (Linn.) Willd. Ayu. 2012;33:
441–3.
49. Yang WQ, Gao Y, Li M, Miao DR, Wang F. New chalcones bearing a
long-chain alkylphenol from the rhizomes of Alpinia galanga. J Asian Nat
Prod Res. 2015;17:783–7.
50. Yang X, Eilerman RG. Pungent principal of Alpinia galanga (L.) Swartz
and its applications. J Agric Food Chem. 1999;47:1657–62.
51. Yang X, Rohr M, Jordan J. Identification of dihydrogalangal acetate in
galangal [Alpinia galanga (L.) Swartz] extracts. J Agric Food Chem. 2009;57:
3286–90.
52. Ye Y, Li B. 1′S-1′-acetoxychavicol acetate isolated from Alpinia galanga
inhibits human immunodeficiency virus type 1 replication by blocking Rev
transport. J Gen Virol. 2006;87(Pt 7):2047–53.
Alpinia officinarum Hance.
(Zingiberaceae)

Abstract
This ginger-like perennial, leafy-stemmed plant is native to southern China and
northern Vietnam, but also grows in Thailand and Japan, and is cultivated in
India. The rhizomes are aromatic, stomachic, stimulant and carminative, and used
to relieve flatulence, promote digestion and prevent vomiting due to indigestible
food, and help reduce polyuria of diabetes. Avicenna recognized it as stomachic
and stimulant, useful for phlegmatic persons, and in humidity of the stomach; it
promotes digestion by its heat and the secretions it causes in the stomach, and
thus relieves colic; gives fragrance to the breath, and warms the kidneys; it sets
the semen in commotion, and when a piece of it is held in mouth it occasions
erections of the membrum virile. The rhizomes are one of the most commonly
used drugs in TCM to treat fungal vaginitis, and galangin is used as a food
additive. Rhizomes contain the oily, acrid resin galangol, sesquiterpene, essential
oil, dioxyflavonol, b-sitosterol, emodin, quercetin, a number of glycosides,
phenylpropanoids with antioxidative activity, and galangin, quercetin and
kaempferol as the main flavonoids, with antifungal activity. Rhizomes supple-
mented in high-fat diet of hamsters completely prevented enlargement of liver,
kidney and spleen, and the rise in serum TC, TGs, LDL-C, and LDL-C/HDL-C
ratio, and increased activities of antioxidant enzymes. Ethanol rhizome extract to
high fat diet-fed rats lowered body weight gain, and decreased TC, TGs, LDL-C
levels, and leptin content. The HDL-C and the ratio of HDL-C/TC also
significantly improved. Antiobesity effect of ethanol extract is suggested to be
due to suppression of adipogenic and lipogenic genes.

Keywords




Al’piniia lekarstvennaia Chinese galangal Galgant Gao liang jiang






Khaa-ling Khulanjan sagheer Lesser galangal Lương khương Petit galangal

Sugandhã

© Springer Nature Switzerland AG 2020 217

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_20
218 Alpinia officinarum Hance.

Vernaculars: Urd.: Kale paan ki jad, Khulanjan sagheer; Hin.: Kulinjan; San.:
Kulanjana bheda, Rastama, Sugandhã; Ben.: Chini kalanjana, Sugandha bacha;
Mal.: Chittaratha, Kolinchi; Mar.: Kulinjan; Tam.: Shitta ratio, Shitta-rattai; Tel.:
Sannaelum-prash-trakum; Ara.: Khulanjan sagheer; Chi.: Gao liang jiang, Gor-
yankang, Kaon-leang-keang, Kuon-cang-keang, Liang-keang; Eng.: Blue ginger,
Chinese galangal, Lesser galangal, Rhizoma galangae; Fre.: Galangal officinal,
Petit galanga; Ger.: Galgant, Siam-ingwer; Ita.: Galanga; Kor.: Gal len gal; Per.:
Kholanjan; Rus.: Al’piniia lekarstvennaia, Kalgan lekarstvennyi; Spa.: Galangal;
Tha.: Khaa-ling; Vie.: Lương khương, Riềng (thuốc).
Description: The plant is native to southern China and northern Vietnam, but also
grows in Thailand and Japan, and is cultivated in India. A ginger-like perennial,
leafy-stemmed herb, 0.7–1.2 m tall, rhizomes creeping, 12–18 mm in diameter,
reddish-brown, glabrous, covered with fibrous scales which leave irregular rings of
a light color; leaves cartilagenous, glabrous, lanceolate, 29–40 cm long by 24 mm
wide [18]. Rhizomes are sold as long transverse pieces 5–8 cm long and 2 cm in
diameter, ramificate, dark reddish or cinnamon-brown, texture fibrous, surface
annulate with yellowish, wavy leaf bases. Dried rhizomes are about as thick as the
little finger or less, odor is aromatic, and the taste aromatic, hot and pungent
(Fig. 1).XL

Fig. 1 Alpinia officinarum, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Alpinia_officinarum_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-156.jpg
Alpinia officinarum Hance. 219

Actions and Uses: In ancient Persian literature, it is mentioned as Khusru-daru

(Chosro’s remedy), and Avicenna recognized it as stomachic and stimulant. It is
useful for phlegmatic persons, and in humidity of the stomach; it promotes digestion
by its heat and the secretions it causes in the stomach, and thus relieves colic; gives
fragrance to the breath, and warms the kidneys; it sets the semen in commotion, and
when a piece of it is held in the mouth it occasions erections of the membrum
virile.XL The rhizomes (temperament, hot 3° and dry 3°) are aromatic, stomachic,
stimulant and carminative, and used to relieve flatulence, promote digestion
and prevent vomiting due to indigestible food, and help reduce polyuria of
diabetes.LXXXI It is commonly used in various oriental cuisines, such as Thai,
Vietnamese and Indonesian. Despite its physical resemblance to ginger, there is
little similarity in taste; it is used as stomachic in dyspepsia, gastralgia and chronic
enteritis.LXXIX The rhizomes are one of the most commonly used drugs in TCM to
treat fungal vaginitis [29], and galangin is used as a food additive [54].
Phytoconstituents: Rhizomes contain the oily, acrid resin galangol, sesquiterpene,
essential oil, and dioxyflavonol,XXI b-sitosterol, emodin, quercetin [31], 1,7-diphenyl-
5-ol-3-heptone, 1-phenyl-7-(3′-methoxyl-4′-hydroxyl)phenyl-5-ol-3- heptone, glan-
din, kaempferol-4′-methyl-ether, 3,4-dihydroxybenzoic acid [6], a number of glyco-
sides [1, 34], phenylpropanoids with antioxidative activity [32, 33], and galangin,
quercetin and kaempferol as the main flavonoids [25], with antifungal activity [5, 15,
37, 38]. Hydroalcohol extract prepared by hot maceration process contains more
phenol and flavonol than extract prepared by cold maceration and methanol extract
prepared by percolation process [44]. Methanol extract contains higher triterpenoid
contents and better antioxidant activity than L-ascorbic acid [7]. There are numer-
ous diarylheptanoids present in the rhizome, with a number of them showing
in vitro cytotoxic activity against human tumor cell lines [2, 3, 47], four with
5a-reductase inhibitory activity [17], and four possessing antiemetic activity [41].
Three diaryl-heptanoids, 6-hydroxy-1,7-diphenyl-4-en-3-heptanone, 1,7- diphenyl-
4-en-3-heptanone, and 1,7-diphenyl-5-methoxy-3-heptanone are potent platelet acti-
vating factor receptor binding inhibitors [9], and three with strong antibacterial activity
against H. pylori [52]. Three dimeric diarylheptanoid, named alpinin B, C and D have
recently been reported [27, 28], where alpinin C has shown selective cytotoxicity
against several human cancer cell lines [27]. Curcumin [26], and alpinisin A [48] have
been isolated from the rhizomes, and Zou et al. [56] reported a new labdane diterpene,
(Z)-12,14-labdadien-15(16)-olide-17-oic acid, and a new natural cadinane sesquiter-
pene from the ethanol extract.
Pharmacology: Rhizomes (8%) supplemented in high-fat diet of hamsters com-
pletely prevented enlargement of liver, kidney and spleen, and the rise in serum TC,
TGs, LDL-C, and LDL-C/HDL-C ratio, and increased activities of antioxidant
enzymes [26]. Aqueous extract and its ethyl acetate fraction significantly lowered
serum TGs level of corn oil-fed triglyceridemic mice, and serum TGs and TC in
Triton WR-1339-induced hyperlipidemic mice, but they did not show hypolipi-
demic activity in high cholesterol diet-induced hyperlipidemic mice. Six-weeks
administration of ethanol rhizome extract to high fat diet-fed rats did not affect food
220 Alpinia officinarum Hance.

intake, but lowered body weight gain, and decreased TC, TGs and LDL-C levels,
and leptin content. The HDL-C and the ratio of HDL-C/TC was significantly
improved [49]. Acetyl-Co A acyltransferase 1 and enoyl CoA hydratase, which
participate in the b-oxidation of fatty acids in high fat diet-fed mice are significantly
increased by treatment with the rhizome extract [4]. Two compounds, methylether-
galangin and 5-hydroxy-7-(4′-hydroxy-3′-methoxyphenyl)-1-phenyl-3-heptanone
were identified to possess pancreatic lipase inhibitory activity [42, 43]. Quercetin
and kaempferol potently and reversibly inhibit fatty acid synthase, while inhibition
by galangin is weaker [25].
The rhizhomes exhibit a broad-spectrum antimicrobial activity [30]; an antibiotic
extracted from the tissue of the plant was used as food preservative [13]. Huang
et al. [12] reported the ethanol extract active against S. aureus, a-hemolytic and
b-hemolytic Streptococci, and S. pneumoniae; while galangin was found effective
against many strains of MRSA, which was synergistic with gentamicin [24].
Hydroalcohol extract prepared by hot and cold maceration processes, and methanol
extract by percolation process exhibit moderate to potent antimicrobial activity
against B. cereus, S. aureas, P. aeruginosa and E. coli, but none of the extracts
showed antifungal activity against A. niger and C. albicans [44]. Methanol extract
inhibited swarming motility of P. aeruginosa, without inhibiting its growth [20].
Three flavonoids, galangin, quercetin and baicalein exhibit synergistic effect with
b-lactam antibiotics against S. aureus, and galangin significantly inhibits penicil-
linase and b-lactamase; the three flavonoids show potential to reverse resistance of
penicillin-resistant S. aureus to b-lactam antibiotics [8]. A flavonoid exhibited
antifungal activity [37], and various extracts exhibited antifungal activity against
C. albicans [29], (contrary to findings by Srividya et al. [44]). Diarylheptanoids are
the most versatile in antimicrobial activity, showing strong antibacterial activity
against H. pylori [52], inhibitory and bactericidal activity against enteropathogenic
E. coli clinical isolates [46]. Various diarylheptanoids show broad-spectrum antiviral
activity against RSV, poliovirus, measles virus, and HSV-1 [19]. Diarylheptanoid,
7-(4ʺ-hydroxy-3ʺ-methoxyphenyl)-1-phenyl-4E-hepten-3-one significantly reduced
body weight loss and prolonged survival times of influenza virus infected mice
without toxicity, and showed in vitro antiviral activity against various strains of
influenza virus, including the oseltamivir-resistant strain [39].
Methanol extract is also reported as a strong free radical scavanger [16], protects
cells against oxidative damage [23], and is remarkably active against DMBA-induced
skin carcinogenesis in mice [51], and also inhibits breast cancer cells MCF-7 pro-
liferation in a dose- and time-dependent manner [10]. The volatile oil promotes
percutaneous penetration of 5-fluorouracil [40]. Galangin induces apoptosis and
autophagy in hepatocellular carcinoma HepG2 cells by activation of the caspase-8
and Bid pathway and by inducing endoplasmic reticulum stress [45, 53, 54], sup-
presses proliferation of melanoma cells, and inhibits formation of tumor colonies in
the lung tissue in C57BL/6J mouse lung metastatic model [55]. An extract of Korean
rhizome with kaempferol, galangin, and kaempferide as the major components, and
Alpinia officinarum Hance. 221

galangin inhibited proliferation of vascular smooth muscle cells [22]. Leaf extracts in
organic solvents of methanol, chloroform, and dichloromethane, also exhibit
antiproliferative activities against acute monocytic leukemia cells [36].
Mechanism of Action: Antiobesity effect of ethanol extract is suggested to be due
to suppression of adipogenic and lipogenic genes [14]. Anti-inflammatory activity of
the plant is credited, in part, to the inhibition of NO production in activated macro-
phages [21, 35, 50], and inhibition of prostaglandin synthetase and 5-LOX [18] by
diarylheptanoids present in the plant. Galangin induces human colon cancer cell
death through alteration of mitochondrial membrane potential and dysfunction [11].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported in publications listed on
PubMed.

References
1. An N, Lin J, Yang SL, et al. A new glycoside from Alpinia officinarum. Yao
Xue Xue Bao. 2006;41:233–5.
2. An N, Xu LZ, Zou ZM, Yang SL. Diarylheptanoids from Alpinia
officinarum. J Asian Nat Prod Res. 2006;8:637–41.
3. An N, Zou ZM, Tian Z, et al. Diarylheptanoids from the rhizomes of Alpinia
officinarum and their anticancer activity. Fitoterapia. 2008;79:27–31.
4. Beattie JH, Nicol F, Gordon MJ, et al. Ginger phytochemicals mitigate the
obesogenic effects of a high-fat diet in mice: a proteomic and biomarker
network analysis. Mol Nutr Food Res. 2011;55 Suppl 2:S203–13.
5. Bleier W, Chirikdjian JJ. Flavonoids from galanga rhizome (Alpinia
officinarum Hance). Planta Med. 1972;22:145–51 (German).
6. Bu X, Xiao G, Gu L, Zhang M. Chemical study of Alpinia officinarum.
Zhong Yao Cai. 2000;23:84–7 (Chinese).
7. Chang CL, Lin CS, Lai GH. Phytochemical characteristics, free radical
scavenging activities, and neuroprotection of five medicinal plant extracts.
Evid Based Complement Alternat Med. 2012;2012:984295.
8. Eumkeb G, Sakdarat S, Siriwong S. Reversing b-lactam antibiotic resistance
of Staphylococcus aureus with galangin from Alpinia officinarum Hance
and synergism with ceftazidime. Phytomedicine. 2010;18:40–5.
9. Fan GJ, Kang YH, Han YN, Han BH. Platelet-activating factor (PAF) receptor
binding antagonists from Alpinia officinarum. Bioorg Med Chem Lett. 2007;
17:6720–2.
10. Ghil S. Antiproliferative activity of Alpinia officinarum extract in the human
breast cancer cell line MCF-7. Mol Med Rep. 2013;7:1288–92.
11. Ha TK, Kim ME, Yoon JH, et al. Galangin induces human colon cancer cell
death via the mitochondrial dysfunction and caspase-dependent pathway.
Exp Biol Med (Maywood). 2013;238:1047–54.
222 Alpinia officinarum Hance.

12. Huang H, Wu D, Tian WX, et al. Antimicrobial effect by extracts of

rhizome of Alpinia officinarum Hance may relate to its inhibition of
beta-ketoacyl-ACP reductase. J Enzyme Inhib Med Chem. 2008;23:362–8.
13. Jensen LB, Sherman JE. Antibiotic from galingale root as food preservative.
U.S. 2,550,269, 24 Apr 1951.
14. Jung CH, Jang SJ, Ahn J, et al. Alpinia officinarum inhibits adipocyte
differentiation and high-fat diet-induced obesity in mice through regulation
of adipogenesis and lipogenesis. J Med Food. 2012;15:959–67.
15. Karlsen J, Beker F. Flavonoids of rhizoma galangae (Alpinia officinarum
Hance). Farm Aikak. 1971;80:95–7.
16. Kim BJ, Kim JH, Kim HP, Heo MY. Biological screening of 100 plant
extracts for cosmetic use (II): antioxidative activity and free radical
scavenging activity. Int J Cosmet Sci. 1997;19:299–307.
17. Kim YU, Son HK, Song HK, et al. Inhibition of 5alpha-reductase activity
by diarylheptanoids from Alpinia officinarum. Planta Med. 2003;69:72–4.
18. Kiuchi F, Iwakami S, Shibuya M, et al. Inhibition of prostaglandin and
leukotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharma-
ceut Bull. 1992;40:387–91.
19. Konno K, Sawamura R, Sun Y, et al. Antiviral activities of diarylheptanoids
isolated from Alpinia officinarum against respiratory syncytial virus,
poliovirus, measles virus, and herpes simplex virus type 1 in vitro. Nat Prod
Commun. 2011;6:1881–4.
20. Lakshmanan D, Nanda J, Jeevaratnam K. Inhibition of swarming motility of
Pseudomonas aeruginosa by methanol extracts of Alpinia officinarum
Hance. and Cinnamomum tamala T. Nees and Eberm. Nat Prod Res. 2017;
15:1–5.
21. Lee HJ, Kim JS, Ryu JH. Suppression of inducible nitric oxide synthase
expression by diarylheptanoids from Alpinia officinarum. Planta Med. 2006;
72:68–71.
22. Lee JJ, Lee JH, Yim NH, Han JH, Ma JY. Application of galangin, an active
component of Alpinia officinarum Hance (Zingiberaceae), for use in drug-
eluting stents. Sci Rep. 2017;7:8207.
23. Lee SE, Hwang HJ, Ha JS, et al. Screening of medicinal plant extracts for
antioxidant activity. Life Sci. 2003;73:167–79.
24. Lee YS, Kang OH, Choi JG, et al. Synergistic effects of the combination of
galangin with gentamicin against methicillin-resistant Staphylococcus
aureus. J Microbiol. 2008;46:283–8.
25. Li BH, Tian WX. Presence of fatty acid synthase inhibitors in the rhizome of
Alpinia officinarum Hance. J Enzyme Inhib Med Chem. 2003;18:349–56.
26. Lin LY, Peng CC, Yeh XY, et al. Antihyperlipidemic bioactivity of Alpinia
officinarum (Hance) Farw Zingiberaceae can be attributed to the coexistance
of curcumin, polyphenolics, dietary fibers and phytosterols. Food Funct.
2015;6:1600–10.
27. Liu D, Liu YW, Guan FQ, Liang JY. New cytotoxic diarylheptanoids from
the rhizomes of Alpinia officinarum Hance. Fitoterapia. 2014;96:76–80.
Alpinia officinarum Hance. 223

28. Liu D, Qu W, Zhao L, et al. A new dimeric diarylheptanoid from the

rhizomes of Alpinia officinarum. Chin J Nat Med. 2014;12:139–41.
29. Liu Q, Luyten W, Pellens K, et al. Antifungal activity in plants from
Chinese traditional and folk medicine. J Ethnopharmacol. 2012;143:772–8.
30. Lu CL, Zhao HY, Jiang JG. Evaluation of multiactivities of 14 edible
species from Zingiberaceae. Int J Food Sci Nutr. 2013;64:28–35.
31. Luo H, Cai C, Zhang J, Mo L. Study on the chemical components of Alpinia
officinarum. Zhong Yao Cai. 1998;21:349–51.
32. Ly TN, Shimoyamada M, Kato K, Yamauchi R. Antioxidative compounds
isolated from the rhizomes of smaller galanga (Alpinia officinarum Hance).
BioFactors. 2004;21:305–8.
33. Ly TN, Shimoyamada M, Kato K, Yamauchi R. Isolation and character-
ization of some antioxidative compounds from the rhizomes of smaller
galanga (Alpinia officinarum Hance). J Agric Food Chem. 2003;51:4924–9.
34. Ly TN, Yamauchi R, Shimoyamada M, Kato K. Isolation and structural
elucidation of some glycosides from the rhizomes of smaller galanga
(Alpinia officinarum Hance). J Agric Food Chem. 2002;50:4919–24.
35. Matsuda H, Ando S, Kato T, et al. Inhibitors from the rhizomes of Alpinia
officinarum on production of nitric oxide in lipopolysaccharide-activated
macrophages and the structural requirements of diarylheptanoids for the
activity. Bioorg Med Chem. 2006;14:138–42.
36. Omoregie SN, Omoruyi FO, Wright VF, et al. Antiproliferative activities of
lesser galangal (Alpinia officinarum Hance Jam1), turmeric (Curcuma longa
L.), and ginger (Zingiber officinale Rosc.) against acute monocytic
leukemia. J Med Food. 2013;16:647–55.
37. Ray PG, Majumdar SK. Antifungal flavonoid from Alpinia officinarum
Hance. Indian J Exp Biol. 1976;14:712–4.
38. Ray PG, Majumdar SK. New antifungal substance from Alpinia officinarum
Hance. Indian J Exp Biol. 1975;13:409.
39. Sawamura R, Shimizu T, Sun Y, et al. In vitro and in vivo anti-influenza
virus activity of diarylheptanoids isolated from Alpinia officinarum. Antivir
Chem Chemother. 2010;21:33–41.
40. Shen Q, Li W, Xu L. The study on Rhizoma Alpiniae officinarum and other
herbs as penetration enhancer for the permeation of 5-fluorouacil. Zhong
Yao Cai. 2000;23:697–9 (Chinese).
41. Shin D, Kinoshita K, Koyama K, Takahashi K. Antiemetic principles of
Alpinia officinarum. J Nat Prod. 2002;65:1315–8.
42. Shin JE, Han MJ, Song MC, et al. 5-Hydroxy-7-(4′-hydroxy-3′-methox-
yphenyl)-1-phenyl-3-heptanone: a pancreatic lipase inhibitor isolated from
Alpinia officinarum. Biol Pharm Bull. 2004;27:138–40.
43. Shin JE, Joo Han M, Kim DH. 3-Methylethergalangin isolated from Alpinia
officinarum inhibits pancreatic lipase. Biol Pharm Bull. 2003;26:854–7.
44. Srividya AR, Dhanabal SP, Misra VK, Suja G. Antioxidant and antimicro-
bial activity of Alpinia officinarum. Indian J Pharm Sci. 2010;72:145–8.
224 Alpinia officinarum Hance.

45. Su L, Chen X, Wu J, et al. Galangin inhibits proliferation of hepatocellular

carcinoma cells by inducing endoplasmic reticulum stress. Food Chem
Toxicol. 2013;62:810–6.
46. Subramanian K, Selvakkumar C, Vinaykumar KS, et al. Tackling multiple
antibiotic resistance in enteropathogenic Escherichia coli (EPEC) clinical
isolates: a diarylheptanoid from Alpinia officinarum shows promising
antibacterial and immunomodulatory activity against EPEC and its
lipopolysaccharide-induced inflammation. Int J Antimicrob Agents. 2009;
33:244–50.
47. Sun Y, Tabata K, Matsubara H, et al. New cytotoxic diarylheptanoids from
the rhizomes of Alpinia officinarum. Planta Med. 2008;74:427–31.
48. Wei N, Zhou Z, Wei Q, et al. A novel diarylheptanoid-bearing sesquiterpene
moiety from the rhizomes of Alpinia officinarum. Nat Prod Res. 2016;30:
2344–9.
49. Xia DZ, Yu XF, Wang HM, et al. Antiobesity and hypolipidemic effects of
ethanolic extract from Alpinia officinarum Hance (Zingiberaceae) in rats fed
high-fat diet. J Med Food. 2010;13:785–91.
50. Yadav PN, Liu Z, Rafi MM. A diarylheptanoid from lesser galangal
(Alpinia officinarum) inhibits proinflammatory mediators via inhibition of
mitogen-activated protein kinase, p44/42, and transcription factor nuclear
factor-kappa B. J Pharmacol Exp Ther. 2003;305:925–31.
51. Yasukawa K, Sun Y, Kitanaka S, et al. Inhibitory effect of the rhizomes of
Alpinia officinarum on TPA-induced inflammation and tumor promotion in
two-stage carcinogenesis in mouse skin. Nat Med (Tokyo). 2008;62:374–8.
52. Zhang BB, Dai Y, Liao ZX, Ding LS. Three new antibacterial active
diarylheptanoids from Alpinia officinarum. Fitoterapia. 2010;81:948–52.
53. Zhang H, Li N, Wu J, et al. Galangin inhibits proliferation of HepG2 cells
by activating AMPK via increasing the AMP/TAN ratio in a LKB1-
independent manner. Eur J Pharmacol. 2013;718:235–44.
54. Zhang HT, Wu J, Wen M, et al. Galangin induces apoptosis in hepatocellular
carcinoma cells through the caspase 8/t-Bid mitochondrial pathway. J Asian
Nat Prod Res. 2012;14:626–33.
55. Zhang W, Tang B, Huang Q, Hua Z. Galangin inhibits tumor growth and
metastasis of B16F10 melanoma. J Cell Biochem. 2013;114:152–61.
56. Zou QY, Wu HF, Tang YL, Chen DZ. A new labdane diterpene from the
rhizomes of Alpinia officinarum. Nat Prod Res. 2016;30:1–6.
Alstonia scholaris (L.) R.Br.
(Apocynaceae)

(Syn.: Echites scholaris L.)

Abstract
A tall evergreen tree widely cultivated throughout India and also found in China,
Africa, southeast Asia, Latin America, and Australia. The bark is reputed in
Hindu medicine for ages as tonic, alterative, useful in fever and skin diseases, a
remedy in chronic diarrhea and advanced stages of dysentery, valued as a
febrifuge, and used in the treatment of gout, rheumatism, in convalescence after
exhausting diseases and fevers. In China, it is widely used to treat respiratory
diseases, such as cough, asthma, phlegm, and COPD. On the island of Luzon,
bark is esteemed by the natives as the most efficient tonic and febrifuge, and used
as decoction since time immemorial for malignant, intermittent, and remittent
fevers. In Nigeria, the bark is widely used as an antipyretic in malaria, and
sometimes, together with leaves and roots, in external application for rheumatic
pains. In Ghana, bark decoction is given after childbirth to help expel placenta.
Bark contains triterpenes: b-amyrine and lupeol; and indole alkaloids: echita-
mine or ditain as the main alkaloid, alstoscholarisines H-J, echitamidine and a
lactone ditamine. Methanol bark extract produced adaptogenic effects in mice,
increased cognitive and memory functions, and exhibited potent antioxidant
activity. Petroleum ether and methanol bark extracts are devoid of antimalarial
activity against P. falciparum (in vitro) and P. berghei (in vivo); methanol
extract, though, delays mortality and improves physical conditions of treated
mice. The spasmolytic activity in isolated preparations is proposed to be due to
calcium channel blockade, and the bronchovasodilatory activity is presumed to
be due to prostaglandins, calcium antagonism and release of NO.

Keywords



Chhatium Devil’s tree Dita bark Hoa sữa

Pulai
Satoona
Saptaparna




Satveni Tang jiao shu Zitronenmahagoni

© Springer Nature Switzerland AG 2020 225

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_21
226 Alstonia scholaris (L.) R.Br.

Vernaculars: Urd.: Satoona, Satwan; Hin.: Chhatium, Datyuni, Sapthaparna,

Satium, Satni, Satparna, Satveni; San.: Gajamadagandhapuspa, Guchha-pushpa,
Sapta-chhada, Saptaparna, Sarada, Sãlmalipatraka, Tvaka, Viśãlatwak, Visamac-
chada, Vishala-tvaka, Vrihat; Ben.: Chhatim, Datyuni, Pulai; Mal.: Aerilampal,
Daivapal, Ezhilampala, Mukan-pala, Pala; Mar.: Hori kowan, Satavin; Tam.:
Aelilappalai, Elilaipalai, Ezhilaip-palai, Wodrasi; Tel.: Aedakularitichettu, Edaku-
lapala, Edakulayaraticettu, Palagaruda; Chi.: 糖胶树, Deng jia shu, Fei zhu ye, Jiu
du ye, Tang jiao shu; Eng.: Devil’s tree, Dita bark, Milkwood pine, Scholar tree,
Stool wood, White cheesewood; Ger.: Teufelsbaum, Weißquirlbaum, Zitronen-
mahagoni; Maly.: Pulai (Indonesia), Pule; Tag.: Dita, Ditáa; Vie.: Hoa sữa.
Description: It is a tall evergreen tree widely cultivated throughout India and found in
the sub-Himalayan tracts from Jammu eastward ascending to 3,000 ft, and also found in
China, Africa, Southeast Asia, Latin America, and Australia. The branches are whorled,
and the bark is dark grey, and somewhat rough; leaves are in whorls, 4–7 in a whorl,
leathery, oblong-obovate, 10–20 cm long, 3–4.5 cm wide, rounded at the tip and
pointed at the base, green and shining on the upper surface, and white or greyish on the
lower. Flowers are crowded, numerous, somewhat hairy, greenish-white, about 1 cm
long.CXVII Unjustifiably, Alstonia macrophylla is used as a substitute in various herbal
pharmaceutical preparations in India [35] (Figs. 1, 2 and 3).
Actions and Uses: The bark is reputed in Hindu medicine for ages as tonic, alterative,
useful in fever and skin diseases, a remedy in chronic diarrhea and advanced stages of

Fig. 1 Alstonia scholaris, Tree, Amar, WikimediaCommons; ShareAlike 2.0 Generic CC BY-SA
2.0, https://commons.wikimedia.org/wiki/File:Alstonia_scholaris.jpg; https://creativecommons.org/
licenses/by-sa/2.0/deed.en
Alstonia scholaris (L.) R.Br. 227

Fig. 2 Alstonia scholaris, Leaves and Flowers, J.M. Garg, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Saptaparni_(Alstonia_scholaris)_
leaves_%26_flowers_in_Kolkata_W_IMG_0534.jpg; https://creativecommons.org/licenses/by-sa/3.0/
deed.en

Fig. 3 Alstonia scholaris, Leaves, Jeevan Jose, WikimediaCommons; ShareAlike 4.0 Interna-
tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Alstonia_scholaris_by_kadavoor.
JPG; https://creativecommons.org/licenses/by-sa/4.0/deed.en

dysentery, valued as a febrifuge,XXI,LXXXI and used in the treatment of gout,

rheumatism, in convalescence after exhausting diseases and fevers.LXXXI Tempera-
ment of the bark is cold and moist, with properties, such as aphrodisiac, galacta-
gogue,LXXVII emmenagogue, antidysenteric, and antipyretic,CXXXXVII and stimulant,
carminative, stomachic, bitter tonic, astringent, expectorant, febrifuge, alterative, and
antiperiodic.CV In China, it is widely used to treat respiratory diseases, such as cough,
228 Alstonia scholaris (L.) R.Br.

asthma, phlegm, and COPD [58]. Milky juice of the plant is applied on wounds and
ulcers to treat pain, earache and also in rheumatic pains as folk medicine in India [53].
Dymock et al.XL mentioned that on the island of Luzon, bark is esteemed by the natives
as the most efficient tonic and febrifuge, and used as decoction since time immemorial
for malignant, intermittent, and remittent fevers. They also describe its use in India for
catarrhal dyspepsia, as anthelmintic, and for enlarged spleen; the juice of fresh bark
with milk is administered in leprosy. In Ayurveda, bark is used in śūla, gulma, kr-
miroga, kustha, jawara, and sãndrameha.LIX Some reports suggest it useful in treating
malaria, abdominal disorders, leprosy, tumors, chronic and foul ulcers, asthma,
bronchitis, helminthiasis, and debility [3, 4]. Tribal practitioners of the Marakh sect of
the Garos indigenous community of Bangladesh use it for the treatment of diabetes
[44]. It is also described as abortifacient, ecbolic and oxytocic [9], and as emmena-
gogue [46]. Several species of Alstonia have been used in the past as antimalarials, and
bark of Indian A. scholaris was included in 1914 edition of British Pharmacopoea, as it
was considered very efficacious against chronic diarrhea.LXXXVIII In the Philippines,
the bark is a known remedy for fever, chronic diarrhea and dysentery.CXVII In Nigeria,
the bark is widely used as an antipyretic in malaria, and sometimes, together with
leaves and roots, in external application for rheumatic pains. Smearing the latex on
calabar swellings caused by filaria has also been recommended. In Ghana, bark
decoction is given after childbirth to help expel placenta.XXX
Phytoconstituents: Eleven Alstonia species are known to contain alkaloids, such as
alstonin, alstoniline, cillastonin and echitamine.CXXXXI Indian species contain several
alkaloids with CNS action; picrinine potentiated hexobarbitone narcosis and mor-
phine analgesia [12]. Bark contains triterpenes: b-amyrine and lupeol; and indole
alkaloids: echitamine or ditain as the main alkaloid, alstoscholarisines H-J [42],
echitamidine and a lactone ditamine. Yield of total alkaloids varies with location; total
alkaloid content of Indian bark is 0.16–0.27%; from Ghana it is 0.38–0.56%; of
Nigeria 0.18–0.31%; and of Cameroons 0.11%. Methanol leaf extract contains fla-
vonoids, proanthocynidins and phenolics [15], pentacyclic triterpenoids: lupeol,
betulin, 3-hydroxy-11-ursen-28,13-olide, betulinic acid, oleanolic acid [55], and
ursolic acid [13, 36, 55], b-sitosterol and n-tetracosane as major sterols, and linoleic
acid as the predominant fatty acid [13]. A number of indole and other alkaloids have
been reported from leaves: nareline, picralinal [6, 11, 12, 41, 45]; 19,20-dihydro-
condylocarpine [1]; echitaminic acid, echitamidine N-oxide, N(b)-demethylal-
stogustine, N(b)-demethylalstogustine N-oxide, echitamidine-N-oxide 19-O-beta-D-
glucopyranoside, akuammiginone, akuammicine N-oxide [47]; (19,20)E-alstoscho-
larine and (19,20)Z-alstoscholarine [7]; manilamine, N4-methylangustilobine B, 19,
20-(E)-vallesamine, angustilobine B N4-oxide, 20(S)-tubotaiwine, and 6,7-seco-
angustilobine B [40], scholarisine A [8], N(1)-methoxymethyl picrinine, alistonitrine
A [59], alstoniascholarines L-Q from inadequately dried leaves [43], and terpenoids:
alstonic acids A and B [56]. Scholaricine and vallesamine are suggested to be
responsible for beneficial effects of total alkaloids in allergic asthma [57]. Triter-
penoids, alstoprenyol, 3-b-hydroxy-28-b-acetoxy-5-olea triterpene and alsto-
prenylene 3b-acetate-24-nor-urs-4,12,2′-triene ester triterpene, and a-amyrin acetate,
Alstonia scholaris (L.) R.Br. 229

a-amyrin, lupeol acetate, and 3b-hydroxy-24-nor-urs-4,12,28-triene triterpene were

isolated from flowers [54]. From fruit pods, indole alkaloids: N-formylscholarine,
picrinine, strictamine and nareline are reported [30]. Leaves contain flavonoids: gal-
lic acid, catechin, epicatechin, ellagic acid kaempferol [53], quercetin, isorham-
netin, kaempferol-3-0-b-D-galactopyranoside, quercetin-3-0-b-D-galactopyranoside,
isorhamnetin-3-0-b-D-galactopyranoside, kaempferol-3-0-b-D-xylopyranosyl-(2-1)-
0-b-D-galactopyranoside, and quercetin-3-0-b-D-xylopyranosyl-(2-1)-0-b-D-galac-
topyranoside [19].
Pharmacology: Methanol bark extract pretreatment produced antistress (adapto-
genic) activity in acute stress restraint model in mice, increased cognitive and
memory functions [37], and exhibited potent in vitro antioxidant activity [27].
Ethanol leaf extract produced neuroleptic effect, and reduced dopamine concen-
tration in frontal cortex of rat brain [31]. Both aqueous and ethanol bark extracts
significantly enhanced phagocytic activity of immunosuppressed mice; aqueous
extract shows higher phagocytic index than ethanol extract [20]. Methanol extract
produced significant antidiarrheal activity against castor-oil induced diarrhea [50].
Hepatoprotective effect against CCl4-, b-D-galactosamine-, APAP- and ethanol-
induced hepatotoxicity has been reported [39]. Treatment of male rats with ethanol
bark extract and lupeol acetate caused loss of reproductive organs weight and sperm
count, resulting in total infertility [16, 17]. Petroleum ether and methanol bark
extracts are devoid of antimalarial activity against P. falciparum (in vitro) and
P. berghei (in vivo); methanol extract, though, delays mortality and improves
physical conditions of treated mice [14, 33]. Methanol leaf extract significantly
attenuated chronic constriction injury of sciatic nerve-induced neuropathic pain in
rats [53].
Ethanol leaves extract produced significant bronchodilation, but did not relax
in vitro tracheal smooth muscle [10]. Ethanol leaves extract and alkaloid fraction
produced antitussive, antiasthmatic and expectorant effects [52], and total alkaloids
from leaves protected rats against LPS-induced airway inflammation [58]. Alka-
loids, picrinine, vallesamine and scholaricine produced in vivo anti-inflammatory
and analgesic effects [51]. Pretreatment of mice with hydroalcohol bark extract
protected against whole body c-irradiation-induced hematological and biochemical
changes and reduced LPO [18]. The extract also shows chemopreventive activity
against B(a)P-induced forestomach carcinoma in mice [21], and enhances antitumor
effect of berberine hydrochloride [22], and CP in EAC-bearing mice [25]. Alkaloid
fraction increases sensitivity of neoplastic cell lines (such as HeLa, KB cells) to
c-irradiation and enhances cell killing. Also, pretreatment of EAC-bearing mice
with alkaloid fraction increases irradiation-induced remission of tumor and survival
time [23, 28]. Pretreatment with the extract significantly decreased tumor incidence,
yield, tumor burden, and cumulative number of DMBA-induced papillomas in mice
[29]. Echitamine regresses 20-MCA-induced fibrosarcoma growth in rats, and
reverses activities of several enzymes to near normal levels [32], restores levels of
drug detoxyfying enzymes in Sarcoma 180-bearing mice, that are reduced in tumor-
bearing animals [48], and inhibits glycolytic enzymes, such as hexokinase and LDH
230 Alstonia scholaris (L.) R.Br.

in Sarcoma S-180 cells, depriving cells of energy and respiration, resulting in loss
of cell viability [49]. Various fractions of stem bark collected during summer
produced maximum killing of HeLa cells, compared to those collected in winter or
monsoon season [26]. Ethanol bark extract reduces skin irritation, strengthens
ability of retinoids to inhibit matrix metalloproteinase-1 expression, suppresses
proinflammatory cytokines, and enhances antiaging effects of topical retinoids
[38].
Methanol leaf extract possesses moderate antibacterial activity against S. aureus,
B. subtilis, E. coli and P. aeruginosa [15]; ethanol extract exhibited significant
inhibitory activity against clinical isolates of MRSA and carbapenemase-producing
K. pneumoniae, and C. albicans [5]. Ursolic acid synergistically enhances effect of
ampicillin and tetracycline against B. cereus and S. aureus [55]. Butanol fractions
of methanol extracts of leaves, stem and root bark, also showed significant
antibacterial activity [34].
Mechanism of Action: The spasmolytic activity in isolated preparations is pro-
posed to be due to calcium channel blockade [50], and the bronchovasodilatory
activity is presumed to be due to prostaglandins, calcium antagonism and release of
NO [10]. The in vivo anti-inflammatory and analgesic effects of alkaloids, picrinine,
vallesamine and scholaricine may be the result of inhibition of inflammatory
mediators, such as COX-1, COX-2, and 5-LOX [51]. Ethanol bark extract also
suppresses proinflammatory cytokines [38].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Toxicity of hydroalcohol bark extract is dose-, route-, species-
and time of bark collection-dependent. Extract of bark collected during monsoon
season was least toxic, while that collected during summer season was most toxic,
followed by that collected during winter. Rats are relatively more sensitive to
toxicity than mice; Swiss albino mice being most sensitive, followed by DBA and C
(57)BL mice. The extract is more toxic by intraperitoneal than by oral route; LD50
(i.p.) in rats being 1,200 mg/kg [2]. Doses up to 20% of the LD50 dose, admin-
istered to Swiss albino mice on day 11 of gestation are nonteratogenic, do not cause
any mortality or affect normal growth of the litter. Higher doses, however, produce
dose-dependent mortality, growth retardation and congenital malformation in litters
born to extract-treated mothers [24].
Commentary: There are no clinical studies reported in the mainstream English
publications listed on PubMed.
Alstonia scholaris (L.) R.Br. 231

References
1. Alvi KA, Muzaffar A. Isolation and 1H/13C-NMR studies on 19,20-dihydro-
condylocarpine: an alkaloid from the leaves of Ervatamia coronaria and
Alstonia scholaris. Planta Med. 1986;52:325–6.
2. Baliga MS, Jagetia GC, Ulloor JN, et al. The evaluation of the acute toxicity
and long-term safety of hydroalcoholic extract of Sapthaparna (Alstonia
scholaris) in mice and rats. Toxicol Lett. 2004;151:317–26.
3. Baliga MS. Alstonia scholaris Linn R Br in the treatment and prevention of
cancer: past, present, and future. Integr Cancer Ther. 2010;9:261–9.
4. Baliga MS. Review of the phytochemical, pharmacological and toxicolog-
ical properties of Alstonia scholaris Linn. R. Br (Saptaparna). Chin J Integr
Med. 28 Mar 2012 (Epub ahead of print).
5. Bonvicini F, Mandrone M, Antognoni F, Poli F, Gentilomi GA. Ethanolic
extracts of Tinospora cordifolia and Alstonia scholaris show antimicrobial
activity towards clinical isolates of methicillin-resistant and carbapenemase-
producing bacteria. Nat Prod Res. 2014;28:1438–45.
6. Boonchuay W, Court WE. Alkaloids of Alstonia scholaris from Thailand.
Planta Med. 1976;29:380–90.
7. Cai XH, Du ZZ, Luo XD. Unique monoterpenoid indole alkaloids from
Alstonia scholaris. Org Lett. 2007;9:1817–20.
8. Cai XH, Tan QG, Liu YP, et al. A cage-monoterpene indole alkaloid from
Alstonia scholaris. Org Lett. 2008;10:577–80.
9. Casey RC. 298 alleged antifertility plants of India. Indian J Med Sci. 1960;
14:590–600.
10. Channa S, Dar A, Ahmed S, Atta-ur-Rahman. Evaluation of Alstonia scholaris
leaves for bronchovasodilatory activity. J Ethnopharmacol. 2005;97:469–76.
11. Dhar DN. Suri SC, Dwivedi. Chemical examination of the flowers of
Alstonia scholaris. Planta Med. 1977;31:33–4.
12. Dutta SC, Bhattacharya SK, Ray AB. Flower alkaloids of Alstonia scholaris.
Planta Med. 1976;30:86–9.
13. El-Askary HI, El-Olemy MM, Salama MM, Sleem AA, Amer MH.
Bioguided isolation of pentacyclic triterpenes from the leaves of Alstonia
scholaris (Linn.) R. Br. growing in Egypt. Nat Prod Res. 2012;26:1755–8.
14. Gandhi M, Vinayak VK. Preliminary evaluation of extracts of Alstonia
scholaris bark for in vivo antimalarial activity in mice. J Ethnopharmacol.
1990;29:51–7.
15. Ganjewala D, Gupta AK. Study on phytochemical composition, antibac-
terial and antioxidant properties of different parts of Alstonia scholaris Linn.
Adv Pharm Bull. 2013;3:379–84.
16. Gupta RS, Bhatnager AK, Joshi YC, et al. Induction of antifertility with
lupeol acetate in male albino rats. Pharmacology. 2005;75:57–62.
17. Gupta RS, Sharma R, Sharma A, et al. Effect of Alstonia scholaris bark
extract on testicular function of Wistar rats. Asian J Androl. 2002;4:175–8.
232 Alstonia scholaris (L.) R.Br.

18. Gupta U, Jahan S, Chaudhary R, Pradeep Kumar Goyal. Amelioration of

radiation-induced hematological and biochemical alterations by Alstonia
scholaris (a medicinal plant) extract. Integr Cancer Ther. 2008;7:155–61.
19. Hui T, Sun Y, Zhu L, et al. Flavonoids in leaves of Alstonia scholaris.
Zhongguo Zhong Yao Za Zhi. 2009;34:1111–3 (Chinese).
20. Iwo MI, Soemardji AA, Retnoningrum DS, Sukrasno UUM. Immunostim-
ulating effect of pule (Alstonia scholaris L. R.Br., Apocynaceae) bark
extracts. Clin Hemorheol Microcirc. 2000;23:177–83.
21. Jagetia GC, Baliga MS, Venkatesh P. Effect of Sapthaparna (Alstonia
scholaris Linn) in modulating the benzo(a)pyrene-induced forestomach
carcinogenesis in mice. Toxicol Lett. 2003;144:183–93.
22. Jagetia GC, Baliga MS. Effect of Alstonia scholaris in enhancing the
anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing
mice. J Med Food. 2004;7:235–44.
23. Jagetia GC, Baliga MS. Evaluation of anticancer activity of the alkaloid
fraction of Alstonia scholaris (Sapthaparna) in vitro and in vivo. Phytother
Res. 2006;20:103–9.
24. Jagetia GC, Baliga MS. Induction of developmental toxicity in mice treated
with Alstonia scholaris (Sapthaparna) in utero. Birth Defects Res B Dev
Reprod Toxicol. 2003;68:472–8.
25. Jagetia GC, Baliga MS. Modulation of antineoplastic activity of cyclophos-
phamide by Alstonia scholaris in the Ehrlich ascites carcinoma-bearing
mice. J Exp Ther Oncol. 2003;3:272–82.
26. Jagetia GC, Baliga MS. The effect of seasonal variation on the antineo-
plastic activity of Alstonia scholaris R. Br. in HeLa cells. J Ethnopharmacol.
2005;96:37–42.
27. Jagetia GC, Baliga MS. The evaluation of nitric oxide scavenging activity of
certain Indian medicinal plants in vitro: a preliminary study. J Med Food.
2004;7:343–8.
28. Jagetia GC, Baliga MS. Treatment with Alstonia scholaris enhances radiosen-
sitivity in vitro and in vivo. Cancer Biother Radiopharm. 2003;18:917–29.
29. Jahan S, Chaudhary R, Goyal PK. Anticancer activity of an Indian medicinal
plant, Alstonia scholaris, on skin carcinogenesis in mice. Integr Cancer Ther.
2009;8:273–9.
30. Jain L, Pandey MB, Singh S, et al. A new indole alkaloid from Alstonia
scholaris. Nat Prod Res. 2009;23:1599–602.
31. Jash R, Chowdary KA. Ethanolic extracts of Alstonia Scholaris and Bacopa
Monniera possess neuroleptic activity due to antidopaminergic effect.
Pharmacognosy Res. 2014;6:46–51.
32. Kamarajan P, Sekar N, Mathuram V, Govindasamy S. Antitumor effect of
echitamine chloride on methylcholonthrene induced fibrosarcoma in rats.
Biochem Int. 1991;25:491–8.
33. Keawpradub N, Kirby GC, Steele JC, Houghton PJ. Antiplasmodial activity
of extracts and alkaloids of three Alstonia species from Thailand. Planta
Med. 1999;65:690–4.
Alstonia scholaris (L.) R.Br. 233

34. Khan MR, Omoloso AD, Kihara M. Antibacterial activity of Alstonia

scholaris and Leea tetramera. Fitoterapia. 2003;74:736–40.
35. Khyade MS, Kasote DM, Vaikos NP. Alstonia scholaris (L.) R. Br. and
Alstonia macrophylla Wall. ex G. Don: a comparative review on traditional
uses, phytochemistry and pharmacology. J Ethnopharmacol. 2014;153:1–18.
36. Kucera M, Marquis VO, Kucerova H. Contribution to the knowledge of
Nigerian medicinal plants. I. TLC separation and quantitative evaluation of
Alstonia boonei alkaloids. Planta Med. 1972;21:343–6.
37. Kulkarni MP, Juvekar AR. Effect of Alstonia scholaris (Linn.) R. Br. on
stress and cognition in mice. Indian J Exp Biol. 2009;47:47–52.
38. Lee SJ, Cho SA, An SS, et al. Alstonia scholaris R. Br. significantly inhibits
retinoid-Induced skin irritation in vitro and in vivo. Evid Based Complement
Alternat Med. 2012;2012:190370.
39. Lin SC, Lin CC, Lin YH, et al. The protective effect of Alstonia scholaris R.
Br. on hepatotoxin-induced acute liver damage. Am J Chin Med. 1996;24:
153–64.
40. Macabeo AP, Krohn K, Gehle D, et al. Indole alkaloids from the leaves of
Philippine Alstonia scholaris. Phytochemistry. 2005;66:1158–62.
41. Morita Y, Hesse M, Schmid H, et al. Alstonia scholaris: the structure of the
indole alkaloid nareline (author’s transl). Helv Chim Acta. 1977;60:1419–32.
42. Pan Z, Qin XJ, Liu YP, et al. Alstoscholarisines H-J, indole alkaloids from
Alstonia scholaris: structural evaluation and bioinspired synthesis of
alstoscholarisine H. Org Lett. 2016;18:654–7.
43. Qin XJ, Zhao YL, Song CW, et al. Monoterpenoid indole alkaloids from
inadequately dried leaves of Alstonia scholaris. Nat Prod Bioprospect.
2015;5:185–93.
44. Rahmatullah M, Azam MN, Khatun Z, et al. Medicinal plants used for
treatment of diabetes by the Marakh sect of the Garo tribe living in
Mymensingh district, Bangladesh. Afr J Tradit Complement Altern Med.
2012;9:380–5.
45. Rastogi RC, Kapil RS, Popli SP. Picralinal—a key alkaloid of picralima
group from Alstonia scholaris R. Br. Experientia. 1970;26:1056.
46. Saha JC, Kasinathan S. Ecbolic properties of Indian medicinal plants. II.
Indian J Med Res. 1961;49:1094–8.
47. Salim AA, Garson MJ, Craik DJ. New indole alkaloids from the bark of
Alstonia scholaris. J Nat Prod. 2004;67:1591–4.
48. Saraswathi V, Mathuram V, Subramanian S, Govindasamy S. Modulation of
the impaired drug metabolism in sarcoma-180-bearing mice by echitamine
chloride. Cancer Biochem Biophys. 1999;17:79–88.
49. Saraswathi V, Ramamoorthy N, Subramaniam S, et al. Inhibition of
glycolysis and respiration of sarcoma-180 cells by echitamine chloride.
Chemotherapy. 1998;44:198–205.
50. Shah AJ, Gowani SA, Zuberi AJ, et al. Antidiarrhoeal and spasmolytic
activities of the methanolic crude extract of Alstonia scholaris L. are
mediated through calcium channel blockade. Phytother Res. 2010;24:28–32.
234 Alstonia scholaris (L.) R.Br.

51. Shang JH, Cai XH, Feng T, et al. Pharmacological evaluation of Alstonia
scholaris: anti-inflammatory and analgesic effects. J Ethnopharmacol.
2010;129:174–81.
52. Shang JH, Cai XH, Zhao YL, et al. Pharmacological evaluation of Alstonia
scholaris: antitussive, antiasthmatic and expectorant activities. J Ethnophar-
macol. 2010;129:293–8.
53. Singh H, Arora R, Arora S, Singh B. Ameliorative potential of Alstonia
scholaris (Linn.) R. Br. against chronic constriction injury-induced
neuropathic pain in rats. BMC Complement Altern Med. 2017;17:63.
54. Sultana N, Saify ZS, Saleem M, Kamal M. Two new triterpenes from
Alstonia scholaris flowers. Nat Prod Res. 2013;27:1277–86.
55. Wang CM, Chen HT, Wu ZY, et al. Antibacterial and synergistic activity of
pentacyclic triterpenoids isolated from Alstonia scholaris. Molecules.
2016;21:139.
56. Wang F, Ren FC, Liu JK. Alstonic acids A and B, unusual 2,3-secofernane
triterpenoids from Alstonia scholaris. Phytochemistry. 2009;70:650–4.
57. Zhao YL, Cao J, Shang JH, et al. Airways antiallergic effect and pharmaco-
kinetics of alkaloids from Alstonia scholaris. Phytomedicine. 2017;27:63–72.
58. Zhao YL, Shang JH, Pu SB, et al. Effect of total alkaloids from Alstonia scholaris
on airway inflammation in rats. J Ethnopharmacol. 2016;178:258–65.
59. Zhu GY, Yao XJ, Liu L, Bai LP, Jiang ZH. Alistonitrine A, a caged monoterpene
indole alkaloid from Alstonia scholaris. Org Lett. 2014;16:1080–3.
Althaea officinalis L.
(Malvaceae)

Abstract
An annual herb that grows in temperate climates, western and northern Asia,
India, and Europe. Marshmallow was held in great esteem by the Greeks and the
Romans due to its healing properties, and has been described by Dioscorides and
Theophrastus. It forms a soft smooth covering to inflammed or irritated parts with
which it comes in contact, and protects them from friction and allows the process
of repair undisturbed. In the days of Dioscorides and Pliny, the decoction was
prescribed for asthma, bronchitis, hoarseness, pleurisy, dysentery, muscular and
nerve injuries, and to counteract loss of blood and relieve inflammations. Root is
stronger in characteristics; strong laxative, anti-inflammatory, antidysentery,
anticolic, expels urinary stones, and is beneficial in cough and pleurisy. The
German Commission E has declared it an effective demulcent, and it is approved
for GI disorders since 2006 by the HMPC of the European Medicines Agency.
Flavonoid glycosides, phenolic acids and coumarins have been isolated from
roots. The taproot, when dried, contains 25–35% mucilage, about 35% starch, and
10% pectin. Althaea extract and its isolated polysaccharide produce antitussive
activity in cats, polysaccharide being more effective; the polysaccharide,
rhamnogalacturonan inhibits cough reflex in conscious cats better than nonnar-
cotic antitussives, and at higher doses, comparable to codeine. Althaea extracts, in
combination with topical steroids potentiate effect of steroids in skin afflictions. In
an RCT, leaf compress along with warm compress before nursing and a cold
compress after nursing, significantly reduced breast engorgement in lactating
women.

Keywords



Althée Echte heemst Gul khairu Khatmi Khitmy


Læge-stokrose




Malvavisco Marshmallow Samtpappel Yàoshǔkuí

© Springer Nature Switzerland AG 2020 235

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_22
236 Althaea officinalis L.

Vernaculars: Urd.: Khatmi; Hin.: Gul-i-khere (flowers), Gul khairu, Khaira,

Khitmi,; Tam.: Shemaitute, Simaitutti; Ara.: Khitmy; Chi.: 药蜀葵, Yào kuí,
Yàoshǔkuí; Dan.: Læge-stokrose; Dut.: Echte heemst; Eng.: Marshmallow; Fin.:
Rohtosalkoruusu; Fre.: Althée, Guimauve officinale, Mauve blanche, Mauve hér-
issée; Ger.: Echter eibisch, Samtpappel; Ita.: Benefischi, Bismalva, Malvacioni,
Malvavisco; Jap.: Birôdo-aoi; Per.: Gul khairu (flowers), Rishah-i-khitmi (roots),
Tukhm-i-khitmi (seeds); Pol.: Prawoślaz lekarski, Ślaz lekarski; Por.: Malvaisco;
Spa.: Altea, Bismalva, Malvavisco, Malvavisco común, Malvi; Swe.: Altearot,
Läkemalva: Tur.: Deli hatmi.
Description: An annual herb with perennial, spindle-shaped or cylindrical, tapering
woody taproot and several erect, stout, downy stems, 30–150 cm, sparsely branched.
It grows in temperate climates, western and northern Asia, India (Kashmir), and
Europe. Found on waste land generally, but on the coast especially, this herb has
thick downy leaves and pretty mauvish flowers, which appear in clusters at the
height of summer.XXVI Leaves are alternate, greyish-green, velvety, being covered
with fine, star-shaped hairs. Lower leaves are nearly circular, 3–8 cm wide; upper
leaves ovate or lanceolate, pointed, deeply lobed and toothed and partly folded.
Flowers, borne in the axils of upper leaves, solitary or 2 or 3 together 2.5–5 cm wide,
with 5 pink or white, obovate, notched petals, and prominent staminal tube tipped
with kidney-shaped anthers. The double velvety calyx has 6–9 outer segments and 5
inner, triangular, long-pointed sepals. Calyx cups the downy, oblate fruit which
consists of numerous carpels, each containing a single, kidney-shaped, brown 3 mm
long seed. Blooming season is from July to September.C The plant is grown from
seed or offset from old plants, the roots being harvestable the second year after
planting offset, and three years from seed. It tolerates a variety of soils, but does best
in deep loam with abundant moisture.V Different parts of the plant used in India were
imported from Persia.XL The taproots are collected in the fall, freed of lateral
rootlets, washed, peeled and dried (Figs. 1, 2 and 3).CLII
Actions and Uses: Marshmallow was held in great esteem by the Greeks and the
Romans due to its healing properties, and has been described by Dioscorides and
Theophrastus. It forms a soft smooth covering to inflamed or irritated parts with
which it comes in contact, and protects them from friction and allows the process of
repair undisturbed.XL Various parts of the plant are mucilaginous, emollient and
demulcent, and protect inflamed parts from irritation by a soothing covering.LXXXI It
was extolled in the days of Dioscorides and Pliny, and the decoction was prescribed
for asthma, bronchitis, hoarseness, pleurisy, dysentery, muscular and nerve injuries,
and to counteract loss of blood and relieve inflammations. It was valued in acute
ophthalmia, and also used as a gargle for gum troubles and sore throat. Powdered or
crushed root was applied externally as a poultice on abrasions, eruptions, muscular
and nerve injuries.XII,C Ibn Jazlah used it to reduce swelling, relieve joint pains, and
in duck fat for sciatica and bee stings.LIII A piece of the root is given to an infant to
chew, when the first teeth are appearing.CXXIV In cystitis, retention of urine, gon-
orrhea and leucorrhea, it is taken to relax urinary passages and relieve pain.CLIV The
flowers, leaves and seeds are also employed in infusions, though they are less
Althaea officinalis L. 237

Fig. 1 Althaea officinalis, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Althaea_officinalis_-_K%C3%B6hler%
E2%80%93s_Medizinal-Pflanzen-008.jpg

Fig. 2 Althaea officinalis, Flower, Salguero, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Althea_officinalis_flor.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
238 Althaea officinalis L.

Fig. 3 Althaea officinalis, Roots, Victor M. Vicente Selvas, WikimediaCommons; Universal CC0
1.0, https://commons.wikimedia.org/wiki/File:Arrels_malvi12.JPG; https://creativecommons.org/
publicdomain/zero/1.0/deed.en

mucilaginous than the root.CXXIV The seeds temperate, and leaves cold and moist in
temperament, are emollient, suppurative, analgesic, anti-inflammatory and antitus-
sive, and the decoction of flowers and seeds is demulcent for respiratory tract.
Externally, the poultice and fomentation are used for breasts inflammation, arthritis,
gout, pleurisy and pneumonia. Internally the root (temperament, cold and moist
according to Galen, while Rhazes and Avicenna described it hot 1° or moderate)
decoction is used for dysuria, dysentery, irritable and inflammatory intestinal con-
ditions, and biliary diarrhea.LXXVII Paste of seeds and leaves relieves headache due
to heat, and is anti-inflammatory and analgesic. Flowers decoction is diuretic,
emmenagogue, lithotriptic, and heals intestinal ulcers. Root is stronger in charac-
teristics; strong laxative, anti-inflammatory, antidysentery, anticolic, expels urinary
stones, and is beneficial in cough and pleurisy.L Internally, flowers are expectorant,
and the root is demulcent; externally, leaves are used for poultice and fomentation,
and mixed with oil the leaves and flowers are applied to burns and venomous
bites.CV
David ConwayXXVI described it as one of the best herbal cough remedies that is
used to treat most pectoral disorders, including pleurisy; it also releases retained
placenta after birth. In all cases a standard infusion or a decoction from several
finely diced roots applied externally will reduce inflammation, and the decoction
relieves soreness in breasts. The demulcent property of Althea root and extracts
make them useful for the treatment of sore throats and coughs, and topically for
skin irritation. The German Commission E has declared it to be an effective
demulcent, and it is approved for GI disorders since 2006 by the HMPC of the
European Medicines Agency [1]. In Peru, the plant is used to treat diarrhea by the
local population [4]. The root must be thoroughly dried, or it will decompose
quickly, and have a sour odor and taste.XII
Althaea officinalis L. 239

Phytoconstituents: Flavonoid glycosides, phenolic acids and coumarins have been

isolated from roots [3]. From seeds, altheahexacosanyl lactone, altheacalamene,
altheacoumarin glucoside, lauric acid, b-sitosterol, and lanosterol have been iso-
lated [15]. The taproot, when dried, contains 25–35% mucilage, about 35% starch,
10% pectin, 10% sugars and 1–2% asparagines; there may be as much as 10%
tannins.LXXXIX Purified mucilage is composed of L-rhamnose, D-galactose, D-
galacturonic acid, and D-glucuronic acid.XLIII
Pharmacology: Althaea reduced transport velocity of isolated ciliated epithelium
cells of frog esophagus in vitro and may be one of the factors responsible for its
usefulness in coughs and cold. It protects mucous layers in hypopharynx and
possesses spasmolytic, antisecretory, and bactericidal activities [12]. Althaea extract
and its isolated polysaccharide produced antitussive activity in cats, polysaccharide
being more effective [13]; the polysaccharide, rhamnogalacturonan inhibited
mechanically-induced cough reflex in conscious cats better than nonnarcotic anti-
tussives [19], and at higher doses, citric acid-induced cough reflex in unsensitized
guinea pigs, comparable to codeine that was decreased by pretreatment with
selective 5-HT2 receptors antagonist, but did not show any bronchodilator effect
[18, 20].
Aqueous flower extract increased serum HDL-C after one-month administration to
rats, produced significant anti-inflammatory effects on acute and chronic inflamma-
tion, protected against ethanol-induced gastric ulcers, and produced time-dependent
inhibition of platelet aggregation [5]. Althaea extracts, in combination with topical
steroids potentiate effect of steroids in skin afflictions [7, 14]. Polysaccharides from
aerial parts also produced significant antioxidant activity, approximately 69% of the
activity of a-tocopherol [9], and Althaea extract pretreatment reduced oxidative stress
and produced neuroprotective effect against 6-OHDA-induced hemiParkinsonism in
rats [16]. Treatment of normal human keratocytes with an Althaea extract reduced
secretion of endothelin-1 (ET-1) by these cells, and treatment of normal human
melanocytes with this extract ameliorated stimulatory effect of ET-1 on proliferation
of cells, and also activation of MAPK in the intracellular signal transduction pathway,
without affecting binding of ET-1 to the endothelin-B receptors or the production of
inositol 1,4,5-trisphosphate [11]. Aqueous extract of hydroponically glasshouse-
grown roots significantly reduced UVA-induced DNA damage in cultured human
lung and skin fibroblasts [2]. A plant decoction was effective in vitro against V. cholera
[4], and methanol root extract showed some activity against periodontopathic bacteria
[6, 8]. Aerial parts tincture showed antibacterial effect against two strains of E. coli
[22]. However, hydroethanol leaf extract was ineffective on E. coli, L. monocytogenes,
and P. aeruginosa, but bactericidal to S. aureus, and improved wound healing in rats
[17], and ethanol root extract exhibited antibacterial effects on S. mutans and L.
acidophilus. Ethanol flower extract was ineffective in protecting against
gentamicin-nephrotoxicity in rats [21].
Clinical Studies: In a randomized trial, leaf compress along with warm compress
before nursing and a cold compress after nursing, significantly reduced breast
engorgement in lactating women [10].
240 Althaea officinalis L.

Human A/Es, Allergy and Toxicity: No known toxicity is attributed to althea

extracts.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies on its demulcent, antitussive and
anti-inflammatory activities except one study on relieving breast engorgement in
lactating mothers.

References
1. Anonymous. Community herbal monograph on Althaea officinalis L., radix.
Committee on herbal medicinal products. European medicines agency
evaluation of medicines for human use. London, 3 July 2008.
2. Curnow A, Owen SJ. An evaluation of root phytochemicals derived from
Althea officinalis (Marshmallow) and Astragalus membranaceus as potential
natural components of UV protecting dermatological formulations. Oxid
Med Cell Longev. 2016;2016:7053897.
3. Gudej J. Flavonoids, phenolic acids and coumarins from the roots of
Althaea officinalis. Planta Med. 1991;57:284–5.
4. Guevara JM, Chumpitaz J, Valencia E. The in vitro action of plants on Vibrio
cholerae. Rev Gastroenterol Peru. 1994;14:27–31 (Article in Spanish).
5. Hage-Sleiman R, Mroueh M, Daher CF. Pharmacological evaluation of
aqueous extract of Althaea officinalis flower grown in Lebanon. Pharm Biol.
2011;49:327–33.
6. Haghgoo R, Mehran M, Afshari E, Zadeh HF, Ahmadvand M. Antibacterial
effects of different concentrations of Althaea officinalis root extract versus
0.2% chlorhexidine and penicillin on Streptococcus mutans and Lacto-
bacillus (in vitro). J Int Soc Prev Community Dent. 2017;7:180–5.
7. Huriez C, Fagez C. On the association of althea and dexamethasone:
Dexalta ointment. Lille Med. 1968;13(Suppl):121.
8. Iauk L, Lo Bue AM, Milazzo I, et al. Antibacterial activity of medicinal plant
extracts against periodontopathic bacteria. Phytother Res. 2003;17:599–604.
9. Kardosová A, Machová E. Antioxidant activity of medicinal plant polysac-
charides. Fitoterapia. 2006;77:367–73.
10. Khosravan S, Mohammadzadeh-Moghadam H, Mohammadzadeh F,
Fadafen SA, Gholami M. The effect of hollyhock (Althaea officinalis L.)
leaf compresses combined with warm and cold compress on breast engorge-
ment in lactating women: a randomized clinical trial. J Evid Based
Complement Altern Med. 2017;22:25–30.
11. Kobayashi A, Hachiya A, Ohuchi A, et al. Inhibitory mechanism of an extract
of Althaea officinalis L. on endothelin-1-induced melanocyte activation. Biol
Pharm Bull. 2002;25:229–34.
12. Müller-Limmroth W, Fröhlich HH. Effect of various phytotherapeutic
expectorants on mucociliary transport. Fortschr Med. 1980;98:95–101.
Althaea officinalis L. 241

13. Nosálova G, Strapková A, Kardosová A, et al. Antitussive action of extracts

and polysaccharides of marshmallow (Althea officinalis L., var. robusta).
Pharmazie. 1992;47:224–6.
14. Piovano PB, Mazzocchi S. Clinical trial of a steroid derivative (9-alpha-
fluoroprednisolone-21-acetate) in association with aqueous extract of Althea
in the dermatological field. G Ital Dermatol Minerva. 1970;45:279.
15. Rani S, Khan SA, Ali M. Phytochemical investigation of the seeds of Althea
officinalis L. Nat Prod Res. 2010;24:1358–64.
16. Rezaei M, Alirezaei M. Protective effects of Althaea officinalis L. extract in
6-hydroxydopamine-induced hemi-Parkinsonism model: behavioral, bio-
chemical and histochemical evidence. J Physiol Sci. 2014;64:171–6.
17. Rezaei M, Dadgar Z, Noori-Zadeh A, et al. Evaluation of the antibacterial
activity of the Althaea officinalis L. leaf extract and its wound healing
potency in the rat model of excision wound creation. Avicenna J Phytomed.
2015;5:105–12.
18. Sutovská M, Capek P, Franova S, et al. Antitussive activity of Althaea
officinalis L. polysaccharide rhamnogalacturonan and its changes in guinea
pigs with ovalbumine-induced airways inflammation. Bratisl Lek Listy.
2011;112:670–5.
19. Sutovská M, Nosalova G, Franova S, Kardosova A. The antitussive activity of
polysaccharides from Althaea officinalis L., var. Robusta, Arctium lappa L., var.
Herkules, and Prunus persica L., Batsch. Bratisl Lek Listy. 2007;108:93–9.
20. Sutovská M, Nosálová G, Sutovský J, et al. Possible mechanisms of
dose-dependent cough suppressive effect of Althaea officinalis rhamnogalac-
turonan in guinea pigs test system. Int J Biol Macromol. 2009;45:27–32.
21. Talebi A, Karimi A, Ouguerram K, et al. Lack of nephroprotective efficacy
of Althaea officinalis flower extract against gentamicin renal toxicity in male
rats. Int J Prev Med. 2014;5:1360–3.
22. Watt K, Christofi N, Young R. The detection of antibacterial actions of
whole herb tinctures using luminescent Escherichia coli. Phytother Res.
2007;21:1193–9.
Ammi majus L. and A. visnaga (L.) Lam.
(Apiaceae/Umbelliferae)

Abstract
Seeds are classified as stimulatory, carminative, anti-inflammatory and extremely
useful for vitiligo and leucoderma. Powdered seeds mixed with honey, that has
been heated to remove scum, 10 g daily with warm water for fifteen days are
claimed to cure vitiligo. It is also used as an emmenagogue to regulate
menstruation, as a diuretic, and for the treatment of leprosy, kidney stones, and
urinary tract infections. Since ancient times, a tea made from the fruit of Ammi
visnaga (khella, as it is known in the Arab world) has been used as a remedy for
renal colic due to kidney stones. In Israel and Morocco, the plant is used for the
treatment of diabetes. Natural coumarins (furocoumarins), isopimpinellin, xan-
thotoxin (8-methoxypsoralen, 8-MOP), imperatorin, bergapten, umbelliprenin,
maurin, alloimperatorin, ammirin, ammajin and marmesin, have been isolated from
the fruits of A. majus. Khellin, visnagin, and khellol glycoside have been isolated
from fruits of A. visnaga. 8-MOP is a purified extract of the root, that has been used
in a crude form for centuries in the Middle East in the treatment of various skin
diseases, and was first utilized in the treatment of vitiligo in 1948. Ethanol seed
extract decreased TC, TGs and LDL-C, and increased HDL-C of rats, and also
produced significant anti-inflammatory, analgesic, and antipyretic effects. Both a
single oral dose and repeated administration of aqueous extract of A. visnaga
significantly lowers blood glucose in normal and diabetic rats. Spontaneous
passage of multiple ureteral stones in a patient, possibly as a result of using a khellin
preparation was reported from Turkey.

Keywords





Asprokefalos Atrilal Bishop’s weed Bischofskraut Bullwort Dà ā mǐ qín





Dokuzerimodoki Khilla Kürdanotu Rizzomolo

© Springer Nature Switzerland AG 2020 243

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_23
244 Ammi majus L. and A. visnaga (L.) Lam.

Vernaculars: Urd.: Atrilal, Khella; Ara.: Hirzul-shaitan, Khilla, Rijal-attair,

Rijal-gharab; Chi.: 大阿米芹, Dà ā mǐ qín; Dan.: Kongekommen; Dut.: Akker-
scherm, Groot akkerscherm; Eng.: Bishop’s weed, Bullwort, Greater ammi, Lace
flower, Lady’s lace; Fin.: Isosudenporkkana, Sudenporkkana; Fre.: Ammi élevé,
Ammi inodore, Ammi majeur, Boucage; Ger.: Bischofskraut, Großes ammei,
Große knorpelmöhre, Knorpelmöhre; Gre.: Ammios megálos, Asprokefalos; Ita.:
Ammi capo bianco, Rizzomolo, Visnaga maggiore; Jap.: Anmi mayusu,
Dokuzerimodoki, Howaitorêsufurawâ; Nor.: Narregulrot; Pol.: Aminek wielki;
Por.: Âmio-maior, Âmio-vulgar, Bisnaguinha-do-campo (Br.), Cicuta-negra (Br.),
Gertrudes (Br.); Rus.: Ammi bol’shaia; Spa.: Abit bord, Ameo, Ammi, Ameo
bastardo, Ameo mayor, Apio cimarrón, Berro cimarrón, Jistra, Siscla, Xistra; Swe.:
Harregulrot, Slöjsilja; Tur.: Kürdanotu.
Description: There is a controversy and confusion about the identity of this plant.
As noted below, A. majus, if it is the khella of Arabs, is native to Middle Eastern
countries, while A. visnaga grows in Europe, Asia and North Africa. However,
khella used by Egyptians has been identified as A. visnaga by some; whereas, all
chemical work reported by Egyptian scientists is on A. majus. This drug is not used
in Indian Ayurveda; it is utilized mainly by Unani physicians. However, what is
sold in India as Atrilal, is identified by Khory and KatrakLXXXI as Anthriscus
cerefolium, with properties similar to A. majus. They mention its internal use with
pyrethrum and honey in patients with vitiligo. Ibn al-BaitarLXIX described the stem,
fruits, and roots similar to dill (Anethum graveolens), except that its flowers are
white, while flowers and fruits of A. graveolens are yellow. He distinguished it from
the khella of Arabs by stating that seeds are similar but longer, and hot and bitter,
cause burning sensation on tongue. The plant is native to Egypt (Nile River Valley),
Mediterranean and other Middle Eastern countries. A. visnaga is native to Europe,
Asia and North Africa, and has been naturalized in southeastern United States. It is
an annual plant that grows to a height of about 120 cm, possesses slightly aromatic
odor, and a very bitter taste. Seeds should be harvested in ‘the early morning as
soon as the oldest flowers were ripe’ (Figs. 1 and 2).CXXXX
Actions and Uses: In Unani medicine, seeds (temperament, hot 2° and dry 2°) are
classified as stimulatory, carminative, anti-inflammatory and extremely useful for
vitiligo and leucoderma.LXXVII Ibn-e-BaitarLXIX quotes Sharif who says that A. majus
seeds (1.5 parts), Euphorbia lathyrus (1 part) and snake’s skin (1 part) ground to
powder and given 10 g daily to a leucoderma patient with grape syrup in the morning
for five days, followed by sitting in sunlight until he/she profusely sweats, cures the
disease. The best season of treatment is summer with strong sunshine. Alternatively,
powdered seeds mixed with honey, that has been heated to remove scum, 10 g daily
with warm water for fifteen days can cure vitiligo. Blowing the powder into nose of a
pregnant woman can cause abortion (Sharif). It is used as an emmenagogue to regulate
menstruation, as a diuretic, and for the treatment of leprosy, kidney stones, and
urinary tract infections [12]. Since ancient times, a tea made from the fruit of Ammi
visnaga (khella, as it is known in the Arab world) has been used as a remedy for renal
colic due to kidney stones. In 1930s, Egyptian scientists determined that the relief
Ammi majus L. and A. visnaga (L.) Lam. 245

Fig. 1 Ammi majus, Illustration, Johann Georg Sturm, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Ammi_majus_Sturm8.jpg

Fig. 2 Ammi majus, Flowers, H. Zell, WikimediaCommons, https://commons.wikimedia.org/

wiki/File:Ammi_majus_002.JPG
246 Ammi majus L. and A. visnaga (L.) Lam.

brought by the plant was due to relaxation of smooth muscle spasm, induced by stones
in kidneys or the ureters. Later, isolated khellin was used in a clinical trial of 38 angina
pectoris patients, of which 35 patients had favorable results. In Israel and Morocco,
the plant is used for the treatment of diabetes [16, 33].
Phytoconstituents: Natural coumarins, isopimpinellin [1], xanthotoxin (8-methoxy-
psoralen), imperatorin and bergapten [17], umbelliprenin [3], maurin [4], alloimper-
atorin [5], ammirin [6], and ammajin and marmesin [9], have been isolated from the
fruits; the coumarins content differ at various stages of fruit maturation [8]. Acetylated
flavonol triglycosides: kaempferol and isorhamnetin 3-O-[2′′-(4′′′-acetylrhamnosyl)-
6′′-glucosyl] glucosides, and flavonol glycosides, isorhamnetin-3-O-rutinoside,
kaempferol-3-O-glucoside, and isorhamnetin-3-O-glucoside [28], and new coumar-
ins, 6-hydroxy-7-methoxy-4 methyl coumarin and 6-hydroxy-7-methoxy coumarin
have been isolated from aerial parts [25]. Two furoquinoline-type alkaloids, 4-hydro-
7-hydroxy-8-methoxyfuroquinoline, and 4-hydro-7-hydroxy-8-prenyloxyfuroquino-
line, with antiproliferative and cytotoxic activities, were reported from A. majus
growing in Egypt [23]. Ivie [15] isolated linear furocoumarins (psoralens) from the
seed of a Texas species of A. majus. Khellin, visnagin, and khellol glycoside have been
isolated from fruits of A. visnaga [13]. Oil from flowering aerial parts of A. visnaga
contains high content of isoamyl 2-methylbutanoate; the flower buds contain
monoterpenes, sabinene (12.5%) and b-pinene (8.5%), and oils extracted from roots
collected in the vegetative, buds floral, and floral stages are rich in monoterpene
aldehydes, oxygenated monoterpenes and monoterpene hydrocarbons [26].
8-Methoxypsoralen (8-MOP) was first utilized in the treatment of vitiligo in 1948 [10].
8-MOP is a purified extract of the root, that has been used in a crude form for centuries
in the Middle East in the treatment of various skin diseases [29].
Pharmacology: Ethanol seed extract exhibited positive effects on lipid profile, as it
decreased TC, TGs and LDL-C, and increased HDL-C, after 2-months of admin-
istration to rats. It also produced significant anti-inflammatory, analgesic, and anti-
pyretic effects [22]. Extraction of seeds in sodium phosphate citrate buffer, and
sodium acetate buffer exhibited significant antibacterial activity against P. vulgaris,
E. coli and S. aureus [7]. The plant and bergapten, a pure furocoumarin, produce
schistosomicidal effect [2]. Oral administration of A. visnaga seed extract signifi-
cantly ameliorated incidence of glycolic acid-induced calcium oxalate nephrolithi-
asis, uremia, hyperbilirubinemia, and decrease in urinary output [19]. Aqueous fruit
extract, as well as khellin and visnagin, also prevent in vitro renal epithelial cell
damage caused by oxalate and calcium oxalate monohydrate [30], and reduced
incidence of calcium oxalate crystal deposition in ethylene glycol and ammonium
chloride-induced hyperoxaluria in rats [31]. Aqueous extract significantly lowers
blood glucose in normal rats six-hours after a single oral administration, and nine
days after repeated oral administration; the hypoglycemic effect is more pronounced
in STZ-diabetic rats [16].
Ammi majus L. and A. visnaga (L.) Lam. 247

Clinical Studies: In a pilot study in 20 nonobese normolipemic subjects, khellin

administration for four-weeks resulted in significant increase in plasma HDL-C
from the first week until one week post-medication, while TC and TGs remained
unchanged. LDL-C/HDL-C ratio was also lowered during the same period [14].
Spontaneous passage of multiple ureteral stones in a patient, possibly as a result of
using a khellin preparation was reported from Turkey [21].
Human A/Es, Allergy and Toxicity: A. majus is known to induce toxic phy-
tophotodermatitis, due to its furocoumarins (psoralens) content, that cause skin damage
by phototoxic mechanisms, when activated by longwave UV radiation [18, 24], but it
has also caused occupational IgE-mediated rhinitis and contact urticaria in a florist
exposed to it [20]. Significant nausea and vomiting resulted in withdrawal of four
volunteers, and two subjects had their ALT and AST elevated in the pilot study on
khellin [14].
Animal Toxicity: LD50s of aqueous extract by intraperitoneal and oral routes were
determined as 3,600 mg and 10,100 mg/kg, respectively [16]. Bishop’s weed can
also cause severe photosensitization in livestock, and severe ophthalmic changes,
especially pigmentary retinopathy in photosensitized domestic fowl [11, 27, 32].
Commentary: There are no clinical studies reported in English publications listed
on PubMed, regarding its main clinical uses in vitiligo or renal stones.

References
1. Abdel-Hay F, Abu-Mustafa EA, Fayez MB. Isolation of isopimpinellin from
the fruits of Ammi majus L.: Natural coumarins IV. Naturwissenschafien
(W Ger). 1966;53:406.
2. Abdulla WA, Kadry H, Mahran SG, et al. Preliminary studies on the
antischistosomal effect of Ammi majus L. Egypt J Bilharz. 1978;4:19–26.
3. Abu-Mustafa EA, El-Bay FK, Fayez MB. Natural coumarins. XII. Umbel-
liprenin, a constituent of Ammi majus L. fruits. J Pharm Sci. 1971;60:788–9.
4. Abu-Mustafa EA, El-Bay FK, Fayez MB. Natural coumarins XIII. Structure
of maurin, a new constituent of Ammi majus fruits. Tetrahadron Lett. 1971;
20:1657–8.
5. Abu-Mastafa EA, el-Bay FK, Fayez MB. Alloimperatorin from Ammi majus
fruits. Natural coumarins, part XX. Naturwissenschaften. 1975;62:40.
6. Abu-Mastafa EA, el-Bay FK, Fayez MB. Ammirin, a new coumarin constituent
from Ammi majus L. fruits. Natural coumatrins, part XVI. Naturwissenschaften.
1975;62:39–40.
7. Al Akeel R, Al-Sheikh Y, Mateen A, et al. Evaluation of antibacterial
activity of crude protein extracts from seeds of six different medical plants
against standard bacterial strains. Saudi J Biol Sci. 2014;21:147–51.
8. Balbaa SI, Hilal SH, Haggag MY. A study of the active constituents of
Ammi majus fruits at different stages of maturity. Planta Med. 1972;22:122–
6 (Eng. abstr.) (German).
248 Ammi majus L. and A. visnaga (L.) Lam.

9. Balbaa SI, Hilal SH, Haggag MY. Separation of ammajin and marmesin
from the fruits of Ammi majus and their chemical estimation. Planta Med.
1973;23:191–5.
10. El Mofty AM. A preliminary clinical report on the treatment of leukoderma
with Ammi majus Linn. J R Egypt Med Assn. 1948;31:651–65.
11. Dollahite JW, Younger RL, Hoffman GO. Photosensitization in cattle and
sheep caused by feeding Ammi majus (greater Ammi; Bishop’s Weed).
Am J Vet Res. 1978;39:193–7.
12. Farnsworth NR, editor. NAPRALERT database. University of Illinois at
Chicago, Chicago, IL (an online database available directly through the
University of Illinois at Chicago or through the Scientific and Technical
Network (STN) of Chemical Abstracts Services). Accessed 9 Feb 2001.
13. Günaydin K, Beyazit N. The chemical investigations on the ripe fruits of
Ammi visnaga (Lam.) Lamarck growing in Turkey. Nat Prod Res. 2004;18:
169–75.
14. Harvengt C, Desager JP. HDL-cholesterol increase in normolipaemic
subjects on khellin: a pilot study. Int J Clin Pharmacol Res. 1983;3:363–6.
15. Ivie GW. Linear furocoumarins (psoralens) from the seed of Texas Ammi
majus L. (Bishop’s Weed). J Agric Food Chem. 1978;26:1394–402.
16. Jouad H, Maghrani M, Eddouks M. Hypoglycemic effect of aqueous extract
of Ammi visnaga in normal and streptozotocin-induced diabetic rats. J Herb
Pharmacother. 2002;2:19–29.
17. Karawya MS, Khayyal SE, Youssef GF. Estimation of xanthotoxin, imperatorin
& bergapten in Ammi majus fruits and formulations. Planta Med. 1970;18:195–
200.
18. Kavli G, Volden G. Phytophotodermatitis. Photodermatol. 1984;1:65–75.
19. Khan ZA, Assiri AM, Al-Afghani HM, Maghrabi TM. Inhibition of oxalate
nephrolithiasis with Ammi visnaga (AI-Khillah). Int Urol Nephrol. 2001;33:
605–8.
20. Kiistala R, Mäkinen-Kiljunen S, Heikkinen K, et al. Occupational allergic
rhinitis and contact urticaria caused by Bishop’s weed (Ammi majus).
Allergy. 1999;54:635–9.
21. Kilicaslan I, Coskun S. Spontaneous stone passage: is it Ammi visnaga
effect? Urol Res. 2012;40:799–800.
22. Koriem KM, Asaad GF, Megahed HA, et al. Evaluation of the antihyper-
lipidemic, anti-inflammatory, analgesic, and antipyretic activities of ethano-
lic extract of Ammi majus seeds in albino rats and mice. Int J Toxicol. 2012;
31:294–300.
23. Mohammed MM, El-Sharkawy ER. Cytotoxic new furoquinoline alkaloid
isolated from Ammi majus L. growing in Egypt. Nat Prod Res. 2017;31:
645–52.
24. Ossenkoppele PM, van der Sluis WG, van Vloten WA. Phototoxic
dermatitis following the use of Ammi majus fruit for vitiligo. Ned Tijdschr
Geneeskd. 1991;135:478–80 (Dutch).
Ammi majus L. and A. visnaga (L.) Lam. 249

25. Selim YA, Ouf NH. Anti-inflammatory new coumarin from the Ammi majus
L. Org Med Chem Lett. 2012;2:1.
26. Sellami HK, Flamini G, Cioni PL, Smiti S. Composition of the essential oils
in various organs at different developmental stages of Ammi visnaga (L.)
Lam. from Tunisia. Chem Biodivers. 2011;8:1990–2004.
27. Shlosberg A, Egyed MN. Examples of poisonous plants in Israel of
importance to animals and man. Arch Toxicol Suppl. 1983;6:194–6.
28. Singab AN. Acetylated flavonol triglycosides from Ammi majus L. Phyto-
chemistry. 1998;49:2177–80.
29. Swift S. 8-Methoxypsoralen—a short review and comment. Calif Med. 1960;
92:139–42.
30. Vanachayangkul P, Byer K, Khan S, Butterweck V. An aqueous extract of Ammi
visnaga fruits and its constituents khellin and visnagin prevent cell damage
caused by oxalate in renal epithelial cells. Phytomedicine. 2010;17:653–8.
31. Vanachayangkul P, Chow N, Khan SR, Butterweck V. Prevention of renal
crystal deposition by an extract of Ammi visnaga L. and its constituents
khellin and visnagin in hyperoxaluric rats. Urol Res. 2011;39:189–95.
32. Witzel DA, Dollahite JW, Jones LP. Photosensitization in sheep fed Ammi
majus (Bishop’s weed) seed. Am J Vet Res. 1978;39:319–20.
33. Yaniv Z, Dafni A, Friedman J, Palevitch D. Plants used for the treatment of
diabetes in Israel. J Ethnopharmacol. 1987;19:145–51.
Anacardium occidentale L.
(Anacardiaceae)

(Syns.: A. microcarpum Ducke; Acajuba occidentalis (L.) Gaertn.)

Abstract
This nutritious nut tree is pantropic in distribution, but is commonly grown in India,
Vietnam, Indonesia, the Philippines, Brazil, and Nigeria. Cashew nuts are rich in
monounsaturated fatty acids. In Unani medicine, the fruit is regarded fattening,
cardiac and brain tonic, refrigerant, kidney tonic, aphrodisiac, and improves
memory and intelligence. In Iran, the fruit extract is used for the management of
pain, and in the Philippines, oil of the pericarp is used as a powerful cathartic, and as
anesthetic in leprosy and psoriasis, and in the treatment of warts, corns and ulcers. In
the coastal lowlands of Guinea-Conakry (the Republic of Guinea), stem bark
decoction is used for the management of diabetes. Fruit, bark and leaves are also
used for their antifungal activity, for sores and rashes, or as antipyretic, and
antidiarrheal. In northern Europe, traditional healers use it for the treatment of
diabetes mellitus, and in popular Brazilian medicine it is used to treat ulcers,
hypertension, and diarrhea; and leaves are used for eczema, psoriasis, scrofula,
dyspepsia, genital problems, and venereal diseases, as well as for impotence,
bronchitis, cough, intestinal colic, leishmaniasis, and syphilis-related skin disorders.
From cashew nuts, phenolic lipids, methyl salicylate, cardols, anacardic acid and
cardanols have been isolated. Aqueous fruit extract protected rats from STZ-
diabetes, and methanol leaf extract lowered blood glucose of moderately diabetic
rats, comparable to tolbutamide. Cashew nut extract and anacardic acid increase
plasma membrane glucose transporters, resulting in elevated glucose uptake by
myoblasts (myotubes), and rat liver mitochondria, by activating AMPK.

Keywords
Acajoeboom

Acajounød

Akajoubaum Akajouäpple

Cajuaçú





Cashewpähkinä Cashew Kaju Kãjūta Yao guo

© Springer Nature Switzerland AG 2020 251

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_24
252 Anacardium occidentale L.

Vernaculars: Urd.: Kaju; Hin.: Kaju; San.: Agnikrita, Bijara-sala,Kãjūta, Kãjūtaka,

Shoephahara, Vrkkabija, Vrttapatra, Vrttãruskara; Ben.: Hidjli badam, Kaju; Guj.:
Kaju; Mal.: Andiparuppu (kernel), Jambu-monat, Kappa-mavu, Kashuvandi (nut),
Kasumavu (tree), Parangimavu; Mar.: Kaju; Tam.: Kala-mavah, Kottai, Kothai-
mundiri, Mindiri-appazham, Mundiri, Mundiri-kai; Tel.: Jaedima-midi, Jedi-mamedi
vittu, Jidi anti, Mokkamamidi, Moonthamamidivittu; Ara.: Kaju; Chi.: 腰果, Yao
guo, Yao guo li, Yao guo shu; Cze.: Kešú oříšky; Dan.: Acajounød; Dut.: Acajoe-
boom, Kasjoe, Mereke; Eng.: Cashew, Cashew apple, Cashew nut; Fin.:
Cashew-paehkinae, Cashewpähkinä, Munuaispuu; Fre.: Acajou à pommes, Andac-
arde, Andacardier, Cajou, Noyer de cajou, Pomme d’acajou, Pommier cajou; Ger.:
Acajubaum, Akajoubaum, Kaschubaum, Westindischer nierenbaum; Gre.: Anakar-
dia, Eidos fistikiou, Fistiki kasious; Ind.: Jambu mortyet; Ita.: Acagiù, Acajou,
Anacardo; Jap.: Anakarudiumu okushidentare, Kashuunatto no ki; Maly.: Gajus,
Jambu golok, Jambu mede (Java), Jambu monyet, Janggus; Per.: Badam-e-pharangi;
Por.: Caju, Cajuaçú, Cajueiro; Rus.: Anakardium zaladnyi, Derevo kesh’iu; Spa.:
Acaju, Anacardo, Marañón; Swe.: Akajouäpple; Tag.: Balubad, Balubag, Kachui,
Kasoi, Kasui; Tha.: Mamuang him maphan; Vie.: Cây điều, Ðào lộn hột.
Description: It is pantropic in distribution, but is commonly grown in India, Viet-
nam, Indonesia, the Philippines, Brazil, and Nigeria. A very small tree (dwarf variety),
otherwise a large evergreen tree growing up to a height of 12 m, with a usually small
and crooked trunk; leaves are simple, smooth, alternate, spirally arranged, ovate or
obviate, 10–20 cm long and 7.5–12 cm wide, with slightly rounded, smooth margins.
Flowers are small, 5–6 mm in diameter, pale-green at first, then turning reddish, with
five slender, acute petals 7–15 mm long, with pink stripes. The nut (fruit) is
kidney-shaped, ash-colored and about 2 cm long (Figs. 1, 2, 3 and 4).
Actions and Uses: Cashew nuts, rich in monounsaturated fatty acids are a popular
snack and food source, and commonly used in Indian cuisines, for garnishing
sweets or in curries. In Unani medicine, the fruit (temperament, hot and moist) is
regarded fattening, cardiac and brain tonic, refrigerant, kidney tonic, aphrodisiac,
and improves memory and intelligence. External use of the oil of rind of cashews
relieves skin insensitivity caused by leprosy.L Black and acrid pericarp oil is not
edible, but is preventive against white ants, and is used by book binders, and
applied to floors and wooden rafters.CV Root is purgative, and the kernels are
demulcent, nutritive and emollient; the fruits are antidiarrheal, and also used as
rubefacient.LIX In Iran, the fruit extract is used for the management of pain [4]. In
the Philippines, oil of the pericarp is used as a powerful cathartic, and as anesthetic
in leprosy and psoriasis, and in the treatment of warts, corns and ulcers.CXVII In the
coastal lowlands of Guinea-Conakry (the Republic of Guinea), stem bark decoction
is used for the management of diabetes [11]. Juice from macerated bark and leaves
is used for dermatoses, and ground seeds are used as poultice for treating snake-
bites; and nut oil is applied to cracked heels or as an antifungal agent in the
traditional medicine of the Patamona of Guyana. Bark soaked in water overnight
and boiled, is used for the treatment of diarrhea, influenza and sore throat, as
contraceptive agent, and during menstruation. Fruit, bark and leaves are also used
Anacardium occidentale L. 253

Fig. 1 Anacardium occidentale, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Anacardium_occidentale_-_K%
C3%B6hler%E2%80%93s_Medizinal-Pflanzen-010.jpg

Fig. 2 Anacardium occidentale, Unripe Cashew Nuts, Vinayaraj, WikimediaCommons; Share-

Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Young_cashew_
nuts.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
254 Anacardium occidentale L.

Fig. 3 Anacardium occidentale, Cashew Fruit ready for Harvest, Abhishek Jacob, Wikime-
diaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/
File:Cashew_apples.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 4 Anacardium occidentale, Brazilian Cashew, Eric Gaba, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Cashew_Brazil_fruit_3.png
Anacardium occidentale L. 255

for their antifungal activity, for sores and rashes, or as antipyretic, and antidiar-
rheal.XXXIV In northern Europe, traditional healers use it for the treatment of dia-
betes mellitus [37], and in popular Brazilian medicine it is used to treat ulcers,
hypertension, and diarrhea [17]; and leaves are used for eczema, psoriasis, scrofula,
dyspepsia, genital problems, and venereal diseases, as well as for impotence,
bronchitis, cough, intestinal colic, leishmaniasis, and syphilis-related skin disorders
[28, 33]. Fresh and processed cashew apple juices are among the most popular
drinks in Brazil, for their nutritional benefits, and antibacterial and antitumor
potential. Chemical constituents of both fresh juice and processed juice (Cajuina)
contain high concentrations of vitamin C, various carotenoids, phenolic com-
pounds, and metals [22]. In Côte d’Ivoire (the Ivory Coast), the plant is used for
treatment of hypertension [39]. Anacardic acids in cashew nutshell liquid are
gastroprotectors, antitumor agents, antioxidants, and inhibitors of activities of
various deleterious enzymes [5]; and also known as antibacterial principles, active
against Gram-positive bacteria and nematodes. Fruit oil is also active against
leprosy, and as anthelmintic.LXXXVIII
Phytoconstituents: From cashew nuts, phenolic lipids, methyl salicylate, cardols,
anacardic acid and cardanols have been isolated [36]. Total phenolic and flavonoid
contents in hydroethanol leaf extract were found to be 35.5% and 2.58%, respec-
tively [18]. Methanol (80%) extract of inner stem bark showed the presence of
tannins (5.75%), saponins (2%), oxalates (2.5%), phytate (0.25%), cyanide
(0.03%), traces of free reducing sugars, and iron from dried crude as 8.92 mg/100 g
[27]. Anacardic acids are found not only in cashew nutshell and oil, but also in the
nut and fruit juice [41].
Pharmacology: Pretreatment of rats with aqueous fruit extract significantly pro-
tected from STZ-diabetes [16], and methanol leaf extract lowered blood glucose of
alloxan-induced moderately diabetic rats, comparable to tolbutamide [13]. Hexane
bark extract also significantly lowered blood glucose in normal, healthy dogs [2],
and ethanol root extract reduced plasma glucose, as well as cholesterol and total
lipids in normoglycemic guinea pigs and albino rats [12]. Swanston-Flatt et al. [37]
reported no effect on glucose homeostasis (basal plasma glucose, insulin, glucose
tolerance, insulin-induced hypoglycemia and HbA1c) in both normal and
STZ-diabetic mice. Hydroethanol leaf extract inhibited HCl/ethanol-induced gastric
lesions in rats, with extract doses higher than 100 mg/kg being more effective than
30 mg/kg of lansoprazol. Methanol fraction of the extract, due to the presence of
phenolic compounds as the major components, reduced gastric lesion by 88% [18].
Anacardic acids also protected against ethanol-induced gastric ulcers, without
affecting gastric secretion or total acidity, and prevented ethanol-induced changes in
oxidative stress markers, such as GSH, MDA, CAT, SOD, and nitrate/nitrite [23].
However, intragastric administration of aqueous leaf extract caused significant
increase in mean gastric acid output [1]. Leaf extract also caused endothelium-
dependent vasorelaxation, mediated by NO, and independent of phenolic contents
or antioxidant capacity [32]. Aqueous bark extract produced a significant fall in BP
256 Anacardium occidentale L.

of normotensive rabbits, which was not reversed by atropine pretreatment; and,

produced negative inotropic and chronotropic effects on isolated rat heart [39].
A bioflavonoid, (−)-epicatechin, isolated from seed coat produced anti-inflammatory
activity in rats and was as effective as phenylbutazone [38]. A mixture of tannins
isolated from bark exhibited anti-inflammatory activity in various models, including
adjuvant-induced polyarthritis in rats, and antagonized permeability-increasing effects
of mediators of inflammation, and inhibited migration of leucocytes to inflammation site
[24]. Aqueous stem-bark extract produced sustained and significant reduction of fresh
egg albumin-induced acute inflammation, approximately 8–15 times less than that of
diclofenac [26]. Dichloromethane leaf extract exhibited potent analgesic, and
anti-inflammatory activities [30], and methanol stem bark extract completely protected
rats from death due to LPS-induced shock [29]. Cashew nut kernel oil improves
antioxidant status of animals as it decreases liver LPO and enhances activities of SOD,
CAT, GST, methylglyoxalase I, and levels of GSH [35]. Nutshell oil exhibits a weak
tumor promoting effect in DMBA-induced skin carcinogenesis [3, 15], and ethanol leaf
extract downregulates VEGF, involved in angiogenesis [21]. Antibacterial activity
against E. coli and P. aeruginosa [19], and antifungal activity, against C. albicans,
T. rubrum and C. neoformans [33], have also been reported.
Clinical Studies: In a randomized, controlled, parallel study, South African sub-
jects with metabolic syndrome (MeS) fed with diet rich in cashew nuts (providing
20% of energy intake) for eight-weeks did not show any significant change in BMI,
waist circumference, BP, TC, LDL-C, HDL-C, triacylglycerol, and serum
high-sensitivity CRP, but the fasting glucose significantly increased [25]; cashew
diet improved antioxidant capacity from baseline, but did not improve serum
antioxidant profiles [7]. A significant improvement in baroreceptor reflex sensitivity
in cashew-fed subjects with MeS, underlining their beneficial cardiovascular effects,
was also reported [34].
Mechanism of Action: Hydroethanol cashew nuts extract and anacardic acid
increase plasma membrane glucose transporters, resulting in elevated glucose uptake
by myoblasts (myotubes), and rat liver mitochondria, by activating AMPK [40].
Human A/Es, Allergy and Toxicity: Cashew allergy among children is associated
with greater chances of anaphylaxis [6, 8–10, 31]. Cashew trees flower once a year
between January and March, and during this period, pollens could trigger asthmatic
response in allergic individuals [14], and cashews share cross-reactivity with wal-
nuts [20].
Animal Toxicity: Hydroalcohol extract was nontoxic to rats up to a dose of 2,000
mg/kg in acute, subacute, and chronic toxicity studies [17]. Oral LD50 of methanol
(80%) extract of inner bark in mice was 2,154 mg/kg [27]. Anacardic acid was
nonmutagenic, and nonlethal to BALB/c mice up to 2,000 mg/kg dose, and doses
up to 1,000 mg/kg for 30-days only slightly decreased hematocrit and Hb levels,
coupled with a moderate increase in urea [5].
Anacardium occidentale L. 257

CYP450s and Potential for Drug-Herb Interactions: Several phenolic lipids,

and cardols, anacardic acid and cardanols, isolated from cashew nuts, exhibited
moderate CYP3A4 inhibitory activity [36].
Commentary: In the clinical trial on patients with metabolic syndrome, cashew-
rich diet offered no benefits except improvement in baroreceptor reflex sensitivity.

References
1. Ajibola ES, Adeleye OE, Okediran BS, Rahman SA. Effect of intragastric
administration of crude aqueous leaf extract of Anacardium occidentale on
gastric acid secretion in rats. Niger J Physiol Sci. 2010;25:59–62.
2. Alexander-Lindo RL, Morrison EY, Nair MG. Hypoglycaemic effect of
stigmast-4-en-3-one and its corresponding alcohol from the bark of
Anacardium occidentale (cashew). Phytother Res. 2004;18:403–7.
3. Banerjee S, Rao AR. Promoting action of cashew nut shell oil in DMBA-initiated
mouse skin tumour model system. Cancer Lett. 1992;62:149–52.
4. Behravan E, Heidari MR, Heidari M, et al. Comparison of gastric
ulcerogenicity of percolated extract of Anacardium occidentale (cashew
nut) with indomethacin in rats. Pak J Pharm Sci. 2012;25:111–5.
5. Carvalho AL, Annoni R, Silva PR, et al. Acute, subacute toxicity and
mutagenic effects of anacardic acids from cashew (Anacardium occidentale
Linn.) in mice. J Ethnopharmacol. 2011;135:730–6.
6. Clark AT, Anagnostou K, Ewan PW. Cashew nut causes more severe
reactions than peanut: case-matched comparison in 141 children. Allergy.
2007;62:913–6.
7. Davis L, Stonehouse W, du Loots T, et al. The effects of high walnut and cashew
nut diets on the antioxidant status of subjects with metabolic syndrome. Eur J
Nutr. 2007;46:155–64.
8. Davoren M, Peake J. Cashew nut allergy is associated with a high risk of
anaphylaxis. Arch Dis Child. 2005;90:1084–5.
9. de Groot H. Allergy to cashew nuts and peanuts. Ned Tijdschr Geneeskd.
2007;151:997–1001 (Dutch).
10. de Silva IL, Mehr SS, Tey D, Tang ML. Paediatric anaphylaxis: a 5 year
retrospective review. Allergy. 2008;63:1071–6.
11. Diallo A, Traore MS, Keita SM, et al. Management of diabetes in Guinean
traditional medicine: an ethnobotanical investigation in the coastal lowlands.
J Ethnopharmacol. 2012;144:353–61.
12. Egwim E. Hypoglycemic potencies of crude ethanolic extracts of cashew
roots and unripe pawpaw fruits in guinea pigs and rats. J Herb Pharma-
cother. 2005;5:27–34.
13. Fagbohun TR, Odufuwa KT. Hypoglycemic effect of methanolic extract of
Anacardium occidentale leaves in alloxan-induced diabetic rats. Niger J
Physiol Sci. 2010;25:87–90.
258 Anacardium occidentale L.

14. Fernandes L, Mesquita AM. Anacardium occidentale (cashew) pollen allergy in

patients with allergic bronchial asthma. J Allergy Clin Immunol. 1995;95:501–4.
15. George J, Kuttan R. Mutagenic, carcinogenic and cocarcinogenic activity of
cashewnut shell liquid. Cancer Lett. 1997;112:11–6.
16. Kamtchouing P, Sokeng SD, Moundipa PF, et al. Protective role of
Anacardium occidentale extract against streptozotocin-induced diabetes in
rats. J Ethnopharmacol. 1998;62:95–9.
17. Konan NA, Bacchi EM, Lincopan N, et al. Acute, subacute toxicity and
genotoxic effect of a hydroethanolic extract of the cashew (Anacardium
occidentale L.). J Ethnopharmacol. 2007;110:30–8.
18. Konan NA, Bacchi EM. Antiulcerogenic effect and acute toxicity of a
hydroethanolic extract from the cashew (Anacardium occidentale L.) leaves.
J Ethnopharmacol. 2007;112:237–42.
19. Kudi AC, Umoh JU, Eduvie LO, Gefu J. Screening of some Nigerian
medicinal plants for antibacterial activity. J Ethnopharmacol. 1999;67:225–8.
20. Kulis M, Pons L, Burks AW. In vivo and T cell cross-reactivity between
walnut, cashew and peanut. Int Arch Allergy Immunol. 2009;148:109–17.
21. Lingaraju SM, Keshavaiah K, Salimath BP. Inhibition of in vivo angiogen-
esis by Anacardium occidentale L. involves repression of the cytokine
VEGF gene expression. Drug Discov Ther. 2008;2:234–44.
22. Melo Cavalcante AA, Rubensam G, Picada JN, et al. Mutagenicity, antioxidant
potential, and antimutagenic activity against hydrogen peroxide of cashew
(Anacardium occidentale) apple juice and cajuina. Environ Mol Mutagen.
2003;41:360–9.
23. Morais TC, Pinto NB, Carvalho KM, et al. Protective effect of anacardic
acids from cashew (Anacardium occidentale) on ethanol-induced gastric
damage in mice. Chem Biol Interact. 2010;183:264–9.
24. Mota ML, Thomas G, Barbosa Filho JM. Anti-inflammatory actions of
tannins isolated from the bark of Anacardium occidentale L. J Ethnophar-
macol. 1985;13:289–300.
25. Mukuddem-Petersen J, Stonehouse Oosthuizen W, Jerling JC, et al. Effects
of a high walnut and high cashew nut diet on selected markers of the
metabolic syndrome: a controlled feeding trial. Br J Nutr. 2007;97:1144–53.
26. Ojewole JA. Potentiation of the anti-inflammatory effect of Anacardium
occidentale (Linn.) stem-bark aqueous extract by grapefruit juice. Methods
Find Exp Clin Pharmacol. 2004;26:183–8.
27. Okonkwo TJ, Okorie O, Okonta JM, Okonkwo CJ. Subchronic hepato-
toxicity of Anacardium occidentale (Anacardiaceae) inner stem bark extract
in rats. Indian J Pharm Sci. 2010;72:353–7.
28. Okpashi VE, Bayim BP, Obi-Abang M. Comparative effects of some
medicinal plants: Anacardium occidentale, Eucalyptus globulus, Psidium
guajava, and Xylopia aethiopica extracts in alloxan-induced diabetic male
Wistar albino rats. Biochem Res Int. 2014;2014:203051.
Anacardium occidentale L. 259

29. Olajide OA, Aderogba MA, Adedapo AD, Makinde JM. Effects of
Anacardium occidentale stem bark extract on in vivo inflammatory models.
J Ethnopharmacol. 2004;95:139–42.
30. Onasanwo SA, Fabiyi TD, Oluwole FS, Olaleye SB. Analgesic and
anti-inflammatory properties of the leaf extracts of Anacardium occidentalis
in the laboratory rodents. Niger J Physiol Sci. 2012;27:65–71.
31. Rancé F, Bidat E, Bourrier T, Sabouraud D. Cashew allergy: observations of
42 children without associated peanut allergy. Allergy. 2003;58:1311–4.
32. Runnie I, Salleh MN, Mohamed S, et al. Vasorelaxation induced by
common edible tropical plant extracts in isolated rat aorta and mesenteric
vascular bed. J Ethnopharmacol. 2004;92:311–6.
33. Schmourlo G, Mendonça-Filho RR, Alviano CS, Costa SS. Screening of
antifungal agents using ethanol precipitation and bioautography of medic-
inal and food plants. J Ethnopharmacol. 2005;96:563–8.
34. Schutte AE, Van Rooyen JM, Huisman HW, et al. Modulation of baroreflex
sensitivity by walnuts versus cashew nuts in subjects with metabolic
syndrome. Am J Hypertens. 2006;19:629–36.
35. Singh B, Kale RK, Rao AR. Modulation of antioxidant potential in liver of
mice by kernel oil of cashew nut (Anacardium occidentale) and its lack of
tumour promoting ability in DMBA induced skin papillomagenesis. Indian J
Exp Biol. 2004;42:373–7.
36. Suo M, Isao H, Ishida Y, et al. Phenolic lipid ingredients from cashew nuts.
J Nat Med. 2012;66:133–9.
37. Swanston-Flatt SK, Day C, Flatt PR, Gould BJ, Bailey CJ. Glycaemic
effects of traditional European plant treatments for diabetes. Studies in
normal and streptozotocin diabetic mice. Diabetes Res. 1989;10:69–73.
38. Swarnalakshmi T, Gomathi K, Sulochana N, Amala Baskar E, Parmar NS.
Anti-inflammatory activity of (−)-epicatechin, a bioflavonoid isolated from
Anacardium occidentale Linn. Indian J Pharm Sci. 1981;43:205–8.
39. Tchikaya FO, Bantsielé GB, Kouakou-Siransy G, et al. Anacardium
occidentale Linn. (Anacardiaceae) stem bark extract induces hypotensive
and cardioinhibitory effects in experimental animal models. Afr J Tradit
Complement Altern Med. 2011;8:452–61.
40. Tedong L, Madiraju P, Martineau LC, et al. Hydroethanolic extract of
cashew tree (Anacardium occidentale) nut and its principal compound,
anacardic acid, stimulate glucose uptake in C2C12 muscle cells. Mol Nutr
Food Res. 2010;54:1753–62.
41. Toyomizu M, Okamoto K, Ishibashi T, et al. Uncoupling effect of anacardic
acids from cashew nut shell oil on oxidative phosphorylation of rat liver
mitochondria. Life Sci. 2000;66:229–34.
Anacyclus pyrethrum (L.) Lag
(Asteraceae/Compositae)

(Syns.: A. depressus Ball; A. freynii Willk; A. officinarum Hayne; Anthemis

pyrethrum L.)

Abstract
This perennial plant, in appearance like chamomile, is found in north India,
Africa, Syria, Algeria, Morocco, and the Mediterranean region. Avicenna said it
purges phlegm and boiling it in vinegar and swishing strengthens loose teeth.
Other uses in traditional medicine include paralysis, epilepsy, fever, pharyngitis,
tonsillitis, and diabetes. It possesses powerful stimulant properties, is a powerful
sialogogue, and a tonic for nervous system; root decoction is useful as gargle in
carious teeth, toothache, sore-throat and tonsillitis, but is scarcely ever employed
in Europe as an internal remedy. As a stimulatory aphrodisiac, is used both
internally and externally for this purpose. In Ayurveda, roots are employed as
“Vajikaran Rasayana,” a category of drugs to treat male sexual dysfunction, and
to increase vitality and virility. If ground root is applied to the tongue of a
stuttering child, the stuttering and tongue thickness is claimed to be cured. In
Iranian traditional medicine, root is utilized in the treatment of epilepsy, and in
Moroccan traditional medicine to treat rheumatism, sciatica, colds, neuralgia,
and paralysis. Thirteen N-alkylamides (five N-isobutylamides, three N-methyl
isobutyl-amides, four tyramides, and one 2-phenylethylamide) were reported
from ethanol root extract; pellitorine being the main alkylamide, that is absorbed
through stratum corneum and subsequent skin layers. Ethanol root extract
exhibited antiepileptic and myorelaxation in mice, and significantly prevented
seizure induced oxidative stress, cognitive impairment, and normalized decrease
in cholinesterase activity. Petroleum ether extract demonstrated significant
aphrodisiac effects in rats.

Keywords
Akarkara

Akarakarabha

Aqarqarha

Bertramsrod

Aud el’attas





Bertramsrod Marokkokamille Mount atlas daisy Pelitre romano Pyrèthre

d’afrique

© Springer Nature Switzerland AG 2020 261

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_25
262 Anacyclus pyrethrum (L.) Lag

Vernaculars: Urd.: Aqarqarha; Hin.: Akalkara, Akarkara; San.: Akallaka, Akar-

akarabha, Akarakarava; Ben.: Akalkara, Akarkara; Guj.: Akorkaro; Mal.: Akkala-
karam, Akkikaruka; Mar.: Akarkara, Akkal kadha; Tam.: Akkarakaaram,
Akki-rakaram; Tel.: Akalakarra, Akarakaram, Akkalakaram; Ara.: Aqarqarha, Aud
el’attas, Ood-e-qarah jabali, Taghandast; Cze.: Bertrám římský; Dan.: Bertramsrod;
Dut.: Atlasmadeliefje, Marokkaanse kamille, Roomse bertram, Roze kamille,
Speekselkruid; Eng.: Mount Atlas daisy, Pellitory of Spain, Spanish chamomile; Fin.:
Marokonraimikki, Raimikki; Fre.: Pariétaire d’Espagne, Pyrèthre d’Afrique, Pyr-
èthre salivaire; Ger.: Franzosenwursel, Marokkokamille, Römischer bertram; Gre.:
Anakiklos o pyrethros, Pyrethron; Ita.: Piretro romano; Jap.: Anakikurusu; Per.:
Aghergherha, Babuna zard, Bekh tarkhoon kohi; Spa.: Pelitre romano, Raíz de pelitre
romano; Swe.: Bertram, Romersk bertram; Tha.: Kot kak kra; Tur.: Pire otu.
Description: This perennial plant, in appearance like chamomile, is found in north
India, Africa, Syria, Algeria, Morocco, and the Mediterranean region. It has stems that
lie on the ground for part of their length, before rising erect. Root is almost cylindrical,
very slightly twisted and tapering, and often crowned with a tuft of grey hairs. Exter-
nally, it is brown and wrinkled, with bright black spots. Root pieces available in the
market are 5–8 cm long and about 1 cm in diameter, cylindrical or tapering. It has
brown, rough, shriveled surface; slightly aromatic smell and a persistent, pungent, sharp
taste exciting tingling, causes burning sensation on tongue, and copious flow of saliva
(Fig. 1).XL
Actions and Uses: Avicenna said it purges phlegm and boiling it in vinegar and
swishing strengthens loose teeth. Other uses in traditional medicine include paralysis,
epilepsy, fever, pharyngitis, tonsillitis, and diabetes.IV Dymock et al.XL described the

Fig. 1 Anacyclus pyrethrum, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Anacyclus_pyrethrum_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-011.jpg
Anacyclus pyrethrum (L.) Lag 263

drug with a hot, astringent, and sweetish taste. The pungency is not perceived till it
has been chewed for a few seconds, when it causes at first a glowing heat in the
mouth, soon followed by pricking sensation in the tongue and lips. If taken fasting it
benumbs the tongue. It possesses powerful stimulant properties, but is scarcely ever
employed in Europe as an internal remedy. A powerful sialogogue, a powerful
irritant, and a tonic for nervous system; root decoction is useful as gargle in carious
teeth, toothache, sore-throat and tonsillitis.XXI,CV In Unani medicine it (temperament,
hot 3° and dry 3°) is regarded as deobstruent, anesthetic, analgesic, antiphlegmatic,
aphrodisiac, sialogogue and emmenagogue, and useful in phlegmatic diseases, such
as stroke, paralysis, arthritis, tremors, sciatica, tetanus, and epilepsy. It is a powerful
stimulatory aphrodisiac, and is used both internally and externally for this purpose. If
ground root is applied to the tongue of a stuttering child, the stuttering and tongue
thickness is cured.L,LXXVII In Ayurveda, roots are employed as “Vajikaran
Rasayana,” a category of drugs to treat male sexual dysfunction, and to increase
vitality and virility [15], and in grdhrasi, paksãghãta, pratiśyãya, kãsa, śvãsa, śotha,
ajirna, śūla roga, udararoga, nastãrtava, and dantaśūla.LIX In Iranian traditional
medicine, root is utilized in the treatment of epilepsy [1], and in Moroccan traditional
medicine to treat rheumatism, sciatica, colds, neuralgia, and paralysis [9]. Mixed
equally with root of Polygonum bistorta and alum, beaten into paste with honey and
placed into carious teeth or held between teeth, relieves toothache.LXXXVIII
Phytoconstituents: Thirteen N-alkylamides (five N-isobutylamides, three N-methyl
isobutylamides, four tyramides, and one 2-phenylethylamide) were reported from
ethanol root extract [4]; pellitorine being the main alkylamide, that is absorbed through
stratum corneum and subsequent skin layers [18]. Following alkamides have been
isolated from the roots: tetradeca-2E,4E-dien-8,10-diynoic acid isobutylamide (ana-
cycline), deca-2E,4E-dienoic acid isobutylamide (pellitorine), deca-2E,4E,9-trienoic
acid isobutylamide, deca-2E,4E-dienoic acid 2-phenylethylamide, undeca-2E,4E-
dien-8,10-diynoic acid isopentylamide, tetradeca-2E,4E,12Z-trien-8,10-diynoic acid
isobutylamide, and dodeca-2E,4E-dien acid 4-hydroxy-2-phenylethylamide [2].
Essential oil contents of aerial parts vary, depending on developmental stage (vegeta-
tive, floral budding and flowering); yielding highest oil content (0.019% w/w) at
flowering stage. Oxygenated sesquiterpenes are the most abundant chemical group,
regardless of the developmental stage, significantly increasing during ripening, and vary
from 37.1% to 58.6% [13].
Pharmacology: Ethanol root extract exhibited antiepileptic activity against
MES-induced convulsions, and myorelaxation in mice [5]. Hydroalcohol extract
completely protected animals against PTZ-induced seizures, slowed PTZ-induced
kindling, and significantly prevented seizure induced oxidative stress, and cognitive
impairment, and normalized decrease in cholinesterase activity [11, 12]. Aqueous
and methanol root extracts exhibit potent antinociceptive, anti-inflammatory, and
antioxidant effects [9]. Ethanol (2%) extract produced significant local anesthetic
effect [10], and methanol extract (50%) also moderately prevented oxidative DNA
damage and showed radical scavenging activity [7]. Hydroalcohol extract protected
rats against isoniazid plus rifampicin-induced hepatotoxicity [17].
264 Anacyclus pyrethrum (L.) Lag

Essential oil from aerial parts is active against C. albicans and S. aureus [13],
and dichloromethane extract showed moderate activity against NF54 strain of
P. falciparum and L. donovani [2]. Methanol extract was modestly active against
E. coli [6]. Sequential ethanol and water root extracts exhibited in vitro inhibitory
activity (88% and 82%, respectively) of porcine pancreatic a-amylase, compared to
51% by acarbose [8]. Hot water polysaccharide extract produced marked stimu-
lating effect on RE system, and increased number of peritoneal exudate cells and
spleen cells of mice; also significantly enhanced proliferation of murine spleen cells
[3]. Petroleum ether extract produced a highly significant immunostimulating effect,
protected against CP-induced myelosuppression, improved survival of C. albicans-
infected animals, increased delayed type hypersensitivity response, percentage
neutrophil adhesion, and in vivo phagocytosis [16]. Methanol extract treated ani-
mals also showed significant improvement in immunoglobulin levels [19].
Oral administration of petroleum ether extract to rats for 28-days significantly
increased penile erection index, and caused four-fold increase in mount and three-
fold increase in intromission frequency. Sexual behavioral parameters persisted
even after 15-days of discontinuance of drug treatment [15]. An alkylamide-rich
ethanol extract significantly increased body weight, sperm count, motility and
viability, along with serum testosterone, LH and FSH concentrations in male Wistar
rats orally treated for 28-days [14].
Human A/Es, Allergy and Toxicity: It is harmful for the lungs.LXXVII
Animal Toxicity: Aqueous and methanol root extracts were nonlethal and non-
toxic to mice up to an oral dose of 5,000 mg/kg body weight [9].
Commentary: There are no clinical studies reported in English publications listed
on PubMed.

References
1. Abdollahi Fard M, Shojaii A. Efficacy of Iranian traditional medicine in the
treatment of epilepsy. Biomed Res Int. 2013;2013:692751.
2. Althaus JB, Malyszek C, Kaiser M, Brun R, Schmidt TJ. Alkamides from
Anacyclus pyrethrum L. and their in vitro antiprotozoal activity. Molecules.
2017;22. pii: E796.
3. Bendjeddou D, Lalaoui K, Satta D. Immunostimulating activity of the
hot water-soluble polysaccharide extracts of Anacyclus pyrethrum, Alpinia
galanga and Citrullus colocynthis. J Ethnopharmacol. 2003;88:155–60.
4. Boonen J, Sharma V, Dixit VK, Burvenich C, De Spiegeleer B. LC-MS
N-alkylamide profiling of an ethanolic Anacyclus pyrethrum root extract.
Planta Med. 2012;78:1787–95.
5. Gautam OP, Verma S, Jain SK. Anticonvulsant and myorelaxation activity
of Anacyclus pyrethrum DC. (Akarkara) root extract. Pharmacologyonline.
2011;1:121–5.
6. Jalayer-Naderi N, Niakan M, Khodadadi E, Mohamadi-Motlagh M. The
antibacterial activity of methanolic Anacyclus pyrethrum and Pistacia
lentiscus L. extract on Escherichia coli. Iran J Microbiol. 2016;8:372–6.
Anacyclus pyrethrum (L.) Lag 265

7. Kalim MD, Bhattacharyya D, Banerjee A, Chattopadhyay S. Oxidative DNA

damage preventive activity and antioxidant potential of plants used in Unani
system of medicine. BMC Complement Altern Med. 2010;10:77.
8. Kumar VK, Lalitha KG. In vitro study on a-amylase inhibitory activity of an
Ayurvedic medicinal plant, Anacyclus pyrethrum DC root. Indian J Pharmacol.
2014;46:350–1.
9. Manouze H, Bouchatta O, Gadhi AC, et al. Anti-inflammatory, antinoci-
ceptive, and antioxidant activities of methanol and aqueous extracts of
Anacyclus pyrethrum roots. Front Pharmacol. 2017;8:598.
10. Muralikrishnan K, Asokan S, Geetha Priya PR, Zameer Ahmed KS,
Ayyappadasan G. Comparative evaluation of the local anesthetic activity of
root extract of Anacyclus pyrethrum and its interaction at the site of injection
in guinea pigs. Anesth Essays Res. 2017;11:444–8.
11. Pahuja M, Mehla J, Reeta KH, et al. Effect of Anacyclus pyrethrum on
pentylenetetrazole-induced kindling, spatial memory, oxidative stress and
rho-kinase II expression in mice. Neurochem Res. 2013;38:547–56.
12. Pahuja M, Mehla J, Reeta KH, et al. Root extract of Anacyclus pyrethrum
ameliorates seizures, seizure-induced oxidative stress and cognitive impair-
ment in experimental animals. Epilepsy Res. 2012;98:157–65.
13. Selles C, Dib Mel A, Djabou N, et al. Antimicrobial activity and evolution
of the composition of essential oil from Algerian Anacyclus pyrethrum L.
through the vegetative cycle. Nat Prod Res. 2013;27:2231–4.
14. Sharma V, Boonen J, Spiegeleer BD, Dixit VK. Androgenic and spermato-
genic activity of alkylamide-rich ethanol solution extract of Anacyclus
pyrethrum DC. Phytother Res. 2013;27:99–106.
15. Sharma V, Thakur M, Chauhan NS, Dixit VK. Effects of petroleum ether
extract of Anacyclus pyrethrum DC. on sexual behavior in male rats. Zhong
Xi Yi Jie He Xue Bao. 2010;8:767–73.
16. Sharma V, Thakur M, Chauhan NS, Dixit VK. Immunomodulatory activity of
petroleum ether extract of Anacyclus pyrethrum. Pharm Biol. 2010;48:1247–54.
17. Usmani A, Mujahid M, Khushtar M, Siddiqui HH, Rahman MA. Hepatopro-
tective effect of Anacyclus pyrethrum Linn. against antitubercular drug-induced
hepatotoxicity in SD rats. J Complement Integr Med. 2016;13:295–300.
18. Veryser L, Taevernier L, Roche N, et al. Quantitative transdermal behavior of
pellitorine from Anacyclus pyrethrum extract. Phytomedicine. 2014;21:1801–7.
19. Yousaf F, Shahid M, Riaz M, Atta A, Fatima H. Immunomodulatory
potential of Anacyclus pyrethrum (L.) and Mucuna pruriens (L.) in male
albino rats. J Biol Regul Homeost Agents. 2017;31:425–9.
Andrographis paniculata (Burm. f.) Nees.
(Acanthaceae)

(Syn.: Justicia paniculata N.Burm.)

Abstract
This plant is found in India, China, Pakistan and Thailand. Known as “king of
bitters,” it is widely used in traditional medicines of India, Pakistan, Bangladesh,
China, Hong Kong, the Philippines, Malaysia, Indonesia, and Thailand for the
treatment of common cold, diarrhea, dysentery, infectious fever, jaundice, as liver
and cardiovascular tonic, as an antioxidant, for snakebite, bugbite, diabetes, and
malaria. Andrographis paniculata and Swertia chirayita are controversial plants
as both are used as Kiriyattu in Ayurveda, and Charayetah in Unani medicines of
India, due to their similar therapeutic actions and their hepatoprotective and
hepatostimulant activities. While A. paniculata commonly grows in the southern
parts of India, S. chirayita is mainly found in the Himalayan region. Juice of fresh
leaves or infusion is given to infants to relieve griping, irregular bowel, and loss
of appetite. Leaves and root are also used in general debility, convalescence after
fevers, dyspepsia associated with gaseous distension, and in advanced stages of
dysentery. In China, the herb derived from the leaves or aerial parts is described
as bitter and “cold”, and is considered to be latent-heat-clearing, antipyretic,
detoxicant, anti-inflammatory, and detumescent, and is thought to remove
pathogenic “heat” from the blood. It is used for the treatment of pharyngolaryn-
gitis, diarrhea, dysentery, cough with thick sputum, carbuncle, sores and
snakebites. In Malaysia, the plant is reputed as an antipyretic, antiperiodic,
anti-inflammatory, antibacterial, antihelmintic and anti-immunosuppressive, and
has been effectively used in the treatment of ulcerative colitis. More than 55
ent-labdane diterpenoids, thirty flavonoids, eight quinic acids, four xanthones,
and five rare noriridoids have been reported from the plant. Andrographolide
diterpenoids, and polyphenols, have been obtained from the whole plant. Leaf
extracts and andrographolide were found hepatoprotective against various
hepatotoxic challenges. Andrographolide also exhibits significant analgesic and
anti-inflammatory activities. Aqueous decoction/extract significantly lowers
blood glucose of diabetic animals, prevents glucose-induced hyperglycemia,
and restores metabolic profile of obese-diabetic rats back to normal. In a double
© Springer Nature Switzerland AG 2020 267
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_26
268 Andrographis paniculata (Burm. f.) Nees.

blind, RCT in Chile, tablets made of an extract (30% total andrographolides)

significantly improved symptoms of patients with rheumatoid arthritis.

Keywords




Aluy Bhunimbaha Chirayetah Chuanxinlian Fa thalai chon

Kalmegh





Nainehavendi Rohtokirata The Creat Vizra-ufar

Vernaculars: Urd.: Charayetah; Hin.: Chirayetah, Kalmegh, Kalpanath, Kiryat,

Mahattia; San.: Bhunimbaha, Kalmegha; Ben.: Cherota, Kalmegh, Kalo megha,
Mahateta; Mal.: Kaakanjiram, Kiriyathth, Kiryattu, Nila veppu, Nilamkanjiram,
Olenkirayat, Ptumba; Mar.: Chimani, Kadu kirayata, Kalpa, Olen kirayata,
Olikiryata; Tam.: Nella vemboo, Nilavembu, Pitumbay, Siriya nangai; Tel.:
Kari-vemu, Nelavemaa, Nilavembu; Ara.: Quasabhuva, Vasab-buva, Vizra-ufar;
Chi.: 见喜, Chuanxinlian, Lanhelian, Yijianxi; Eng.: Green chiretta, Kalmegh, The
Creat; Fin.: Rohtokirata; Ind.: Sambiloto; Lao.: La xa bee; Maly.: Hempedu bumi;
Per.: Nainehavendi; Sin.: Hīn kohomba; Tag.: Aluy, Likha, Serpentina, Sinta;
Tha.: Fa thalai chon; Vie.: Xuyên tâm liên.
Description: The plant is found in India, China, Pakistan and Thailand. An annual
branched, erect and herbaceous plant, 30–90 cm high, common in hedge rows
throughout the plains of India and cultivated in gardens specially in Bengal. Stem is
green, woody, quadrangular, smooth, about 1 m high, with profuse branching. Leaves
are green, opposite, on short petioles, lanceolate, glabrous with slightly undulate
margin, upper surface is dark green and shining; under surface paler and finely

Fig. 1 Andrographis paniculate, Twig with Flower, J.M. Garg, WikimediaCommons; ShareA-
like 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Andrographis_
paniculata_(Kalpa)_in_Narshapur_forest,_AP_W2_IMG_0867.jpg; https://creativecommons.org/
licenses/by-sa/3.0/deed.en
Andrographis paniculata (Burm. f.) Nees. 269

granular. They vary in size but the larger are usually 7.5 cm in length and 2.5 cm in
width. Corolla is light pink in color, hairy and bilipped. Flowers are small, solitary,
on long petioles, downy, rose colored or white with purple streaks [91] (Fig. 1).
Actions and Uses: Andrographis paniculata and Swertia chirayita are controversial
plants as both are used as Kiriyattu in Ayurveda, and Charayetah in Unani medicines
of India, due to their similar therapeutic actions and their hepatoprotective and hep-
atostimulant activities. While A. paniculata commonly grows in southern parts of
India, S. chirayita is mainly found in the Himalayan region [60]. A. paniculata is
generally known as “king of bitters,” and is widely used in traditional herbal
medicines of India, Pakistan, Bangladesh, China, Hong Kong, the Philippines,
Malaysia, Indonesia, and Thailand for the treatment of common cold, diarrhea,
dysentery, infectious fever, jaundice, as liver and cardiovascular tonic, as an
antioxidant, for snakebite, bugbite, diabetes, and malaria [39]. In Unani medicine it
(temperament, hot 2° and dry 2°) is considered aperient, anti-inflammatory, emollient,
astringent, diuretic, emmenagogue, gastric and liver tonic, carminative, anthelmintic
and antipyretic, and used in cases of leprosy, gonorrhea, scabies, boils, skin eruptions,
chronic and seasonal fevers, due to its blood purifying activity.LXXVII Juice of fresh
leaves or infusion is given to infants to relieve griping, irregular bowel, and loss of
appetite.XXI,XL,LXXXI Leaves and root are also used in general debility, convalescence
after fevers, dyspepsia associated with gaseous distension, and in advanced stages of
dysentery.XXI,LXXXI It is reported as antibacterial, antifungal, antiviral, chloretic,
hypoglycemic/hypocholesterolemic and adaptogenic [15, 38]. In rural Indonesia, it is
one of the most commonly used medicinal plants by diabetic patients, alone or in
combination with oral antidiabetic agents to achieve better blood glucose control
[114]. In China, the herb derived from the leaves or aerial parts is described as bitter
and “cold”, and is considered to be latent-heat-clearing, antipyretic, detoxicant,
anti-inflammatory, and detumescent, and is thought to remove pathogenic “heat” from
the blood. It is used for the treatment of pharyngolaryngitis, diarrhea, dysentery,
cough with thick sputum, carbuncle, sores and snakebites.XVIII In Malaysia, the plant
is reputed as an antipyretic, anti-inflammatory, antiperiodic, antibacterial, anti-
helmintic and anti-immunosuppressive [119]. It has been effectively used in the
treatment of ulcerative colitis [80], and has also shown potent neutralizing effect
against rattle snake venom in mice [78]. Andrographolide is known as anti-
inflammatory, antithrombotic, antiviral, hypotensive, and antiatherosclerotic agent,
and is used for the prevention and treatment of common cold in Scandinavia
[8, 105]. Kan Jang® is a widely used standardized fixed combination of A. paniculata
and Eleutherococcus senticosus extracts.
Phytoconstituents: Phytoconstituents widely differ in different parts of the plant, with
place of growth, season, and time of harvest. Methanol leaf extract tests positive for
alkaloids, flavonoids, terpenoids, saponins, tannins and steroids, whereas water extract
lacks flavonoids [53]. Flavonoids mainly exist in the root, but have also been isolated
from the leaves; aerial parts also contain alkanes, ketones and aldehydes. Andro-
grapholide was reported more stable in dry herb stored at room temperature, than
contents of 14-deoxy-11,12-didehydroandrographolide and neoandrographolide [71].
270 Andrographis paniculata (Burm. f.) Nees.

More than 55 ent-labdane diterpenoids, thirty flavonoids, eight quinic acids, four xan-
thones, and five rare noriridoids have been reported from the plant [39]. Andro-
grapholide diterpenoids, and polyphenols, have been obtained from the whole plant
[48]. Diterpenoids of ent-labdane type, andrographic acid, andrographolide, andro-
graphidine A, neoandrographolide, 3,14-di-deoxyandrographolide, 14-deoxy-11,
12-didehydroandrographolide, 19-hydroxy-8(17),13-labdadien-15,16-olide, 14-deoxy-
andrographolide, isoandrographolide, 3-oxo-14-deoxyandrographolide, 14-deoxy-12-
methoxyandrographolide, 12-epi-14-deoxy-12-methoxyandrographolide, 14-deoxy-
12-hydroxyandrographolide, 21-nor-3,19-isopropylidine-14-deoxy-ent-labda-8(17),13-
dien-16,15-olide, 14-epi-andrographolide, and 14-deoxy-11-hydroxyandrographo-
lide; diterpene glucosides, deoxyandrographolide-19beta-D-glucoside, 14-deoxy-11,
12-didehydroandrographiside and 6′-acetylneoandrographolide, and diterpene
dimers, bis-andrograpolides A, B, C and D, deoxyandrographiside, 14-deoxy-
11,12-didehydroandrographiside, andrographiside [22, 23, 31, 50, 55, 74, 112, 116,
126] and two acids, cinnamic acid, and ferulic acid have been isolated from aerial
parts [74]. A natural flavone, 5-hydroxy-7,8,2′,3′-tetramethoxy [33], and 1,8-di-
hydroxy-3,7-dimethoxyxanthone, 4,8-dihydroxy-2,7-dimethoxyxanthone, 1,2-dihy-
droxy-6,8-dimethoxyxanthone and 3,7,8-trimethoxy-1-hydroxyxanthone were iso-
lated from roots [31]. Two compounds A (C23H36O3, m.p.101) and B (C23H38O8, m.p.
170) were reported by Singh et al. [91]. A number of flavonoids: 7-O-methylwogonin,
7-O-methyldihydrowogonin, 5-hydroxy-7,8,2′,5′-tetramethoxyflavone, skullcapflavone-
2′-methoxylether, 5-hydroxy-7,8,2′,3′-tetramethoxyflavone, 5,4′-dihydroxy-7,8,2′,3′-
tetramethoxyflavone, dihydroskullcapflavone, 5,7,8-trimethoxydihydroflavone, 5,2′-
dihydroxy-7,8-dimethoxyflvone, andrographidine C, 5,7,4′-trihydroxyflavone, 5,7,3′,4′-
tetrahydroxyflavone [24, 25], 5,7,2′,3′-tetramethoxyflavanone and 5-hydroxy-7,2′,3′-tri-
methoxyflavone [48], and flavones: andropaniculosin A and andropaniculoside A, from
whole plant [115], and 5-hydroxy-7,8,2′-trimethoxyflavone 1,5-hydroxy-7,8-dimethoxy-
flavone 2 and 5-hydroxy-7,8,2′,5′-tetramethoxyflavone 3 from roots and stem [73]; fla-
vone glucosides, andrographidine G, andrographidine A, andropanoside, acanthoside B,
andrographiside, neoandrographiside, andrographolide, procumbide, procumboside,
(2R)-5-hydroxy-7,8-dimethoxyflavanone-5-O-beta-D-glucopyranoside, 14-deoxy-11,12-
didehydroandrographiside, 14-deoxy-11,12-didehydroandrographolide, 6-epi-8-O-
acetylharpagide, and curvifloruside F [37]; flavonoid glycosides, 5-hydroxy-7,
8-dimethoxy(2R)-flavanone-5-O-beta-D-glucopyranoside and 5-hydroxy-7,8,2′,5′-
tetramethoxyflavone-5-O-beta-D-glucopyranoside [50] have been isolated from aerial
parts.
Pharmacology: Ethanol leaf extract protected against thioacetamide- [1], and ethyl
alcohol-hepatotoxicity [28], and reversed CCl4-hepatotoxicity in rats [47, 76], and
pretreatment with both A. paniculata or S. chirayita extract was also protective
against APAP-hepatotoxicity in mice [60]. Leaf extract was more protective
against CCl4-hepatotoxicity than andrographolide [26]. However, pre- and/or post-
treatment with i.p. or oral andrographolide before galactosamine-induced hepato-
toxicity or with i.p. treatment after APAP challenge, completely ameliorated hep-
atotoxicity in rats [35], and was protective against ethanol-hepatotoxicity [95].
Andrographis paniculata (Burm. f.) Nees. 271

Andrographiside and neoandrographolide were more hepatoprotective than andro-

grapholide against CCl4-hepatotoxicity in mice [45]. Andrographolide produced
significant choleretic effect in conscious rats and anesthetized guinea pigs, and
prevented APAP-induced decrease in bile flow, better than silymarin treatment [90].
Aqueous and ethanol leaf extracts exhibit significant anti-inflammatory, anal-
gesic and antioxidant properties [3], and methanol extract completely inhibited
carageenan-induced inflammation [87]. An extract lowered body temperature in
pyrexic animals, prolonged pentobarbitone-induced sleeping time, and significantly
reduced spontaneous motor activity [54]. Andrographolide also exhibits significant
analgesic [98], and anti-inflammatory activities, reduces level of LPS-induced
proinflammatory cytokines, such as TNF-a, IL-6, IL-1b and IL-10, [68, 88] and
significantly inhibits elevation of bronchoalveolar fluid levels of TNF-a and
GM-CSF, and almost completely abolishes accumulation of lymphocytes and
eosinophils in OVA-immunized and nasally-challenged mice [2, 13]. Neoandro-
grapholide also significantly suppressed dimethylbenzene-induced ear edema, and
reduced acetic acid-induced increase in vascular permeability in mice [52]. Aqu-
eous extract (higher concentration of total flavanoid) possesses better antioxidant
activity than ethanol extract [51], and is more effective than doxorubicin in
improving CAT, SOD, and GST, and reducing LDH activities in liver of lymphoma
bearing mice [110]. Methanol and ethanol leaf extracts are reported to show
strongest antioxidant activity [53]. A therapeutically used standardized hydro-
methanol extract and andrographolide exhibit adaptogenic property, and signifi-
cantly ameliorate stress-induced pathological changes, including expression of
cytokines, TNF-a, IL-10 and IL-1b in blood and brain of rats [102, 104], and
attenuate diabetes-associated cognitive deficit, reduce AChE activity, oxidative
stress, improve hyperglycemia, and insulin deficiency in diabetic rats [103].
Oral administration of aqueous decoction/extract significantly lowers blood
glucose [30, 41, 77], increases activity of SOD and CAT in diabetic animals [30],
and prevents glucose-induced hyperglycemia in rabbits [16]. Aqueous leaf extract
was also very effective in restoring metabolic profile of obese-diabetic rats back to
normal [6]. Ethanol extract significantly improved diabetes-caused oxidative stress,
increased bodyweight and reduced FBG in diabetic rats, but did not affect body
weight and serum glucose in normal rats [123], and showed appreciable in vitro
a-glucosidase inhibitory, and a weak a-amylase inhibitory activity [97]. Oral
administration of leaf extract activated brush-border membrane-bound hydrolases,
viz. lactase, maltase and sucrase in small intestine of adult male rats, accelerating
intestinal digestion, and absorption of carbohydrates [27]. Andrographolide
decreased plasma glucose concentrations in normal rats more than in diabetic rats,
and significantly attenuated increase of plasma glucose induced by intravenous
glucose challenge in normal rats [118]. Methanol extract and andrographolide
exhibit in vitro aldose reductase inhibitory activity, that might contribute to
decreased complications associated with diabetes [109].
Pretreatment with an hydroalcohol extract restored hemodynamic parameters
and left ventricular function, and significantly prevented depletion of endogenous
antioxidants in isoproterenol-induced MI [63], and I/R induced myocardial injury in
272 Andrographis paniculata (Burm. f.) Nees.

rats [64], and dogs [34]. Aqueous extract supplementation also significantly ame-
liorated high-fat diet-induced pathological cardiac hypertrophy, and apoptosis in
mice [40]. Intravenous injection of aqueous extract remarkably increased PGI2,
inhibited synthesis of TXA2, and elevated cAMP in platelets of dogs, after MI
[125]. Andrographolide inhibits PAF-induced [8], and thrombin-induced platelet
aggregation, but 14-deoxy-11,12-didehydroandrographolide (AP3) exhibits higher
antiplatelet activity than andrographolide. However, an extract with high level of
AP3 showed lesser inhibitory activity, than the extract with lower level of AP3
[105]. Aqueous extract [121, 122], and AP3 produced significant fall in mean
arterial BP and HR of anesthetized rats [120], and AP3 was also reported the most
potent compound for inducing vasorelaxation and decreasing HR [117]. Treatment
with a purified extract, containing 16% andrographolide, or andrographolide for
five-days, after fifty-days of high-fructose-fat diet, significantly decreased levels of
blood glucose, TGs, and LDL-C in rats [62].
Aqueous extract possesses significant antimicrobial activity [94], and was potently
active against P. aeruginosa, and moderately active against MRSA [119]. but the
plant powder suspended in water was inactive against Salmonella, Shigella, E. coli, gr.
A Streptococci, and S. aureus [49]. Ethanol extract significantly inhibited growth of
E. coli, S. aureus, Sh. boydii, Sh. sonnei, S. typhi, S. typhimurium, and V. cholerae
[57]. Aqueous, ethanol, methanol and chloroform leaf extracts exhibited antibacterial
activity against B. cereus and S. aureus [53]. Methanol extract inhibited growth of
choloroquine sensitive and resistant strains of P. falciparum [56], and chloroform
extract completely inhibited growth of malarial parasites [61]. Methanol extract was
also fungicidal against T. mentagrophytes, T. rubrum, M. canis, C. albicans, C.
tropicalis, and A. niger [99]. Andrographolide was active against S. aureus, S. ther-
mophilus, B. subtilis, E. coli, M. smegmatis, K. pneumonia, and P. aeruginosa, but not
effective against C. albicans and S. cerevisiae [9]. Andrographolide, neoandro-
grapholide and AP3 also exhibited virucidal activity against HSV-1 [113]. Subcuta-
neous injections of leaves aqueous decoction into infected dogs reduced the number of
microfilariae in blood by more than 85% [32]. Alcoholic extract of the rhizome
showed good in vitro activity against human A. lumbricoides [44], and water-soluble
fraction containing flavones showed a strong inhibitory action against Sh. dysenteriae,
but was found clinically ineffective. Contrarily, water-insoluble lactones, which
showed no antibacterial activity, had clinical value in many infections. Isolated
purified lactones and many of their soluble derivatives were devoid of any in vitro
antibacterial effect. Animal experiments with large doses did not reveal any evidence
of transformation of these compounds into active metabolites.XVIII Topical applica-
tion of the extract significantly enhances rate of wound healing in rats, with markedly
less scar, more collagen and absence of inflammatory cells [7].
Ethanol extract pretreatment (i.p.) of mice significantly protects against CP-
toxicity [86], and inhibits tumor-specific angiogenesis [85]. Andrographolide inhibits
proliferation of different tumor cell lines [75], has potent anticancer activity against
human colorectal carcinoma Lovo cells [89], and significantly reduces overexpres-
sion of VEGF to arrest cell cycle [108, 124]. Pretreatment of rats with aqueous and
ethanol extracts protects against ethanol-induced gastric mucosal lesions [111], and
Andrographis paniculata (Burm. f.) Nees. 273

hydroethanol extract significantly reduced acidity, pepsin concentration, myeloper-

oxidase and H+K+-ATPase activities [66, 81]. Pretreatment with aqueous extract of
the whole plant significantly ameliorated gentamicin-nephrotoxicity in rats [92].
Oral administration of the herb to mice produced contraceptive effect [83].
Supplementation of diet of male mice with powdered stems prolongs gestational
period of untreated female mice, probably by lowering male libido [84]. Similarly,
female mice consuming powdered drug for six weeks did not conceive when mated
with untreated male mice of proven fertility [127]. Dry leaf powder administration
to male rats for 60-days also produced antispermatogenic and/or antiandrogenic
effects [4], that was attributed to andrographolide [5]. However, Burgos et al.[17]
reported no testicular toxicity of a standardized dried extract given to male Sprague
Dawley rats for 60-days; powdered extract administration also did not affect plasma
progesterone level of pregnant rats [67].
Clinical Studies: In a prospective, double blind, RCT in Chile, tablets made of an
extract (30% total andrographolides) administered three times a day for 14-weeks to
patients with rheumatoid arthritis, reduced intensity of joint pain, significantly
decreased number of swollen joints, number of tender joints, total grade of swollen
and tender joints, and reduced rheumatoid factor, IgA, and C4 [18]. Administration
of A. paniculata tablets to patients significantly ameliorated post-ESWL UTI, and
reduced pyuria and hematuria, comparable to cotrimoxazole and norfloxacin [58].
Also, patients with relapsing-remitting multiple sclerosis, receiving interferon b,
supplemented with one tablet containing 170 mg of a purified extract (total
andrographolides: 85 mg per tablet) or placebo every 12 h for 12 consecutive
months, showed a significant reduction in their Fatigue Severity Scores compared
to placebo [14]. Another standardized extract, marketed as KalmCold®, was
reported significantly efficacious in relieving symptoms over placebo in patients
with uncomplicated URTI [82]. In Thai patients with modest hypertriglyceridemia,
treatment with an extract standardized to andrographolide reduced TG levels,
comparable to gemfibrozil [72]. A review of clinical trials showed it superior to
placebo in alleviating subjective symptoms of uncomplicated URTI [29], and sig-
nificantly decreasing nasal secretions but not symptoms of URTI of children [20].
In China, various preparations and compound formulae of the herb have been widely
used to treat infectious and non-infectious diseases with significant effective rates; such
as epidemic encephalitis B, suppurative otitis media, neonatal subcutaneous annular
ulcer, vaginitis, cervical erosion, pelvic inflammation, herpes zoster, chicken pox and
mumps, neurodermatitis, eczema, and burns. Many preparations of the herb have shown
therapeutic value in acute bacillary dysentery and enteritis. Aqueous ethanol extract
(HMPL-004), available in China, was found equally efficacious to meselamine in
patients with mild-to-moderately active ulcerative colitis [101], and at a dose of
1,800 mg daily, patients were more likely to achieve clinical response than placebo
[79]. Administration of ethanol extract tablets or andrographolide is reported to have
cured many cases of acute bacillary dysentery, acute gastroenteritis. pulmonary
tuberculosis especially the exudative type, tuberculous meningitis, and acute
pyelonephritis, in which the results were similar to nitrofurantoin but with less side
274 Andrographis paniculata (Burm. f.) Nees.

effects. Intra-arterial or retrograde intravenous injections of the herb were effective in

thromboangitis obliterans, especially of “heat toxic type.” Ten cases of viper bites were
all cured, mostly in 3–5 days, by a compound formula which has A. peniculata as the
chief herb.XVIII
Mechanism of Action: Hepatoprotective effect of A. paniculata and andographolide
is suggested to be due to their ability to activate antioxidant enzymes and prevent to
catalyze reactions of oxidants involved in causing hepatotoxicity [106, 107].
a-glucosidase inhibition may possibly be one of the mechanisms for antidiabetic
effect [97], whereas andrographolide is suggested to increase glucose utilization
[118]. An extract of the plant potently activates TRPV4 channels; andrographolide
does not activate or block activation of TRPV4 channels, but the active compound
was identified as bisandrographolide A [96].
Human A/Es, Allergy and Toxicity: Large oral doses may cause gastric dis-
comfort and loss of appetite. Injection of crude extract caused anaphylactic
shock,XVIII and a phase 1 trial of andrographolide in HIV positive patients was
interrupted at 6 weeks due to adverse events, including anaphylactic reaction in one
patient [19]. Nevertheless, multiple oral dosing of a standardized crude powder at
the normal therapeutic doses used for common cold and uncomplicated URTI, do
not significantly affect physiological parameters in healthy subjects, except a
transient but significant reduction in mean SBP [100].
Animal Toxicity: Oral ethanol leaf extract at a dose of 2,500 mg/kg to adult
female Sprague Dawley rats produced no mortality or toxicity-related behavioral, or
macroscopic organ changes [1]. LD50 (i.p.) of andrgrapholide in male mice was
reported to be 11,460 mg/kg [36].
CYP450 and Potential for Drug-Herb Interactions: Pretreatment of rats with
ethanol extract or andrographolide for 5-days increased activities of CYP2C6/11,
CYP1A1/2, and CYP3A1/2, and significantly reduced AUC of tolbutamide [21].
Coadministration of ethanol extract or andrographolide with etoricoxib, nabume-
tone or naproxen to rats significantly decreased their Cmax, and AUC, but coad-
ministration of the extract with the drugs exhibited significant synergistic
antiarthritic activity [10–12]. Administration of hydroalcohol (80%) extract to mice
for 14-days significantly increased liver levels of acid soluble sulphydryl (-SH)
content, CYP450, CYP450 reductase, CYP b5 reductase, GST, DT-diaphorase, and
SOD, indicating chemopreventive potential against chemical carcinogens [93].
Both aqueous and alcohol extracts significantly affected activities of hepatic
CYP1A1 and CYP2B isoforms, though the contents of CYP450 were not signifi-
cantly modified [43]; andrographolide was identified as a significant in vitro inducer
of CYP1A1 [42]. Contrarily, an extract was reported competitive inhibitor of
CYP3A4 in human microsomes [69, 70], and Kar et al. [46] also reported the plant
as weak in vitro inhibitor of human CYP3A4 and CYP2D6, while Muthiah et al.
[59] reported it a weak inhibitor of CYP2C8. Ethanol and methanol extracts were
reported more potent in vitro inhibitors of CYP3A4 and CYP2C9 activities than the
aqueous and hexane extracts [65].
Andrographis paniculata (Burm. f.) Nees. 275

Commentary: RCTs have corroborated its anti-inflammatory effects in arthritis

and ulcerative colitis; it was also effective in URTI and UTI. However, the varia-
tions in effects on CYP450s by various extracts need to be delineated, for its use in
combination with prescription drugs. Coadministration of ethanol extract or
andrographolide with etoricoxib, nabumetone or naproxen to rats significantly
decreased their Cmax, and AUC, but exhibited significant synergistic antiarthritic
activity [10–12]. This plant probably holds more clinical potentials than have so far
been realized.

References
1. Abdulaziz Bardi D, Halabi MF, Hassandarvish P, et al. Andrographis
paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in
rats. PLoS ONE. 2014;9:e109424.
2. Abu-Ghefreh AA, Canatan H, Ezeamuzie CI. In vitro and in vivo
anti-inflammatory effects of andrographolide. Int Immunopharmacol. 2009;
9:313–8.
3. Adedapo AA, Adeoye BO, Sofidiya MO, Oyagbemi AA. Antioxidant,
antinociceptive and anti-inflammatory properties of the aqueous and
ethanolic leaf extracts of Andrographis paniculata in some laboratory
animals. J Basic Clin Physiol Pharmacol. 2015;26:327–34.
4. Akbarsha MA, Manivannan B, Hamid KS, Vijayan B. Antifertility effect
of Andrographis paniculata (Nees) in male albino rat. Indian J Exp Biol.
1990;28:421–6.
5. Akbarsha MA, Murugaian P. Aspects of the male reproductive
toxicity/male antifertility property of andrographolide in albino rats: effect
on the testis and the cauda epididymidal spermatozoa. Phytother Res.
2000;14:432–5.
6. Akhtar MT, Bin Mohd Sarib MS, Ismail IS, et al. Antidiabetic activity and
metabolic changes induced by Andrographis paniculata plant extract in
obese diabetic rats. Molecules. 2016;21. pii: E1026.
7. Al-Bayaty FH, Abdulla MA, Abu Hassan MI, Ali HM. Effect of
Andrographis paniculata leaf extract on wound healing in rats. Nat Prod
Res. 2012;26:423–9.
8. Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H. Inhibitory
effect of andrographolide from Andrographis paniculata on PAF-induced
platelet aggregation. Phytomedicine. 1999;6:27–31.
9. Arifullah M, Namsa ND, Mandal M, et al. Evaluation of antibacterial and
antioxidant potential of andrographolide and echiodinin isolated from
callus culture of Andrographis paniculata Nees. Asian Pac J Trop Biomed.
2013;3:604–10 (discussion 609–10).
10. Balap A, Atre B, Lohidasan S, Sinnathambi A, Mahadik K. Pharmaco-
kinetic and pharmacodynamic herb-drug interaction of Andrographis pani-
culata (Nees) extract and andrographolide with etoricoxib after oral
administration in rats. J Ethnopharmacol. 2016;183:9–17.
276 Andrographis paniculata (Burm. f.) Nees.

11. Balap A, Lohidasan S, Sinnathambi A, Mahadik K. Herb-drug interaction

of Andrographis paniculata (Nees) extract and andrographolide on
pharmacokinetic and pharmacodynamic of naproxen in rats. J Ethnophar-
macol. 2017;195:214–21.
12. Balap A, Lohidasan S, Sinnathambi A, Mahadik K. Pharmacokinetic and
pharmacodynamic interaction of andrographolide and standardized extract
of Andrographis paniculata (Nees) with nabumetone in Wistar rats.
Phytother Res. 2017;31:75–80.
13. Bao Z, Guan S, Cheng C, et al. A novel anti-inflammatory role for
andrographolide in asthma via inhibition of the nuclear factor-{kappa}B
pathway. Am J Respir Crit Care Med. 2009;179:657–65.
14. Bertoglio JC, Baumgartner M, Palma R, et al. Andrographis paniculata
decreases fatigue in patients with relapsing-remitting multiple sclerosis: a
12-month double-blind placebo-controlled pilot study. BMC Neurol.
2016;16:77.
15. Bhatnagar SS, Santapau H, Desa JD, et al. Biological activity of Indian
medicinal plants. I. Antibacterial, antitubercular and antifungal action.
Indian J Med Res. 1961;49:799–813.
16. Borhanuddin M, Shamsuzzoha M, Hussain AH. Hypoglycaemic effects of
Andrographis paniculata Nees on nondiabetic rabbits. Bangladesh Med
Res Counc Bull. 1994;20:24–6.
17. Burgos RA, Caballero EE, Sánchez NS, et al. Testicular toxicity assessment
of Andrographis paniculata dried extract in rats. J Ethnopharmacol.
1997;58:219–24.
18. Burgos RA, Hancke JL, Bertoglio JC, et al. Efficacy of an Andrographis
paniculata composition for the relief of rheumatoid arthritis symptoms: a
prospective randomized placebo-controlled trial. Clin Rheumatol. 2009;
28:931–46.
19. Calabrese C, Berman SH, Babish JG, et al. A phase I trial of andrographolide
in HIV positive patients and normal volunteers. Phytother Res. 2000;14:
333–8.
20. Carr RR, Nahata MC. Complementary and alternative medicine for upper
respiratory tract infection in children. Am J Health Syst Pharm. 2006;63:
33–9.
21. Chen HW, Huang CS, Liu PF, et al. Andrographis paniculata extract and
andrographolide modulate the hepatic drug metabolism system and plasma
tolbutamide concentrations in rats. Evid Based Complement Alternat Med.
2013;2013:982689.
22. Chen L, Zhu H, Wang R, et al. ent-Labdane diterpenoid lactone stereoiso-
mers from Andrographis paniculata. J Nat Prod. 2008;71:852–5.
23. Chen LX, Qu GX, Qiu F. Studies on diterpenoids from Andrographis
paniculata. Zhongguo Zhong Yao Za Zhi. 2006;31:1594–7 (Article in
Chinese).
24. Chen LX, Qu GX, Qiu F. Studies on flavonoids of Andrographis paniculata.
Zhongguo Zhong Yao Za Zhi. 2006;31:391–5 (Article in Chinese).
Andrographis paniculata (Burm. f.) Nees. 277

25. Chen LX, He H, Xia GY, Zhou KL, Qiu F. A new flavonoid from the
aerial parts of Andrographis paniculata. Nat Prod Res. 2014;28:138–43.
26. Choudhury BR, Poddar MK. Andrographolide and kalmegh (Andro-
graphis paniculata) extract: in vivo and in vitro effect on hepatic lipid
peroxidation. Methods Find Exp Clin Pharmacol. 1984;6:481–5.
27. Choudhury BR, Poddar MK. Andrographolide and kalmegh (Andro-
graphis paniculata) extract: effect on intestinal brush-border membrane-
bound hydrolases. Methods Find Exp Clin Pharmacol. 1985;7:617–21.
28. Choudhury BR, Poddar MK. Effect of Kalmegh extract on rat liver and
serum enzymes. Methods Find Exp Clin Pharmacol. 1983;5:727–30.
29. Coon JT, Ernst E. Andrographis paniculata in the treatment of upper
respiratory tract infections: a systematic review of safety and efficacy.
Planta Med. 2004;70:293–8.
30. Dandu AM, Inamdar NM. Evaluation of beneficial effects of antioxidant
properties of aqueous leaf extract of Andrographis paniculata in
STZ-induced diabetes. Pak J Pharm Sci. 2009;22:49–52.
31. Dua VK, Ojha VP, Roy R, et al. Antimalarial activity of some xanthones
isolated from the roots of Andrographis paniculata. J Ethnopharmacol.
2004;95:247–51.
32. Dutta A, Sukul NC. Filaricidal properties of a wild herb, Andrographis
paniculata. J Helminthol. 1982;56:81–4.
33. Govindachari TR, Pai BR, Srinivasan M, Kalyanaraman PS. Chemical
investigation of Andrographis paniculata. Indian J Chem. 1969;7:306.
34. Guo ZL, Zhao HY, Zheng XH. The effect of Andrographis paniculata
Nees (APN) in alleviating the myocardial ischemic reperfusion injury.
J Tongji Med Univ. 1994;14:49–51.
35. Handa SS, Sharma A. Hepatoprotective activity of andrographolide against
galactosamine & paracetamol intoxication in rats. Indian J Med Res.
1990;92:284–92.
36. Handa SS, Sharma A. Hepatoprotective activity of andrographolide from
Andrographis paniculata against carbon tetrachloride. Indian J Med Res.
1990;92:276–83.
37. Hapuarachchi SD, Ali Z, Abe N, et al. Andrographidine G, a new flavone
glucoside from Andrographis paniculata. Nat Prod Commun. 2013;8:333–4.
38. Hemadri K, Rao SS. Jaundice: tribal medicine. Ancient Sci Life. 1984;3:
209–12.
39. Hossain MS, Urbi Z, Sule A, Hafizur Rahman KM. Andrographis
paniculata (Burm.f.) Wall. ex Nees: a review of ethnobotany, phytochem-
istry, and pharmacology. Sci World J. 2014;2014:274905.
40. Hsieh YL, Shibu MA, Lii CK, et al. Andrographis paniculata extract
attenuates pathological cardiac hypertrophy and apoptosis in high-fat diet
fed mice. J Ethnopharmacol. 2016;192:170–7.
41. Husen R, Pihie AH, Nallappan M. Screening for antihyperglycaemic
activity in several local herbs of Malaysia. J Ethnopharmacol. 2004;95:
205–8.
278 Andrographis paniculata (Burm. f.) Nees.

42. Jaruchotikamol A, Jarukamjorn K, Sirisangtrakul W, et al. Strong

synergistic induction of CYP1A1 expression by andrographolide plus
typical CYP1A inducers in mouse hepatocytes. Toxicol Appl Pharmacol.
2007;224:156–62.
43. Jarukamjorn K, Don-in K, Makejaruskul C, et al. Impact of Andrographis
paniculata crude extract on mouse hepatic cytochrome P450 enzymes.
J Ethnopharmacol. 2006;105:464–7.
44. Kaleysa Raj R. Screening of indigenous plants for anthelmintic action
against human Ascaris lumbricoides. Part I. Indian J Physiol Pharmacol.
1975;19:47–9.
45. Kapil A, Koul IB, Banerjee SK, Gupta BD. Antihepatotoxic effects of
major diterpenoid constituents of Andrographis paniculata. Biochem
Pharmacol. 1993;46:182–5.
46. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety
assessment of selected medicinal food plants used in Ayurveda through
CYP450 enzyme inhibition study. J Sci Food Agric. 2017;97:333–40.
47. Koh PH, Mokhtar RA, Iqbal M. Andrographis paniculata ameliorates
carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity:
diminution of oxidative stress. Redox Rep. 2011;16:134–43.
48. Koteswara Rao Y, Vimalamma G, Rao CV, Tzeng YM. Flavonoids and
andrographolides from Andrographis paniculata. Phytochemistry. 2004;65:
2317–21.
49. Leelarasamee A, Trakulsomboon S, Sittisomwong N. Undetectable
antibacterial activity of Andrographis paniculata (Burma) wall. ex ness.
J Med Assoc Thai. 1990;73:299–304.
50. Li W, Xu X, Zhang H, et al. Secondary metabolites from Andrographis
paniculata. Chem Pharm Bull (Tokyo). 2007;55:455–8.
51. Lin FL, Wu SJ, Lee SC, Ng LT. Antioxidant, antioedema and analgesic
activities of Andrographis paniculata extracts and their active constituent
andrographolide. Phytother Res. 2009;23:958–64.
52. Liu J, Wang ZT, Ji LL. In vivo and in vitro anti-inflammatory activities of
neoandrographolide. Am J Chin Med. 2007;35:317–28.
53. Malahubban M, Alimon AR, Sazili AQ, Fakurazi S, Zakry FA. Phyto-
chemical analysis of Andrographis paniculata and Orthosiphon stamineus
leaf extracts for their antibacterial and antioxidant potential. Trop Biomed.
2013;30:467–80.
54. Mandal SC, Dhara AK, Maiti BC. Studies on psychopharmacological
activity of Andrographis paniculata extract. Phytother Res. 2001;15:253–6.
55. Matsuda T, Kuroyanagi M, Sugiyama S, et al. Cell differentiation-inducing
diterpenes from Andrographis paniculata Nees. Chem Pharm Bull
(Tokyo). 1994;42:1216–25.
56. Mishra K, Dash AP, Swain BK, Dey N. Antimalarial activities of
Andrographis paniculata and Hedyotis corymbosa extracts and their
combination with curcumin. Malar J. 2009;8:26.
Andrographis paniculata (Burm. f.) Nees. 279

57. Mishra US, Mishra A, Kumari R, Murthy PN, Naik BS. Antibacterial
activity of ethanol extract of Andrographis paniculata. Indian J Pharm Sci.
2009;71:436–8.
58. Muangman V, Viseshsindh V, Ratana-Olarn K, Buadilok S. The usage of
Andrographis paniculata following Extracorporeal Shock Wave Litho-
tripsy (ESWL). J Med Assoc Thai. 1995;78:310–3.
59. Muthiah YD, Ong CE, Sulaiman SA, Ismail R. Inhibition of human
Cytochrome P450 2c8-catalyzed amodiaquine N-desethylation: effect of five
traditionally and commonly used herbs. Pharmacognosy Res. 2016;8:292–7.
60. Nagalekshmi R, Menon A, Chandrasekharan DK, Nair CK. Hepatopro-
tective activity of Andrographis paniculata and Swertia chirayita. Food
Chem Toxicol. 2011;49:3367–73.
61. Najib Nik A, Rahman N, Furuta T, et al. Antimalarial activity of extracts of
Malaysian medicinal plants. J Ethnopharmacol. 1999;64:249–54.
62. Nugroho AE, Andrie M, Warditiani NK, et al. Antidiabetic and anti-
hiperlipidemic effect of Andrographis paniculata (Burm. f.) Nees and
andrographolide in high-fructose-fat-fed rats. Indian J Pharmacol. 2012;44:
377–81.
63. Ojha S, Bharti S, Golechha M, et al. Andrographis paniculata extract protect
against isoproterenol-induced myocardial injury by mitigating cardiac
dysfunction and oxidative injury in rats. Acta Pol Pharm. 2012;69:269–78.
64. Ojha SK, Bharti S, Joshi S, Kumari S, Arya DS. Protective effect of
hydroalcoholic extract of Andrographis paniculata on ischaemia-reperfusion
induced myocardial injury in rats. Indian J Med Res. 2012;135:414–21.
65. Pan Y, Abd-Rashid BA, Ismail Z, et al. In vitro determination of the effect
of Andrographis paniculata extracts and andrographolide on human
hepatic cytochrome P450 activities. J Nat Med. 2011;65:440–7.
66. Panneerselvam S, Arumugam G. A biochemical study on the gastropro-
tective effect of hydroalcoholic extract of Andrographis paniculata in rats.
Indian J Pharmacol. 2011;43:402–8.
67. Panossian A, Kochikian A, Gabrielian E, et al. Effect of Andrographis
paniculata extract on progesterone in blood plasma of pregnant rats.
Phytomedicine. 1999;6:157–61.
68. Parichatikanond W, Suthisisang C, Dhepakson P, Herunsalee A. Study of
anti-inflammatory activities of the pure compounds from Andrographis
paniculata (Burm.f.) Nees and their effects on gene expression. Int Immuno-
pharmacol. 2010;10:1361–73.
69. Pekthong D, Blanchard N, Abadie C, et al. Effects of Andrographis
paniculata extract and andrographolide on hepatic cytochrome P450
mRNA expression and monooxygenase activities after in vivo administra-
tion to rats and in vitro in rat and human hepatocyte cultures. Chem Biol
Interact. 2009;179:247–55.
70. Pekthong D, Martin H, Abadie C, et al. Differential inhibition of rat and
human hepatic cytochrome P450 by Andrographis paniculata extract and
andrographolide. J Ethnopharmacol. 2008;115:432–40.
280 Andrographis paniculata (Burm. f.) Nees.

71. Pholphana N, Rangkadilok N, Thongnest S, et al. Determination and

variation of three active diterpenoids in Andrographis paniculata (Burm.f.)
Nees. Phytochem Anal. 2004;15:365–71.
72. Phunikhom K, Khampitak K, Aromdee C, Arkaravichien T, Sattaya-
sai J. Effect of Andrographis paniculata extract on triglyceride levels of
the patients with hypertriglyceridemia: a randomized controlled trial.
J Med Assoc Thai. 2015;98 Suppl 6:S41–7.
73. Radhika P, Prasad YR, Lakshmi KR. Flavones from the stem of
Andrographis paniculata Nees. Nat Prod Commun. 2010;5:59–60.
74. Radhika P, Prasad YR, Sowjanya K. A new diterpene from the leaves of
Andrographis paniculata Nees. Nat Prod Commun. 2012;7:485–6.
75. Rajagopal S, Kumar RA, Deevi DS, et al. Andrographolide, a potential
cancer therapeutic agent isolated from Andrographis paniculata. J Exp
Ther Oncol. 2003;3:147–58.
76. Rana AC, Avadhoot Y. Hepatoprotective effects of Andrographis panic-
ulata against carbon tetrachloride-induced liver damage. Arch Pharm Res.
1991;14:93–5.
77. Reyes BA, Bautista ND, Tanquilut NC, et al. Antidiabetic potentials of
Momordica charantia and Andrographis paniculata and their effects on
estrous cyclicity of alloxan-induced diabetic rats. J Ethnopharmacol.
2006;105:196–200.
78. Samy RP, Thwin MM, Gopalakrishnakone P, Ignacimuthu S. Ethno-
botanical survey of folk plants for the treatment of snakebites in Southern
part of Tamilnadu. India. J Ethnopharmacol. 2008;115:302–12.
79. Sandborn WJ, Targan SR, Byers VS, et al. Andrographis paniculata
extract (HMPL-004) for active ulcerative colitis. Am J Gastroenterol.
2013;108:90–8.
80. Santana MT, Cercato LM, Oliveira JP, Camargo EA. Medicinal plants in
the treatment of colitis: evidence from preclinical studies. Planta Med.
2017;83:588–614.
81. Saranya P, Geetha A. Antiulcer activity of Andrographis paniculata
(Burm. f.) Wall against cysteamine-induced duodenal ulcer in rats. Indian J
Exp Biol. 2011;49:525–33.
82. Saxena RC, Singh R, Kumar P, et al. A randomized double blind placebo
controlled clinical evaluation of extract of Andrographis paniculata
(KalmCold) in patients with uncomplicated upper respiratory tract
infection. Phytomedicine. 2010;17:178–85.
83. Shamsuzzoha M, Rahman MS, Ahmed MM, Islam AK. Antifertility effect
in mice of medicinal plant of family Acanthaceae. Lancet. 1978;2:900.
84. Shamsuzzoha M, Rahman MS, Ahmed MM. Antifertility activity of a
medicinal plant of the genus Andrografis Wall (family Acanthaceae)
Part II. Bangladesh Med Res Counc Bull. 1979;5:14–8.
Andrographis paniculata (Burm. f.) Nees. 281

85. Sheeja K, Guruvayoorappan C, Kuttan G. Antiangiogenic activity of

Andrographis paniculata extract and andrographolide. Int Immunophar-
macol. 2007;7:211–21.
86. Sheeja K, Kuttan G. Ameliorating effects of Andrographis paniculata
extract against cyclophosphamide-induced toxicity in mice. Asian Pac J
Cancer Prev. 2006;7:609–14.
87. Sheeja K, Shihab PK, Kuttan G. Antioxidant and anti-inflammatory
activities of the plant Andrographis paniculata Nees. Immunopharmacol
Immunotoxicol. 2006;28:129–40.
88. Sheeja K, Kuttan G. Andrographis paniculata downregulates proinflamma-
tory cytokine production and augments cell mediated immune response in
metastatic tumor-bearing mice. Asian Pac J Cancer Prev. 2010;11:723–9.
89. Shi MD, Lin HH, Lee YC, et al. Inhibition of cell-cycle progression in
human colorectal carcinoma Lovo cells by andrographolide. Chem Biol
Interact. 2008;174:201–10.
90. Shukla B, Visen PK, Patnaik GK, Dhawan BN. Choleretic effect of
andrographolide in rats and guinea pigs. Planta Med. 1992;58:146–9.
91. Singh A, Kapoor LD, Chandra V. Pharmacobotanic studies of kalmegh.
J Res Indian Med. 1972;7:93.
92. Singh P, Srivastava MM, Khemani LD. Renoprotective effects of Andro-
graphis paniculata (Burm.f.) Nees in rats. Ups J Med Sci. 2009;114:136–9.
93. Singh RP, Banerjee S, Rao AR. Modulatory influence of Andrographis
paniculata on mouse hepatic and extrahepatic carcinogen metabolizing
enzymes and antioxidant status. Phytother Res. 2001;15:382–90.
94. Singha PK, Roy S, Dey S. Antimicrobial activity of Andrographis paniculata.
Fitoterapia. 2003;74:692–4.
95. Singha PK, Roy S, Dey S. Protective activity of andrographolide and
arabinogalactan proteins from Andrographis paniculata Nees against
ethanol-induced toxicity in mice. J Ethnopharmacol. 2007;111:13–21.
96. Smith PL, Maloney KN, Pothen RG, et al. Bisandrographolide from
Andrographis paniculata activates TRPV4 channels. J Biol Chem.
2006;281:29897–904.
97. Subramanian R, Asmawi MZ, Sadikun A. In vitro alpha-glucosidase and
alpha-amylase enzyme inhibitory effects of Andrographis paniculata
extract and andrographolide. Acta Biochim Pol. 2008;55:391–8.
98. Sulaiman MR, Zakaria ZA, Abdul Rahman A, et al. Antinociceptive and
antiedematogenic activities of andrographolide isolated from Andro-
graphis paniculata in animal models. Biol Res Nurs. 2010;11:293–301.
99. Sule A, Ahmed QU, Latip J, et al. Antifungal activity of Andrographis
paniculata extracts and active principles against skin pathogenic fungal
strains in vitro. Pharm Biol. 2012;50:850–6.
100. Suriyo T, Pholphana N, Ungtrakul T, et al. Clinical parameters following
multiple oral dose administration of a standardized Andrographis panic-
ulata capsule in healthy Thai subjects. Planta Med. 2017;83:778–89.
282 Andrographis paniculata (Burm. f.) Nees.

101. Tang T, Targan SR, Li ZS, et al. Randomised clinical trial: herbal extract
HMPL-004 in active ulcerative colitis—a double-blind comparison with
sustained release mesalazine. Aliment Pharmacol Ther. 2011;33:194–202.
102. Thakur AK, Chatterjee SS, Kumar V. Adaptogenic potential of andro-
grapholide: an active principle of the king of bitters (Andrographis
paniculata). J Tradit Complement Med. 2014;5:42–50.
103. Thakur AK, Rai G, Chatterjee SS, Kumar V. Beneficial effects of an
Andrographis paniculata extract and andrographolide on cognitive
functions in streptozotocin-induced diabetic rats. Pharm Biol. 2016;54:
1528–38.
104. Thakur AK, Soni UK, Rai G, Chatterjee SS, Kumar V. Protective effects of
Andrographis paniculata extract and pure andrographolide against chronic
stress-triggered pathologies in rats. Cell Mol Neurobiol. 2014;34:1111–21.
105. Thisoda P, Rangkadilok N, Pholphana N, et al. Inhibitory effect of
Andrographis paniculata extract and its active diterpenoids on platelet
aggregation. Eur J Pharmacol. 2006;553:39–45.
106. Trivedi NP, Rawal UM, Patel BP. Hepatoprotective effect of andro-
grapholide against hexachlorocyclohexane-induced oxidative injury. Integr
Cancer Ther. 2007;6:271–80.
107. Trivedi NP, Rawal UM. Hepatoprotective and antioxidant property of
Andrographis paniculata (Nees) in BHC induced liver damage in mice.
Indian J Exp Biol. 2001;39:41–6.
108. Tung YT, Chen HL, Tsai HC, et al. Therapeutic potential of andro-
grapholide isolated from the leaves of Andrographis paniculata Nees for
treating lung adenocarcinomas. Evid Based Complement Alternat Med.
2013;2013:305898.
109. Veeresham C, Swetha E, Rao AR, Asres K. In vitro and in vivo aldose
reductase inhibitory activity of standardized extracts and the major
constituent of Andrographis paniculata. Phytother Res. 2013;27:412–6.
110. Verma N, Vinayak M. Antioxidant action of Andrographis paniculata on
lymphoma. Mol Biol Rep. 2008;35:535–40.
111. Wasman SQ, Mahmood AA, Chua LS, Alshawsh MA, Hamdan S.
Antioxidant and gastroprotective activities of Andrographis paniculata
(Hempedu Bumi) in Sprague Dawley rats. Indian J Exp Biol. 2011;49:
767–72.
112. Weiming C, Xiaotian L. Deoxyandrographolide-19beta-D-glucoside from
the leaves of Andrographis paniculata. Planta Med. 1982;45:245–6.
113. Wiart C, Kumar K, Yusof MY, et al. Antiviral properties of ent-labdene
diterpenes of Andrographis paniculata Nees, inhibitors of herpes simplex
virus type 1. Phytother Res. 2005;19:1069–70.
114. Wibudi A, Kiranadi B, Manalu W, et al. The traditional plant, Andrographis
paniculata (Sambiloto), exhibits insulin-releasing actions in vitro. Acta Med
Indones. 2008;40:63–8.
Andrographis paniculata (Burm. f.) Nees. 283

115. Wu TS, Chern HJ, Damu AG, et al. Flavonoids and ent-labdane
diterpenoids from Andrographis paniculata and their antiplatelet aggre-
gatory and vasorelaxing effects. J Asian Nat Prod Res. 2008;10:17–24.
116. Xu C, Chou GX, Wang ZT. A new diterpene from the leaves of
Andrographis paniculata Nees. Fitoterapia. 2010;81:610–3.
117. Yoopan N, Thisoda P, Rangkadilok N, et al. Cardiovascular effects of
14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata
extracts. Planta Med. 2007;73:503–11.
118. Yu BC, Hung CR, Chen WC, Cheng JT. Antihyperglycemic effect of
andrographolide in streptozotocin-induced diabetic rats. Planta Med. 2003;
69:1075–9.
119. Zaidan MR, Noor Rain A, Badrul AR, et al. In vitro screening of five local
medicinal plants for antibacterial activity using disc diffusion method. Trop
Biomed. 2005;22:165–70.
120. Zhang C, Kuroyangi M, Tan BK. Cardiovascular activity of 14-deoxy-
11,12-didehydroandrographolide in the anaesthetised rat and isolated right
atria. Pharmacol Res. 1998;38:413–7.
121. Zhang CY, Tan BK. Hypotensive activity of aqueous extract of Andro-
graphis paniculata in rats. Clin Exp Pharmacol Physiol. 1996;23:675–8.
122. Zhang CY, Tan BK. Mechanisms of cardiovascular activity of Andro-
graphis paniculata in the anaesthetized rat. J Ethnopharmacol. 1997;56:
97–101.
123. Zhang XF, Tan BK. Antihyperglycaemic and antioxidant properties of
Andrographis paniculata in normal and diabetic rats. Clin Exp Pharmacol
Physiol. 2000;27:358–63.
124. Zhao F, He EQ, Wang L, Liu K. Antitumor activities of andrographolide, a
diterpene from Andrographis paniculata, by inducing apoptosis and
inhibiting VEGF level. J Asian Nat Prod Res. 2008;10:467–73.
125. Zhao HY, Fang WY. Protective effects of Andrographis paniculata Nees
on post-infarction myocardium in experimental dogs. J Tongji Med Univ.
1990;10:212–7.
126. Zhou KL, Chen LX, Zhuang YL, et al. Two new ent-labdane diterpenoid
glycosides from the aerial parts of Andrographis paniculata. J Asian Nat
Prod Res. 2008;10:939–43.
127. Zoha MS, Hussain AH, Choudhury SA. Antifertility effect of Andro-
graphis paniculata in mice. Bangladesh Med Res Counc Bull. 1989;15:
34–7.
Anethum graveolens (L.) Benth. & Hook
(Apiaceae/Umbelliferae)

(Syns.: A. sowa Roxb. Ex Fleming; Peucedanum graveolens (L.) Benth. & Hook.;
P. sowa (Roxb. Ex Fleming) Kurz)

Abstract
This annual herb is a native of southwest Asia and southeast Europe, and is also
indigenous to Mediterranean region, southern Russia and central Asia. Ibn
Jazlah used it for brain diseases, nose, ear and throat illnesses. It is also used to
induce vomiting in cases of poisoning, after mixing it with oil and boiling in
water and drunk warm. Seed (fruits) oil is used for abdominal colic, and
externally for earache, arthritis, neuronal pain, and paralysis. In Ayurveda, dried
ripe fruits are used in jwara, netraroga, vrana, śūla, and atisãra. In Iran, aerial
parts are used as hypolipidemic agent. Volatile components of dill seeds (fruits)
and herb include carvone, the predominant odorant of dill seeds, a-phellandrene,
limonene, dill ether, myristicin, coumarins, flavonoids, phenolic acids and
steroids. Ten flavonol glycosides were isolated from leaves; two major
flavonoids being quercetin 3-O-b-D-glucuronide and isorhamnetin 3-O-b-D-
glucuronide. Aqueous leaf extract exhibits potential antiradical and antioxidant
activity, and significantly reduces fasting blood glucose of diabetic rats, and a
commercial dill tablet protected rats against CCl4-hepatotoxicity. Various
extracts and the commercial dill tablet significantly decreased TC, LDL-C,
VLDL, and TGs, increased HDL, and significantly inhibited HMG CoA-
reductase in hypercholesterolemic animals. However, effect of dill tablets in
hypercholesterolemic patients has been inconsistent. Three monoterpenes,
anethofuran, carvone, and limonene exhibited cancer chemoprevention by
inducing detoxifying enzyme GST, in several mouse target tissues.

Keywords



Ameldo Anithi Celer hlíznatý
Chou qian hu
Dill
Dild
Faux anis



Satapuspa Shibith Soya

Vernaculars: Urd.: Shibt, Soya; Hin.: Anithi, Sotapa, Soya; San.: Chatrã, Mis-
reya, Śatãhwã, Śatapuspã, Shatapushpa, Sita, Siva; Ben.: Shulupa, Soolpha,
© Springer Nature Switzerland AG 2020 285
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_27
286 Anethum graveolens (L.) Benth. & Hook

Sovalakinda, Sowa; Guj.: Suvani bhaji; Mal.: Adas-manis, Anisi, Jemuju, Sata-
kuppa, Satha kuppa; Mar.: Balantashopa, Shipu, Suva; Tam.: Sadakuppi,
Satakuppay, Satakuppi; Tel.: Shatakupi-vitla, Shatakupivittulu, Shatapushpamu,
Soyikura, Vittulu; Ara.: Bazarul shibbit (seeds), Halwa, Sabat, Shibith, Sjamar
(Egypt); Bur.: Samin; Chi.: 洋茴香, Chou qian hu, Ou zhou shi luo, Shí luó; Cze.:
Celer bulvový, Celer hlíznatý, Celer naťový; Dan.: Dild; Dut.: Dille, Stinkende
vinke; Eng.: Common dill; Fin.: Maustetilli, Ryytitilli; Fre.: Aneth odorant, Anise,
Faux anis, Fenouil bâtard; Ger.: Dill, Dillfenchel, Gartendill, Gurkenkraut,
Teufelsdill; Ind.: Adas manis; Ita.: Aneto odoroso, Aneto puzzolente; Jap.: Deiru,
Inondo; Kor.: Inondu; Lao.: Phak si; Maly.: Adas china; Nor.: Dill; Per.: Shada,
Shevid, Tukhme shibbat (seeds), Valane khurda; Pol.: Koper ogrodowy; Por.:
Aneto, Endro, Funcho (Br.); Rus.: Ukrop; Sin.: Endaru; Spa.: Ameldo, Aneldo,
Anetaverón, Nerdo, Hinojo hediondo; Swe.: Dill; Tha.: Pakchee lao,
Thian-khaopluak; Tur.: Börek out, Dereotu, Tarak out; Vie.: Thì là, Tiêu hồi
hương.
Description: A native of southwest Asia and southeast Europe, and is also indige-
nous to Mediterranean region, southern Russia and central Asia. An annual herb with
hollow slender stems, and finely divided, softly delicate, strongly aromatic alternate

Fig. 1 Anethum graveolens, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://commons.
wikimedia.org/wiki/File:Illustration_Anethum_graveolens0.jpg
Anethum graveolens (L.) Benth. & Hook 287

Fig. 2 Anethum graveolens, Dried Umbels, Mnolf, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Dill_dried_umbel.jpg

leaves, 10–20 cm long, finally divided three or four times into pinnate sections, and
grows up to a height of 90 cm. The ultimate leaf divisions are 1–2 mm broad, slightly
broader than the leaves of fennel which are threadlike, less than 1 mm broad, but
harder in texture. Flowers are white to yellow, in small umbels 2–9 cm in diameter,
and the seeds are not true seeds, but halves of very small, dry fruits called schizocarps,
which are 4–5 mm long and 1 mm thick, and straight to slightly curved with a
longitudinally ridged surface and a pleasant aromatic odor (Figs. 1 and 2) [17].
Actions and Uses: Ibn Jazlah used it for brain diseases, nose, ear and throat illnesses.
It is also used to induce vomiting in cases of poisoning, after mixing it with oil and
boiling in water and drunk warm. Al-Kindi employed it for arthritic conditions, and in
a remedy for kidneys and bladder.LIII In Unani medicine, seeds (fruits) (temperament,
hot 2° and dry 2°) are emmenagogue and emetic, in addition to being stomachic,
carminative and digestive, and used for abdominal colic and flatulence. Seed oil is
used for abdominal colic, and externally for earache, arthritis, nerve pain, and
paralysis.LXXVII GhaniL quotes Gilani that in ancient times, green leaves used to be
applied to the head as sedative and hypnotic; and in India it is also smelled for the same
purpose. Leaves are digestive, carminative, deobstruent, antidysenteric, analgesic and
anti-inflammatory.L In Ayurveda, dried ripe fruits are used in jwara, netraroga, vrana,
śūla, and atisãra.LIX In Iran, aerial parts are used as hypolipidemic agent [12]. Seed
decoction is used for the treatment of flatulent colic.LXXXVIII
288 Anethum graveolens (L.) Benth. & Hook

Phytoconstituents: Ten flavonol glycosides were isolated from leaves; two major
flavonoids being quercetin 3-O-b-D-glucuronide and isorhamnetin 3-O-b-D-glucur-
onide [42]. Minor components are 3-glucosides, 3-galactosides and 3-rhamno-
glucosides of quercetin and isorhamnetin. Volatile components of dill seeds (fruits)
and herb include carvone, the predominant odorant of dill seeds, a-phellandrene,
limonene, dill ether, myristicin, coumarins, flavonoids, phenolic acids and steroids
[17]. b-D-glucopyranosides, p-menth-2-ene-1,6-diol, and 8-hydroxygeraniol have
also been isolated from the herb [5]. A furanocoumarin, 5-[4ʺ-hydroxy-3ʺ-methyl-2ʺ-
butenyloxy]-6,7-furocoumarin, and oxypeucedanin, oxypeucedanin hydrate and
falcarindiol, with the last three being active against rapidly growing mycobacteria,
were isolated from the plant [41]. Paper chromatography in several systems revealed at
least 14 coumarins derivatives in 60% ethanol extract of fruits; five were identified as
bergaptin, umbelliprenin, scopoletin, esculetin, and umbelliferone. Another com-
pound was isolated and preliminarily identified as a derivative of oxycoumarin. Fruit
also contained phenolic acids: caffeic, ferulic and chlorogenic acids. a-phellandrene
was the main component in EOs, either cultivated conventionally (AG-C, 27.94%) or
in organic conditions (AG-O, 47.75%) in Turkey, while oleic acid was dominant in
fruit oils (36.39% for AG-O and 53.87% for AG-C), and rosmarinic acid was the major
phenolic acid [31]. Seeds also contain high amount of potassium [9]. Essential oil
obtained from aerial parts of Iranian dill, by hydrodistillation contained a-phellandrene
(19.12%), limonene (26.34%), dill ether (15.23%), sabinene (11.34%), a-pinene (2%),
n-tetracosane (1.54%), neophytadiene (1.43%), n-docosane (1.04), n-tricosane (1%),
n-nonadecane (1%), n-eicosane (0.78%), n-heneicosane (0.67%), b-myrcene (0.23%)
and a-thujene (0.21%), as the major constituents; limonene and sabinene were identified
as the main antioxidant compounds [20].
Pharmacology: Aqueous leaf extract exhibits potential antiradical and antioxidant
activities [33, 38], and significantly reduces FBG of diabetic rats [33], and a
commercial dill tablet protected rats against CCl4-hepatotoxicity [32]. Leaf extract
pretreatment also decreased serum glucose and insulin in dexamethasone-induced
diabetic rats, and reversed alterations in levels of thyroid hormones, hepatic LPO,
SOD, CAT, and GSH [34]. Concurrent use of leaf powder significantly decreased
ALT, TC, glucose, fibrinogen and LDL-C in hypercholesterolemic rabbits [39].
Aqueous extract administration for 14-days to diet-induced hypercholesterolemic
rats reduced TGs and TC levels, by almost 50 and 20%, respectively; whereas the
EO reduced TGs levels by almost 42%, but not the TC [44]. Both hydroethanol
extract and the commercial dill tablet (having higher contents of total phenols,
flavonols and flavonoids than the extract), significantly decreased TC, LDL-C,
VLDL, and TGs, increased HDL, and significantly inhibited HMG CoA-reductase
in hypercholesterolemic hamsters [1]. Oral EO to high cholesterol-diet fed Wistar
rats for 2-weeks, significantly reduced TC, TGs, and LDL-C, and significantly
increased HDL-C [12]. Treatment with diethyl ether, ethyl acetate and water
fractions of the extract increased hepatic antioxidant system activities, such as SOD,
CAT and GSH, along with decrease in LPO in high cholesterol-fed rats, with
diethyl ether fraction showing the highest and water fraction showing the lowest
Anethum graveolens (L.) Benth. & Hook 289

increase [3]. Aqueous seed extract also significantly reduced body weight, food
intake, and significantly increased 5-HT, 5-HIAA, and tryptophan level in brain and
plasma of treated obese rats [4]. A commercial dill essence is reported to protect
mice from scopolamine-induced memory impairment [23]. Aqueous leaf extract
increased latency, and decreased duration of PTZ-induced seizures in mice [2];
similar results were reported with hydroalcohol seed extract [36].
Seed EO shows significant activity against a number of human pathogenic
bacteria [40]. Even oil obtained from seeds stored for more than 35 years, showed
significant antimicrobial activity against A. niger and S. cerevisiae and C. albicans
[18]. The oil and its constituents, carvone and piperitone increased bactericidal
activity of nitrofurantoin against E. cloacae [35]. The oil was highly effective
against Candida species, C. tropicalis, C. parapsilosis, and C. krusei and six iso-
lated C. albicans strains, and highly efficacious in accelerating C. albicans clear-
ance from experimentally infected vagina of immunocompromized mice [45].
Water and acetone seed extracts showed considerable antibacterial activity against a
number of bacteria except K. pneumoniae and one strain of P. aeruginosa [19].
Three monoterpenes, anethofuran, carvone, and limonene exhibited cancer
chemoprevention by inducing detoxifying enzyme GST in several mouse target
tissues [46]. Essential oil also shows a very high inhibitory activity (over 80%)
against AChE and BChE, whereas individual components of the oil are not as active
as the EO [30]. The oil exerts protection against Aedes aegypti mosquitoes [8].
Gastric mucosa protective and antisecretory effects of high doses of water and
ethanol extracts in mice against various gastric mucosal insults were similar to
sucralfate. The acidity and total acid content were reduced by both orally and
intraperitoneally administered extracts [15].
High doses of aqueous and ethanol extracts for 10-days significantly increased
duration of estrous cycle and the diestrus phase in female rats, without any sig-
nificant changes in volumes of ovaries and graafian follicles [25], and aqueous
extract treatment significantly increased duration of mating to pregnancy and
decreased weight and crown-rump length of newborns [27]. Treatment of male rats
with high dose of ethanol extract for 6-weeks resulted in prevention of pregnancy in
female rats mated with treated rats, despite no significant changes in sperm count,
sperm motility or testosterone concentration in the treated rats [26]. Fourteen-days
treatment of male rats with a dill extract did not affect sperm count, acrosome
reaction, and histological structures of testes and epididymis, but is reported to
significantly increase mounting frequency on days 1 and 7 [16].
Clinical Studies: Treatment of hypercholesterolemic patients with dill tablets for
two-months significantly reduced TC (18%) and TGs (7%) [24]. However, in a
single-blind, placebo controlled study, anethum tablet (650 mg) twice daily to 50
hyperlipidemic patients for 6-weeks increased TGs by 6%, and had no significant
effect on TC and LDL-C [21]. Contrarily, a double-blind, RCT in patients with
metabolic syndrome, 12-weeks of dill extract treatment reduced TGs from baseline
with no significant improvement in MeS related markers compared to control group
290 Anethum graveolens (L.) Benth. & Hook

[22]. An infusion made of A. graveolens, Urtica dioica and Gingko biloba sig-
nificantly reduced blood sugar level in type II diabetic Hungarian patients [10].
In a double-blind, RCT, 75 single female Iranian pharmacy and nursing students,
18–28 years old, suffering from primary dysmenorrhea, received either 1 g of
powdered leaves, 250 mg mefenamic acid, or a placebo twice daily for 5-days
starting 2-days before the beginning of menstruation for two cycles. Dill was as
effective as mefenamic acid in reducing the pain severity [13]. Boiled seed (10 g)
solution or placebo administered to 153 Iranian women during labor produced a
significantly better cervical dilatation, and significantly reduced length of all stages
of labor in treated subjects [14]. Aqueous leaf extract treatment of 28 G. lamblia
infected pediatric patients, younger than one year, for 5-days produced comparable
results to metronidazole [37].
Mechanism of Action: Plasma membrane of C. albicans is damaged by dill seed
EO, and, ROS production is an important mediator of antifungal action of EO [6],
leading to apoptosis [7]. Antifungal activity of the oil against A. flavus is also
reported to be due to its ability to disrupt permeability barrier of the plasma
membrane and from mitochondrial dysfunction-induced ROS accumulation [43].
Human A/Es, Allergy and Toxicity: Emetic, bad for brain, eyesight and libi-
do.LXXVII Dill may cause occupational contact dermatitis and urticaria [28, 29].
Animal Toxicity: LD50 (i.p.) of the aqueous and ethanol seed extracts in mice are
3,040 mg/kg and 6,980 mg/kg, respectively [15]. Aqueous extracts of the leaves
and seeds were also reported mutagenic to S. typhimurium [11].
Commentary: Its clinical trials, effects on blood lipids were inconsistent and
should be investigated in larger number of patients, and a correlation with chemical
constituents, if one exists, be established. Analgesic effect in dysmenorrhea and
effect on cervical dilatation during labor were observed in Iranian women, who, by
cultural bias toward natural (herbal) medicine may be more amenable to positive
outcome, and, therefore, need verification in other populations.

References
1. Abbasi Oshaghi E, Khodadadi I, Saidijam M, et al. Lipid lowering effects of
hydroalcoholic extract of Anethum graveolens L. and dill tablet in high
cholesterol fed hamsters. Cholesterol. 2015;2015:958560.
2. Arash A, Mohammad MZ, Jamal MS, Mohammad TA, Azam A. Effects of
the aqueous extract of Anethum graveolens leaves on seizure induced by
pentylenetetrazole in mice. Malays J Med Sci. 2013;20:23–30.
3. Bahramikia S, Yazdanparast R. Efficacy of different fractions of Anethum
graveolens leaves on serum lipoproteins and serum and liver oxidative
status in experimentally induced hypercholesterolaemic rat models. Am J
Chin Med. 2009;37:685–99.
Anethum graveolens (L.) Benth. & Hook 291

4. Bano F, Ahmed A, Ahmed M, Parveen T. Anethum graveolens seeds aqueous

extract stimulates whole brain 5-hydroxytryptamine metabolism and reduces
feeding behavior and body weight in obese rats. Pak J Pharm Sci. 2015;28:221–5.
5. Bonnländer B, Winterhalter P. 9-Hydroxypiperitone beta-D-glucopyranoside
and other polar constituents from dill (Anethum graveolens L.) herb. J Agric
Food Chem. 2000;48:4821–5.
6. Chen Y, Zeng H, Tian J, et al. Antifungal mechanism of essential oil from
Anethum graveolens seeds against Candida albicans. J Med Microbiol.
2013;62:1175–83.
7. Chen Y, Zeng H, Tian J, et al. Dill (Anethum graveolens L.) seed essential oil
induces Candida albicans apoptosis in a metacaspase-dependent manner.
Fungal Biol. 2014;118:394–401.
8. Choochote W, Chaithong U, Kamsuk K, et al. Repellent activity of selected
essential oils against Aedes aegypti. Fitoterapia. 2007;78:359–64.
9. Fatima I, Waheed S, Zaidi JH. Elemental analysis of Anethum gravedlens,
Sismbrium irio Linn. and Veronia anthelmintica seeds by instrumental
neutron activation analysis. Appl Radiat Isot. 2013;71:57–61.
10. Fodor JI, Keve T. New phytotherapical opportunity in the prevention and
treatment of 2-type of diabetes mellitus. Acta Pharm Hung. 2006;6:200–7
(Article in Hungarian).
11. Fukuoka M, Yoshihira K, Natori S, et al. Characterization of mutagenic
principles and carcinogenicity of dill weed and seeds. J Pharmacobiodyn.
1980;3:236–44.
12. Hajhashemi V, Abbasi N. Hypolipidemic activity of Anethum graveolens in
rats. Phytother Res. 2008;22:372–5.
13. Heidarifar R, Mehran N, Heidari A, et al. Effect of dill (Anethum graveolens)
on the severity of primary dysmenorrhea in compared with mefenamic acid:
a randomized, double-blind trial. J Res Med Sci. 2014;19:326–30.
14. Hekmatzadeh SF, Bazarganipour F, Malekzadeh J, Goodarzi F, Aramesh S.
A randomized clinical trial of the efficacy of applying a simple protocol of
boiled Anethum graveolens seeds on pain intensity and duration of labor
stages. Complement Ther Med. 2014;22:970–6.
15. Hosseinzadeh H, Karimi GR, Ameri M. Effects of Anethum graveolens L.
seed extracts on experimental gastric irritation models in mice. BMC
Pharmacol. 2002;2:21.
16. Iamsaard S, Prabsattroo T, Sukhorum W, et al. Anethum graveolens Linn.
(dill) extract enhances the mounting frequency and level of testicular tyrosine
protein phosphorylation in rats. J Zhejiang Univ Sci B. 2013;14:247–52.
17. Jana S, Shekhawat GS. Anethum graveolens: an Indian traditional medicinal
herb and spice. Pharmacogn Rev. 2010;4:179–84.
18. Jirovetz L, Buchbauer G, Stoyanova AS, et al. Composition, quality control,
and antimicrobial activity of the essential oil of long-time stored dill (Anethum
graveolens L.) seeds from Bulgaria. J Agric Food Chem. 2003;51:3854–7.
292 Anethum graveolens (L.) Benth. & Hook

19. Kaur GJ, Arora DS. Antibacterial and phytochemical screening of Anethum
graveolens, Foeniculum vulgare and Trachyspermum ammi. BMC Com-
plement Altern Med. 2009;9:30.
20. Kazemi M. Phenolic profile, antioxidant capacity and anti-inflammatory
activity of Anethum graveolens L. essential oil. Nat Prod Res. 2015;29:551–3.
21. Kojuri J, Vosoughi AR, Akrami M. Effects of Anethum graveolens and garlic
on lipid profile in hyperlipidemic patients. Lipids Health Dis. 2007;6:5.
22. Mansouri M, Nayebi N, Keshtkar A, et al. The effect of 12 weeks Anethum
graveolens (dill) on metabolic markers in patients with metabolic syndrome;
a randomized double blind controlled trial. Daru. 2012;20:47.
23. Mesripour A, Rafieian-Kopaei M, Bahrami B. The effects of Anethum
graveolens essence on scopolamine-induced memory impairment in mice.
Res Pharm Sci. 2016;11:145–51.
24. Mirhosseini M, Baradaran A, Rafieian-Kopaei M. Anethum graveolens and
hyperlipidemia: a randomized clinical trial. J Res Med Sci. 2014;19:758–61.
25. Monsefi M, Ghasemi M, Bahaoddini A. The effects of Anethum graveolens
L. on female reproductive system. Phytother Res. 2006;20:865–8.
26. Monsefi M, Zahmati M, Masoudi M, Javidnia K. Effects of Anethum
graveolens L. on fertility in male rats. Eur J Contracept Reprod Health Care.
2011;16:488–97.
27. Monsefi M, Ghasemi A, Alaee S, Aliabadi E. Effects of Anethum graveolens
L. (dill) on oocyte and fertility of adult female rats. J Reprod Infertil.
2015;16:10–7.
28. Monteseirín J, Pérez-Formoso JL, Hérnandez M, et al. Contact urticaria
from dill. Contact Dermatitis. 2003;48:275.
29. Monteseirín J, Pérez-Formoso JL, Sánchez-Hernández MC, et al. Occupa-
tional contact dermatitis to dill. Allergy. 2002;57:866–7.
30. Orhan I, Kartal M, Kan Y, Sener B. Activity of essential oils and individual
components against acetyl- and butyrylcholinesterase. Z Naturforsch [C].
2008;63:547–53.
31. Orhan IE, Senol FS, Ozturk N, et al. Phytochemical contents and enzyme
inhibitory and antioxidant properties of Anethum graveolens L. (dill) samples
cultivated under organic and conventional agricultural conditions. Food
Chem Toxicol. 2013;59:96–103.
32. Oshaghi EA, Khodadadi I, Tavilani H, Goodarzi MT. Effect of dill tablet
(Anethum graveolens L.) on antioxidant status and biochemical factors on
carbon tetrachloride-induced liver damage on rat. Int J Appl Basic Med Res.
2016;6:111–4.
33. Oshaghi EA, Khodadadi I, Tavilani H, Goodarzi MT. Aqueous extract of
Anethum graveolens L. has potential antioxidant and antiglycation effects.
Iran J Med Sci. 2016;41:328–33.
34. Panda S. The effect of Anethum graveolens L. (dill) on corticosteroid induced
diabetes mellitus: involvement of thyroid hormones. Phytother Res. 2008;22:
1695–7.
Anethum graveolens (L.) Benth. & Hook 293

35. Rafii F, Shahverdi AR. Comparison of essential oils from three plants for
enhancement of antimicrobial activity of nitrofurantoin against enterobac-
teria. Chemotherapy. 2007;53:21–5.
36. Rostampour M, Ghaffari A, Salehi P, Saadat F. Effects of hydroalcoholic
extract of Anethum graveolens seed on pentylenetetrazol-induced seizure in
adult male mice. Basic Clin Neurosci. 2014;5:199–204.
37. Sahib AS, Mohammed IH, Sloo SA. Antigiardial effect of Anethum
graveolens aqueous extract in children. J Intercult Ethnopharmacol. 2014;3:
109–12.
38. Satyanarayana S, Sushruta K, Sarma GS, et al. Antioxidant activity of the
aqueous extracts of spicy food additives—evaluation and comparison with
ascorbic acid in in-vitro systems. J Herb Pharmacother. 2004;4:1–10.
39. Setorki M, Rafieian-Kopaei M, Merikhi A, et al. Suppressive impact of
Anethum graveolens consumption on biochemical risk factors of atheroscle-
rosis in hypercholesterolemic rabbits. Int J Prev Med. 2013;4:889–95.
40. Singh G, Kapoor IP, Pandey SK, et al. Studies on essential oils: part 10;
antibacterial activity of volatile oils of some spices. Phytother Res. 2002;
16:680–2.
41. Stavri M, Gibbons S. The antimycobacterial constituents of dill (Anethum
graveolens). Phytother Res. 2005;19:938–41.
42. Teuber H, Herrmann K. Flavonol glycosides of leaves and fruits of dill
(Anethum graveolens L.). II. Phenolics of spices (author’s transl). Z Lebensm
Unters Forsch. 1978;167:101–4 (German).
43. Tian J, Ban X, Zeng H, et al. The mechanism of antifungal action of essential
oil from dill (Anethum graveolens L.) on Aspergillus flavus. PLoS ONE.
2012;7:e30147.
44. Yazdanparast R, Alavi M. Antihyperlipidaemic and antihypercholesterolaemic
effects of Anethum graveolens leaves after the removal of furocoumarins.
Cytobios. 2001;105:185–91.
45. Zeng H, Tian J, Zheng Y, et al. In vitro and in vivo activities of essential oil
from the seed of Anethum graveolens L. against Candida spp. Evid Based
Complement Alternat Med. 2011;2011:659704.
46. Zheng GQ, Kenney PM, Lam LK. Anethofuran, carvone, and limonene:
potential cancer chemopreventive agents from dill weed oil and caraway oil.
Planta Med. 1992;58:338–41.
Apium graveolens L.
(Apiaceae/Umbelliferae)

Abstract
A glabrous herb that grows wild and is also cultivated throughout the world as a
vegetable. Celery is used in various forms, such as fresh herb, stalk, seeds, oil,
and oleoresin for flavoring of foods, and for medicinal purposes. Galen described
celery root as diuretic, emmenagogue, carminative, and antiflatulent. Seeds are
described as deobstruent and resolvent, and used in the form of a poultice with
barley meal; and, internally recommended as pectoral and tonic, and carminative
adjunct to purgatives, as diuretic, emmenagogue, lithotriptic, alexipharmic, and
also as antiphlegmatic, antinauseant, and anthelmintic. Seeds are also stimulant,
cardiotonic, and pectoral, and are used in cough, bronchitis, asthma, pleurisy,
sciatica, and liver and spleen diseases. In traditional medicine of Morelos state of
Mexico, the plant is used to treat diarrhea, hypertension, and bronchopulmonary
diseases, and root decoction is used in women to reduce milk production. In
Danish folk medicine, it is used to treat depression and anxiety, and in the
Philippines, decoction of whole plant is considered diuretic and emmenagogue.
Celery contains crude protein, fat, vitamin C, b-carotene, calcium, sodium, and
phosphorus, caffeic acid, p-coumaric acid, ferulic acid, apigenin, luteolin, tannin,
saponin and kaempferol. It also contains significant amounts of a-tocopherol,
and acts as a powerful antioxidant. Essential oil from seeds showed tranquil-
lizing activity, and protected mice against seizures; only the nitrogenous portion
of the EO possesses CNS activity. Methanol extract of whole plant improved
memory in mice, and reduced brain LPO, AChE and MAO-A activities.
Methanol and aqueous extracts of both aerial parts and seeds also protected
against experimental gastric lesions, similar to omeprazole.

Keywords



Ache Ajmud Apio acuático
Bladselderij
Eppich
Karafs
Kharãśwa




Qin Sedano Selleri

© Springer Nature Switzerland AG 2020 295

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_28
296 Apium graveolens L.

Vernaculars: Urd.: Ajmud, Karafs; Hin.: Ajmoda, Ajmud, Bhut-jata; San.:

Ajamodã, Dipyakah, Kãravi, Kharãśwa, Mãyūri; Ben.: Chandani, Chanoo rha-
dodni, Chiluri, Randhuni; Guj.: Ajmoda; Mar.: Ajamoda-nova; Tam.: Ajamoda,
Asham-tagam, Celer-keerai; Tel.: Ashu-madaga-vomam; Ara.: Karafs; Chi.: 旱芹,
Ch’in-nst’ai, Qin; Cze.: Celer; Dan.: Bladselleri, Selleri; Dut.: Bladselderij,
Selderij, Struikselderij; Eng.: Celery, Marsh parsley; Fin.: Ruokaselleri; Fre.:
Ache, Ache odorante, Céleri; Ger.: Echter eppich, Echter sellerie, Eppich, Sellerie;
Ita.: Apio, Sedano, Sedano comune; Jap.: Oranda-mutsuba; Kor.: Sel-reo-ri,
Sel-reo-ri si-deu; Lao.: Si sang; Maly.: Daun sop; Nor.: Hageselleri, Selleri; Per.:
Karafs; Pol.: Seler zwyczajny; Por.: Aipo, Aipo-bravo, Aipo-dos-charcos,
Aipo-dos-pântanos, Aipo-inculto, Aipo-silvestre, Salsa-do-monte; Rus.: Sel’derei;
Spa.: Apio, Apio acuático, Apio bastardo, Apio de agua, Apio de huerta, Apio
dulce; Swe.: Selleri; Tag.: Apyo, Guichai, Kinchai, Kintsai; Tha.: Ceun chai,
Khuen chai; Tur.: Kereviz; Vie.: Cần tây.
Description: It is a glabrous herb that grows wild and is also cultivated throughout
the world as a vegetable. In India it is grown at the base of northwestern Himalayas,
and outlying hills in Punjab, and in western India. It grows up to a height of 1 m;
leaves are pinnate or bipinnate with rhombic leaflets 3–6 cm long and 2–4 cm wide.
Flowers are creamy-white, 2–3 mm in diameter, and are produced in dense
compound umbels; seeds are broad ovoid to globose, 1.5–2 mm long and wide.
A very small fruit, almost globular, quite smooth and remarkable for its size and
prominent ridges, known as karafs used to be imported into India from Persia.XL A
Chinese variety, known as Kinchai or Qincai is widely cultivated in China (Figs. 1,
2 and 3).XVIII,CXVII
Actions and Uses: Celery is used in various forms, such as fresh herb, stalk, seeds,
oil, and oleoresin for flavoring of foods, and for medicinal purposes [61]. Galen
described celery root as diuretic, emmenagogue, carminative, and antiflatulent,LXIX

Fig. 1 Apium graveolens, Celery Root, DocteurCosmos, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:C%C3%A9leri-rave-fendu.jpg
Apium graveolens L. 297

Fig. 2 Apium graveolens, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://commons.wikimedia.
org/wiki/File:Illustration_Apium_graveolens0.jpg

Fig. 3 Apium graveolens, Celery Seeds, Howcheng, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Celery_seed.jpg; https://creativecommons.
org/licenses/by-sa/3.0/deed.en
298 Apium graveolens L.

and is used in anasarca and colic.XXI,LXXXIV Seeds (temperament, hot 2° and dry 2°) are
described as deobstruent and resolvent, and used in the form of a poultice with barley
meal; and, internally recommended as pectoral and tonic, and carminative adjunct to
purgatives;XL as diuretic, emmenagogue, lithotriptic, and alexipharmic,XXI,LXXVII,
LXXXI
and also as antiphlegmatic, antinauseant, and anthelmintic.L Seeds are also
stimulant, cardiotonic, and pectoral, and are used in cough, bronchitis, asthma, pleurisy,
sciatica, and liver and spleen diseases.XXI,LXXXIV,CV Celery is preventive of rheuma-
tism, and gout,CV and used as condiment in Ethiopia [42]. Roots decoction (50 g in 1 L
water) is laxative, and anthelmintic [43], and the root and seeds are reported abortifa-
cient, ecbolic, and oxytocic [58]. In traditional medicine of Morelos state of Mexico, the
plant is used to treat diarrhea, hypertension, and bronchopulmonary diseases [29], and
root decoction is used in women to reduce milk production.XCVI Volatile oil is reported
uterine stimulant and abortifacient.CL In Trinidad and Tobago, it is used by traditional
healers as heart tonic, and to treat low blood pressure, and kidney ailments [41]. In
Danish folk medicine, it is used to treat depression and anxiety [25], and in the
Philippines,CXVII decoction of whole plant is considered diuretic and emmenagogue
[20]. In China, it is known as Qincai, and described as sweet and slightly acrid in taste,
and “cool” in property; it has hypotensive, diuretic, and hemostatic actions, and removes
pathogenic “heat” from blood. It is used as a remedy for vertigo with headache, flushing
of face in acute conjunctivitis, hematuria, and carbuncle.XVIII
Phytoconstituents: Celery contains crude protein, fat, vitamin C, b-carotene, cal-
cium, sodium, and phosphorus [59], caffeic acid, p-coumaric acid, ferulic acid,
apigenin, luteolin, tannin, saponin and kaempferol, and acts as a powerful antiox-
idant [36]. It also contains significant amounts of a-tocopherol [11]; total amount of
phenolic compounds and radical scavenging activity is the highest in celery leaves,
and lowest in celery roots [62]. Stem, leaves and seeds contain a glucoside—apiin,
a jelly-like substance, and volatile oil. Seeds also contain alkaloids [40], b-selinene,
3-n-butyl-4,5-dihydrophthalide, 5-allyl-2-methoxyphenol, senkyunolide-N, senky-
unolide-J, sedanolide, and L-tryptophan; 3-n-butyl-4,5-dihydrophthalide is lethal to
nematodes, Panagrellus redivivus and Caenorhabditis elegans [50–52]. Celery
contains 15% fatty oil, with fatty acids: petroselenic (64.3%), oleic (8.1%), linoleic
(18%), linolenic (0.6%), and palmitic acids. Fruits (seeds) contain 2–3% of oil
consisting of terpenes, with smaller quantities of anhydride of sedanonic acid,
lactone of sedanolic acid, and phenols.CXXXXI Seeds volatile oil is used for
flavoring of foods, and in perfumery. Important flavor constituents of the oil
responsible for the typical aroma are sedanenolide, 3-n-butyl phthalide, sedanolide,
and sedanonic anhydride. Limonene and selinene form about 60% and 20% of
the oil, respectively [61]. Triterpenoids: 11,21-dioxo-2b,3b,15a-trihydroxyurs-12-
ene-2-O-b-D-glucopyranoside, 11,21-dioxo-3b,15a,24-trihydroxyurs-12-ene-24-O-b-
D-glucopyranoside, and 11,21-dioxo-3b,15a,24-trihydroxyolean-12-ene-24-O-b-D-
glucopyranoside, flavonoids: apigenin-7-O-[2ʺ-O-(5′ʺ-O-feruloyl)-b-D-apiofuranosyl]-
b-D-glucopyranoside, and chrysoeriol-7-O-[2ʺ-O-(5′ʺ-O-feruloyl)-b-D-apiofuranosyl]-
b-D-glucopyranoside, were isolated from the whole plant of fresh celery [72]. Five
sesquiterpenoid glucosides (celerioside A-E), three phthalide glycosides (celephtalide
Apium graveolens L. 299

A-C), six aromatic compound glucosides, two norcarotenoid glucosides, and a lignan
glucoside were reported from seeds [31]. Coumarin glucosides, apiumoside, celerin (a
coumarin), celeroside, a dihydrofurocoumarin glucoside, and isoquercitrin were iso-
lated from seeds [15–17]. Three furocoumarins, bergapten, xanthotoxin and iso-
pimpinellin were isolated from methanol extract of whole herb [23]. Concentration of
bergapten was highest (145 ug/10 g of dried herb) in July; whereas, xanthotoxin and
isopimpinellin were at maximum concentration in samples collected in September
(183 and 122 ug/10 g of dried herb, respectively). Constituents of EO from seeds are
d-limonene, d-selinene, sesquiterpene alcohols, sedanolide acid anhydride [33],
p-mentha-2,8-dien-1-ol, p-mentha-8(9)-en-1,2-diol, 3-n-butyl phthalide, and sedano-
lide [71]. Major components of EO from leaves are, 4-chloro-4,4-dimethyl-3-(1-
imidazolyl)-valerophenone (19.90%), 1-dodecanol (16.55%), 9-octadecen-12-ynoic
acid, methyl ester (4.93%), ethyl 4,4-D2-N-hexyl ether (4.11%), 3-(hydroxymethyl)-
1-phenyl-1-heptadecyn-3-ol (3.28%), 1,4-methano-1H-indene, octahydro-4-methyl-
8-methylene-7-(1-methylethyl)-[1S-(1a,3aa,4a,7a,7aa)]- (2.99%), 3,4-dihydro-2H-
1,5-(3ʺ-t-butyl) benzodioxepine (2.56%), Z-10-tetradecen-1-ol acetate (2.53%), and
9H-pyrrolo[3′,4′:3,4]pyrrolo [2,1-a]phthalazine-9, 11(10H)-dione, 10-ethyl-8-phenyl
(2.07%) [53]. EO of plants collected from Potugal and Italy varied in composition, but
showed presence of sedanenolide, neocnidilide and neophytadiene as main compo-
nents; the oil from Italy was rich in neophytadiene, and exhibited better antifungal
activity against C. albicans, C. tropicalis, C. krusei, C. guilliermondii, C. parapsilosis,
C. neoformans, T. mentagrophytes, T. rubrum, T. verrucosum, M. canis, M. gypseum,
E. floccosum, A. niger, A. fumigatus and A. flavus [48].
Pharmacology: Essential oil from seeds showed tranquillizing activity, potentiating
pentobarbital narcosis in mice, and loss of CAR in rats. The oil also protected mice
against MES seizures. Out of nitrogenous and non-nitrogenous portions of the EO,
only the nitrogenous part possesses CNS activity [39]. Alkaloidal fraction from seeds
showed tranquillizing activity as that of EO; it reduced mortality by amphetamine in
aggregated mice, and protected mice against MES seizures, but was ineffective against
metrazol and strychnine-induced convulsions [40]. Pretreatment of mice with celery
juice prolonged action of pentobarbital, and increased and prolonged analgesic action
of aminopyrine and APAP [27]. Methanol extract of whole plant improved memory in
mice, and reduced brain LPO, AChE and MAO-A activities [8]. Ethanol leaf extract
also significantly inhibited in vitro MAO-A [25]. Aqueous and ethanol extracts, and a
phytosterol isolated from celery stem significantly inhibited inflammation in rats
[2, 44, 49], and produced antinociceptive effects [4]. Ethanol extract was significantly
protective against various models of gastric ulcerogenesis, and replenished depleted
levels of gastric wall mucus [3]. Methanol and aqueous extracts of both aerial parts and
seeds also protected against HCl- and ethanol-induced gastric lesions, similar to that
induced by omeprazole [5].
Aqueous extract significantly reduced serum TC, LDL-C, and TGs in hyper-
lipidemic rats, with hepatic TG concentration being significantly higher, and tria-
cylglycerol lipase activity significantly lower [66]. Hexane seed extract significantly
decreased glucose, TGs, and TC levels, and increased insulin and HDL levels of
300 Apium graveolens L.

STZ-diabetic rats [65], and ethanol seed extract reduced TC, TGs, LDL-C levels,
and significantly increased HDL-C in olive oil-induced hyperlipidemic rats [24].
Dichloromethane and ethyl acetate extracts caused concentration-dependent relax-
ation of precontracted aortic rings, with and without endothelium [29]; apigenin
also relaxed rat thoracic aorta [32]. Use of celery roots and leaves juices was
protective against doxorubicine-induced cardiotoxicity [35]. Methanol seed extract
demonstrated significant hepatoprotective activity against APAP or thioacetamide-
[60], and CCl4-induced hepatotoxicity [1].
Ethanol extract inhibited cell viability of human prostatic carcinoma cells [34].
p-mentha-2,8-dien-1-ol,3-n-butyl phthalide and sedanolide exhibited high induction
of detoxifying enzyme GST. Treatment with 3-n-butyl phthalide and sedanolide
significantly reduced incidence and tumor multiplicity of B(a)P-induced tumors in
mice, that correlated with the GST-inducing ability [71]. Methanol seed extract also
protected against DEN+AAF+ partial hepatectomy induced hepatocarcinogenesis
[64]. Methanol extracts of the root and leaves possess antioxidant activity [54], and
methanol extract of whole plant ameliorated liver oxidative stress in arthritic rats
[63], and the flavonoid extract prevented decline in activities of SOD, GST and
CAT, due to dichlorvos-induced oxidative stress in rats [9]. Antioxidant capacity of
celery increases by most cooking methods (microwaving, pressure-cooking, grid-
dling, frying, and baking), except boiling when it loses 14% of that capacity [28].
The flavonoid, apiin shows remarkable scavenging activity on maleic dialdehyde
and lipofuscin, promotes total antioxidant capacity in the serum, brain, heart, liver
and kidney, and significantly enhances activities of SOD, GPx, and CAT [45].
Essential oil of seeds showed antifungal activity against H. capsulatum and C.
albicans, and had synergistic antifungal action with ferulic oil [26], but was inef-
fective against A. lumbricoides [14]. Methanol and aqueous extracts showed
moderate antimicrobial activity against MDR S. typhi [56], and alcohol seed extract,
and fractions thereof, exhibited anti-inflammatory, gastroprotective, and anti-H.
pylori activities [55, 73]. Ethanolic hexane extract provided remarkable repellency
to mosquitoes, with a median protection time of 4.5 h, which was greater than the
best commercial repellent, N,N-diethyl-3-methylbenzamide solution (25% DEET,
3.5 h) [67–69]. The EO [10], and seed extract [12] exerted promising adulticidal
efficacy on topical application, against both laboratory and natural field strains of
Aedes aegypti. Petroleum ether, ether and water extracts of seeds given on 1–7 days
of pregnancy showed no inhibition of implantation in rats [18]. Hydroalcohol leaf
extract significantly increased sperm count, sertoli cells, and primary spermatocyte
[37], and was protective against PEG-induced testicular changes in rats [38].
Aqueous leaf extract administered for 30-days also improved spermatogenesis in
rats [22]. An extract was reported to protect against testicular toxicity of sodium
valproate in rats; apigenin was the major fraction of the extract [21].
Mechanism of Action: Aortic dilatory effect of dichloromethane and ethyl acetate
extracts is suggested to be mediated through calcium antagonism [29]; relaxation of
rat thoracic aorta by apigenin was also mediated via suppression of Ca2+ influx
through both voltage- and receptor-operated calcium channels [32]. Induction of
Apium graveolens L. 301

apoptosis and downregulation of VEGF expression were responsible for the cyto-
toxicity of ethanol extract of human prostatic carcinoma cells [34]. Induction of
detoxifying enzyme, GST, is also involved in its anticancer activity [71].
Human A/Es, Allergy and Toxicity: Celery can cause allergic reaction in many
patients [6, 47]. Profilin is a food allergen in celery [70]; phototoxic reaction may
also result due to substantial amounts of psoralen in the roots [7, 13, 19, 46]. Celery
has also caused significant adverse effects in some individuals. A middle-aged
Iranian man developed hyperthyroidism, after daily consuming 4 g of dried celery
leaves for 45-days to reduce weight [57]. It is toxic during pregnancy, and detri-
mental to people with hot temperament, and epileptic patients.LXXVII
Animal Toxicity: Administration of alcohol seed extract for 28-days in doses of
up to 5,000 mg/kg per day produced no toxicologically significant effects [55].
Potential for Drug-Herb Interactions: A U.S. female patient with depression,
stabilized on venlafaxine and St John’s Wort, developed a manic episode due to
elevated serum venlafaxine levels after she started taking celery root extract for
menopause-related issues [30].
Commentary: There are no clinical studies reported in the publications listed on
PubMed.

References
1. Ahmed B, Alam T, Varshney M, Khan SA. Hepatoprotective activity of two
plants belonging to the Apiaceae and the Euphorbiaceae family. J Ethnophar-
macol. 2002;79:313–6.
2. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory
activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26:
163–8.
3. Al-Howiriny T, Alsheikh A, Alqasoumi S, et al. Gastric antiulcer, antisecretory
and cytoprotective properties of celery (Apium graveolens) in rats. Pharm Biol.
2010;48:786–93.
4. Atta AH, Alkofahi A. Antinociceptive and anti-inflammatory effects of some
Jordanian medicinal plant extracts. J Ethnopharmacol. 1998;60:117–24.
5. Baananou S, Bouftira I, Mahmoud A, et al. Antiulcerogenic and antibac-
terial activities of Apium graveolens essential oil and extract. Nat Prod Res.
2013;27:1075–83.
6. Ballmer-Weber BK, Vieths S, Lüttkopf D, et al. Celery allergy confirmed by
double-blind, placebo-controlled food challenge: a clinical study in 32
subjects with a history of adverse reactions to celery root. J Allergy Clin
Immunol. 2000;106:373–8.
7. Bitter RC. Psoralen and other furocoumarins as photoalexins in celery
Apium graveolens. Phytochem. 1983;22:2595–8.
8. Boonruamkaew P, Sukketsiri W, Panichayupakaranant P, et al. Apium
graveolens extract influences mood and cognition in healthy mice. J Nat
Med. 2017;71:492–505.
302 Apium graveolens L.

9. Cao J, Zhang X, Wang Q, et al. Influence of flavonoid extracts from celery on

oxidative stress induced by dichlorvos in rats. Hum Exp Toxicol. 2012;31:
617–25.
10. Chaiyasit D, Choochote W, Rattanachanpichai E, et al. Essential oils as
potential adulticides against two populations of Aedes aegypti, the laboratory
and natural field strains, in Chiang Mai province, northern Thailand. Parasitol
Res. 2006;99:715–21.
11. Ching LS, Mohamed S. Alpha-tocopherol content in 62 edible tropical
plants. J Agric Food Chem. 2001;49:3101–5.
12. Choochote W, Tuetun B, Kanjanapothi D, et al. Potential of crude seed
extract of celery, Apium graveolens L., against the mosquito Aedes aegypti
(L.) (Diptera: Culicidae). J Vector Ecol. 2004;29:340–6.
13. Dobson J, Ondhia C, Skellett AM, Coelho R. Image Gallery: Phototoxic
rash from celery diet. Br J Dermatol. 2016;175:e133.
14. El Garhy MF, Mahmoud LH. Anthelminthic efficacy of traditional herbs on
Ascaris lumbricoides. J Egypt Soc Parasitol. 2002;32:893–900.
15. Garg SK, Gupta SR, Sharma ND. A new dihydrofurocoumarin from Apium
graveolens. Planta Med. 1981;43:306–8.
16. Garg SK, Gupta SR, Sharma ND. Celerin, a new coumarin from Apium
graveolens. Planta Med. 1980;38:186–8.
17. Garg SK, Gupta SR, Sharma ND. Glucosides of Apium graveolens. Planta
Med. 1980;38:363–5.
18. Garg SK, Saksena SK, Chaudhury RR. Antifertility screening of plants. VI.
Effect of five indigenous plants on early pregnancy in albino rats. Indian J
Med Res. 1970;58:1285–9.
19. Gral N, Beani JC, Bonnot D, et al. Plasma levels of psoralens after celery
ingestion. Ann Dermatol Venereol. 1993;120:599–603 (Article in French).
20. Guerrero Leon MA. Medicinal uses of Philippine plants. Philip Bur Forestry
Bull. 1921;22:149–246.
21. Hamza AA, Amin A. Apium graveolens modulates sodium valproate-induced
reproductive toxicity in rats. J Exp Zool Part A Ecol Genet Physiol. 2007;307:
199–206.
22. Hardani A, Afzalzadeh MR, Amirzargar A, Mansouri E, Meamar Z. Effects
of aqueous extract of celery (Apium graveolens L.) leaves on spermatoge-
nesis in healthy male rats. Avicenna J Phytomed. 2015;5:113–9.
23. Innocenti G, Dall’Acqua F, Coporale G. Investigations of the content of
furocoumarins in Apium graveolens and in Petroselinum sativum. Planta
Med. 1976;29:165–70.
24. Iyer D, Patil UK. Effect of chloroform and aqueous basic fraction of
ethanolic extract from Apium graveolens L. in experimentally-induced
hyperlipidemia in rats. J Complement Integr Med. 2011;8.
25. Jäger AK, Gauguin B, Andersen J, Adsersen A, Gudiksen L. Screening of
plants used in Danish folk medicine to treat depression and anxiety for affinity
to the serotonin transporter and inhibition of MAO-A. J Ethnopharmacol.
2013;145:822–5.
Apium graveolens L. 303

26. Jain SR, Jain MR. Effect of some common essential oils on pathogenic
fungi. Planta Med. 1973;24:127–32.
27. Jakovljevic V, Raskovic A, Popovic M, Sabo J. The effect of celery and
parsley juices on pharmacodynamic activity of drugs involving cytochrome
P450 in their metabolism. Eur J Drug Metab Pharmacokinet. 2002;27:153–6.
28. Jiménez-Monreal AM, García-Diz L, Martínez-Tomé M, Mariscal M, Mur-
cia MA. Influence of cooking methods on antioxidant activity of vegetables.
J Food Sci. 2009;74:H97–103.
29. Jorge VG, Ángel JR, Adrián TS, et al. Vasorelaxant activity of extracts
obtained from Apium graveolens: possible source for vasorelaxant molecules
isolation with potential antihypertensive effect. Asian Pac J Trop Biomed.
2013;3:776–9.
30. Khalid Z, Osuagwu FC, Shah B, et al. Celery root extract as an inducer of
mania induction in a patient on venlafaxine and St John’s Wort. Postgrad
Med. 2016;128:682–3.
31. Kitajima J, Ishikawa T, Satoh M. Polar constituents of celery seed.
Phytochemistry. 2003;64:1003–11.
32. Ko FN, Huang TF, Teng CM. Vasodilatory action mechanisms of apigenin
isolated from Apium graveolens in rat thoracic aorta. Biochim Biophys
Acta. 1991;1115:69–74.
33. Kohli RP, Dua PR, Shankar K, Saxena RC. Some central effects of an
essential oil of Apium graveolens (Linn.). Indian J Med Res. 1967;55:1099.
34. Köken T, Koca B, Özkurt M, et al. Apium graveolens extract inhibits cell
proliferation and expression of vascular endothelial growth factor and
induces apoptosis in the human prostatic carcinoma cell line LNCaP. J Med
Food. 2016;19:1166–71.
35. Kolarovic J, Popovic M, Mikov M, Mitic R, Gvozdenovic L. Protective effects
of celery juice in treatments with doxorubicin. Molecules. 2009;14:1627–38.
36. Kooti W, Daraei N. A review of the antioxidant activity of celery (Apium
graveolens L). J Evid Based Complementary Altern Med. 2017;22:1029–34.
37. Kooti W, Mansouri E, Ghasemiboroon M, et al. The effects of hydro-
alcoholic extract of Apium graveolens leaf on the number of sexual cells and
testicular structure in rat. Jundishapur J Nat Pharm Prod. 2014;9:e17532.
38. Kooti W, Mansouri E, Ghasemiboroon M, Harizi M, Amirzargar A. Protective
effects of celery (Apium graveolens) on testis and cauda epididymal
spermatozoa in rat. Iran J Reprod Med. 2014;12:365–6.
39. Kulshrestha VK, Saxena RC, Kohli RP. Some central effects of Apium
graveolens (Linn.) II. Indian J Physiol Pharmacol. 1967;12:37.
40. Kulshrestha VK, Singh N, Saxena RC, Kohli RP. A study of central
pharmacological activity of alkaloid fraction of Apium graveolens L. Indian J
Med Res. 1970;58:99–102.
41. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary
problems and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2:45.
42. Lemordant D. Contribution a l’ethnobotanique ethiopienne. J Agric Trop
Bot Appl. 1971;18:1–35; 18:142–79.
304 Apium graveolens L.

43. Leporatti ML, Losocco E, Pavesi A. Some new therapeutic uses of several
medicinal plants in the province of Terni (Umbria, Central Italy). J Ethnophar-
macol. 1985;14:65–8.
44. Lewis DA, Tharib SM, Veitch GBA. The anti-inflammatory activity of celery
Apium graveolens L. (Fam. Umbelliferae). Int J Crude Drug Res. 1985;23:27–32.
45. Li P, Jia J, Zhang D, et al. In vitro and in vivo antioxidant activities of a
flavonoid isolated from celery (Apium graveolens L. var. dulce). Food
Funct. 2014;5:50–6.
46. Ljunggren B. Severe phototoxic burn following celery ingestion. Arch
Dermatol. 1990;126:1334–6.
47. Lüttkopf D, Ballmer-Weber BK, Wüthrich B, Vieths S. Celery allergens in
patients with positive double-blind placebo-controlled food challenge.
J Allergy Clin Immunol. 2000;106:390–9.
48. Marongiu B, Piras A, Porcedda S, et al. Isolation of the volatile fraction from
Apium graveolens L. (Apiaceae) by supercritical carbon dioxide extraction
and hydrodistillation: chemical composition and antifungal activity. Nat
Prod Res. 2013;27:1521–7.
49. Mencherini T, Cau A, Bianco G, et al. An extract of Apium graveolens var. dulce
leaves: structure of the major constituent, apiin, and its anti-inflammatory
properties. J Pharm Pharmacol. 2007;59:891–7.
50. Momin RA, Nair MG. Mosquitocidal, nematicidal, and antifungal compounds
from Apium graveolens L. seeds. J Agric Food Chem. 2001;49:142–5.
51. Momin RA, Nair MG. Antioxidant, cyclooxygenase and topoisomerase
inhibitory compounds from Apium graveolens Linn. seeds. Phytomedicine.
2002;9:312–8.
52. Momin RA, Ramsewak RS, Nair MG. Bioactive compounds and 1,3-Di
[(cis)-9-octadecenoyl]-2-[(cis, cis)-9, 12-octadecadienoyl]glycerol from Apium
graveolens L. seeds. J Agric Food Chem. 2000;48:3785–8.
53. Nagella P, Ahmad A, Kim SJ, Chung IM. Chemical composition, antioxidant
activity and larvicidal effects of essential oil from leaves of Apium graveolens.
Immunopharmacol Immunotoxicol. 2012;34:205–9.
54. Popović M, Kaurinović B, Trivić S, et al. Effect of celery (Apium graveolens)
extracts on some biochemical parameters of oxidative stress in mice treated
with carbon tetrachloride. Phytother Res. 2006;20:531–7.
55. Powanda MC, Rainsford KD. A toxicological investigation of a celery seed
extract having anti-inflammatory activity. Inflammopharmacology. 2011;19:
227–33.
56. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
57. Rouhi-Boroujeni H, Hosseini M, Gharipour M, Rouhi-Boroujeni H. Is herbal
therapy safe in obesity? A case of Apium graveolens (Celery) induced
hyperthyroidism. ARYA Atheroscler. 2016;12:248–9.
58. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
Apium graveolens L. 305

59. Shad AA, Bakht J, Shah HU, Hayat Y. Antioxidant activity and nutritional
assessment of underutilized medicinal plants. Pak J Pharm Sci. 2016;29:
2039–45.
60. Singh A, Handa SS. Hepatoprotective activity of Apium graveolens and
Hygrophila auriculata against paracetamol and thioacetamide intoxication
in rats. J Ethnopharmacol. 1995;49:119–126.
61. Sowbhagya HB. Chemistry, technology, and nutraceutical functions of
celery (Apium graveolens L.): an overview. Crit Rev Food Sci Nutr.
2014;54:389–98.
62. Stankevičius M, Akuņeca I, Jãkobsone I, Maruška A. Comparative analysis
of radical scavenging and antioxidant activity of phenolic compounds
present in everyday use spice plants by means of spectrophotometric and
chromatographic methods. J Sep Sci. 2011;34:1261–7.
63. Sukketsiri W, Chonpathompikunlert P, Tanasawet S, Choosri N,
Wongtawatchai T. Effects of Apium graveolens extract on the oxidative
stress in the liver of adjuvant-induced arthritic rats. Prev Nutr Food Sci.
2016;21:79–84.
64. Sultana S, Ahmed S, Jahangir T, Sharma S. Inhibitory effect of celery seeds
extract on chemically induced hepatocarcinogenesis: modulation of cell
proliferation, metabolism and altered hepatic foci development. Cancer Lett.
2005;221:11–20.
65. Tashakori-Sabzevar F, Ramezani M, Hosseinzadeh H, et al. Protective and
hypoglycemic effects of celery seed on streptozotocin-induced diabetic rats:
experimental and histopathological evaluation. Acta Diabetol. 2016;53:609–19.
66. Tsi D, Das NP, Tan BK. Effects of aqueous celery (Apium graveolens) extract
on lipid parameters of rats fed a high fat diet. Planta Med. 1995;61:18–21.
67. Tuetun B, Choochote W, Kanjanapothi D, et al. Repellent properties of
celery, Apium graveolens L., compared with commercial repellents, against
mosquitoes under laboratory and field conditions. Trop Med Int Health.
2005;10:1190–8.
68. Tuetun B, Choochote W, Pongpaibul Y, et al. Celery-based topical repellents as
a potential natural alternative for personal protection against mosquitoes.
Parasitol Res. 2008;104:107–15.
69. Tuetun B, Choochote W, Rattanachanpichai E, et al. Mosquito repellency of
the seeds of celery (Apium graveolens L.). Ann Trop Med Parasitol. 2004;
98:407–17.
70. Vieths S, Lüttkopf D, Reindl J, et al. Allergens in celery and zucchini.
Allergy. 2002;57 Suppl 72:100–5.
306 Apium graveolens L.

71. Zheng GQ, Kenney PM, Zhang J, Lam LK. Chemoprevention of benzo[a]
pyrene-induced forestomach cancer in mice by natural phthalides from
celery seed oil. Nutr Cancer. 1993;19:77–86.
72. Zhou K, Zhao F, Liu Z, et al. Triterpenoids and flavonoids from celery
(Apium graveolens). J Nat Prod. 2009;72:1563–7.
73. Zhou Y, Taylor B, Smith TJ, et al. A novel compound from celery seed with
a bactericidal effect against Helicobacter pylori. J Pharm Pharmacol.
2009;61:1067–77.
Argemone mexicana L.
(Papaveraceae)

Abstract
The plant is a native of tropical America, West Indies, and India. It is used in
Indian traditional medicines as diuretic, anti-inflammatory, antibacterial, anti-
fungal, and for its wound-healing property. In Unani medicine, decoction of all its
parts is used to induce diuresis, and to relieve urinary burning; seeds are more
sedative and hypnotic than opium, and cause nausea. Yellow juice of the plant is
used for the treatment of dropsy, jaundice, and cutaneous afflictions, and with the
juice of Aristolochia bracteata used in syphilis, leprosy and gonorrhea. Seed oil is
a drastic purgative, nauseant, expectorant, aperient, and sedative, and used in
cholera, dropsy, and painful colic. In Mexico, infusion of the entire plant is used
to relieve kidney pain, to help expel torn placenta, and to cleanse body after
childbirth, as narcotic, sedative and analgesic, and the seeds are used as antidote
to snake venom. The plant contains alkaloids, flavonoids, tannins, and sterols
and/or triterpenes. Ethanol extract of aerial parts, and an alkaloid-enriched extract
produced anxiolytic-like effects without affecting locomotor activity, and signifi-
cantly reduced severity of pilocarpine-induced status epilepticus in rats, and
reduced oxidative stress. A decoction of the plant was effective in 89% cases of
uncomplicated malaria in a remote Malian village, compared to 95% success with
artesunate-amodiaquine therapy. Consumption of adulterated mustard oil with
Argemone oil (AO) has caused “Epidemic Dropsy” in India. Safe limit of AO in
humans was calculated as 0.00001%; i.e. 100 ppb or 100 ng AO/g oil.

Keywords
Amapola montes

Bharbhand

Lao chou

Mexican poppy Papavero

messicano

Satyanasi

Stekelpapaver

Swarnaksiri Teshimizing


Teufelsfeige

© Springer Nature Switzerland AG 2020 307

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_29
308 Argemone mexicana L.

Vernaculars: Urd.: Satyanasi; Hin.: Bharbhand, Firangi dhotra, Kutila, Satya-

nasa, Shiyal-kanda, Siyal-kanta, Ujar-kanta; San.: Haimavathi, Hemaksiri, Hima-
vatel brahma-danda, Kãñcanaksiri, Katuparni, Pitadugdhã, Srigalakantaka,
Swarnaksiri; Ben.: Buro shyala-kanta, Shialkanta, Sialkanta; Mal.: Brahma-danti,
Ponnummattum; Mar.: Daruri, Kanta-dhotra, Pivla dhotra; Tam.: Birama-dandu,
Brahmmadandu, Karukkansedi, Kudiyotti, Kurukkum, Pirammathandu; Tel.:
Brahmadandi, Brahmdandidandu, Bramha-dandi-chettu, Datturi, Pichy kusama
chettu; Ara.: Teshimizing; Chi.: Lao chou; Dut.: Stekelpapaver; Eng.: Golden
thistle of Peru, Mexican poppy, Mexican prickly poppy; Fre.: Chardon bénit,
Chardon du pays, Pavot du Mexique, Pavot épineux, Tache de l’oeil; Ger.:
Mexikanischer stachelmohn, Teufelsfeige; Ita.: Papavero messicano, Papavero
mexicano, Papavero spinosa; Per.: Khashkhash khardar; Por.: Papoula-do-méxico
(Br.); Spa.: Amapola montes, Cardo santo; Tag.: Kachumba.
Description: The plant is a native of tropical America, West Indies, and India. It is
an erect, stout, branched, annual herb, up to one meter high. Leaves are 5–11 cm
long, more or less blotched with green and white, galucous, broad at the base, half
clasping the stem, prominently sinuate-lobed and spiny. Flowers are terminal,
yellow, scentless, and 4–5 cm in diameter; the seeds are spherical, shining black
and pitted (Fig. 1).CXVII
Actions and Uses: In Indian traditional medicines, the plant is used as diuretic,
anti-inflammatory, antibacterial, antifungal, and for its wound-healing property
[16]. In Unani medicine, decoction of all its parts is used to induce diuresis, and to
relieve urinary burning; seeds are more sedative and hypnotic than opium, and
cause nausea.L Yellow juice of the plant is diuretic, alterative, anodyne, and hyp-
notic,CV is used for the treatment of dropsy, jaundice, and cutaneous afflictions,XXI,
LXXXIV,CXXII
and with the juice of Aristolochia bracteata used in syphilis, leprosy
and gonorrhea.CV Seeds are laxative, nauseant, emetic, expectorant, demulcent and

Fig. 1 Argemone mexicana, Leaves and Flower, B. Navez, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Argemone_mexicana_
flower_2.jpg; https://creativecommons.org/licenses/by-sa/3.0/
Argemone mexicana L. 309

narcotic, and are useful for the treatment of coughs and catarrhal afflictions of
throat, pulmonary mucous membrane, and in whooping cough and asthma. Seed oil
is a drastic purgative, nauseant, expectorant, aperient, and sedative,LXXXIV,CV and
used in cholera, dropsy, and painful colic.LXXXI In Ayurveda, it is used in kustha,
kandū, krmi, and ãnãha.LIX In Mexico, infusion of the entire plant, both fresh and
dried, is used to relieve kidney pain, to help expel torn placenta, and to cleanse
body after childbirth,XLIV as narcotic, sedative and analgesic [10],XCVII,XCIX,CXIX
and the seeds are used as antidote to snake venom [10]. Latex is used externally for
indolent ulcers, and on eyelids in case of conjunctivitis [10].CIX
Phytoconstituents: The plant contains alkaloids, flavonoids, tannins, and sterols
and/or triterpenes, and numerous studies on alkaloids have been reported [8, 9, 13,
19, 22, 24, 26, 31, 46]. Total alkaloid content (0.125%), consisting of protopine and
berberine, tannins (1.1%), resin (1.75%) and a toxic principle in argemone oil [8];
flavonoids from flowers [23, 29, 30], and seeds [21], and two phenolic compounds
from the seeds [6], are reported. Seed oil yield, by various methods, varies between
26.7 and 39.5%. Benzophenanthridine-type alkaloids, N-demethyloxysanguinarine
and pancorine; benzylisoquinoline-type alkaloids, (+)-1,2,3,4-tetrahydro-1-
(2-hydroxymethyl-3,4-dimethoxyphenyl-methyl)-6,7-methylenedioxyisoquinoline,
(+)-higenamine and (+)-reticuline [12]; and protopine-type alkaloids, argemexi-
caine A and B from aerial parts have been reported [11]. A benzylisoquinoline
alkaloid, argemexirine, and two protoberberine alkaloids, dl-tetrahydrocoptisine
and dihydrocoptisine [36], and four quaternary isoquinoline alkaloids, dehydroco-
rydalmine, jatrorrhizine, columbamine, and oxyberberine [37], were isolated from
whole plant. A new protopine alkaloid, protomexicine and a new isoflavonoid,
mexitin, and 8-methoxydihydrosanguinarine, 13-oxoprotopine, quercetrin and rutin
have been isolated from aerial parts [35].
Pharmacology: Ethanol extract of aerial parts, and an alkaloid-enriched extract
produced anxiolytic-like effects without affecting locomotor activity in rats [2], and
the ethanol extract pretreatment also significantly reduced severity of pilocarpine-
induced status epilepticus in rats, and reduced oxidative stress [3]. Aqueous and
methanol extracts of the plant increased healing of gastric ulceration and prevented
development of cysteamine-induced duodenal ulceration in rats; aqueous extract
showing better activity than the methanol extract [16]. Methanol, cold water and hot
water extracts of leaves and seeds exhibited antibacterial activity against pathogenic
MDR Gram-positive (S. aureus and B. subtilis) and Gram-negative (E. coli and
P. aeruginosa) bacteria; methanol extract showed maximum inhibition, followed by
hot water extract and cold water extract [7]. Cold aqueous and methanol extracts of
stem and leaves inhibited growth of M. indicus, A. flavus, A. niger and P. notatum,
comparable to Amphotericin-B [25]. Acetone fraction of petroleum ether seed
extract also exhibits larvicidal and growth inhibiting activity against larvae of Aedes
aegypti [33]. Different parts exhibited antioxidant activity which was correlated
with levels of total phenolic and flavonoid contents [39].
310 Argemone mexicana L.

Clinical Studies: In a quasi-clinical trial, A. mexicana decoction produced ade-

quate clinical response in children aged less than one year and 5 years or older,
suffering from malaria, with very few adverse effects. However, the response
was better in older children, but very few patients had complete parasite clear-
ance [45]. The decoction was effective in 89% cases of uncomplicated malaria in a
remote Malian village, compared to 95% success with artesunate-amodiaquine
therapy [18].
Mechanism of Action: Berberine and sanguinarine, at very low concentrations,
significantly inhibit diamine oxidase or histaminase that leads to decreased cata-
bolism of histamine, causing some of the clinical features of epidemic dropsy [43].
Human A/Es, Allergy and Toxicity: Consumption of adulterated mustard oil with
argemone oil (AO) has caused “Epidemic Dropsy” in India and continue to do so
[15, 17, 20, 28, 32, 34, 40, 44]. Body massage with contaminated mustard oil has
produced manifestations of epidemic dropsy due to transcutaneous absorption [38].
Edema of leg is the most common presenting clinical symptom; pigmentation was
found in one-third of patients, hair loss in three-fourth, and nontender hepatomegaly
in a quarter of patients, and presence of sanguinarine, the toxic principle, in urine
samples was reported [38, 40]. Total cholesterol, TGs, LDL-C and VLDL-C were
significantly increased, with a significant decrease in HDL-C, and antioxidant
enzymes in dropsy patients [15]. Bilateral wasting of deltoids, supraspinatus and
infraspinatus muscles, sluggish upper limbs biceps reflex, and bilateral pansensory
loss on skin over deltoids were reported in two cases of argemone oil poisoning
[28]. Visual field defects, independent of rise in intraocular pressure, occur in
epidemic dropsy patients [34]. Retinal changes including venous dilatation, tortu-
osity, hemorrhages, and optic disc edema have also been observed in affected
patients [32]. Safe limit of AO in humans was calculated as 0.00001%; i.e. 100 ppb
or 100 ng AO/g oil containing only 0.55% of sanguinarine equivalent to 0.6 ng
sanguinarine per gram oil [4].
Animal Toxicity: Feeding of seeds to rats produced sedation, passiveness, slug-
gishness, feeble or no muscular jerks, abdominal contractions, increased defecation,
weight loss, corneal opacity, piloerection, and edema of the hind legs, followed by
death [27]. Sixty-days dietary intake of AO produced significant stimulation of
LPO, liver fibrosis, hyperplasia of bile ducts, glomerular congestion, and degen-
erative changes in cardiac muscle fibers of rats [42]. The alkaloid, sanguinarine
contained in AO is genotoxic and possesses skin tumor initiating activity [1, 5].
Sanguinarine, in a dose of 10 mg/kg, caused progressive hepatocellular degenera-
tion in rats, substantially increasing activities of SGPT and SGOT, and significant
loss of microsomal CYP450 [14].
CYP450 and Potential for Drug-Herb Interaction: A single dose of AO caused
inhibition of CYP450, and its dependent mixed-function oxidases; and depletion of
endogenous hepatic GSH content, with substantial increase in LPO, and decrease in
GST activity [41].
Argemone mexicana L. 311

Commentary: There are no clinical studies reported in the publications listed on

PubMed.

References
1. Ansari KM, Das M. Skin tumor promotion by argemone oil/alkaloid in
mice: evidence for enhanced cell proliferation, ornithine decarboxylase,
cyclooxygenase-2 and activation of MAPK/NF-kappaB pathway. Food
Chem Toxicol. 2010;48:132–8.
2. Arcos-Martínez AI, Muñoz-Muñiz OD, Domínguez-Ortiz MÁ, et al.
Anxiolytic-like effect of ethanolic extract of Argemone mexicana and its
alkaloids in Wistar rats. Avicenna J Phytomed. 2016;6:476–88.
3. Asuntha G, Raju YP, Sundaresan CR, et al. Effect of Argemone mexicana
(L.) against lithium-pilocarpine induced status epilepticus and oxidative
stress in Wistar rats. Indian J Exp Biol. 2015;53:31–5.
4. Babu ChK, Khanna SK, Das M. Safety evaluation studies on argemone oil
through dietary exposure for 90 days in rats. Food Chem Toxicol. 2006;44:
1151–7.
5. Babu CK, Ansari KM, Mehrotra S, et al. Alterations in redox potential of
glutathione/glutathione disulfide and cysteine/cysteine disulfide couples in
plasma of dropsy patients with argemone oil poisoning. Food Chem
Toxicol. 2008;46:2409–14.
6. Bhardwaj DK, Bisht MS, Jain RK, Munjal A. Phenolics from the seeds of
Argemone mexicana. Phytochemistry. 1982;21:2154–6.
7. Bhattacharjee I, Chatterjee SK, Chatterjee S, Chandra G. Antibacterial
potentiality of Argemone mexicana solvent extracts against some pathogenic
bacteria. Mem Inst Oswaldo Cruz. 2006;101:645–8.
8. Bose BC, Vijayvargiya R, Saifi AQ, Sharma SK. Chemical and pharma-
cological studies on Argemone mexicana. J Pharm Sci. 1963;52:1172–5.
9. Bui Thi Yu. Murav’eva, DA: Isolation and determination of the alkaloids of
Argemone mexicana grown in different geographic regions. Rast Resur.
1973;9:200–2.
10. Caius JF. Medicinal and poisonous plants of India. Waterlilies, Poppywrots.
Fumitorius. J Bombay Nat Hist Soc. 1938;40:513–27.
11. Chang YC, Chang FR, Khalil AT, et al. Cytotoxic benzophenanthridine and
benzylisoquinoline alkaloids from Argemone mexicana. Z Naturforsch [C].
2003;58:521–6.
12. Chang YC, Hsieh PW, Chang FR, et al. Two new protopines argemexi-
caines A and B and the anti-HIV alkaloid 6-acetonyldihydrochelerythrine
from formosan Argemone mexicana. Planta Med. 2003;69:148–52.
13. Chelombit’ko VA, Murav’eva DA, El-Sawy Y. Protopine and allocryp-
topine from Argemone mexicana. Khim Prir Soedin. 1971;7:208.
14. Dalvi RR. Sanguinarine: its potential as a liver toxic alkaloid present in the
seeds of Argemone mexicana. Experientia. 1985;41:77–8.
312 Argemone mexicana L.

15. Das M, Babu K, Reddy NP, Srivastava LM. Oxidative damage of plasma
proteins and lipids in epidemic dropsy patients: alterations in antioxidant
status. Biochim Biophys Acta. 2005;1722:209–17.
16. Das PK, Pillai S, Kar D, Pradhan D, Sahoo S. Pharmacological efficacy of
Argemone mexicana plant extract, against cysteamine-induced duodenal
ulceration in rats. Indian J Med Sci. 2011;65:92–9.
17. Dhayal GL, Agarwal H, Mathur A, et al. Case report of a small outbreak of
epidemic dropsy. J Indian Med Assoc. 2013;111:200–1.
18. Graz B, Willcox ML, Diakite C, et al. Argemone mexicana decoction versus
artesunate-amodiaquine for the management of malaria in Mali: policy and
public-health implications. Trans R Soc Trop Med Hyg. 2010;104:33–41.
19. Haisova K, Slavik J. Minor alkaloids from Argemone mexicana. Collect
Czech Chem Commun. 1975;40:1576–8.
20. Hakim SA, Jehangir RP. Argemone oil poisoning. J Trop Med Hyg.
1977;80:149–51.
21. Harborne JB, Williams CA. Flavonoids in the seeds of Argemone mexicana:
a reappraisal. Phytochemistry. 1983;22:1520–1521.
22. Hussain SF, Nakkady S, Khan L, Shamma M. Oxyhydrastinine, an
isoquinolone alkaloid from the Papaveraceae. Phytochemistry. 1983;22:
319–20.
23. Krishnamurti M, Ramanathan JD, Seshadri TR, Shankaran PR. Flavonol
glycosides of Argemone mexicana flowers. Indian J Chem. 1965;3:270–2.
24. Misra PS, Bhakuni DS, Sharma VN, Kaul KN. Chemical constituents of
Argemone mexicana. J Sci Ind Res. 1961;20B:186.
25. More NV, Kharat AS. Antifungal and anticancer potential of Argemone
mexicana L. Medicines (Basel). 2016;3, pii: E28.
26. Murav’eva DA. Bui Thi Yu: study of alkaloid composition of Argemone
mexicana. Aktual Vopr Farm. 1974;2:24–6.
27. Pahwa R, Chatterjee VC. The toxicity of Mexican poppy (Argemone
mexicana L.) seeds to rats. Vet Hum Toxicol. 1989;31:555–8.
28. Prabhakar S, Khurana D, Gill KD, et al. Neurologic complications of
dropsy: from possibility to reality. Neurol India. 2000;48:144–8.
29. Rahman W, Ilyas M. Flavone glycosides of the flowers of Argemone
mexicana Linn. (Papaveraceae). C R Acad Sci (Par). 1961;252:1974–5.
30. Rahman W, Ilyas M. Flower pigments. Flavonoids from Argemone
mexicana. J Org Chem. 1962;27:153–5.
31. Razdan BK, Bhattacharya IC. Phytochemical survey of Rajasthan. I. Alka-
loids. Proc Rajasthan Acad Sci. 1963;10:59–65.
32. Sachdev MS, Sood NN, Mohan M, Sachdev HP, Gupta SK. Optic disc
vasculitis in epidemic dropsy. Jpn J Ophthalmol. 1987;31:467–74.
33. Sakthivadivel M, Thilagavathy D. Larvicidal and chemosterilant activity of
the acetone fraction of petroleum ether extract from Argemone mexicana L.
seed. Bioresour Technol. 2003;89:213–6.
34. Singh K, Singh MJ, Das JC. Visual field defects in epidemic dropsy. Clin
Toxicol (Phila). 2006;44:159–63.
Argemone mexicana L. 313

35. Singh S, Pandey VB, Singh TD. Alkaloids and flavonoids of Argemone
mexicana. Nat Prod Res. 2012;26:16–21.
36. Singh S, Singh TD, Singh VP, Pandey VB. A new benzylisoquinoline
alkaloid from Argemone mexicana. Nat Prod Res. 2010;24:63–7.
37. Singh S, Singh TD, Singh VP, Pandey VB. Quaternary alkaloids of
Argemone mexicana. Pharm Biol. 2010;48:158–60.
38. Sood NN, Sachdev MS, Mohan M, Gupta SK, Sachdev HP. Epidemic
dropsy following transcutaneous absorption of Argemone mexicana oil.
Trans R Soc Trop Med Hyg. 1985;79:510–2.
39. Srivastava N, Chauhan AS, Sharma B. Isolation and characterization of
some phytochemicals from Indian traditional plants. Biotechnol Res Int.
2012;2012:549850.
40. Tandon RK, Singh DS, Arora RR, Lal P, Tandon BN. Epidemic dropsy in
New Delhi. Am J Clin Nutr. 1975;28:883–7.
41. Upreti KK, Das M, Khanna SK. Biochemical toxicology of argemone oil.
I. Effect on hepatic cytochrome P-450 and xenobiotic metabolizing
enzymes. J Appl Toxicol. 1991;11:203–9.
42. Upreti KK, Das M, Kumar A, et al. Biochemical toxicology of argemone
oil. IV. Short-term oral feeding response in rats. Toxicology. 1989;58:
285–98.
43. Vaidya AB, Rajagopalan TG, Kale AG, Levine RJ. Inhibition of human
pregnancy plasma diamine oxidase with alkaloids of Argemone mexicana—
berberine and sanguinarine. J Postgrad Med. 1980;26:28–33.
44. Verma SK, Dev G, Tyagi AK, et al. Argemone mexicana poisoning: autopsy
findings of two cases. Forensic Sci Int. 2001;115:135–41.
45. Willcox ML, Graz B, Falquet J, et al. Argemone mexicana decoction for the
treatment of uncomplicated falciparum malaria. Trans R Soc Trop Med
Hyg. 2007;101:1190–8.
46. Woo WS, Chi HJ, Yun HS. Alkaloid screening of some Saudi Arabian
plants. Sengyak Hakhoe Chi. 1977;8:109–13.
Aristolochia bracteolata Lam.
(Aristolochiaceae)

(Syn.: A. bracteata Retz.)

Abstract
A small glabrous shrub or a perennial herb, that grows in India and found in Africa,
especially the Sahel region from Mali to northern Nigeria, tropical East Africa,
and in Saudi Arabia. All parts of the plant are extremely bitter, purgative,
emmenagogue, anthelmintic, alterative and antiperiodic. Leaves are administered
with castor oil as a remedy for colic, and the juice of fresh leaves or powder of dried
leaves is a favorite application for sores, obstinate itch, and to destroy maggots.
Root and leaves yield a thick yellowish juice, which is mixed with boiled milk and
used in cases of syphilis; and combined with opium it is used for gonorrhea with
great success. The plant increases or induces uterine contractions, and hence used
in difficult labor, dysmenorrhea and amenorrhea. Its anthelmintic property is also
doubtless, and in Africa it is mostly used in veterinary practice. It is indigenous to
central Sudan, and medicinally used for its analgesic and diuretic effects, treatment
of tumors, malaria and/or fevers; other uses in Sudanese folk medicine include,
leaves for the treatment of malaria, and the roots as anti-inflammatory, and for
scorpion stings. In Nigeria, dried leaves infusion is used as anthelmintic; freshly
bruised leaves mixed with castor-oil are topically used on pimples, and roots
mixed with lime juice are taken for snakebite and scorpion stings. A nauseous
volatile substance, an alkaloid and a large quantity of salts especially potassium
chloride have been reported from the plant. Aristolochic acid, which is a
nephrotoxic, carcinogenic and mutagenic substance, has been isolated from roots
and stem with yield of 0.01%. From leaves and fruits, ceryl alcohol, b-sitosterol,
aristolochic acid and potassium chloride have been isolated. Ethanol extract of
shade-dried leaves has been reported to have significantly increased wound
healing, and levels of antioxidant enzymes, SOD and CAT, in granuloma tissue.

Keywords


Aristolochia bracteolata Birth wort
Dhñmrapatrã
Gandhni
Gridhrani




Kiramar Sarrasine Snake wort

© Springer Nature Switzerland AG 2020 315

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_30
316 Aristolochia bracteolata Lam.

Vernaculars: Urd.: Kiramaar; Hin.: Bhringi, Gandan, Gandhni, Gadhatee, Kiramar;

San.: Dhñmrapatrã, Gridhrani, Kitamãri, Pattrabungha; Mal.: Aduthinnapala,
Atu-tintap, Atutintappala, Karalakam; Mar.: Gadhani, Gaval; Tam.: Aaduthinna-
palai, Adu-tinna-palai; Tel.: Gadathigadaparaku, Gaddithaigadapara, Gadide, Kada-
para; Eng.: Birth wort, Dutchman’s pipe, Snake wort, Worm-killer; Sud.: Um galagel.
Description: It is a small glabrous shrub or a perennial herb, that grows in India
along the banks of Ganges and Jamuna, and in Bundelkhand and Konkan, and in
Madras (Chennai) it is found on black cotton soil.XXI It is also found in Africa,
especially the Sahel region from Mali to northern Nigeria, tropical East Africa [8],
and in Saudi Arabia.LXXXV Stems are striated, wavy, slender, and of a pale-brown
color; leaves very obtuse, heart-shaped, curled at the margins, surface wrinkled or
tubercled and of a pale, glaucous, green or darkish-brown color below. Flowers are
solitary, axillary, peduncled and drooping; capsules are ribbed, depressed at the
apex, 2 cm long, six celled and each cell contains a column of heart-shaped closely
packed flat seeds. Appearance of seeds is characteristic with one side as flat, black
and rough due to a number of irregular projections; the other side is almost entirely
occupied by two brown, comparatively smooth lobular projections of a soft corky
structure. Microscopically, those projections are composed of ovate, empty, doted
cells. The roots are fibrous (Fig. 1).XXI
Actions and Uses: All parts of the plant are extremely bitter, purgative, emme-
nagogue, anthelmintic, alterative and antiperiodic.CV Leaves are administered with
castor oil as a remedy for colic, and the juice of fresh leaves or powder of dried
leaves is a favorite application for sores, obstinate itch, and to destroy maggots.XXI,
XL,LXXXI
Native tribals in southern India use its leaves for rapid healing of cuts and
wounds [16]. Root and leaves yield a thick yellowish juice, which is mixed with
boiled milk and used in cases of syphilis; and combined with opium it is used for
gonorrhea with great success. The plant has a certain action on uterus to increase or

Fig. 1 Aristolochia bracteolata, Plant, Thamizhpparithi Maari, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:A_image_of_Aristolochia_
bracteolata.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Aristolochia bracteolata Lam. 317

induce uterine contractions, and hence used in difficult labor, dysmenorrhea and
amenorrhea.XL,LXXXI Leaf is reported abortifacient, ecbolic and oxytocic [4], and
the whole plant as emmenagogue [14]. Its anthelmintic property is also doubtless,
and in Africa it is mostly used in veterinary practice. It is used as aphrodisiac, and
for leg itch in Ethiopia [11]; east of Lake Chad, the root is applied to scorpion stings
[8]. It is indigenous to central Sudan, and medicinally used for its analgesic and
diuretic effects, treatment of tumors, malaria and/or fevers [1]; other uses in
Sudanese folk medicine include, leaves for the treatment of malaria, and the roots as
anti-inflammatory, and for scorpion stings [2]. In Nigeria, dried leaves infusion is
used as anthelmintic; freshly bruised leaves mixed with castor-oil are topically used
on pimples, and roots mixed with lime juice are taken for snakebite and scorpion
stings [8]. Flowers are sometimes worn in northern Nigeria as charm against sna-
kebite and scorpion stings.XVI
Phytoconstituents: A nauseous volatile substance, an alkaloid and a large quantity
of salts especially potassium chloride have been reported.XXI,XL,LXXXI The alkaloid
is amorphous and gives no color reactions with strong mineral acids; ash calculated
of air-dried plant was 17.75%, and strong alkaline fumes are given off the plant on
burning.XL Aristolochic acid was isolated from roots and stem with an yield of
0.01% [6]. Aristolochic acids are nephrotoxic, carcinogenic and mutagenic [1].
From leaves and fruits, ceryl alcohol, b-sitosterol, aristolochic acid and potassium
chloride have been isolated. The roots contain KCl and nitrates as major con-
stituents, besides aristolochic acid, and a yellow microcrystalline compound.
Maximum ceryl alcohol content (0.38%) was found in leaves, while fruits showed
only 0.12% content [15]. From etheral part of alcoholic extract residue of defatted
seeds, aristolochic acid, aristo red and yellow acidic compounds have been isolated;
while the quaternary fraction of this alcoholic extract contained a major crystalline
alkaloid identified as magnoflorine (thalactrine), along with two minor alkaloids (A
and B) in trace quantities [9]. Petroleum ether/chloroform (1:1) extract of whole
plant showed presence of alkaloids and sterols [2]. Powdered roots, collected during
rainy season in Nigeria, showed presence of alkaloids, cardenolides and saponins
[8]. The active principle is aristolochic acid.
Pharmacology: Successive extracts of roots with ethyl acetate, acetone, methanol,
and water showed broad-spectrum antibacterial activity against both Gram-positive
and Gram-negative bacteria, with ethyl acetate extract being the most active [13].
Methanol extract of the whole plant was active against M. catarrhalis [17], and
methanol and chloroform extracts of leaf and bark powder were moderately active
against B. subtilis, S. typhi, P. aeruginosa, and E. coli [10]. Ethanol root extract and EO
exhibited potent antifungal activity against several strains of C. albicans isolates [8].
Petroleum ether/chloroform (1:1) extract of whole plant completely inhibited growth
of schizonts of P. falciparum [2]. Ethanol extract of shade-dried leaves significantly
increased wound healing, and levels of antioxidant enzymes, SOD and CAT, in
granuloma tissue [16]. Chloroform leaf extract significantly inhibited compound
48/80-induced pruritus and dermatitis, stabilized mast cells, and reduced blood his-
tamine levels in mice [5]. Various fractions of petroleum ether and methanol leaf
318 Aristolochia bracteolata Lam.

extracts significantly reduced serum uric acid and creatinine levels, and increased
urinary uric acid and creatinine levels in hyperuricemic rats [12]. Alcoholic cold water
and hot water extracts of roots and stem, produced contractions of the uteri of virgin rat
and guinea pig [6, 18].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Oral administration to goats caused diarrhea, dyspnea, tympany,
arching of the back, loss of condition, and loss of hair from the back. There were
hemorrhages in the lungs, heart, and kidneys, fatty change and congestion in the liver,
mucoid abomasitis and enteritis and straw-colored fluid in serous cavities [3, 7].
Commentary: There are no clinical studies reported in English publications listed
on PubMed.

References
1. Abdelgadir AA, Ahmed EM, Eltohami MS. Isolation, characterization and
quantity determination of aristolochic acids, toxic compounds in Aris-
tolochia bracteolata L. Environ Health Insights. 2011;5:1–8.
2. Ahmed HM, Nour BY, Mohammed YG, Khalid HS. Antiplasmodial
activity of some medicinal plants used in Sudanese folk-medicine. Environ
Health Insights. 2010;4:1–6.
3. Barakat SE, Wasfi IA, Adam SE. The toxicity of Aristolochia bracteata in
goats. Vet Pathol. 1983;20:611–6.
4. Casey RC. 298 alleged antifertility plants of India. Indian J Med Sci.
1960;14:590–600.
5. Chitme HR, Malipatil M, Chandrashekhar VM, Prashant PM. Antiallergic
activity of Aristolochia bracteolata Lank in animal model. Indian J Exp
Biol. 2010;48:46–52.
6. Dutta NK, Sastry MS. Pharmacological action of Aristolochia bracteata
Retz on the uterus. Indian J Pharm. 1959;20:302.
7. el Dirdiri NI, Barakat SE, Adam SE. The combined toxicity of Aristolochia
bracteata and Cadaba rotundifolia to goats. Vet Hum Toxicol. 1987;29:
133–7.
8. Gbadamosi IT, Egunyomi A. In-vitro propagation and antimycotic potential
of extracts and essential oil of roots of Aristolochia bracteolata Linn.
(Aristolochiaceae). Afr J Tradit Complement Altern Med. 2011;9:50–5.
9. Hussein FT. A phytochemical investigation of the seeds of Aristolochia
bracteata. Planta Med. 1970;18:30–5.
10. Kavitha D, Nirmaladevi R. Assessment of Aristolochia bracteolate leaf
extracts for its biotherapeutic potential. Afr J Biotech. 2009;8:4242–4.
11. Lemordant D. Contribution a l’ethnobotanique Ethiopienne. J Agric Trop
Bot Appl. 1971;18:1–35; 18:142–79.
Aristolochia bracteolata Lam. 319

12. Li YP, Wu S, Ran A, et al. Aristolochia bracteolate Retz. attenuates

hyperuricemia in a metabolic arthritis rat model. Afr J Tradit Complement
Altern Med. 2017;14:180–7.
13. Negi PS, Anandharamakrishnan C, Jayaprakasha GK. Antibacterial activity
of Aristolochia bracteata root extracts. J Med Food. 2003;6:401–3.
14. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
15. Sastry MS. Chemical investigations on Aristolochia bracteata Retz. Indian J
Pharm. 1965;27:265.
16. Shirwaikar A, Somashekar AP, Udupa AL, Udupa SL, Somashekar S. Wound
healing studies of Aristolochia bracteolata Lam. with supportive action of
antioxidant enzymes. Phytomedicine. 2003;10:558–62.
17. Suliman Mohamed M, Timan Idriss M, Khedr AI, et al. Activity of Aristolochia
bracteolate against Moraxella catarrhalis. Int J Bacteriol. 2014;2014:481686.
18. Tewari PV, Prasad DN, Das PK. Preliminary studies on uterine activity of
some Indian medicinal plants. J Res Indian Med. 1966;1:68.
Aristolochia fontanesii Boiss. & Reut.
(Aristolochiaceae)

(Syn.: A. longa L.)

Abstract
The roots are described as diuretic, emmenagogue, resolvent, rubefacient,
expectorant, anthelmintic, and detergent, and used in Unani medicine in the
treatment of amenorrhea, cough, asthma, intestinal worms, and to expel fetus. It is
also described as deobstruent, and alexipharmic, and also used as nervine tonic in
headaches and brain diseases, and for dysmenorrhea; locally it is applied to gum
ulcers. Roots are widely used in Algerian and Moroccan traditional medicines in the
treatment of breast cancer in women, and crushed roots mixed with honey, milk,
water or other medicinal plants are used for skin infections, diabetes and
gastrointestinal ailments. Aqueous root extract showed presence of polyphenols,
flavonoids, catechic tannins and saponins. Oil obtained from aerial parts of wildly
grown plant in Tunisia was rich in linolenic and linoleic acids as polyunsaturated
fatty acids, and palmitic and stearic acids being the most prominent saturated fatty
acids; whereas, oleic and linoleic acids were the major fatty acids in the roots.
Aqueous extract inhibited cell growth of Burkitt’s lymphoma cells, inducing
apoptosis. Aristolochia species are known to cause nephrotoxicity due to the
presence of aristolochic acid, even leading to fatal renal failure. A retrospective
study of the use of A. longa by postmenopausal women with breast cancer, revealed
signs of nephrotoxicity, and a very significant increase of mean concentrations of
bone resorption markers.

Keywords


Algerian-piippuköynnös Aristoloche pale
Aristolochia longa
Berrostom



Birthwort Zarawand-e-taweel

Vernaculars: Urd.: Zarawand-e-taweel; Alg.: Berrostom; Eng.: Birthwort; Fin.:

Algerian-piippuköynnös; Fre.: Aristoloche pale, Sarrasine; Mor.: Bereztem.

© Springer Nature Switzerland AG 2020 321

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_31
322 Aristolochia fontanesii Boiss. & Reut.

Description: The plant resembles A. rotunda and have a similar habitat; it differs
in having petioled leaves, yellow flowers with brown strips, and a cylindrical root
similar in taste and odor to A. rotunda.XL The roots are whitish, twisted, tasteless,
cylindrical pieces of the size of a finger (Fig. 1).
Actions and Uses: The temperament of roots is hot 3° and dry 2°, and ascribed
properties of diuretic, emmenagogue, resolvent, rubefacient, expectorant, anthel-
mintic, and detergent in Unani medicine; used in the treatment of amenorrhea,
cough, asthma, intestinal worms, and to expel fetus.LXXVII Dymock et al.XL also
described roots as deobstruent, and alexipharmic. It is also used as nervine tonic in
headaches and brain diseases, and for dysmenorrhea; locally it is applied to ulcer
affections of gums.LXXXI Roots are widely used in Algerian and Moroccan tradi-
tional medicines in the treatment of breast cancer in women [2, 11], and crushed
roots mixed with honey, milk, water or other medicinal plants are used for skin
infections, diabetes and gastrointestinal ailments. For skin infections and rheuma-
tism, the plant ground with olive oil or water is applied externally [3]. Fruit of
A. debilis, described incorrectly as synonym of A. longa, is used in Chinese
medicine as antitussive, and expectorant in asthma and bronchitis.LXXIX

Fig. 1 Aristolochia fontanesii, Illustration, Argenta, Vicente Martin de, WikimediaCommons, https://
commons.wikimedia.org/wiki/File:Album_de_la_flora_m%C3%A9dico-farmac%C3%A9utica_%C3
%A9_industrial,_ind%C3%ADgena_y_ex%C3%B3tica_(Pl._54)_(8157679532).jpg
Aristolochia fontanesii Boiss. & Reut. 323

Phytoconstituents: Aqueous root extract showed presence of polyphenols, fla-

vonoids, catechic tannins and saponins [3]. Oil obtained from aerial parts of wildly
grown plant in Tunisia was rich in linolenic and linoleic acids as polyunsaturated
fatty acids, and palmitic and stearic acids being the most prominent saturated fatty
acids; whereas, oleic and linoleic acids were the major fatty acids in the roots [7].
Pharmacology: Aqueous extract inhibited growth of Burkitt’s lymphoma cells,
inducing apoptosis [1], and induced growth inhibition of fungus, S. cerevisiae cells
[3]. Root lipid extract exhibited moderate antibacterial activity against E. feacium
and S. agalactiae [7], and protein extract showed significant immunostimulatory
activity [4].
Human A/Es, Allergy and Toxicity: Aristolochia species are known to cause
nephrotoxicity due to the presence of aristolochic acid [5, 6, 8, 9], even leading to
fatal renal failure [10]. A retrospective study of the use of A. longa by post-
menopausal women with breast cancer, revealed signs of nephrotoxicity with sig-
nificant increase in serum creatinine, urea, and uric acid, and a very significant
increase of mean concentrations of bone resorption markers (deoxypyridinoline and
pyridinoline) [2].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It is one of those plants that is used in traditional medicines but has
been sparingly investigated pharmacologically, and there have not been any clinical
studies conducted on it. Since it is widely used in Algerian and Moroccan tradi-
tional medicines in the treatment of breast cancer in postmenopausal women, it
deserves to be investigated for its clinical efficacy in breast cancer patients.

References
1. Benarba B, Ambroise G, Aoues A, Meddah B, Vazquez A. Aristolochia
longa aqueous extract triggers the mitochondrial pathway of apoptosis in
BL41 Burkitt’s lymphoma cells. Int J Green Pharm. 2012;6:45–9.
2. Benarba B, Meddah B, Tir Touil A. Response of bone resorption markers to
Aristolochia longa intake by Algerian breast cancer postmenopausal
women. Adv Pharmacol Sci. 2014;2014:820589.
3. Benarba B, Meddah B. Ethnobotanical study, antifungal activity, phyto-
chemical screening and total phenolic content of Algerian Aristolochia
longa. J Intercult Ethnopharmacol. 2014;3:150–4.
4. Daoudi A, Aarab L, Abdel-Sattar E. Screening of immunomodulatory
activity of total and protein extracts of some Moroccan medicinal plants.
Toxicol Ind Health. 2013;29:245–53.
5. Debelle FD, Nortier JL, De Prez EG, et al. Aristolochic acids induce chronic
renal failure with interstitial fibrosis in salt-depleted rats. J Am Soc Nephrol.
2002;13:431–6.
324 Aristolochia fontanesii Boiss. & Reut.

6. Debelle FD, Vanherweghem JL, Nortier JL. Aristolochic acid nephropathy:

a worldwide problem. Kidney Int. 2008;74:158–69.
7. Dhouioui M, Boulila A, Jemli M, et al. Fatty acids composition and anti-
bacterial activity of Aristolochia longa L. and Bryonia dioïca Jacq. growing
wild in Tunisia. J Oleo Sci. 2016;65:655–61.
8. Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma
associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J
Med. 2000;342:1686–92.
9. Nortier JL, Schmeiser HH, Muniz Martinez MC, et al. Invasive urothelial
carcinoma after exposure to Chinese herbal medicine containing aristolochic
acid may occur without severe renal failure. Nephrol Dial Transplant.
2003;18:426–8.
10. Tazi I, Nafil H, Mahmal L. Fatal renal failure due to self administration
of Aristolochia longa after treatment with chemotherapy. Arab J Nephrol
Transplant. 2012;5:54 (discussion 55).
11. Yamani A, Bunel V, Antoine MH, et al. Substitution between Aristolochia
and Bryonia genus in North-Eastern Morocco: toxicological implications.
J Ethnopharmacol. 2015;166:250–60.
Aristolochia indica L.
(Aristolochiaceae)

(Syns.: A. lanceolata Wight; A. maysorensis Fisch. ex Duch.; A. pandurata Wall.

ex Duch.)

Abstract
A twining perennial herb growing all over the tropical regions of India and Sri
Lanka. It is considered attenuant, deobstruent, emmenagogue, antiarthritic and a
valuable medicine in bowel affections of children during teething. Root and leaves
are antidote against snakebites and poisonous insects. It is a strong purgative of
adust humours, and along with Cassia fistula is recommended for use in
inflammation of organs, and as anthelmintic. In Sri Lanka, its root and stem are used
as febrifuge, attenuant, emmenagogue, for arthritis, snakebite and insect bites. In
the Philippines, powdered roots are considered tonic, carminative, and emmena-
gogue, and a very effective remedy for infantile tympanites if the pulverized roots
are applied to the abdomen. Roots contain aristolochic acid or aristolochic acid A, a
yellow very bitter principle, isoaristolochic acid, and allantoin. The characteristic
odor of the root is due to an EO that contains 3% of carbonyl compound,
sesquiterpenoid compounds and a small quantity of camphor. A sesquiterpene
ishwarene, a sesquiterpene ketone ishwarone and a sesquiterpene alcohol ishwarol
have also been isolated. Aqueous root extract possesses strong gelatinolytic,
collagenase, peroxidase and nuclease inhibitory activities, and prolongs survival of
animals administered with Russell’s viper venom. Water and ethanol root extracts
significantly reduced frequency and severity of castor oil-induced diarrhea, and
delayed intestinal transit of charcoal meal in mice. Ethanol and petroleum ether root
extracts showed significant anti-inflammatory, mast cells stabilizing, and antipru-
ritic activities. Ethanol extract decreased fertility in both rats and hamsters, when
administered post-coitus.

Keywords




Altán Aristoloche d’inde Aristolochia indica Indian birthwort Isharmul







Naagadamani Rudrajata Shah pasand Sunanda Zarawand-e-Hindi

© Springer Nature Switzerland AG 2020 325

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_32
326 Aristolochia indica L.

Vernaculars: Urd.: Shahpasand; Hin.: Isharmul; San.: Ahiganda, Irkamula, Ish-

wari, Naagadamani, Rudrajata, Sunanda, SudhiUpasaya; Ben.: Ishora-mula, Rudra-
jata, Sopsan; Mal.: Eeshvaramulla, Garudakodi, Ishvara-muri, Kadalivegam,
Karalekam, Karandavalli, Kudukkamooli, Urikizhangu; Mar.: Ishora-mula, Rudra-
jata, Sopsan; Tam.: Ichchuramula, Kozhikkundu’s, Perumarindu, Perumarun-
thukodi, Perumarunthuu, Thazhaisurulikodi, Urikkalchedi; Tel.: Ishveraveru; Ara.:
Zarawand-e-hindi; Eng.: Indian birthwort; Fre.: Aristoloche d’Inde; Per.: Izaravand-
e-hindi, Zarawand-e-hindi; Sin.: Sapsanda: Tag.: Altán, Malaúbi, Parolparúlan,
Talatalárum, Timbáñgan, Timbang-Timbáñgan.
Description: It is a twining perennial herb growing all over the tropical regions of
India and Sri Lanka. The marketed drug consists of root and stems, the latter being
the larger proportion. It is either in short pieces or whole stem may be twisted into a
kind of circular bundle. The thickest portion of stem is 0.6–1.3 cm or more in
diameter. The bark is thick and corky, marked with longitudinal ridges and
numerous small warty projections. It is of yellowish-brown color, bitter and cam-
phoraceous in taste, and with an agreeable aromatic odor (Fig. 1).XL
Actions and Uses: It is considered attenuant, deobstruent, emmenagogue, anti-
arthritic and a valuable medicine in bowel affections of children during teething.XXI,
XL,LXXVII,LXXXI
Root and leaves are antidote against snakebites and poisonous
insects.XXI NadkarniCV described root as a tonic, stimulant, emmenagogue, alexi-
teric, and antiarthritic; and a valuable antidote to snake, scorpion and other poi-
sonous insect bites. It (temperament, hot 3° and dry 3°) is a strong purgative of
adust humours, and along with Cassia fistula is recommended for use in inflam-
mation of organs,LXXVII and as anthelmintic.L Also mentioned to be useful in
chronic cough, asthma, sciatica, gout, pleurisy and splenitis,LXXXI and is regarded a
substitute of Aristolochia longa.XL In Sri Lanka, its root and stem are used as

Fig. 1 Aristolochia indica, Leaves, Delonix, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Aristolochia_indica_-_leaves.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Aristolochia indica L. 327

febrifuge, attenuant, emmenagogue, for arthritis, snakebite and insect bites. In the
Philippines, powdered roots are considered tonic, carminative, and emmenagogue,
and a very effective remedy for infantile tympanites if the pulverized roots are
applied to the abdomen.CXVII The root and whole plant are also reported aborti-
facient [3, 11, 18].
Phytoconstituents: Primary alkaloid tests are positive [1]. Roots contain an
alkaloid aristolochine (aristolochic acid or aristolochic acid A), a yellow very bitter
principle, isoaristolochic acid (sparingly soluble in most organic solvents), and
allantoin; the characteristic odor of the root is due to an EO (0.5%).IV Oil contains
3% of carbonyl compound, sesquiterpenoid compounds, and a small quantity of
camphor. A sesquiterpene ishwarene, a sesquiterpene ketone ishwarone and a
sesquiterpene alcohol ishwarol have also been isolated. Fixed oil contains glyc-
erides of palmitic, stearic, lignoceric, cerotic, oleic, and linolic acids. Considerable
amounts of reducing sugars are also present in the root.XXI Aristolochic acid content
of aqueous root extract are reported to be 3.08 ± 1.88 µg/ml [2].
Pharmacology: Aqueous root extract possesses strong gelatinolytic, collagenase,
peroxidase and nuclease inhibitory activities, and prolongs survival of animals
administered with Russell’s viper venom [2]. Orally administered extract and
partially purified fraction potently neutralized and protected mice against rat-
tlesnake venom [19]. Water and ethanol root extracts significantly reduced fre-
quency and severity of castor oil-induced diarrhea, and delayed intestinal transit of
charcoal meal in mice [5]. Ethanol and petroleum ether root extracts showed sig-
nificant anti-inflammatory, mast cells stabilizing, and antipruritic activities [12].
Ethanol and aqueous extracts of the whole plant showed significant antimicrobial
activity against MDR S. aureus, S. epidermidis, B. subtilis, E. coli, K. pneumoniae,
P. aeruginosa, P. mirabilis, E. aerogenes, E. faecalis, and V. cholera [22]. The EO,
containing b-caryophyllene and a-humulene as major constituents, showed mod-
erate antibacterial activity [20]. From sequentially extracted hexane, chloroform and
water extracts of roots, the latter two showed antibacterial activity against B.
pumilus and E. coli, while hexane extract was active only against B. pumilus [21].
Butanol extract was active against L. monocytogenes [17]. Aristolic acid was found
active against adenocarcinoma [9].
Single dose of crude petroleum ether, chloroform and alcoholic root extracts
showed 100% interceptive activity in mature female mice; the chloroform extract
with the most significant effect [13]. Later, a sesquiterpene isolated from the roots
also exerted 100% interceptive activity and 91.7% anti-implantation activity in mice,
with a single oral dose [15]. A methyl ester of aristolic acid caused 100% abortions
[16], and one compound, identified as p-coumaric acid, also showed 100% inter-
ceptive activity [14]. Ethanol extract decreased fertility in both rats and hamsters,
when administered postcoitally, whereas petroleum ether, chloroform, and aqueous
extracts were inactive and/or toxic. Aristolochic acid is also inactive when
administered postcoitally to rats, and toxic to hamsters. Aristolic acid, methyl aris
tolate and cis- and trans-p-coumaric acid were also inactive [4]. Ganguly et al. [6]
328 Aristolochia indica L.

inferred that aristolic acid interferes with steroidal conditioning of the uterus and
renders it hostile to ovum implantation. Aristolochine, the alkaloid, causes cardiac
and respiratory paralysis in frogs and mice, increases respiratory rate in rabbits, and
stimulates skeletal muscle in small doses, but paralyzes in large doses. It causes
hemorrhagic nephritis in rabbits, and gastrointestinal irritation in dogs.XXI
Mechanism of Action: Aristolochic acid was suggested responsible for antifer-
tility activity due to its cytotoxicity [7, 10].
Human A/Es, Allergy and Toxicity: More than 100 cases of nephropathy over
10 years due to systemic and longer use of Chinese snakeroot (Aristolochia fang-
chi) have been reported [8]. However, no such reports are available from Asia,
where A. indica is commonly used in traditional medicines. There is, however,
mention in Unani medicine for its nonspecific adverse effects on head and urinary
bladder.LXXVII
Animal Toxicity: Aqueous root extract does not produce any acute and subchronic
toxicity in animals at lower doses, but high doses cause liver and kidney damage [2].
Commentary: There are no clinical studies reported in the English publications
listed on PubMed. Despite nephrotoxicity potential, the antifertility activity is worth
further exploration.

References
1. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies on medicinal
plants of Sri Lanka. Part 14. Toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–35.
2. Bhattacharjee P, Bhattacharyya D. Characterization of the aqueous extract
of the root of Aristolochia indica: evaluation of its traditional use as an
antidote for snake bites. J Ethnopharmacol. 2013;145:220–6.
3. Casey RC. 298 alleged antifertility plants of India. Indian J Med Sci.
1960;14:590–600.
4. Che CT, Ahmed MS, Kang SS, et al. Studies on Aristolochia III. Isolation
and biological evaluation of constituents of Aristolochia indica roots for
fertility-regulating activity. J Nat Prod. 1984;47:331–41.
5. Dharmalingam SR, Madhappan R, Ramamurthy S, et al. Investigation on
antidiarrhoeal activity of Aristolochia indica Linn. root extracts in mice.
Afr J Tradit Complement Altern Med. 2014;11:292–4.
6. Ganguly T, Pakrashi A, Pal AK. Disruption of pregnancy in mouse by
aristolic acid: I. Plausible explanation in relation to early pregnancy events.
Contraception. 1986;34:625–37.
7. Hartwell JL, Abbott BJ. Antineoplastic principles in plants: recent develop-
ments in the field. Adv Pharmacol. 1969;7:117–209.
Aristolochia indica L. 329

8. Heinrich M, Chan J, Wanke S, Neinhuis C, Simmonds MS. Local uses of

Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2—a
global assessment based on bibliographic sources. J Ethnopharmacol. 2009;
125:108–44.
9. Kupchan SM, Doskotch RW. Tumor inhibitors. I. Aristolochic acid, the
active principle of Aristolochia indica. J Med Pharm Chem. 1962;5:657–9.
10. Kupchan SM, Merianos JJ. The isolation and structural elucidation of novel
derivatives of aristolochic acid from Aristolochia indica. J Org Chem.
1968;33:3735–8.
11. Malhi BS, Trivedi VP. Vegetable antifertility drugs of India. Quart J Crude
Drug Res. 1972;12:1922.
12. Mathew JE, Kaitheri SK, Dinakaranvachala S, Jose M. Anti-inflammatory,
antipruritic and mast cell stabilizing activity of Aristolochia indica. Iran J
Basic Med Sci. 2011;14:422–7.
13. Pakrashi A, Chakrabarty B, Dasgupta A. Effect of the extracts from
Aristolochia indica Linn. on interception in female mice. Experientia.
1976;32:394–5.
14. Pakrashi A, Pakrasi P. Antifertility efficacy of the plant Aristolochia indica
Linn. on mouse. Contraception. 1979;20:49–54.
15. Pakrashi A, Shaha C. Effect of a sesquiterpene from Aristolochia indica
Linn. on fertility in female mice. Experientia. 1977;33:1498–9.
16. Pakrashi A, Shaha C. Effect of methyl ester of aristolic acid from
Aristolochia indica Linn. on fertility of female mice. Experientia. 1978;34:
1192–3.
17. Ravikumar S, Nazar S, Nuralshiefa A, Abideen S. Antibacterial activity of
traditional therapeutic coastal medicinal plants against some pathogens.
J Environ Biol. 2005;26(2 Suppl):383–6.
18. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants, I. Indian J Med Sci. 1961;49:130.
19. Samy RP, Thwin MM, Gopalakrishnakone P, Ignacimuthu S. Ethnobotan-
ical survey of folk plants for the treatment of snakebites in Southern part of
Tamilnadu, India. J Ethnopharmacol. 2008;115:302–12.
20. Shafi PM, Rosamma MK, Jamil K, Reddy PS. Antibacterial activity of the
essential oil from Aristolochia indica. Fitoterapia. 2002;73:439–41.
21. Sini S, Malathy NS. Antimicrobial properties of roots of medicinal plants.
Anc Sci Life. 2005;25:62–5.
22. Venkatadri B, Arunagirinathan N, Rameshkumar MR, et al. In vitro
antibacterial activity of aqueous and ethanol extracts of Aristolochia indica
and Toddalia asiatica against multidrug-resistant bacteria. Indian J Pharm
Sci. 2015;77:788–91.
Aristolochia rotunda L.
(Aristolochiaceae)

Abstract
It is the female of A. longa, commonly found in the Mediterranean countries,
south of Europe, Central Asia, and Kashmir; both A. longa and A. rotunda also
grow in Iran and Iraq. The plant is regarded resolvent, deobstruent, expectorant,
emollient, emmenagogue, aphrodisiac, and analgesic; also described as stom-
achic, stimulating and cephalic, and for the treatment of amenorrhea, pectoral
diseases, such as chronic cough and asthma. Its decoction (internally) and paste
(externally), are used in arthritis, sciatica, pleurisy, chronic pains, hepatitis and
splenitis. This is one of the plants included in this book that has not been
investigated, though unlikely, phytochemically and pharmacologically.

Keywords



Aristoloche arrondie Aristoloquia redonda Nukhud-alward Round-leaved





birthwort Knollige osterluzei Smearwort Zarawand-e-gird Zarawand-



mudahraj Zeravent otu

Vernaculars: Urd.: Zarawand-mudahraj; Hin.: Zarawand-gird; Ara.: Nukhud-

alward, Zarawand-e-gird; Eng.: Apple of the Earth, Mercury goosefoot, Round-
leaved birthwort, Smearwort; Fin.: Sepopiippuköynnös; Fre.: Aristoloche à feuilles
rondes, Aristoloche arrondie, Aristoloche ronde; Ger.: Knollige osterluzei, Rund-
blättrige osterluzei, Runde osterluzei, Rundknollige osterluzei; Ita.: Aristolochia
rotonda; Per.: Zãrãwand-gird, Zãrãwand-mudahraj; Spa.: Aristoloquia redonda;
Tur.: Zeravent otu.
Description: It is the female of A. longa, commonly found in the Mediterranean
countries, south of Europe, Central Asia, and Kashmir; both A. longa and A. rotunda
also grow in Iran and Iraq. A small plant with slender stems and almost sessile,
obtusely cardiform leaves; flowers are solitary in the axils of the leaves, tubular, yellow
outside and orange-brown within. Whole plant is acrid, aromatic and bitter. The root is

© Springer Nature Switzerland AG 2020 331

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_33
332 Aristolochia rotunda L.

tuberous, placentiform, hard and heavy when dry; more or less mammillated on the
undersurface, of a reddish-brown color; on the upper surface are the remains of several
stems or small pits showing where they were attached. On undersurface one central
scar marking the attachment of the rootlets. It has a bitterish, somewhat aromatic taste,
and camphoraceous odor (Figs. 1 and 2).XL

Fig. 1 Aristolochia rotunda, Plant (Italy), Hectonichus, WikimediaCommons; ShareAlike 3.0 Un-
ported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Aristolochiaceae_-_Aristolochia_
rotunda-3.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Aristolochia rotunda, Plant (Greece), Haplochromis, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Aristolochia_rotunda.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Aristolochia rotunda L. 333

Actions and Uses: It is a different species of Aristolochia than many others used
around the world. It is described hot 2° and dry 2° in temperament, and is regarded
resolvent, deobstruent, expectorant, emollient, emmenagogue, aphrodisiac, and
analgesic.LXXVII Dymock et al.XL also mentioned it stomachic, stimulating and
cephalic, and for the treatment of amenorrhea, pectoral diseases, such as chronic
cough and asthma, and as an ingredient of polyherbal aphrodisiac preparations. Its
decoction (internally) and paste (externally), are used in arthritis, sciatica, pleurisy,
chronic pains, hepatitis and splenitis.L,LXXVII,LXXXI Externally, wounds are washed
with it, and the powder is sprinkled on them.1 It is also added to ointments used for
foul ulcers. It is also described as carminative and anti-inflammatory, and beneficial
in headaches, migraine, epilepsy, melancholy, hiccough and jaundice; and also as
an antidote to plant and animal poisons.L
Phytoconstituents: This species has not been studied, though very unlikely, but
there are no reports on its phytochemistry or pharmacology listed on PubMed until
08/03/2018.
Human A/Es, Allergy and Toxicity: Toxic to spleen; and causes ‘dryness of
nerves.’LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: One of the commonly used plants in Unani medicine that has been
completely ignored for any phytochemical, pharmacological or clinical studies.

1
Tayyab M: Personal Communication.
Artemisia absinthium L.
(Asteraceae/Compositae)

(Syns.: A. absinthia St.-Lag.; A. baldaccii Degen; A. doonense Royle; A. inodora

Mill.; A. pendula Salisb.; A. rehan Chiov.; A. rhaetica Brügger; Absinthium officinale
Brot.; A. vulgare (L.) Lam.)

Abstract
An herbaceous perennial ornamental plant indigenous to Europe, Asia and
mountainous districts of India, cultivated in the United States, and grows in
waste places on chalky soils. The abortive properties and the toxicity of its
essential oil are known since antiquity; its abortifacient effect has been observed
in humans; its leaves and flowers are reported emmenagogue. Pliny said that
traveler who has the herb tied about him feel no wearisomeness and cannot be
hurt by poisonous medicines, nor by any wild beast. It is described as astringent,
deobstruent, anti-inflammatory, diuretic, expels bilious humours, strengthens
stomach and liver, and is beneficial in chronic fevers and scorpion bites. Steeped
in vinegar it is used as fomentation to head in cephalalgia, to joints in gout and
rheumatism, and for painful sprains and bruises. It is also used in hysteria, in
spasmodic afflictions like epilepsy, in nervous irritability, depression, and mental
exhaustion. The herbage or its juices are used for various types of cancers and
indurations of the breast, foot, larynx, liver, sinax, spleen, stomach, testicles,
tongue, and uterus, but the oil is a narcotic poison. In Iranian traditional
medicine, it is known as an orexigenic (appetite stimulating) herb, and applied
topically to abdomen for stomach weakness, swelling and pain, gastric abscess,
vomiting, diarrhea and intestinal worms, and used as insect and mosquito
repellent. In Uighur traditional medicine, it is used for the treatment of liver
disorders. It is the most commonly used herbs for treatment of neonatal jaundice,
and is available in China as a decoction. In Korean traditional medicine, it has
been used to clear ‘damp heat’ and to treat uteritis, and jaundice. In rural
Dominican medical practices, wormwood is used to treat intestinal parasites. In
Trinidad and Tobago, it is used for menstrual pain, reproductive issues, and
unspecified female complaints. In Central Italy, it is used as antiparasitic and
insect repellent, and for tendon inflammation. It was also the main ingredient of
a bitter alcoholic drink marketed in Europe as ‘Absinthe’ which was popular in

© Springer Nature Switzerland AG 2020 335

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_34
336 Artemisia absinthium L.

certain artistic circles and reputed to stimulate creativity and possessed exciting,
aphrodisiacal and healing properties. A. absinthium is approved for GI disorders
use in Europe since Nov. 2005, by the HMPC of the European Medicines
Agency.

Keywords
Absinthe
Afsantin
Damanaka-bheda
Machiparna
Mugwort
Pelinotu

Qaisoom
Shih-rumi
Wormwood
Yang ai

Vernaculars: Urd.: Afsantin, Qaisoom (BaitarTrans.); Hin.: Duna murwa, Gund-

marmastaru, Machiparna, Vilayatiafsantin; San.: Damanaka-bheda, Indhana; Ben.:
Mastaru, Nagdoni; Mal.: Nilampala, Tirunitri-pachcha; Mar.: Surpana; Tam.:
Machipattri; Tel.: Maachipatri, Moshe-patre, Tartiha; Ara.: Afsantin-e-hindi, Kasus-
rumi, Shih-rumi; Chi.: 中亚苦蒿, Ai-yeh, Ou zhou ai (Taiwan), Yang ai; Cze.:
Pelyněk pravý; Dan.: Havemalurt, Malurt; Dut.: Absint, Absint-alsem, Alsem; Eng.:
Absinthium, Absinth sagewort, Mugwort, Wormwood; Fin.: Koiruoho, Mali; Fre.:
Absinthe, Aluine, Armoise absinthe, Armoise amère, Genépi, Grande absinthe; Ger.:
Absinth, Echter wermut, Wurmkraut; Gre.: Awέmsi, Awihiά; Ita.: Assenzio maggiore,
Assenzio romano, Assenzio vero; Jap.: Niga-yomogi, Wamuddo; Kor.: Weom-u-deu,
Weomudu; Nor.: Ekte malurt, Malurt; Per.: Afsantin, Barunjasif-i-kohi, Boyi madran;
Pol.: Bylica piołun, Piołun; Por.: Absinto, Acinto, Amargoso, Citronela-maior,
Erva-das-sezões, Grande-absinto, Losna; Rus.: Polyn’ gor’kaia; Spa.: Absintio,
Ajenjo, Ajenjo mayor; Swe.: Äkta malört, Malört; Tur.: Acı pelin, Pelinotu; Vie.: Cây
ngải đắng, Ngải áp xanh, Ngải đắng.
Description: An ornamental plant indigenous to Europe, Asia and mountainous
districts of India, cultivated in the United States, and grows in waste places on chalky
soils. Arab physicians, such as Ghafiqi, Al-Biruni and Ibn Masawaiyh described
various kinds of wormwood, viz. Nabataean, Khurasanian, Syrian and North African;
the Syrian was considered to be the best.LIII An herbaceous perennial plant, 0.8–1.2 m
tall, that grows naturally on uncultivated arid ground, or rocky slopes; stems are
grooved, branched, and silvery-green. Leaves, greenish-grey above and white below,
covered with silky silvery-white trichomes, are spirally arranged, and bear minute
oil-producing glands. Basal leaves are up to 25 cm long, bipinnate to tripinnate with
long petioles, and the cauline leaves smaller, 5–10 cm long, less divided, and with
short petioles. It flowers from early summer to early autumn; flowers are pale-yellow,
tubular, and clustered (Figs. 1 and 2).
Actions and Uses: The abortive properties and the toxicity of the essential oil are
known since antiquity [46]; its abortifacient effect has been observed in humans [45];
and leaves and flowers are reported emmenagogue.CXII Pliny said that traveler who has
the herb tied about him feel no wearisomeness and cannot be hurt by poisonous
medicines, nor by any wild beast, and it is drunk against opium and juice of black
poppy.VI Ibn al-BaitarLXIX quoting various references mentioned it to be astringent,
Artemisia absinthium L. 337

Fig. 1 Artemisia absinthium, Plant, David Monniaux, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Artemisia_absinthium_
P1210748.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Artemisia absinthium, Leaves and Flowers, H. Zell, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Artemisia_absinthium_0002.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en
338 Artemisia absinthium L.

deobstruent, anti-inflammatory, diuretic, expels bilious humours, strengthens stom-

ach and liver, and is beneficial in chronic fevers and scorpion bites. It is one of the
frequently cited drugs (16 times) in The Chilandar Medical Codex, the best preserved
medieval Serbian manuscript on European medical science from the 12th to fifteenth
centuries [16]. A. maritima is the species that is indigenous to Europe and Russia, and
is known as sea wormwood, and Old Woman. In Unani medicine, A. absinthium
(temperament, hot 3° and dry 3°) is regarded deobstruent, carminative, demulcent,
diaphoretic, emmenagogue, appetizer, expels bilious and black bile from the body; its
decoction is used in chronic humoural fevers due to blood infection, and phlegmatic
diseases, such as paralysis, facial palsy, tremors, and epilepsy.L Tayyab1 regarded it as
the ‘Drug of Choice’ in patients with ascites, liver diseases and fever. It is a bitter
stomachic tonic, increases appetite, promotes digestion, and is used for dyspepsia;
stimulates heart and the brain, irritates stomach, and causes morning nausea and
vomiting. Steeped in vinegar it is used as fomentation to head in cephalalgia, to joints
in gout and rheumatism, and for painful sprains and bruises. It is also used in hysteria,
in spasmodic afflictions like epilepsy, in nervous irritability, depression, and mental
exhaustion.LXXXI The herbage or its juices are used for various types of cancers and
indurations of the breast, foot, larynx, liver, sinax, spleen, stomach, testicles, tongue,
and uterus,XXXVIII but the oil is a narcotic poison.CV In Iranian traditional medicine,
it is known as an orexigenic (appetite stimulating) herb [4], and applied topically to
abdomen for stomach weakness, swelling and pain, gastric abscess, vomiting, diarrhea
and intestinal worms [48], and used as insect and mosquito repellent [7]. In Uighur
traditional medicine, it is used for the treatment of liver disorders [2]. It is the most
commonly used herbs for treatment of neonatal jaundice (95%), and is available in
China as a decoction, Artemisia Composite, and as an intravenous preparation [9, 14].
Another species of Artemisia, also described as wormwood, A. argyi is known as the
herb of moxibustion, and is used for treatment of irregular menstruation, leucorrhea
with or without blood, unstable fetus, prolonged diarrhea, hemoptysis, nosebleed and
as an assistant drug for gynecological disorders.LXVI In Korean traditional medicine, it
has been used to clear ‘damp heat’ and to treat uteritis, and jaundice [31]. In rural
Dominican medical practices, wormwood is used to treat intestinal parasites [41].
In Trinidad and Tobago, it is used for menstrual pain, reproductive issues, and
unspecified female complaints [30]. Crushed in vinegar and applied to the body, it
repels fleas and flies; and mice are said not to eat books written with ink in which
wormwood was boiled. Fresh branches are placed to repel mosquitoesC and the
volatile oil kills house flies.
In Central Italy, it is used as antiparasitic and insect repellent [12], and for
tendon inflammation [13]. It was also the main ingredient of a bitter alcoholic drink
marketed in Europe as ‘Absinthe’ which was popular in certain artistic circles and
reputed to stimulate creativity and possessed exciting, aphrodisiacal and healing
properties [10]. Absinthe was banned at the beginning of the twentieth century
because of its supposed unique adverse effects (absinthism), attributed to its thujone
contents, manifesting as hallucinations, sleeplessness and convulsions [27, 28, 40].

1
Tayyab M: Personal Communication.
Artemisia absinthium L. 339

Vincent van Gogh’s experience with hallucinations were attributed to congenital

psychosis, episodes of heavy drinking and addiction to Absinthe [3]. A. absinthium
is approved for GI disorders use in Europe since Nov. 2005, by the HMPC of the
European Medicines Agency.
Phytoconstituents: The herb contains EO, bitter glucoside absinthin, absinthic
acid, anabsinthin, astabsin, artametin, succinic acid, together with tannin, resin,
starch, malates and nitrates of potassium and other salts. The EO is a dark-green
liquid of strong camphoraceous odor and aromatic taste (yield up to 1.7%), contains
phellandrene, pinene, thujone (3–12%), thujyl alcohol, thujyl acetate, thujyl iso-
valerate, bisabolene, thujyl palmitate, camphene, cadinene, nerol and azulene.LXXXI
(Z)-anethole, (Z)-b-ocimene, (E)-b-ocimene, limonene, methyleugenol, camphor,
chamazulene, 1,8-cineole, nuciferol propionate, nuciferol butanoate, caryophyllene
oxide, borneol, a-terpineol, spathulenol, cubenol, b-eudesmol, and terpinen-4-ol are
the major constituents of EO of Turkish A. absinthium [23, 24]; whereas high
amounts of myrcene, trans-thujone and trans-sabinyl acetate out of 110 constituents
in Canadian samples were reported, and the oil showed significant antimicrobial
activity against Staphylococcus strains [32]. The oil from Iranian samples contained
twenty-eight components representing 93.3% of the oil; monoterpenes (b-pinene
and b-thujone) were the main components [42]. In the oil from Indian variety 64
compounds were identified; major ones being borneol, methyl hinokiate, isobornyl
acetate, b-gurjunene and caryophyllene oxide [17]. Characteristic volatiles from leaf
extracts of Swedish A. absinthium are reported as sabinene, oxygenated monoter-
penes, e.g. thujenol and linalool, and geranyl acetate [15]. Essential oil from aerial
parts in Serbia yielded 47 compounds, corresponding to 94.65% of the total oil, with
the main constituents being sabinene, sabinyl acetate, and a-phellandrene [34]. The
oil obtained from aerial parts in Romania had b-thujone and nerol as major com-
pounds, along with estragole, spathulenol, a-bisabolol and herniarin; whereas the
commercial sample had b-thujone, sabinyl acetate and a-thujone as the main com-
pounds [38]. The EO of French origin contain (Z)-epoxyocimene and chrysanthenyl
acetate as major components, while oils of Croatian origin contain mainly (Z)-
epoxyocimene and b-thujone [18]. Lactones include arabsin, artabin, and ketope-
lenolide, and the total content of bitter principle fluctuates between 0.1 and 0.4%; the
bitter principles were identified as: artamarine, artamarinine, artamaridine and
artamaridinine [44].
Pharmacology: Aqueous ethanol and methanol extracts show antioxidative activ-
ity, and inhibit LPO [5, 8, 19]. Brain oxidative stress and damage, and behavioral
deficit caused by focal I/R injury is significantly attenuated by pretreatment with
methanol extract [6]. Pretreatment of rats with aqueous methanol extract signifi-
cantly prevents APAP- and CCl4-induced rise in serum transaminases, and
post-treatment with three successive doses restricts APAP-induced hepatic damage.
While APAP in a dose of 1 g/kg caused 100% mortality in mice, pretreatment with
wormwood extract (500 mg/kg) reduced death rate to 20% [11]. Pretreatment with
340 Artemisia absinthium L.

aqueous extract was also significantly hepatoprotective against CCl4- or immuno-

logically induced liver damage, and significantly reduced LPO in the liver tissue, and
restored activities of antioxidant enzymes to normal levels [2, 43]. Hydroalcohol
extract did not produce any orexigenic effects in rats [4].
Methanol extract inhibits carrageenan- and viper venom-induced paw inflammation
in rats [37], while hexane extract exhibits significant antipyretic activity against
yeast-induced pyrexia in rabbits, comparable to aspirin [20]. The EO shows antifungal
activity against C. albicans [38], and topical application of hydroalcohol extract to
infected wound shows significant antibacterial activity against S. aureus [35]. French
origin EO inhibited growth of C. albicans and S. cerevisiae var. chevalieri [18].
Aqueous and methanol extracts exhibited significant antitrypanosomal potential
against T. congolense, as they reduced parasitemia, maintained body weight, and
prolonged lives of infected animals [21], whereas EO demonstrated in vitro antile
ishmania activity [49]. Incubation of human breast cancer estrogen-unresponsive
(MDA-MB-231) and estrogen-responsive (MCF-7) cells with the extract triggers
apoptosis in both cell lines [47].
Clinical Studies: Supplementation of 10 German patients with biopsy-proven early
stage IgA nephropathy and at least a history of 3-months proteinuria, with 1.8 g/d of
thujone-free wormwood preparation for 6-months without discontinuing their dual
renin-angiotensin system blockade resulted in a significant decrease in urine
protein-creatinine ratio and a significant decrease in mean arterial BP that was stable
during supplement-free follow-up of another 6 months [25]. Addition of 3  750 mg
dried powdered wormwood for 6-weeks to standard treatment in 10 patients with
Crohn’s Disease (CD) significantly decreased TNF-a level from 24.5 ± 3.5 pg/ml at
baseline to 8.0 ± 2.5 pg/ml after six-weeks, with remission of symptoms in eight
patients and improvement in patients’ mood [26]. In a double-blind, placebo con-
trolled trial of 40 CD patient, addition of wormwood to standard treatment, 18 patients
(90%) who received wormwood had steady improvement in CD symptoms in spite of
tapering of steroids and almost complete remission of symptoms in 13 (65%) patients
compared to none in the placebo group after 8-weeks of treatment. The remission
persisted till the end of 20-week observation period, and did not require addition of
steroids [39].
Mechanism of Action: Some authors proposed that the mind-altering effect of
wormwood is due to thujone reacting with the same receptor sites in the brain as
those that interact with tetrahydrocannabinol (THC). Thujone and THC have similar
functional groups allowing them to ‘fit’ a common receptor site without changing
orientations or relative positions.CXXXIII Meschler and Howlett [33], however,
reported that thujone exhibits low affinity for cannabinoid receptors and does not
evoke cannabimimetic responses. If threshold concentrations are exceeded, thujone
can exhibit neurotoxic properties leading to dose-dependent tonic-clonic seizures in
animals, likely caused by GABA type A receptor modulation [29]. Antioxidative
activity, and inhibition of LPO may contribute to amelioration of brain oxidative
stress damage [5, 8, 19]. Modulation of Bcl-2 family proteins and the MEK/ERK
pathway were suggestively involved in the apoptosis of human breast cancer cell
Artemisia absinthium L. 341

lines [47]. Reduction in proinflammatory cytokines, such as TNF-a may contribute

to its anti-inflammatory effect [26].
Human A/Es, Allergy and Toxicity: Extremely bad for stomach (Galen). Habitual
use or large doses may cause convulsions, insomnia, nausea, nightmare, restlessness,
tremors and vertigo in humans.XXXVIII Flowers and leaves are photosensitizers;CXXXV
though, none of the 30 healthy volunteers developed a positive skin irritant reaction to
application of undiluted EO from Serbia [34]. A 10-month-old male infant suffered
from progressive severe diarrhea and persistent metabolic acidosis after administra-
tion of home-prepared A. absinthium extract to treat common cold [22].
Animal Toxicity: Wormwood extract did not cause any observable adverse effects
in Wistar Hannover rats following repeated administration of 2% extract in water
(equivalent to 1.27 g/kg/day in males and 2.06 g/kg/day in females) for 13-weeks
[36]. Acute oral exposure to EO did not cause mortality in mice, but it did cause
neurological, muscle and gastrointestinal problems [34].
Potential for Drug-Herb Interactions: An 82-year-old Turkish woman, being
treated with warfarin for atrial fibrillation, developed gastrointestinal bleeding as a
result of extremely elevated INR after consuming A. absinthium [1]. Potentiation of
the anticoagulant effect of warfarin could be the result of a direct anticoagulant
effect of wormwood or inhibition of metabolism of warfarin, or some other unlikely
mechanism that needs to be determined. Intake of Absinthii herba preparations
might also influence effects of prescription drugs acting via GABA receptor (e.g.
barbiturates, benzodiazepines), even if not yet observed clinically.
Commentary: This is one of the most commonly used herbs for liver disorders in
traditional medicines, yet no organized clinical studies are reported for this effect. It
also offered potential clinical benefits in nephropathy and Crohn’s Disease, that
could be further explored clinically through RCTs in larger number of patients.

References
1. Açıkgöz SK, Açıkgöz E. Gastrointestinal bleeding secondary to interaction
of Artemisia absinthium with warfarin. Drug Metabol Drug Interact. 2013;28:
187–9.
2. Amat N, Upur H, Blazeković B. In vivo hepatoprotective activity of the
aqueous extract of Artemisia absinthium L. against chemically and immuno-
logically induced liver injuries in mice. J Ethnopharmacol. 2010;131:478–84.
3. Arnold WN. Vincent van Gogh and the thujone connection. JAMA. 1988;260:
3042–4.
4. Baghban Taraghdari S, Nematy M, Mazidi M, et al. The effect of hydroalco-
holic extract of Artemisia absinthium on appetite in male rats. Avicenna J
Phytomed. 2015;5:78–83.
5. Bora KS, Sharma A. Evaluation of antioxidant and free-radical scavenging
potential of Artemisia absinthium. Pharm Biol. 2011;49:1216–23.
342 Artemisia absinthium L.

6. Bora KS, Sharma A. Neuroprotective effect of Artemisia absinthium L. on

focal ischemia and reperfusion-induced cerebral injury. J Ethnopharmacol.
2010;129:403–9.
7. Cheraghi Niroumand M, Farzaei MH, Karimpour Razkenari E, et al. An
evidence-based review on medicinal plants used as insecticide and insect
repellent in traditional Iranian medicine. Iran Red Crescent Med J. 2016;18:
e22361.
8. Craciunescu O, Constantin D, Gaspar A, et al. Evaluation of antioxidant and
cytoprotective activities of Arnica montana L. and Artemisia absinthium L.
ethanolic extracts. Chem Cent J. 2012;6:97.
9. Fok TF. Neonatal jaundice—traditional Chinese medicine approach. J
Perinatol 21 Suppl 1: S98-S100; discussion. 2001;S104–7.
10. Gambelunghe C, Melai P. Absinthe: enjoying a new popularity among
young people? Forensic Sci Int. 2002;130:183–6.
11. Gilani AH, Janbaz KH. Preventive and curative effects of Artemisia
absinthium on acetaminophen and CCl4-induced hepatotoxicity. Gen Phar-
macol. 1995;26:309–15.
12. Guarrera PM. Traditional antihelmintic, antiparasitic and repellent uses of
plants in Central Italy. J Ethnopharmacol. 1999;68:183–92.
13. Guarrera PM. Traditional phytotherapy in Central Italy (Marche, Abruzzo,
and Latium). Fitoterapia. 2005;76:1–25 (Review).
14. Ho NK. Traditional Chinese medicine and treatment of neonatal jaundice.
Singapore Med J. 1996;37:645–51 (Review).
15. Jaenson TG, Pålsson K, Borg-Karlson AK. Evaluation of extracts and oils
of tick-repellent plants from Sweden. Med Vet Entomol. 2005;19:345–52.
16. Jarić S, Mitrović M, Djurdjević L, et al. Phytotherapy in medieval Serbian
medicine according to the pharmacological manuscripts of the Chilandar
Medical Codex (15-16th centuries). J Ethnopharmacol. 2011;137:601–19.
17. Joshi RK. Volatile composition and antimicrobial activity of the essential oil
of Artemisia absinthium growing in Western Ghats region of North West
Karnataka India. Pharm Biol. 2013;51:888–92.
18. Juteau F, Jerkovic I, Masotti V, et al. Composition and antimicrobial
activity of the essential oil of Artemisia absinthium from Croatia and
France. Planta Med. 2003;69:158–61.
19. Kharoubi O, Slimani M, Krouf D, Seddik L, Aoues A. Role of wormwood
(Artemisia absinthium) extract on oxidative stress in ameliorating lead induced
haematotoxicity. Afr J Tradit Complement Altern Med. 2008;5:263–70.
20. Khattak SG, Gilani SN, Ikram M. Antipyretic studies on some indigenous
Pakistani medicinal plants. J Ethnopharmacol. 1985;14:45–51.
21. Kifleyohannes T, Terefe G, Tolossa YH, Giday M, Kebede N. Effect of
crude extracts of Moringa stenopetala and Artemisia absinthium on
parasitaemia of mice infected with Trypanosoma congolense. BMC Res
Notes. 2014;7:390.
22. Kocaoglu C, Ozel A. Persistent metabolic acidosis and severe diarrhoea due
to Artemisia absinthium poisoning. J Pak Med Assoc. 2014;64:1081–3.
Artemisia absinthium L. 343

23. Kordali S, Cakir A, Mavi A, et al. Screening of chemical composition and

antifungal and antioxidant activities of the essential oils from three Turkish
artemisia species. J Agric Food Chem. 2005;53:1408–16.
24. Kordali S, Kotan R, Mavi A, et al. Determination of the chemical composition
and antioxidant activity of the essential oil of Artemisia dracunculus and of
the antifungal and antibacterial activities of Turkish Artemisia absinthium, A.
dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils.
J Agric Food Chem. 2005;53:9452–8.
25. Krebs S, Omer B, Omer TN, Fliser D. Wormwood (Artemisia absinthium)
for poorly responsive early-stage IgA nephropathy: a pilot uncontrolled
trial. Am J Kidney Dis. 2010;56:1095–9.
26. Krebs S, Omer TN, Omer B. Wormwood (Artemisia absinthium) suppresses
tumour necrosis factor alpha and accelerates healing in patients with Crohn’s
disease—a controlled clinical trial. Phytomedicine. 2010;17:305–9.
27. Lachenmeier DW, Emmert J, Kuballa T, Sartor G. Thujone—cause of
absinthism? Forensic Sci Int. 2006;158:1–8.
28. Lachenmeier DW, Walch SG, Padosch SA, Kröner LU. Absinthe—a
review. Crit Rev Food Sci Nutr. 2006;46:365–77.
29. Lachenmeier DW. Wormwood (Artemisia absinthium L.)—a curious plant
with both neurotoxic and neuroprotective properties? J Ethnopharmacol.
2010;131:224–7.
30. Lans C. Ethnomedicines used in Trinidad and Tobago for reproductive
problems. J Ethnobiol Ethnomed. 2007;3:13.
31. Lee HG, Kim H, Oh WK, et al. Tetramethoxyhydroxyflavone p7F down-
regulates inflammatory mediators via the inhibition of nuclear factor kappaB.
Ann N Y Acad Sci. 2004;1030:555–68.
32. Lopes-Lutz D, Alviano DS, Alviano CS, Kolodziejczyk PP. Screening of
chemical composition, antimicrobial and antioxidant activities of Artemisia
essential oils. Phytochemistry. 2008;69:1732–8.
33. Meschler JP, Howlett AC. Thujone exhibits low affinity for cannabinoid
receptors but fails to evoke cannabimimetic responses. Pharmacol Biochem
Behav. 1999;62:473–80.
34. Mihajilov-Krstev T, Jovanović B, Jović J, et al. Antimicrobial, antioxida-
tive, and insect repellent effects of Artemisia absinthium essential oil. Planta
Med. 2014;80:1698–705.
35. Moslemi HR, Hoseinzadeh H, Badouei MA, Kafshdouzan K, Fard RM.
Antimicrobial activity of Artemisia absinthium against surgical wounds
infected by Staphylococcus aureus in a rat model. Indian J Microbiol. 2012;
52:601–4.
36. Muto T, Watanabe T, Okamura M, et al. Thirteen-week repeated dose
toxicity study of wormwood (Artemisia absinthium) extract in rats. J Toxicol
Sci. 2003;28:471–8.
37. Nalbantsoy A, Erel SB, Köksal C, et al. Viper venom induced inflammation
with Montivipera xanthina (Gray, 1849) and the antisnake venom activities
of Artemisia absinthium L. in rat. Toxicon. 2013;65C:34–40.
344 Artemisia absinthium L.

38. Obistioiu D, Cristina RT, Schmerold I, et al. Chemical characterization by

GC-MS and in vitro activity against Candida albicans of volatile fractions
prepared from Artemisia dracunculus, Artemisia abrotanum, Artemisia
absinthium and Artemisia vulgaris. Chem Cent J. 2014;8:6.
39. Omer B, Krebs S, Omer H, Noor TO. Steroid-sparing effect of wormwood
(Artemisia absinthium) in Crohn’s disease: a double-blind placebo-controlled
study. Phytomedicine. 2007;14:87–95.
40. Padosch SA, Lachenmeier DW, Kröner LU. Absinthism: a fictitious 19th
century syndrome with present impact. Subst Abuse Treat Prev Policy. 2006;
1:14.
41. Quinlan MB, Quinlan RJ, Nolan JM. Ethnophysiology and herbal treatments
of intestinal worms in Dominica. West Indies. J Ethnopharmacol. 2002;80:
75–83.
42. Rezaeinodehi A, Khangholi S. Chemical composition of the essential oil of
Artemisia absinthium growing wild in Iran. Pak J Biol Sci. 2008;11:946–9.
43. Saxena M, Shukla S. Reversal of carbon tetrachloride-induced hepatic injury
by aqueous extract of Artemisia absinthium in Sprague-Dawley rats.
J Environ Pathol Toxicol Oncol. 2012;31:325–34.
44. Schenk G, Schuster NE. The bitter principles of Artemisia absinthium. Arch
Pharm U Ber Deutsch Pharm Ges. 1956;289:1–8.
45. Schifferli E. Deut Z Gesamte Gerichtl Med. 1939;31:239.
46. Schifferli E. Quoted by Farnsworth N et al in Potential value of plant
sources as new antifertility agents. II. J Pharmaceut Sci 1975;64:535–98.
47. Shafi G, Hasan TN, Syed NA, et al. Artemisia absinthium (AA): a novel
potential complementary and alternative medicine for breast cancer. Mol
Biol Rep. 2012;39:7373–9.
48. Tafti LD, Shariatpanahi SM, Damghani MM, Javadi B. Traditional Persian
topical medications for gastrointestinal diseases. Iran J Basic Med Sci. 2017;
20:222–41.
49. Tariku Y, Hymete A, Hailu A, Rohloff J. In vitro evaluation of antileish-
manial activity and toxicity of essential oils of Artemisia absinthium and
Echinops kebericho. Chem Biodivers. 2011;8:614–23.
Artemisia vulgaris L.
(Asteraceae/Compositae)

(Syn.: A. superba Pamp.)

Abstract
This perennial herb is found in China, Asia, Europe, and North Africa. In Unani
medicine, aerial parts are described as deobstruent, counterirritant, diuretic,
emmenagogue, lithotriptic, anti-inflammatory and antipyretic, and used for urine
and menstrual retention, to help in delivery and expulsion of placenta. The plant
has been used for cancerous lesions, indurations, scirrhus, especially of spleen,
stomach and uterus. Infusion of leaves and flowering tops is administered in
nervous and spasmodic affections, in asthma and diseases of the brain; leaves are
smoked to alleviate asthma. In the Philippines and Brazil, leaves are widely used
as analgesic, anti-inflammatory and antispasmodic agents. In Java, poultices of
the herb are applied to old sores, scurvy and other skin afflictions. Native
Americans used leaf decoction for bladder ailments, cold, bronchitis, colic,
dysmenorrhea, epilepsy, fever, gout, hysteria, kidney ailments, poisoning,
sciatica, rheumatism, worms and wounds. Fresh plant is said to ease itch of
poison ivy. Russians use the herb for abortion, amenorrhea, dysmenorrhea,
bladder stones, cold, convulsions, cramps, epilepsy, fever, fear, gall stones,
gastritis, inflammation, as diuretic, for kidney stones, labor, nervousness,
neurasthenia, rickets, sores, tuberculosis, and wounds. The leaves, per 100 g
contain 35 calories, protein, fat, carbohydrate, fiber, ash, Ca, P, iron, b-carotene,
thiamine, riboflavin, niacin, and ascorbic acid. EO contains mainly cineol, along
with quebrachitol, tauremisin, sitosterol, tetracosanol, fernenol, thujone,
a-amyrin, stigmasterol, b-sitosterol, and a- and b-pinene. Aqueous infusion of
aerial parts protects mice against CCl4-hepatotoxicity. Pretreatment of mice with
aqueous-methanol extract of aerial parts significantly reduced toxin-induced rise
in plasma ALT and AST, against D-galactosamine- and LPS-induced hepatitis.

Keywords





Armoise citronnelle Beifuß Bijvoet Biranjasif Bue-maadran
Common



wormwood Indhana Nagadouna Sisim Ye ai


© Springer Nature Switzerland AG 2020 345
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_35
346 Artemisia vulgaris L.

Fig. 1 Artemisia vulgaris, Young Plant, Sten Porse, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Artemisia-vulgaris-young.JPG

Vernaculars: Urd.: Biranjasif1; Hin.: Dunamurwa, Gund-mar mastaru, Machi-

parna, Nagadouna; San.: Indhana, Nagadamani; Ben.: Mastaru, Nagadona,
Nagdoni; Mal.: Tirunitri-pachcha; Mar.: Surpana; Tam.: Machi-pattiri; Tel.:
Moshe-patre, Tartiha; Ara.: Shawela, Shih-Jabali; Chi.: His-ai, Shen-ai, Ye ai, Ye ai
hao; Dan.: Almindelig gråbynke, Bynke, Grå bynke, Uægte malurt; Dut.: Alsem-
soort, Bijvoet, Gewone bijvoet; Eng.: Common wormwood, Mugwort; Fin.: Pujo;
Fre.: Armoise citronnelle, Armoise commune, Armoise vulgaire, Ceinture de
Saint-Jean; Ger.: Beifuß, Echter beifuß, Gemeiner beifuß, Gewöhnlicher beifuß;
Gre.: Aqselirίa; Ita.: Amarella, Artemisia, Assenzio selvatico; Jap.: Arutemishia,
Ōshū-yomogi, Yomogi; Nor.: Burot; Per.: Biranjasif, Bue-maadran; Pol.: Bylica;
Por.: Artemisia; Rus.: Polyn’ obyknovennaia; Spa.: Corona de San Juan, Hierba de
San Juan, Sisim; Swe.: Gråbo; Tag.: Damong-maria, Kamaria, Maria, Tinisas; Vie.:
Cây ngải, Ngải cứu, Thuốc cứu, Thuộc học cúc.
Description: This perennial herb, found in China, Asia, Europe, and North Africa,
is an erect, hairy, rank-smelling, often half-woody, and 0.5–0.8 m in height. Leaves
are pinnately lobed, dark-green, 5–14 cm long, with dense white tomentose hairs on
the underside, and nearly smooth above. Flowering heads numerous, ovoid, and
3–4 mm long are radially symmetrical with many yellow or dark red petals, and
occur in large numbers in spike-like, ascending, branched inflorescences. It flowers
from July to September; the fruit (achene) is minute.CXVII Ibn al-BaitarLXIX quoting
Dioscorides describes it as an annual plant that grows near river banks and secretes
a sticky liquid; it has whitish small flowers (Figs. 1 and 2).
Actions and Uses: Ibn al-BaitarLXIX mentioned it as emmenagogue, oxytocic,
lithotriptic, and useful in anuria, and Avicenna said its paste relieves headache due
to cold, and relieves nasal congestion. In Unani medicine, aerial parts (tempera-
ment, hot 1° and dry 2°) are described as deobstruent, counterirritant, diuretic,

1
Anthemis nobilis and Matricaria chamomile are also referred to as Biranjasif in Unani Medicine.
Artemisia vulgaris L. 347

Fig. 2 Artemisia vulgaris, Mature Plant, Christian Fischer, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:ArtemisiaVulgaris.jpg

emmenagogue, lithotriptic, anti-inflammatory and antipyretic,L,LXXVII and used for

urine and menstrual retention, to help in delivery and expulsion of placenta.
Dymock et al.XL considered it a valuable stomachic, deobstruent and antispas-
modic; prescribed as an infusion in cases of obstructed menstruation and hysteria.
The plant has been used for cancerous lesions, indurations, scirrhus, especially of
spleen, stomach and uterus. Infusion of leaves and flowering tops is administered in
nervous and spasmodic affections, in asthma and diseases of the brain; leaves are
smoked to alleviate asthma.XL In the Philippines and Brazil, leaves are widely used
as analgesic, anti-inflammatory and antispasmodic agents [15, 19]. In Java, poul-
tices of the herb are applied to old sores, scurvy and other skin afflictions. Juice of
the leaves is used externally as a vulnerary, and the decocted leaves and flowering
tops are also considered expectorant and emmenagogue in the Philippines. Its
stomachic, carminative and tonic properties are also well known [8].CXVII
Expressed juice of the plant is used in diseases of children, and is applied to head of
young children to prevent convulsions [3]. In Uruguay, the plant is used as an
anthelmintic.CXX Native Americans used leaf decoction for bladder ailments, cold,
348 Artemisia vulgaris L.

bronchitis, colic, dysmenorrhea, epilepsy, fever, gout, hysteria, kidney ailments,

poisoning, sciatica, rheumatism, worms and wounds. Fresh plant is said to ease itch
of poison ivy. Russians use the herb for abortion, amenorrhea, dysmenorrhea,
bladder stones, cold, convulsions, cramps, epilepsy, fever, fear, gall stones, gas-
tritis, inflammation, as diuretic, for kidney stones, labor, nervousness, neurasthenia,
rickets, sores, tuberculosis, and wounds. Homeopaths prescribe a tincture of the
fresh root for catalepsy, chorea, convulsions, hydrocephalus, epilepsy, hysteria,
somnambulism, and worms;XXXVIII whole plant is hemostatic, and stomachic.LXXIX
Phytoconstituents: The leaves, per 100 g contain 35 calories, protein, fat, carbo-
hydrate, fiber, ash, Ca, P, iron, 2,140 µg b-carotene equivalent, thiamine, riboflavin,
niacin, and ascorbic acid. On a zero moisture basis, tops contain 11.4% crude protein,
33.5% crude fiber, ash, Ca, P, K and Mg, inulin, resin, tannin, and artemisin.XXXVIII
Aqueous infusion of aerial parts collected from Brazil contained carbohydrates
(40%), proteins (2.9%) and phenolic compounds (9.8%) [5], whereas, rutin and
caffeic acid derivatives were identified as major constituents in the hydroalcohol
extract [15]. Two guaiane sesquiterpene lactones, vulgarolides A and B have been
isolated from aerial parts [9]. Two caffeoylquinic acids, 3,5-di-O-caffeoylquinic acid
and 1,5-di-O-caffeoylquinic acid were isolated from flowering tops [4]. The plant
yields 0.03–0.2% EO, which is used as a larvicide and weak insecticide. EO contains
mainly cineol, along with quebrachitol, tauremisin, sitosterol, tetracosanol, fernenol,
thujone, a-amyrin, stigmasterol, b-sitosterol, and a- and b-pinene.XC Germacrene D,
caryophyllene, a-zingiberene and borneol are major components of leaf oil, while the
buds were rich in 1,8-cineole, camphor, borneol, and caryophyllene in widely
growing plant in Pennsylvania [21]. Davanone, estragole, davanone oil, b-thujone,
sabinyl acetate, herniarin, cis-chrysanthenyl acetate, 1,8-cineol, and terpineol were
reported in plant oil from Romania, that showed some antifungal activity against C.
albicans [14].
Pharmacology: Aqueous infusion of aerial parts protected mice against CCl4-
hepatotoxicity [5]. Hydroalcohol extract did not affect response time in hot plate, or in
immediate or late response in formalin test [15]. Aqueous and chloroform leaf extracts
do not significantly alter baseline BP, but reverse NE-induced increase in mean sys-
tolic and diastolic pressures, without any significant effect on heart rate [19, 20]. The
extract protected against castor oil-induced diarrhea and carbachol-mediated bron-
choconstriction in rodents [11]. Aqueous extract treated rats showed increased
antioxidant status, with a significant increase in blood GSH level, SOD activity, and
serum ascorbic acid level [18]. Pretreatment of mice with aqueous-methanol extract of
aerial parts significantly reduced toxin-induced rise in plasma ALT and AST, against
D-galactosamine- and LPS-induced hepatitis [7]. Essential oil extracted from buds
and leaves inhibited growth of HL-60 cells in a dose- and time-dependent manner.
Both were more efficient to induce apoptosis in different cancer cell lines than in
noncancerous cells [16].
Ethanol extract significantly inhibited parasitemia in a P. berghei ANKA murine
malaria model [1], increased survival, reversed profound thrombocytopenia/
Artemisia vulgaris L. 349

thrombocytosis, altered end-stage disease (cerebral malaria), and produced signif-

icant antipyretic and antinociceptive effects [2]. Methanol leaf extract completely
inhibited implant formation in female Wistar rats, and exerted a strong estrogenic
effect with a significant increase in uterine weight in immature ovariectomized
rats [17].
Mechanism of Action: Bronchodilatory and smooth muscle relaxant effects are
suggested to be mediated via a combination of anticholinergic, Ca2+ antagonist
[11], and histamine H1 receptors antagonism [12]. Induction of apoptosis in dif-
ferent cancer cell lines was mediated via caspase-dependent pathways [16].
Human A/Es, Allergy and Toxicity: Pollens are known to cause allergy [13],
which contain a number of cross-reactive allergens with ragweed [10, 22], and
chamomile [6]. Listed as nonspecifically harmful for kidneys,LXXVII and in large
doses, the plant is toxic, and thujone can cause epileptic spasms.
Animal Toxicity: Chronic administration of high dose of ethanol extract did not
cause any overt signs of hepatotoxicity, renotoxicity and hematotoxicity, as well as
stress in mice [1].
Commentary: There are no clinical studies reported in the publications listed on
PubMed, despite being extensively used in traditional medicines.

References
1. Bamunuarachchi GS, Ratnasooriya WD, Premakumara S, Udagama PV.
Antimalarial properties of Artemisia vulgaris L. ethanolic leaf extract in a
Plasmodium berghei murine malaria model. J Vector Borne Dis. 2013;50:
278–84.
2. Bamunuarachchi GS, Ratnasooriya WD, Premakumara S, Udagama PV.
Artemisia vulgaris L. ethanolic leaf extract reverses thrombocytopenia/
thrombocytosis and averts end-stage disease of experimental severe Plas-
modium berghei murine malaria. J Vector Borne Dis. 2014;51:286–93.
3. Caius JF. The medicinal and poisonous composites of India. J Bombay Nat
Hist Soc. 1940;41:607.
4. Carnat A, Heitz A, Fraisse D, et al. Major dicaffeoylquinic acids from
Artemisia vulgaris. Fitoterapia. 2000;71:587–9.
5. Corrêa-Ferreira ML, Verdan MH, Dos Reis Lívero FA, et al. Inulin-type
fructan and infusion of Artemisia vulgaris protect the liver against carbon
tetrachloride-induced liver injury. Phytomedicine. 2017;24:68–76.
6. de la Torre Morín F, Sánchez Machín I, García Robaina JC, et al. Clinical
cross-reactivity between Artemisia vulgaris and Matricaria chamomilla
(chamomile). J Investig Allergol Clin Immunol. 2001;11:118–22.
7. Gilani AH, Yaeesh S, Jamal Q, Ghayur MN. Hepatoprotective activity of
aqueous-methanol extract of Artemisia vulgaris. Phytother Res. 2005;19:
170–2.
350 Artemisia vulgaris L.

8. Guerrero Leon MA. Medicinal uses of Philippine plants. Philip Bur Forestry
Bull. 1921;22:149–246.
9. Hanh TTH, Hang LTT, Huong PTT, et al. Two new guaiane sesquiterpene
lactones from the aerial parts of Artemisia vulgaris. J Asian Nat Prod
Res. 2017;25:1–5.
10. Hirschwehr R, Heppner C, Spitzauer S, et al. Identification of common
allergenic structures in mugwort and ragweed pollen. J Allergy Clin
Immunol. 1998;101:196–206.
11. Khan AU, Gilani AH. Antispasmodic and bronchodilator activities of
Artemisia vulgaris are mediated through dual blockade of muscarinic
receptors and calcium influx. J Ethnopharmacol. 2009;126:480–6.
12. Natividad GM, Broadley KJ, Kariuki B, et al. Actions of Artemisia vulgaris
extracts and isolated sesquiterpene lactones against receptors mediating
contraction of guinea pig ileum and trachea. J Ethnopharmacol. 2011;137:
808–16.
13. Nilsen BM, Paulsen BS. Isolation and characterization of a glycoprotein
allergen, Art v II, from pollen of mugwort (Artemisia vulgaris L.). Mol
Immunol. 1990;27:1047–56.
14. Obistioiu D, Cristina RT, Schmerold I, et al. Chemical characterization by
GC-MS and in vitro activity against Candida albicans of volatile fractions
prepared from Artemisia dracunculus, Artemisia abrotanum, Artemisia
absinthium and Artemisia vulgaris. Chem Cent J. 2014;8:6.
15. Pires JM, Mendes FR, Negri G, et al. Antinociceptive peripheral effect of
Achillea millefolium L. and Artemisia vulgaris L.: both plants known
popularly by brand names of analgesic drugs. Phytother Res. 2009;23:212–9.
16. Saleh AM, Aljada A, Rizvi SA, et al. In vitro cytotoxicity of Artemisia
vulgaris L. essential oil is mediated by a mitochondria-dependent apoptosis
in HL-60 leukemic cell line. BMC Complement Altern Med. 2014;14:226.
17. Shaik A, Kanhere RS, Cuddapah R, et al. Antifertility activity of Artemisia
vulgaris leaves on female Wistar rats. Chin J Nat Med. 2014;12:180–5.
18. Temraz A, El-Tantawy WH. Characterization of antioxidant activity of
extract from Artemisia vulgaris. Pak J Pharm Sci. 2008;21:321–6.
19. Tigno XT, de Guzman F, Flora AM. Phytochemical analysis and
hemodynamic actions of Artemisia vulgaris L. Clin Hemorheol Microcirc.
2000;23:167–75.
20. Tigno XT, Gumila E. In vivo microvascular actions of Artemisia vulgaris L.
in a model of ischemia-reperfusion injury in the rat intestinal mesentery.
Clin Hemorheol Microcirc. 2000;23:159–65.
21. Williams JD, Saleh AM, Acharya DN. Composition of the essential oil of
wild growing Artemisia vulgaris from Erie. Pennsylvania. Nat Prod
Commun. 2012;7:637–40.
22. Wopfner N, Gadermaier G, Egger M, et al. The spectrum of allergens in
ragweed and mugwort pollen. Int Arch Allergy Immunol. 2005;138:337–46.
Asparagus adscendens (Roxb.) Kunth
(Asparagaceae)

(Syns.: A. satawur James a. Murray; Protasparagus adscendens (Roxb.) Kamble)

Abstract
It is an herbaceous, erect, thorny plant, native to the Himalayas. Europeans
generally used it as an article of diet. The roots are used in the Indian traditional
systems of medicine for various disorders, such as to improve general state of
health, for stress-related immune disorders, nutritive, tonic, and demulcent.
Boiled in milk and sugar, it is used in nocturnal emissions (wet dreams), gleet,
and chronic leucorrhea, as nerve tonic, and remedy for memory impairment, in
the treatment of diarrhea, dysentery, diabetes, senile pruritus, asthma, fatigue, as
antifilarial, and antifungal. Root extract significantly improved memory, and
reduced AChE, and oxidative stress markers in the cortex and hippocampus
regions of mice, significantly increased body and testes weights, penile erections,
mounting/intromission frequency, and ejaculation latency of rats. Diet supple-
mented with root significantly reduced tumor incidence in the DMBA-induced
skin and B(a)P-induced forestomach papillomagenesis in mice, inhibited phase I,
and activated phase II enzyme systems, and antioxidant enzymes in the liver.
Aqueous root extract induced a significant increase in glucose-dependent
insulinotropic actions in clonal pancreatic b-cell line, and a highly significant
increase in glucose uptake in 3T3-L1 adipocytes.

Keywords
Asparagus satawur

Asperge de l’inde
Dholi musali
Musli safed



Shaqaqul-e-hindi Shweta musali

Vernaculars: Urd.: Musli safed; Hin.: Dholi musali, Ujli musali; San.: Shweta
musali; Mal.: Shada veli, Tannirvittagam; Mar.: Safed musli; Tam.: Tannir vittang;
Tel.: Tsalla gadda; Ara.: Shaqaqul-e-hindi; Fre.: Asperge de l’Inde

© Springer Nature Switzerland AG 2020 351

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_36
352 Asparagus adscendens (Roxb.) Kunth

Fig. 1 Asparagus adscendens, Plant, Atudu, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Asparagus_adscendens_DSC_6913.JPG

Description: It is an herbaceous, erect, thorny plant, native to the Himalayas.

Commercial roots marketed in India are ivory white, shrivelled, often twisted, hard
and brittle, 5–6 cm long decorticated tubers. When soaked in water, they swell up,
and become spindle-shaped, with an agreeable mucilaginous taste (Fig. 1).XL
Actions and Uses: Europeans generally used it as an article of diet.XL The roots
are used in the Indian traditional systems of medicine for various disorders, such as
to improve general state of health, for stress-related immune disorders [2], nutritive,
tonic, and demulcent. Boiled in milk and sugar, it is used in nocturnal emissions
(wet dreams), gleet, and chronic leucorrhea,LXXXI as nerve tonic, and remedy for
memory impairment [3, 6], in the treatment of diarrhea, dysentery, diabetes, senile
pruritus, asthma, fatigue, as antifilarial, and antifungal [1]. Root is regarded hot 1°
and dry 2° in Unani medicine with aphrodisiac property, and used for sexual
debility/seminal weakness and nocturnal emissions.LXXVII
Phytoconstituents: Beta-sitosterol, b-D-glucoside, spirostanol glycosides (aspar-
anin C and asparanin D), and furostanol glycosides (asparoside C and asparoside D)
have been isolated from methanol root extract [7].
Pharmacology: Pretreatment of mice with root extract for 15-days significantly
improved memory, and reduced AChE, and oxidative stress markers in the cortex
and hippocampus regions [6]. Thirty-days administration of root extract to rats
significantly increased body and testes weights, penile erections, mounting/
intromission frequency, and ejaculation latency [1]. Diet supplemented with 4%
root significantly reduced tumor incidence in the DMBA-induced skin and B(a)
P-induced forestomach papillomagenesis in mice, inhibited phase I, and activated
phase II enzyme systems, and antioxidant enzymes in the liver [8]. Methanol and
aqueous extracts exert inhibitory effect on proinflammatory cytokines, IL1b and
TNFa, and in vitro production of NO in LPS-stimulated mouse macrophage cells
[2]. Aqueous root extract induced a significant increase in glucose-dependent
Asparagus adscendens (Roxb.) Kunth 353

insulinotropic actions in clonal pancreatic b-cell line, and produced highly signifi-
cant increase in glucose uptake in 3T3-L1 adipocytes [5]. Methanol root extract
exhibited antibacterial potential against Gram-positive bacteria [4], while the aque-
ous and alcohol root extracts inhibited spontaneous motility of whole worm, and
caused in vitro death of the microfilariae S. cervi [9].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It is a very commonly used drug as a tonic for sexual debility, in
both the Ayurveda and Unani systems of Indian traditional medicines, but there are
no organized clinical studies (RCTs) reported in the publications listed on PubMed.

References
1. Bansode FW, Arya KR, Singh RK, Narender T. Dose-dependent effects of
Asparagus adscendens root (AARR) extract on the anabolic, reproductive,
and sexual behavioral activity in rats. Pharm Biol. 2015;53:192–200.
2. Kanwar AS, Bhutani KK. Effects of Chlorophytum arundinaceum, Asparagus
adscendens and Asparagus racemosus on proinflammatory cytokine and
corticosterone levels produced by stress. Phytother Res. 2010;24:1562–6.
3. Khan I, Nisar M, Khan N, et al. Structural insights to investigate cony-
pododiol as a dual cholinesterase inhibitor from Asparagus adscendens.
Fitoterapia. 2010;81:1020–5.
4. Khan KM, Nahar L, Mannan A, et al. Evaluation of resazurin microtiter
plate assay and HPLC-photodiode array analysis of the roots of Asparagus
adscendens. Nat Prod Res. 2017;19:1–4.
5. Mathews JN, Flatt PR, Abdel-Wahab YH. Asparagus adscendens (Shweta
musali) stimulates insulin secretion, insulin action and inhibits starch diges-
tion. Br J Nutr. 2006;95:576–81.
6. Pahwa P, Goel RK. Asparagus adscendens root extract enhances cognition
and protects against scopolamine induced amnesia: an in-silico and in-vivo
studies. Chem Biol Interact. 2016;260:208–18.
7. Sharma SC, Chand R, Bhatti BS, Sati OP. New oligospirostanosides and
oligofurostanosides from Asparagus adscendens roots. Planta Med. 1982;46:
48–51.
8. Singh M, Singh S, Kale RK. Chemomodulatory potential of Asparagus
adscendens against murine skin and forestomach papillomagenesis. Eur J
Cancer Prev. 2011;20:240–7.
9. Singh R, Khan NU, Singhal KC. Potential antifilarial activity of roots of
Asparagus adscendens Roxb, against Setaria cervi in vitro. Indian J Exp
Biol. 1997;35:168–72.
Asparagus officinalis L.
(Asparagaceae)

(Syns.: A. altilis (L.) Asch.; A. caspius Schult. & Schult.f.; A. esculentus Salisb.;
A. fiori Sennen; A. littoralis Steven; A. longifolius Fisch. ex Steud.; A. oxycarpus
Steven)

Abstract
A common perennial vegetable, native to Europe, Turkey, Russia, Persia, and
north India. The root and seeds are considered deobstruent, resolvent, diuretic,
emmenagogue, lithotriptic and aphrodisiac. Dioscorides and Pliny used root in
wine for calculus affections, and pains in uterus, and also considered it beneficial
in elephantiasis. Ibn Jazlah considered it good for sciatica, while Galen used it
for obstruction of liver and kidneys, and Razi considered it good for backache,
lumbago, and pain in the lungs. Roots are considered diuretic in Brazil, and also
useful for bronchial catarrh, and pulmonary tuberculosis. It contains high levels
of mineral concentrations, higher than typical edible vegetables, and the amino
acid and inorganic mineral contents are much higher in leaves than in shoots; it
also served as a source of steroidal glycosides in the 1970s. Root contains
asparagin, a yellow resin, sugar, gum, albumin, chlorides, phosphates, malates,
sarsasapogenin M, sarsasapogenin N, yamogenin, b-sitosterol, and sitosterol-
b-d-glucoside, and seeds contain a fixed oil, aromatic resin, crystallizable sugar,
and a crystalline bitter principle spargin. Total flavonoid contents of Triguero
asparagus range from 400 to 700 mg/kg fresh weight; rutin being the most
abundant, an important source of not only quercetin derivatives, but also
kaempferol and isorhamnetin glycosides. Aqueous extract of the indigestible
bottom part of asparagus significantly decreased FBG and TGs in diabetic rats,
with marked increase in body weight and hepatic glycogen level. Ethanol,
aqueous and n-butanol extracts also significantly decreased serum TC and
LDL-C in high-fat diet-induced hyperlipidemic mice, and aqueous extract also
increased HDL-C level. Feeding green asparagus in diet to male SHR
significantly lowered SBP, urinary protein and creatinine excretion, and ACE
activity in kidney. A. officinalis powder tablets used in German individuals to
reduce weight, improved mean weight, BP, physical and emotional well-being
and the quality of life.

© Springer Nature Switzerland AG 2020 355

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_37
356 Asparagus officinalis L.

Keywords
Aspárago

Asparagus Asperge


Gartenspargel
Haliyun
Isferaj




Kuşkonmaz Lùsǔn Marchuba Parsa

Vernaculars: Urd.: Haliyun; Hin.: Haliyun, Marchuba, Margiyeh, Nakdoun,

Paragus, VilayatiKarua; Ben.: Hikua, Hillua; Mal.: AkarParsi; Mar.: Safedmusli;
Ara.: Halyun, Isferaj, Khashbul-hayya; Chi.: 石刁柏, Louhséun, Lùsǔn; Cze.:
Chřestlékařský, Chřestobecný; Dan.: Almindeligasparges, Asparges; Dut.: Asperge,
Spargel, Tuinasperge; Eng.: Common asparagus Garden asparagus, Sparrow grass;
Fin.: Parsa, Ruokaparsa; Fre.: Asperge, Asperge officinale; Ger.: Gartenspargel,
Gemeiner spargel, Gemüsespargel, Spargel; Gre.: Sparaggi; Ita.: Asparagio,
Asparago comune, Spaghero; Jap.: Asuparagasu, Matsubaudo, Oranda-kiji-kakushi;
Kor.: Yakpijjaru; Nor.: Asparges; Per.: Marchubeh; Pol.: Szparag lekarski; Por.:
Corruda, Espargo, Espargo-hortense; Rus.: Sparža aptečnaja; Spa.: Aspárago (Br.),
Espargo, Esparguera, Esparquer, Esparraguera, Espárrago; Swe.: Sparris; Tag.:
Asparagus; Tha.: Normai farang; Tur.: Kuşkonmaz; Vie.: Măng tây.
Description: It is a flowering perennial plant, a common vegetable, native to
Europe, Turkey, Russia, Persia, and north India. The root and seeds (ripe fruits),
and sometime the whole plant, are used medicinally. Root consists of short hori-
zontal succulent shoots or rhizomes; upper side scaly and marked with stem scars,
below it gives off numerous whitish simple roots which become wrinkled on
drying. It has no odor but a mawkish and sweet taste. Berries 3-celled, scarlet,
pea-sized and containing 1–2 seeds in each cell, globose with an albumen horny,
and a transverse embryo, far out of center (Figs. 1 and 2).XL
Actions and Uses: Hippocrates mentioned that the berries taken in wine promote
conception. Dioscorides and Pliny used root in wine for calculus affections, and
pains in uterus, and also considered it beneficial in elephantiasis.XL Ibn Jazlah
considered it good for sciatica, while Galen used it for obstruction of liver and
kidneys, and Razi considered it good for backache, lumbago, and pain in the
lungs.LIII Root decoction relieves dysuria, jaundice and abdominal pain.LXIX In
Unani medicine, the root and seeds (temperament, hot 2° and dry 2°) are considered
deobstruent, resolvent, diuretic, emmenagogue, lithotriptic and aphrodisiac.LXXVII
A mild aperient (laxative), and sedative; asparagin stimulates kidneys and imparts a
strong smell to urine; the green resin produces a sedative effect on heart, calming
palpitations, and is used as a remedy for flatulence, renal calculi, cardiac dropsy,
rheumatism and chronic gout.LXXXI,CV Roots are considered diuretic in Brazil, and
also useful for bronchial catarrh, and pulmonary tuberculosis.XXVII,CXVII The bulb
root of another species of asparagus, A. cochinchinensis is used in TCM as a
nutritive tonic, antipyretic, expectorant, antitussive and diuretic, as it is effective in
coughing, dysuria, gout, heart disorders, and dropsy.LXVI
Phytoconstituents: It contains high levels of mineral concentrations, higher than
typical edible vegetables [1], and the amino acid and inorganic mineral contents are
Asparagus officinalis L. 357

Fig. 1 Asparagus officinalis, Bundle of Asparagus Spears, Evan-Amos, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Asparagus-
Bundle.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
358 Asparagus officinalis L.

Fig. 2 Asparagus officinalis, Shoots, SeanMack, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Asparagus_Tip.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

much higher in leaves than in shoots [13]. It served as a source of steroidal glycosides
in the 1970s [7, 14]. From the aerial parts, asparagusic acid, anti-S-oxide methyl
ester, asparagusic acid syn-S-oxide methyl ester, 2-hydroxyasparenyn [3′,4′-
trans-2-hydroxy-1-methoxy-4-[5-(4-methoxy-phenoxy)-3-penten-1-ynyl]-benzene],
asparenyn, asparenyol, (+/−)-1-monopalmitin, ferulic acid, 1,3-O-di-p-coumar-
oylglycerol, 1-O-feruloyl-3-O-p-coumaroyl-glycerol, blumenol C, (+/−)-epipinor-
esinol, linoleic acid, 1,3-O-diferuloyl-glycerol, and 1,2-O-diferuloylglycerol, were
isolated [12]. Root contains asparagin, a yellow resin, sugar, gum, albumin, chlorides,
phosphates, and malates, and seeds contain a fixed oil, aromatic resin, crystallizable
sugar, and a crystalline bitter principle spargin.XL Sarsasapogenin M, sarsasapogenin N,
(25S)-5b-spirostan-3b, 17a-diol, (25S)-5b-spirostan-3b-ol-3-O-b-D-glucopyranosyl
(1,2)-[b-D-xylopyranosyl-(1,4)]-b-D-glucopyranoside, (25S)-5b-spirostan-3b-ol-3-O-
b-D-glucopyranosyl-(1,2)-b-D-glucopyranoside, (25S)-5b-spirostan-3b-ol-3-O-a-l-
rhamnopyranosyl-(1,2)-[a-l-rhamnopyranosyl-(1,4)]-b-D-glucopyranoside, (25S)26-
O-b-D-glucopyranosyl-5b-furost-20(22)-ene-3b,26-diol-3-O-b-D-glucopyranosyl-(1,2)-
b-D-glucopyranoside, yamogenin, b-sitosterol, and sitosterol-b-D-glucoside were iso-
lated from the roots [10, 11], and yamogenin II from the stem [20]. Total flavonoid
contents of Triguero asparagus ranged from 400 to 700 mg/kg fresh weight; rutin being
the most abundant (55–98%), an important source of not only quercetin derivatives, but
also kaempferol and isorhamnetin glycosides [5]. Two anthocyanins were isolated from
peels of the spears [16], and two oligofurostanosides were isolated from seeds [19].
Asparagus officinalis L. 359

Pharmacology: Administration of aqueous extract of the indigestible bottom part

of asparagus for 21-days significantly decreased FBG and TGs in STZ-diabetic rats,
with marked increase in body weight and hepatic glycogen level [24]. Ethanol,
aqueous and n-butanol extracts significantly decreased body weight gain, serum TC
and LDL-C in high-fat diet-induced hyperlipidemic mice at a daily dose of
200 mg/kg for 8-weeks. Serum HDL-C level was also increased in aqueous
extract-treated group [25, 26]. Feeding freeze-dried asparagus to cholesterol-rich
diet-fed rats for five-weeks significantly reduced TC and LDL-C levels, with
insignificant increase in HDL-C, and improved antioxidant status [6]. Methanol
seed extract also suppressed elevated blood glucose in a dose- and time-dependent
manner, and at higher dose significantly improved serum insulin levels in
STZ-diabetic rats [8]. Feeding 5% green asparagus in diet to male SHR for
10-weeks significantly lowered SBP, urinary protein and creatinine excretion, and
ACE activity in kidney. ACE inhibitory activity was also observed in a boiling
water extract; the purified ACE inhibitor was identified as 2″-hydroxynicotianamine
[17]. Treatment with leaves and shoots extracts significantly alleviated cellular
toxicities induced by treatment with hydrogen peroxide, ethanol, or CCl4; and the
activities of alcohol dehydrogenase and aldehyde dehydrogenase were upregulated
by more than two-fold [13]. A German traditional herbal medicinal product,
Asparagus-P, consisting of a combination of asparagus roots and parsley leaves in
equal parts, is used to support kidney function. Asparagus-P inactivates reactive
oxygen radicals, primarily due to parsley leaves, but asparagus roots enhance this
efficacy, producing a synergistic effect [4].
Asparagus was reported active against 37 Sarcoma [2]; crude saponins, dose and
time dependently inhibited growth and the synthesis of DNA, RNA and protein,
with DNA synthesis being irreversible in human leukemia HL-60 cells in culture,
and were cytocidal at higher concentrations [18].
Clinical Studies: A officinalis powder tablets (providing 19 mg saponins per day)
used in German individuals to reduce weight, improved mean weight, BP, physical
and emotional well-being and the quality of life, and the effectiveness and tolera-
bility were rated as very good or good by most of the completers [3].
Human A/Es, Allergy and Toxicity: Asparagus is well known to cause allergic
contact dermatitis [9, 15, 21, 22].
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interaction: Asparagus significantly induces
phenolsulfotransferases activity, traditionally known as phase II drug-metabolizing or
detoxifying enzymes [23].
Commentary: The weight lowering study in German patients was significant, but
there are no clinical studies (RCTs) on any of its uses in traditional medicines.
360 Asparagus officinalis L.

References
1. Aberoumand A. Preliminary assessment of nutritional value of plant-based
diets in relation to human nutrients. Int J Food Sci Nutr. 2009;60 Suppl 4:
155–62.
2. Belkin M, Fitzgerald DB, Felix MD. Tumor-damaging capacity of plant
materials. II. Plants used as diuretics. J Natl Cancer Inst. 1952;13:741–4.
3. Chrubasik C, Maier T, Dawid C, et al. An observational study and quantification
of the actives in a supplement with Sambucus nigra and Asparagus officinalis
used for weight reduction. Phytother Res. 2008;22:913–8.
4. Dartsch PC. The potential of Asparagus-P to inactivate reactive oxygen
radicals. Phytother Res. 2008;22:217–22.
5. Fuentes-Alventosa JM, Rodríguez G, Cermeño P, et al. Identification of
flavonoid diglycosides in several genotypes of asparagus from the Huétor-
Tájar population variety. J Agric Food Chem. 2007;55:10028–35.
6. García MD, De la Puerta R, Sáenz MT, Marquez-Martín A, Fernández-
Arche MA. Hypocholesterolemic and hepatoprotective effects of “triguero”
asparagus from andalusia in rats fed a high cholesterol diet. Evid Based
Complement Alternat Med. 2012;2012:814752.
7. Gorianu GM, Krokhmaliuk VV, Kintia PK, Glyzin VI. Asparagus (Aspara-
gus officinalis L.) as a source of steroid glycosides. Farmatsiia. 1976;25:66
(Russian).
8. Hafizur RM, Kabir N, Chishti S. Asparagus officinalis extract controls blood
glucose by improving insulin secretion and b-cell function in streptozotocin-
induced type 2 diabetic rats. Br J Nutr. 2012;108:1586–95.
9. Hausen BM, Wolf C. 1,2,3-Trithiane-5-carboxylic acid, a first contact
allergen from Asparagus officinalis (Liliaceae). Am J Contact Dermat.
1996;7:41–6 (Review).
10. Huang X, Kong L. Steroidal saponins from roots of Asparagus officinalis.
Steroids. 2006;71:171–6.
11. Huang XF, Lin YY, Kong LY. Steroids from the roots of Asparagus
officinalis and their cytotoxic activity. J Integr Plant Biol. 2008;50:717–22.
12. Jang DS, Cuendet M, Fong HH, et al. Constituents of Asparagus officinalis
evaluated for inhibitory activity against cyclooxygenase-2. J Agric Food Chem.
2004;52:2218–22.
13. Kim BY, Cui ZG, Lee SR, et al. Effects of Asparagus officinalis extracts on
liver cell toxicity and ethanol metabolism. J Food Sci. 2009;74:H204–8.
14. Lazur’evskii GV, Gorianu GM, Kintia PK. Steroid glycosides from Aspara-
gus officinalis L. Doklady Akademii Nauk SSSR. 1976;231:1479–81
(Russian).
15. Rademaker M, Yung A. Contact dermatitis to Asparagus officinalis.
Australas J Dermatol. 2000;41:262–3.
Asparagus officinalis L. 361

16. Sakaguchi Y, Ozaki Y, Miyajima I, et al. Major anthocyanins from purple

asparagus (Asparagus officinalis). Phytochemistry. 2008;69:1763–6.
17. Sanae M, Yasuo A. Green asparagus (Asparagus officinalis) prevented
hypertension by an inhibitory effect on angiotensin-converting enzyme
activity in the kidney of spontaneously hypertensive rats. J Agric Food Chem.
2013;61:5520–5.
18. Shao Y, Chin CK, Ho CT, et al. Antitumor activity of the crude saponins
obtained from asparagus. Cancer Lett. 1996;104:31–6.
19. Shao Y, Poobrasert O, Kennelly EJ, et al. Steroidal saponins from Asparagus
officinalis and their cytotoxic activity. Planta Med. 1997;63:258–62.
20. Sun Z, Huang X, Kong L. A new steroidal saponin from the dried stems of
Asparagus officinalis L. Fitoterapia. 2010;81:210–3.
21. Tabar AI, Alvarez MJ, Celay E, et al. Allergy to asparagus. An Sist Sanit
Navar. 2003;26 Suppl 2:17–23 (Review, Spanish).
22. Tabar AI, Alvarez-Puebla MJ, Gomez B, et al. Diversity of asparagus allergy:
clinical and immunological features. Clin Exp Allergy. 2004;34:131–6.
23. Yeh CT, Yen GC. Effect of vegetables on human phenolsulfotransferases in
relation to their antioxidant activity and total phenolics. Free Radic Res.
2005;39:893–904.
24. Zhao J, Zhang W, Zhu X, et al. The aqueous extract of Asparagus officinalis
L. byproduct exerts hypoglycaemic activity in streptozotocin-induced
diabetic rats. J Sci Food Agric. 2011;9:2095–9.
25. Zhu X, Zhang W, Pang X, et al. Hypolipidemic effect of n-butanol extract
from Asparagus officinalis L. in mice fed a high-fat diet. Phytother Res.
2011;25:1119–24.
26. Zhu X, Zhang W, Zhao J, Wang J, Qu W. Hypolipidaemic and hepatopro-
tective effects of ethanolic and aqueous extracts from Asparagus officinalis L.
by-products in mice fed a high-fat diet. J Sci Food Agric. 2010;90:1129–35.
Asparagus racemosus Willd.
(Asparagaceae)

(Syns.: A. rigidulus Nakai, A. schoberioides Kunth, A. volubilis Buch.-Ham.,

Protasparagus racemosus (Willd.) Oberm)

Abstract
A perennial woody shrub found throughout India. Shatawari means “curer of a
hundred diseases” and “hundred roots.” In traditional systems of Indian medicines,
such as Ayurveda, Unani and Siddha, it is recognized for its phytoestrogenic
properties. Roots are highly mucilaginous, antidiarrheal, refrigerant, diuretic,
antidysenteric, nutritive, tonic, demulcent, galactagogue, antispasmodic, and
aphrodisiac, remove bilious and rheumatic humours. The root is particularly used
in seminal debility by the Unani medicine practitioners. Chief use of the drug is in
the preparation of medicated oils for external application in nervous and rheumatic
affections, and urinary disorders. In Ayurveda, it is used in the treatment of
diarrhea and dysentery, and is considered a rasayana herb, and extensively used as
an adaptogen to increase nonspecific resistance against a variety of stresses. In
Livingstone, a southern Province of Zambia, the plant was utilized to treat two or
more HIV/AIDS-related infections during the epidemic. Several steroidal
saponins, shatavarin I, shatavarin IV-X, shatavaroside A-C, immunoside and
schidigerasaponin D5, filiasparoside C, racemoside A, and a diphenylpentendiol,
shatavarol, b-sitosterol, stigmasterol and ursolic acid, have been isolated from the
roots. Dietary supplementation of hypercholesterolemic rats with root powder
reduced plasma and hepatic lipid profiles, increased fecal excretion of cholesterol,
neutral sterol and bile acid, increased hepatic HMG-CoA reductase activity, and
improved hepatic antioxidant status. Methanol extract exhibits significant
antidepressant activity, via serotonergic and noradrenergic systems, and augments
antioxidant defenses. In a comparative crossover study, A. racemosus markedly
decreased gastric emptying time in healthy male volunteers that was not
significantly different from metoclopramide.

Keywords





Abhiru Chang ci tian men dong Doodhali Gazar dashti Măng tây Satawar






Shaqaqul Shatavari Spiny asparagus Terttuparsa

© Springer Nature Switzerland AG 2020 363

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_38
364 Asparagus racemosus Willd.

Vernaculars: Urd.: Satawar, Shaqaqul; Hin.: Doodhali, Sadabori, Satawar, Sha-

kakul, Shatavari; San.: Abhiru, Dvipa-satru, Dvipika, Hiranyasringi, Náráyani,
Sata-padi, Shatavari, Sutamuli, Vara-gantica; Ben.: Halarru-makkal, Jayibem,
Satmuli, Sutamuli; Mal.: Chatavali, Satavali, Sathavari; Mar.: Asvel, Satvari,
Shatavari-mull, Shatmuli; Tam.: Ammaikodi, Kadumulla, Kilavari, Paniyanaku,
Shimai shadavari, Tamur, Tannirvittan-kizhangu; Tel.: Challa-gaddalu, Phillitaga,
Pilli-gaddalu, Sadavari; Ara.: Shaqaqul; Chi.: 长刺天门冬, Chang ci tian men
dong; Eng.: Spiny asparagus; Fin.: Terttuparsa; Fre.: Asperge à longues épines,
Asperge de l’Inde; Per.: Gazar dashti, Shaqaqul; Sin.: Hatawariya; Tha.: Chuang
khruea, Rag samsib; Vie.: Măng tây.
Description: A perennial woody shrub, is found throughout India, especially north
India. Roots are numerous, fusiform, smooth, brownish-white in color, 15–20 cm in
length, and in breath resembling a slender quill; deeply furrowed and rugous; on
section, tough, resinous, or starchy; in the center a thin, slender, and wiry wood;
fresh tubers mucilaginous, white and somewhat translucent; smell like burnt sugar,
with mawkish, insipid flavor (Figs. 1 and 2).XL,LXXXI
Actions and Uses: Shatawari means “curer of a hundred diseases” and “hundred
roots.” In traditional systems of Indian medicines, such as Ayurveda, Unani and
Siddha, it is recognized for its phytoestrogenic properties. Roots are highly
mucilaginous, antidiarrhetic, refrigerant, diuretic, antidysenteric, nutritive, tonic,
demulcent, galactagogue, antispasmodic, and aphrodisiac,CV remove bilious and
rheumatic humours; fresh juice of root is used with honey as demulcent in bilious
dyspepsia or diarrhea (Sárangadhara),XL and used for the treatment of dysentery,
as a refrigerant, diuretic and antispasmodic,LXXXI,CV antiseptic, antitubercular, and
for snake and scorpion bites.XXI The root (temperament, hot 1° and moist 2°) is
particularly used in seminal debility by the Unani medicine practitioners.LXXVII

Fig. 1 Asparagus racemosus, Plant, Neha Vindhya in Pune, India, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Asparagus_
racemosus.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Asparagus racemosus Willd. 365

Fig. 2 Asparagus racemosus, Flowers, Silk666, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Asparagus_racemosus_fleurs.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Chief use of the drug is in the preparation of medicated oils for external application
in nervous and rheumatic affections, and urinary disorders.XL In Ayurveda, it is used
in the treatment of diarrhea and dysentery, and is considered a rasayana herb, and
extensively used as an adaptogen to increase nonspecific resistance against a variety
of stresses.LIX The plant also has potent antioxidant, immunostimulant, antidys-
pepsia, and antitussive effects [6]. It is also recommended in Ayurvedic texts for
prevention and treatment of gastric ulcers, dyspepsia and as galactogogue [17]. It is
one of the most preferred plant species to treat epilepsy by the Tharu community of
the sub-Himalayan region of Uttarakhand, India [51]. In Livingstone, a southern
Province of Zambia, the plant was utilized to treat two or more HIV/AIDS-related
infections, where 68% of those seeking counselling and testing for HIV/AIDs
utilize traditional medicine [7]. In Thailand, the root is claimed as a galacta-
gogue, antidysenteric, antipeptic, antipruritic, antirheumatic, tonic and longevity
enhancer [41].
Phytoconstituents: Several steroidal saponins, shatavarin I (or asparoside B),
shatavarin IV (or asparinin B), shatavarin V, shatavarins VI-X, shatavaroside
A, shatavaroside B, shatavaroside C, immunoside and schidigerasaponin D5 (or
asparanin A), filiasparoside C, and a diphenylpentendiol, shatavarol, racemoside
A, b-sitosterol, stigmasterol and ursolic acid, have been isolated from the roots [20,
54, 55]. Racemoside A is a water-soluble, antileishmanial saponin, that induces
programmed cell death in L. donovani [11]. A unique immunostimulant steroidal
sapogenin acid [53], an isoflavone, 8-methoxy-5,6,4′-trihydroxyisoflavone 7-O-beta-
D-glucopyranoside [50], and racemofuran with antioxidant activity, asparagamine
A and racemosol [62], have also been isolated from the roots. Extraction of dried root
in various solvents yielded a number of saponins in alcohol, ethyl acetate and acetone
extracts which showed antioxytocic activity. Saponin A4, on acid hydrolysis, yielded
sarsasapogenin, glucose and rhamnose. Saponin A7 and glycoside A8 were obtained
366 Asparagus racemosus Willd.

after repeated crystallization from methanol. Previous isolation of asparagamine A

from materials claimed to originate from A. racemosus was likely caused by
misidentification of Stemona plants as A. racemosus, because A. racemosus does not
contain asparagamine A [29]. Three steroidal saponins, racemosides A, B and C were
isolated from methanol extract of the fruits [30].
Pharmacology: A standardized aqueous extract reversed effects of cisplatin on
gastric emptying, normalized intestinal hypermotility, and produced immunostim-
ulation [44]. Ethanol and aqueous extracts show significant inhibitory activity
against castor oil-induced diarrhea, PGE2-induced enteropooling in rats, and sig-
nificantly reduce gastrointestinal motility [60]. Methanol extract significantly pro-
tects against acute gastric ulcers induced by various methods, and also healed
chronic gastric ulcers; but was ineffective against aspirin- and ethanol-induced
gastric ulcers. It significantly increased mucosal defensive factors like mucus
secretion, and also exerted antioxidant effect, but had little or no effect on acid and
pepsin levels [49]. However, methanol extract given orally for 15-days significantly
reduced ulcer index, volume of gastric secretion, free acidity, and total acidity
in experimental gastric ulcers, increased antioxidant enzymes, SOD, CAT, and
ascorbic acid, and significantly decreased LPO [4, 5].
Dietary supplementation of hypercholesterolemic rats with root powder reduced
plasma and hepatic lipid profiles, increased fecal excretion of cholesterol, neutral
sterol and bile acid, increased hepatic HMG-CoA reductase activity, and improved
hepatic antioxidant status [61]. Ethanol extract decreased serum glucose, increased
pancreatic insulin, plasma insulin, liver glycogen, total oxidant status, suppressed
sucrose-induced hyperglycemia, and increased unabsorbed sucrose content in gut of
type 2 diabetic rats [18]. Ethanol extract also stimulated insulin secretion in isolated
perfused rat pancreas, rat islet cells, and clonal b-cells [19], lowered restraint
stress-induced elevation of blood glucose, TG and TC levels, elevated weight of
adrenal glands, and levels of LPO, NO, protein and GSH content in mouse brain
[23], and significantly decreased plasma glucose, creatinine, urea nitrogen, TC and
TG levels, and attenuated renal hypertrophy, polyuria, hyperfiltration, microalbu-
minuria, as well as oxidative stress in diabetic nephropathy in rats [57].
Methanol extract exhibits significant antidepressant activity, via serotonergic and
noradrenergic systems, augmentation of antioxidant defenses [56], decreased
plasma corticosterone and NE levels, and increased levels of all monoamines in
hypothalamus [27]. Supplementation of rats with methanol extract also protected
against LPS-induced oxidative stress, restored brain GSH, CAT and SOD, and
decreased levels of MDA, NO and cytokines in brain [3]; improved GPx activity,
GSH content and reduced membrane LPO in hippocampal and striatal neuronal
damage in mice [39].
Aqueous extract protected against radiation-induced loss of protein and thiols in rat
liver mitochondria [24], ameliorated oxidative stress and hepatotoxicity [2], and pre-
vented isoniazid- and CCl4-hepatotoxicity, and markedly attenuated oxidative stress
[1, 36]. Methanol and aqueous extracts exert an inhibitory effect on proinflammatory
cytokines, IL1b and TNF- a, and in vitro production of NO in LPS-stimulated mouse
Asparagus racemosus Willd. 367

macrophage cells [25]. Pretreatment with A. racemosus significantly decreased

intraperitoneal adhesions, with significant increase in activity of macrophages [43].
Ethanol extract reduced serum concentrations of calcium, phosphorus, urea, and cre-
atinine in ethylene glycol- and ammonium chloride-induced lithiasis in rats, prevented
histological damage to kidneys [21], and reduced urinary concentration of calcium,
oxalate, and phosphate that contribute to renal stone formation [8]. Aqueous extract
prevents DEN-induced hepatocarcinogenesis, ameliorates oxidative stress and hepa-
totoxicity in rats [2], and prevents CP-induced leucopenia [58]. Shatavarins-rich frac-
tion to EAC tumor-bearing mice significantly reduced increase in body weight, tumor
volume, PCV, viable tumor cell count, and increased nonviable cell count [33].
DMBA-induced mammary carcinogenesis in rats was also inhibited [42]. Various
extracts inhibited lipofectamine-induced apoptosis [26].
Oral administration of A. racemosus extract in combination with cisplatin to L.
donovani-infected BALB/c mice had better parasites killing activity and clearance
of parasites than cisplatin alone [48]. Methanol extract exhibits considerable in vitro
antibacterial activities against both Gram-positive and Gram-negative bacteria;
E. coli, Sh. dysenteriae, Sh. sonnei, Sh. flexneri, V. cholerae, S. typhi, S. typhi-
murium, P. putida, B. subtilis and S. aureus [31], and anticandidal activity against
C. albicans, C. tropicalis, C. krusei, C. guillermondii, C. parapsilosis and C.
stellatoida, isolated from vaginal thrush patients [59]. Acetone extract exhibited
good antibacterial activity against S. aureus, S. epidermis, P. vulgaris, P. mirabilis,
K. pneumonia, P. aeruginosa and E. coli, and antifungal activity against C. albi-
cans isolated from oral cancer patients [38]. Ethanol extract of roots collected in
Thailand was active against E. faecalis, S. velterans, Sh. dysenteriae, S. aureus,
S. mutans, E. coli, S. epidermidis, P. aeruginosa, K. pneumoniae, P. acnes, C. albicans,
Bacteroides spp., Clostridium spp., Peptococcus spp., Lactobacillus spp. and Strep-
tococcus spp. [41]. Multiple antibiotic resistant uropathogens P. aeruginosa and
S. epidermidis were very susceptible to chloroform, methanol, acetone and ethanol
extracts, and S. marcescens, E. cloaceae, C. koseri, and C. freundii were least sus-
ceptible [34]. An inhibitory effect on E. histolytica growth was reported by aqueous
solution of alcohol extract [46].
Alcohol extract to pregnant rats for 15-days produced estrogenic effect on female
mammary glands and genital organs, significantly increasing uterine horns weight,
proliferation of lumen of mammary gland duct, hyperplasia of glandular and
muscular tissue, and hypertrophy of genital organs [37], and caused increase in
weight of mammary glands in postpartum and estrogen-primed animals, and
developed lobuloalveolar tissue with milk secretion [22, 47]. Alcohol extract,
containing several saponins, exhibited antioxytocic activity, and saponin-glucoside
blocked spontaneous uterine motility, and produced specific competitive block of
pitocin (syntocinon)-induced contractions of uteri in vitro [12–14]. Initial increase
in force and rate of contraction of isolated frog’s heart by aqueous solution of
alcohol extract was followed with cardiac arrest at higher doses. Alcohol extract
caused a fall in BP, blocked by atropine, and respiratory depression in cats. The
extract also increased bleeding time in rabbits, and produced mild diuretic effect in
rats [45]. A significant increase in milk yield in buffaloes has also been reported
368 Asparagus racemosus Willd.

[40]. Aqueous extracts of both fresh and dried roots showed amylase and lipase
activities; the activity being higher in the fresh one [10].
Clinical Studies: In a comparative crossover study in 8 healthy male volunteers,
gastric emptying time was markedly decreased by both A. racemosus and meto-
clopramide, which did not significantly differ [9].
Mechanism of Action: Aqueous extract exerts hepatoprotective activity by reduc-
ing free radical generation via inhibition of hepatic CYP2E1 [36]. Anxiolytic activity
of methanol extract is suggested to involve GABA and serotonergic mechanisms [15],
and nootropic, antiamnesic, and memory enhancing activities are probably mediated
through augmentation of cholinergic system due to its AChE inhibitory activity in
prefrontal cortex, hippocampus and hypothalamus [32, 35, 52].
Human A/Es, Allergy and Toxicity: It causes anorexia and headache.LXXVII
Animal Toxicity: Aqueous extract was nontoxic to rats up to a dose of
3,200 mg/kg [28]. However, methanol extract to Charles Foster rats for 60-days
caused teratogenic effects; increased resorption of fetuses, gross malformations e.g.
swelling in legs and intrauterine growth retardation, with a small placental size.
Pups showed significant decrease in body weight and length, and delay of various
developmental parameters [16].
CYP450 and Potential for Drug-Herb Interaction: Aqueous extract inhibited
hepatic CYP2E1 [36].
Commentary: There are no clinical studies (RCTs) on any of its most common
uses in traditional medicines, such as seminal debility and as an aphrodisiac.

References
1. Acharya SR, Acharya NS, Bhangale JO, Shah SK, Pandya SS. Antioxidant
and hepatoprotective action of Asparagus racemosus Willd. root extracts.
Indian J Exp Biol. 2012;50:795–801.
2. Agrawal A, Sharma M, Rai SK, et al. The effect of the aqueous extract of
the roots of Asparagus racemosus on hepatocarcinogenesis initiated by
diethylnitrosamine. Phytother Res. 2008;22:1175–82.
3. Ahmad MP, Hussain A, Siddiqui HH, Wahab S, Adak M. Effect of
methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide
induced-oxidative stress in rats. Pak J Pharm Sci. 2015;28:509–13.
4. Bhatnagar M, Sisodia SS, Bhatnagar R. Antiulcer and antioxidant activity
of Asparagus racemosus Willd. and Withania somnifera Dunal in rats. Ann
NY Acad Sci. 2005;1056:261–78.
5. Bhatnagar M, Sisodia SS. Antisecretory and antiulcer activity of Asparagus
racemosus Willd. against indomethacin plus phyloric ligation-induced
gastric ulcer in rats. J Herb Pharmacother. 2006;6:13–20.
Asparagus racemosus Willd. 369

6. Bopana N, Saxena S. Asparagus racemosus—ethnopharmacological eval-

uation and conservation needs. J Ethnopharmacol. 2007;110:1–15.
7. Chinsembu KC. Ethnobotanical study of plants used in the management of
HIV/AIDS-related diseases in Livingstone, Southern Province Zambia. Evid
Based Complement Alternat Med. 2016;2016:4238625.
8. Christina AJ, Ashok K, Packialakshmi M, et al. Antilithiatic effect of
Asparagus racemosus Willd. on ethylene glycol-induced lithiasis in male
albino Wistar rats. Methods Find Exp Clin Pharmacol. 2005;27:633–8.
9. Dalvi SS, Nadkarni PM, Gupta KC. Effect of Asparagus racemosus
(Shatavari) on gastric emptying time in normal healthy volunteers.
J Postgrad Med. 1990;36:91–4.
10. Dange PS, Kanitkar UK, Pendse GS. Amylase and lipase activities in the
root of Asparagus racemocus. Planta Med. 1969;17:393.
11. Dutta A, Ghoshal A, Mandal D, et al. Racemoside A, an antileishmanial,
water-soluble, natural steroidal saponin, induces programmed cell death in
Leishmania donovani. J Med Microbiol. 2007;56:1196–204.
12. Gaitonde BB, Jetmalani MH. Antioxytocic action of saponin isolated from
Asparagus racemosus Willd. (Shatavari) on uterine muscle. Arch Int Pharma-
codyn Ther. 1969;179:121–9.
13. Gaitonde BB, Jetmalani MH. Antioxytocic and anti-ADH activity of
saponin fraction isolated from Asparagus racemosus Willd. Indian J Pharm.
1969;31:175.
14. Gaitonde BB, Jetmalani MH. Pharmacological studies of Asparagus race-
mosa. In: Proceedings of II Indo Soviet symposium on the chemistry of
natural products including pharmacology, New Delhi; 1970. p. 1485.
15. Garabadu D, Krishnamurthy S. Asparagus racemosus attenuates anxiety-
like behavior in experimental animal models. Cell Mol Neurobiol. 2014;34:
511–21.
16. Goel RK, Prabha T, Kumar MM, et al. Teratogenicity of Asparagus
racemosus Willd. root, a herbal medicine. Indian J Exp Biol. 2006;44:
570–3.
17. Goyal RK, Singh J, Lal H. Asparagus racemosus—an update. Indian J Med
Sci. 2003;57:408–14 (Review).
18. Hannan JM, Ali L, Khaleque J, et al. Antihyperglycaemic activity of
Asparagus racemosus roots is partly mediated by inhibition of carbohydrate
digestion and absorption, and enhancement of cellular insulin action. Br J
Nutr. 2011;8:1–8.
19. Hannan JM, Marenah L, Ali L, et al. Insulin secretory actions of extracts of
Asparagus racemosus root in perfused pancreas, isolated islets and clonal
pancreatic beta-cells. J Endocrinol. 2007;192:159–68.
20. Hayes PY, Jahidin AH, Lehmann R, et al. Steroidal saponins from the roots
of Asparagus racemosus. Phytochemistry. 2008;69:796–804.
21. Jagannath N, Chikkannasetty SS, Govindadas D, Devasankaraiah G. Study
of antiurolithiatic activity of Asparagus racemosus on albino rats. Indian J
Pharmacol. 2012;44:576–9.
370 Asparagus racemosus Willd.

22. Jetmalani MH, Sabnis PB, Gaitonde BB. A study on the pharmacology of
various extracts of Shatavari (Asparagus racemosus Willd.). J Res Ind Med.
1967;2:1.
23. Joshi T, Sah SP, Singh A. Antistress activity of ethanolic extract of
Asparagus racemosus Willd. roots in mice. Indian J Exp Biol. 2012;50:
419–24.
24. Kamat JP, Boloor KK, Devasagayam TPA, Venkatachalam SR. Antioxidant
properties of Asparagus racemosus against damage induced by c-radiation
in rat liver mitochondria. J Ethnopharmacol. 2000;71:425–35.
25. Kanwar AS, Bhutani KK. Effects of Chlorophytum arundinaceum, Aspara-
gus adscendens and Asparagus racemosus on proinflammatory cytokine and
corticosterone levels produced by stress. Phytother Res. 2010;24:1562–6.
26. Kongkaneramit L, Witoonsaridsilp W, Peungvicha P, et al. Antioxidant
activity and antiapoptotic effect of Asparagus racemosus root extracts in
human lung epithelial H460 cells. Exp Ther Med. 2011;2:143–8.
27. Krishnamurthy S, Garabadu D, Reddy NR. Asparagus racemosus modu-
lates the hypothalamic-pituitary-adrenal axis and brain monoaminergic
systems in rats. Nutr Neurosci. 2013;16:255–61.
28. Kumar MC, Udupa AL, Sammodavardhana K, et al. Acute toxicity and
diuretic studies of the roots of Asparagus racemosus Willd. in rats. West
Indian Med J. 2010;59:3–6.
29. Kumeta Y, Maruyama T, Wakana D, Kamakura H, Goda Y. Chemical
analysis reveals the botanical origin of shatavari products and confirms the
absence of alkaloid asparagamine A in Asparagus racemosus. J Nat Med.
2013;67:168–73.
30. Mandal D, Banerjee S, Mondal NB, et al. Steroidal saponins from the fruits
of Asparagus racemosus. Phytochemistry. 2006;67:1316–21.
31. Mandal SC, Kumar CKA, Mohana Lakshmi S, et al. Antitussive effect of
Asparagus racemosus root against sulfur dioxide-induced cough in mice.
Fitoterapia. 2000;71:686–9.
32. Meena J, Ojha R, Muruganandam AV, Krishnamurthy S. Asparagus race-
mosus competitively inhibits in vitro the acetylcholine and monoamine
metabolizing enzymes. Neurosci Lett. 2011;503:6–9.
33. Mitra SK, Prakash NS, Sundaram R. Shatavarins (containing Shatavarin IV)
with anticancer activity from the roots of Asparagus racemosus. Indian J
Pharmacol. 2012;44:732–6.
34. Narayanan AS, Raja SS, Ponmurugan K, et al. Antibacterial activity of
selected medicinal plants against multiple antibiotic resistant uropathogens: a
study from Kolli Hills, Tamil Nadu India. Benef Microbes. 2011;2:235–43.
35. Ojha R, Sahu AN, Muruganandam AV, Singh GK, Krishnamurthy S.
Asparagus recemosus enhances memory and protects against amnesia in
rodent models. Brain Cogn. 2010;74:1–9.
36. Palanisamy N, Manian S. Protective effects of Asparagus racemosus on
oxidative damage in isoniazid-induced hepatotoxic rats: an in vivo study.
Toxicol Ind Health. 2012;28:238–44.
Asparagus racemosus Willd. 371

37. Pandey SK, Sahay A, Pandey RS, Tripathi YB. Effect of Asparagus
racemosus rhizome (Shatavari) on mammary gland and genital organs of
pregnant rat. Phytother Res. 2005;19:721–4.
38. Panghal M, Kaushal V, Yadav JP. In vitro antimicrobial activity of ten
medicinal plants against clinical isolates of oral cancer cases. Ann Clin
Microbiol Antimicrob. 2011;10:21.
39. Parihar MS, Hemnani T. Experimental excitotoxicity provokes oxidative
damage in mice brain and attenuation by extract of Asparagus racemosus.
J Neural Transm. 2004;111:1–12.
40. Patel AB, Kanitkar UK. Asparagus racemosus Willd. from Bordi as a
galactagogue in buffaloes. Indian Vet J. 1969;46:718.
41. Potduang B, Meeploy M, Giwanon R, et al. Biological activities of
Asparagus racemosus. Afr J Tradit Complement Altern Med. 2008;5:230–7.
42. Rao AR. Inhibitory action of Asparagus racemosus on DMBA-induced
mammary carcinogenesis in rats. Int J Cancer. 1981;28:607–10.
43. Rege NN, Nazareth HM, Isaac A, Karandikar SM, Dahanukar SA.
Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus
racemosus. J Postgrad Med. 1989;35:199–203.
44. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six rasayana
herbs used in Ayurvedic medicine. Phytother Res. 1999;13:275–91.
45. Roy RN, Bhagwager S, Chavan SR, Dutta NK. Preliminary pharmacolog-
ical studies on extracts of root of Asparagus racemosus (Shatavari) Willd.
N. O. Liliaceae. J Res Ind Med. 1971;6:132.
46. Roy RN, Chavan SR, Bhagwager S, et al. Preliminary pharmacological
studies on different extracts of root of Asparagus racemosus (Satawari)
Willd. Indian J Pharm. 1968;30:289.
47. Sabnis PB, Gaitonde BB, Jetmalani M. Effects of alcoholic extracts of
Asparagus racemosus on mammary glands of rats. Indian J Exp Biol. 1968;
6:55–7.
48. Sachdeva H, Sehgal R, Kaur S. Asparagus racemosus ameliorates cisplatin
induced toxicities and augments its antileishmanial activity by immunomod-
ulation in vivo. Parasitol Int. 2014;63:21–30.
49. Sairam K, Priyambada S, Aryya NC, Goel RK. Gastroduodenal ulcer
protective activity of Asparagus racemosus: an experimental, biochemical
and histological study. J Ethnopharmacol. 2003;86:1–10.
50. Saxena VK, Chourasia S. A new isoflavone from the roots of Asparagus
racemosus. Fitoterapia. 2001;72:307–9.
51. Sharma J, Gairola S, Gaur RD, Painuli RM, Siddiqi TO. Ethnomedicinal
plants used for treating epilepsy by indigenous communities of sub-Himalayan
region of Uttarakhand India. J Ethnopharmacol. 2013;150:353–70.
52. Sharma K, Bhatnagar M, Kulkarni SK. Effect of Convolvulus pluricaulis
Choisy and Asparagus racemosus Willd. on learning and memory in young
and old mice: a comparative evaluation. Indian J Exp Biol. 2010;48:479–85.
372 Asparagus racemosus Willd.

53. Sharma P, Chauhan PS, Dutt P, et al. A unique immunostimulant steroidal

sapogenin acid from the roots of Asparagus racemosus. Steroids. 2011;76:
358–64.
54. Sharma U, Kumar N, Singh B. Furostanol saponin and diphenylpentendiol
from the roots of Asparagus racemosus. Nat Prod Commun. 2012;7:995–8.
55. Sharma U, Saini R, Kumar N, Singh B. Steroidal saponins from Asparagus
racemosus. Chem Pharm Bull (Tokyo). 2009;57:890–3.
56. Singh GK, Garabadu D, Muruganandam AV, Joshi VK, Krishnamurthy S.
Antidepressant activity of Asparagus racemosus in rodent models. Pharmacol
Biochem Behav. 2009;91:283–90.
57. Somania R, Singhai AK, Shivgunde P, Jain D. Asparagus racemosus Willd.
(Liliaceae) ameliorates early diabetic nephropathy in STZ induced diabetic
rats. Indian J Exp Biol. 2012;50:469–75.
58. Thatte UM, Dahanukar SA. Comparative study of immunomodulating
activity of Indian medicinal plants, lithium carbonate and glucan. Meth Find
Exp Clin Pharmacol. 1988;10:639–44.
59. Uma B, Prabhakar K, Rajendran S. Anticandidal activity of Asparagus
racemosus. Indian J Pharm Sci. 2009;71:342–3.
60. Venkatesan N, Thiyagarajan V, Narayanan S, et al. Antidiarrhoeal potential
of Asparagus racemosus wild root extracts in laboratory animals. J Pharm
Pharm Sci. 2005;8:39–46.
61. Visavadiya NP, Narasimhacharya AV. Asparagus root regulates cholesterol
metabolism and improves antioxidant status in hypercholesteremic rats.
Evid Based Complement Alternat Med. 2009;6:219–26.
62. Wiboonpun N, Phuwapraisirisan P, Tip-pyang S. Identification of antioxidant
compound from Asparagus racemosus. Phytother Res. 2004;18:771–3.
Atropa belladonna L.
(Solanaceae)

Abstract
The plant is indigenous to south and central Europe and naturalized in southern
England. It is cultivated in central Europe, England, the United States, and
northern India. It was known to the ancients only as a noxious herb, and its
medicinal use is relatively recent. Indian and Chinese physicians also appear to be
not aware of this plant. However, Italian ladies utilized its pupil dilating property
in the 16th century. All animals are not equally affected by this plant; rabbits can
feed upon this plant with impunity, and their pupils may be dilated by application
of their own urine. Birds feed on its fruits without any effect on their eyes, and
snails and slugs feed upon its leaves. It is, however, regarded as a poisonous plant
for humans. By Unani physicians of India, its leaves are used externally as
analgesic and anesthetic; internally, it dries up secretions, acts as antispasmodic
and anti-inflammatory, and used in the treatment of asthma, pleurisy, stomach and
intestinal ulcers, arthritis, gout and all pains of nerve origin. It is also used to
decrease perspiration, and to reduce milk production (lactifuge). All parts of the
plant contain alkaloids, chiefly l-hyoscyamine plus a little atropine and hyoscine;
also, certain volatile bases, pyridine and N-methylpyrroline. Succinic acid,
asparagin and b-methylaesculetin (scopoletin) are found in the leaves. In 1831,
pure alkaloid, atropine was isolated from the plant. Alkaloid contents are highest in
fresh ripe fruit, fresh seeds and fresh leaves. A. belladonna tincture produces
greater anticholinergic effects than that suggested by its alkaloid content,
indicating the presence in leaves of unknown compounds with a significant
biological activity. Pretreatment with water extract shortens the process of
inflammation and accelerates collagen formation, and improves early phases of skin
wound healing in rats. In an RCT, a single belladonna combination with opium rectal
suppository preoperatively in patients undergoing Robotic Assisted Laparoscopic
Prostatectomy significantly improved postoperative pain from bladder spasms
during the first two hours and significantly reduced 24-h morphine use. However,
retrospective analysis of similar use in another hospital did not find any benefit.

© Springer Nature Switzerland AG 2020 373

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_39
374 Atropa belladonna L.

Keywords




Belladonna Bouton-noir Deadly nightshade Galnebær Gemeine






tollkirsche Girisambhawã Luffah Luffana Suci Yabrujussanam

Vernaculars: Urd.: Angurshefa, Luffah, Yabrujussanam; Hin.: Lacchmana lac-

chmani, Sagangur, Suchi; San.: Girisambhawã, Suci; Ben.: Belladona, Yebruj;
Mar.: Girbuti; Ara.: Yabruj-us-sanam; Chi.: 颠茄; Cze.: Rulík zlomocný; Dan.:
Galnebær; Dut.: Dodelijke nachtschade, Gewone wolfskers; Eng.: Belladonna,
Deadly nightshade, Dwale, Sleeping nightshade, Poison black cherry; Fin.: Bel-
ladonna; Fre.: Belladonne commune, Belle-dame, Bouton-noir; Ger.: Gemeine
tollkirsche, Gewöhnliche tollkirsche; Ita.: Belladonna comune; Nor.: Belladon-
naurt; Per.: Inab-es-salib, Luffana; Pol.: Pokrzyk, Pokrzyk wilcza jagoda; Por.:
Beladona-comum, Erva-midriática, Erva-moura-furiosa; Spa.: Belladona común,
Solano furioso; Swe.: Belladonna, Vanlig belladonna; Tur.: Güzelavratotu.
Description: The plant is indigenous to south and central Europe and naturalized in
southern England. It is cultivated in central Europe, England, the United States, and
northern India from Shimla to Kashmir, growing abundantly at altitudes between
1,800–3,600 m.C An erect shrub-like herbaceous plant, with a long, spread-
ing, slender, cylindrical, sometimes slightly downy, often purplish, branches, 1.8 m
high, fleshy, creeping, perennial root, varying from 2.5 to 15 cm in length,LXXXII
yellow-brown externally, white within.CLIV Its leaves are alternate, but on the upper
branches, each leaf is usually accompanied by a smaller, stipule-like leaf.XXV The
blade is ovate, pointed, entire, soft, with conspicuous veins and frequently with a
purplish midrib which may be hairy beneath. Flowers, borne singly in the leaf axils
or in the forks of the branches are drooping; the bell-like corolla five-lobed,

Fig. 1 Atropa belladonna, Plant, Kurt Stüber, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Atropa_bella-donna1.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Atropa belladonna L. 375

dull-purple within, yellowish outside; two celled fruits contain many kidney-shaped
seeds embedded in the pulp, which is somewhat sweet,LXXIV,C and yields a purple
juice (Figs. 1, 2 and 3).CII

Fig. 2 Atropa belladonna, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Atropa_belladonna_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-018.jpg

Fig. 3 Atropa belladonna, Flowers, Tom Oates, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Atropa_Bella-donna3.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
376 Atropa belladonna L.

Actions and Uses: It was known to the ancients only as a noxious herb, and its
medicinal use is relatively recent. Indian and Chinese physicians also appear to be
not aware of this plant. However, Italian ladies utilized its pupil dilating property in
the 16th century.XL All animals are not equally affected by this plant; rabbits can
feed upon this plant with impunity, and their pupils may be dilated by application of
their own urine. Birds feed on its fruits without any effect on their eyes, and snails
and slugs feed upon its leaves.XL It is regarded as a poisonous plant (temperament,
cold 4° and dry 4°) by Unani physicians of India. Externally, its leaves are used as
analgesic and anesthetic; internally, it dries up secretions, acts as antispasmodic and
anti-inflammatory, and used in the treatment of asthma, pleurisy, stomach and
intestinal ulcers, arthritis, gout and all pains of nerve origin. It is also used to
decrease perspiration, and to reduce milk production (lactifuge).LXXVII Belladona is
mydriatic, antispasmodic, anodyne, diuretic and lactifuge, a cardiac, respiratory and
spinal stimulant in low doses; and at high doses, depresses respiratory center in the
medulla.XXI,LXXXI Extract of belladonna is externally applied to relieve pain, and
internally to relieve excessive perspiration.CV In Ayurveda, it is used in the treat-
ment of śula, śotha, kãsa, śwāsa, and kandū.LIX Belladona leaves were introduced
into London Pharmacopoeia in 1809,CXXXXI made official in the United States in
1820, and the root became official in the United States and in Great Britain in
1860;CXXXXI,CLII but no longer official in the United States. Belladonna leaves were
used for preparation of tincture, extract and fluidextract. The tincture contained
30 mg alkaloid/100 ml; the extract 1.25 g alkaloid/100 g; the fluidextract 300 mg
alkaloid/100 ml.CXI These belladonna preparations were administered in carefully
measured subtoxic doses, as an anodyne, relaxant, sedative, antigalactagogue,
antidiuretic or as a means of limiting other glandular secretionsCXXIV or as
mydriatic or antiasthmatic. It was employed in ophthalmology, bradycardia,
Parkinson’s disease (first successfully used drug for it), psychiatry, in treating
convulsions, epilepsy,LXXXII whooping cough, nocturnal emissions, night sweats,
gastric ulcers, kidney and gall bladder stones,CLIV and also as an antidote for
depressant poisons such as opium, muscarine and chloral hydrate.IV,CXXIV
Phytoconstituents: All parts of the plant contain alkaloids, chiefly l-hyoscyamine
plus a little atropine and hyoscine; also, certain volatile bases, pyridine and
N-methylpyrroline. Succinic acid, asparagin and b-methylaesculetin (scopoletin)
are found in the leaves.CXXXXI In 1831, pure alkaloid l-atropine was isolated from
the plant [15]. Alkaloid contents are highest in fresh ripe fruit, fresh seeds and fresh
leaves. When dried, the unripe fruit is the most potent, secondly the leaves and
thirdly, the ripe fruit;XX the alkaloid content of root is highest just before flowers
appear. The entire plant is deficient in alkaloids during prolonged periods of cool
and cloudy weather. Maximum total alkaloid content is 0.8% in seeds, 0.7% in
roots and 0.6% in leavesLXVII Osol mentioned 1.25% alkaloids in leaves extract.CXI
The wood of the plant contains an even higher concentration of alkaloids than the
ripe fruits [2]. Hellaridine present in root resembles atropine in action and is in
proportion of 0.002%.XX Old large stems have low alkaloid content.CLIV For the
drug trade, leaves must contain at least 0.35% hyoscyamine USP, 0.30%
BP;CXXXXI roots 0.45% USP and 0.4% BP.V,CLII
Atropa belladonna L. 377

Pharmacology: Pretreatment with water extract improved early phases of skin

wound healing in rats, as it shortened the process of inflammation and accelerated
collagen formation, and significantly increased wound stiffness as compared to
control tissues [8]. Crude seed extract as well as the purified compounds did not show
significant antimicrobial activity [13]. A. belladonna tincture produced greater anti-
cholinergic effects than that suggested by its alkaloid content, indicating the presence
in leaves of unknown compounds with a significant biological activity [17]. Low
doses produced significant neurotropic and protective effects on stress-induced
behavioral, immunological and gastric alterations [3]. Methanol extract exhibited
significant analgesic, anti-inflammatory and sedative effects in animals [19] while
ethanol root extract showed antibacterial activity against S. aureus and E. coli [18].
Clinical Studies: In an RCT, a single belladonna combination with opium rectal
suppository (B & O) preoperatively in patients undergoing Robotic Assisted
Laparoscopic Prostatectomy (RALP) significantly improved postoperative pain
from bladder spasms during the first two hours and significantly reduced 24-h
morphine use [16]. However, retrospective analysis of similar use in another hos-
pital did not find any benefit [20]. A similar observation was made in patients in
which three B&O suppositories, every 8 h, were used post vaginal surgeries, as
they did not lower pain or substantially lower narcotic use [4]. In a controlled
single-blind trial, male patients with symptomatic and radiologically proven duo-
denal ulcers treated with either glycopyrronium, or 1-hyoscyamine tablets for one
year, were not significantly superior to placebo [12] and prolonged anticholinergic
therapy did not reduce parietal cell mass in patients with duodenal ulcer [11].
Human A/Es, Allergy and Toxicity: Accidental poisoning with belladonna is
common in both children [5, 14, 21] and adults [7, 10] or for suicidal intent [9].
Poisonings may also occur when belladonna tincture or extracts are used for
therapeutic purposes [1]. A case of belladonna poisoning with subdural hematoma
was reported from Turkey [6]. Children have died after eating only three ber-
riesLXVII and the whole plant should be considered toxic due to its alkaloids. These
affect particularly the parasympathetic nervous system; pupils are dilated (near-
blindness from large doses), flushed skin, dryness of mouth and throat, dyspha-
gia,LXXXII nausea, vomiting, muscular weakness, incoordination, rapid heart rate,
weak pulse, with trembling, excitement, delirium and hallucination.XLVI Some
hours later or sooner, depending on the amount consumed, CNS depression [22]
painful respiration, drowsiness, prostration, coma and death occur due to respiratory
and cardiac failure.XXV,CXXXV
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It has not proven very beneficial in scientific studies, and its use in
traditional medicines also seems to be limited due to toxicity.
378 Atropa belladonna L.

References
1. Berdai MA, Labib S, Chetouani K, Harandou M. Atropa belladonna in-
toxication: a case report. Pan Afr Med J. 2012;11:72.
2. Berney C, Wolfensberger TJ. Mydriasis induced by splinter from bella-
donna bush. Klin Monatsbl Augenheilkd. 2000;216:346–7 (French).
3. Bousta D, Soulimani R, Jarmouni I, et al. Neurotropic, immunological and
gastric effects of low doses of Atropa belladonna L., Gelsemium semper-
virens L. and Poumon histamine in stressed mice. J Ethnopharmacol. 2001;
74:205–15.
4. Butler K, Yi J, Wasson M, et al. Randomized controlled trial of post-
operative belladonna and opium rectal suppositories in vaginal surgery.
Am J Obstet Gynecol. 2017;216:491.e1–6.
5. Caksen H, Odabaş D, Akbayram S, et al. Deadly nightshade (Atropa bella-
donna) intoxication: an analysis of 49 children. Hum Exp Toxicol. 2003;
22:665–8.
6. Cikla U, Turkmen S, Karaca Y, et al. An Atropa belladonna L. poisoning
with acute subdural hematoma. Hum Exp Toxicol. 2011;30:1998–2001.
7. Demirhan A, Tekelioğlu ÜY, Yıldız İ, et al. Anticholinergic toxic syndrome
caused by Atropa belladonna fruit (Deadly Nightshade): a case report.
Turk J Anaesthesiol Reanim. 2013;41:226–8.
8. Gál P, Toporcer T, Grendel T, et al. Effect of Atropa belladonna L. on skin
wound healing: biomechanical and histological study in rats and in vitro
study in keratinocytes, 3T3 fibroblasts, and human umbilical vein endothe-
lial cells. Wound Repair Regen. 2009;17:378–86.
9. Heindl S, Binder C, Desel H, et al. Etiology of initially unexplained
confusion of excitability in deadly nightshade poisoning with suicidal intent.
Symptoms, differential diagnosis, toxicology and physostigmine therapy of
anticholinergic syndrome. Dtsch Med Wochenschr. 2000;125:1361–5
(German).
10. Joshi P, Wicks AC, Munshi SK. Recurrent autumnal psychosis. Postgrad
Med J. 2003;79:239–40.
11. Kaye MD, Beck P, Rhodes J, Sweetnam PM. Gastric acid secretion in
patients with duodenal ulcer treated for one year with anticholinergic drugs.
Gut. 1969;10:774–8.
12. Kaye MD, Rhodes J, Beck P, et al. A controlled trial of glycopyrronium and
l-hyoscyamine in the long-term treatment of duodenal ulcer. Gut. 1970;11:
559–66.
13. Khan FZ, Alam M, Saleem R, Rashid I. Biological studies of indigenous
medicinal plants–I: physicochemical and antimicrobial screening of non-
alkaloidal constituents of some solanaceous seeds. Pak J Pharm Sci. 1992;5:
55–61.
14. Laffargue F, Oudot C, Constanty A, Bedu A, Ketterer-Martinon S. Deadly
nightshade (Atropa belladonna) intoxication in a 2-year-old child. Arch
Pediatr. 2011;18:186–8 (Article in French).
Atropa belladonna L. 379

15. Lee MR. Solanaceae IV: Atropa belladonna, deadly nightshade. J R Coll
Physicians Edinb. 2007;37:77–84.
16. Lukasewycz S, Holman M, Kozlowski P, et al. Does a perioperative bella-
donna and opium suppository improve postoperative pain following robotic
assisted laparoscopic radical prostatectomy? Results of a single institution
randomized study. Can J Urol. 2010;17:5377–82.
17. Mazzanti G, Tita B, Bolle P, et al. A comparative study of behavioural and
autonomic effects of atropine and Atropa belladonna. Pharmacol Res
Commun. 1988;20 Suppl 5:49–53.
18. Munir N, Iqbal AS, Altaf I, et al. Evaluation of antioxidant and antimicrobial
potential of two endangered plant species Atropa belladonna and Matricaria
chamomilla. Afr J Tradit Complement Altern Med. 2014;11:111–7.
19. Owais F, Anwar S, Saeed F, et al. Analgesic, anti-inflammatory and neuro-
pharmacological effects of Atropa belladonna. Pak J Pharm Sci. 2014;27:
2183–7.
20. Scavonetto F, Lamborn DR, McCaffrey JM, et al. Prophylactic belladonna
suppositories on anesthetic recovery after robotic assisted laparoscopic
prostatectomy. Can J Urol. 2013;20:6799–804.
21. Trabattoni G, Visintini D, Terzano GM, Lechi A. Accidental poisoning with
deadly nightshade berries: a case report. Hum Toxicol. 1984;3:513–6.
22. Youngken HW. Ergot—a blessing and a Scourge. Econ Bot. 1947;1:372–80.
Azadirachta indica A. Juss.
(Meliaceae)

(Syns.: Melia azadirachta L.; M. indica (A. Juss) Brandis)

Abstract
A fast-growing, evergreen tree, native to the Indian subcontinent, India, Pakistan,
Myanmar, Nepal, Bangladesh, Sri Lanka, and Maldives, widely cultivated in
Africa, and in southern part of Iran, but typically grown in tropical and
semi-tropical regions. It is described as anti-inflammatory, analgesic, antipyretic,
laxative, blood purifier, antibacterial, anthelmintic, antiseptic and wound healer.
Usually, the leaves are pounded and applied to indurations and inflammations,
and wounds are washed with leaves boiled in water, and also powdered leaves are
sprinkled on wounds. Dried flowers are used as a tonic after fever. Leaves are
used in the traditional Nigerian medicine in the treatment of diabetes, and by the
native healers for the treatment of malaria in Meru and Kilifi Districts of Kenya
and Cote d’Ivoire. Neem contains more than 35 biologically active principles;
azadirachtin is the predominant insecticidal active ingredient in seed, leaves, and
other parts of neem tree. Nimbidin, azadirachtin and nimbinin are reportedly the
active compounds responsible for its antibacterial activity. Freshly prepared juice
of green leaves, macerated in water, daily for one month to male mice reduced
number of pregnancies and the litter size, which returned to normal after 6 weeks
of drug free interval, and crude aqueous leaf extract to male rats for 10-weeks
caused a significant decrease in serum testosterone levels, and to mice for 4-weeks
produced reversible but appreciable antiandrogenic effects on male reproductive
organs. Hydroalcohol leaf extract possesses significant blood sugar-lowering
activity in normal and diabetic rats, and aqueous leaf extract highly significantly
lowered FBG, reduced oxidative stress and increased levels of GSH and SOD of
diabetic rats. Aqueous leaf extract is also an effective in vitro aldose reductase
inhibitor, potentially able to reduce cataractogenic effect of diabetes. Freshly
prepared, and dried leaves aqueous extracts produced significant anxiolytic
effects, improved memory and spatial learning in rats with experimental
Alzheimer’s disease, and significantly reduced cerebral hypoperfusion-induced
functional disturbances in rats. Leaf aqueous extract treatment of Nigerian
patients with malaria also lowered serum TC and LDL-C, and significantly
© Springer Nature Switzerland AG 2020 381
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_40
382 Azadirachta indica A. Juss.

increased triacylglycerol and HDL-C. Neem mouthwash inhibited growth of S.

mutans, reduced plaque-induced gingivitis, and reduced ability of some
Streptococci to colonize tooth surfaces, and the gel application significantly
reduced the plaque index and bacterial count.

Keywords
Azadarac

Azâdirakht

Indian lilac Lian shu

Margousier
Neem





Niembaum Paraiso Picumarda Tesbih ağaçı

Vernaculars: Urd. and Hin.: Neem; San.: Arista, Nimba, Picumanda, Picumarda,
Tiktaka; Ben.: Neem, Nim, Nimb; Guj.: Dhanujhada, Limba; Mal.: Aria bepon,
Ariyaveppu, Veppa, Vembu, Veppu; Mar.: Kadunimba, Limba, Nimbay; Tam.:
Sengumaru, Vembu, Veppa vepam, Veppu; Tel.: Bevu, Veepachettu, Vepa, Yeppa
nimbarnu; Ara.: Azâdirakht, Margosa, Neem, Zanzalakht; Bur.: Tamaka, Tamar;
Chi.: Ku lian, Ku-lien-taze, Lian shu, Lientaze; Eng.: Ash-leaved bead tree, Indian
lilac, Margosa tree; Fin.: Neembuu; Fre.: Azadirachta de l’Inde, Lilas des Indes,
Margousier, Neem des Indes; Ger.: Niembaum, Nimbaum; Ind.: Mind; Ita.: Albero
dei paternostri, Albero della pazienza, Azadarac, Lilacco delle Indie; Maly.:
Mambu, Sadu; Per.: Azaddarakhti, Charish; Sin.: Kohomba; Spa.: Paraiso; Tha.:
Cha-tang, Sadao; Tur.: Azadiraht, Tesbih ağaçı, Zehri zemin; Vie.: Sàu-dàu.
Description: It is a fast-growing, evergreen tree, that reaches a height of 15–20 m,
and sometimes even higher. A native to the Indian subcontinent, India, Pakistan,
Myanmar, Nepal, Bangladesh, Sri Lanka, and Maldives, widely cultivated in
Africa, and in southern part of Iran, but typically grown in tropical and semi-tropical
regions. Branches are wide and spreading, forming a fairly dense roundish crown of
15–20 m diameter in old trees. Leaves opposite, pinnate 20–40 cm long; with 20–
31 medium to dark-green leaflets about 3–8 cm long, glabrous, ovate-lanceolate to
lanceolate, sickle-shaped; base highly asymmetric; margin coarsely serrate. White,
fragrant flowers, 5–6 mm long and 8–11 mm wide are arranged in more-or-less
drooping axillary panicles, up to 25 cm long. Fruit is smooth, glabrous, olive-
like drupe, varying in shape from elongate oval to nearly roundish; when ripe
1.4–2.8 cm by 1–1.5 cm. Fruit skin is thin, the bitter-sweet pulp is yellowish-white,
and very fibrous. White, hard inner shell of the fruit encloses one, rarely two, or
three, elongated seeds. Dried fruit resembles a small raisin, the inner portion of the
pulp is adherent to the stone. Fruits and seeds are the source of neem oil. Neem oil is
of pale-yellow color, bitter taste and a powerful garlic-like odor. Neem bark is
coarsely fibrous, and its thickness varies with the age of the tree; the external
surface is rough, fissured, of rusty grey color, while the inner surface is yellowish.
All parts of the tree have medicinal properties. Leaves, flowers, and neem oil are
normally used therapeutically, but bark and fruits are also used (Figs. 1, 2 and 3).XL
Actions and Uses: While in Unani medicine, its temperament is regarded as hot 1°
and dry 1°, Ayurvedic Vaids consider it cold 1° and dry 1°. It is described as
anti-inflammatory, analgesic, antipyretic, laxative, blood purifier, antibacterial,
Azadirachta indica A. Juss. 383

Fig. 1 Azadirachta indica, Tree, Mamun2a, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Neem_tree.JPG

Fig. 2 Azadirachta indica, Leaves, Prabhupuducherry, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Neem_tree_leaves.JPG; https://
creativecommons.org/licenses/by/3.0/deed.en
384 Azadirachta indica A. Juss.

Fig. 3 Azadirachta indica, Leaves and Flowers, J.M. Garg, WikimediaCommons; Unported CC
BY 3.0, https://commons.wikimedia.org/wiki/File:Neem_(Azadirachta_indica)_in_Hyderabad_
W_IMG_6976.jpg; https://creativecommons.org/licenses/by/3.0/deed.en

anthelmintic, antiseptic and wound healer. Usually, the leaves are pounded and
applied to indurations and inflammations, and wounds are washed with leaves
boiled in water, and also powdered leaves are sprinkled on wounds. Neem twigs are
used as toothbrush to treat halitosis.LXXVII In Ayurveda, the stem bark is used in
vrana, kustha, prameha, kandū, krmiroga, jwara, dãha, and raktapitta; and the
dried leaves are used in the treatment of kustha, prameha, krmiroga, jwara, vrana,
dãha, raktapitta, ãmaśotha, netraroga, and visaroga.LIX Dried flowers are used as a
tonic after fever.XL A poultice of green leaves is used for boils, and fruits are used
for leprosy and other skin diseases. An infusion of the bark, fruits and petiols is
used in fever and diabetes, and as a tonic. Smoke of dried leaves drives away
mosquitoes, and they are also used as mothballs [137]. Leaves are used in the
traditional Nigerian medicine in the treatment of diabetes [15], and by the native
healers for the treatment of malaria in Meru and Kilifi Districts of Kenya [85] and
Cote d’Ivoire [24]. On the island of Bali in Indonesia, neem leaves are used as
diuretic, and for the treatment of diabetes, headache, heartburn, and to stimulate
appetite; whereas cold pressed seed oil is chiefly used as insecticide, but also for
cosmetic, medicinal and agricultural purposes [154].
Phytoconstituents: Neem contains more than 35 biologically active principles;
azadirachtin is the predominant insecticidal active ingredient in seeds, leaves, and
other parts of neem tree [107]. Nimbidin, azadirachtin and nimbinin are reportedly
the active compounds responsible for its antibacterial activity [94]. Nimbidin is a
mixture of tetranortriterpenes and is the major active principle of seed oil [77].
Triterpenoids from methanol extracts of seed kernels [96], from fresh leaves
Azadirachta indica A. Juss. 385

[41, 145, 146], and from fruits [92]; limonoid and steroidal saponin [95], limonoids:
azadirachtin A, azadirachtin B, salannin, nimbin, azadirone, azadiradione,
epoxyazadiradione, 17b-hydroxyazadiradione [125], and gedunin, an antimalarial
agent [79], azadiraindins E-G [170] from the leaves; hydrocarbons: icosane, doc-
osane, 2-methyltricosane, and docosene from fruit coats [147], and limonoids (te-
tranortriterpenoids) from n-hexane seed extract [4], have been isolated. Other
compounds isolated from leaves include nimbocinone, nimolinone, kulactone,
nimocinolides, isonimocinolide, flavonoids, myricetin, meldenindiol, margosino-
lide, isomargosinolide, vilasinin, and desacetyldihydronimbic acid [8, 23]. Steam
distillate of fresh matured leaves yielded an odorous viscous oil, exhibiting anti-
fungal activity against T. mentagrophytes, and was identified as a mixture of cyclic
tri- and tetrasulfides [110]. A quick drying of leaves at 110 °C followed by
air-drying is reported to maximally retain bioactive compounds and antioxidant
activity [170]. Seeds contain 45% oil [42]; mahmoodin, azadirone, azadiradione,
epoxyazadiradione, nimbin, gedunin, deacetylnimbin, 17-hydroxyazadiradione and
naheedin have been isolated from it [147]. Nimbolide and 28-deoxonimbolide [84],
margosone and margosolone [9] were reported from stem bark.
Pharmacology: It is reported antibacterial, antifungal, antiviral, diuretic, antihis-
taminic, anticancer, hypoglycemic, hypocholesterolemic, anti-inflammatory, anti-
pyretic and adaptogenic [26, 29, 43, 131].CXXIII,CXXVI Freshly prepared juice of
green leaves, macerated in water, daily for one month to male mice reduced number
of pregnancies and the litter size, which returned to normal after 6 weeks of drug
free interval [48], and crude aqueous leaf extract to male rats for 10-weeks caused a
significant decrease in serum testosterone levels [122], and to mice for 4-weeks
produced reversible but appreciable anti-androgenic effects on male reproductive
organs [102]. Aqueous leaves extract makes human sperms completely immotile
in vitro within 20 s at 3 mg concentration, and is also spermicidal [81]. Ethanol leaf
extract in oral doses of 100 mg/kg daily for 21-days to male rats did not interfere
with spermatogenesis, but caused anti-implantation and abortifacient effects in
females mated by the males fed with the leaf extract [44]. Antiandrogenic activity
of leaves in male rats has also been reported [5–7, 59, 60, 72, 75, 76]. A purified
seed extract caused complete resorption of embryos by day 15 of pregnancy in rats
[106], and caused abortion in both baboon and monkeys [105, 156]. A mixture of
six components, comprising of saturated, mono- and di-unsaturated FFAs and their
methyl esters was identified as the active fraction [56] that acts by activating cell
mediated immune reactions [104]. Ethanol bark extract (i.p.) to rats for ten-weeks
significantly reduced serum testosterone, and adversely affected sperm counts,
morphology and viability of male rats, and reduced serum LH levels without
affecting FSH levels in female rats [130]. Methanol leaves extract also significantly
reduced only LH levels in rats [118]. Seed oil treatment significantly reduced
spermatozoan motility and density, leading to reduced fertility rate in rats and
rabbits [140]. As a postcoital contraceptive, neem oil at subcutaneous doses of up to
0.3 ml/rat did not show any estrogenic, antiestrogenic or progestational or
antiprogesterone activity [126]. However, intravaginal administration of 25 µl of
386 Azadirachta indica A. Juss.

neem oil in rats produced anti-implantation effect due to its antiestrogenic activity;
the resorption or expulsion of implanted fetuses may be due to direct toxicity, or
antiprogesterone effect [133], Intravaginal application of the oil, pre and post coital
also prevented pregnancy in rhesus monkeys [22] (though it was reported to show
no antiestrogenic or antiprogesterone activities via subcutaneous route). Intrauterine
application of neem oil induced a reversible, but long-lasting preimplantation block
in fertility in rats, lasting for 107–180 days, even after repeated matings [165]. The
intra-vas administration of neem oil blocked spermatogenesis without affecting
testosterone production in rats [164].
Hydroalcohol leaf extract possesses significant blood sugar-lowering activity in
normal and diabetic rats [36], and aqueous leaf extract highly significantly lowered
FBG of diabetic rats, reduced oxidative stress and increased levels of GSH and
SOD of diabetic rats [31, 97]. Aqueous leaf extract also normalized the high-fat
and fructose-induced altered levels of blood glucose, serum insulin, lipid profile and
insulin signaling molecules in rats [134, 138], and attenuated stress-induced ele-
vations of cholesterol and urea levels [136]. Both pretreatment and postdiabetes
treatment of rabbits with leaf extract or seed oil significantly prevents rise in blood
glucose and lowers it [82]. Aqueous leaf extract is also an effective in vitro aldose
reductase inhibitor, potentially able to reduce cataractogenic effect of diabetes [64].
Ethanol leaf extract showed modest antihyperglycemc effect in diabetic rats [74],
without affecting serum cortisol level [58]. Petroleum ether extracts of kernel and
husk of seeds prevented diabetes-caused oxidative stress, and protected rats from
cardiac damage [62, 63]. Treatment of diabetic rats with ethanol leaf extract
ameliorated diabetes-caused nephropathy [117]. Pretreatment with ethanol and
aqueous leaf extracts significantly lowered diabetes-induced oxidative stress [138,
144], MNNG-induced [152] and DMBA-induced hamster buccal pouch carcino-
genesis [100], by decreasing LPO and enhancing antioxidant status.
Intravenous administration of aqueous leaf extract caused profound hypotension
with a minimal decrease in HR, and a weak antiarrhythmic activity in anesthetized
rabbits [159], but alcohol leaf extract produced significant fall in BP with initial
bradycardia followed by cardiac arrhythmia in rats [37, 86]. Aqueous leaf extract
protected against isoprenalin (isoproterenol)-induced MI in rats [123], protected
mice against doxorubicin cardiotoxicity [89], and produced negative inotropic and
chronotropic effects in isolated hearts [83]. Concurrent administration of aqueous
extract prevents development of DOCA-induced hypertension in rats [114].
Freshly prepared, and dried leaves aqueous extracts produced significant anxiolytic
effects [71, 128], improved memory and spatial learning in rats with experimental
Alzheimer’s disease [128], and significantly reduced cerebral hypoperfusion-induced
functional disturbances in rats [171].
Oral pretreatment with water soluble fraction of alcoholic leaves extract exerts
significant anti-inflammatory activity in rats [38]; chloroform leaves extract
sequentially extracted after petroleum ether, and its fractions also showed significant
anti-inflammatory effect; the overall anti-inflammatory activity is suggested to result
from cumulative and synergistic effects of its constituents [162]. Carbon tetrachlo-
ride extract of fruit skin and azadiradione also exhibit significant antinociceptive
Azadirachta indica A. Juss. 387

and anti-inflammatory activities in rats [70]. Okpanyi [116] reported potent

anti-inflammatory effect of the tincture; that was a more potent inhibitor of PG
synthetase than acetylsalicylic acid, and Okpanyi and Ezeukwu [115] also reported
antipyretic effect. Leaf extracts are protective against APAP-induced liver damage in
rats [27, 35, 172], against DEN-hepatotoxicity [87], cisplatin-hepatotoxicity [49],
DMBA-hepatotoxicity [90], and cisplatin-nephrotoxicity and oxidative stress in rats
[2]. Aqueous leaf and bark extracts are equipotent to ranitidine in gastric acid
antisecretory effect in rats, but more potent than omeprazole, and significantly block
LPO and prevent oxidative damage of gastric mucosa [19, 34]. Aqueous leaf extract
significantly inhibited basal and histamine-induced gastric acid secretion [129],
attenuated stress-induced gastric ulcerogenesis [136], and exhibited antiulcer and
ulcer-healing activities in NIDDM rats [51]. Ethanol (50%) extract of dried leaves
also effectively healed TNBSA-induced colitis in rats [57]. Nimbidin significantly
inhibits gastric acid secretion in rats and cats [124], and azadiradione, isolated from
seeds, exhibits potent antiulcer activity through inhibition of proton pump activity
[148].
Aqueous twigs extract significantly inhibited growth of S. mutans, S. salivavius,
S. mitis, and S. sanguis [127]. Ethanol leaf extract showed higher inhibition for
S. aureus [98], while aqueous and methanol extracts were active against P. testos-
teroni, S. epidermidis, K. pneumoniae, B. subtilis, P. morganii, and M. flavus [109].
Leaf extract exhibited significant antimicrobial activity against E. faecalis [108,
135], and neem oil inhibited growth of E. coli and also influenced the virulence of
E. coli viable cells [46]. Aqueous leaf extract inhibited both in vitro and in vivo
Dengue virus type-2 replication [121], and aqueous bark extract potently inhibited
entry of HSV-1 virus into natural target cells [160]. A crude acetone/water leaves
extract completely inhibited growth of asexual and the sexual forms of P. falci-
parum parasites at a concentration of 5.0 µg/mL [161]. Oral dosing with methanol
leaf extract for four days significantly suppressed P. berghei parasitemia in mice
[1]. Tella [157, 158] reported that oral and subcutaneous administration of aqueous
leaf extract was ineffective in P. berghei malaria. Oral aqueous leaf extract at doses
of 1,000 and 2,000 mg/kg for 4-days to mice with malaria infection-induced renal
toxicity restored BUN and creatinine levels to near normal [149]. Ethanol extracts
of leaves and seeds exhibited significant in vitro antileishmanial activity [30], and
methanol leaf extract showed both in vitro and in vivo antileishmanial activity [73].
Aqueous, ethanol and acetone fruit extracts are reported to inhibit growth of E. coli,
K. pneumonae, P. aeruginosa, and E. faecalis [139]. Commercial shampoos based
on seed extract are reportedly more effective than permethrin-based products in
killing lice collected from school children [3, 66].
Aqueous and ethanol leaf extracts suppressed DMBA-initiated oral carcino-
genesis and reduced incidence of neoplasms in hamster buccal pouch [18, 150],
DMBA-initiated skin carcinogenesis [12, 13], NDEA-induced hepatocarcinogene-
sis [28], significantly lowered LPO and enhanced hepatic levels of glutathione and
glutathione dependent enzymes in chemically-induced carcinogeneses in rodents
[10, 11, 45, 88, 151, 153]. Aqueous leaf extract did not show in vitro cytotoxicity
on Ehrlich carcinoma and B16 melanoma cells, but inhibited growth of tumors and
388 Azadirachta indica A. Juss.

prolonged survival of mice [21, 65]. Ethanol leaf extract caused death of prostate
cancer cells by inducing apoptosis, reducing level of antiapoptotic protein, Bcl-2
and increasing level of apoptosis promoter Bax protein [91]. Extracts of leaves and
stem bark act as immunostimulator [25, 99, 111, 132, 155], significantly attenuate
stress-induced suppression of humoral immunity [136], prevent CP hematological
toxicity, reducing extent of leucopenia and neutropenia in normal and tumor
bearing CP-treated mice [61]. Neem oil is a nonspecific immunostimulant, but
selectively activates cell-mediated immune mechanisms [163]. A compound puri-
fied from methanol leaf extract inhibits phospholipase A2 enzymes of Cobra and
Russell’s viper venoms [103].
Clinical Studies: Powdered seeds, or their aqueous and alcoholic extracts in doses
of 2 g tid for 14-days to treatment naïve, and uncontrolled on oral antidiabetic
agents, type 2 diabetic Pakistani patients significantly lowered blood glucose levels
[167]. Leaf aqueous extract treatment of Nigerian patients with malaria also low-
ered serum TC and LDL-C, and significantly increased triacylglycerol and HDL-C
[112]. Lyophilized powder of bark aqueous extract administered in a dose of 30–
60 mg twice daily to Indian patients with gastroduodenal ulcers for 10-days, caused
a significant decrease in gastric acid secretion and its pepsin activity, and almost
completely healed duodenal ulcers after 10-weeks [20]. Neem mouthwash inhibited
growth of S. mutans [166], reduced plaque-induced gingivitis [33, 141], and
reduced ability of some Streptococci to colonize tooth surfaces [169], and the gel
application significantly reduced the plaque index and bacterial count [120].
Dressing with a combination of extract of Hypericum perforatum flowers and
neem oil (Hyperoil®) saved a 67-year-old obese Italian woman, with type 2 diabetes
for 25 years, poor glycemic control and a history of painful diabetic neuropathy for
8-years, from potential amputation due to diabetic ulcers of the third and fourth toes
[67, 68]. Application of 2% neem oil mixed with coconut oil to exposed body parts
of volunteers, offered about 90% protection against Anopheles mosquitoe bites for
12 h [101, 142]. Application of a paste of neem leaves and turmeric cured 97% of
814 Indian patients of scabies within 3–15-days of treatment [32]. Burning of neem
oil (1%) mixed in kerosene also significantly reduced biting of human volunteers by
Anopheles mosquitoes than against Culex [143].
Mechanism of Action: Hydroalcohol leaf extract significantly blocks in vitro
inhibitory effect of serotonin on glucose-mediated insulin secretion from rat pan-
creas [39], and blocks epinephrine-induced reduction in peripheral utilization of
glucose and glycogenolytic effect in diabetic rabbits [40]. Aqueous leaf extract is a
potent a-amylase inhibitor, while acetone extract exhibits a very strong a-
glucosidase inhibitory activity [78]. Two limonoids, azadiradione and gedunin also
exhibit human pancreatic a-amylase inhibitory activity [125]. The mechanism in
gastric acid antisecretory and ulcer healing properties involves histamine H2
receptors [129], and the gastric mucosal proton pump inhibition [50]. Aqueous leaf
extract potentially increases detoxification of carcinogens for its anticancer effects
[53, 54], increases Hb, RBCs, and WBCs [55].
Azadirachta indica A. Juss. 389

Human A/Es, Allergy and Toxicity: A 35-year-old Hispanic man in the United
States with G-6-PD deficiency suffered an episode of hemolytic anemia after
ingesting a Mexican tea of the Neem tree. The patient was overdosing himself
several folds with the tea [119].
Animal Toxicity: Aqueous extract administered to mice up to a dose of
2,000 mg/kg was nontoxic [149]. Feeding of leaves 2 and 5% of diet to Brown
Hisex chicks from their 7 to 35th day of age caused significant hematological
changes and hepatonephropathy [69], and oral crude ethanol leaf extract to mice for
6-weeks was detrimental to normal spermatogenesis [16]; the genotoxic effect was
attributed to azadirachtin [80]. Ethanol bark extract, orally administered to male rats
for three-weeks significantly decreased WBC and platelet counts, serum triacyl-
glycerol and HDL-C, and increased serum TC, LDL-C and atherogenic index [14].
LD50 (i.p.) of aqueous leaf and seed extracts were reported to be 6.2 and
9.4 mL/kg, respectively [17]. Oral LD50 of neem seed oil was 14 ml/kg in rats, and
24 ml/kg in rabbits [52]. Deng et al. [47] reported oral LD50 of neem oil as
31.95 g/kg in mice, but no significant subacute toxicity up to a dose of 1,600 mg/kg
for 28 days. Oral administration of the oil to mice at a dose of 1,600 mg/kg/day for
90-days produced varying degrees of damage to testicles, liver and kidneys; the
no-observed-adverse-effect level (NOAEL) dose was found to be 177 mg/kg for
mice of either sex [168]. However, a bitterless, odorless and colorless neem seed oil
(10%), fed to three generations of rats was nontoxic and showed no adverse effects
on the reproductive parameters [42].
Potential for Drug-Herb Interactions: Feeding rats with diet containing 12.5%
neem flowers for 2-weeks strongly induced phase II enzymes (GST) in rat liver,
while markedly reducing levels of most phase I reactions [93]. Concurrent
administration of aqueous leaf extract with chloroquin resulted in a significant
decrease in serum concentration, slower absorption, elimination, AUC, and longer
half-life of chloroquine in rabbits [113].
Commentary: Neem has been known for its antibacterial activity for centuries. Its
use as antidiabetic agent in various cultures was also corroborated in clinical trials,
though further studies in larger number of patients would be preferred. The
antifertility effect of Neem oil also requires clinical studies.

References
1. Abatan MO, Makinde MJ. Screening Azadirachta indica and Pisum
sativum for possible antimalarial activities. J Ethnopharmacol. 1986;17:
85–93.
2. Abdel Moneim AE, Othman MS, Aref AM. Azadirachta indica attenuates
cisplatin-induced nephrotoxicity and oxidative stress. Biomed Res Int. 2014;
2014:647131.
3. Abdel-Ghaffar F, Semmler M. Efficacy of neem seed extract shampoo on
head lice of naturally infected humans in Egypt. Parasitol Res. 2007;100:
329–32.
390 Azadirachta indica A. Juss.

4. Akihisa T, Takahashi A, Kikuchi T, et al. The melanogenesis-inhibitory,

anti-inflammatory, and chemopreventive effects of limonoids in n-hexane
extract of Azadirachta indica A. Juss. (neem) seeds. J Oleo Sci. 2011;60:
53–9.
5. Aladakatti RH, Ahamed RN. Changes in Sertoli cells of albino rats induced
by Azadirachta indica A. Juss. leaves. J Basic Clin Physiol Pharmacol.
2005;16:67–80.
6. Aladakatti RH, Ahamed RN. Effect of Azadirachta indica leaves on rat
spermatozoa. Indian J Exp Biol. 1999;37:1251–4.
7. Aladakatti RH, Nazeer Ahamed R, Ahmed M, Ghosesawar MG. Sperm
parameters changes induced by Azadirachta indica in albino rats. J Basic
Clin Physiol Pharmacol. 2001;12:69–76.
8. Anonymous. Neem: a tree for solving global problems. Washington, DC,
USA: National Research Council, National Academy Press; 1992.
9. Ara I, Siddiqui BS, Faizi S, Siddiqui S. Tricyclic diterpenes from the stem
bark of Azadirachta indica. Planta Med. 1990;56:84–6.
10. Arakaki J, Suzui M, Morioka T, et al. Antioxidative and modifying effects of a
tropical plant Azadirachta indica (Neem) on azoxymethane-induced pre-
neoplastic lesions in the rat colon. Asian Pac J Cancer Prev. 2006;7:467–71.
11. Arivazhagan S, Balasenthil S, Nagini S. Garlic and neem leaf extracts
enhance hepatic glutathione and glutathione dependent enzymes during
N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcino-
genesis in rats. Phytother Res. 2000;14:291–3.
12. Arora N, Koul A, Bansal MP. Chemopreventive activity of Azadirachta
indica on two-stage skin carcinogenesis in murine model. Phytother Res.
2011;25:408–16.
13. Arora N, Bansal MP, Koul A. Modulatory effects of Azadirachta indica leaf
extract on cutaneous and hepatic biochemical status during promotion phase
of DMBA/TPA-induced skin tumorigenesis in mice. Indian J Biochem
Biophys. 2013;50:105–13.
14. Ashafa AO, Orekoya LO, Yakubu MT. Toxicity profile of ethanolic
extract of Azadirachta indica stem bark in male Wistar rats. Asian Pac J
Trop Biomed. 2012;2:811–7.
15. Atangwho IJ, Ebong PE, Eyong EU, Asmawi MZ, Ahmad M. Synergistic
antidiabetic activity of Vernonia amygdalina and Azadirachta indica:
biochemical effects and possible mechanism. J Ethnopharmacol. 2012;141:
878–87.
16. Awasthy KS. Genotoxicity of a crude leaf extract of neem in male germ
cells of mice. Cytobios. 2001;106 Suppl 2:151–64.
17. Bakr SA. Evaluation of acute toxicity of water extract of Azadirachta
indica leaves and seeds in rats. Pak J Biol Sci. 2013;16:697–700.
18. Balasenthil S, Arivazhagan S, Ramachandran CR, et al. Chemopreventive
potential of neem (Azadirachta indica) on 7,12-dimethylbenz[a]anthracene
(DMBA) induced hamster buccal pouch carcinogenesis. J Ethnopharmacol.
1999;67:189–95.
Azadirachta indica A. Juss. 391

19. Bandyopadhyay U, Biswas K, Chatterjee R, et al. Gastroprotective effect

of Neem (Azadirachta indica) bark extract: possible involvement of H(+)-
K(+)-ATPase inhibition and scavenging of hydroxyl radical. Life Sci.
2002;71:2845–65.
20. Bandyopadhyay U, Biswas K, Sengupta A, et al. Clinical studies on the
effect of Neem (Azadirachta indica) bark extract on gastric secretion and
gastroduodenal ulcer. Life Sci. 2004;75:2867–78.
21. Baral R, Chattopadhyay U. Neem (Azadirachta indica) leaf mediated
immune activation causes prophylactic growth inhibition of murine Ehrlich
carcinoma and B16 melanoma. Int Immunopharmacol. 2004;4:355–66.
22. Bardhan J, Riar SS, Sawhney RC, et al. Neem oil—a fertility controlling
agent in rhesus monkey. Indian J Physiol Pharmacol. 1991;35:278–80.
23. Basak SP, Chakroborty DP. Chemical investigation of Azadirachta indica
leaf (M. azadirachta). J Indian Chem Soc. 1969;45:466–7.
24. Benoit F, Valentin A, Pelissier Y, et al. In vitro antimalarial activity of
vegetal extracts used in West African traditional medicine. Am J Trop Med
Hyg. 1996;54:67–71.
25. Beuth J, Schneider H, Ko HL. Enhancement of immune responses to neem
leaf extract (Azadirachta indica) correlates with antineoplastic activity in
BALB/c-mice. In Vivo. 2006;20:247–51.
26. Bhakuni DS, Dhar ML, Dhar MM, et al. Screening of Indian plants for
biological activity II. Indian J Exp Biol. 1969;7:250.
27. Bhanwra S, Singh J, Khosla P. Effect of Azadirachta indica (Neem) leaf
aqueous extract on paracetamol-induced liver damage in rats. Indian J
Physiol Pharmacol. 2000;44:64–8.
28. Bharati S, Rishi P, Koul A. Azadirachta indica exhibits chemopreventive
action against hepatic cancer: studies on associated histopathological and
ultrastructural changes. Microsc Res Tech. 2012;75:586–95.
29. Bhide NK, Mehta DJ, Altekar WW, Lewis RA. Toxicity of sodium
nimbidinate. Indian J Med Sci. 1958;12:146–9.
30. Carneiro SM, Carvalho FA, Santana LC, et al. The cytotoxic and
antileishmanial activity of extracts and fractions of leaves and fruits of
Azadirachta indica (A. Juss.). Biol Res. 2012;45:111–6.
31. Chandra A, Mahdi AA, Singh RK, et al. Effect of Indian herbal hypogly-
cemic agents on antioxidant capacity and trace elements content in diabetic
rats. J Med Food. 2008;11:506–12.
32. Charles V, Charles SX. The use and efficacy of Azadirachta indica ADR
(‘Neem’) and Curcuma longa (‘Turmeric’) in scabies. A pilot study. Trop
Geogr Med. 1992;44:178–81.
33. Chatterjee A, Saluja M, Singh N, Kandwal A. To evaluate the antigin-
givitis and antipalque effect of an Azadirachta indica (neem) mouthrinse
on plaque induced gingivitis: a double-blind, randomized, controlled trial.
J Indian Soc Periodontol. 2011;15:398–401.
34. Chattopadhyay I, Nandi B, Chatterjee R, et al. Mechanism of antiulcer
effect of Neem (Azadirachta indica) leaf extract: effect on H+-K+-ATPase,
392 Azadirachta indica A. Juss.

oxidative damage and apoptosis. Inflammopharmacology. 2004;12:

153–76.
35. Chattopadhyay RR, Sarkar SK, Ganguly S, et al. Hepatoprotective activity
of Azadirachta indica leaves on paracetamol induced hepatic damage in
rats. Indian J Exp Biol. 1992;30:738–40.
36. Chattopadhyay RR. A comparative evaluation of some blood sugar
lowering agents of plant origin. J Ethnopharmacol. 1999;67:367–72.
37. Chattopadhyay RR. Effect of Azadirachta indica hydroalcoholic leaf
extract on the cardiovascular system. Gen Pharmacol. 1997;28:449–51.
38. Chattopadhyay RR. Possible biochemical mode of anti-inflammatory
action of Azadirachta indica A. Juss. in rats. Indian J Exp Biol. 1998;36:
418–20.
39. Chattopadhyay RR. Possible mechanism of antihyperglycemic effect of
Azadirachta indica leaf extract: part V. J Ethnopharmacol. 1999;67:373–6.
40. Chattopadhyay RR. Possible mechanism of antihyperglycemic effect of
Azadirachta indica leaf extract. Part IV. Gen Pharmacol. 1996;27:431–4.
41. Chen J, Chen J, Sun Y, et al. Cytotoxic triterpenoids from Azadirachta
indica. Planta Med. 2011;77:1844–7.
42. Chinnasamy N, Harishankar N, Kumar PU, Rukmini C. Toxicological
studies on debitterized Neem oil (Azadirachta indica). Food Chem
Toxicol. 1993;31:297–301.
43. Chopra IC, Gupta KC, Nazir BN. Preliminary study of antibacterial
substances from Melia azidirachta. Indian J Med Res. 1952;40:511–5.
44. Choudhary DN, Singh JN, Verma SK, Singh BP. Antifertility effects of
leaf extracts of some plants in male rats. Indian J Exp Biol. 1990;28:714–6.
45. Dasgupta T, Banerjee S, Yadava PK, Rao AR. Chemopreventive potential
of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model
systems. J Ethnopharmacol. 2004;92:23–36.
46. Del Serrone P, Toniolo C, Nicoletti M. Neem (Azadirachta indica A.
Juss.) oil to tackle enteropathogenic Escherichia coli. Biomed Res
Int. 2015;2015:343610.
47. Deng YX, Cao M, Shi DX, et al. Toxicological evaluation of neem
(Azadirachta indica) oil: acute and subacute toxicity. Environ Toxicol
Pharmacol. 2013;35:240–6.
48. Deshpande VY, Mendulkar KN, Sadre NL. Male antifertility activity of
Azadirachta indica in mice. J Postgrad Med. 1980;26:167–70.
49. Dkhil MA, Al-Quraishy S, Aref AM, et al. The potential role of Azadirachta
indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in
female rats. Oxid Med Cell Longev. 2013;2013:741817.
50. Dorababu M, Joshi MC, Bhawani G, et al. Effect of aqueous extract of
neem (Azadirachta indica) leaves on offensive and diffensive gastric
mucosal factors in rats. Indian J Physiol Pharmacol. 2006;50:241–9.
51. Dorababu M, Prabha T, Priyambada S, et al. Effect of Bacopa monniera
and Azadirachta indica on gastric ulceration and healing in experimental
NIDDM rats. Indian J Exp Biol. 2004;42:389–97.
Azadirachta indica A. Juss. 393

52. Gandhi M, Lal R, Sankaranarayanan A, et al. Acute toxicity study of the

oil from Azadirachta indica seed (neem oil). J Ethnopharmacol. 1988;
23:39–51.
53. Gangar SC, Koul A. Azadirachta indica leaf extract modulates initiation
phase of murine forestomach tumorigenesis. Indian J Biochem Biophys.
2007;44:209–15.
54. Gangar SC, Koul A. Azadirachta indica modulates carcinogen biotrans-
formation and reduced glutathione at periinitiation phase of benzo(a)
pyrene induced murine forestomach tumorigenesis. Phytother Res. 2008;22:
1229–38.
55. Gangar SC, Sandhir R, Koul A. Effects of Azadirachta indica on certain
hematological parameters during benzo(a)pyrene induced murine forestom-
ach tumorigenesis. Eur Rev Med Pharmacol Sci. 2010;14:1055–72.
56. Garg S, Talwar GP, Upadhyay SN. Immunocontraceptive activity guided
fractionation and characterization of active constituents of neem (Azadir-
achta indica) seed extracts. J Ethnopharmacol. 1998;60:235–46.
57. Gautam MK, Goel S, Ghatule RR, et al. Azadirachta indica attenuates
colonic mucosal damage in experimental colitis induced by trinitrobenzene
sulfonic acid. Indian J Pharm Sci. 2013;75:602–6.
58. Gholap S, Kar A. Hypoglycaemic effects of some plant extracts are
possibly mediated through inhibition in corticosteroid concentration.
Pharmazie. 2004;59:876–8.
59. Ghosesawar MG, Ahamed RN, Ahmed AW, Aladakatti RH. Ultrastruc-
tural changes in cauda epididymidal epithelial cell types of Azadirachta
indica leaf treated rats. Indian J Exp Biol. 2004;42:1091–5.
60. Ghosesawar MG, Ahamed RN, Ahmed M, Aladakatti RH. Azadirachta
indica adversely affects sperm parameters and fructose levels in vas deferens
fluid of albino rats. J Basic Clin Physiol Pharmacol. 2003;14:387–95.
61. Ghosh D, Bose A, Haque E, Baral R. Pretreatment with neem (Azadirachta
indica) leaf preparation in Swiss mice diminishes leukopenia and enhances
the antitumor activity of cyclophosphamide. Phytother Res. 2006;20:814–8.
62. Gupta NK, Srivastva N, Bubber P, Puri S. The antioxidant potential of
Azadirachta indica ameliorates cardioprotection following diabetic
mellitus-induced microangiopathy. Pharmacogn Mag. 2016;12 Suppl 3:
S371–8.
63. Gupta S, Kataria M, Gupta PK, et al. Protective role of extracts of neem
seeds in diabetes caused by streptozotocin in rats. J Ethnopharmacol. 2004;
90:185–9.
64. Halder N, Joshi S, Gupta SK. Lens aldose reductase inhibiting potential of
some indigenous plants. J Ethnopharmacol. 2003;86:113–6.
65. Haque E, Mandal I, Pal S, Baral R. Prophylactic dose of neem (Azadirachta
indica) leaf preparation restricting murine tumor growth is nontoxic,
hematostimulatory and immunostimulatory. Immunopharmacol Immuno-
toxicol. 2006;28:33–50.
394 Azadirachta indica A. Juss.

66. Heukelbach J, Oliveira FA, Speare R. A new shampoo based on neem

(Azadirachta indica) is highly effective against head lice in vitro. Parasitol
Res. 2006;99:353–6.
67. Iabichella ML, Caruso C, Lugli M. The use of an extract of Hypericum
perforatum and Azadirachta indica in a neuropathic patient with advanced
diabetic foot. BMJ Case Rep. 2014;2014. pii: bcr2014205706.
68. Iabichella ML. The use of an extract of Hypericum perforatum and
Azadirachta indica in advanced diabetic foot: an unexpected outcome.
BMJ Case Rep. 2013;2013. pii: bcr2012007299.
69. Ibrahim IA, Khalid SA, Omer SA, Adam SE. On the toxicology of
Azadirachta indica leaves. J Ethnopharmacol. 1992;35:267–73.
70. Ilango K, Maharajan G, Narasimhan S. Antinociceptive and anti-inflam-
matory activities of Azadirachta indica fruit skin extract and its isolated
constituent azadiradione. Nat Prod Res. 2013;27:1463–7.
71. Jaiswal AK, Bhattacharya SK, Acharya SB. Anxiolytic activity of
Azadirachta indica leaf extract in rats. Indian J Exp Biol. 1994;32:489–91.
72. Joshi AR, Ahamed RN, Pathan KM, Manivannan B. Effect of Azadirachta
indica leaves on testis and its recovery in albino rats. Indian J Exp Biol.
1996;34:1091–4.
73. Jumba BN, Anjili CO, Makwali J, et al. Evaluation of leishmanicidal
activity and cytotoxicity of Ricinus communis and Azadirachta indica
extracts from western Kenya: in vitro and in vivo assays. BMC Res Notes.
2015;8:650.
74. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
75. Kasturi M, Manivannan B, Ahamed RN, et al. Changes in epididymal
structure and function of albino rat treated with Azadirachta indica leaves.
Indian J Exp Biol. 1995;33:725–9.
76. Kasutri M, Ahmed RN, Pathan KM, et al. Effects of Azadirachta indica
leaves on the seminal vesicles and ventral prostate in albino rats. Indian J
Physiol Pharmacol. 1997;41:234–40.
77. Kaur G, Sarwar Alam M, Athar M. Nimbidin suppresses functions of
macrophages and neutrophils: relevance to its anti-inflammatory mecha-
nisms. Phytother Res. 2004;18:419–24.
78. Kazeem MI, Dansu TV, Adeola SA. Inhibitory effect of Azadirachta
indica A. Juss. leaf extract on the activities of alpha-amylase and alpha-
glucosidase. Pak J Biol Sci. 2013;16:1358–62.
79. Khalid SA, Duddeck H, Gonzalez-Sierra M. Isolation and characterization
of an antimalarial agent of the neem tree Azadirachta indica. J Nat Prod.
1989;52:922–6.
80. Khan PK, Awasthy KS. Cytogenetic toxicity of neem. Food Chem
Toxicol. 2003;41:1325–8.
81. Khillare B, Shrivastav TG. Spermicidal activity of Azadirachta indica
(neem) leaf extract. Contraception. 2003;68:225–9.
Azadirachta indica A. Juss. 395

82. Khosla P, Bhanwra S, Singh J, et al. A study of hypoglycaemic effects of

Azadirachta indica (Neem) in normal and alloxan diabetic rabbits. Indian J
Physiol Pharmacol. 2000;44:69–74.
83. Khosla P, Gupta A, Singh J. A study of cardiovascular effects of
Azadirachta indica (neem) on isolated perfused heart preparations. Indian J
Physiol Pharmacol. 2002;46:241–4.
84. Kigodi PG, Blaskó G, Thebtaranonth Y, Pezzuto JM, Cordell GA. Spec-
troscopic and biological investigation of nimbolide and 28-deoxonimbolide
from Azadirachta indica. J Nat Prod. 1989;52:1246–51.
85. Kirira PG, Rukunga GM, Wanyonyi AW, et al. Antiplasmodial activity
and toxicity of extracts of plants used in traditional malaria therapy in
Meru and Kilifi Districts of Kenya. J Ethnopharmacol. 2006;106:403–7.
86. Koley KM, Lal J. Pharmacological effects of Azadirachta indica (neem)
leaf extract on the ECG and blood pressure of rat. Indian J Physiol
Pharmacol. 1994;38:223–5.
87. Koul A, Binepal G, Gangar SC. Impediment of diethylnitrosamine induced
hepatotoxicity in male Balb/c mice by pretreatment with aqueous
Azadirachta indica leaf extract. Indian J Exp Biol. 2007;45:359–66.
88. Koul A, Mukherjee N, Gangar SC. Inhibitory effects of Azadirachta indica
on DMBA-induced skin carcinogenesis in Balb/c mice. Mol Cell Biochem.
2006;283:47–55.
89. Koul A, Goyal R, Bharati S. Protective effect of Azadirachta indica A.
Juss. against doxorubicin-induced cardiac toxicity in tumour bearing mice.
Indian J Exp Biol. 2014;52:323–31.
90. Koul A, Mohan V, Bharati S. Azadirachta indica mitigates DMBA-
induced hepatotoxicity: a biochemical and radiometric study. Indian J
Biochem Biophys. 2014;51:37–45.
91. Kumar S, Suresh PK, Vijayababu MR, et al. Anticancer effects of ethanolic
neem leaf extract on prostate cancer cell line (PC-3). J Ethnopharmacol.
2006;105:246–50.
92. Kurimoto S, Takaishi Y, Ahmed FA, Kashiwada Y. Triterpenoids from the
fruits of Azadirachta indica (Meliaceae). Fitoterapia. 2014;92:200–5.
93. Kusamran WR, Ratanavila A, Tepsuwan A. Effects of neem flowers, Thai
and Chinese bitter gourd fruits and sweet basil leaves on hepatic monooxy-
genases and glutathione S-transferase activities, and in vitro metabolic
activation of chemical carcinogens in rats. Food Chem Toxicol. 1998;36:
475–84.
94. Lakshmi T, Krishnan V, Rajendran R, Madhusudhanan N. Azadirachta
indica: a herbal panacea in dentistry—an update. Pharmacogn Rev. 2015;
9:41–4.
95. Liu L, Zhao YL, Cheng GG, et al. Limonoid and steroidal saponin from
Azadirachta indica. Nat Prod Bioprospect. 2014;4:335–40.
96. Luo XD, Wu SH, Ma YB, Wu DG. A new triterpenoid from Azadirachta
indica. Fitoterapia. 2000;71:668–72.
396 Azadirachta indica A. Juss.

97. Mahdi AA, Chandra A, Singh RK, et al. Effect of herbal hypoglycemic
agents on oxidative stress and antioxidant status in diabetic rats. Indian J
Clin Biochem. 2003;18:8–15.
98. Mahfuzul Hoque MD, Bari ML, Inatsu Y, et al. Antibacterial activity of
guava (Psidium guajava L.) and Neem (Azadirachta indica A. Juss.)
extracts against foodborne pathogens and spoilage bacteria. Foodborne
Pathog Dis. 2007;4:481–8.
99. Mandal-Ghosh I, Chattopadhyay U, Baral R. Neem leaf preparation
enhances Th1 type immune response and antitumor immunity against
breast tumor associated antigen. Cancer Immun. 2007;7:8.
100. Manikandan P, Letchoumy PV, Gopalakrishnan M, Nagini S. Evaluation of
Azadirachta indica leaf fractions for in vitro antioxidant potential and
in vivo modulation of biomarkers of chemoprevention in the hamster buccal
pouch carcinogenesis model. Food Chem Toxicol. 2008;46:2332–43.
101. Mishra AK, Singh N, Sharma VP. Use of neem oil as a mosquito repellent
in tribal villages of Mandla district. Madhya Pradesh. Indian J Malariol.
1995;32:99–103.
102. Mishra RK, Singh SK. Effect of aqueous leaf extract of Azadirachta indica
on the reproductive organs in male mice. Indian J Exp Biol. 2005;43:
1093–103.
103. Mukherjee AK, Doley R, Saikia D. Isolation of a snake venom phospho-
lipase A2 (PLA2) inhibitor (AIPLAI) from leaves of Azadirachta indica
(Neem): mechanism of PLA2 inhibition by AIPLAI in vitro condition.
Toxicon. 2008;51:1548–53.
104. Mukherjee S, Garg S, Talwar GP. Early post implantation contraceptive
effects of a purified fraction of neem (Azadirachta indica) seeds, given
orally in rats: possible mechanisms involved. J Ethnopharmacol. 1999;
67:287–96.
105. Mukherjee S, Lohiya NK, Pal R, et al. Purified neem (Azadirachta indica)
seed extracts (Praneem) abrogate pregnancy in primates. Contraception.
1996;53:375–8.
106. Mukherjee S, Talwar GP. Termination of pregnancy in rodents by oral
administration of praneem, a purified neem seed extract. Am J Reprod
Immunol. 1996;35:51–6.
107. Mulla MS, Su T. Activity and biological effects of neem products against
arthropods of medical and veterinary importance. J Am Mosq Control
Assoc. 1999;15:133–52.
108. Mustafa M. Antibacterial efficacy of neem (Azadirachta indica) extract
against Enterococcus faecalis: an in vitro study. J Contemp Dent Pract.
2016;17:791–4.
109. Nair R, Kalariya T, Chanda S. Antibacterial activity of some plant extracts
used in folk medicine. J Herb Pharmacother. 2007;7:191–201.
110. Neerja Pant, Garg HS, Madhusudanan KP, Bhakuni DS. Sulfurous
compounds from Azadirachta indica leaves. Fitoterapia. 1986;57:302–4.
Azadirachta indica A. Juss. 397

111. Njiro SM, Kofi-Tsekpo MW. Effect of an aqueous extract of Azadirachta

indica on the immune response in mice. Onderstepoort J Vet Res. 1999;
66:59–62.
112. Njoku OU, Alumanah EO, Meremikwu CU. Effect of Azadirachta indica
extract on plasma lipid levels in human malaria. Boll Chim Farm. 2001;
140:367–70.
113. Nwafor SV, Akah PA, Okoli CO, et al. Interaction between chloroquine
sulphate and aqueous extract of Azadirachta indica A. Juss. (Meliaceae) in
rabbits. Acta Pharm. 2003;53:305–11.
114. Obiefuna I, Young R. Concurrent administration of aqueous Azadirachta
indica (neem) leaf extract with DOCA-salt prevents the development of
hypertension and accompanying electrocardiogram changes in the rat.
Phytother Res. 2005;19:792–5.
115. Okpanyi SN, Ezeukwu GC. Anti-inflammatory and antipyretic activities of
Azadirachta indica. Planta Med. 1981;41:34–9.
116. Okpanyi SN. Perspectives in medicinal plant research. Nigeria: Drug
Research and Production Unit, University of Ife; 1977. p. 89.
117. Oluwole Busayo A, Laura Z, Olufunke Olubusola D, et al. Ameliorative
effects of ethanolic leaf extract of Azadirachta indica on renal histologic
alterations in streptozotocin-induced diabetic rats. Am J Chin Med.
2011;39:903–16.
118. Owolabi LL, Gbotolorun SC, Akpantah AO, et al. Effect of methanolic
extract of Neem leaf (Azadirachta indica) on ovarian histology and
hormonal milleu. Nig Q J Hosp Med. 2008;18:194–7.
119. Page C, Hawes EM. Haemolytic anaemia after ingestion of Neem
(Azadirachta indica) tea. BMJ Case Rep. 2013;2013. pii: bcr2013200890.
120. Pai MR, Acharya LD, Udupa N. Evaluation of antiplaque activity of
Azadirachta indica leaf extract gel—a 6-week clinical study. J Ethnophar-
macol. 2004;90:99–103.
121. Parida MM, Upadhyay C, Pandya G, Jana AM. Inhibitory potential of
neem (Azadirachta indica Juss.) leaves on dengue virus type-2 replication.
J Ethnopharmacol. 2002;79:273–8.
122. Parshad O, Singh P, Gardner M, et al. Effect of aqueous neem (Azadir-
achta indica) extract on testosterone and other blood constituents in male
rats. A pilot study. West Indian Med J. 1994;43:71–4.
123. Peer PA, Trivedi PC, Nigade PB, et al. Cardioprotective effect of Azadir-
achta indica A. Juss. on isoprenaline induced myocardial infarction in rats.
Int J Cardiol. 2008;126:123–6.
124. Pillai NR, Santhakumari G. Effect of nimbidin on gastric acid secretion.
Anc Sci Life. 1985;5:91–7.
125. Ponnusamy S, Haldar S, Mulani F, et al. Gedunin and azadiradione: human
pancreatic alpha-amylase inhibiting limonoids from neem (Azadirachta
indica) as antidiabetic agents. PLoS ONE. 2015;10:e0140113.
398 Azadirachta indica A. Juss.

126. Prakash AO, Tewari RK, Mathur R. Nonhormonal postcoital contraceptive

action of neem oil in rats. J Ethnopharmacol. 1988;23:53–9.
127. Prashant GM, Chandu GN, Murulikrishna KS, Shafiulla MD. The effect of
mango and neem extract on four organisms causing dental caries:
Streptococcus mutans, S. salivavius, S. mitis, and S. sanguis: an in vitro
study. Indian J Dent Res. 2007;18:148–51.
128. Raghavendra M, Maiti R, Kumar S, Acharya S. Role of aqueous extract of
Azadirachta indica leaves in an experimental model of Alzheimer’s
disease in rats. Int J Appl Basic Med Res. 2013;3:37–47.
129. Raji Y, Ogunwande IA, Osadebe CA, John G. Effects of Azadirachta
indica extract on gastric ulceration and acid secretion in rats. J Ethnophar-
macol. 2004;90:167–70.
130. Raji Y, Udoh US, Mewoyeka OO, et al. Implication of reproductive
endocrine malfunction in male antifertility efficacy of Azadirachta indica
extract in rats. Afr J Med Sci. 2003;32:159–65.
131. Rao AR, Sukumar S, Parmasivam TV, et al. Study of antiviral activity of
tender leaves of Margosa tree (Melia azadericta) on vaccinia and variola
virus: a preliminary report. Indian J Med Res. 1969;57:495–502.
132. Ray A, Banerjee BD, Sen P. Modulation of humoral and cell-mediated
immune responses by Azadirachta indica (Neem) in mice. Indian J Exp
Biol. 1996;34:698–701.
133. Riar SS, Bardhan J, Thomas P, et al. Mechanism of antifertility action of
neem oil. Indian J Med Res. 1988;88:339–42.
134. Satyanarayana K, Sravanthi K, Shaker IA, Ponnulakshmi R. Molecular
approach to identify antidiabetic potential of Azadirachta indica.
J Ayurveda Integr Med. 2015;6:165–74.
135. Saxena D, Saha SG, Saha MK, Dubey S, Khatri M. An in vitro evaluation
of antimicrobial activity of five herbal extracts and comparison of their
activity with 2.5% sodium hypochlorite against Enterococcus faecalis.
Indian J Dent Res. 2015;26:524–7.
136. Sen P, Mediratta PK, Ray A. Effects of Azadirachta indica A. Juss. on
some biochemical, immunological and visceral parameters in normal and
stressed rats. Indian J Exp Biol. 1992;30:1170–5.
137. Shah NC. Herbal folk medicines in Northern India. J Ethnopharmacol.
1982;6:293–301.
138. Shailey S, Basir SF. Strengthening of antioxidant defense by Azadirachta
indica in alloxan-diabetic rat tissues. J Ayurveda Integr Med. 2012;3:130–5.
139. Sharma A, Chandraker S, Patel VK, Ramteke P. Antibacterial activity of
medicinal plants against pathogens causing complicated urinary tract
infections. Indian J Pharm Sci. 2009;71:136–9.
140. Sharma JD, Jha RK, Gupta I, Jain P, Dixit VP. Antiandrogenic properties
of neem seed oil (Azadirachta indica) in male rat and rabbit. Anc Sci Life.
1987;7:30–8.
141. Sharma S, Saimbi CS, Koirala B, Shukla R. Effect of various mouthwashes
on the levels of interleukin-2 and interferon-gamma in chronic gingivitis.
J Clin Pediatr Dent. 2008;32:111–4.
Azadirachta indica A. Juss. 399

142. Sharma VP, Ansari MA, Razdan RK. Mosquito repellent action of neem
(Azadirachta indica) oil. J Am Mosq Control Assoc. 1993;9:359–60.
143. Sharma VP, Ansari MA. Personal protection from mosquitoes (Diptera:
Culicidae) by burning neem oil in kerosene. J Med Entomol. 1994;31:505–7.
144. Shrivastava A, Chaturvedi U, Sonkar R, et al. Antioxidant effect of
Azadirachta indica on high fat diet induced diabetic Charles Foster rats.
Appl Biochem Biotechnol. 2012;167:229–36.
145. Siddiqui BS, Afshan F, Faizi S, et al. Two new triterpenoids from
Azadirachta indica and their insecticidal activity. J Nat Prod. 2002;65:
1216–8.
146. Siddiqui BS, Afshan F, Gulzar T, et al. Tetracyclic triterpenoids from the
leaves of Azadirachta indica and their insecticidal activities. Chem Pharm
Bull (Tokyo). 2003;51:415–7.
147. Siddiqui S, Faizi S, Siddiqui BS. Ghiasuddin: constituents of Azadirachta
indica: isolation and structure elucidation of a new antibacterial tetranor-
triterpenoid, mahmoodin, and a new protolimonoid, naheedin. J Nat Prod.
1992;55:303–10.
148. Singh R, Mishra V, Pandeti S, et al. Cytoprotective and antisecretory
effects of Azadiradione isolated from the seeds of Azadirachta indica
(neem) on gastric ulcers in rat models. Phytother Res. 2015;29:910–6.
149. Somsak V, Chachiyo S, Jaihan U, Nakinchat S. Protective effect of
aqueous crude extract of neem (Azadirachta indica) leaves on Plasmodium
berghei-induced renal damage in mice. J Trop Med. 2015;2015:961205.
150. Subapriya R, Bhuvaneswari V, Ramesh V, Nagini S. Ethanolic leaf extract
of neem (Azadirachta indica) inhibits buccal pouch carcinogenesis in
hamsters. Cell Biochem Funct. 2005;23:229–38.
151. Subapriya R, Kumaraguruparan R, Abraham SK, Nagini S. Protective
effects of ethanolic neem leaf extract on DMBA-induced genotoxicity and
oxidative stress in mice. J Herb Pharmacother. 2005;5:39–50.
152. Subapriya R, Kumaraguruparan R, Chandramohan KV, Nagini S. Chemo-
protective effects of ethanolic extract of neem leaf against MNNG-induced
oxidative stress. Pharmazie. 2003;58:512–7.
153. Subapriya R, Nagini S. Ethanolic neem leaf extract protects against
N-methyl-N-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in
Wistar rats. Asian Pac J Cancer Prev. 2003;4:215–23.
154. Sujarwo W, Keim AP, Caneva G, Toniolo C, Nicoletti M. Ethnobotanical
uses of neem (Azadirachta indica A. Juss.; Meliaceae) leaves in Bali
(Indonesia) and the Indian subcontinent in relation with historical back-
ground and phytochemical properties. J Ethnopharmacol. 2016;189:186–93.
155. Talwar GP, Raghuvanshi P, Misra R, et al. Plant immunomodulators for
termination of unwanted pregnancy and for contraception and reproductive
health. Immunol Cell Biol. 1997;75:190–2.
156. Talwar GP, Shah S, Mukherjee S, Chabra R. Induced termination of
pregnancy by purified extracts of Azadirachta indica (Neem): mechanisms
involved. Am J Reprod Immunol. 1997;37:485–91.
400 Azadirachta indica A. Juss.

157. Tella A. Studies on Azadirachta indica in malaria [proceedings]. Br J

Pharmacol. 1976;58:318P.
158. Tella A. The effects of Azadiracta indica in acute Plasmodium berghei
malaria [proceedings]. West Afr J Pharmacol Drug Res. 1976;3:80P.
159. Thompson EB, Anderson CC. Cardiovascular effects of Azadirachta
indica extract. J Pharm Sci. 1978;67:1476–8.
160. Tiwari V, Darmani NA, Yue BY, Shukla D. In vitro antiviral activity of
neem (Azardirachta indica L.) bark extract against herpes simplex virus
type-1 infection. Phytother Res. 2010;24:1132–40.
161. Udeinya JI, Shu EN, Quakyi I, Ajayi FO. An antimalarial neem leaf extract
has both schizonticidal and gametocytocidal activities. Am J Ther.
2008;15:108–10.
162. Umar MI, Asmawi MZ, Sadikun A, et al. Multiconstituent synergism is
responsible for anti-inflammatory effect of Azadirachta indica leaf extract.
Pharm Biol. 2014;52:1411–22.
163. Upadhyay SN, Dhawan S, Garg S, Talwar GP. Immunomodulatory effects of
neem (Azadirachta indica) oil. Int J Immunopharmacol. 1992;14:1187–93.
164. Upadhyay SN, Dhawan S, Talwar GP. Antifertility effects of neem
(Azadirachta indica) oil in male rats by single intra-vas administration: an
alternate approach to vasectomy. J Androl. 1993;14:275–81.
165. Upadhyay SN, Kaushic C, Talwar GP. Antifertility effects of neem
(Azadirachta indica) oil by single intrauterine administration: a novel
method for contraception. Proc Biol Sci. 1990;242:175–9.
166. Vanka A, Tandon S, Rao SR, et al. The effect of indigenous Neem
Azadirachta indica [correction of (Adirachta indica)] mouth wash on
Streptococcus mutans and lactobacilli growth. Indian J Dent Res. 2001;
12:133–44.
167. Waheed A, Miana GA, Ahmad SI. Clinical investigation of hypoglycemic
effect of seeds of Azadirachta inidca in type-2 (NIDDM) diabetes mellitus.
Pak J Pharm Sci. 2006;19:322–5.
168. Wang C, Cao M, Shi DX, et al. A 90-day subchronic toxicity study of
neem oil, Azadirachta indica oil, in mice. Hum Exp Toxicol. 2013;32:
904–13.
169. Wolinsky LE, Mania S, Nachnani S, Ling S. The inhibiting effect of
aqueous Azadirachta indica (Neem) extract upon bacterial properties
influencing in vitro plaque formation. J Dent Res. 1996;75:816–22.
170. Yan YX, Liu JQ, Chen JX, Chen JC, Qiu MH. Three new limonoids from
Azadirachta indica. J Asian Nat Prod Res. 2015;17:14–9.
171. Yanpallewar S, Rai S, Kumar M, et al. Neuroprotective effect of
Azadirachta indica on cerebral post-ischemic reperfusion and hypoperfu-
sion in rats. Life Sci. 2005;76:1325–38.
172. Yanpallewar SU, Sen S, Tapas S, et al. Effect of Azadirachta indica on
paracetamol-induced hepatic damage in albino rats. Phytomedicine. 2003;
10:391–6.
Bacopa monnieri (L.) Wettst.
(Plantaginaceae)

(Syns.: Bramia indica Lam; B. monnieri (L.) Pennell; Gratiola monnieri L.; Herpestis
monnieri (L.) Kunth; Lysimachia monnieri L.)

Abstract
A perennial, creeping, somewhat fleshy herb, found throughout India in marshy
grounds, other Asian countries, Australia, Europe, Africa, and North and South
America. It has frequently been mistaken for Hydrocotyl asiatica, because both
of these plants are known in many places in India by the same Hindi name
Brahmi. In Ayurveda, the plant is considered as nervine tonic, and useful for
insanity, epilepsy, and hoarseness of voice, to promote mental health and
improve memory and intellect, and as anti-inflammatory, analgesic, antipyretic,
sedative and antiepileptic, and to relieve anxiety. Bose had also used powdered
dried leaves of the Brahmi plant with very satisfactory results in cases of asthma,
nervous breakdown, and other run-down conditions. Decoction of the whole
plant is utilized by the Filipinos as diuretic. Main alkaloid ‘herpestine’ was
isolated in a pure crystalline form in 1947, while isolation of the alkaloid,
‘Brahmin’ had been reported in 1931. Other constituents isolated from the plant
are stigmasterol, triterpenoid glycosides (bacopasides) and bacopasaponins.
Anxiolytic activity of a standardized methanol extract in rats, qualitatively
comparable to that of lorazepam but with a significant advantage to promote
cognition unlike the amnesic action of benzodiazepines, and significant reversal
of diazepam-, MK-801-, and L-NAME-induced memory deficit in rats have been
observed. Aqueous, ethanol and methanol extracts exhibit highly significant
antioxidant activity, and aqueous extract also prevents I/R-induced cerebral
injury. Treatment with a commercial preparation of the extract for 12-weeks
significantly improved speed of visual information processing, learning rate and
memory consolidation, and state of anxiety in healthy individuals. Increase in
oxidative free radical scavenging activity, inhibition of AChE and/or choline
acetyltransferase activation, b-amyloid reduction, increased cerebral blood flow,
and modulation of neurotransmitters, are suggested to be involved in its central
nervous system effects.

© Springer Nature Switzerland AG 2020 401

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_41
402 Bacopa monnieri (L.) Wettst.

Keywords




Bacopa Bama Barahmi English daisy Graciola

Jalanimba
Litet




tjockblad Nirbrami Pa-chi-t’ien Pikkubakopa

Vernaculars: Urd.: Brahmi; Hin.: Bama, Barahmi, Barambhi, Brambhiv, Jal nim,
Manduka parni, Neer brahmi, Nirbrami, Safed chamni; San.: Aindri, Jalanimba,
Jali-nim, Jalla brahmi, Lavanikã, Vañgiya-brãhmi; Ben.: Aaghabini, Adha-birni,
Brādramī śāka, Brahmi, Brahmi-sak, Chamini, Jalanimba, Shwete dhop-chamni,
Udhabini; Guj.: Baam, Bamanevari, Jalanevari; Mal.: Beami, Bhahmi, Bhrammi,
Kodakan, Muttil, Nirbrahmi; Mar.: Bamba, Bama, Brahmi, Jalnam, Nirbrahmi;
Tam.: Beami, Neerbrahmi, Niirpirami, Nilappachai, Nirbirhmi, Piramiyapundu;
Tel.: Sambarani, Sambarenu, Sambrani-aku; Ara.: Farfakh, Watwaat; Chi.: 假马齿
苋, Jia ma chi xian, Pa-chi-t’ien; Eng.: Brain plant, Coastal water-hyssop, English
daisy, Herb of grace, Monnier’s hedge hyssop, Thyme leaved gratiola, Water
hyssop; Fin.: Pikkubakopa; Fre.: Bacopa de Monnier; Ger.: Bacopa, Kleine
fettblatt; Jap.: Bakopa, Otomeazena; Nep.: Medha giree; Pol.: Bakopa drobno-
listna; Por.: Bacopa; Sin.: Lunuvila; Spa.: Graciola; Swe.: Litet tjockblad; Tag.:
Ulasimang-aso; Tha.: Phak mi; Vie.: Rau đắng biển.
Description: It is a perennial, creeping, smooth, somewhat fleshy herb, found
throughout India in marshy grounds, other Asian countries, Australia, Europe, Africa,
and North and South America. Branches 5–20 cm long; the succulent leaves are

Fig. 1 Bacopa monnieri, Leaves and Flower, J.M. Garg, WikimediaCommons; 3.0 Unported CC
BY 3.0, https://commons.wikimedia.org/wiki/File:Bacopa_monnieri_W_IMG_1612.jpg; https://
creativecommons.org/licenses/by/3.0/deed.en
Bacopa monnieri (L.) Wettst. 403

stalkless, entire, oblong-ovate to spatulate, 8–15 mm long, up to 4 mm in width,

widest near the blunt tip, and tapering toward the base. Flowers are borne singly in the
axils of the leaves, on stalks which are usually as long as the leaves or longer. Calyx is
about 5 mm long, the outer sepals being oval and the others ovate-lanceolate or
lanceolate; corolla 8–10 mm long; the tube which is nearly as long as the calyx, has
white or pale violet lobes. The capsules are ovoid and shorter than the calyx; the seeds
are numerous and pale (Fig. 1).CXVII
Actions and Uses: It has frequently been mistaken for Hydrocotyl asiatica (Umbel-
liferae) because both of these plants are known in many places in India by the same
Hindi name Brahmi, and NadkarniCV has described only Hydrocotyl asiatica as
Brahmi. In Ayurveda, the plant is considered as nervine tonic, and useful for insanity,
and hoarseness of voice, to promote mental health and improve memory and intellect
[8],LXXXIV and as anti-inflammatory, analgesic, antipyretic, sedative and antiepileptic
[60], and to relieve anxiety.XXI Other uses include kustha, jwara, śopha, pãndu,
śotha, prameha, apasmãra, mūtrakrcchra, and mãnasa vikãra.LX It is described as
diuretic, aperient and tonic; given in stoppage of urine (anuria), in nervous debility,
and seminal weakness. With petrolatum, the juice is rubbed on to rheumatic painful
parts. The plant is applied hot to the chest in cases of bronchitis and cough in
children.LXXXI Bose had also used powdered dried leaves of the Brahmi plant with
very satisfactory results in cases of asthma, nervous breakdown, and other run-down
conditions. In Unani medicine, it (temperament, hot 2° and dry 2°) is described as a
brain and memory tonic, sedative, blood purifying, also used in seminal debility, and
for hair darkening properties; using it with black pepper enhances its activity.LXXVII
The nomadic Gujjar community of sub-Himalayan region of Uttarakhand (India)
traditionally treats epilepsy patients with this plant [70]. Decoction of the whole plant
is utilized by the Filipinos as diuretic.CXVII
Phytoconstituents: Main alkaloid ‘herpestine’ was isolated in a pure crystalline
form in 1947, while isolation of the alkaloid, ‘Brahmin’ had been reported in 1931,
and Banerjee and Chakravarti [5] had isolated stigmasterol. Other constituents
isolated from the plant are triterpenoid glycosides (bacopasides) [9, 10, 28, 48, 56,
78], and bacopasaponins [26, 38, 77]. Three triterpenoid saponins, bacopasides IX–
XI, together with their known analogues bacopaside I, bacopaside II, bacopas-
aponsin C, and bacopasaponsin D, were isolated by Zhou et al. [99].
Pharmacology: Behavioral and neuropharmacological effects of the herb and its
constituents have been reported since the early 1960s [19, 24, 25, 39, 40].
Improvement in learning, better acquisition, improved retention and delayed
extinction in avoidance tests of rats were reported [73]. Bhattacharya and Ghosal
[8] observed dose-related anxiolytic activity of a standardized methanol extract in
rats, qualitatively comparable to that of lorazepam but with a significant advantage
to promote cognition unlike the amnesic action of benzodiazepines (lorazepam),
and caused a significant reversal of diazepam-[50, 68], MK-801 (an NMDA
receptor antagonist)-, and L-NAME-induced memory deficit in rats [65]. B. mon-
nieri extract pretreatment prevented cognition deficit induced by various agents
404 Bacopa monnieri (L.) Wettst.

[2, 4, 15, 18, 23, 36, 52, 55, 67, 94], prevented alterations in morphine-induced
brain mitochondrial enzymes [85], multiple agents-induced cerebral oxidative stress
[3, 20, 33, 35, 47, 81, 84, 89], cerebral neurotoxicity [32, 72, 74, 88], inhibited
brain AChE [18, 46], reduced b-amyloid deposits in the brain of Alzheimer’s
disease animal model [20], stimulated neuronal dendritic growth in immature rat
pups and mature rats [95–97] and enhanced learning and memory during growth
spurt period of neonatal rats [98]. Aqueous, ethanol and methanol extracts exhibit
highly significant antioxidant activity [41, 43]. Aqueous extract also prevents
I/R-induced cerebral injury [57, 66], and the ethanol extract produced antipsychotic
activity by reducing dopamine concentration in frontal cortex region of rat brain
[31]. The extract induced a dose-dependent increase in SOD, CAT and GPx
activities in frontal cortical, striatal and hippocampal regions of rat brain, and
showed a synergistic effect with rivastigmine [87]. Significant antidepressant
activity comparable to imipramine [61], and antistress (adaptogenic) activity [14,
54], and attenuation of stress-induced changes in plasma corticosterone and
monoamine levels in cortex and hippocampus regions in rats [71] have been
reported. Bacopasides XI and I, and bacopasaponsin C, showed nootropic activity
in scopolamine-induced memory impairment [64, 99]. Bacopaside I also signifi-
cantly reversed reserpine-induced depressive-like behaviors in mice, without
affecting brain MAO-A or MAO-B activity [37].
Ethanol extract of whole dried herb exhibited significant anti-inflammatory
activity, and selectively inhibited PGE2-induced inflammation [11]. Methanol
extract inhibited collagen- and adjuvant-induced arthritis in rats with inhibition of
COX and LOX, and decreased neutrophil infiltration [90, 93], and downregulated
TNF-a [91, 92]. Antinociceptive activity of aqueous extract was blocked by pre-
treatment with yohimbin, atenolol, cyproheptadine and naloxone in various animal
models [6]. Ethanol extract significantly decreased levels of TC, TGs, LDL-C,
VLDL-C, atherogenic index, LDL/HDL ratio, and TC/HDL ratio, and significantly
increased HDL-C in high-cholesterol diet-induced hypercholesterolemia in rats
[34]. Aqueous extract exhibited 41.8% in vitro thrombolytic activity, compared to
86.2% shown by streptokinase [51]. Administration of ethanol extract for three-
weeks augmented myocardial antioxidants, SOD, CAT and GSH, and induced heat
shock protein 72 (HSP72) of healthy rats, and significantly prevented I/R-induced
biochemical and histopathological perturbations, restored antioxidant activity of
myocardium, and reduced myocardial apoptosis, caspase 3 and Bax protein
expression [42].
Ethanol extract induces a dose- and time-dependent loss of mouse S-180 cells
viability by inducing apoptosis [58]. Bacopaside E and bacopaside VII showed
cytotoxicity to human tumor cell lines MDA-MB-231, SHG-44, HCT-8, A-549 and
PC-3 M, and inhibition in mouse implanted with Sarcoma S180 [49]; whereas
bacoside A co-treatment prevented NDEA-hepatotoxicity, hepatocarcinogenesis
and asociated biochemical and histopathological alterations in rats [29, 30], and
d-galactosamine-hepatotoxicity [83]. Ethanol extract was also hepatoprotective
against morphine induced liver toxicity [82, 86].
Bacopa monnieri (L.) Wettst. 405

Methanol extract produces antiulcerogenic effects on various gastric ulcer models

with no effect on acid-pepsin secretion, but increases mucin secretion and decreases
cell shedding, and significant antioxidant effect per se and in stressed animals [62].
Ulcer protective effects are more pronounced in nondiabetic than in NIDDM
rats [21]. Ethanol extract and its fractions produced in vitro bronchodilatory effect
due to calcium channel blocking activity [12, 13, 16, 17], and enhanced incision
wound contraction, skin collagen tissue formation, and early epithelization period
with low scar area, decrease in myeloperoxidase, free radical generated tissue
damage, promoting antioxidant status, faster collagen deposition, and antibacterial
activity against skin pathogens [44].
Clinical Studies: In a double-blind RCT, independent-group design of healthy
individuals, treatment with a commercial preparation of the extract (KeenMind®)
for 12-weeks significantly improved speed of visual information processing,
learning rate and memory consolidation, and state of anxiety compared to placebo
[80], but failed to show any significant acute effect [45]. After a single low dose of a
standardized extract in a crossover, double-blind, placebo-controlled study in 24
healthy Australian volunteers, performance on Cognitive Demand Battery test was
improved [22]. A 90-days treatment of seventy-six healthy individuals, aged 40–
65 years, showed significant improvement in the retention of new information but
the rate of learning was unaffected, suggesting that it decreases the rate of forgetting
of newly acquired information [59, 69]. However, one RCT involving 72 healthy
urban educated Indian adults, both men and women, aged 35–60 years, found no
improvement in cognition or reduction in anxiety scores after 12-weeks of treatment
with an extract [79]. Another study reported significant improvement in mental
control, logical memory and paired associated learning in Australian subjects with
age-associated memory impairment without any evidence of dementia or psychi-
atric disorder [53].
Mechanism of Action: Increase in oxidative free radical scavenging activity may,
in part, explain cognition-facilitating action [7, 27, 63]. Other effects on nervous
functions are also suggested to be via inhibition of AChE and/or choline acetyl-
transferase activation, b-amyloid reduction, increased cerebral blood flow, and
modulation of neurotransmitters (ACh, 5-HT, and DA) [1].
Human A/Es, Allergy and Toxicity: Not suitable for individuals with hot
temperament.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interaction: A standardized alcoholic
extract showed inhibitory activity of liver and intestinal CYP3A, and decreased
expression of intestinal P-glycoprotein, but did not alter expression of hepatic
P-gp. These effects manifested in significant increase in AUC and Cmax of carba-
mazepine and digoxin, respectively [75]. A mixture of two active constituents,
bacopaside I and bacoside A also inhibits recombinant human MAO-A and MAO-B
enzymes. Bacopaside I selectively inhibits activity of MAO-A enzyme [76].
406 Bacopa monnieri (L.) Wettst.

Commentary: This plant is highly regarded in Ayurveda for its memory and
mental acuity-enhancing effects. However, results of clinical studies showed some
inconsistency and need validation by more studies in larger and varied populations.

References
1. Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb
Bacopa monnieri. Rejuvenation Res. 2013;16:313–26.
2. Anand A, Saraf MK, Prabhakar S. Antiamnesic effect of B. monniera on
L-NNA induced amnesia involves calmodulin. Neurochem Res. 2010;35:
1172–81.
3. Anand T, Phani Kumar G, Pandareesh MD, et al. Effect of bacoside extract
from Bacopa monniera on physical fatigue induced by forced swimming.
Phytother Res. 2012;26:587–93.
4. Balaji B, Kumar EP, Kumar A. Evaluation of standardized Bacopa
monniera extract in sodium fluoride-induced behavioural, biochemical, and
histopathological alterations in mice. Toxicol Ind Health. 2015;31:18–30.
5. Banerjee SK, Chakravarti RN. Stigmasterol from Herpestis monniera. Bull
Calcutta Sch Trop Med. 1963;11:57–8.
6. Bhaskar M, Jagtap AG. Exploring the possible mechanisms of action behind
the antinociceptive activity of Bacopa monniera. Int J Ayurveda Res. 2011;
2:2–7.
7. Bhattacharya SK, Bhattacharya A, Kumar A, Ghosal S. Antioxidant activity
of Bacopa monniera in rat frontal cortex, striatum and hippocampus.
Phytother Res. 2000;14:174–9.
8. Bhattacharya SK, Ghosal S. Anxiolytic activity of a standardized extract of
Bacopa monniera: an experimental study. Phytomedicine. 1998;5:77–82.
9. Chakravarty AK, Garai S, Masuda K, Nakane T, Kawahara N. Bacopasides
III-V: three new triterpenoid glycosides from Bacopa monniera. Chem
Pharm Bull (Tokyo). 2003;51:215–7.
10. Chakravarty AK, Sarkar T, Masuda K, et al. Bacopaside I and II: two
pseudojujubogenin glycosides from Bacopa monniera. Phytochemistry. 2001;
58:553–6.
11. Channa S, Dar A, Anjum S, Yaqoob M, Atta-Ur-Rahman. Anti-inflammatory
activity of Bacopa monniera in rodents. J Ethnopharmacol. 2006;104:286–9.
12. Channa S, Dar A, Yaqoob M, et al. Bronchovasodilatory activity of
fractions and pure constituents isolated from Bacopa monniera. J Ethnophar-
macol. 2003;86:27–35.
13. Channa S, Dar A. Calcium antagonistic activity of Bacopa monniera in
guinea-pig trachea. Indian J Pharmacol. 2012;44:516–8.
14. Chatterjee M, Verma P, Palit G. Comparative evaluation of Bacopa
monniera and Panax quniquefolium in experimental anxiety and depressive
models in mice. Indian J Exp Biol. 2010;48:306–13.
Bacopa monnieri (L.) Wettst. 407

15. Christinal J, Sumathi T. Effect of Bacopa monniera extract on methylmercury-

induced behavioral and histopathological changes in rats. Biol Trace Elem
Res. 2013;155:56–64.
16. Dar A, Channa S. Bronchodilatory and cardiovascular effects of an ethanol
extract of Bacopa monniera in anaesthetized rats. Phytomedicine. 1997;4:
319–23.
17. Dar A, Channa S. Calcium antagonistic activity of Bacopa monniera on
vascular and intestinal smooth muscles of rabbit and guinea-pig. J Ethnophar-
macol. 1999;66:167–74.
18. Das A, Shanker G, Nath C, et al. A comparative study in rodents of standardized
extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and
cognitive enhancing activities. Pharmacol Biochem Behav. 2002;73:893–900.
19. Dhalla NS, Sastry MS, Malhotra CL. Some in vitro effects of Herpestis
monniera Linn. on the respiration of rat brain. Indian J Med Res. 1961;
49:781–7.
20. Dhanasekaran M, Tharakan B, Holcomb LA, et al. Neuroprotective mecha-
nisms of ayurvedic antidementia botanical Bacopa monniera. Phytother Res.
2007;21:965–9.
21. Dorababu M, Prabha T, Priyambada S, et al. Effect of Bacopa monniera and
Azadirachta indica on gastric ulceration and healing in experimental
NIDDM rats. Indian J Exp Biol. 2004;42:389–97.
22. Downey LA, Kean J, Nemeh F, et al. An acute, double-blind, placebo-
controlled crossover study of 320 mg and 640 mg doses of a special extract
of Bacopa monnieri (CDRI 08) on sustained cognitive performance.
Phytother Res. 2013;27:1407–13.
23. Dwivedi S, Nagarajan R, Hanif K, et al. Standardized extract of Bacopa
monniera attenuates okadaic acid induced memory dysfunction in rats:
effect on Nrf2 pathway. Evid Based Complement Alternat Med. 2013;2013:
294501.
24. Ganguly DK, Malhotra CL. Some behavioural effects of an active fraction
from Herpestis monniera Linn. (Brahmi). Indian J Med Res. 1967;55:473–82.
25. Ganguly DK, Malhtora CL. Some neuropharmacological and behavioural
effects of an active fraction from Herpestis monniera Linn. (Brahmi).
Indian J Physiol Pharmacol. 1967;11:33–43.
26. Garai S, Mahato SB, Ohtani K, Yamasaki K. Dammarane-type triterpenoid
saponins from Bacopa monniera. Phytochemistry. 1996;42:815–20.
27. Hota SK, Barhwal K, Baitharu I, et al. Bacopa monniera leaf extract
ameliorates hypobaric hypoxia induced spatial memory impairment. Neuro-
biol Dis. 2009;34:23–39.
28. Hou CC, Lin SJ, Cheng JT, Hsu FL. Bacopaside III, bacopasaponin G, and
bacopasides A, B, and C from Bacopa monniera. J Nat Prod. 2002;65:
1759–63.
29. Janani P, Sivakumari K, Geetha A, Ravisankar B, Parthasarathy C. Chemo-
preventive effect of bacoside A on N-nitrosodiethylamine-induced hepato-
carcinogenesis in rats. J Cancer Res Clin Oncol. 2010;136:759–70.
408 Bacopa monnieri (L.) Wettst.

30. Janani P, Sivakumari K, Parthasarathy C. Hepatoprotective activity of

bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult
rats. Cell Biol Toxicol. 2009;25:425–34.
31. Jash R, Chowdary KA. Ethanolic extracts of Alstonia Scholaris and Bacopa
Monniera possess neuroleptic activity due to antidopaminergic effect.
Pharmacognosy Res. 2014;6:46–51.
32. Jyoti A, Sethi P, Sharma D. Bacopa monniera prevents from aluminium
neurotoxicity in the cerebral cortex of rat brain. J Ethnopharmacol. 2007;111:
56–62.
33. Jyoti A, Sharma D. Neuroprotective role of Bacopa monniera extract
against aluminium-induced oxidative stress in the hippocampus of rat brain.
Neurotoxicology. 2006;27:451–7.
34. Kamesh V, Sumathi T. Antihypercholesterolemic effect of Bacopa
monniera Linn. on high cholesterol diet induced hypercholesterolemia in
rats. Asian Pac J Trop Med. 2012;5:949–55.
35. Khan MB, Ahmad M, Ahmad S, et al. Bacopa monniera ameliorates
cognitive impairment and neurodegeneration induced by intracerebroven-
tricular streptozotocin in rat: behavioral, biochemical, immunohistochemical
and histopathological evidences. Metab Brain Dis. 2015;30:115–27.
36. Kishore K, Singh M. Effect of bacosides, alcoholic extract of Bacopa
monniera Linn. (Brahmi), on experimental amnesia in mice. Indian J Exp
Biol. 2005;43:640–5.
37. Liu X, Liu F, Yue R, et al. The antidepressant-like effect of bacopaside I:
possible involvement of the oxidative stress system and the noradrenergic
system. Pharmacol Biochem Behav. 2013;110:224–30.
38. Mahato SB, Garai S, Chakravarty AK. Bacopasaponins E and F: two
jujubogenin bis-desmosides from Bacopa monniera. Phytochemistry. 2000;
53:711–4.
39. Malhotra CL, Das PK, Dhalla NS. Some neuropharmacological actions of
hersaponin—an active principle from Herpestis monniera. Linn. Arch Int
Pharmacodyn Ther. 1960;129:290–302.
40. Malhotra CL, Das PK. Pharmacological studies of Herpestis monniera
Linn., (Brahmi). Indian J Med Res. 1959;47:294–305.
41. Meena H, Pandey HK, Pandey P, Arya MC, Ahmed Z. Evaluation of
antioxidant activity of two important memory enhancing medicinal plants
Baccopa monnieri and Centella asiatica. Indian J Pharmacol. 2012;44:114–7.
42. Mohanty IR, Maheshwari U, Joseph D, Deshmukh Y. Bacopa monniera
protects rat heart against ischaemia-reperfusion injury: role of key apoptotic
regulatory proteins and enzymes. J Pharm Pharmacol. 2010;62:1175–84.
43. Mukherjee S, Dugad S, Bhandare R, et al. Evaluation of comparative free-
radical quenching potential of Brahmi (Bacopa monnieri) and Mandook-
parni (Centella asiatica). Ayu. 2011;32:258–64.
44. Murthy S, Gautam MK, Goel S, et al. Evaluation of in vivo wound healing
activity of Bacopa monniera on different wound model in rats. Biomed Res
Int. 2013;2013:972028.
Bacopa monnieri (L.) Wettst. 409

45. Nathan PJ, Clarke J, Lloyd J, et al. The acute effects of an extract of Bacopa
monniera (Brahmi) on cognitive function in healthy normal subjects. Hum
Psychopharmacol. 2001;16:345–51.
46. Pandareesh MD, Anand T. Attenuation of smoke induced neuronal and
physiological changes by bacoside rich extract in Wistar rats via down
regulation of HO-1 and iNOS. Neurotoxicology. 2014;40:33–42.
47. Pandareesh MD, Anand T. Neuroprotective and antiapoptotic propensity of
Bacopa monniera extract against sodium nitroprusside induced activation of
iNOS, heat shock proteins and apoptotic markers in PC12 cells. Neurochem
Res. 2014;39:800–14.
48. Pawar R, Gopalakrishnan C, Bhutani KK. Dammarane triterpene saponin
from Bacopa monniera as the superoxide inhibitor in polymorphonuclear
cells. Planta Med. 2001;67:752–4.
49. Peng L, Zhou Y, de Kong Y, Zhang WD. Antitumor activities of dammarane
triterpene saponins from Bacopa monniera. Phytother Res. 2010;24:864–8.
50. Prabhakar S, Saraf MK, Pandhi P, Anand A. Bacopa monniera exerts
antiamnesic effect on diazepam-induced anterograde amnesia in mice.
Psychopharmacology. 2008;200:27–37.
51. Prasad S, Kashyap RS, Deopujari JY, et al. Effect of Fagonia arabica
(Dhamasa) on in vitro thrombolysis. BMC Complement Altern Med. 2007;
7:36.
52. Prisila Dulcy C, Singh HK, Preethi J, Rajan KE. Standardized extract of
Bacopa monniera (BESEB CDRI-08) attenuates contextual associative
learning deficits in the aging rat’s brain induced by D-galactose. J Neurosci
Res. 2012;90:2053–64.
53. Raghav S, Singh H, Dalal PK, Srivastava JS, Asthana OP. Randomized
controlled trial of standardized Bacopa monniera extract in age-associated
memory impairment. Indian J Psychiatry. 2006;48:238–42.
54. Rai D, Bhatia G, Palit G, et al. Adaptogenic effect of Bacopa monniera
(Brahmi). Pharmacol Biochem Behav. 2003;75:823–30.
55. Rajan KE, Singh HK, Parkavi A, Charles PD. Attenuation of 1-(m-chlor-
ophenyl)-biguanide induced hippocampus-dependent memory impairment by a
standardised extract of Bacopa monniera (BESEB CDRI-08). Neurochem Res.
2011;36:2136–44.
56. Rastogi S, Pal R, Kulshreshtha DK. Bacoside A3—a triterpenoid saponin
from Bacopa monniera. Phytochemistry. 1994;36:133–7.
57. Rehni AK, Pantlya HS, Shri R, Singh M. Effect of chlorophyll and aqueous
extracts of Bacopa monniera and Valeriana wallichii on ischaemia and
reperfusion-induced cerebral injury in mice. Indian J Exp Biol. 2007;45:
764–9.
58. Rohini G, Devi CS. Bacopa monniera extract induces apoptosis in murine
sarcoma cells (S-180). Phytother Res. 2008;22:1595–8.
59. Roodenrys S, Booth D, Bulzomi S, et al. Chronic effects of Brahmi (Bacopa
monnieri) on human memory. Neuropsychopharmacology. 2002;27:279–81.
410 Bacopa monnieri (L.) Wettst.

60. Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an

overview. Phytomedicine. 2005;12:305–17.
61. Sairam K, Dorababu M, Goel RK, Bhattacharya SK. Antidepressant activity
of standardized extract of Bacopa monniera in experimental models of
depression in rats. Phytomedicine. 2002;9:207–11.
62. Sairam K, Rao CV, Babu MD, Goel RK. Prophylactic and curative effects of
Bacopa monniera in gastric ulcer models. Phytomedicine. 2001;8:423–30.
63. Sandhya T, Sowjanya J, Veeresh B. Bacopa monniera (L.) Wettst amelio-
rates behavioral alterations and oxidative markers in sodium valproate
induced autism in rats. Neurochem Res. 2012;37:1121–31.
64. Saraf MK, Anand A, Prabhakar S. Scopolamine induced amnesia is reversed
by Bacopa monniera through participation of kinase-CREB pathway.
Neurochem Res. 2010;35:279–87.
65. Saraf MK, Prabhakar S, Anand A. Bacopa monniera alleviates N(omega)-
nitro-L-arginine arginine-induced but not MK-801-induced amnesia: a
mouse Morris water maze study. Neuroscience. 2009;160:149–55.
66. Saraf MK, Prabhakar S, Anand A. Neuroprotective effect of Bacopa monniera
on ischemia induced brain injury. Pharmacol Biochem Behav. 2010;97:192–7.
67. Saraf MK, Prabhakar S, Khanduja KL, Anand A. Bacopa monniera attenu-
ates scopolamine-induced impairment of spatial memory in mice. Evid
Based Complement Alternat Med. 2011;2011:236186.
68. Saraf MK, Prabhakar S, Pandhi P, Anand A. Bacopa monniera ameliorates
amnesic effects of diazepam qualifying behavioral-molecular partitioning.
Neuroscience. 2008;155:476–84.
69. Sathyanarayanan V, Thomas T, Einöther SJ, et al. Brahmi for the better? New
findings challenging cognition and antianxiety effects of Brahmi (Bacopa
monniera) in healthy adults. Psychopharmacology. 2013;227:299–306.
70. Sharma J, Gairola S, Gaur RD, Painuli RM, Siddiqi TO. Ethnomedicinal plants
used for treating epilepsy by indigenous communities of sub-Himalayan region
of Uttarakhand. India. J Ethnopharmacol. 2013;150:353–70.
71. Sheikh N, Ahmad A, Siripurapu KB, et al. Effect of Bacopa monniera on
stress induced changes in plasma corticosterone and brain monoamines in
rats. J Ethnopharmacol. 2007;111:671–6.
72. Shobana C, Kumar RR, Sumathi T. Alcoholic extract of Bacopa monniera
Linn. protects against 6-hydroxydopamine-induced changes in behavioral and
biochemical aspects: a pilot study. Cell Mol Neurobiol. 2012;32:1099–112.
73. Singh HK, Dhawan BN. Effect of Bacopa monniera Linn. (Brahmi) extract
on avoidance responses in rat. J Ethnopharmacol. 1982;5:205–14.
74. Singh M, Murthy V, Ramassamy C. Neuroprotective mechanisms of the
standardized extract of Bacopa monniera in a paraquat/diquat-mediated
acute toxicity. Neurochem Int. 2013;62:530–9.
75. Singh R, Panduri J, Kumar D, et al. Evaluation of memory enhancing clinically
available standardized extract of Bacopa monniera on p-glycoprotein and
cytochrome P450 3A in Sprague-Dawley rats. PLoS ONE. 2013;8:e72517.
Bacopa monnieri (L.) Wettst. 411

76. Singh R, Ramakrishna R, Bhateria M, Bhatta RS. In vitro evaluation of

Bacopa monniera extract and individual constituents on human recombinant
monoamine oxidase enzymes. Phytother Res. 2014;28:1419–22.
77. Sinha J, Raay B, Das N, et al. Bacopasaponin C: critical evaluation of
antileishmanial properties in various delivery modes. Drug Deliv. 2002;9:
55–62.
78. Sivaramakrishna C, Rao CV, Trimurtulu G, Vanisree M, Subbaraju GV.
Triterpenoid glycosides from Bacopa monnieri. Phytochemistry. 2005;66:
2719–28.
79. Stough C, Downey LA, Lloyd J, et al. Examining the nootropic effects of a
special extract of Bacopa monniera on human cognitive functioning: 90-day
double-blind placebo-controlled randomized trial. Phytother Res. 2008;22:
1629–34.
80. Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of
Bacopa monniera (Brahmi) on cognitive function in healthy human
subjects. Psychopharmacology. 2001;156:481–4.
81. Sumathi T, Nathiya VC, Sakthikumar M. Protective effect of bacoside-A
against morphine-induced oxidative stress in rats. Indian J Pharm Sci.
2011;73:409–15.
82. Sumathi T, Niranjali Devaraj S. Effect of Bacopa monniera on liver and
kidney toxicity in chronic use of opioids. Phytomedicine. 2009;16:897–903.
83. Sumathi T, Nongbri A. Hepatoprotective effect of Bacoside-A, a major
constituent of Bacopa monniera Linn. Phytomedicine. 2008;15:901–5.
84. Sumathi T, Shobana C, Christinal J, Anusha C. Protective effect of Bacopa
monniera on methylmercury-induced oxidative stress in cerebellum of rats.
Cell Mol Neurobiol. 2012;32:979–87.
85. Sumathy T, Govindasamy S, Balakrishna K, Veluchamy G. Protective role
of Bacopa monniera on morphine-induced brain mitochondrial enzyme
activity in rats. Fitoterapia. 2002;73:381–5.
86. Sumathy T, Subramanian S, Govindasamy S, Balakrishna K, Veluchamy G.
Protective role of Bacopa monniera on morphine induced hepatotoxicity in
rats. Phytother Res. 2001;15:643–5.
87. Thippeswamy AH, Rafiq M, Viswantha GL, et al. Evaluation of Bacopa
monniera for its synergistic activity with rivastigmine in reversing
aluminum-induced memory loss and learning deficit in rats. J Acupunct
Meridian Stud. 2013;6:208–13.
88. Tripathi S, Mahdi AA, Hasan M, Mitra K, Mahdi F. Protective potential of
Bacopa monniera (Brahmi) extract on aluminum induced cerebellar toxicity
and associated neuromuscular status in aged rats. Cell Mol Biol (Noisy-
le-grand). 2011;57:3–15.
89. Velaga MK, Basuri CK, Robinson Taylor KS, et al. Ameliorative effects of
Bacopa monniera on lead-induced oxidative stress in different regions of rat
brain. Drug Chem Toxicol. 2014;37:357–64.
412 Bacopa monnieri (L.) Wettst.

90. Vijayan V, Shyni GL, Helen A. Efficacy of Bacopa monniera (L.) Wettst in
alleviating lysosomal instability in adjuvant-induced arthritis in rats.
Inflammation. 2011;34:630–8.
91. Viji V, Helen A. Inhibition of lipoxygenases and cyclooxygenase-2 enzymes
by extracts isolated from Bacopa monniera (L.) Wettst. J Ethnopharmacol.
2008;118:305–11.
92. Viji V, Helen A. Inhibition of proinflammatory mediators: role of Bacopa
monniera (L.) Wettst. Inflammopharmacology. 2011;19:283–91.
93. Viji V, Kavitha SK, Helen A. Bacopa monniera (L.) Wettst inhibits type II
collagen-induced arthritis in rats. Phytother Res. 2010;24:1377–83.
94. Vohora D, Pal SN, Pillai KK. Protection from phenytoin-induced cognitive
deficit by Bacopa monniera, a reputed Indian nootropic plant. J Ethnophar-
macol. 2000;71:383–90.
95. Vollala VR, Upadhya S, Nayak S. Enhanced dendritic arborization of
amygdala neurons during growth spurt periods in rats orally intubated with
Bacopa monniera extract. Anat Sci Int. 2011;86:179–88.
96. Vollala VR, Upadhya S, Nayak S. Enhanced dendritic arborization of
hippocampal CA3 neurons by Bacopa monniera extract treatment in adult
rats. Rom J Morphol Embryol. 2011;52:879–86.
97. Vollala VR, Upadhya S, Nayak S. Enhancement of basolateral amygdaloid
neuronal dendritic arborization following Bacopa monniera extract treat-
ment in adult rats. Clinics (Sao Paulo). 2011;66:663–71.
98. Vollala VR, Upadhya S, Nayak S. Learning and memory-enhancing effect
of Bacopa monniera in neonatal rats. Bratisl Lek Listy. 2011;112:663–9.
99. Zhou Y, Peng L, Zhang WD, Kong DY. Effect of triterpenoid saponins from
Bacopa monniera on scopolamine-induced memory impairment in mice.
Planta Med. 2009;75:568–74.
Bauhinia tomentosa L./Bauhinia variegata L.
(Fabaceae/Leguminosae)

Abstract
Both species of Bauhinia, i.e. B. tomentosa and B. variegata are described as
Kachnal or Kuchnar/Kachnar in Unani medicine literature. Bark is described as
alterative, tonic, and astringent, useful in skin diseases and ulcers, to prevent
decomposition of blood and humours, and used for leprosy and scrofula. Bruised
bark is applied externally to wounds and tumors, and an infusion of the bark is
used as an astringent gargle. Decoction of the root bark is used in the treatment
of inflammation of liver, and as a vermifuge. Dried small buds and young
flowers are used for dysentery, bleeding piles and hematuria, and fruits are
considered diuretic. It is known as Pata-de-vaca and Mororó in Brazil and
widely used in traditional medicine as an antidiabetic agent; a protein with
insulin-like action has been isolated from leaves. Leaves contain amino acids
and proteins, seeds and seed oil contain fatty acids and minerals, and flowers
contain rutin, quercetin, and isoquercetin. Aqueous leaf extract significantly
reduced blood glucose, HbA1c, TC, TGs, LDL, VLDL, and liver enzymes, and
significantly increased insulin and HDL of diabetic rats. Both aqueous and
ethanol extracts of stem bark and root also showed significant antioxidant
activity, and reduced plasma TC, TG, LDL, and VLDL, and increased plasma
HDL levels.

Keywords





Asamantaka Bell bauhinia Filzige bauhinie Flor de azufre Huang hua yang





ti jia Kachnal Kellobauhinia Kuchnar Kuvidara Mariposa

Vernaculars: Urd.: Kachnal; Hin.: Kuchnar, Kuvidara, Sona-kauraj; San.:

Asamantaka, Kanchanára, Kovidara, Kuvidara, Phalgu; Ben.: Bedal, Kánchan; Mal.:
Kanchanamaram, Kanchanapoovu, Kanjanam, Kanjenapoovu, Manjamanaram;
Mar.: Kanchana; Tam.: Manthaarai, Segapu-menthari; Tel.: Adattige, Adaviman-
daramu; Chi.: 黄花羊蹄甲, Huang hua yang ti jia; Eng.: Bell bauhinia, Orchid shrub,
© Springer Nature Switzerland AG 2020 413
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_42
414 Bauhinia tomentosa L./Bauhinia variegata L.

St. Thomas-tree, Yellow bauhinia, Yellow butterfly tree (B. tomentosa), Butterfly tree,
Mountain ebony, Orchid tree (B. variegata); Fin.: Kellobauhinia; Fre.: Fleur du sacré-
coeur; Ger.: Filzige bauhinie (B. tomentosa), Bunte bauhinia, Buntfarbene vauhinie
(B. variegata), Gelber orchideenbaum; Por.: Mariposa (B. tomentosa), Arvore de
São-Thomaz, Unha-de-vaca (Br.)(B. variegata); Spa.: Flor de azufre (Argentina),
Guacamaya americana (B. tomentosa), Arbol orquídea, Pata de vaca (B. variegata);
Tag.: Baho-baho; Zul.: IsiThibathibana.
Description: Bauhinia tomentosa is an erect, branched shrub, reaching a height of
1.5–3 m. Branchlets, lower surfaces of the leaves, and pods are somewhat hairy.
Leaves are 4–7 cm long, about as wide, split about one-third to the base, into two, with
oval, rounded lobes. It blooms and fruits from September to May; flowers are pale
lemon-yellow, usually in pairs on axillary peduncles. The pods are 9–11 cm long,
about 1.5 cm wide, flattened, and contain 6–10 small seeds (Figs. 1, 2 and 3).CXVII
Actions and Uses: Both species of Bauhinia, i.e. B. tomentosa and B. variegata are
described as Kachnal or Kuchnar/Kachnar in Unani medicine literature. Dymock
et al.XL described B. variegata as kachnár, but mentioned two varieties with similar
properties, one having purple or deep rose-colored flowers, while the other with
white, yellow and green flowers. Bark is described as alterative, tonic, and astrin-
gent, and useful in skin diseases and ulcers. They also referred to Makhzan-al-
Advia, and mentioned that Muslim physicians in India use bark to prevent
decomposition of blood and humours, and use it for leprosy and scrofula.XL Dried
small buds and young flowers (temperament, cold 2° and dry 2°) are used for
dysentery, bleeding piles and hematuria, and fruits are considered diuretic. Bruised
bark is applied externally to wounds and tumors, and an infusion of the bark is used
as an astringent gargle.LXXVII Decoction of the root bark is used in the treatment of
inflammation of liver, and as a vermifuge.LXXXIV NadkarniCVI credited seeds with

Fig. 1 Bauhinia tomentosa, Leaves, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Bauhinia_tomentosa_(Camel_foot_tree)
_in_Hyderabad,_AP_W_IMG_9477.jpg; https://creativecommons.org/licenses/by/3.0/deed.en
Bauhinia tomentosa L./Bauhinia variegata L. 415

Fig. 2 Bauhinia tomentosa, Flower, J.M. Garg, WikimediaCommons, https://commons.wiki

media.org/wiki/File:Bauhinia_tomentosa_(Camel_foot_tree)_in_Hyderabad,_AP_W_IMG_9479.
jpg; http://tropical.theferns.info/image.php?id=Bauhinia+tomentosa

Fig. 3 Bauhinia variegata, Flower, Peter, WikimediaCommons, https://commons.wikimedia.org/

wiki/File:Bauhinia_variegata_flower.jpg

tonic and aphrodisiac properties; whereas bark and buds are described as alterative
and astringent, and buds decoction used for menorrhagia, hemorrhoids and hema-
turia,LXXXI the bark decoction is used in leprosy, scrofula, skin diseases and
ulcers.LXXXI B. variegata, also called Kachnar or Rakta Kanchnar in Hindi due to
its blood-red flowers, is used in Ayurveda as a liver tonic [3]. Stem bark is also used
in the treatment of asthma, jaundice, tuberculosis, leprosy, and skin diseases [15].
416 Bauhinia tomentosa L./Bauhinia variegata L.

It is known as Pata-de-vaca and Mororó in Brazil and widely used in traditional

medicine as an antidiabetic agent; a protein with insulin-like action has been iso-
lated from its leaves [2]. Bark infusion is also used as an astringent and tonic in
scrofula, skin diseases, and ulcers, and the roots decoction is used in dyspepsia and
as an antidote to snake poison [1].
Phytoconstituents: Leaves of B. tomentosa contain amino acids and proteins, seeds
and seed oil contain fatty acids [5] and minerals [4], and flowers contain rutin,
quercetin [26], and isoquercetin [28]. Compounds, 1-(2′-hydroxy-4′-methox-
yphenyl)-3-(4″-methoxyphenyl)-2-hydroxypropane-1,3-dione,5-hydroxyflavone, 3,
5,7,3′,4′-pentahydroxyflavone, 3,5,7,2′,4′-pentahydroxyflavone, and 5,7,3′,4′-tetra-
hydroxyflavone-3-O-rhamnoside have been isolated from air dried flowering buds
[19]. Various extracts of leaves of B. variegata showed the presence of reducing
sugar, anthraquinone, saponins, terpenoids, alkaloids and flavonoids [16, 27].
Six flavonoids: kaempferol, ombuin, kaempferol 7,4′-dimethyl ether 3-O-b-D-
glucopyranoside, kaempferol 3-O-b-D-glucopyranoside, isorhamnetin 3-O-b-D-glu-
copyranoside and hesperidin together with one triterpene caffeate with significant
in vitro anti-inflammatory activity were identified in aerial parts [24]. Triterpene
saponin [17], a phenanthraquinone, named bauhinione in the stems [31], a flavanone,
a dihydrodibenzoxepin and flavonoids in the root bark [25], and flavone glycosides
from seeds [29], and the root [30], have been isolated.
Pharmacology: Aqueous leaf extract of B. tomentosa to diabetic rats significantly
reduced blood glucose, HbA1c, TC, TGs, LDL, VLDL, and liver enzymes, and
significantly increased insulin and HDL [6]. Aqueous leaf extract of B. variegata
also significantly decreased plasma levels of creatinine and BUN of diabetic rats
[13], while ethanol leaf extract and its major constituent, roseoside, produced
insulinotropic activity in insulin-secreting cell line INS-1 [8]. Ethanol extract of
defatted stem bark of B. variegata did not lower blood glucose in normoglycemic
rats, but significantly reduced blood glucose in hyperglycemic rats, and normalized
impaired glucose tolerance [14]. Ethyl acetate extract of leaves of B. tomentosa
showed modest antimicrobial activity against B. subtilis, B. pumilus, E. faecalis,
E. coli, P. aeruginosa, and P. vulgaris [7]. Intraperitoneal administration of the
methanol leaf extract exhibited significant immunomodulatory, antioxidant, and
anti-inflammatory activities [10], significantly ameliorated acetic acid-induced
ulcerative colitis [9], protected against cisplatin- nephrotoxicity in rats [12], and
significantly increased life span of BALB/c mice with Dalton’s ascites lymphoma,
and coadministration of the extract with CP significantly reduced tumor volume and
hematological toxicity [11].
Pretreatment with aqueous and ethanol stem bark extracts of B. variegata sig-
nificantly reduced milk-induced leukocytosis and eosinophilia in albino mice [15].
Both aqueous and ethanol extracts of stem bark and root showed significant
antioxidant activity, and significantly reduced plasma TC, TG, LDL, and VLDL,
and increased plasma HDL levels [20]. Whole stem ethanol extract was protective
against cisplatin-nephropathy in rats [18], and stem bark alcohol extract signifi-
cantly protected against CCl4-induced hepatic damage in Sprague-Dawley rats [3].
Bauhinia tomentosa L./Bauhinia variegata L. 417

Various leaf extracts exhibited significant anticancer, antioxidant and antimicrobial

activity against K. pneumonia, pathogenic strains of E. coli, Proteus spp. and
Pseudomonas spp. Methanol leaf extract of B. variegata also significantly delayed
appearance and reduced cumulative numbers of DMBA-induced skin papillomas
[1]. Ethanol extract significantly enhanced mean survival time of Dalton’s ascitic
lymphoma tumor-bearing Swiss albino mice [22], improved antioxidant status of
NDEA-induced liver tumors bearing rats, and was cytotoxic to human cancer cell
lines [21]. A flavanone isolated from stems showed cytotoxic activity against a
number of human cancer cell lines [23].
Human A/Es, Allergy and Toxicity: It delays digestion and causes
flatulence.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported in English journals listed on
PubMed.

References
1. Agrawal RC, Pandey S. Evaluation of anticarcinogenic and antimutagenic
potential of Bauhinia variegata extract in Swiss albino mice. Asian Pac J
Cancer Prev. 2009;10:913–6.
2. Azevedo CR, Maciel FM, Silva LB, et al. Isolation and intracellular locali-
zation of insulin-like proteins from leaves of Bauhinia variegata. Braz J
Med Biol Res. 2006;39:1435–44.
3. Bodakhe SH, Ram A. Hepatoprotective properties of Bauhinia variegata
bark extract. Yakugaku Zasshi. 2007;127:1503–7.
4. Chowdhury AR, Banerji R, Misra G, Nigam SK. Fatty acid composition and
mineral composition of the seeds of some species of Bauhinia. Feete Seifen
Anstrichmittel. 1984;86:237–9.
5. Daulatabad CD, Mulla GM, Mirajkar AM. Vernolic acid from Lager-
storoemia thomsonil and Bauhinia tomentosa seed oils. J Oil Technol Assoc
India. 1991;23:53–4.
6. Devaki K, Beulah U, Akila G, Narmadha R, Gopalakrishnan VK. Glucose
lowering effect of aqueous extract of Bauhinia tomentosa L. on alloxan
induced type 2 diabetes mellitus in wistar albino rats. J Basic Clin Pharm.
2011;2:167–74.
7. Dugasani S, Balijepalli MK, Tandra S, Pichika MR. Antimicrobial activity
of Bauhinia tomentosa and Bauhinia vahlii roots. Pharmacogn Mag. 2010;
6:204–7.
8. Frankish N, de Sousa Menezes F, Mills C, Sheridan H. Enhancement of
insulin release from the beta-cell line INS-1 by an ethanolic extract of
Bauhinia variegata and its major constituent roseoside. Planta Med. 2010;
76:995–7.
418 Bauhinia tomentosa L./Bauhinia variegata L.

9. Kannan N, Guruvayoorappan C. Protective effect of Bauhinia tomentosa on

acetic acid induced ulcerative colitis by regulating antioxidant and inflam-
matory mediators. Int Immunopharmacol. 2013;16:57–66.
10. Kannan N, Renitta RE, Guruvayoorappan C. Bauhinia tomentosa stimulates
the immune system and scavenges free radical generation in vitro. J Basic
Clin Physiol Pharmacol. 2010;21:157–68.
11. Kannan N, Sakthivel KM, Guruvayoorappan C. Antitumor and chemopro-
tective effect of Bauhinia tomentosa by regulating growth factors and
inflammatory mediators. Asian Pac J Cancer Prev. 2015;16:8119–26.
12. Kannan N, Sakthivel KM, Guruvayoorappan C. Nephroprotective effect of
Bauhinia tomentosa Linn. against cisplatin-induced renal damage. J Environ
Pathol Toxicol Oncol. 2016;35:99–107.
13. Kulkarni YA, Garud MS. Bauhinia variegata (Caesalpiniaceae) leaf extract:
an effective treatment option in type I and type II diabetes. Biomed Pharmaco-
ther. 2016;83:122–9.
14. Kumar P, Baraiya S, Gaidhani SN, Gupta MD, Wanjari MM. Antidiabetic
activity of stem bark of Bauhinia variegata in alloxan-induced hyper-
glycemic rats. J Pharmacol Pharmacother. 2012;3:64–6.
15. Mali RG, Dhake AS. Evaluation of effects of Bauhinia variegata stem bark
extracts against milk-induced eosinophilia in mice. J Adv Pharm Technol
Res. 2011;2:132–4.
16. Mishra A, Sharma AK, Kumar S, Saxena AK, Pandey AK. Bauhinia
variegata leaf extracts exhibit considerable antibacterial, antioxidant, and
anticancer activities. Biomed Res Int. 2013;2013:915436.
17. Mohamed MA, Mammoud MR, Hayen H. Evaluation of antinociceptive
and anti-inflammatory activities of a new triterpene saponin from Bauhinia
variegata leaves. Z Naturforsch C. 2009;64:798–808.
18. Pani SR, Mishra S, Sahoo S, Panda PK. Nephroprotective effect of Bauhinia
variegata (Linn.) whole stem extract against cisplatin-induced nephropathy
in rats. Indian J Pharmacol. 2011;43:200–2.
19. Radha R, Vasantha VS, Pitchumani K. Chemical constituents from the
flowering buds of Bauhinia tomentosa Linn. (FBBT). Nat Prod Res. 2016;30:
1670–4.
20. Rajani GP, Ashok P. In vitro antioxidant and antihyperlipidemic activities
of Bauhinia variegata Linn. Indian J Pharmacol. 2009;41:227–32.
21. Rajkapoor B, Jayakar B, Murugesh N, Sakthisekaran D. Chemoprevention
and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine
induced liver tumors and human cancer cell lines. J Ethnopharmacol. 2006;
104:407–9.
22. Rajkapoor B, Jayakar B, Murugesh N. Antitumour activity of Bauhinia
variegata on Dalton’s ascitic lymphoma. J Ethnopharmacol. 2003;89:107–9.
23. Rajkapoor B, Murugesh N, Rama Krishna D. Cytotoxic activity of a
flavanone from the stem of Bauhinia variegata Linn. Nat Prod Res. 2009;
23:1384–9.
Bauhinia tomentosa L./Bauhinia variegata L. 419

24. Rao YK, Fang SH, Tzeng YM. Anti-inflammatory activities of flavonoids
and a triterpene caffeate isolated from Bauhinia variegata. Phytother Res.
2008;22:957–62.
25. Reddy MV, Reddy MK, Gunasekar D, Caux C, Bodo B. A flavanone and a
dihydrodibenzoxepin from Bauhinia variegata. Phytochemistry. 2003;
64:879–82.
26. Row LR, Viswanathan N. Coloring matter of the flower petals of Bauhinia
tomentosa. Proc Indian Acad Sci, Section A. 1954;39:240–2.
27. Sayago CT, Camargo VB, Barbosa F, et al. Chemical composition and
in vitro antioxidant activity of hydroethanolic extracts from Bauhinia
forficata subsp. pruinosa and B. variegata. Acta Biol Hung. 2013;64:21–33.
28. Subramanian SS, Nair AG. Isolation of isoquercitrin from flowers of
Bauhinia tomentosa. Indian J Chem. 1963;1:450.
29. Yadava RN, Reddy VM. A new flavone glycoside, 5-hydroxy 7,3′,4′,5′-tetra-
methoxyflavone 5-O-beta-D-xylopyranosyl-(1– > 2)-alpha-L-rhamnopyrano-
side from Bauhinia variegate Linn. J Asian Nat Prod Res. 2001;3:341–6.
30. Yadava RN, Reddy VM. Anti-inflammatory activity of a novel flavonol
glycoside from the Bauhinia variegata Linn. Nat Prod Res. 2003;17:165–9.
31. Zhao YY, Cui CB, Cai B, Han B, Sun QS. A new phenanthraquinone from
the stems of Bauhinia variegata L. J Asian Nat Prod Res. 2005;7:835–8.
Berberis aristata DC.
(Berberidaceae)

(Syns.: B. bussmul K. Koch ex Miq.; B. coccinea K. Koch; B. elegans K. Koch; B. gracilis

Lindl.; B. macrophylla K. Koch; B. umbellata Lindl.)

Abstract
A deciduous evergreen shrub found in temperate and subtropical regions of
Asia, Africa, Europe and North and South Americas. It is useful as antipyretic,
antimicrobial, hepatoprotective, antihyperglycemic, anticancer, antioxidant, and
antilipidemic agent. Bark and stem are tonic, diaphoretic, stomachic, antiperiodic,
and gentle aperients, and used in malarial fevers, diarrhea, dyspepsia, dysentery,
ague, during convalescence from fevers and acute diseases; the root is purgative.
The extract and its formulations have also been used in the treatment of diarrhea,
hemorrhoids, gynecological disorders, HIV-AIDS, osteoporosis, diabetes, wound
healing, eye and ear infections, jaundice, skin diseases, enlargement of spleen,
leprosy, rheumatism, morning/evening sickness, and snakebite. The plant mainly
contains isoquinoline alkaloids; major alkaloids identified are berberine, berber-
rubine, jatrorrhizine, ketoberberine, palmatine, dihydropalmatine, berbamine and
pakistanamine. Aqueous-alcoholic root extract significantly lowered FBG in
diabetic rats, without causing hypoglycemia, increased glucokinase and G-6-PD
activities, and decreased activity of glucose-6-phosphatase. Hydroalcoholic bark
extract produced significant anti-inflammatory and antigranuloma effects with
significant reduction in proinflammatory markers. A pilot study of a combination
product of B. aristata extract and Silybum marianum extract to twenty-six Italian
type-2 diabetic patients with suboptimal glycemic control, showed significant
reduction in HbA1c, basal insulin, TC, LDL-C, and TGs, after 90-days of
treatment. A comparative study of the standardized extract of B. aristata with the
fixed combination containing the same standardized extract of B. aristata plus
standardized extract of S. marianum showed similar improved fasting glucose,
TC, LDL-C, TGs, and liver enzyme levels in both groups, except the HbA1c

B. aristata and B. vulgaris are used interchangeably in Unani and Ayurveda.

© Springer Nature Switzerland AG 2020 421

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_43
422 Berberis aristata DC.

values were reduced to a greater extent by the fixed combination. Addition of the
combination to statin regimen was effective in reducing doses of statins by half in
dyslipidemic patients who could not tolerate high doses of statins, without
affecting the lipid profile.

Keywords
Amber baarees

Begrannter sauerdorn Chitra

Darhalad

Darchoba





Dãruharidrã Indian barberry Lofiyun Rasaut Zarishk

Vernaculars: Urd.: Darchoba, Darhald (stem wood), Rasot (extract), Zarishk

(fruit); Hin.: Chitra, Darhalad (stem wood), Jharki-halad, Kash-mal, Rasaut, Ras-
wanti (extract), Raswat; San.: Chitra, Dãruharidrã, Dãruniśã, Darvi, Katamkateri,
Rasãñjana (dry extract), Pitã, Pitadãru, Parjanyã; Ben.: Darhaldi, Daruharidra;
Mal.: Kasturimanjal, Maramanjal, Maradarisina; Mar.: Daruhalad; Tam.: Kastu-
rimanjal, Maramanjal, Mullabubla, Puttar; Tel.: Daruharidra, Kasturipaspu, Manu-
pasupu; Ara.: Amber baarees (fruit); Eng.: Indian barberry, Nepal barberry, Root
bark of berberis, Turmeric wood, Tree turmeric; Ger.: Begrannter sauerdorn; Gre.:
Lofiyun; Nep.: Chitra; Per.: Darchob (stem wood), Darhald, Filzahrah, Zarishk
(fruit).
Description: A deciduous evergreen shrub found in temperate and subtropical
regions of Asia (north India, Nepal, Sri Lanka), Africa, Europe and North and South
Americas. The roots of B. aristata are considered as the official drug in the
Ayurvedic Pharmacopoeia of India. However, in different parts of India, other
species of Berberis, namely B. asiatica, B. chitria, and B. lycium are also used
under the name of Daruharidra [24]. Rasout is the water extract of powdered stem
or wood.LXXXI In India, Darhalad is available as pieces of 2.5–5.0 cm in diameter,
covered by a soft, corky, light brown bark, with a hard layer of stony cells beneath,
forming a complete coating of the stem. Rasot or rusot is the dark brown extract of
the consistence of opium, having a bitter and astringent taste. Zarishk is a moist
sticky mass of small black fruit; most of them abortive, but a few contain one or two
oblong seeds about 0.4 cm long, with a thin roughish brown testa. Root bark is
brittle, externally light-brown and corky, beneath which is a dark brown layer, with
a greenish-yellow tinge, fibrous, and very bitter (Figs. 1 and 2).XL
Actions and Uses: Ibn-al-BaitarLXIX quoted Ghafiqi that the decoction of the root in
wine or vinegar is beneficial for inflammation and pain of liver. Rose-water in which
Zarishk has been soaked is preventive and curative as eye drops for chronic
inflammation. Ibn al-Baitar also quoted Galen that it is beneficial for gastric ulcers,
diarrhea and nosebleed in women. Galen assigned the temperament of moderately
hot and dry 2° to this plant; some authors consider it cold 1° and dry 2°. Dioscorides
mentioned it useful for cough and hemoptysis. In Iran, fruits of B. vulgaris
are known as Zereshk. The tree is called Zarishk in Unani medicine, the bark
is known as Dar-e-hald, and the resin obtained from the tree is called Rasaut.
Externally, Rasaut is astringent, anti-inflammatory and counterirritant; and inter-
nally, astringent, blood purifier, and styptic; internally it is used after dissolving in
Berberis aristata DC. 423

Fig. 1 Berberis aristata, Plant, L. Shyamal, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:BerberisAculeata.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Berberis aristata, Fruits, Buddhika.jm, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Berberis_aristata_fruit.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

rose-water.1 Decoction of Zarishk as enema is beneficial for ulcerative colitis.

KabeeruddinLXXVII mentions that Zarishk reduces excessive heat due to blood and

1
Tayyab M: Personal Communication.
424 Berberis aristata DC.

yellow bile, reduces stomach and liver heat, and relieves thirst, nausea and vomiting.
It is useful as antipyretic, antimicrobial, hepatoprotective, antihyperglycemic, anti-
cancer, antioxidant, and antilipidemic agent. Bark and stem are tonic, diaphoretic,
stomachic, antiperiodic, and gentle aperients, and used in malarial fevers, diarrhea,
dyspepsia, dysentery, ague, during convalescence from fevers and acute dis-
easesLXXXI; the root is purgative.CV The extract and its formulations have also been
used in the treatment of hemorrhoids, gynecological disorders, HIV-AIDS, osteo-
porosis, diabetes, wound healing, eye and ear infections, jaundice, skin diseases, and
malarial fever [22], enlargement of spleen, leprosy, rheumatism, fever, morning/
evening sickness, and snakebite [28]. In Ayurveda, the stem is used in the treatment
of kapharoga, amatisara, medoroga, urustambha, karnaroga, mukharoga, netraroga,
kandū, vrana, and meha.LX The alkaloid, berberine, isolated from the plant has also
shown significant antimicrobial activity against bacteria, viruses, fungi, protozoans,
helminths, and chlamydia; and is clinically used for bacterial diarrhea, intestinal
parasitic infections, and ocular trachoma infections [2].
Phytoconstituents: The plant mainly contains isoquinoline alkaloids; major alka-
loids identified are berberine, berberrubine, jatrorrhizine, ketoberberine, palmatine,
dihydropalmatine or 7,8-dihydro-8-hydroxyberberine, berbamine and pakistana-
mine. Berberine, mainly reported from root and stem bark, was also identified in
leaves along with chlorogenic acid [3]. Hydroalcoholic stem bark extract showed
the presence of 25.44% alkaloids (the isoquinoline alkaloids: berbamine, berberine,
reticuline, jatrorrhizine, palmatine and piperazine) [29].
Pharmacology: Aqueous-alcoholic (50%) root extract, mainly containing berber-
ine, berbamine and palmatine, significantly lowered FBG in diabetic rats, without
causing hypoglycemia. The glucokinase and G-6-PD activities were increased, and
activity of glucose-6-phosphatase was decreased [25]. Berberine shows hypo-
glycemic activity comparable to metformin in diabetic mice [4]. Aqueous fruit
extract exhibited a positive inotropic action, and activity-directed fractionation led
to n-butanolic fraction (BF) with cardiotonic activity; that produced a dose-
dependent positive inotropic action with little effect on HR. Pretreatment of atria
with propranolol did not abolish the cardiotonic effect of BF, and carbachol par-
tially reversed the effect, indicating that a cAMP-independent mechanism underlies
the inotropic action [14].
Pretreatment of rats with hydroalcoholic bark extract produced significant
anti-inflammatory and antigranuloma effects with significant reduction in proinflam-
matory markers, IL-1b, IL-6, TNF-R1, and COX-2 [20]. Hydroalcohol root extract
inhibited growth of B. cereus, E. coli, S. aureus and A. flavus; while the stem extract
was active against B. cereus and S. pneumoniae [26]. Ethanol and aqueous bark
extracts inhibited growth of Shigella, with MIC and MBC between 125–500 and
300–600 µg/mL, respectively. Both extracts delayed the onset of castor oil-induced
diarrhea and reduced the number of diarrheal episodes [17]. The extract significantly
inhibits generation of ROS from H. pylori-infected gastric epithelial cells [33].
Hydroalcoholic stem bark extract exhibited synergistic effect with colistin, tigecy-
cline and amoxicillin/clavulanate, and antagonism with ertapenem and meropenem
[29], produced synergistic bactericidal effect against carbapenem-resistant E. coli
Berberis aristata DC. 425

[30], and ameliorated carbapenem-resistant E. coli-induced peritonitis in rats [31].

B. aristata extract protected rats against anti-TB drugs (INH, RIF, and PZA)-
induced testicular damage [24]. Administration of aqueous-methanol extract to
ovariectomized rats for 42-days exhibited antiosteoporotic effect, significantly
increased uterine weight, femur BMD and lumber hardness, and increased serum
levels of calcium and phosphorus [32]. Ethanol extract (i.p.) attenuated percent
increase in weight gain due to tumor cell proliferation, increased survival time,
reversed alterations in hematology of EAC-bearing mice [21]. Berberine also sig-
nificantly inhibited incidence of tumors, induced by 20-MCA or NDEA in mice
and rats, and increased their life span [1]. Topical instillation of aqueous extract
showed potent anti-inflammatory activity against endotoxin-induced uveitis in
rabbits [15].
Berberine exhibited antidepressant activity, and enhanced antimobility effect of
subeffective doses of desipramine, imipramine, fluoxetine, venlafaxine, bupropion
and tranylcypromine in forced-swim test of mice, and increased levels of NE, 5-HT
and DA [19]. Chronic administration of berberine for 15-days significantly increased
brain levels of NE, 5-HT, as well as DA; but at a higher dose of 10 mg/kg, i.p., only
5-HT and DA were significantly increased [18]. Berberine was effective against T.
vaginalis, comparable to metronidazole [27], and markedly diminished parasitic
load, improved hematological picture of L. donovani-infected hamsters, with less
toxicity than pentamidine [13]. Berberine inhibits secretory responses of heat-labile
enterotoxins of V. cholerae and E. coli, and also markedly inhibits secretory
response of E. coli heat-stable enterotoxin; however it does not inhibit stimulation of
adenylate cyclase by cholera enterotoxin [23]. Pretreatment with berberine for
2-days also prevented APAP- or CCl4-hepatotoxicity, and post-treatment with three
successive oral doses reduced APAP-induced hepatic damage, but not the CCl4-
hepatotoxicity [16].
Clinical Studies: Berberine has poor oral bioavailability due to the presence of P-
glycoprotein in enterocytes—that extrudes berberine back into the intestinal lumen,
thus limiting its absorption. Silymarin, derived from Silybum marianum, is con-
sidered a P-glycoprotein inhibitor by some. A pilot study of a combination product
of B. aristata extract and Silybum marianum extract (Berberol®) to twenty-six
Italian type-2 diabetic patients with suboptimal glycemic control, showed significant
reduction in HbA1c, basal insulin, TC, LDL-C, and TGs, after 90-days of treatment
[12]. In another RCT of dyslipidemic, euglycemic patients, the same combination
reduced TC, TGs and LDL-C, and increased HDL-C and insulin secretion after
three-months of treatment. However, the lipid profile worsened when treatment was
interrupted for two months, and improved again when the treatment was reintro-
duced [5, 6]. A comparative study of the standardized extract of B. aristata with the
fixed combination containing the same standardized extract of B. aristata plus
standardized extract of S. marianum (Berberol®) showed similar improved fasting
glucose, TC, LDL-C, TGs, and liver enzyme levels in both groups, except the
HbA1c values were reduced to a greater extent by the fixed combination [11].
Addition of the combination (Berberol®) to statin regimen was effective in reducing
doses of statins by half in dyslipidemic patients who could not tolerate high doses of
426 Berberis aristata DC.

statins, without affecting the lipid profile [8]. Similar results were reported in
hypercholesterolemic, type-2 diabetic patients, wherein addition of Berberol® either
as a single therapy or as an add-on therapy to low-dose statin or to ezetimibe reduced
TGs, LDL-C, FBG, and HbA1c in a significant manner without inducing toxicity
[10]. The combination also reduced fasting plasma glucose, insulin, and HOMA-index
in euglycemic, dyslipidemic subjects, intolerant to high dosages of statins after
six-months of treatment, with no reduction in levels of TC, LDL-C and TGs [9].
Addition of the combination to insulin therapy in type 1 DM patients resulted in
reduction of insulin dose for the same level of glycemic control [7].
Human A/Es, Allergy and Toxicity: Harmful in individuals with phlegmatic
constitution.LXXVII
Animal Toxicity: Oral LD50 of both ethanol and aqueous bark extracts were
>5,000 mg/kg body weight in the acute toxicity studies with Swiss albino mice
[15]. The no observed adverse effect level (NOAEL) of hydroalcoholic stem bark
extract in rats was up to a dose of 2,000 mg/kg BW [31].
CYP450 and Potential for Drug-Herb Interactions: Hepatic mRNA levels of
CYP1A1, CYP2B9, CYP2B10, CYP3A11, CYP4A10, and CYP4A14 are increased
in STZ-diabetic mice. Berberine restores expression of CYP3A11, CYP4A10, and
CYP4A14 to normal levels, but suppresses the expression of CYP2E1, an adverse
hepatic event-associated enzyme. Berberine treatment alone increases the expression
of CYP2B9 and CYP2B10 in primary mouse hepatocytes [4].
Commentary: Antidiabetic and antidyslipidemic effects obtained in RCTs of the
combination of standardized extracts of B. aristata and S. marianum as adjunct to
standard treatments are encouraging, and worthy of consideration in patients with
suboptimal glycemic control.

References
1. Anis KV, Rajeshkumar NV, Kuttan R. Inhibition of chemical carcinogen-
esis by berberine in rats and mice. J Pharm Pharmacol. 2001;53:763–8.
2. Anonymous. Berberine. Altern Med Rev. 2000;5:175–7.
3. Bajpai V, Singh A, Arya KR, Srivastava M, Kumar B. Rapid screening for the
adulterants of Berberis aristata using direct analysis in real-time mass
spectrometry and principal component analysis for discrimination. Food Addit
Contam Part A Chem Anal Control Expo Risk Assess. 2015;32:799–807.
4. Chatuphonprasert W, Nemoto N, Sakuma T, Jarukamjorn K. Modulations
of cytochrome P450 expression in diabetic mice by berberine. Chem Biol
Interact. 2012;196:23–9.
5. Derosa G, Bonaventura A, Bianchi L, et al. Berberis aristata/Silybum mari-
anum fixed combination on lipid profile and insulin secretion in dyslipi-
demic patients. Expert Opin Biol Ther. 2013;13:1495–506.
6. Derosa G, Bonaventura A, Bianchi L, et al. Effects of Berberis aristata/
Silybum marianum association on metabolic parameters and adipocytokines
Berberis aristata DC. 427

in overweight dyslipidemic patients. J Biol Regul Homeost Agents. 2013;27:

717–28.
7. Derosa G, D’Angelo A, Maffioli P. The role of a fixed Berberis aristata/
Silybum marianum combination in the treatment of type 1 diabetes mellitus.
Clin Nutr. 2016;35:1091–5.
8. Derosa G, Romano D, D’Angelo A, Maffioli P. Berberis aristata combined
with Silybum marianum on lipid profile in patients not tolerating statins at
high doses. Atherosclerosis. 2015;239:87–92.
9. Derosa G, Romano D, D’Angelo A, Maffioli P. Berberis aristata/Silybum
marianum fixed combination (Berberol®) effects on lipid profile in dyslipi-
demic patients intolerant to statins at high dosages: a randomized, placebo-
controlled, clinical trial. Phytomedicine. 2015;22:231–7.
10. Di Pierro F, Bellone I, Rapacioli G, Putignano P. Clinical role of a fixed
combination of standardized Berberis aristata and Silybum marianum
extracts in diabetic and hypercholesterolemic patients intolerant to statins.
Diabetes Metab Syndr Obes. 2015;8:89–96.
11. Di Pierro F, Putignano P, Villanova N, et al. Preliminary study about the
possible glycemic clinical advantage in using a fixed combination of Ber-
beris aristata and Silybum marianum standardized extracts versus only Ber-
beris aristata in patients with type 2 diabetes. Clin Pharmacol. 2013;5:
167–74.
12. Di Pierro F, Villanova N, Agostini F, et al. Pilot study on the additive effects
of berberine and oral type 2 diabetes agents for patients with suboptimal
glycemic control. Diabetes Metab Syndr Obes. 2012;5:213–7.
13. Ghosh AK, Bhattacharyya FK, Ghosh DK. Leishmania donovani: amastig-
ote inhibition and mode of action of berberine. Exp Parasitol. 1985;60:
404–13.
14. Gilani AH, Janbaz KH, Aziz N, et al. Possible mechanism of selective
inotropic activity of the n-butanolic fraction from Berberis aristata fruit.
Gen Pharmacol. 1999;33:407–14.
15. Gupta SK, Agarwal R, Srivastava S, et al. The anti-inflammatory effects of
Curcuma longa and Berberis aristata in endotoxin-induced uveitis in
rabbits. Invest Ophthalmol Vis Sci. 2008;49:4036–40.
16. Janbaz KH, Gilani AH. Studies on preventive and curative effects of
berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia.
2000;71:25–33.
17. Joshi PV, Shirkhedkar AA, Prakash K, Maheshwari VL. Antidiarrheal
activity, chemical and toxicity profile of Berberis aristata. Pharm Biol.
2011;49:94–100.
18. Kulkarni SK, Dhir A. On the mechanism of antidepressant-like action of
berberine chloride. Eur J Pharmacol. 2008;589:163–72.
19. Kulkarni SK, Dhir A. Possible involvement of L-arginine-nitric oxide (NO)-
cyclic guanosine monophosphate (cGMP) signaling pathway in the anti-
depressant activity of berberine chloride. Eur J Pharmacol. 2007;569:77–83.
428 Berberis aristata DC.

20. Kumar R, Gupta YK, Singh S. Anti-inflammatory and antigranuloma activity

of Berberis aristata DC. in experimental models of inflammation. Indian J
Pharmacol. 2016;48:155–61.
21. Pai KS, Srilatha P, Suryakant K, et al. Anticancer activity of Berberis
aristata in Ehrlich ascites carcinoma-bearing mice: a preliminary study.
Pharm Biol. 2012;50:270–7.
22. Potdar D, Hirwani RR, Dhulap S. Phytochemical and pharmacological
applications of Berberis aristata. Fitoterapia. 2012;83:817–30.
23. Sack RB, Froehlich JL. Berberine inhibits intestinal secretory response of
Vibrio cholerae and Escherichia coli enterotoxins. Inf Immun. 1982;35:471–5.
24. Sharma R, Goyal N, Singla M, Sharma VL. Berberis aristata ameliorates
testicular toxicity induced by combination of first-line tuberculosis drugs
(rifampicin + isoniazid + pyrazinamide) in normal Wistar rats. J Diet Suppl.
2018;28:1–14.
25. Singh J, Kakkar P. Antihyperglycemic and antioxidant effect of Berberis
aristata root extract and its role in regulating carbohydrate metabolism in
diabetic rats. J Ethnopharmacol. 2009;123:22–6.
26. Singh M, Srivastava S, Rawat AK. Antimicrobial activities of Indian
Berberis species. Fitoterapia. 2007;78:574–6.
27. Soffar SA, Metwali DM, Abdel-Aziz SS, et al. Evaluation of the effect of a
plant alkaloid (berberine derived from Berberis aristata) on Trichomonas
vaginalis in vitro. J Egypt Soc Parasitol. 2001;31:893–904.
28. Srivastava S, Rawat AK. Quality evaluation of ayurvedic crude drug
daruharidra, its allied species, and commercial samples from herbal drug
markets of India. Evid Based Complement Alter Med. 2013;2013:472973.
29. Thakur P, Chawla R, Goel R, et al. Augmenting the potency of third-line
antibiotics with Berberis aristata: in vitro synergistic activity against
carbapenem-resistant Escherichia coli. J Glob Antimicrob Resist. 2016;6:10–6.
30. Thakur P, Chawla R, Narula A, et al. In vitro bactericidal activity of
Berberis aristate extract against clinical isolates of carbapenem-resistant
Escherichia coli. J Complement Integr Med. 2016;13:229–37.
31. Thakur P, Chawla R, Narula A, Sharma RK. Protective effect of Berberis
aristata against peritonitis induced by carbapenem-resistant Escherichia
coli in a mammalian model. J Glob Antimicrob Resist. 2017;9:21–9.
32. Yogesh HS, Chandrashekhar VM, Katti HR, et al. Antiosteoporotic activity
of aqueous-methanol extract of Berberis aristata in ovariectomized rats.
J Ethnopharmacol. 2011;134:334–8.
33. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and
cytoprotective effects of selected Pakistani medicinal plants in Helicobacter
pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
Berberis vulgaris L.
(Berberidaceae)

Abstract
A deciduous shrub, native to central and southern Europe, northwest Africa and
western Asia, naturalized in northern Europe, North America, and other countries.
B. vulgaris was reportedly used by the native Americans in cases of general
debility, and to improve appetite. When early settlers observed this, they employed
root as bitter tonic, and also used it in the treatment for ulcers, heartburn and
stomach problems in small doses. In small doses, it is a tonic, and in large doses, a
purgative, and largely used to relieve heat, thirst and nausea; especially useful in
scarlet fever and brain affection. In Bulgarian folk medicine, root extracts have
been used in rheumatic and other chronic inflammatory disorders, and in Russia to
treat chronic cholecystitis. In Iranian traditional medicine the fruits are credited
with antiarrhythmic and sedative properties. Twenty-two alkaloids have been
reported from root, stem, leaves and fruit of B. vulgaris. Major constituents are
berberine, palmatine, berbamine and jatrorrhizine; other constituents include
columbamine, oxyacanthine, bervulcine, coptisine isotetrandrine and magno-
florine. Aqueous fruit extract significantly reduces mean arterial BP and HR in
normotensive and hypertensive rats; and antagonizes phenylephrine effects on
isolated rat aortic rings. Antihypertensive and vasodilatory effects are suggested to
be mainly endothelium-independent. The aqueous fruit extract also significantly
reduced blood glucose of normal and diabetic rats, with significant decreases in TC
and TGs levels; protected mice against lead-induced oxidative stress and liver
toxicity, and exhibited antihistaminic and anticholinergic activity. In a
double-blind, RCT, type 2 diabetic patients, administered fruit extract for
3-months had significant decreases in serum TC, LDL-C, TGs, apo B, glucose,
and insulin levels, and significant increase in total antioxidant capacity.

Keywords





Agracejo Amber baarees Berbéris vulgaire Berberitze Berbero Common





barberry Darhalad Darchoba Dãruharidrã Kızıl karamuk

© Springer Nature Switzerland AG 2020 429
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_44
430 Berberis vulgaris L.

Vernaculars: Urd.: Darchoba, Darhald (stem wood), Rasaut (extract), Zarishk

(fruit); Hin.: Darhalad (stem wood), Rasaut, Raswanti (extract); San.: Daru-haridra
(stem wood); Tam.: Mullabubla, Puttar (stem wood); Ara.: Amber baarees (fruit),
Athrar, Barbarees; Chi.: Cihuangliaan, Sankezhen; Dan.: Almindelig berberis;
Dut.: Zuurbes, Zuurdoorn; Eng.: Common barberry, Berbéris vulgaire, European
barberry, True barberry, Pipperidge; Fin.: Ruostehappomarja; Fre.: Berbéris
commun, Épine-vinette, Oseille des bois, Pisse-vinaigre, Vinaigrette, Vinettier;
Ger.: Beerdorn, Berberitze, Gemeine berberitze, Gemeiner sauerdorn, Heckenber-
beritze, Sauerdorn; Ita.: Berberis vulgaris, Berbero, Crespino, Crespino comune;
Mor.: Aghriss; Per.: Bedana, Darhald, Darchob (stem wood), Sereshk (fruit), Zarij,
Zarishk; Pol.: Berberys zwyczajny; Por.: Bérberis, Uva-espim; Rus.: Barbaris
obyknovennyj; Spa.: Acetín, Agracejo, Agracillo, Agrazón, Alarguiz, Arlo, Bér-
bero, Coralet, Espino cambrón, Tapaculo; Swe.: Berberis; Tur.: Kızıl karamuk.
Description: A pretty deciduous shrub, native to central and southern Europe,
northwest Africa and western Asia, naturalized in northern Europe, North America,
and other countries. It grows up to 4 m high; the drooping chains of yellow flowers
brighten many woods and hedges. Leaves are borne in clusters of 2–5 together,
edged with spiky teeth; flowers are yellow, 4–6 mm across, produced on 3–6 cm
long panicles in late spring; fruit is an oblong red berry about 1.25 cm long,
ripening in late summer or autumn, edible but very sour (Figs. 1, 2 and 3).XXVI

Fig. 1 Berberis vulgaris, Shrub with Red Berries, Arnstein Rønning, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Berberis_
vulgaris_.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Berberis vulgaris L. 431

Fig. 2 Berberis vulgaris, Leaves with Flowers, Sten Porse, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Berberis-vulgaris-flowers.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Berberis vulgaris, Full Bloom, J.F. Gaffard, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Berberis_vulgaris3.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
432 Berberis vulgaris L.

Actions and Uses: B. vulgaris was reportedly used by the native Americans in
cases of general debility, and to improve appetite. When early settlers observed this,
they employed root as bitter tonic, and also used it in the treatment for ulcers,
heartburn and stomach problems in small doses; when given in large doses it has
cathartic effect.LXVIII In Unani medicine, it (temperament, cold 2° and dry 3°) is
regarded analgesic, moderating yellow bile, reducing heat of stomach and liver, and
strengthening stomach and intestines, and is beneficial in the treatment of bilious
diseases, such as bilious fever, bilious vomiting, bilious diarrhea, and cirrhosis of
liver.LXXVII Ibn al-BaitarLXIX described it as stomach and liver tonic, beneficial for
hot inflammations, and with reference to Rhazes mentioned it as an antidiarrheal,
quenches thirst, purges bile, and benefits liver and stomach inflammations. In small
doses, it is a tonic, and in large doses, a purgative, and largely used to relieve heat,
thirst and nausea; especially useful in scarlet fever and brain affection.CV In China,
the drug, known as Sankezhen or Cinhuanglian, is the root of Berberis soulieana,
B. wilsonae, B. poirettii or B. vernae. However, B. vulgaris root is also used as
Sankezhen in some places.XVIII In Bulgarian folk medicine, root extracts have been
used in rheumatic and other chronic inflammatory disorders [9, 21], and in Russia to
treat chronic cholecystitis [24]. In Iranian traditional medicine the fruits (barberry)
are credited with antiarrhythmic and sedative properties [11]. An ethnomedical
survey of traditional healers of Shiraz (Iran) showed the fruit decoction was being
used by more than half to treat hypertension [6]. In Moroccan traditional medicine, it
is used to treat liver disorders [22].
Phytoconstituents: Chemical composition of various Berberis species is very sim-
ilar. Twenty-two alkaloids of medicinal importance have been reported from root,
stem, leaves and fruit of B. vulgaris [4]. Major constituents are berberine, palmatine,
berbamine and jatrorrhizine; other constituents include columbamine, oxyacanthine,
bervulcine, coptisine isotetrandrine and magnoflorine, in addition to organic acids
such as chelidonic acid, citric acid, malic acid, resin, and mucilaginous substances
[40]. B. vulgaris also contains berberrubine. However, most of the pharmacological
activities are due to berberine, the chief alkaloid of Berberis plants [19].XVIII Berberine
is found in roots, rhizomes, and stem bark of the plant [3]. It also contains carbohy-
drates, organic acids, some vitamins, pectin, polyphenolic compounds, tannin, and
mineral elements [32]. A new isoquinoline-isoquinolone alkaloid, isolated from root
bark, has been named berbanine [17].
Pharmacology: Aqueous fruit extract significantly reduces mean arterial BP and
HR in anesthetized normotensive and desoxycorticosterone acetate-induced hyper-
tensive rats; and antagonizes phenylephrine effects on isolated rat aortic rings [11].
Antihypertensive and vasodilatory effects are suggested to be mainly endothelium-
independent [12]. Saponins and aqueous fruit extract produced significant hypo-
glycemic activity in normal rats, and in STZ-diabetic rats, with significant decreases
in TC and TGs levels [30]. Two-weeks oral treatment of diabetic rats with
hydroalcohol fruit extract significantly reduced FBG to normoglycemic level, along
with significant decrease in TGs and VLDL, and increase in adiponectin [15].
Coadministration of defatted ethanol root extract significantly reduced high-fat
Berberis vulgaris L. 433

diet-induced insulin resistance, hyperglycemia, elevated insulin levels, and

retinol-binding protein 4 expression [10]. Oral seed powder exhibited gastropro-
tective effects against aspirin-induced ulcers in mice, significantly reducing tissue
proliferation, infiltration of cells and sloughing [28]. Aqueous fruit extract signifi-
cantly protected mice against lead-induced oxidative stress and liver toxicity [22],
and ethanol (70%) fruit extract to diabetic rats for 8-weeks lowered blood glucose
and protected liver from deleterious effects of diabetes [33]. Aqueous fruit extract
also exhibited antihistaminic and anticholinergic activity on isolated guinea pig
ileum [36], and reduced acquisition and reinstatement of morphine-induced condi-
tioned place preference [20]. Berberine was protective against MES and kainic
acid-induced convulsions and reduced mortality [8]. B. vulgaris has shown bene-
ficial effects in reducing blood pressure, enhancing cardiac contractility, and pro-
tection from reperfusion injury in pharmacological studies [2].
Both aqueous and ethanol fruit extracts demonstrated antioxidant activity and
inhibited proliferation of breast cancer cells (MCF-7), but not the normal human
breast epithelial cells (MCF10-A); the ethanol extract being richer in antioxidant and
anthocyanins [14, 16]. Ethanol fruit extract exhibited potent antioxidative capacity,
and its inhibitory effect on a-glucosidase was more potent than berberine chloride,
while both had the same AChE inhibitory effect. Both berberine and ethanol extract
also inhibited growth of breast, liver, and colon cancer cell lines [1]. Hydroalcohol
root extract significantly decreased levels of ALT and ALP enzymes in high-fat
diet-fed rats, with no significant change in AST level [38]. Aqueous-methanol root
bark extract inhibited calcium oxalate crystal deposition in renal tubules, and pro-
tected against polyuria, weight loss, impaired renal function and development of
oxidative stress in kidneys [7]. Ethanol extracts of roots, twigs and leaves, all possess
some degree of radical-scavenging and antioxidant activities, that are correlated well
with the phenols and flavonols contents [34, 41]. Cannabisin G and (+/−)-lyonir-
esinol, two of the phenolic compounds from root bark exhibit antioxidant activity in
hydroxyl radical-scavenging bioassay. Cannabisin G also showed cytoprotective
activity in cultured MCF-7 cells modulated by hydrogen peroxide [39]. Comparative
study of anti-inflammatory activity of ethanol root extract, alkaloidal fractions, and
berberine, showed ethanol extract to be the most effective in both acute and chronic
inflammatory models of adjuvant arthritis [21]. Fruit extract was also effective
in acetic acid-induced colitis in rats, which was attributed to its anthocyanin
contents [31].
Several alkaloids exhibit antibacterial properties against S. pneumoniae, S.
hemolyticus, S. aureus, Sh. dysenteriae, P. vulgaris, P. aeruginosa and E. coli; ber-
berine is also effective against both amoeba and trypnosomes. Berbamine has
demonstrated anticonvulsant, sedative and uterine stimulant properties, and
hypotensive effect,LXXXVII and ameliorated CP-induced leucopenia and thrombocy-
topenia [23]. Ethanol root bark extract produced 90% recovery of BALB/c mice
infected with cutaneous leishmaniasis [35]. Various extracts of fruits, and berberine
showed antidermatophytic activity against T. mentagrophytes, T. rubrum, M. canis,
and M. gypseum [25]. Ethanol fruit extract significantly reduced viability of
434 Berberis vulgaris L.

promastigotes of L. tropica [26], while berberine significantly inhibited growth rate of

promastigote stage of L. tropica and L. infantum [27].
Clinical Studies: In a double-blind, RCT, thirty-one Iranian type 2 diabetic patients,
randomly assigned to 3 g/d fruit extract for 3-months had significant decreases in
serum TC, LDL-C, TGs, apo B, glucose, and insulin levels, and significant increase
in total antioxidant capacity compared to placebo group; but no significant effect on
homocysteine, HbA1c and HDL-C [37]. In a randomized, placebo-controlled study
of eighty Iranian patients with nonalcoholic fatty liver disease (NAFLD), aqueous
fruit extract (750 mg bid) for 90-days significantly reduced weight, serum levels of
TC, TGs, and ALT and AST, with no effect on FBG, LDL-C or HDL-C [18]. In a
randomized, comparative trial, a vaginal gel formulated with ethanol fruit extract
was superior to metronidazole gel in Iranian married women suffering from bac-
terial vaginosis [29]. In a triple-blind RCT of 85 Iranian women with benign breast
disease, daily use of B. vulgaris fruit juice for 8-weeks statistically insignificantly
reduced serum insulin by 19%, C-peptide by 8%, HOMA-IR by 16% and glucose
to insulin ratio by 22% [5]. Iranian adolescents with moderate to severe acne
vulgaris were randomly given oral gelatin capsules containing either aqueous
extract of dried barberry (600 mg) or placebo daily for 4-weeks. Mean number of
noninflamed, inflamed, and total lesions, as well as mean Michaelson’s acne
severity score all declined significantly among the extract treated patients [13].
Human A/Es, Allergy and Toxicity: Diarrhea in three patients and mild consti-
pation in one patient were reported from one of the clinical studies on NAFLD [18].
Not suitable for individuals with phlegmatic constitution.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Like B. aristata, this plant also exhibited beneficial antidiabetic and
antidyslipidemic effects in diabetic patients that requires further validation in more
RCTs.

References
1. Abd El-Wahab AE, Ghareeb DA, Sarhan EE, et al. In vitro biological
assessment of Berberis vulgaris and its active constituent, berberine: anti-
oxidants, antiacetylcholinesterase, antidiabetic and anticancer effects. BMC
Complement Altern Med. 2013;13:218.
2. Abushouk AI, Salem AMA, Abdel-Daim MM. Berberis vulgaris for cardio-
vascular disorders: a scoping literature review. Iran J Basic Med Sci. 2017;
20:503–10.
3. Anonymous. Berberine. Altern Med Rev. 2000;5:175–7.
4. Arayne MS, Sultana N, Bahadur SS. The berberis story: Berberis vulgaris in
therapeutics. Pak J Pharm Sci. 2007;20:83–92 (Review).
5. Asemani S, Montazeri V, Baradaran B, Tabatabiefar MA, Pirouzpanah S.
The effects of Berberis vulgaris juice on insulin indices in women with
Berberis vulgaris L. 435

benign breast disease: a randomized controlled clinical trial. Iran J Pharm

Res. 2018;17(Suppl):110–21.
6. Baharvand-Ahmadi B, Bahmani M, Tajeddini P, Rafieian-Kopaei M,
Naghdi N. An ethnobotanical study of medicinal plants administered for the
treatment of hypertension. J Renal Inj Prev. 2016;5:123–8.
7. Bashir S, Gilani AH, Siddiqui AA, et al. Berberis vulgaris root bark extract
prevents hyperoxaluria induced urolithiasis in rats. Phytother Res. 2010;24:
1250–5.
8. Bhutada P, Mundhada Y, Bansod K, et al. Anticonvulsant activity of berberine,
an isoquinoline alkaloid in mice. Epilepsy Behav. 2010;18:207–10.
9. Boikinova IN. Treatment of true rheumatism with ‘common berberry’
(Berberis vulgaris). Suvr Med (Sofia). 1960;11:111–5.
10. El-Sayed MM, Ghareeb DA, Talat HA, Sarhan EM. High fat diet induced
insulin resistance and elevated retinol binding protein 4 in female rats;
treatment and protection with Berberis vulgaris extract and vitamin A. Pak J
Pharm Sci. 2013;26:1189–95.
11. Fatehi M, Saleh TM, Fatehi-Hassanabad Z, et al. A pharmacological study
on Berberis vulgaris fruit extract. J Ethnopharmacol. 2005;102:46–52.
12. Fatehi-Hassanabad Z, Jafarzadeh M, Tarhini A, Fatehi M. The antihyper-
tensive and vasodilator effects of aqueous extract from Berberis vulgaris
fruit on hypertensive rats. Phytother Res. 2005;19:222–5.
13. Fouladi RF. Aqueous extract of dried fruit of Berberis vulgaris L. in acne
vulgaris, a clinical trial. J Diet Suppl. 2012;9:253–61.
14. Ghafourian E, Sadeghifard N, Pakzad I, et al. Ethanolic extract of Berberis
vulgaris fruits inhibits the proliferation of MCF-7 breast cancer cell line
through induction of apoptosis. Infect Disord Drug Targets. 2017;17:192–8.
15. Hemmati M, Asghari S, Zohoori E, Karamian M. Hypoglycemic effects of
three Iranian edible plants; jujube, barberry and saffron: correlation with
serum adiponectin level. Pak J Pharm Sci. 2015;28:2095–9.
16. Hoshyar R, Mahboob Z, Zarban A. The antioxidant and chemical properties
of Berberis vulgaris and its cytotoxic effect on human breast carcinoma
cells. Cytotechnology. 2016;68:1207–13.
17. Host’álková A, Novák Z, Pour M, et al. Berbanine: a new isoquinoline-
isoquinolone alkaloid from Berberis vulgaris (Berberidaceae). Nat Prod
Commun. 2013;8:441–2.
18. Iloon Kashkooli R, Najafi SS, Sharif F, et al. The effect of Berberis vul-
garis extract on transaminase activities in nonalcoholic fatty liver disease.
Hepat Mon. 2015;15:e25067.
19. Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of
Berberis vulgaris and its active constituent, berberine. Phytother Res. 2008;
22:999–1012 (Review).
20. Imenshahidi M, Qaredashi R, Hashemzaei M, Hosseinzadeh H. Inhibitory
effect of Berberis vulgaris aqueous extract on acquisition and reinstatement
effects of morphine in conditioned place preferences (CPP) in mice.
Jundishapur J Nat Pharm Prod. 2014;9:e16145.
436 Berberis vulgaris L.

21. Ivanovska N, Philipov S. Study on the anti-inflammatory action of Berberis

vulgaris root extract, alkaloid fractions and pure alkaloids. Int J Immunophar-
macol. 1996;18:553–61.
22. Laamech J, El-Hilaly J, Fetoui H, et al. Berberis vulgaris L. effects on oxida-
tive stress and liver injury in lead-intoxicated mice. J Complement Integr
Med. 2017;14.
23. Liu CX, et al. Chinese Tradit Herb Drugs Commun. 1979;9:36.
24. Lomakina VA. Treatment of chronic cholecystitis with a tincture of Berberis
vulgaris leaves. Soviet Med. 1961;25:139–44 (Russian).
25. Mahmoudvand H, Ayatollahi Mousavi SA, Sepahvand A, et al. Antifungal,
antileishmanial, and cytotoxicity activities of various extracts of Berberis
vulgaris (Berberidaceae) and its active principle berberine. ISRN Pharma-
col. 2014;2014:602436.
26. Mahmoudvand H, Sharififar F, Rahmat MS, et al. Evaluation of antileishma-
nial activity and cytotoxicity of the extracts of Berberis vulgaris and Nigella
sativa against Leishmania tropica. J Vector Borne Dis. 2014;51:294–9.
27. Mahmoudvand H, Sharififar F, Sharifi I, et al. In vitro inhibitory effect of
Berberis vulgaris (Berberidaceae) and its main component, berberine
against different Leishmania species. Iran J Parasitol. 2014;9:28–36.
28. Majeed W, Aslam B, Javed I, et al. Histopathological evaluation of
gastroprotective effect of Berberis vulgaris (Zereshk) seeds against aspirin
induced ulcer in albino mice. Pak J Pharm Sci. 2015;28:1953–8.
29. Masoudi M, Miraj S, Rafieian-Kopaei M. Comparison of the effects of
Myrtus communis L, Berberis vulgaris and metronidazole vaginal gel alone
for the treatment of bacterial vaginosis. J Clin Diagn Res. 2016;10:QC04–7.
30. Meliani N, Dib Mel A, Allali H, Tabti B. Hypoglycaemic effect of Berberis
vulgaris L. in normal and streptozotocin-induced diabetic rats. Asian Pac J
Trop Biomed. 2011;1:468–71.
31. Minaiyan M, Ghannadi A, Mahzouni P, Jaffari-Shirazi E. Comparative
study of Berberis vulgaris fruit extract and berberine chloride effects on
acetic acid-induced colitis in rats. Iran J Pharm Res. 2011;10:97–104.
32. Pozniakovskiĭ VM, Golub OV, Popova DG, Kovalevskaia IN. The use of
barberry berries in human nutrition. Vopr Pitan. 2003;72:46–9 (Russian).
33. Rahimi-Madiseh M, Karimian P, Kafeshani M, Rafieian-Kopaei M. The
effects of ethanol extract of Berberis vulgaris fruit on histopathological
changes and biochemical markers of the liver damage in diabetic rats. Iran J
Basic Med Sci. 2017;20:552–6.
34. Rodov V, Vinokur Y, Gogia N, Chkhikvishvili I. Hydrophilic and lipophilic
antioxidant capacities of Georgian spices for meat and their possible health
implications. Georgian Med News. 2010;179:61–6.
35. Salehabadi A, Karamian M, Farzad MH, Namaei MH. Effect of root bark
extract of Berberis vulgaris L. on Leishmania major on BALB/c mice.
Parasitol Res. 2014;113:953–7.
Berberis vulgaris L. 437

36. Shamsa F, Ahmadiani A, Khosrokhavar R. Antihistaminic and anticholin-

ergic activity of barberry fruit (Berberis vulgaris) in the guinea-pig ileum.
J Ethnopharmacol. 1999;4:161–6.
37. Shidfar F, Ebrahimi SS, Hosseini S, et al. The effects of Berberis
vulgaris fruit extract on serum lipoproteins, apoB, apoA-I, homocysteine,
glycemic control and total antioxidant capacity in Type 2 diabetic patients.
Iran J Pharm Res. 2012;11:643–52.
38. Taheri S, Zarei A, Changizi Ashtiyani S, Rezaei A, Zaheiri S. Evaluation of
the effects of hydroalcoholic extract of Berberis vulgaris root on the activity
of liver enzymes in male hypercholesterolemic rats. Avicenna J Phytomed.
2012;2:153–61.
39. Tomosaka H, Chin YW, Salim AA, et al. Antioxidant and cytoprotective
compounds from Berberis vulgaris (barberry). Phytother Res. 2008;22:979–81.
40. Zarei A, Changizi-Ashtiyani S, Taheri S, Ramezani M. A quick overview on
some aspects of endocrinological and therapeutic effects of Berberis vul-
garis L. Avicenna J Phytomed. 2015;5:485–97.
41. Zovko Koncić M, Kremer D, Karlović K, Kosalec I. Evaluation of anti-
oxidant activities and phenolic content of Berberis vulgaris L. and Berberis
croatica Horvat. Food Chem Toxicol. 2010;48:2176–80.
Bombyx mori L.
(Bombycidae)

Abstract
Silkworm is the larva or caterpillar of domesticated silk moth, Bombyx mori,
that thrives on white mulberry leaves. It is described in Unani medicine as the
top-notch refrigerant, beneficial for heart, memory, and liver; and used in the
treatment of cough, asthma, cold and flu, especially when phlegm is thick and
sticky. In Chinese medicine, dried larva of silkworm is known as Jiangcan and is
regarded anticonvulsant, mucolytic, sedative, analgesic, expectorant and dis-
cutient, and useful in laryngitis, tuberculosis, lymph node tuberculosis, infantile
convulsions, night crying, various sores and scars, wind rash and erysipelas. White
powder of dried larva contains ammonium oxalate, proteins and fat. Bombyx mori
silk fibroin has been suggested for use as scaffold for bone regeneration, and in
bioengineering as a small-diameter vascular graft. Ethanol-water extract, either
injected s.c., i.p, or administered orally to albino mice, or injected intravenously to
rabbits, produced hypnotic effect; in mice, the extract produced hypnotic effect
similar to phenobarbital. Administration of the decoction decreased strychnine-
induced convulsion mortality of mice, that was lost if ammonium oxalate was
removed from the decoction; ammonium oxalate was therefore believed to be
mainly responsible for antagonizing strychnine-induced convulsions. Treatment
with Jiangcan of 27 Chinese diabetic patients of type-2 DM of up to 30 years
duration, resulted in remission of symptoms in 24 cases, 9 cases became negative
for glucosuria, and 1 case had glucosuria improved; more satisfactory results were
achieved in mild to moderately severe cases.

Keywords




Aabresham Bicho-da-seda Bombyx du mûrier Echter seidenspinner






Gusano de seda Jiangcan Kaiko Silkesfjäril Silkworm Zijdervlinder

© Springer Nature Switzerland AG 2020 439

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_45
440 Bombyx mori L.

Vernaculars: Urd.: Aabresham; Hin.: Resham ka keeda; Ben.: Bōmbēksa mōri;

Mal.: Bēāmbeks mēāri; Mar.: Reshmacha keeda; Tam.: Kuṇṭu vīccu; Tel.:
Paṭṭupurugu; Ara.: Dudatal qar tutia; Chi.: 蚕, Baijiangcan, Chiang-tsan, Jiangcan;
Dut.: Zijdervlinder; Eng.: Common silk moth, Mulberry silk worm, Silkworm;
Fre.: Bombyx du mûrier, Ver à soie; Ger.: Echter seidenspinner, Zahmer seiden-
spinner; Ita.: Baco da seta, Bombyx mori; Jap.: Kaiko; Per.: Karm abresham; Por.:
Bicho-da-seda; Spa.: Gusano de seda, Mariposa de seda; Swe.: Silkesfjäril; Vie.:
Con nhộng.
Description: Silkworm is the larva or caterpillar of domesticated silk moth, Bombyx
mori, the primary producer of silk. It thrives on white mulberry leaves as its preferred
food. The cocoon cleared of larvae is used medicinally. It is made up of a thread of
raw silk, from 300 to about 900 m long (Figs. 1 and 2).
Actions and Uses: Ibn al-BaitarLXIX described it as the top-notch refrigerant,
especially beneficial for heart, memory, and liver, and Avicenna mentioned it in his
Canon of Medicine, and regarded it cardiotonic.CXXXXVII In Unani medicine, it
(temperament is hot 1° and dry 1°) is regarded refrigerant, detergent, liquefying
phlegm (mucolytic), tonic for heart and lungs, and used in the treatment of cough,
asthma, cold and flu, especially when phlegm is thick and sticky.LXXVII Silkworm
excreta acts as a sedative, analgesic in arthritis, paralysis and headache. Silkworm
cocoon acts as antiemetic, anthelmintic, and antidiabetic, and stiffened silkworm is
used for infantile convulsions, night cries, tonsillitis, tracheitis, apoplexy, as a nerve
stimulant, in deafness and impotence.LXXIX It is known as Jiangcan in Chinese, and
is referred to the dried larva of silkworm Bombyx mori. It tastes pungent, salty, with
‘mild’ property, and is regarded anticonvulsant, mucolytic, and discutient, and is
useful in laryngitis, tuberculosis, lymph node tuberculosis, infantile convulsions,
night crying, various sores and scars, wind rash and erysipelasXVIII also described
as sedative, analgesic and expectorant.LXVI

Fig. 1 Bombyx mori, Silkworm larvae, Fastily, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Silkworms3000px.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Bombyx mori L. 441

Fig. 2 Bombyx mori, Cocoon, Krish Dulal, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cocoon.jpg; https://creativecommons.org/
licenses/by-sa/3.0/deed.en

Phytoconstituents: White powder of dried larva contains ammonium oxalate,

proteins and fat. Cultured B. bassiana can produce pyridine-2,6-dicarboxylic acid
and large quantities of oxalic acid and fat.XVIII
Pharmacology: Bombyx mori silk fibroin has been suggested for use as scaffold for
bone regeneration [6], and in bioengineering as a small-diameter vascular graft [10].
Silkworm feces prepared with hot phosphate-buffered saline and purified with
ammonium sulfate precipitation, inhibited Sendai virus, HSV-1, and HIV-1, but not
poliovirus [2]. Ethanol-water extract, either injected s.c., i.p, or administered orally to
albino mice, or injected intravenously to rabbits, produced hypnotic effect; in mice, the
extract produced hypnotic effect similar to that of phenobarbital 50 mg/kg s.c [7].
Intragastric administration of the decoction decreased strychnine-induced convulsion
mortality of mice; however, no significant antagonism to MES-, PTZ- and caffeine-
induced convulsions was observed [8]. Protective effect against strychnine-induced
convulsions was lost if ammonium oxalate was removed from the decoction.
Ammonium oxalate was therefore believed to be mainly responsible for antagonizing
strychnine-induced convulsions [8]. Weak antibacterial activity was reported against
S. aureus, E. coli and P. aeruginosa [4]. Daily intragastric administration of 20 and
50% decoction (0.2 ml/mouse per day), starting 24-h after inoculation of Sarcoma
180, inhibited tumor growth, but caused weight loss [4].
Clinical Studies: In a study involving 27 cases of type-2 DM of up to 30 years
duration, treatment with Jiangcan resulted in remission of symptoms in 24 cases, 9
cases became negative for glucosuria, and 1 case had glucosuria improved. More
satisfactory results were achieved in mild to moderately severe cases [14]. The drug
was also tried in 25 cases of arteriosclerotic heart disease, hypertension, and fatty
442 Bombyx mori L.

liver with elevated serum cholesterol levels; 14 of them had reduction in cholesterol
level after 20–30 days of medication; and a- and b-lipoproteins were also decreased
[4]. Jiangcan is often used in combination with drugs having ‘heat-clearing and
detoxicant’ actions, such as fruit of Forsythia suspensa, the root of Isatis tinctoria,
and the root of Scutellaria baicalensis to treat furuncles and carbuncles [16].
Human A/Es, Allergy and Toxicity: A number of children [15] and workers in
silk industry [12], and others [1, 5, 11, 13], develop silk-allergy induced asthma. In
Unani medicine, it is considered harmful for kidneys.LXXVII
Animal Toxicity: Ethanol extract (0.5–5 g/kg, i.p.) to mice and rats was nontoxic
[9]. Oral dose of 35,000 mg/kg of the decoction to mice, produced decreased motor
activity, ataxia and cyanosis in some animals. Oral administration of decoction
(2,000 mg/kg daily) to mice for 22-days caused no abnormalities of the liver,
kidneys and spleen [7]; oral LD50 of the decoction in mice was 44,500 mg/kg [3].
Commentary: Its antidiabetic and antidyslipidemic effects need further corrobo-
rative clinical studies in larger and diverse patient populations.

References
1. Araujo LM, Rosário Filho NA, Riedi CA. Respiratory allergy to moth: the
importance of sensitization to Bombyx mori in children with asthma and
rhinitis. J Pediatr (Rio J). 2014;90:176–81.
2. Hiraki A, Ikuno Y, Kim J, Ueda S. Suppression of enveloped virus produc-
tion with a substance from silkworm faeces. Cell Struct Funct. 1996;21:
501–14.
3. Institute of Materia Medica, Preliminary Studies of the pharmacological
actions and active components of Jiangcan and Jiangyong (Bombyx mori).
Chinese Academy of Medical Sciences. October 1974. Cited by Chang and
ButXVIII.
4. Institute of Zoology, Chinese Academy of Sciences et al. Chinese Tradi-
tional and Herbal Drugs Communications (6):5, 1972. Cited by Chang and
ButXVIII.
5. Komase Y, Sakata M, Azuma T, et al. IgE antibodies against midge and
moth found in Japanese asthmatic subjects and comparison of allergenicity
between these insects. Allergy. 1997;52:75–81.
6. Miyamoto S, Koyanagi R, Nakazawa Y, et al. Bombyx mori silk fibroin
scaffolds for bone regeneration studied by bone differentiation experiment.
J Biosci Bioeng. 2013;115:575–8.
7. Neurology and Psychiatry Section, Dalian Medical College. Acta Acade-
miae Medicinae Dalian 2(2):26, 1961. Cited by Chang and ButXVIII.
8. Neurology Section of the Pharmacology and Phytochemistry Departments,
Institute of Materia Medica of the Chinese Academy of Medical Sciences.
Chinese Traditional Herbal Drugs Communications (12):24, 1978. Cited by
Chang and ButXVIII.
Bombyx mori L. 443

9. Siddiqui HH. Indian J Pharm. 1962;24:183.

10. Soffer L, Wang X, Zhang X, et al. Silk-based electrospun tubular scaffolds
for tissue-engineered vascular grafts. J Biomater Sci Polym Ed. 2008;19:
653–64.
11. Suzuki M, Itoh H, Sugiyama K, et al. Causative allergens of allergic rhinitis
in Japan with special reference to silkworm moth allergen. Allergy. 1995;
50:23–7.
12. Uragoda CG, Wijekoon PN. Asthma in silk workers. J Soc Occup Med.
1991;41:140–2.
13. Vovolis V, Galatas I. Silk-induced asthma. Allergy Asthma Proc. 1999;20:
107–8.
14. Ward of Combined Western and Traditional Chinese Medicine, Internal
Medicine Department of Wuxi First People’s Hospital. Wuxi Med J—Special
Issue on Combined Western and Traditional Chinese Medicine (12):29, 1976.
Cited by Chang and ButXVIII.
15. Wen CM, Ye ST, Zhou LX, Yu Y. Silk-induced asthma in children: a report
of 64 cases. Ann Allergy. 1990;65:375–8.
16. Zhongshan Medical College: Clinical Applications of Chinese Traditional
Drugs, 1975, p. 477. Cited by Chang and ButXVIII.
Borago officinalis L.
(Boraginaceae)

(Syn.: B. hortensis L.)

Abstract
An annual herbaceous and hairy herb, native to the Mediterranean region, but
naturalized in other parts of the world, North Africa and Asia Minor; cultivated as
an ornamental and medicinal plant, and very widely introduced in most of Europe.
In Iranian traditional medicine, the flowers are known to possess sedative property,
the leaves are used for their anticonvulsant, bronchodilator, vasodilator, and
cardiodepressant properties, and borage seed oil is used for treatment of diseases
such as, multiple sclerosis, diabetes, heart diseases, arthritis and eczema. In many
parts of Italy, wild plants are consumed as vegetables, and borage is one of the most
commonly used plants in both southern and northern Italy, and also used in local
traditional medicine to treat inflammatory diseases. In Mexico, it is also regarded to
have nutritional value, and is used to treat gastrointestinal diseases, and respiratory
diseases. It is used in Danish folk medicine to treat depression and anxiety, and
borage oil is promoted in the United States as a treatment for rheumatoid arthritis,
atopic dermatitis, diabetic neuropathy, and menopause-related symptoms. Leaves
contain small amount of pyrrolizidine alkaloids, rosmarinic acid, officinalioside,
actinidioionoside, roseoside, crotalionoside C and kaempferol 3-O-b-D-galacto-
pyranoside, essential oil, fatty acids, and a significant amount of manganese. Mice
fed with borage diet ad lib for 12-months showed reversal of age-related
inflammatory and senile osteoporosis. Ethanol extract of aerial parts possesses
MAO-A inhibitory activity, showed affinity to serotonin transporter, and potential
as a serotonin reuptake inhibitor. Daily administration of hydroethanol extract to
patients with moderate asthma, significantly ameliorated cough, dyspnea,
wheezing, nocturnal symptoms, and airway hyperresponsiveness, and signifi-
cantly reduced exacerbation attacks per month.

Keywords



Boriji Borragine Borraja Gaozaban

Gurkenkraut
Hamham
Hodan




Lisan al-thaur Purasruoho Starflower

© Springer Nature Switzerland AG 2020 445

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_46
446 Borago officinalis L.

Vernaculars: Urd.: Gaozaban; Tam.: Akumpai; Ara.: Hamham, Himhim, Lisan

al-thaur; Bul.: Poreč; Chi.: 琉璃苣; Cze.: Bořeč, Brotnák, Brutnák lékařský; Dan.:
Hjulkrone; Dut.: Bernagie, Borage, Komkommerkruid; Eng.: Beebread, Bee plant,
Borage, Cool tankard, Cow’s tongue plant, Starflower, Talewort; Fin.: Kurkkuyrtti,
Purasruoho, Rohtopurasruoho; Fre.: Bourrache commune, Bourrache officinale;
Ger.: Einjähriger borretsch, Gemeiner borretsch, Gurkenkraut; Ita.: Borragine,
Borandella, Borrana commune; Jap.: Boriji, Ruridisa; Kor.: Bo-ri-ji, Poriji; Nor.:
Agurkurt; Per.: Gol gao zaban; Pol.: Ogórecznik lekarski; Por.: Borragem; Rus.:
Ogurečnik aptečnyj; Spa.: Alcohelo, Borraina, Borraja; Swe.: Gurkört, Stof-
ferblomma, Vanlig gurkört; Tur.: Hodan, Ispıt, Sığırdili, Zembil çiçeği.
Description: It is an annual herbaceous and hairy herb which is native to the
Mediterranean region, but naturalized in other parts of the world, North Africa and
Asia Minor; cultivated as an ornamental and medicinal plant, and very widely
introduced in most of Europe, commercially cultivated for its seed oil, and for
medicinal and culinary uses [3]. It can reach the height of up to 1 m; stems are
hollow, straight, often branched; leaves are alternate, simple, with white spots,
resembling cow’s tongue, and 5–15 cm long; flowers have five narrow,
triangular-pointed petals, most often blue, although pink flowers are sometimes
observed; white flowered types are also cultivated (Figs. 1 and 2).LXXXVII
Actions and Uses: In Iranian traditional medicine, the flowers are known to
possess sedative property [26], and the leaves are used for their anticonvulsant,
bronchodilator, vasodilator, and cardiodepressant properties [3], and borage seed oil
is used for treatment of diseases such as multiple sclerosis, diabetes, heart diseases,
arthritis and eczema [3]. An ethnomedical survey of Shiraz region of Iran revealed
that it was the first choice of more than half of the traditional healers to treat
hypertension [6]. In Mexico, it is regarded to have nutritional value, and is used to

Fig. 1 Borago officinalis, White Flowers Cultiver, Victor M. Vicente Selvas, WikimediaCom-
mons, https://commons.wikimedia.org/wiki/File:Borago_officinalis_white_flower.jpg
Borago officinalis L. 447

Fig. 2 Borago officinalis, Younger (Pink) and Older (Violet) Flowers, Hans Bernhard (Schnobby),
WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/
wiki/File:Borago_officinalis,_two_blossoms.jpg; https://creativecommons.org/licenses/by-sa/3.0/
deed.en

treat gastrointestinal diseases [15], and respiratory diseases [2]. In many parts of
Italy, wild plants are consumed as vegetables, and borage is one of the most
commonly used plants in both southern and northern Italy, though southern Italians
prefer more wild vegetables with strong and bitter taste [9], and also used in local
traditional medicine to treat inflammatory diseases [7]. It was also reported as one
of the most important medicinal plants traditionally used by the people of Madeira
and Porto Santo Islands of Spain [24], and used in Danish folk medicine to treat
depression and anxiety [11]. Borage oil is promoted in the United States as a
treatment for rheumatoid arthritis, atopic dermatitis, diabetic neuropathy, and
menopause-related symptoms [1]. The leaves and flowers of both Caccinia
macrenthera var. glauca and B. officinalis are sold in Indian bazaars as Gaozaban
and are used in Unani medicine (temperament, hot 1° and moist 1° when fresh; and
hot and dry when dried). The plant is refrigerant and cardiotonic, and mainly used
in the treatment of melancholia, insanity, palpitation due to black bile, cough,
asthma, and pulmonary irritation.LXXVII
Phytoconstituents: Leaves contain small amount of pyrrolizidine alkaloids, potas-
sium, calcium [3], rosmarinic acid [4], officinalioside, actinidioionoside, roseoside,
crotalionoside C and kaempferol 3-O-b-D-galactopyranoside [25], essential oil,
fatty acids [19], and a significant amount of manganese [23]. Seed oil yield from
Iran is reported to be 31.46–33.7% [21], with linoleic acid (35–38%), palmitic (10–
11%), oleic acid (16–20%), stearic acid (3.5–4.5%), eicosenoic acid (3.5–5.5%),
erucic acid (1.5–3.5%) and c-linolenic acids (26–38%), as the major fatty acids.
Gamma-linolenic acid is used as dietary or food supplement [3]. Seeds also contain
pyrrolizidine alkaloids [16], but they are not co-extracted with seed oil, or in a
448 Borago officinalis L.

detectable amount [27]. Thesinine-4′-O-b-D-glucoside, a glycosylated pyrrolizidine

alkaloid was isolated from the seeds [10].
Pharmacology: Mice fed with ad lib borage diet for 12-months showed reversal of
age-related inflammatory and senile osteoporosis [28]. Hydroalcohol extract exhibits
topical in vivo anti-inflammatory, and in vitro radical scavenging and modest
antioxidant activities [7, 12], and significantly reduces acute and chronic pain per-
ception in rats [26]. Ethanol extract of aerial parts showed affinity to serotonin
transporter, and potential as a serotonin reuptake inhibitor; it also possesses MAO-A
inhibitory activity [11]. Rosmarinic acid has been identified as the dominant
antioxidative compound [5]. Borage oil moderately reversed experimentally-
induced epidermal hyperproliferation in guinea pigs [14]. Borage formulation also
exhibits strong in vitro a-amylase inhibitory activity [18].
Clinical Studies: In a double-blinded RCT, hydroethanol extract administered in a
dose of 5 ml thrice daily for a month to Iranian patients with moderate asthma,
significantly ameliorated cough, dyspnea, wheezing, nocturnal symptoms, and
airway hyperresponsiveness, and significantly reduced exacerbation attacks per
month [20]. An analysis of clinical trials of borage oil in the treatment of atopic
dermatitis revealed mixed results, but nutritional supplementation with borage oil
could be useful in some patients with less severe atopic dermatitis [8].
Mechanism of Action: c-linolenic acid increases PGE level that increases cAMP
level which, in turn, suppresses TNF-a synthesis, a central mediator of inflam-
matory and joint destructive processes in rheumatoid arthritis [13]. Affinity to
serotonin transporter, its potential serotonin reuptake inhibitor and MAO-A inhi-
bitory activities could be the basis for its antidepressant effects [11].
Human A/Es, Allergy and Toxicity: A middle aged healthy female in the U.S.
suffered from status epilepticus after consuming borage oil (1,500–3,000 mg/day)
for one week [1]. In Italy, where the plant is traditionally consumed in diet, indi-
viduals suffered with digitalis toxicity [17], and Mandragora autumnalis poisoning
[22], due to contamination of borage leaves with Digitalis purpurea leaves and
mistaking Mandragora autumnalis for borage, respectively. Borage oil should be
contraindicated in pregnancy due to the teratogenic and labor inducing effects of
prostaglandin E agonists [13]. In Unani medicine, it is considered harmful for
spleen.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Potential for Drug-Herb Interactions: Concomitant use of NSAIDs would under-
mine anti-inflammatory effects of borage oil, as it acts by increasing PGE [13].
Commentary: There are no pharmacological and clinical studies on its effects on
heart, and insanity and melancholy, for which the leaves and flowers are chiefly used
in Unani medicine. The antiasthmatic effects in Iranian patients were encouraging but
need further validation in large RCTs.
Borago officinalis L. 449

References
1. Al-Khamees WA, Schwartz MD, Alrashdi S, Algren AD, Morgan BW.
Status epilepticus associated with borage oil ingestion. J Med Toxicol.
2011;7:154–7.
2. Andrade-Cetto A. Ethnobotanical study of the medicinal plants from
Tlanchinol, Hidalgo. México. J Ethnopharmacol. 2009;25:163–71.
3. Asadi-Samani M, Bahmani M, Rafieian-Kopaei M. The chemical compo-
sition, botanical characteristic and biological activities of Borago officinalis:
a review. Asian Pac J Trop Med. 2014;7S1:S22–8.
4. Bandoniene D, Murkovic M, Venskutonis PR. Determination of rosmarinic
acid in sage and borage leaves by high-performance liquid chromatography
with different detection methods. J Chromatogr Sci. 2005;43:372–6.
5. Bandoniene D, Murkovic M. The detection of radical scavenging com-
pounds in crude extract of borage (Borago officinalis L.) by using an on-line
HPLC-DPPH method. J Biochem Biophys Methods. 2002;53:45–9.
6. Baharvand-Ahmadi B, Bahmani M, Tajeddini P, Rafieian-Kopaei M,
Naghdi N. An ethnobotanical study of medicinal plants administered for the
treatment of hypertension. J Renal Inj Prev. 2016;5:123–8.
7. Conforti F, Sosa S, Marrelli M, et al. In vivo anti-inflammatory and in vitro
antioxidant activities of Mediterranean dietary plants. J Ethnopharmacol.
2008;116:144–51.
8. Foster RH, Hardy G, Alany RG. Borage oil in the treatment of atopic
dermatitis. Nutrition. 2010;26:708–18.
9. Ghirardini MP, Carli M, del Vecchio N, et al. The importance of a taste.
A comparative study on wild food plant consumption in twenty-one local
communities in Italy. J Ethnobiol Ethnomed. 2007;3:22.
10. Herrmann M, Joppe H, Schmaus G. Thesinine-4′-O-beta-D-glucoside the first
glycosylated plant pyrrolizidine alkaloid from Borago officinalis. Phyto-
chemistry. 2002;60:399–402.
11. Jäger AK, Gauguin B, Andersen J, Adsersen A, Gudiksen L. Screening of
plants used in Danish folk medicine to treat depression and anxiety for
affinity to the serotonin transporter and inhibition of MAO-A. J Ethnophar-
macol. 2013;145:822–5.
12. Jaradat NA, Damiri B, Abualhasan MN. Antioxidant evaluation for Urtica
urens, Rumex cyprius and Borago officinalis edible wild plants in Palestine.
Pak J Pharm Sci. 2016;29(1 Suppl):325–30.
13. Kast RE. Borage oil reduction of rheumatoid arthritis activity may be
mediated by increased cAMP that suppresses tumor necrosis factor-alpha.
Int Immunopharmacol. 2001;1:2197–9.
14. Kim J, Kim H, Jeong do H, et al. Comparative effect of gromwell (Lithosper-
mum erythrorhizon) extract and borage oil on reversing epidermal hyperpro-
liferation in guinea pigs. Biosci Biotechnol Biochem. 2006;70:2086–95.
450 Borago officinalis L.

15. Leos-Rivas C, Verde-Star MJ, Torres LO, et al. In vitro amoebicidal activity
of borage (Borago officinalis) extract on Entamoeba histolytica. J Med
Food. 2011;14:866–9.
16. Lüthy J, Brauchli J, Zweifel U, Schmid P, Schlatter C. Pyrrolizidine
alkaloids in medicinal plants of Boraginaceal: Borago officinalis L. and
Pulmonaria officinalis L. Pharm Acta Helv. 1984;59:242–6 (German).
17. Maffè S, Cucchi L, Zenone F, et al. Digitalis must be banished from the
table: a rare case of acute accidental digitalis intoxication of a whole family.
J Cardiovasc Med (Hagerstown). 2009;10:727–32.
18. Marrelli M, Loizzo MR, Nicoletti M, Menichini F, Conforti F. In vitro
investigation of the potential health benefits of wild Mediterranean dietary
plants as antiobesity agents with a-amylase and pancreatic lipase inhibitory
activities. J Sci Food Agric. 2014;94:2217–24.
19. Mhamdi B, Aidi Wannes W, Marzouk B. Biochemical evaluation of borage
(Borago officinalis) rosette leaves through their essential oil and fatty acid
composition. Ital J Biochem. 2007;56:176–9.
20. Mirsadraee M, Khashkhashi Moghaddam S, Saeedi P, Ghaffari S. Effect
of Borago officinalis extract on moderate persistent asthma: a phase two
randomized, double blind, placebo-controlled clinical trial. Tanaffos. 2016;
15:168–74.
21. Morteza E, Akbari GA, Moaveni P, et al. Compositions of the seed oil of
the Borago officinalis from Iran. Nat Prod Res. 2015;29:663–6.
22. Piccillo GA, Miele L, Mondati E, et al. Anticholinergic syndrome due to
‘Devil’s herb’: when risks come from the ancient time. Int J Clin Pract.
2006;60:492–4.
23. Renna M, Cocozza C, Gonnella M, Abdelrahman H, Santamaria P. Elemental
characterization of wild edible plants from countryside and urban areas.
Food Chem. 2015;177:29–36.
24. Rivera D, Obón C. The ethnopharmacology of Madeira and Porto Santo
Islands, a review. J Ethnopharmacol. 1995;46:73–93.
25. Samy MN, Hamed AN, Sugimoto S, et al. Officinalioside, a new lignan
glucoside from Borago officinalis L. Nat Prod Res. 2016;30:967–72.
26. Shahraki MR, Ahmadimoghadm M, Shahraki AR. The antinociceptive
effects of hydroalcoholic extract of Borago Officinalis flower in male rats
using formalin test. Basic Clin Neurosci. 2015;6:285–90.
27. Vacillotto G, Favretto D, Seraglia R, et al. A rapid and highly specific method to
evaluate the presence of pyrrolizidine alkaloids in Borago officinalis seed oil.
J Mass Spectrom. 2013;48:1078–82.
28. Wauquier F, Barquissau V, Léotoing L, et al. Borage and fish oils lifelong
supplementation decreases inflammation and improves bone health in a
murine model of senile osteoporosis. Bone. 2012;50:553–61.
Boswellia serrata Roxb. ex Colebr.
(Burseraceae)

(Syns.: B. balsamifera Spreng.; B. glabra Roxb.; B. thurifera Roxb. ex Fleming)

Abstract
A moderate to large sized branching tree that grows in dry mountainous regions of
India, Northern Africa, Somalia, and the Middle East. Oleo gum-resin is tapped
from an incision made on the trunk of the tree, and is then stored in specially made
bamboo basket for removal of oil content and getting the resin solidified. After
processing, the gum-resin is then graded according to its flavor, color, shape and
size. Dioscorides described it as a universal styptic, relieves epistaxis, and heals
chronic weeping wounds, and healthy people become fearless and strong after
eating it; mixed with olive oil it cures eczema. Nadkarni mentioned the gum used in
rheumatic and nervous diseases, scrofulous affections, urinary disorders, and skin
diseases; it acts as stimulant expectorant in pulmonary diseases, such as bronchitis.
Long-term use is also credited to reduce obesity. In traditional Iranian medicine, it
is used as an effective remedy for inflammatory bowel diseases, and in Ayurveda, it
has been called as one of the most promising traditional plant that shows best
efficacy for the treatment of pain and inflammatory conditions. Oleo gum-resins
contain 30–60% resin (consisting of monoterpenes, diterpenes, triterpenes,
tetracyclic triterpenic acids and four major pentacyclic triterpenic acids), 5–10%
essential oil, and polysaccharides. Various animal studies and limited clinical trials
validate the usefulness of the gum resin extract for treatment of a variety of
inflammatory diseases, like inflammatory bowel diseases, rheumatoid arthritis,
osteoarthritis, asthma, cerebral edema, chronic pain syndrome, and cancer.
Treatment of patients with primary or secondary malignant cerebral tumors
undergoing radiotherapy resulted in a reduction of cerebral edema by >75% in 60%
of patients who received resin compared to 26% of placebo-treated patients, with
no significant impact on quality of life or cognitive function.

Keywords
Albero dell’incenso
Boswellie-dentelee
Kondor
Kundur
Loban



Olibanum Rǔ xiāng
Salaibaum
Salai guggal
Śallaki
© Springer Nature Switzerland AG 2020 451
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_47
452 Boswellia serrata Roxb. ex Colebr.

Vernaculars: Urd.: Kundur, Loban; Hin.: Awul, Dupsalai sukha, Ganda biroza,
Kundur, Luban, Salai guggal, Shallaki; San.: Guggula, Kapitthaparni, Konkanad-
hoopam, Kunduru, Kunduruki, Kundurya-salaki-neryasan, Palank, Parvati, Śallaki,
Sruva, Susravã,; Ben.: Guaiggul, Kundro, Luban, Salai, Salai-gund; Mal.: Kun-
durukkam, Kungilyam, Kunthurukkam, Parangi-saambraani, Salamaram, Sam-
brani, Samprani; Mar.: Dhup, Kurunda, Loban, Pandhri esesh, Pandhri salai,
Salphullie; Tam.: Kumancam, Kundrikam, Kunkiliyam, Marattu-vellai, Parangi-
shambirani, Vellai-k-kirai; Tel.: Anduga pisunni, Guggilamu, Kunduruk kam-
pishin, Parangi-sambrani-chettu, Sallaki; Ara.: Kundur, Loban; Chi.: Chǐ yè
rǔxiāng shù, Rǔ Xiāng; Eng.: Frankincense, Indian frankincense, Indian olibanum,
Olibanum; Fin.: Salai-olibaani; Fre.: Arbre à encens de l'Inde, Boswellie-dentelee;
Ger.: Indischer weihrauchbaum, Salaibaum; Ita.: Albero dell'incenso; Per.: Kon-
dor; Rus.: Bosvelliia pil'chataia; Tha.: Sanlaki.
Description: B. serrata is a moderate to large sized branching tree growing in dry
mountainous regions of India, northern Africa, Somalia, and the Middle East. Oleo
gum-resin is tapped from an incision made on the trunk of the tree, and is then
stored in specially made bamboo basket for removal of oil content and getting the
resin solidified. After processing, the gum-resin is then graded according to its
flavor, color, shape and size [70]. Three kinds have been described of this gum
exudate from the tree of B. serrata or B. glabra. One is called male frankincense
(Kundura zakara), which is reddish-white or deep yellow in color outside and white
inside; the other is called female frankincense (Kundura unsa), which is externally
yellowish-white, translucent or in pale tears, and the third kind is Madahraja
kundur, with artificial spherical tears made by shaking the moist exudation in a
basket.LXXVII,LXXXI Sanskrit writers described guggulu as moist, viscid, fragrant,
and of a golden color when freshly exuded.XL Dioscorides mentioned that it is
adulterated with gum acacia and pine gum; gum acacia does not burn like kundur
and pine gum burns easily with kundur, but has no fragrance. Wahid and Siddiqui
mentioned B. serrata as Loban, and B. glabra as Kundur (Figs. 1 and 2).CXXXXVII
Actions and Uses: DioscoridesXL described it as a universal styptic, relieves
epistaxis, and heals chronic weeping wounds, and healthy people become fearless
and strong after eating it, but it can kill if taken in large quantity with wine; mixed
with olive oil it cures eczema. Abu-Jareej said that it acts as a brain tonic, and
improves memory if a person daily uses 4.5 g soaked in water, but the person
develops constant headache; and Razi (Rhazes) recommends it in anxiety.LXIX
Galen described its temperament as hot 3° and dry 1°. Sanskrit writers described it
as demulcent, aperient, alterative, and a purifier of blood;XL others called it a
stimulant, expectorant, demulcent, emmenagogue and discutient, and chiefly used
in the treatment of chronic pulmonary affections, such as bronchitis, bronchorrhea,
chronic laryngitis and pharyngitis.LXXXI NadkarniCV mentioned the gum is used in
rheumatic and nervous diseases, scrofulous affections, urinary disorders, and skin
diseases; it acts as stimulant expectorant in pulmonary diseases, such as bronchitis.
Long-term use is also credited to reduce obesity. The gum is also used as dia-
phoretic, diuretic, astringent, emmenagogue, and in rheumatism.XXI In Unani
Boswellia serrata Roxb. ex Colebr. 453

Fig. 1 Boswellia serrata, Tree Branches, Kinnerasani Wildlife Sanctuary, J.M. Garg, Wikime-
diaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:
Boswellia_serrata_(Salai)_in_Kinnarsani_WS,_AP_W_IMG_5843.jpg; https://creativecommons.
org/licenses/by-sa/3.0/deed.en

Fig. 2 Boswellia serrata, Flowers and Fruits, Kinnerasani Wildlife Sanctuary, J.M. Garg,
WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/
wiki/File:Boswellia_serrata_(Salai)_in_Kinnarsani_WS,_AP_W_IMG_5840.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

medicine, it is considered anti-inflammatory, aphrodisiac, antiseptic, liver tonic,

expectorant, stomachic and antipyretic.LXXVII In traditional Iranian medicine, it is
used as an effective remedy for inflammatory bowel diseases [67]. In Ayurveda, it
has been called as one of the most promising traditional plants that shows best
efficacy for the treatment of pain and inflammatory conditions [22]. Various animal
studies and limited clinical trials validate the usefulness of the gum resin extract for
the treatment of a variety of inflammatory diseases, like inflammatory bowel
454 Boswellia serrata Roxb. ex Colebr.

diseases (Crohn’s disease and ulcerative colitis), rheumatoid arthritis, osteoarthritis,

asthma [1, 6, 19, 23, 89], cerebral edema, chronic pain syndrome, and cancer [32].
The European Medicines Agency in 2002 classified the extract as an ‘orphan drug’
for the treatment of peritumoral brain edema [1, 49]. In a clinical survey of 413
German patients suffering from inflammatory bowel diseases, 52% patients
reporting present or past use of CAM, B. serrata extracts (36%) were one of the
most frequently used CAM methods, and reported more positive therapeutic effects
than others [42].
Phytoconstituents: More than 340 volatiles in Boswellia genus have been
reported in the literature [39]. Oleo gum-resins contain 30–60% resin (consisting of
monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major
pentacyclic triterpenic acids), 5–10% essential oil (soluble in organic solvents), and
polysaccharides [77]. Pentacyclic triterpenes or boswellic acids are the active
compounds of frankincense, and 3-O-acetyl-11-keto-b-boswellic acid (AKBA) is
the most important and the most potent inhibitor of 5-LOX, and inhibitor of leu-
kotrienes biosynthesis [32, 73, 77]. Wang et al. [85] isolated five boswellic acids,
viz: a-boswellic acid, b-boswellic acid, 3-acetyl-b-boswellic acid, 11-keto-
b-boswellic acid and 11-keto-b-acetylboswellic acid. Oleogum resin oil contains
isoincensole and isoincensole acetate as the main diterpenic components [13].
Tricosane (75.32%) was identified as the major compound in lipoidal matter of the
resin with also the presence of cholesterol, stigmasterol and b-sitosterol [3]. In one
systematic analysis, AKBA content of commercially available B. serrata extracts
varied from 3.83 ± 0.10 to 0.03 ± 0.004%; the extract with the highest AKBA
concentration also exhibited highest antioxidant power and phenolic content [10].
Pharmacology: Alcohol extract produced marked anti-inflammatory and anti-
arthritic activities in various models, and was equally effective in adrenalectomised
rats, without any analgesic or antipyretic effects [79]; though, analgesic effects were
earlier reported [43]. The extract was effective in collagen-induced arthritis, and
significantly reduced levels of inflammatory mediators (IL-1b, IL-6, TNF-a, IFN-c
and PGE2), and increased level of IL-10 [84]. It was observed that the resin, its
extract or constituents reduce leukotrienes production in stimulated rat peritoneal
neutrophils by inhibiting 5-LOX [4, 5, 54, 68, 70, 71, 78, 80, 87], and other
inflammatory mediators like TNF-a, IL-b, NO [25], and NF-jB [20, 60]. Injection
(i.p.) of the extract to diabetic mice prevented increase of blood glucose levels and
increase of proinflammatory cytokines IL-1a, IL-1b, IL-2, IL-6, IFN-c and TNF-a
[76]. Significant diuretic, kaliuretic and natriuretic effects of aqueous extract of the
oleo-gum resin in rats at a relatively low dose of 50 mg/kg were reported [8].
Aqueous extract also significantly lowered serum TC and increased HDL-C in
atherogenic diet-fed rats [61]. Hexane extract and boswellic acids protected against
hepatotoxicity of various agents [69, 88].
Nonphenolic fraction of gum resin exhibited significant sedative and analgesic
effects, decreased spontaneous motor activity, potentiated secobarbitone-induced
hypnosis, and caused ptosis in rats. Secondary conditioned response was specifi-
cally blocked in trained rats, but CAR was not significantly affected [56]. Incensole
Boswellia serrata Roxb. ex Colebr. 455

acetate produced anxiolytic-like and antidepression-like behavioral effects in

wild-type mice, through activation of transient receptor potential vanilloid (TRPV
3) channels, with concomitant c-Fos activation in the brain [59]. Aqueous extract
offsets harmful effects of seizures on cognitive function and improves learning
ability in epileptic animals [40], and significantly increases number of pyramidal
neurons and dendritic spines in hippocampal region, Cornu Ammonis (CA1)
[36, 41]. Alcohol extracts of roots and fruits also produced CNS depressant activity
in mice; hypoglycemic activity was reported with both fruits and stem extracts [21].
Boswellia extract depresses electrical-, ACh-, and barium chloride-induced
contractions of isolated guinea-pig ileum, inhibits upper gastrointestinal transit in
croton oil- as well as castor oil-induced diarrhea, without affecting intestinal
motility [12]. Boswellia extract was, though, ineffective in dextran sulfate- or
TNBSA-induced colitis in mice, and was hepatotoxic in higher doses, associated
with pronounced hepatomegaly and steatosis; and individual boswellic acids
increased basal and IL-1b-stimulated NF-jB activity in intestinal epithelial cells
[45]. However, the extract produced significant protective effects in acetic acid-
induced colitis in rats, with significant reduction in LPO and SOD enzyme activity
[33, 34]. Boswellia combined with Scutellaria extracts also effectively prevents
colonic fibrosis in TNBSA-induced colitis in rats [51]. Boswellic acids are also
reported to possess antiulcer effect against different ulcerogenic agents [81]. Bos-
wellia resin SCCD extract significantly reduced AOM/DSS-induced colonic tumor
formation in mice, and reduced levels of iNO synthase and COX-2 in colonic
mucosa [18]. Petroleum ether and methanol extracts elicited pronounced cytotoxic
effect on HepG2 cells, comparable to doxorubicin, and on HCT cells, comparable to
5-fluorouracil [3]. Boswellic acids, inhibit synthesis of DNA, RNA and protein in
human leukemia cells; AKBA inhibiting DNA synthesis irreversibly [11, 38, 75];
are cytotoxic to malignant glioma cells, human colon cancer cells [52], human
prostate cancer cells [53, 90], and hepatocellular carcinoma cells [44], inducing
apoptosis, and unlike steroids do not interfere with cancer drug toxicity of glioma
cells [27]. Ethanol extract showed cytotoxicity and caused apoptosis in five leu-
kemia and two brain tumor cell lines [37], and human cervical carcinoma cells [46].
Alcohol root extract also showed anticancer activity against human epidermal
carcinoma of the nasopharynx in tissue culture. AKBA also suppressed growth and
metastasis of human pancreatic tumors in an orthotopic nude mouse model [62].
Clinical Studies: In a multicenter study of 37 rheumatoid arthritis outpatients,
addition of B. serrata to existing treatment for 12-weeks, failed to show a signif-
icant or clinically relevant change in subjective, clinical or laboratory parameter
from baseline or difference from placebo group at any time point of observation
[72]. However, in double-blinded RCTs, clinically and statistically significant
improvements in pain scores and physical function scores were reported in patients
with osteoarthritis of knee [31, 47, 74]. A randomized, double-blind, placebo
controlled, crossover study of 12 healthy volunteers showed significant analgesic
activity of a single dose of B. serrata (Shellaki®) [66]. B. serrata extract treatment
of patients with collagenous colitis produced clinical improvement in 44% of 31
456 Boswellia serrata Roxb. ex Colebr.

patients compared to 27% of placebo-treated patients that was statistically

insignificant [14–16]. Treatment of patients with chronic diarrhea and histologically
proven collagenous colitis had significantly higher clinical remission but no effect
on histology and quality of life with B. serrata, compared to placebo-treated group
[55]. In a trial of German patients with Crohn’s disease, B. serrata extract
(Boswelan®) maintained remission comparative to placebo [35]. Another German
study compared B. serrata extract with mesalazine (mesalamine) in patients with
Crohn’s disease, and found the extract efficacious and non-inferior to mesalazine,
but superior to mesalazine in terms of a benefit-risk-evaluation [26]. A comparison
of B. serrata gum resin with sulfasalazine treatment in patients with ulcerative
colitis (UC) grade II and III, showed similar remission rates [29, 30]. A novel
lecithin-based delivery form of Boswellia extract (Casperome®) to Italian patients
with UC during minimally symptomatic remission phase, attenuated symptoms, and
reduced the use of conventional drugs [64].
Treatment of patients with primary or secondary malignant cerebral tumors
undergoing radiotherapy resulted in a reduction of cerebral edema by >75% in 60%
of patients who received resin compared to 26% of placebo-treated patients, with no
significant impact on quality of life or cognitive function [48]. In patients with
diffuse axonal injury, treatment with the resin caused an insignificant trend for
improvement of disability rating scale, but significant improvement in ‘cognitive
ability to self-care’ [58]. Treatment of four chronic cluster headache patients with
the resin reduced intensity and frequency of headaches [50]. Supplementation
with gum resin of type-2 diabetic Iranian patients, maintained on conventional
treatments, significantly lowered FBG, HbA1c, insulin, TC, LDL-C and TGs levels
[2, 9]. However, in another double-blind RCT, supplementation of conventional
treatment with 250 mg gum resin twice-daily for 8-weeks of Iranian type-2 diabetic
patients, further improved FBG, HbA1c, and TGs, but at the end was not signifi-
cantly different from the placebo [57]. In a double-blind RCT, treatment with a
preparation of gum resin, 300 mg thrice daily for 6-weeks, improved asthma
symptoms in 70% of the 40 patients, as well as decreased eosinophil counts and
ESR [28]. Supplementation with Boswellia, betaine and myoinositol reduced vol-
ume of breast fibroadenoma in young Italian women [63], and Mediterranean diet
of healthy Italian male athletes supplemented with curcumin and Boswellia gum
resin for 3-months significantly reduced the production of advanced glycation
end-products (AGEs) as a result of chronic intensive exercise [17].
Mechanism of Action: Effectiveness of B. serrata extract in inflammatory dis-
eases is credited to the inhibition of 5-LOX enzyme by boswellic acids, especially,
KBA and AKBA [7, 65]. AKBA was identified as a natural inhibitor of the tran-
scription factor NF-jB, which is a prerequisite for the formation/action of
cytokines/chemokines involved in inflammatory reactions [20]. However, boswellic
acids do not inhibit leukotriene formation in human whole blood, and poor
absorption following oral administration achieves very low plasma concentrations
of AKBA and KBA [86], far below the effective concentrations for bioactivity
in vitro. b-boswellic acid achieves 100-fold higher plasma concentrations and
Boswellia serrata Roxb. ex Colebr. 457

inhibits microsomal PGE synthase-1 and the serine protease cathepsin G, and has
been suggested to be responsible for the anti-inflammatory effects of the extract [1].
High fat meal to healthy volunteers is reported to increase several-fold AUCs, as
well as peak concentrations of b-boswellic acid, KBA and AKBA [83]. Inhibition
of intestinal motility by the gum resin extract is suggested to involve L-type Ca2+
channels [12].
Human A/Es, Allergy and Toxicity: Unani physicians regard it not suitable for
individuals with hot temperament.LXXVII
Animal Toxicity: The aqueous extract of the oleo-gum resin was nontoxic and
nonlethal up to a dose of 3,000 mg/kg in mice [8], and was relatively safe in rats up
to a dose of 500 mg/kg body weight for 90 days [82].
CYP450 and Potential for Drug-Herb Interactions: The extract is a potent,
nonselective inhibitor of CYP450 metabolizing enzymes CYP1A2/2C8/2C9/2C19/
2D6 and 3A4, with significant potential for drug-herb interactions; but the inhibi-
tory activity is not exclusively due to boswellic acids [24].
Commentary: Double-blinded, randomized clinical trials of the gum-resin in the
treatment of arthritis, inflammatory bowel diseases, diabetes and asthma, showed
significant potential for improvement. Nevertheless, more extensive RCTs are
needed to validate these results. Its nonselective inhibition of CYP450s and the
potential for interactions with prescription drugs, though, would be a concern.

References
1. Abdel-Tawab M, Werz O, Schubert-Zsilavecz M. Boswellia serrata: an
overall assessment of in vitro, preclinical, pharmacokinetic and clinical data.
Clin Pharmacokinet. 2011;50:349–69.
2. Ahangarpour A, Heidari H, Fatemeh RA, et al. Effect of Boswellia ser-
rata supplementation on blood lipid, hepatic enzymes and fructosamine
levels in type 2 diabetic patients. J Diabetes Metab Disord. 2014;13:29.
3. Ahmed HH, Abd-Rabou AA, Hassan AZ, Kotob SE. Phytochemical
analysis and anticancer investigation of Boswellia serrata bioactive con-
stituents in vitro. Asian Pac J Cancer Prev. 2015;16:7179–88.
4. Ammon HP, Mack T, Singh GB, Safayhi H. Inhibition of leukotriene B4
formation in rat peritoneal neutrophils by an ethanolic extract of the gum
resin exudate of Boswellia serrata. Planta Med. 1991;57:203–7.
5. Ammon HP, Safayhi H, Mack T, Sabieraj J. Mechanism of anti-inflammatory
actions of curcumine and boswellic acids. J Ethnopharmacol. 1993;38:113–9.
6. Ammon HP. Boswellic acids (components of frankincense) as the active
principle in treatment of chronic inflammatory diseases. Wien Med Wochen-
schr. 2002;152:373–8.
7. Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Med.
2006;72:1100–16.
458 Boswellia serrata Roxb. ex Colebr.

8. Asif M, Jabeen Q, Abdul-Majid AM, Atif M. Diuretic activity of Boswellia

serrata Roxb. oleo gum extract in albino rats. Pak J Pharm Sci. 2014;27:
1811–7.
9. Azadmehr A, Ziaee A, Ghanei L, et al. A randomized clinical trial study:
antioxidant, antihyperglycemic and antihyperlipidemic effects of Olibanum
gum in type 2 diabetic patients. Iran J Pharm Res. 2014;13:1003–9.
10. Beghelli D, Isani G, Roncada P, et al. Antioxidant and ex vivo immune
system regulatory properties of Boswellia serrata extracts. Oxid Med Cell
Longev. 2017;2017:7468064.
11. Bhushan S, Kumar A, Malik F, et al. A triterpenediol from Boswellia
serrata induces apoptosis through both the intrinsic and extrinsic apoptotic
pathways in human leukemia HL-60 cells. Apoptosis. 2007;12:1911–26.
12. Borrelli F, Capasso F, Capasso R, et al. Effect of Boswellia serrata on
intestinal motility in rodents: inhibition of diarrhoea without constipation.
Br J Pharmacol. 2006;148:553–60.
13. Camarda L, Dayton T, Di Stefano V, et al. Chemical composition and
antimicrobial activity of some oleogum resin essential oils from Boswellia
spp. (Burseraceae). Ann Chim. 2007;97:837–44.
14. Chande N, MacDonald JK, McDonald JW. Interventions for treating
microscopic colitis: a Cochrane Inflammatory Bowel Disease and Func-
tional Bowel Disorders Review Group systematic review of randomized
trials. Am J Gastroenterol. 2009;104:235–41.
15. Chande N, McDonald JW, MacDonald JK. Interventions for treating collage-
nous colitis. Cochrane Database Syst Rev. 2006;4:CD003575 (Review).
16. Chande N, McDonald JW, Macdonald JK. Interventions for treating collage-
nous colitis. Cochrane Database Syst Rev. 2008;2:CD003575 (Review).
17. Chilelli NC, Ragazzi E, Valentini R, et al. Curcumin and Boswellia
serrata modulate the glycooxidative status and lipooxidation in master
athletes. Nutrients. 2016;8, pii: E745.
18. Chou YC, Suh JH, Wang Y, et al. Boswellia serrata resin extract alleviates
azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumori-
genesis. Mol Nutr Food Res. 2017;61.
19. Clarke JO, Mullin GE. A review of complementary and alternative approaches
to immunomodulation. Nutr Clin Pract. 2008;23:49–62 (Review).
20. Cuaz-Pérolin C, Billiet L, Baugé E, et al. Anti-inflammatory and antiathero-
genic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in
LPS-challenged ApoE-/- mice. Arterioscler Thromb Vasc Biol. 2008;28:272–7.
21. Dhar ML, Dhar MM, Dhawan BN, et al. Screening of Indian plants for
biological activity. Part-I. Ind J Exp Biol. 1968;6:232.
22. Di Lorenzo C, Dell'Agli M, Badea M, et al. Plant food supplements with
anti-inflammatory properties: a systematic review (II). Crit Rev Food Sci
Nutr. 2013;53:507–16.
23. Ernst E. Frankincense: systematic review. BMJ. 2008;337:a2813.
Boswellia serrata Roxb. ex Colebr. 459

24. Frank A, Unger M. Analysis of frankincense from various Boswellia species

with inhibitory activity on human drug metabolising cytochrome P450
enzymes using liquid chromatography mass spectrometry after automated
on-line extraction. J Chromatogr A. 2006;1112:255–62.
25. Gayathri B, Manjula N, Vinaykumar KS, et al. Pure compound from
Boswellia serrata extract exhibits anti-inflammatory property in human
PBMCs and mouse macrophages through inhibition of TNFalpha, IL-1beta,
NO and MAP kinases. Int Immunopharmacol. 2007;7:473–82.
26. Gerhardt H, Seifert F, Buvari P, et al. Therapy of active Crohn disease with
Boswellia serrata extract H 15. Z Gastroenterol. 2001;39:11–7 (German).
27. Glaser T, Winter S, Groscurth P, et al. Boswellic acids and malignant
glioma: induction of apoptosis but no modulation of drug sensitivity. Br J
Cancer. 1999;80:756–65.
28. Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in
patients with bronchial asthma: results of a double-blind, placebo-controlled,
6-week clinical study. Eur J Med Res. 1998;3:511–4.
29. Gupta I, Parihar A, Malhotra P, et al. Effects of Boswellia serrata gum resin
in patients with ulcerative colitis. Eur J Med Res. 1997;2:37–43.
30. Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia
serrata in patients with chronic colitis. Planta Med. 2001;67:391–5.
31. Gupta PK, Samarakoon SM, Chandola HM, Ravishankar B. Clinical
evaluation of Boswellia serrata (Shallaki) resin in the management of
Sandhivata (osteoarthritis). Ayu. 2011;32:478–82.
32. Hamidpour R, Hamidpour S, Hamidpour M, Shahlari M. Frankincense (rǔ
xiāng; Boswellia species): from the selection of traditional applications to
the novel phytotherapy for the prevention and treatment of serious diseases.
J Tradit Complement Med. 2013;3:221–6.
33. Hartmann RM, Morgan Martins MI, Tieppo J, Fillmann HS, Marroni
NP. Effect of Boswellia serrata on antioxidant status in an experimental model
of colitis rats induced by acetic acid. Dig Dis Sci. 2012;57:2038–44.
34. Hartmann RM, Fillmann HS, Martins MI, Meurer L, Marroni NP. Boswellia
serrata has beneficial anti-inflammatory and antioxidant properties in a
model of experimental colitis. Phytother Res. 2014;28:1392–8.
35. Holtmeier W, Zeuzem S, Preiss J, et al. Randomized, placebo-controlled,
double-blind trial of Boswellia serrata in maintaining remission of Crohn's
disease: good safety profile but lack of efficacy. Inflamm Bowel Dis. 2011;17:
573–82.
36. Hosseini-sharifabad M, Esfandiari E. Effect of Boswellia serrata gum resin
on the morphology of hippocampal CA1 pyramidal cells in aged rat. Anat
Sci Int. 2015;90:47–53.
37. Hostanska K, Daum G, Saller R. Cytostatic and apoptosis-inducing activity
of boswellic acids toward malignant cell lines in vitro. Anticancer Res.
2002;22:2853–62.
38. Huang MT, Badmaev V, Ding Y, et al. Antitumor and anticarcinogenic
activities of triterpenoid, beta-boswellic acid. BioFactors. 2000;13:225–30.
460 Boswellia serrata Roxb. ex Colebr.

39. Hussain H, Al-Harrasi A, Al-Rawahi A, Hussain J. Chemistry and biology

of essential oils of genus boswellia. Evid Based Complement Alternat Med.
2013;2013:140509.
40. Jalili C, Salahshoor MR, Moradi S, Pourmotabbed A, Motaghi M. The
therapeutic effect of the aqueous extract of Boswellia serrata on the
learning deficit in kindled rats. Int J Prev Med. 2014;5:563–8.
41. Jalili C, Salahshoor MR, Pourmotabbed A, et al. The effects of aqueous
extract of Boswellia Serrata on hippocampal region CA1 and learning
deficit in kindled rats. Res Pharm Sci. 2014;9:351–8.
42. Joos S, Rosemann T, Szecsenyi J, et al. Use of complementary and
alternative medicine in Germany—a survey of patients with inflammatory
bowel disease. BMC Complement Altern Med. 2006;6:19.
43. Kar A, Menon MK. Analgesic effect of the gum resin of Boswellia serrata
Roxb. Life Sci. 1969;8:1023–8.
44. Khan MA, Singh M, Khan MS, Najmi AK, Ahmad S. Caspase mediated
synergistic effect of Boswellia serrata extract in combination with doxoru-
bicin against human hepatocellular carcinoma. Biomed Res Int. 2014;2014:
294143.
45. Kiela PR, Midura AJ, Kuscuoglu N, et al. Effects of Boswellia serrata in
mouse models of chemically induced colitis. Am J Physiol Gastrointest
Liver Physiol. 2005;288:G798–808.
46. Kim HR, Kim MS, Kwon DY, et al. Boswellia serrata-induced apoptosis is
related with ER stress and calcium release. Genes Nutr. 2008;2:371–4.
47. Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of
Boswellia serrata extract in treatment of osteoarthritis of knee—a randomized
double-blind placebo-controlled trial. Phytomedicine. 2003;10:3–7.
48. Kirste S, Treier M, Wehrle SJ, et al. Boswellia serrata acts on cerebral
edema in patients irradiated for brain tumors: a prospective, randomized,
placebo-controlled, double-blind pilot trial. Cancer. 2011;117:3788–95.
49. Krüger P, Daneshfar R, Eckert GP, et al. Metabolism of boswellic acids
in vitro and in vivo. Drug Metab Dispos. 2008;36:1135–42.
50. Lampl C, Haider B, Schweiger C. Long-term efficacy of Boswellia serrata in
four patients with chronic cluster headache. Cephalalgia. 2012;32:719–22.
51. Latella G, Sferra R, Vetuschi A, et al. Prevention of colonic fibrosis by
Boswellia and Scutellaria extracts in rats with colitis induced by 2,4,5-
trinitrobenzene sulphonic acid. Eur J Clin Invest. 2008;38:410–20.
52. Liu JJ, Nilsson A, Oredsson S, et al. Boswellic acids trigger apoptosis via a
pathway dependent on caspase-8 activation but independent on Fas/Fas ligand
interaction in colon cancer HT-29 cells. Carcinogenesis. 2002;23:2087–93.
53. Lu M, Xia L, Hua H, Jing Y. Acetyl-keto-beta-boswellic acid induces
apoptosis through a death receptor 5-mediated pathway in prostate cancer
cells. Cancer Res. 2008;68:1180–6.
Boswellia serrata Roxb. ex Colebr. 461

54. Mack T, Ammon HP, Safayhi H: Inhibition of leukotriene generation by a

gum resin exudate of Boswellia serrata in rat peritoneal leukocyets. In:
Proceedings of international joint symposium on pharmacognosy; 1990 July
17–22; Bonn.
55. Madisch A, Miehlke S, Eichele O, et al. Boswellia serrata extract for the
treatment of collagenous colitis. A double-blind, randomized, placebo-
controlled, multicenter trial. Int J Colorectal Dis. 2007;22:1445–51.
56. Menon MK, Kar A. Analgesic and psychopharmacological effects of the
gum resin of Boswellia serrata. Planta Med. 1971;19:333.
57. Mehrzadi S, Tavakolifar B, Huseini HF, Mosavat SH, Heydari M. The
effects of Boswellia serrata gum resin on the blood glucose and lipid profile
of diabetic patients: a double-blind randomized placebo-controlled clinical
trial. J Evid Based Integr Med. 2018;23:2515690X18772728.
58. Moein P, Abbasi Fard S, Asnaashari A, et al. The effect of Boswellia
Serrata on neuro-recovery following diffuse axonal injury. Brain Inj. 2013;
27:1454–60.
59. Moussaieff A, Rimmerman N, Bregman T, et al. Incensole acetate, an
incense component, elicits psychoactivity by activating TRPV3 channels in
the brain. FASEB J. 2008;22:3024–34.
60. Moussaieff A, Shohami E, Kashman Y, et al. Incensole acetate, a novel
anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear
factor-kappa B activation. Mol Pharmacol. 2007;72:1657–64.
61. Pandey RS, Singh BK, Tripathi YB. Extract of gum resins of Boswellia
serrata L. inhibits lipopolysaccharide induced nitric oxide production in rat
macrophages along with hypolipidemic property. Indian J Exp Biol. 2005;
43:509–16.
62. Park B, Prasad S, Yadav V, Sung B, Aggarwal BB. Boswellic acid suppresses
growth and metastasis of human pancreatic tumors in an orthotopic nude mouse
model through modulation of multiple targets. PLoS ONE. 2011;6:e26943.
63. Pasta V, Dinicola S, Giuliani A, et al. A randomized trial of Boswellia in
association with betaine and myoinositol in the management of breast
fibroadenomas. Eur Rev Med Pharmacol Sci. 2016;20:1860–5.
64. Pellegrini L, Milano E, Franceschi F, et al. Managing ulcerative colitis in
remission phase: usefulness of Casperome®, an innovative lecithin-based
delivery system of Boswellia serrata extract. Eur Rev Med Pharmacol Sci.
2016;20:2695–700.
65. Poeckel D, Werz O. Boswellic acids: biological actions and molecular
targets. Curr Med Chem. 2006;13:3359–69 (Review).
66. Prabhavathi K, Chandra US, Soanker R, Rani PU. A randomized, double-
blind, placebo controlled, crossover study to evaluate the analgesic activity of
Boswellia serrata in healthy volunteers using mechanical pain model. Indian
J Pharmacol. 2014;46:475–9.
67. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J
Gastroenterol. 2010;16:4504–14.
462 Boswellia serrata Roxb. ex Colebr.

68. Safayhi H, Boden SE, Schweizer S, Ammon HP. Concentration-dependent

potentiating and inhibitory effects of Boswellia extracts on 5-lipoxygenase
product formation in stimulated PMNL. Planta Med. 2000;66:110–3.
69. Safayhi H, Mack T, Ammon HP. Protection by boswellic acids against
galactosamine/endotoxin-induced hepatitis in mice. Biochem Pharmacol.
1991;41:1536–7.
70. Safayhi H, Mack T, Sabieraj J, et al. Boswellic acids: novel, specific, nonredox
inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther. 1992;261:1143–6.
71. Safayhi H, Sailer ER, Ammon HP. Mechanism of 5-lipoxygenase inhibition
by acetyl-11-keto-beta-boswellic acid. Mol Pharmacol. 1995;47:1212–6.
72. Sander O, Herborn G, Rau R: Is H15 (resin extract of Boswellia serrata,
“incense”) a useful supplement to established drug therapy of chronic
polyarthritis? Results of a double-blind pilot study. Z Rheumatol. 1998;
57:11–6 (German).
73. Schweizer S, von Brocke AF, Boden SE, et al. Workup-dependent formation of
5-lipoxygenase inhibitory boswellic acid analogues. J Nat Prod. 2000;63:
1058–61.
74. Sengupta K, Alluri KV, Satish AR, et al. A double-blind, randomized,
placebo controlled study of the efficacy and safety of 5-Loxin for treatment
of osteoarthritis of the knee. Arthritis Res Ther. 2008;10:R85.
75. Shao Y, Ho CT, Chin CK, et al. Inhibitory activity of boswellic acids from
Boswellia serrata against human leukemia HL-60 cells in culture. Planta
Med. 1998;64:328–31.
76. Shehata AM, Quintanilla-Fend L, Bettio S, Singh CB, Ammon HP. Preven-
tion of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an
extract from gum resin of Boswellia serrata (BE). Phytomedicine. 2011;18:
1037–44.
77. Siddiqui MZ. Boswellia serrata, a potential anti-inflammatory agent: an
overview. Indian J Pharm Sci. 2011;73:255–61.
78. Siemoneit U, Pergola C, Jazzar B, et al. On the interference of boswellic
acids with 5-lipoxygenase: mechanistic studies in vitro and pharmacological
relevance. Eur J Pharmacol. 2009;606:246–54.
79. Singh GB, Atal CK. Pharmacology of an extract of salal guggal ex-Boswellia
serrata, a new nonsteroidal anti-inflammatory agent. Agents Actions. 1986;
18:407–12.
80. Singh S, Khajuria A, Taneja SC, et al. Boswellic acids: a leukotriene
inhibitor also effective through topical application in inflammatory disor-
ders. Phytomedicine. 2008;15:400–7.
81. Singh S, Khajuria A, Taneja SC, et al. The gastric ulcer protective effect of
boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats.
Phytomedicine. 2008;15:408–15.
82. Singh P, Chacko KM, Aggarwal ML, et al. A 90-day gavage safety
assessment of Boswellia serrata in rats. Toxicol Int. 2012;19:273–8.
Boswellia serrata Roxb. ex Colebr. 463

83. Sterk V, Büchele B, Simmet T. Effect of food intake on the bioavailability of

boswellic acids from a herbal preparation in healthy volunteers. Planta Med.
2004;70:1155–60.
84. Umar S, Umar K, Sarwar AH, et al. Boswellia serrata extract attenuates
inflammatory mediators and oxidative stress in collagen induced arthritis.
Phytomedicine. 2014;21:847–56.
85. Wang C, Xia L, Song Z, et al. Determination of five boswellic acids in
Boswellia serrata. Zhongguo Zhong Yao Za Zhi. 2011;36:1330–3 (Article
in Chinese).
86. Weber CC, Reising K, Müller WE, et al. Modulation of Pgp function by
boswellic acids. Planta Med. 2006;72:507–13.
87. Wildfeuer A, Neu IS, Safayhi H, et al. Effects of boswellic acids extracted
from a herbal medicine on the biosynthesis of leukotrienes and the course of
experimental autoimmune encephalomyelitis. Arzneimittelforschung. 1998;
48:668–74.
88. Y.J., Kamath JV, Asad M. Effect of hexane extract of Boswellia serrata oleo-
gum resin on chemically induced liver damage. Pak J Pharm Sci. 2006;19:
129–33.
89. Yuan G, Wahlqvist ML, He G, et al. Natural products and anti-inflammatory
activity. Asia Pac J Clin Nutr. 2006;15:143–52 (Review).
90. Yuan HQ, Kong F, Wang XL, et al. Inhibitory effect of acetyl-11-keto-
beta-boswellic acid on androgen receptor by interference of Sp1 binding
activity in prostate cancer cells. Biochem Pharmacol. 2008;75:2112–21.
Brassica nigra (L.) K. Koch.
(Brassicaceae)

(Syns.: B. sinapoides Roth; Sinapis nigra L.)

Abstract
An annual plant that has been cultivated since ancient times as a condiment, and
grows in southern Europe and Mediterranean region, China, India, and the
United States. Pliny mentioned three varieties of it, and both Greeks and Romans
used it as condiment and medicine. In Iran and Iraq, it is used as an emetic in
cases of poisoning or drug overdose of narcotics. Hindu physicians of Ayurvedic
medicine use it internally with other stimulants in dyspepsia and as emetic;
externally it is used as rubefacient, as it is a strong counterirritant. Muslim
practitioners of Unani medicine describe seeds as detergent and digestive, and
most valuable counterirritant in neuralgic and rheumatic pains, and internal
congestion. In rural Nepal, approximately 99% of newborns are massaged at
least once daily with mustard oil in the 2-weeks after birth, and 80% are
massaged at least twice daily. Promotion of strength, maintenance of health, and
provision of warmth are the most commonly cited reasons for application of
mustard oil. A similar practice is prevalent in other countries of the Indian
subcontinent. Seeds contain the glucoside, sinigrin and the enzyme myrosin;
predominant phenolic compounds in the leaves are gallic acid, followed by
quercetin, ferulic acid, caffeic acid, and rutin. Aqueous seed extract and seed oil
lowered FBG and increased insulin levels of diabetic animals. Mustard oil
caused colitis in mice with significant increases in neuronal receptors, cytokines,
and chemokines. Methanol leaf extract demonstrated hepatoprotective and
nephroprotective activity against D-galactosamine-induced toxicity in Wistar
rats.

Keywords




Braunsenf Black mustard Hēi gài Kali rai Kali sarson

Khardal aswad




Moutarde noire Rajakshavak Rayi Sort sennep

© Springer Nature Switzerland AG 2020 465

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_48
466 Brassica nigra (L.) K. Koch.

Vernaculars: Urd.: Rayi; Hin.: Banarasi rai, Kali rai, Kali sarson, Rayi, Taramira;
San.: Asuri (sorceress), Rajakshavak, Rajika-bheda, Sarshapaha; Ben.: Kalo sorse,
Krishnrai, Rai, Raisarisha, Rai sores; Mal.: Kadu, Kadugu, Katuka, Savi sasavi;
Mar.: Kali mohari, Mohari rai; Tam.: Kadagu, Sirukadugu; Tel.: Avalu, Nal-
laavalli; Ara.: Khardal, Khardal aswad; Chi.: 黑芥, Hēi gài, Hei jie; Cze.: Brukev
černá, Hořčice černá; Dan.: Sort sennep; Dut.: Bruine mosterd, Zwarte mosterd;
Eng.: Black mustard, Chou noir; Fin.: Mustasinappi; Fre.: Moutarde brune,
Moutarde de Chine, Moutarde de l’Inde, Moutarde noire, Moutarde sauvage;
Ger.: Braunsenf, Brauner senf, Französchischer senf, Gartensenf, Grüner senf,
Holländischer senf, Schwarzer senf, Senfkohl; Gre.: Sinapasporos (seeds); Hun.:
Fekete mustár; Ita.: Senape nera, Cavolo senape nera; Jap.: Burakku-masutado,
Kuro-garashi; Kor.: Kas; Nor.: Svartsennep; Per.: Sar-shaf; Pol.: Gorczyca czarna,
Kapusta gorczyca; Por.: Mostarda-negra, Rinchões; Rus.: Gorchítsa chërnyi; Sin.:
Aba; Spa.: Mostaza negra; Swe.: Brunsenap; Tag.: Mustasa; Tha.: Mastartd; Tur.:
Kara hardal, Siyah hardal; Vie.: Hắc giới.
Description: An annual plant that grows in southern Europe and Mediterranean
region, China, India, and the United States, and has been cultivated since ancient
times as a condiment. It grows to a height of 0.6–2.5 m, with racemes of small
yellow flowers that are usually up to about 1 cm across, with four petals each.
Leaves are covered in small hairs; they can wilt on hot days, but recover at night.
Seeds are 1 mm in diameter, hard, varying in color from dark brown to black with
almost no aroma. Finest mustard is obtained from small reddish-brown seeds of
B. nigra. Nepal is one of the major producers of mustard seeds (Figs. 1 and 2).
Actions and Uses: Pliny mentioned three varieties of it, and both Greeks and
Romans used it as condiment and medicine [4]. Ibn Jazlah used it as a remedy for
menstruation disorders, whereas Ibn Buţlän found it useful for gout and to reduce
indurations. In Iran and Iraq, it is used as an emetic in cases of poisoning or drug
overdose of narcotics [5]. Hindu physicians of Ayurvedic medicine use it internally
with other stimulants in dyspepsia and as emetic; externally it is used as rubefacient,
as it is a strong counterirritant. Muslim practitioners of Unani medicine describe
seeds (temperament, hot 4° and dry 4°) as detergent and digestive, and most valuable
counterirritant in neuralgic and rheumatic pains, and internal congestion. When
applied externally as a paste or poultice to stimulate circulation in ‘cold diseases,’
such as paralysis, arthritis, gout, sciatica, pleurisy, pneumonia, and pain in stomach,
spleen and liver; it causes heat, redness and pain if the application is short, but
vesication and too much irritation if application is prolonged. Applied as a hip bath it
acts as an indirect emmenagogue by stimulating circulation. As the seeds are
intensely irritant, they cause emesis, and if large doses are taken orally, they could be
toxic. For internal use, it is added to compound drugs meant to improve digestion,
improve appetite, and for inflammation of liver and spleen.XL,LXXVII,CV In Ayurveda,
seeds are considered stimulant and stomachic, and used in neuralgia and rheumatic
afflictions, and with warm water to induce vomiting in cases of poisoning. A paste of
seeds is applied to chest in cases of pleurisy and pneumonia.LX In rural Nepal,
approximately 99% of newborns are massaged at least once daily with mustard oil in
Brassica nigra (L.) K. Koch. 467

Fig. 1 Brassica nigra, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wikimedia-
Commons, https://commons.wikimedia.org/wiki/File:Brassica_nigra_-_K%C3%B6hler%E2%80%
93s_Medizinal-Pflanzen-170.jpg

Fig. 2 Brassica nigra, Seeds, Prof. Akbar, Original

468 Brassica nigra (L.) K. Koch.

the 2-weeks after birth, and 80% are massaged at least twice daily. Promotion of
strength, maintenance of health, and provision of warmth are the most commonly
cited reasons for application of mustard oil [8]. A similar practice is prevalent in
other countries of the Indian subcontinent. In Bangladesh, a survey showed that 86%
babies delivered at home are given mustard oil massage that is started, in most cases,
within one hour of birth [1].
Phytoconstituents: Predominant phenolic compounds in the leaves are gallic acid,
followed by quercetin, ferulic acid, caffeic acid, and rutin [11]. Seeds contain the
glucoside, sinigrin and the enzyme myrosin; when macerated in water they release
volatile oil containing 0.7–1.3% allyl isothiocyanate (sinigrin),CXXXXI and are
potentially toxic.LXXXIII The bitter taste and pungent odor of black mustard is due to
the presence of isothiocyanates. Predominant fatty acid of black mustard seed oil is
oleic (22.96%), followed by linoleic (6.63%) and linolenic (3.22%) acids [7].
Pharmacology: Treatment of STZ-diabetic rats with aqueous, ethanol, acetone and
chloroform extracts of seeds lowered increase in serum glucose between 0 and 1 h of
glucose tolerance test, water extract allowing the least increase. Aqueous extract to
diabetic animals once daily for a month lowered FBG, with a lesser increase in
HbA1c, and serum lipids, compared with untreated diabetic controls [2]; continu-
ation of the extract for two-months decreased FBG, increased insulin levels, and
restored regulatory enzyme activities of carbohydrate metabolism and glycogen
content [3]. Seed oil also showed antidiabetic activity, decreasing serum glucose and
increasing insulin levels, and antioxidant activity in STZ-nicotinamide-induced
diabetic rats, decreasing MDA and increasing levels of GSH [6]. Seed extract
reduced intensity and duration of seizures in PTZ-kindled mice, with increased SOD
and NO levels, and decreased MDA level in brain tissues of mice [4]. Mustard oil
causes colitis in mice with significant increases in neuronal receptors, cytokines, and
chemokines [5]. Methanol leaf extract was hepatoprotective and nephroprotective
against D-galactosamine-induced toxicity in Wistar rats [12]. Methanol (80%) seed
extract demonstrated good chemosuppressive and moderate chemoprophylactic
activities against chloroquine-sensitive Plasmodium berghei-induced malaria in
mice [9]. Ethanol (50%) seed extract (200 mg/kg) showed no anti-implantation
activity in rats [10].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Oral LD50 of aqueous extract in rats was >3,000 mg/kg, more
than fifteen times the effective dose (200 mg/kg) [3].
Commentary: There are no clinical studies reported on this widely used plant,
despite favorable pharmacological indications about the effects of its seeds and seed
oil on blood glucose.
Brassica nigra (L.) K. Koch. 469

References
1. Ahmed AS, Saha SK, Chowdhury MA, et al. Acceptability of massage with
skin barrier-enhancing emollients in young neonates in Bangladesh.
J Health Popul Nutr. 2007;25:236–40.
2. Anand P, Murali KY, Tandon V, et al. Preliminary studies on antihyper-
glycemic effect of aqueous extract of Brassica nigra (L.) Koch in strepto-
zotocin induced diabetic rats. Indian J Exp Biol. 2007;45:696–701.
3. Anand P, Murali YK, Tandon V, Murthy PS, Chandra R. Insulinotropic
effect of aqueous extract of Brassica nigra improves glucose homeostasis in
streptozotocin induced diabetic rats. Exp Clin Endocrinol Diabetes. 2009;
117:251–6.
4. Kiasalari Z, Khalili M, Roghani M, Sadeghian A. Antiepileptic and antioxi-
dant effect of Brassica nigra on pentylenetetrazol-induced kindling in mice.
Iran J Pharm Res. 2012;11:1209–17.
5. Kimball ES, Prouty SP, Pavlick KP, et al. Stimulation of neuronal receptors,
neuropeptides and cytokines during experimental oil of mustard colitis.
Neurogastroenterol Motil. 2007;19:390–400.
6. Kumar M, Sharma S, Vasudeva N. In vivo assessment of antihyperglycemic
and antioxidant activity from oil of seeds of Brassica nigra in streptozotocin
induced diabetic rats. Adv Pharm Bull. 2013;3:359–65.
7. Mejia-Garibay B, Guerrero-Beltrán JÁ, Palou E, López-Malo A. Physical
and antioxidant characteristics of black (Brassica nigra) and yellow mus-
tard (Brassica alba) seeds and their products. Arch Latinoam Nutr. 2015;
65:128–35 (Article in Spanish).
8. Mullany LC, Darmstadt GL, Khatry SK, Tielsch JM. Traditional massage of
newborns in Nepal: implications for trials of improved practice. J Trop
Pediatr. 2005;51:82–6.
9. Muluye AB, Melese E, Adinew GM. Antimalarial activity of 80% methano-
lic extract of Brassica nigra (L.) Koch. (Brassicaceae) seeds against Plas-
modium berghei infection in mice. BMC Complement Altern Med. 2015;
15:367.
10. Prakash AO. Potentialities of some indigenous plants for antifertility
activity. Int J Crude Drug Res. 1986;24:19–24.
11. Rajamurugan R, Selvaganabathy N, Kumaravel S, et al. Polyphenol
contents and antioxidant activity of Brassica nigra (L.) Koch. leaf extract.
Nat Prod Res. 2012;26:2208–10.
12. Rajamurugan R, Suyavaran A, Selvaganabathy N, et al. Brassica nigra
plays a remedy role in hepatic and renal damage. Pharm Biol. 2012;50:
1488–97.
Butea monosperma (Lam.) Taub.
(Fabaceae/Leguminosae)

(Syns.: B. braamania DC. B. frondosa Roxb. ex Willd.; Erythrina monosperma

Lam.; Phaso monosperma (Lam.) Kuntze)

Abstract
A tree, native to tropical and subtropical parts of the Indian subcontinent and
Southeast Asia: India, Bangladesh, Nepal, Sri Lanka, Myanmar, Thailand,
Cambodia, Laos, Malaysia, Vietnam, and western Indonesia. The tree is
considered sacred by both Hindus and Buddhists, and is called the treasurer of
the gods of sacrifice; its bark, leaves, flowers, seeds and gum are mainly used as
anthelmintic, appetizer, aphrodisiac, and laxative. While the stem bark is used to
treat dyspepsia, diarrhea, dysentery, diabetes, ulcers, sore throat and snake bites;
leaves (young shoots) are astringent, alterative, anthelmintic, diuretic, emme-
nagogue, aphrodisiac, and thicken semen, and are used in the treatment of
diarrhea, leucorrhea and spermatorrhea. Bark decoction is also used to wash in
cases of leucorrhea. Seeds are carminative, anthelmintic, and antipyretic; and
their powder or decoction is used to kill and expel intestinal tapeworms and
roundworms. Important active principles are butin, butein, butrin, isobutrin,
palasitrin, coreopsin and isocoreopsin, chalcones, and aurones triterpene
phenolics. Methanol flower extract exhibits significant anti-inflammatory and
hepatoprotective activities in rats. Ethanol leaf extract significantly reduced
FBG, and TC, and improved HDL-C of diabetic rats, and increased insulin
secretion from isolated rat islets. Aqueous and butanol flower extracts possess
antioxidant and radical scavenging activities, which are credited to their butein
contents. Antioxidant and radical scavenging activities of leaves and stem bark
correlate with their total phenolic content. Butrin and isobutrin have been
identified as the constituents responsible for anti-inflammatory activity through
inhibition of secretion of proinflammatory cytokines.

Keywords





Bastard teak Butee-feuillue Bûtîyah Chunnia gond Dhaak Gul-e-tessu






Kinobaum Palăśa Plaspapda Sacred tree

© Springer Nature Switzerland AG 2020 471

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_49
472 Butea monosperma (Lam.) Taub.

Vernaculars: Urd.: Chunnia gond, Gul-e-tessu, Plaspapda; Hin.: Chalcha, Chi-

chra tesu (dye), Chuniagond (gum), Desuka jhad, Dhaak, Kankrei, Palaash; San.:
Kinsuka, Lakshataru, Palăśa, Palasha, Samidha; Ben.: Kamarkas (gum), Kinshuk,
Palasha-kinaka, Polash, Polashi; Guj.: Kesuudo, Khakda; Mal.: Brahmavriksham,
Chamatha, Muriku, Murukha monum, Murukkanmaram, Palasinsamatha, Pilac-
ham, Shamata; Mar.: Palas, Palasha-kakra; Tam.: Murkampoo (dye), Murukkam,
Murukkanmaram, Palasam, Palas-muram, Porasum, Porasu; Tel.: Kimshuka,
Moduga (dye), Modugu chettu, Paladulu; Ara.: Bûtîyah, Samagh-e-plaas; Bur.:
Pauk; Chi.: 紫铆柳; Eng.: Bastard teak, Bengal kino (gum), Flame of the forest,
Gum of the palas, Palas, Parrot tree, Sacred tree; Fin.: Bengalinleiskupuu; Fre.:
Arbre à laque, Butee-feuillue, Butée à une graine, Flamme de forêt; Ger.: Kino-
baum, Lackbaum, Malabar-lackbaum, Plossobaum, Waldfeuer; Ita.: Butea; Maly.:
Palasa, Ploso (Java); Per.: Darakht-e-palasha, Palah; Sin.: Kela; Tha.: Tong-
kwoaw; Tur.: Yalan sac ağaçı.
Description: A famous tree, native to tropical and subtropical parts of the Indian
subcontinent and Southeast Asia: India, Bangladesh, Nepal, Sri Lanka, Myanmar,
Thailand, Cambodia, Laos, Vietnam, Malaysia, and western Indonesia. In India, it
is called Dhaak that has three leaves on a branch. Due to its orange-red beautiful
flowers, it is called Flame of the Forest. In Unani medicine, leaves are called Plaas,
the flowers Gul-e-Tessu, the seeds, Plaaspaapda, and the gum is referred to as
Chunnia Gond or Kamarkas.1 Dried twigs of the plant called Samidhás are used to
feed the Hom, the sacred fire. The tree is also known in Sanskrit as Lâkashataru or
lac tree, because large quantities of lac are collected from its branches.XL It is a
medium-sized slow growing, dry season deciduous tree, growing up to 15 m tall;
leaves are pinnate, with 8–16 cm petiole and three leaflets, each leaflet 10–20 cm
long. Flowers are 2.5 cm long, bright orange-red, and produced in racemes up to
15 cm long; fruit is a pod 15–20 cm long and 4–5 cm broad (Figs. 1 and 2).
Actions and Uses: Palăśa is considered sacred by both Hindus and Buddhists, and
is called the treasurer of the gods of sacrifice; its bark, leaves, flowers, seeds and
gum are mainly used as anthelmintic, appetizer, aphrodisiac, and laxative [23]. The
tree is said to be a form of Agni, ‘god of fire’, which was a punishment from
goddess Parvati for disturbing her privacy with Shiva.IV While the stem bark is
used to treat dyspepsia, diarrhea, dysentery, diabetes, ulcers, sore throat and snake
bites;LXXIII,CXXXXV leaves (young shoots) are astringent, alterative, anthelmintic,
diuretic, emmenagogue, aphrodisiac, and thicken semen, and are used in the
treatment of diarrhea, leucorrhea and spermatorrhea. Bark decoction is also used to
wash in cases of leucorrhea. Seeds are carminative, anthelmintic, and antipyretic;
and their powder or decoction is used to kill and expel intestinal tapeworms and
roundworms.LXXVII,LXXXI In Unani medicine, temperament of leaves and flowers is
cold and dry, while seeds and gum are considered hot and dry.LXXVII Nadkarni,CV
with reference to Chakradatta (a treatise on Hindu medicine) states that the gum is
astringent, seeds are laxative and anthelmintic, and the leaves and flowers are tonic,

1
Tayyab M: Personal Communication.
Butea monosperma (Lam.) Taub. 473

Fig. 1 Butea monosperma, A Tree in Full Bloom (Ranchi, India), Gurpreet Singh, Wikimedia-
Commons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:
Palash_Tree.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Butea monosperma, Flowers (Kolkata, India), Suma Tagadur, WikimediaCommons; Share-
Alike 2.5 Generic CC BY-SA 2.5. https://commons.wikimedia.org/wiki/File:STS_001_Butea_
monosperma.jpg; https://creativecommons.org/licenses/by-sa/2.5/deed.en

astringent, aphrodisiac, depurative and diuretic. A decoction of leaves is also

reportedly used for sweating of pthisis, diabetes, menorrhagia, and as retention
enema in cases of diarrhea and dysentery, and into the vagina in cases of leucorrhea.
Seed decoction and flowers infusion are used as diuretic in dysuria and retention of
urine.LXXXI Externally, leaves are used to disperse boils, pimples, buboes, and
tumorous hemorrhoides; and internally, for flatulent colic, worms and piles.CV
474 Butea monosperma (Lam.) Taub.

In Sri Lanka, stem bark is used in indigenous medicine for treatment of dyspepsia,
diarrhea, dysentery, diabetes, ulcers, sore throat and snake bites.LXXIII
Phytoconstituents: Important active principles are butin, butein, butrin, isobutrin,
palasitrin, coreopsin and isocoreopsin, chalcones, and aurones triterpene phenolics
[14]. Stigmasterol, stigmasterol-b-D-glucopyranoside, nonacosanoic acid, 3a-hydroxy-
euph-25-ene and 2,14-dihydroxy-11,12-dimethyl-8-oxo-octadec-11-enylcyclohexane
have been isolated from stem [21]. Buteaspermin A, buteaspermin B and buteasper-
manol were isolated from stem bark [19], and (−)-medicarpin, isolated from stem bark
is a fungicide against Cladosporium cladosporiodes, a mold most common in outdoor
air where its spores are responsible for seasonal allergies [3]. From flowers, dihy-
drochalcone (dihydromonospermoside), chalcones (butein, monospermoside and
isoliquiritigenin), flavone (7,3′,4′-trihydroxyflavone), flavanones ((−)-butin, (−)-butrin,
(+)-isomonospermoside and (−)-liquiritigenin), and isoflavones (formononetin, afror-
mosin and formononetin-7-O-beta-D-glucopyranoside) have been reported, with butein
showing strong antimycobacterial activity [7]. Flavones glycosides, 5,2′-dihydroxy-
3,6,7-trimethoxyflavone-5-O-b-D-xylopyranosyl-(1!4)-O-b-D-glucopyranoside from
seeds [44], and 5,7-dihydroxy-3,6,4′-trimethoxyflavone-7-O-a-L-xylopyranosyl-
(1!3)-O-a-L-arabinopyranosyl-(1!4)-O-b-D-galactopyranoside from flowers
[45], have been isolated; the former is reported to be a potential antiviral agent.
Isobutrin is a bright yellow pigment belonging to chalcone class [1]; both iso-
butrin and butrin were identified as the antihepatotoxic principles in flowers [43].
Pharmacology: Methanol flower extract showed significant anti-inflammatory
activity [31], reversed 2-acetylaminofluorine-induced hepatic toxicity markers, such
as hepatic glutathione content, metabolizing enzymes and antioxidant enzymes
[30], and was hepatoprotective against thioacetamide-induced liver carcinogenesis
in rat [28]; the extract and polyphenols isolated from it, butrin, isobutrin, and
butein, reduced phorbol 12-myristate 13-acetate and calcium ionophore A23187-
induced inflammatory gene expression and production of TNF-a, IL-6, and IL-8 in
human mast cells by inhibiting activation of NF-jB [26]. Hydroalcohol flower
extract also decreased secretion of proinflammatory cytokines, IL-1b, IL-6 and IL-8
from human epidermis keratinocytes, along with reduction in PGE2 and metallo-
proteinases [17]. Aqueous flower extract caused apoptotic death in hepatoma cell
lines, and protected mice from hepatocellular carcinoma [6]. Petroleum ether flower
extract exhibited anticonvulsant activity; the acetone soluble fraction of the extract
protected mice from MES-, electrical kindling- and PTZ-induced convulsions, and
raised brain contents of GABA and serotonin, but was anxiogenic and general CNS
depressant [15]; the active principle was identified to be a triterpene [16]. Lyo-
philized hydroalcohol leaves extract ameliorated scopolamine-induced amnesia in
rats [18]. Ethanol leaves extract significantly attenuated vincristine-induced painful
neuropathy (hyperalgesia and allodynic pain sensation) [42], and chronic con-
striction injury of sciatic nerve-induced neuropathic pain in rats [41].
Ethanol leaf extract treatment of diabetic rats significantly reduced FBG, and
TC, and improved HDL-C [27, 38], and increased insulin secretion from isolated rat
Butea monosperma (Lam.) Taub. 475

islets [27]. Ethanol extracts of leaves, flowers, seeds and bark also produced sig-
nificant hypoglycemic and antioxidant activity in diabetic mice [32–35]. Ethanol
bark extract reduced blood glucose (40%) and increased plasma insulin (37%),
partially restored altered levels of serum lipids, lipoproteins, and activities of
lipogenic enzymes in diabetic rats [9], decreased body weight, daily food intake,
internal organs’ weight, and glucose and lipids levels in obese rats [10]. Aqueous
extracts of leaves and bark administered to diabetic rats for 6-weeks, however,
insignificantly reduced blood glucose levels by 28 and 11%, respectively [2].
Ethanol seed extract also exhibited significant antidiabetic, hypolipemic and
antiperoxidative effects in diabetic rats [4]. Aqueous and butanol flower extracts
also possess antioxidant and radical scavenging activities, which were credited to
their butein contents [29]. Antioxidant and radical scavenging activities of leaves
and stem bark correlated with their total phenolic content [8, 37].
Ethanol extract of defatted aerial parts containing flavonoids, phenolics and
alkaloids, was protective against gentamicin-nephrotoxicity [39]. Aqueous flower
extract [36], and the ethanol bark extract [13] significantly protected rats against
CCl4-hepatotoxicity. Ethanol stem bark extract reduced gastrointestinal motility,
and inhibited castor oil-induced diarrhea, and PGE2-induced enteropooling in rats
[12]. Methanol extract showed significant in vitro anthelmintic activity [24], and
against MDR S. typhi [25]; whereas, seed oil was significantly bactericidal and
fungicidal against several human pathogenic bacteria and fungi [20]. Topical
application of alcohol bark extract significantly improved wound healing, and
increased cellular proliferation and collagen synthesis in rats [40]. Stigmasterol,
isolated from bark, to normal mice for 20-days reduced serum T3, T4 and glucose
levels, and improved antioxidant potential [22]. Butin, isolated from seeds and
administered orally to adult female rats from day 1 to day 5 of pregnancy showed
anti-implantation activity [5].
Mechanism of Action: Butrin and isobutrin were identified as the constituents
responsible for anti-inflammatory activity, through inhibition of secretion of
proinflammatory cytokines [17]. CNS depressant and anticonvulsant activities were
suggested to involve GABA and serotonin [15]. The antiamnesic effect may be due
to a significant decrease in brain AChE activity [18].
Human A/Es, Allergy and Toxicity: Unani physicians consider the flowers,
leaves, bark and gum nonspecifically harmful for intestines.LXXVII
Animal Toxicity: Powdered seeds suspension in distilled water, administered
orally to rats in a dose of 800 mg/kg/day for 90-days significantly decreased Hb,
RBC count, hematocrit, total protein, albumin, and bilirubin levels, and signifi-
cantly increased VLDL and TGs [11]. Ethanol extract of defatted aerial parts, was
nonlethal and nontoxic to rats up to a dose of 4,000 mg/kg [39].
Commentary: There are no clinical studies reported in English journals listed on
PubMed.
476 Butea monosperma (Lam.) Taub.

References
1. Agarkar SA, Kulkarni RR, Dhas VV, et al. Isobutrin from Butea mono-
sperma (flame of the forest): a promising new natural sensitizer belonging
to chalcone class. ACS Appl Mater Interfaces. 2011;3:2440–4.
2. Ahmed F, Siddaraju NS, Harish M, Urooj A. Effect of Butea monosperma
Lam. leaves and bark extracts on blood glucose in streptozotocin-induced
severely diabetic rats. Pharmacognosy Res. 2012;4:33–6.
3. Bandara BM, Kumar NS, Samaranayake KM. An antifungal constituent
from the stem bark of Butea monosperma. J Ethnopharmacol. 1989;25:73–5.
4. Bavarva JH, Narasimhacharya AV. Preliminary study on antihyperglycemic
and antihyperlipaemic effects of Butea monosperma in NIDDM rats. Fito-
terapia. 2008;79:328–31.
5. Bhargava SK. Estrogenic and postcoital anticonceptive activity in rats of
butin isolated from Butea monosperma seed. J Ethnopharmacol. 1986;18:
95–101.
6. Choedon T, Shukla SK, Kumar V. Chemopreventive and anticancer proper-
ties of the aqueous extract of flowers of Butea monosperma. J Ethnophar-
macol. 2010;129:208–13.
7. Chokchaisiri R, Suaisom C, Sriphota S, et al. Bioactive flavonoids of the
flowers of Butea monosperma. Chem Pharm Bull (Tokyo). 2009;57:428–32.
8. Choudhary RK, Swarnkar PL. Antioxidant activity of phenolic and flavonoid
compounds in some medicinal plants of India. Nat Prod Res. 2011;25:
1101–9.
9. Divya BT, Mini S. Ethanol extract of Butea monosperma bark modulates
dyslipidemia in streptozotocin-induced diabetic rats. Pharm Biol. 2014;52:
1021–7.
10. Dixit P, Prakash T, Karki R, Kotresha D. Antiobese activity of Butea
monosperma (Lam) bark extract in experimentally induced obese rats.
Indian J Exp Biol. 2012;50:476–83.
11. Donga S, Shukla VJ, Ravishankar B, Ashok BK, Mishtry IU. Chronic toxi-
city study of Butea monosperma (Linn.) Kuntze seeds in albino rats. Ayu.
2011;32:120–5.
12. Gunakkunru A, Padmanaban K, Thirumal P, et al. Antidiarrhoeal activity of
Butea monosperma in experimental animals. J Ethnopharmacol. 2005;98:
241–4.
13. Gupta A, Sheth NR, Pandey S, et al. Evaluation of protective effect of
Butea monosperma (Lam.) Taub in experimental hepatotoxicity in rats.
J Pharmacol Pharmacother. 2012;3:183–5.
14. Gupta SR, Ravindranath B, Seshadri TR. Glucosides of Butea monosperma.
Phytochemistry. 1970;9:2231–5.
15. Kasture VS, Chopde CT, Deshmukh VK. Anticonvulsive activity of
Albizzia lebbeck, Hibiscus rosa sinesis and Butea monosperma in experi-
mental animals. J Ethnopharmacol. 2000;71:65–75.
Butea monosperma (Lam.) Taub. 477

16. Kasture VS, Kasture SB, Chopde CT. Anticonvulsive activity of Butea
monosperma flowers in laboratory animals. Pharmacol Biochem Behav.
2002;72:965–72.
17. Krolikiewicz-Renimel I, Michel T, Destandau E, et al. Protective effect of a
Butea monosperma (Lam.) Taub. flowers extract against skin inflammation:
antioxidant, anti-inflammatory and matrix metalloproteinases inhibitory
activities. J Ethnopharmacol. 2013;148:537–43.
18. Malik J, Kumar M, Deshmukh R, Kumar P. Ameliorating effect of lyophi-
lized extract of Butea frondosa leaves on scopolamine-induced amnesia in
rats. Pharm Biol. 2013;51:233–9.
19. Maurya R, Yadav DK, Singh G, et al. Osteogenic activity of constituents
from Butea monosperma. Bioorg Med Chem Lett. 2009;19:610–3.
20. Mehta BK, Dubey A, Bokadia MM, Mehta SC. Isolation and in vitro
antimicrobial efficiency of Butea monosperma seed oil on human pathogenic
bacteria and phytopathogenic fungi. Acta Microbiol Hung. 1983;30:75–7.
21. Mishra M, Shukla YN, Kumar S. Euphane triterpenoid and lipid consti-
tuents from Butea monosperma. Phytochemistry. 2000;54:835–8.
22. Panda S, Jafri M, Kar A, Meheta BK. Thyroid inhibitory, antiperoxidative
and hypoglycemic effects of stigmasterol isolated from Butea monosperma.
Fitoterapia. 2009;80:123–6.
23. Prasad PV, Subhaktha PK, Narayana A, Rao MM. Palăśa (Butea mono-
sperma (Lamk.) Taub.) and its medicohistorical study. Bull Indian Inst Hist
Med Hyderabad. 2006;36:117–28.
24. Prashanth D, Asha MK, Amit A, Padmaja R. Anthelmintic activity of Butea
monosperma. Fitoterapia. 2001;72:421–2.
25. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
26. Rasheed Z, Akhtar N, Khan A, Khan KA, Haqqi TM. Butrin, isobutrin, and
butein from medicinal plant Butea monosperma selectively inhibit nuclear
factor-kappaB in activated human mast cells: suppression of tumor necrosis
factor-alpha, interleukin (IL)-6, and IL-8. J Pharmacol Exp Ther. 2010;333:
354–63.
27. Samad MB, Kabir AU, D’Costa NM, et al. Ethanolic extract of Butea
monosperma leaves elevate blood insulin level in type 2 diabetic rats,
stimulate insulin secretion in isolated rat islets, and enhance hepatic
glycogen formation. Evid Based Complement Alternat Med. 2014;2014:
356290.
28. Sehrawat A, Khan TH, Prasad L, Sultana S. Butea monosperma and
chemomodulation: protective role against thioacetamide-mediated hepatic
alterations in Wistar rats. Phytomedicine. 2006;13:157–63.
29. Sehrawat A, Kumar V. Butein imparts free radical scavenging, anti-
oxidative and proapoptotic properties in the flower extracts of Butea mono-
sperma. Biocell. 2012;36:63–71.
478 Butea monosperma (Lam.) Taub.

30. Sehrawat A, Sultana S. Chemoprevention by Butea monosperma of hepatic

carcinogenesis and oxidative damage in male wistar rats. Asian Pac J
Cancer Prev. 2006;7:140–8.
31. Shahavi VM, Desai SK. Anti-inflammatory activity of Butea monosperma
flowers. Fitoterapia. 2008;79:82–5.
32. Sharma N, Garg V. Antidiabetic and antioxidant potential of ethanolic
extract of Butea monosperma leaves in alloxan-induced diabetic mice.
Indian J Biochem Biophys. 2009;46:99–105.
33. Sharma N, Garg V. Antihyperglycemic and antioxidant effect of hydroethano-
lic extract of Butea monosperma bark in diabetic mice. Indian J Biochem
Biophys. 2012;49:55–62.
34. Sharma N, Garg V. Antihyperglycemic and antioxidative attribute of
hydroethanolic extract of Butea monosperma (Lam.) seeds and its active
constituents. Indian J Exp Biol. 2011;49:756–66.
35. Sharma N, Garg V. Antihyperglycemic and antioxidative potential of
hydroalcoholic extract of Butea monosperma Lam flowers in alloxan-
induced diabetic mice. Indian J Exp Biol. 2009;47:571–6.
36. Sharma N, Shukla S. Hepatoprotective potential of aqueous extract of Butea
monosperma against CCl(4) induced damage in rats. Exp Toxicol Pathol.
2011;63:671–6.
37. Singh A, Kaur M, Choudhary A, Kumar B. Effect of Butea monosperma
leaf extracts on cyclophosphamide induced clastogenicity and oxidative
stress in mice. Pharmacognosy Res. 2015;7:85–91.
38. Somani R, Kasture S, Singhai AK. Antidiabetic potential of Butea
monosperma in rats. Fitoterapia. 2006;77:86–90.
39. Sonkar N, Ganeshpurkar A, Yadav P, et al. An experimetal evaluation of
nephroprotective potential of Butea monosperma extract in albino rats.
Indian J Pharmacol. 2014;46:109–12.
40. Sumitra M, Manikandan P, Suguna L. Efficacy of Butea monosperma on
dermal wound healing in rats. Int J Biochem Cell Biol. 2005;37:566–73.
41. Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A, Singh N.
Ameliorative potential of Butea monosperma on chronic constriction injury
of sciatic nerve induced neuropathic pain in rats. An Acad Bras Cienc.
2012;84:1091–104.
42. Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A, Singh N.
Antinociceptive effect of Butea monosperma on vincristine-induced neuro-
pathic pain model in rats. Toxicol Ind Health. 2013;29:3–13.
43. Wagner H, Geyer B, Fiebig M, Kiso Y, Hikino H. Isobutrin and butrin, the
antihepatotoxic principles of Butea monosperma flowers. Planta Med. 1986;
2:77–9.
44. Yadava RN, Tiwari L. A potential antiviral flavone glycoside from the seeds
of Butea monosperma O. Kuntze. J Asian Nat Prod Res. 2005;7:185–8.
45. Yadava RN, Tiwari L. New antifungal flavone glycoside from Butea
monosperma O. Kuntze. J Enzyme Inhib Med Chem. 2007;22:497–500.
Caccinia macranthera var. glauca (Savi) Govaerts
(Boraginaceae)

(Syn.: C. glauca Savi)

Abstract
Dioscorides described its leaves like Verbascum (a genus of plants from Scrophu-
lariaceae family), procumbent, but rough and blacker, like a bullock’s tongue.
Forskahl identified the Lisan-et-thour of the Arabs with borage (Borago
officinalis), and Dioscorides also emphasized that Bugloss of the ancients was
borage. However, various other plants sold in the Indian markets under the name of
Gaozaban, (Onosma bracteata, Anisomeles malabarlica, Trichodesma indicum,
and Cacalia kleinia) do not include borage. The plant has been mentioned by
Dioscorides, Paulus, Ægineta, Pliny and other Greek and Latin writers as useful in
the cold stage offevers as a stimulant when added to wine. In India, it is held in high
esteem as an alterative tonic in syphilis, leprosy, and rheumatism; it also has
diuretic and demulcent properties. In Persia, Gaozaban is used as a demulcent in
colds and cough, and the ashes are applied to cure scald head in children. Unani
physicians use leaves and flowers for the treatment of melancholy, insanity, and
palpitation due to black bile, and in combination with other drugs for colds and
cough, breathlessness and pulmonary irritation. A pyrrolizidine alkaloid, a diester
of retronecine and benzoic acid, have been isolated from the flowers. However, no
pharmacological or clinical studies on this plant are reported in mainstream
literature.

Keywords
Darvipatraa
Gaozaban
Gojihvaa
Kharpatra
Lisan-et-thour
Vrishjhavaa

Vernaculars: Urd.: and Hin.: Gaozaban; San.: Darvipatraa, Gojihvaa, Kharpatra,

Vrishjhavaa; Ben., Mar. and Tam.: Gaozaban; Ara.: Lisan-et-thour; Per.:
Gaozaban.

In India, Borago officinalis is also marketed as Gaozaban.

© Springer Nature Switzerland AG 2020 479

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_50
480 Caccinia macranthera var. glauca (Savi) Govaerts

Description: Dioscorides described its leaves like Verbascum (a genus of plants

from figwort, Scrophulariaceae family, also known as velvet plants), procumbent,
but rough and blacker, like a bullock’s tongue (hence the Urdu and Persian name
Gaozaban, meaning cow’s tongue). Forskahl identified the Lisan-et-thour of the
Arabs with borage (Borago officinalis), and Dioscorides also emphasized that
Bugloss of the ancients was borage.XL However, various other plants sold in the
Indian markets under the name of Gaozaban, (Onosma bracteata, Anisomeles
malabarlica, Trichodesma indicum, and Cacalia kleinia) do not include bor-
age.LXXXI The author of Makhzan-al Adwiya and other Persian writers also
assumed that the Gaozaban of Persia is the same as the Bugloss of the Greeks and
Romans.XL Missouri and Kew Botanical Gardens have stated that Caccinia glauca
is a synonym for Caccinia macranthera var. glauca, though International Plant
Names Index mentions that it was originally described as Caccinia glauca Savi, and
it was reclassified by Rafaël Herman Anna Govaerts in 1999. It is a subshrub that
reaches a height of 50–60 cm, flowers during May and June, and is a native of Iran.
Some sources mentioned that it was imported into India from Iran, Afghanistan and
Pakistan (Figs. 1 and 2).

Fig. 1 Caccinia macranthera, Illustration, Cels, Jacques Martin; Redouté, Henri-Joseph; Vente-
nat, Etienne Pierre, WikimediaCommons, https://commons.wikimedia.org/wiki/File:Description_
des_plantes_nouvelles_et_peu_connues_(Plate_100)_(9343436678).jpg
Caccinia macranthera var. glauca (Savi) Govaerts 481

Fig. 2 Caccinia macranthera, Plant, Krzysztof Ziarnek, Kenraiz, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Caccinia_macranthera_kz02.jpg

Actions and Uses: Fresh aerial parts, including flowers (temperament, moderate or
hot 1° and moist 1°), are refrigerant, tonic for heart, lungs and liver, and expec-
torant; dried Gaozaban (temperament, hot 1° and dry 1°) is astringent and drying.
The plant has been mentioned by Dioscorides, Paulus, Ægineta, Pliny and other
Greek and Latin writers as useful in the cold stage of fevers as a stimulant when
added to wine. In India, it is held in high esteem as an alterative tonic in syphilis,
leprosy, and rheumatism; it also has diuretic and demulcent properties. In Persia,
Gaozaban is used as a demulcent in colds and cough, and the ashes are applied to
cure scald head in children.XL Both leaves and flowers are used in Unani medicine
for the treatment of melancholy, insanity, and palpitation due to black bile, and
combined with other drugs for colds and cough, breathlessness and pulmonary
irritation.LXXVII The leaves are considered moderating the humours, and used in the
treatment of cold and cough, pleurisy, and pneumonia; while flowers are refrigerant,
heart and brain tonic.1 Khory and KatrakLXXXI also described it as alterative, tonic,
diuretic, and demulcent, and its use in the treatment of chronic fevers, syphilis,
rheumatism, leprosy, hypochondriasis, kidney diseases, gonorrhea and dysuria.
Phytoconstituents: A pyrrolizidine alkaloid, a diester of retronecine and benzoic
acid, were isolated from the flowers [1].
Pharmacology: There are no pharmacology studies reported on this plant in
journals listed on PubMed.
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.

1
Tayyab M: Personal Communication.
482 Caccinia macranthera var. glauca (Savi) Govaerts

Commentary: This is one of the virgin plants that is significantly used in Unani
medicine but has not been investigated; at least no information could be retrieved
from different sources.

Reference
1. Siddiqi MA, Suri KA, Suri OP, Atal CK. A new pyrrolizidine alkaloid
from Caccinia glauca. Phytochemistry. 1978;17:2049–50.
Caesalpinia bonduc (L.) Roxb.
(Fabaceae/Caesalpiniaceae)

(Syns.: C. bonducella (L.) Fleming; C. crista Thun.; Guilandina bonduc L.; G. bonducella L.)

Abstract
A large, flowering, straggling, very thorny shrub, from the Senna family with
pantropical distribution. The nuts and root-bark are described as antiperiodic,
antispasmodic, bitter-tonic, anthelmintic and febrifuge; powdered seeds as tonic,
febrifuge and antiperiodic; leaves as deobstruent and emmenagogue, and the root
as gastric tonic. In Ayurveda, the plant is used to treat various diseases, specifically
tumors, cysts and cystic fibrosis; leaves mitigate Kapha and Vata, are anthelmintic,
emmenagogue and febrifuge, and are useful in piles, intestinal worms, elephan-
tiasis, splenomegaly, hepatomegaly, amenorrhea, dysmenorrhea, pharyngodynia,
and fevers. In Hawaii, half a ground bean (seed) is given twice daily to 20-days old
babies with constitutional debility, as a laxative; the dose is increased to one bean
for 40–80-days old babies, and to two beans for one year or older. Beans are also
used as blood purifier, and to clear chest of tough sticky phlegm. In the Philippines,
seeds are considered a good remedy for stomach troubles, and a mild purgative, and
as powder, tonic and febrifuge. This species has been declared extinct in the wild,
but is still grown in home gardens for medicinal use of its seeds, roots, and leaves in
the West African nation of Benin. It is traditionally used to treat snakebites in the
West African nation of Ivory Coast, and as anticancer drug in other African
traditional medicines. Seeds contain a bitter substance named bonducin, phytos-
terinin, fatty acids, caesalpins (a, b, c, d and w), bonducellin and citrulline.
Seed-coat as well as kernel’s ethanol extracts show significant antistress activity
and efficiently control hyperlipidemic condition due to stress in rats, and the
seed-coat extract exhibits analgesic and anti-inflammatory activities.

Keywords





Bonduc Bunduq Ci guo su mu Fundaq Gray nickerbean Khayahe-i-iblis





Kugelstrauch Mate amarillo Putikaranja Sagargoti

© Springer Nature Switzerland AG 2020 483

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_51
484 Caesalpinia bonduc (L.) Roxb.

Vernaculars: Urd.: Bunduq, Fundaq, Karanja; Hin.: Gajga, Karaijo, Kat-kaleja,

Kat-karanj, Pattil, Putikaranj, Sagargoti; San.: Angarhavallari, Kāṇṭākarañja,
Kubarakshi-phalam, Kuberaksha, Latakaranja, Putikaranja, Vitapakaranja; Ben.:
Dahara, Jhagra-gula, Nata koranja, Natarphal; Mal.: Kalanchikuru, Kāḻañci, Kaz-
hanchikkuru; Mar.: Gajra, Katukaranja, Sagara-gota; Tam.: Gajega, Kaccuram,
Kalangu, Kalarkodi, Kazharchikkaai, Kazhar-shikkay, Mulal, Vajrapijam; Tel.:
Gatchkaya, Gatstsa, Sukajambuka, Yakshakshi, Yalakhi; Ara.: Akit makit,
Bonduq-i-hindi; Chi.: 大花托云实, Ci guo su mu; Eng.: Bonduc seeds, Cae-
salpinia, Gray nickerbean, Molucca bean, Nicker-nut, Sea pearl, Yellow nickers;
Fre.: Bonduc, Bonduc jaune, Césalpinie bonduc, Cniquier, Guilandina bonduc;
Ger.: Kugelstrauch, Molukkenbohne; Haw.: Kalakalaioa; Maly.: Gorek, Kelichi,
Tinglur (Java); Per.: Khayahe-i-iblis (devil’s testicles); Por.: Carnica, Juquirionano
(Br.), Noz de bonduque; Sin.: Kalu vavuletiya, Kumburu wel, Wael kumburu;
Spa.: Guacolote, Mate amarillo, Mate de costa, Mato de playa, Semilla del pasmo;
Tag.: Bayag-kambing, Calumbibit, Dalagdag, Kalumbibit, Kamot-kabag; Tha.:
Sawad; Vie.: Điệp mắt mèo, Móc mèo.
Description: It is a large, flowering, straggling, very thorny shrub, from the Senna
family with pantropical distribution, found in India in Bengal, Mumbai and southern
India. It reaches a length of 6 m, scrambles over other vegetation, has large leaves
and its gray seeds are like lima beans, only larger, and are called Nickernuts, that are
buoyant and tough enough to survive ocean currents and dispersed by it. Its Hindi
and Marathi names Sagargota are a testament to it; the branches are armed with
hooks and straight, hard yellow prickles [7] (Figs. 1, 2 and 3).
Actions and Uses: The nuts and root-bark are described as antiperiodic,
antispasmodic, bitter-tonic, anthelmintic and febrifuge; powdered seeds as tonic,
febrifuge and antiperiodic; leaves as deobstruent and emmenagogue, and the root as

Fig. 1 Caesalpinia bonduc, Leaves, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Caesalpinia_bonduc_leaves_1.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Caesalpinia bonduc (L.) Roxb. 485

Fig. 2 Caesalpinia bonduc, Racème, Guadeloupe, Pancrat, WikimediaCommons; ShareAlike 2.5

Generic, 2.0 Generic and 1.0 Generic license, https://commons.wikimedia.org/wiki/File:Caesalpinia_
bonduc_inflo.jpg; https://creativecommons.org/licenses/by-sa/2.5/deed.en

Fig. 3 Caesalpinia bonduc, Fruits with Seeds, Louise Wolff (darina), WikimediaCommons;
ShareAlike 2.5 Unported CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Cayos_pict088.
jpg; https://creativecommons.org/licenses/by-sa/2.5/deed.en

gastric tonic.CV In Ayurveda, the plant is used to treat various diseases, specifically
tumors, cysts and cystic fibrosis [1]; leaves mitigate Kapha and Vata, are anthel-
mintic, emmenagogue and febrifuge, and are useful in piles, intestinal worms,
elephantiasis, splenomegaly, hepatomegaly, amenorrhea, dysmenorrhea, pharyn-
godynia, and fevers [17], and the traditional Siddha healers of Malabar region use
its leaves for treatment of psoriasis [18]. Ibn al-BaitarLXIX described hazel nut
(Corylus avellana or nuts of other species of Corylus) as Bunduq or bundaq, with
486 Caesalpinia bonduc (L.) Roxb.

Jalooz and Fundaq as Arabic names, and Bunduq, Badam-kohi, and Badam-
Kashmiri as Persian names, and quotes Galen for its properties similar to walnut. It
is not digested easily and produces flatulence and borborygmi or stomach rumble.
In Unani medicine, the fruit is aphrodisiac, expectorant and nerve tonic, and its uses
are similar to almond for nutrition and mental weakness.LXXVII The properties and
the scientific studies mentioned here are of C. bonduc and not of hazelnut or
Bunduq except in Unani context. The kernels are bitter tonic, antiperiodic and
anthelmintic; while the juice of fresh leaves and powdered seeds are antipyretic,
used in periodic fevers. Powdered seeds mixed with black pepper are also used as
alterative tonic in general debility, and to check hemorrhage.LXXXI In Hawaii, half a
ground bean (seed) is given twice daily to 20-days old babies with constitutional
debility, as a laxative; the dose is increased to one bean for 40–80-days old babies,
and to two beans for one year or older. Beans are also used as blood purifier, and to
clear chest of tough sticky phlegm.LXXVI It is an ingredient in remedies for parasitic
diseases, used by traditional healers of southern border provinces of Thailand [14].
In the Philippines, seeds are considered a good remedy for stomach troubles, and a
mild purgative,CXVII and as powder, tonic and febrifuge.LVI This species has been
declared extinct in the wild, but is still grown in home gardens for medicinal use of
its seeds, roots, and leaves in the West African nation of Benin [19]. It is tradi-
tionally used to treat snakebites in the West African nation of Ivory Coast [3], and
as anticancer drug in other African traditional medicines [4].
Phytoconstituents: Seeds contain a bitter substance named bonducin, phy-
tosterinin, fatty acids, caesalpins (a, b, c, d and w), bonducellin and citrulli-
ne.CXXVIII Ethanol and methanol seed extracts show the presence of cardiac
glycosides [24]. Cassane diterpenes, neocaesalpins C, D [11], bondenolide [23],
neocaesalpin P, neocaesalpin H, cordylane A, caesalpinin B, bonducellpin E,
caesalpinolide A, and 17-methylvouacapane-8(14),-9(11)-diene [2], caesalpinolide-
C, D and E, and one cassane furanoditerpene from seeds [28], three cassane
furanoditerpenoids with good antimalarial activity against MDR K1 strain of
P. falciparum, and many cassane diterpenoids [26, 27] from seed kernel [18], and
thirty different fatty acids, with 8 saturated and 22 unsaturated, were extracted
from nonpolar fraction of seeds [21]. Ten new cassane-type diterpenoids, caesal-
bonducins D–F, 6-deacetoxybonducellpin B, 3-acetoxy-a-caesalpin, 2(3)-en-a-
caesalpin, 1a-hydroxycaesalpinin J, 1a-hydroxy-6-decaetoxysalpinin J, 6a-hydro
xycaesall M, and 6a-hydroxy-14(17)-dehydrocaesalpin F were isolated from peri-
carps [29], and 17-hydroxy-campesta-4,6-dien-3-one, and 13,14-seco-stigmasta-
5,14-dien-3alpha-ol, 13,14-seco-stigmasta-9(11),14-dien-3alpha-ol, caesaldekarin J
and pipataline were isolated from bark [25]. Seven cassane diterpenes, including
caesaldekarin A, were isolated from roots [12]. Cytotoxic flavonoids have been
isolated from young twigs and leaves [15].
Pharmacology: Seed-coat as well as kernel’s ethanol extracts show significant
antistress activity and efficiently control hyperlipidemic condition due to stress in
rats [9], and the seed coat extract exhibits analgesic and anti-inflammatory activities
[10]. Hydromethanol extract of dried seeds administered orally for 21-days
Caesalpinia bonduc (L.) Roxb. 487

significantly restored activities of carbohydrate metabolic enzymes and corrected

FBG and glycogen levels, and improved activities of antioxidant enzymes in diabetic
rats, comparable to effects of glibenclamide [7]. The extract also exhibited strong
radical scavenging activity and inhibition of LPO [8]. Methanol seed extract exhibits
significant antibacterial activity against S. aureus, Sh. flexneri, S. typhi, S. paratyphi,
S. typhimurium, P. vulgaris, K. pneumoniae and E. aerogenes; whereas ethanol
extract was active against E. coli, S. typhi, S. paratyphi, S. typhimurium, K. pneu-
moniae and S. flexneri [24]. Hydroalcohol extracts of seed kernel and seed coat
show antibacterial activity against sensitive and methicillin resistant S. aureus and
ampicillin resistant P. aeruginosa, and the kernel extract also caused significant
bacterial clearance from lungs and less severe incidence of lung abscess in rats
injected with P. aeruginosa [1]. Hot alcohol extract inhibits growth of P. falciparum
by 76% [6]. Petroleum ether and ethanol leaf extracts are hundred percent larvicidal
to C. quinquefasciatus [20]. Aqueous, ethanol and chloroform extracts possess
significant free radical scavenging activity and significantly inhibit aldose reductase
enzyme, and exhibit anticataract activity [5]. Aqueous fraction of hydroalcohol leaf
extract shows significant antipsoriatic activity [13], and aqueous seed extract also
showed in vivo immunomodulatory activity [22].
Human A/Es, Allergy and Toxicity: It causes constipation and headache.LXXVII
Animal Toxicity: Ethanol extract of leaves and young twigs administered orally to
rats up to a single of 5,000 mg/kg body weight, and administered daily for 28-days
in doses from 200 to 1,600 mg/kg body weight was nonfatal, but caused significant
alterations in the biomarkers of liver damage [16].
Commentary: There are no clinical studies reported in journals listed on PubMed.

References
1. Arif T, Mandal TK, Kumar N, et al. In vitro and in vivo antimicrobial
activities of seeds of Caesalpinia bonduc (Lin.) Roxb. J Ethnopharmacol.
2009;123:177–80.
2. Ata A, Udenigwe CC, Gale EM, Samarasekera R. Minor chemical
constituents of Caesalpinia bonduc. Nat Prod Commun. 2009;4:311–4.
3. Datté JY, Yapo PA, Kouamé-Koffi GG, et al. Leaf extract of Cae-
salpinia bonduc Roxb. (Caesalpiniaceae) induces an increase of contractile
force in rat skeletal muscle in situ. Phytomedicine. 2004;11:235–41.
4. Erharuyi O, Engel-Lutz N, Ahomafor J, et al. Anticancer activity of five
forest crops used in African folklore: antiproliferative and proapoptotic
effects. Nat Prod Res. 2014 (Epub ahead of print).
5. Gacche RN, Dhole NA. Aldose reductase inhibitory, anticataract and
antioxidant potential of selected medicinal plants from the Marathwada
region, India. Nat Prod Res. 2011;25:760–3.
6. Irshad S, Mannan A, Mirza B. Antimalarial activity of three Pakistani
medicinal plants. Pak J Pharm Sci. 2011;24:589–91.
488 Caesalpinia bonduc (L.) Roxb.

7. Jana K, Chatterjee K, Ali KM, et al. Antihyperglycemic and antioxidative

effects of the hydromethanolic extract of the seeds of Caesalpinia bonduc on
streptozotocin-induced diabetes in male albino rats. Pharmacognosy Res.
2012;4:57–62.
8. Jana K, Chatterjee K, Ali KM, et al. Antioxidant potential of hydromethano-
lic extract of seed of Caesalpinia bonduc: an in vitro study. J Adv Pharm
Technol Res. 2011;2:260–5.
9. Kannur DM, Hukkeri VI, Akki KS. Adaptogenic activity of Caesalpinia
bonduc seed extracts in rats. J Ethnopharmacol. 2006;108:327–31.
10. Kannur DM, Paranjpe MP, Sonavane LV, Dongre PP, Khandelwal KR.
Evaluation of Caesalpinia bonduc seed coat extract for anti-inflammatory
and analgesic activity. J Adv Pharm Technol Res. 2012;3:171–5.
11. Kinoshita T. Chemical studies on the Philippine crude drug calumbibit
(seeds of Caesalpinia bonduc): the isolation of new cassane diterpenes
fused with alpha, beta-butenolide. Chem Pharm Bull (Tokyo). 2000;48:
1375–7.
12. Lyder DL, Peter SR, Tinto WF, et al. Minor cassane diterpenoids of Caesal-
pinia bonduc. J Nat Prod. 1998;61:1462–5.
13. Muruganantham N, Basavaraj KH, Dhanabal SP, et al. Screening of
Caesalpinia bonduc leaves for antipsoriatic activity. J Ethnopharmacol.
2011;133:897–901.
14. Neamsuvan O, Tuwaemaengae T, Bensulong F, Asae A, Mosamae K. A survey
of folk remedies for gastrointestinal tract diseases from Thailand’s three
southern border provinces. J Ethnopharmacol. 2012;144:11–21.
15. Ogunlana OO, He WJ, Fan JT, et al. Report: cytotoxic flavonoids from the
young twigs and leaves of Caesalpini bonduc (Linn) Roxb. Pak J Pharm
Sci. 2015;28:2191–8.
16. Ogunlana OO, Ogunlana OE, Adeneye AA, et al. Evaluation of the
toxicological profile of the leaves and young twigs of Caesalpinia bon-
duc (Linn) Roxb. Afr J Tradit Complement Altern Med. 2013;10:504–12.
17. Prasad GP, Trimurtulu G, Reddy KN, Naidu ML. Analytical study of
Kuberaksha/Kantaki Karanja Patra Churna [Caesalpinia Bonduc (L.) Roxb.
leaf powder]. Ayu. 2010;31:251–4.
18. Pudhom K, Sommit D, Suwankitti N, Petsom A. Cassane furanoditer-
penoids from the seed kernels of Caesalpinia bonduc from Thailand. J Nat
Prod. 2007;70:1542–4.
19. Quiroz D, Towns A, Legba SI, et al. Quantifying the domestic market in
herbal medicine in Benin, West Africa. J Ethnopharmacol. 2014;151:1100–8.
20. Saravanan KS, Periyanayagam K, Ismail M. Mosquito larvicidal properties
of various extract of leaves and fixed oil from the seeds of Caesalpinia bon-
duc (L) Roxb. J Commun Dis. 2007;39:153–7.
21. Shameel S, Usmanghani K, Ali MS, Ahmad VU. Caesalpinia bonduc (L.)
Roxb. seed oil: lipid composition assessment. Pak J Pharm Sci. 1997;10:
29–38.
Caesalpinia bonduc (L.) Roxb. 489

22. Shukla S, Mehta A, Mehta P, Vyas SP, Shivaprasad HN. In vivo immunomod-
ulatory activities of the aqueous extract of bonduc nut Caesalpinia bonducella
seeds. Pharm Biol. 2010;48:227–30.
23. Simin K, Khaliq-Uz-Zaman SM, Ahmad VU. Antimicrobial activity of
seed extracts and bondenolide from Caesalpinia bonduc (L.) Roxb. Phy-
tother Res. 2001;15:437–40.
24. Tambekar DH, Khante BS, Chandak BR, et al. Screening of antibacterial
potentials of some medicinal plants from Melghat forest in India. Afr J
Tradit Complement Altern Med. 2009;6:228–32.
25. Udenigwe CC, Ata A, Samarasekera R. Glutathione S-transferase inhibiting
chemical constituents of Caesalpinia bonduc. Chem Pharm Bull (Tokyo).
2007;55:442–5.
26. Wu L, Luo J, Zhang Y, et al. Cassane-type diterpenoids from the seed
kernels of Caesalpinia bonduc. Fitoterapia. 2014;93:201–8.
27. Wu L, Wang X, Shan S, Luo J, Kong L. New cassane-type diterpenoids
from Caesalpinia bonduc. Chem Pharm Bull (Tokyo). 2014;62:729–33.
28. Yadav PP, Maurya R, Sarkar J, et al. Cassane diterpenes from Caesalpinia bon-
duc. Phytochemistry. 2009;70:256–61.
29. Zhang P, Tang C, Yao S, et al. Cassane diterpenoids from the pericarps of
Caesalpinia bonduc. J Nat Prod. 2016;79:24–9.
Cannabis sativa L.
(Cannabaceae)

(Syn.: C. indica Lam.)

Abstract
A strong-smelling, annual herb that grows in China, India, Afghanistan, Iran,
Indonesia, North Africa, and cultivated in many countries. Cannabis plant has
been known to humanity for over 6000 years for its medicinal uses, as a remedy
for pain, diarrhea and inflammation, and for autoimmune diseases like rheumatoid
arthritis. In Sanskrit, Bhanga and Indrasana (Indra’s hemp) is mentioned along
with the Vedic plant Janjida, which has magic and medicinal properties, and
which is described in Atharvaveda. The gods are said to have three times created
this herb. The Greeks were acquainted with hemp more than 2000 years ago.
Herodotus mentioned it as being cultivated by the Scythians, who used its fiber for
making their garments, and seeds to medicate vapor baths. Dioscorides mentioned
that if seeds are eaten too freely, they destroy the virile power. Galen described
seeds as carminative and antiflatulence, and the fresh seeds’ water as ear drops in
ear diseases. Razi said that it produces headache and weakens eyesight. In Sicily,
the peasant women believed in hemp as an infallible means of attaching their
sweethearts. Cannabis seeds are described as a superior drug in the Chinese classic
The Herbal. Seeds are considered nutritive tonic with vermifuge and emollient
properties, and are used for the treatment of constipation and internal heat of
intestines. All parts of the plant are intoxicating, stomachic, antispasmodic,
analgesic, stimulant, aphrodisiac, and sedative. The resinous exudate, charas, is a
powerful narcotic, and is chiefly used in cases of mania and hysteria. Amber-
colored resin obtained from flowering tops and leaves of the female hemp plant
contains most of the active principle, Δ-9-tetrahydrocannabinol (THC). THC
is the most psychoactive of the 100 or so of the plant’s 21-carbon–containing
terpenophenolic compounds known as cannabinoids.

Keywords






Ananda Bhâng Cannabis Cañamón Chanvre Dàmáshǔ Ganja Hennep





Hint keneviri Siddhi

© Springer Nature Switzerland AG 2020 491

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_52
492 Cannabis sativa L.

Vernaculars: Urd.: Bhâng; Hin.: Bhâng, Charas (resin), Ganja (flowering and
fruiting tops of female plant), Sabji (leaves), Siddhi; San.: Ananda, Bhanga,
Chapola, Charma (resin), Dnayana vardhani, Harasini, Indrasana, Mahini (leaves),
Siddhapatri, Vajaya, Vriga patta; Ben.: Bhâng (leaves), Charas (resin), Ganja, Jia;
Mal.: Cherukanchava, Ganji palu (resin), Ginjilachilachi, Kanchavu, Lacki (leaves);
Mar.: Bhamgi, Bhang, Bhangâ-châ-pana, Ganja; Tam.: Bangi-elai (leaves), Gan-
japal (resin), Kanja, Madamattagam, Pangi; Tel.: Ganjari-chettu, Ganjayi, Jada-
ganja; Ara.: Nabâtul (leaves), Qinnab, Hashish (resin); Bur.: Segiyav; Chi.: 大麻,
Dàmáshǔ, Ta-ma-jen, Ye ma; Cze.: Konopí seté Dan.: Hamp; Dut.: Gewone hen-
nep, Hennep; Eng.: Cannabis, Hashish, Indian hemp, Marijuana, Mary jane; Fin.:
Hamppu; Fre.: Chanvre, Chanvre commun, Chanvre cultivé; Ger.: Gebauter hanf,
Gewöhnlicher hanf; Ita.: Canapé, Jap.: Asa, Mashinin; Nep.: Cares, Gajima, Ganja;
Nor.: Hamp; Per.: Bang (leaves), Kinnah (resin), Shahdanah (seeds); Pol.: Konopie
siewne; Por.: Cânhamo-comum, Maconha (Br.); Spa.: Cáñamo, Cáñamo común,
Cañamón; Swe.: Hampa; Tag.: Marihuana; Tha.: Porkanchaa; Tur.: Hint keneviri.
Description: A strong-smelling, annual herb that grows in China, India, Afghani-
stan, Iran, Indonesia, North Africa, and cultivated in many countries. Stem erect,
woody, rough, 1–3 m tall; leaves opposite, sometimes alternate at the top of the plant,
compound palmate: leaflets 3–7, acute, dentate, provided with persistent stipules.
Seeds are ovoid, 5 mm long and 3 mm in diameter, beige, glossy, sweet in taste with
aromatic odor.LXXIX Seeds are used medicinally and are called Bazar-ul-qinnab in
Arabic, and the resinous matter on the leaves, stems and fruits is called Charas in India.
Charas is of dark-green or brown color with a powerful odor, but little taste.CV The
plant attains its highest therapeutic value when grown in tropical or subtropical cli-
mates, maximizing the resin content, and harvested before becoming fully ripe, to
avoid seedling. Seeds quickly lose their germinating power and should not be more
than one season old (Figs. 1 and 2).CV

Fig. 1 Cannabis sativa, Plant, Chmee2, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA
3.0, https://commons.wikimedia.org/wiki/File:Cannabis_sativa_plant_(4).JPG; https://creativecomm
ons.org/licenses/by-sa/3.0/deed.en
Cannabis sativa L. 493

Fig. 2 Cannabis sativa, Flowers of hybrid Cannabis indica, Psychonaught, WikimediaCommons,

https://commons.wikimedia.org/wiki/File:Sativa.jpg

Actions and Uses: Cannabis plant has been known to humanity for over 6000 years
for its medicinal uses, as a remedy for pain, diarrhea and inflammation [19], and for
autoimmune diseases like rheumatoid arthritis [14]. In Sanskrit, Bhanga and Indra-
sana (Indra’s hemp) is mentioned along with the Vedic plant Janjida, which has magic
and medicinal properties, and which is described in Atharvaveda. The gods are said to
have three times created this herb.XL The Greeks were acquainted with hemp more
than 2000 years ago. Herodotus mentioned it as being cultivated by the Scythians,
who used its fiber for making their garments, and seeds to medicate vapor baths.
Dioscorides mentioned that if seeds are eaten too freely, they destroy the virile
power.XL Galen described seeds as carminative and antiflatulence, and the fresh seeds’
water as ear drops in ear diseases. Razi said that it produces headache and weakens
eyesight.LXIX In Sicily, the peasant women believed in hemp as an infallible means of
attaching their sweethearts.XL Cannabis seeds are described as a superior (noble,
harmless) drug in the Chinese classic The Herbal (compiled 25–220 A.D.) by the
emperor Shen Nung, who lived 2800 B.C. Seeds are considered nutritive tonic with
vermifuge and emollient properties, and are used for the treatment of constipation and
internal heat of intestines.LXV All parts of the plant are intoxicating, stomachic,
antispasmodic, analgesic, stimulant, aphrodisiac, and sedative. The resinous exudate,
charas, is a powerful narcotic, and is chiefly used in cases of mania and hysteria.CV It is
analgesic, soporific, reduces excitement, and increases sexual retention; thus mainly
used for sexual weakness and nocturnal emissions.1 In India, Bhang or Ganja are
prescribed by Hakims and Vaids (practitioners of traditional Indian medicines) in

1
Tayyab M: Personal Communication.
494 Cannabis sativa L.

bowel complaints, as appetizers, nervous stimulant, and as a source of great staying

power under severe exertion or fatigue.CV Tharu tribe of Gonda and Baharaich dis-
tricts (India) treats piles by wrapping leaves in a piece of cloth, warming it slightly, and
then pressing on the outgrown mass of hemorhoids at bedtime [20]. Seeds are tonic and
emollient, and do not possess any marijuana activity.LXXIX Currently cannabis is
being clinically studied for treatment of diseases like multiple sclerosis, epilepsy,
dystonia, chronic pain, and inflammatory conditions, rheumatoid arthritis and Crohn’s
disease [19].
Abrams [2], the oncologist at University of San Francisco asserts that only
cannabis is an effective antiemetic in cancer patients, where other pharmaceuticals
have failed, and the only antiemetic that is also orexigenic. It is also effective in a
number of neuropathic pain syndromes, and many cancer patients decrease their
dose of narcotics or wean off of them with the addition of cannabis to their regimen.
Some patients claim to have cured their cancer by using highly concentrated oil
extractions of cannabis, enriched for THC, CBD, or both. Dr. Abrams [2] says “If
I have a single medicine that I can recommend to assist with nausea, anorexia,
insomnia, depression, and pain rather than prescribing five or six pharmaceuticals
that may interact with each other or the patient’s chemotherapy, I consider it an
attractive option for my patients”.
Recreational Use: As it is called, the “trip” after smoking marijuana begins by
feeling of inner joy (euphoria) that is out of proportion to reality and is described as
being high. The user may “trip off” and be quiet and drowsy when alone, or may sit
and experience colored illusions as the toxicity increases; some may experience
phantasmagoria—the sensation that figures are rushing toward him at tremendous
speed, increasing in size as they approach. With company, the user may feel relaxed,
uninhibited and at ease and more self-confident, becomes talkative and hilarious,
with altered perception of time and space, with impaired intellectual capacities.
Some may experience, what is known as a “bring down,” a “downer,” or a “bum-
mer” instead of euphoria, when the user may become anxious, irritated, slightly
paranoid, and apprehensive. At high enough dose, confusion, disorientation and fear
of death may set in. The trip lasts from three to five hours, followed by slight
lethargy and hunger [7]. After ingestion, the subject experiences feeling of euphoria
and exaltation with extravagant dream fantasies and loses his sense of time; the effect
is transitory and wears off in 3–5 h, though it may persist for 12 h or more with no
lasting ill-effects [16].
In the late 1960s and 1970s, the extensive use of marijuana in the United States
was associated with experimentation with many other drugs: LSD, mescaline,
amphetamines, barbiturates, and hashish [8]. A typical marijuana user in the 1970s
had strong political opinions, used alcohol, engaged in risky behaviour, and sought
stimulation [13]. Charalampous [10] opined that “weak preparations of cannabis
may not be detrimental to the health of the user, but potent preparations like
purified hashish, after prolonged use, can be expected to cause damage.” Chun [12]
also reported “when domestic strength marijuana is smoked recreationally, the sub-
jective effects include relaxation, mild euphoria and increased sensory awareness.
Cannabis sativa L. 495

The objective effects include tachycardia, reddening of the conjunctivae and a

distorted sense of time. Undesirable effects such as panic reactions, amotivational
behaviour, and acute toxic psychosis occur infrequently and are reversible with proper
therapy. Other effects which have been attributed to marijuana are unsubstantiated.”
Phytoconstituents: Amber-colored resin obtained from flowering tops and leaves of
the female hemp plant contains most of the active principle, Δ-9-tetrahydrocanna
binol (THC). THC is the most psychoactive of the 100 or so of the plant’s 21-carbon–
containing terpenophenolic compounds known as cannabinoids. However, the psy-
chotoxic activity produced by the plant seems to be due to composite effect of its
individual components. Hence, various samples of the crude material vary consid-
erably in potency and effect [7]. Cannabidiol (CBD) and cannabinol, and a highly
effective compound similar to THC were isolated from natural source [3]. Some
studies suggest that C. indica has higher levels of THC to CBD, whereas C. sativa
has higher levels of CBD compared to THC.
Pharmacology: Cannabidiol has shown significant anticonvulsant effects in ani-
mal models of seizures [18].
Legal Status: In the United States any drug covered by the Harrison Narcotic Act
of 1914 is considered a narcotic, though marijuana is not medically considered to be
a narcotic, but a true hallucinogen which possesses elements of both stimulation
and depression [21], and is classified as a Schedule I substance with no therapeutic
utility. National Institute on Drug Abuse (NIDA) is the only legal source of can-
nabis for research in the United States, but it has a congressional mandate to study
substances of abuse only as substances of abuse and not as therapeutic interven-
tions, thus legally obstructing any controlled clinical trials. Cannabis was removed
from the US Pharmacopeia in 1942 [2].
Clinical Studies: In one of the early double-blind crossover trials, eight volunteers
showed clear decrement in performance on motor and mental tasks after smoking
cannabis [5].
CBD is believed to be analgesic and anti-inflammatory but is not psychoactive.
Synthetic THC (dronabinol; MarinolR) is available as a licensed medicine in the
United States for the treatment of chemotherapy-induced nausea and vomiting
(CINV) since 1986. Its indication was expanded in 1992 to include treatment of
anorexia associated with the AIDS wasting syndrome [2]. When cannabis is
inhaled, either as combusted or vaporized plant matter, the peak concentration of
THC occurs in 2–5 min, with a rapid drop-off. When ingested by mouth, the oral
bioavailability is low and variable, estimated to be 5–20% of the ingested dose. In
studies conducted, the peak plasma concentration of THC taken by mouth was
achieved at 2.5 h and declined much more slowly. Terminal half-life of orally
ingested THC is 25–30 h, and when Δ-9-THC passes through liver it is metabolized
into a psychoactive 11-hydroxy-THC, which may be even more psychoactive than
the Δ-9-THC. This is why people eating cannabis-baked products or capsules report
a more significant psychoactive effect compared with those who inhale it. If a
496 Cannabis sativa L.

patient wants better control over the onset, depth, and duration of the effect,
inhalation may be the better mode of delivery. However, for sustained effects or
overnight benefits, oral ingestion may be a more convenient mode of delivery than
inhalation, once proper dosing has been ascertained [2].
Mechanism of Action: Principal site of action of C. indica is the brain, particularly
the cerebral cortex; it causes excitation in some cases, and depression of higher
functions in others [4, 11, 16]. Cannabinoids activate cannabinoid receptors, par-
ticularly CB1 found predominantly in CNS, and CB2 found predominantly in cells
involved with immune function [1].
Abuse Potential: Marijuana’s abuse pattern includes psychological dependence,
some tolerance and certain undesirable side effects, such as depression of BP and
respiration, the hypoglycemia that increases the user’s appetite, engorgement of
ciliary vessels, pupillary dilatation, oropharyngitis, and chronic bronchitis, and
asthma may result from continued use [7]. Bensusan [6] described his encounter with
three males and two females, aged 19–29 years, in the south-west African desert,
who suffered from anxiety symptoms and restlessness, with acute abdominal cramps,
nausea, sweating, increased pulse rate but no fever, low BP, and muscular aches.
There was no loss of appetite, rather a craving for sweets and particularly chocolate.
These individuals were later identified to suffer from marijuana withdrawal.
Human A/Es, Allergy and Toxicity: Dust in a factory processing soft hemp can
cause byssinosis and at least temporary impairment of ventilatory function, varying
in severity according to the level of dust exposure and the presence of respiratory
disease [22]. Habitual use of marijuana leads to indigestion, weight loss, melan-
cholia, impotence,CV headache and eyesight weakness.LXXVII In large doses, it first
produces mental exhilaration, intoxication, a sense of double consciousness, and
finally loss of memory and gloominess.CV Cannabis smoking causes symptoms of
chronic bronchitis, can weaken immune system leading to pneumonia [23]. Cere-
bral atrophy was reported in ten male patients, average age 22 years, who con-
sistently smoked cannabis over a period of 3–11 years [9]. An 18-year-old Indian
male ate food containing C. indica, had difficulty in turning his eyes to the left, and
until after a week his eyes remained fixed in dextroverted position; all ocular
movements were absent, but the fundi were normal. The patient was given vitamin
B1 and B12 intramuscularly, and he slowly but completely recovered after about
6-weeks with no residual weakness of extraocular muscles [18].
Animals Toxicity: Delta-9-tetrahydrocannabinol administered to rats, either i.p. or
orally daily for 70-days, ate significantly less and gained significantly less weight [17].
Commentary: Despite being a controversial plant due to its recreational use and/or
abuse potential, the plant potentially offers some unique clinical benefits that should
be fully explored in an unbiased and objective manner.
Cannabis sativa L. 497

References
1. Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther.
2015;97:575–86.
2. Abrams DI. Using medical cannabis in an oncology practice. Oncology
(Williston Park). 2016;30:397–404.
3. Adams R. The Harvey Lectures 1941–1942, series 37, 1942, p. 168.
4. Allentuck S. In: The marihuana problem in the city of New York. Lancaster:
Jaques Cattell Press; 1944, p. 35.
5. Anonymous. New research on cannabis. Br Med J. 1971;2:293–4.
6. Bensusan AD. Marihuana withdrawal symptoms. Br Med J. 1971;3:112.
7. Bloomquist ER. Marijuana: social benefit or social detriment? Calif Med.
1967;106:346–53.
8. Brill NQ. The marijuana problem. Calif Med. 1971;114:55–7.
9. Campbell AM, Evans M, Thomson JL, Williams MJ. Cerebral atrophy in
young cannabis smokers. Lancet. 1971;2:1219–24.
10. Charalampous KD. Drug culture in the seventies. Am J Public Health.
1971;61:1225–8.
11. Chopra RN, Chopra GS, Chopra IC. Indian J Med Res. 1942;30:155.
12. Chun G. Marijuana: a realistic approach. Calif Med. 1971;114:7–13.
13. Crumpton E, Brill NQ. Personality factors associated with frequency of
marijuana use. Calif Med. 1971;115:11–5.
14. Katz D, Katz I, Golan A. Medical cannabis—a source for a new treatment
for autoimmune disease? Harefuah. 2016;155:74–78, 133.
15. Lippiello P, Balestrini S, Leo A, et al. From cannabis to cannabidiol to treat
epilepsy, where are we? Curr Pharm Des. 2016;22:6426–33.
16. Loewe S. In: The marihuana problem in the city of New York. Lancaster:
Jaques Cattell Press; 1944, p. 149.
17. Manning FJ, McDonough JH Jr, Elsmore TF, Saller C, Sodetz FJ. Inhibition
of normal growth by chronic administration of delta-9-tetrahydrocannabinol.
Science. 1971;174:424–6.
18. Mohan H, Sood GC. Conjugate deviation of the eyes after Cannabis indica
intoxication. Br J Ophthalmol. 1964;48:160–1.
19. Naftali T. Medical Cannabis. Harefuah. 2016;155:79–82, 133 (Article in
Hebrew).
20. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
21. Solursh LP, Clement WR. Hallucinogenic drug abuse: manifestations and
management. Can Med Assoc J. 1968;98:407–10.
22. Valić F, Zuskin E, Walford J, Kersić W, Pauković R. Byssinosis, chronic
bronchitis, and ventilatory capacities in workers exposed to soft hemp dust.
Br J Ind Med. 1968;25:176–86.
23. Yayan J, Rasche K. Damaging effects of cannabis use on the lungs. Adv
Exp Med Biol. 2016;952:31–4.
Capparis spinosa L.
(Capparaceae)

(Syn.: Blumea grandiflora Zipp. ex Span.)

Abstract
The plant was mentioned by both Greek and Latin writers, who introduced it to
Arabs, and through Muslim physicians it was introduced to India. A perennial
prostrate, glabrescent, winter-deciduous climbing shrub, that grows on bare
rocks, crevices, cracks and sand dunes. It grows spontaneously in wall joints of
antique Roman fortresses, on the Western Wall of Jerusalem’s Temple Mount,
and on the ramparts of the castle of Santa Bárbara (Alicante, Spain). The plant is
best known for the edible flower buds, often used as a seasoning, and the fruit,
both of which are usually consumed pickled. In Iran, the fruit is traditionally
used as an antihyperglycemic food by diabetic patients, and also in Israel, as
antihyperglycemic agent. In the Mediterranean basin and in central and west
Asia, fruits are widely used as food and in folk medicines. It is assumed that
capers had been used in China thousands of years ago, as its seed clumps have
been unearthed in the Yanghai Tombs, Turpan District in Xinjiang. In southern
Italy, decoction of roots is widely used in the traditional folk medicine. Unani
physicians of Indian subcontinent mainly use the root bark for neurogenic and
phlegmatic conditions, such as paresthesia, paralysis, arthritis, gout, sciatica,
cough, dropsy, and inflammation of spleen and lymphatic glands. Capers contain
glucosinolates, polyphenols, alkaloids, lipids, vitamins, minerals, saccharides,
glycosides, terpenoids, volatile oils, fatty acids and steroides. Aqueous fruit
extract has shown significant anti-inflammatory activity, and hydroalcohol
extract demonstrated significant antiarthritic activity. Powdered root, decoction
and hydroethanol root extract significantly increased threshold to articular pain
in rats. Methanol leaf extract was protective against cisplatin-nephrotoxicity and
CCl4-hepatotoxicity in animals. Caper fruit extract, as adjunct to standard
antidiabetic therapy, improved glycemic control of patients with type-2 diabetes.

© Springer Nature Switzerland AG 2020 499

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_53
500 Capparis spinosa L.

Keywords







Alcaparrón Assaf Caper Câpre Ci shan gan Himsra Kabar-karak Karu




Kebere Kibr

Vernaculars: Urd.: Kibr; Hin.: Kabra, Karer (oil), Karu; San.: Cabra, Himsra,
Kakadani-karira; Ben.: Kabra; Tel.: Kobilakshamu, Kokilakshmu; Ara.: Assaf,
Kabar, Kiabara, Lasaf, Malaath, Shaflah, Wardul-jabal; Bul.: Kapersi; Chi.: 刺山柑,
Ci shan gan; Cze.: Kapara; Dan.: Kapers; Dut.: Gewone kapperstruik, Kappertjes;
Eng.: Caper, Caper bush; Fin.: Kapris, Kaprispensas, Pyörökapris; Fre.: Câpre,
Câprier commun, Câprier épineux, Fabagelle; Ger.: Gemeiner Kapernstrauch,
Kaper; Gre.: Kappari; Ita.: Cappero comune; Jap.: Keipa; Kor.: Ke-i-peo; Maly.:
Melada; Nor.: Kapers; Per.: Kabar-karak (fruit); Pol.: Kapar ciernisty; Por.: Alca-
parras, Alcaparreira-comum; Rus.: Kapersy; Spa.: Alcaparra, Alcaparrón, Caparra,
Tápana; Swe.: Kapris, Vanlig kapris; Tag.: Alcaparras; Tur.: Kebere; Vie.: Cáp.
Description: The plant was mentioned by both Greek and Latin writers, who
introduced it to Arabs, and through Muslim physicians it was introduced to India.XL
A perennial prostrate, glabrescent, winter-deciduous climbing shrub, many-
branched, with divaricate light-yellow thorns, and alternate fleshy leaves, thick
and shiny, round to ovate in shape. Flowers are complete, sweetly fragrant, showy,
with four sepals, and four white to pinkish-white petals, many long violet-colored
stamens, and a single stigma usually rising well above the stamens. It grows on bare
rocks, crevices, cracks and sand dunes in Pakistan, Central Asia, Himalayas, East
Africa, Madagascar, in dry calcareous escarpments of the Adriatic region, in dry
coastal ecosystems of Egypt, Libya and Tunisia, in transitional zones between the
littoral salt marsh and the coastal deserts of the Asian Red Sea coast, in the rocky arid
bottoms of the Jordan valley, in calcareous sandstone cliffs at Ramat Aviv, Israel,
and in central west and northwest coastal dunes of Australia. It grows spontaneously
in wall joints of antique Roman fortresses, on the Western Wall of Jerusalem’s
Temple Mount, and on the ramparts of the castle of Santa Bárbara (Alicante, Spain).
Clinging caper plants are dominant on the medieval limestone-made ramparts of
Alcudia, and the bastions of Palma (Majorca, Spain) (Figs. 1, 2 and 3).
Actions and Uses: The plant is best known for the edible flower buds (Capers), often
used as a seasoning, and the fruit (Caper berry), both of which are usually consumed
pickled. In Iran, the fruit (Caper) is traditionally used as an antihyperglycemic food by
diabetic patients [17], and also in Israel, as antihyperglycemic agent [35]. In the
Mediterranean basin and in central and west Asia, fruits are widely used as food and in
folk medicines [36]. It is assumed that capers had been used in China thousands of
years ago, as its seed clumps have been unearthed in the Yanghai Tombs, Turpan
District in Xinjiang [18]. In southern Italy, decoction of C. spinosa roots is widely
used in the traditional folk medicine [6]. The root bark (temperament, hot 3° and dry
3°) is described as detergent and astringent, expelling cold humours,XL deobstruent,
expectorant, analgesic, stomachic, appetite stimulant, carminative, anthelmintic,
aphrodisiac, emmenagogue, and diuretic, and mainly used for neurogenic and
Capparis spinosa L. 501

Fig. 1 Capparis spinosa, Leaves and Buds, Lazaregagnidze, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:%E1%83%99%E1%83%90%E1%83%9E%E1%83%90%E1%83%A0%
E1%83%98_Capparis_spinosa_Kapernstrauch.JPG

Fig. 2 Capparis spinosa, Flower (Nahal Neqarot, Israel), Mark A. Wilson, WikimediaCommons,
https://commons.wikimedia.org/wiki/File:Capparis_spinosa_Negev.JPG
502 Capparis spinosa L.

Fig. 3 Capparis spinosa, Ripe Caper Fruit (Berry), Clematis, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Capparis_fruit.JPG;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

phlegmatic conditions, such as paresthesia, paralysis, arthritis, gout, sciatica, cough,

dropsy, and inflammation of spleen and lymphatic glands. Leaves juice is dropped into
ear to kill worms, and the root bark powder is applied to malignant sores, boils and
swellings; fruits have similar but weaker properties.LXIX,LXXVII,LXXXI NadkarniCV
mentioned its uses in palsy, dropsy, gout and rheumatism. In Ayurveda, the dried
flower buds are useful in scurvy, and the bark is bitter, aperient, diuretic and expec-
torant, used in splenic, renal and hepatic complaints.LX
Phytoconstituents: Capers contain glucosinolates, polyphenols, alkaloids, lipids,
vitamins and minerals [22], saccharides, glycosides, terpenoids, volatile oils, fatty
acids and steroides [34]. Nine compounds, rutin, resveratrol, coumarin, catechin,
epicatechin, luteolin, kaempferol, vanillic acid and gallic acid were detected in
methanol leaf extract of C. spinosa of Tunisian origin [30]. Determination of car-
otenoids (b-carotene, lutein, neoxanthin, and violaxanthin), and tocopherols in
leaves, buds, and flowers of Tunisian C. spinosa showed maximum contents of
carotenoids in leaves with proportionally high contents of lutein, and lowest of
violaxanthin. Principal form of tocopherol in leaves was a-tocopherol, whereas
buds and flowers contained both a- and c-tocopherol, and an appreciable amount of
vitamin C [31, 32]. A number of flavonoids, quercetin 7-rutinoside, rutin, quercetin
3-glucoside-7-rhamnoside, kaempferol-3-rutinoside, kaempferol-3-glucoside, and
kaempferol-3-rhamnorutinoside have been identified [28]. Amounts of rutin in
leaves, fruits and flowers, of samples from wildly growing plants in Iran, were 61, 6
and 43.7 mg per 100 g of dried powder, respectively [27]. Methanol extract of
flowering buds contains flavonoids (kaempferol and quercetin derivatives) and
hydrocinammic acids [26]. According to U.S. Department of Agriculture, it con-
tains more quercetin per gm weight than any other plant. Biflavonoids, isoginkgetin
and ginkgetin, and sakuranetin have also been isolated from caper [36], and
Capparis spinosa L. 503

polyprenols, cappaprenol-12, cappaprenol-13 and cappaprenol-14 were isolated

from alcohol extracts [3]. Several free and glycosylated spermidine alkaloids, and a
more polar alkaloid, stachydrine, have been isolated from root; total alkaloids yield
in a Syrian sample was almost double in hydroalcoholic extract than in decoction,
and the cortex contained more stachydrine than the whole root [20]. Seed oil
content ranged from 27.3 to 37.6 g/100 g, with dominating fatty acids being
linoleic acid (24.6–50.5%), oleic acid and its isomer, vaccenic acid, tocopherols,
sterols (sitosterol, campesterol, stigmasterol and Δ5-avenasterol), and glucosino-
lates [24], and minerals Al, P, Na, Mg, Fe, and Ca [25].
Pharmacology: Aqueous fruits (seeds) extract showed significant anti-inflammatory
activity [36], and hydroalcohol extract containing, p-hydroxybenzoic acid,
5-(hydroxylmethyl) furfural, bis(5-formylfurfuryl) ether, daucosterol, a-D-fructofur-
anosides methyl, uracil and stachydrine showed significant antiarthritic activity [13].
Powdered root, decoction and hydroethanol root extract significantly increased
threshold to articular pain in rats [23]. Methanol extract of flowering buds protected
against harmful effects of IL-1b, greater than that by indomethacin [26]. Methanol leaf
extract was protective against cisplatin-nephrotoxicity and CCl4-hepatotoxicity, and
p-methoxybenzoic acid isolated from methanol soluble fraction of aqueous fruits
extract, also exhibited significant protective activity against CCl4- and APAP-
hepatotoxicity in vivo, and thioacetamide- and galactosamine-hepatotoxicity in iso-
lated rat hepatocytes [14]. Methanol hot extract of flowering tops protected against
bronchospasm due to antigen challenge in sensitized guinea pigs, and cold methanol
extract pretreatment significantly decreased responsiveness to histamine [33]. Aqu-
eous caper bud extract protected CA1 region of hippocampus from LPS-induced
neurodegeneration, and the resulting learning and memory deficit in rats [16].
Oral administration of a single dose or 14-daily doses of aqueous fruit extract did
not produce any significant change in blood glucose level in normal rats, but
significantly decreased blood glucose levels of STZ-diabetic rats, and nearly nor-
malized blood glucose levels after 2-weeks daily administration, without any sig-
nificant alteration in basal plasma insulin in either normal or diabetic rats [10]. The
extract also significantly decreased plasma TGs and TC levels in normal and
STZ-diabetic rats, after two-weeks treatment [11], and improved insulin sensitivity
of peripheral tissues [12]. Four-weeks treatment of diabetic rats with ethanol root
extract significantly lowered FBG, and LDL, and increased HDL levels [19].
Various extracts of capers exhibit antioxidant activity which is attributed to their
phenolic content [7, 8, 15, 29].
Aqueous extract exhibits strong antifungal activity, completely preventing
growth of M. canis and T. violaceum [2]. Butanol extract of aerial parts showed
very strong antibacterial activity against both Gram-positive (B. cerreus, S. aureus),
and Gram-negative bacteria (E. coli, P. aeruginosa), as well as moderate to good
antifungal activity against C. albicans and A. flavus; while aqueous extract showed
weak activity against these organisms [21]. Methanol root extract potentiated effects
of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid, against
standard strain of E. coli [9]. Methanol extract of capers interferes with HSV-2
504 Capparis spinosa L.

replication in human peripheral blood mononuclear cells (PBMCs), inhibiting

extracellular virus release and upregulating the production of IL-12, IFN-c and
TNF-a, contributing to improved immune surveillance of PBMCs toward virus
infection [5].
Clinical Studies: In a randomized clinical trial of Iranian patients with type-2
diabetes on standard antidiabetic therapy, administration of caper fruit extract for
two-months produced significant decrease in FBG, HbA1c, and TGs levels [17].
Cold methanol extract gel formulation significantly inhibited histamine-induced skin
erythema in humans [33].
Human A/Es, Allergy and Toxicity: Occasional reports of food allergy and
allergic contact dermatitis have surfaced [1, 4].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Clinical studies in diabetic patients should involve larger number and
diverse populations of patients to validate the beneficial antidiabetic effects. More-
over, clinical studies should also evaluate its antioxidant, nephroprotective and hep-
atoprotective effects.

References
1. Alcántara M, Morales M, Carnés J. Food allergy to caper (Capparis
spinosa). J Investig Allergol Clin Immunol. 2013;23:67–9.
2. Ali-Shtayeh MS, Abu Ghdeib SI. Antifungal activity of plant extracts
against dermatophytes. Mycoses. 1999;42:665–72.
3. al-Said MS, Abdelsattar EA, Khalifa SI, el-Feraly FS. Isolation and identifi-
cation of an anti-inflammatory principle from Capparis spinosa. Pharmazie.
1988;43:640–1.
4. Angelini G, Vena GA, Filotico R, et al. Allergic contact dermatitis from
Capparis spinosa L. applied as wet compresses. Cont Derm. 1991;24:382–3.
5. Arena A, Bisignano G, Pavone B, et al. Antiviral and immunomodulatory
effect of a lyophilized extract of Capparis spinosa L. buds. Phytother Res.
2008;22:313–7.
6. Boga C, Forlani L, Calienni R, et al. On the antibacterial activity of roots of
Capparis spinosa L. Nat Prod Res. 2011;25:417–21.
7. Bonina F, Puglia C, Ventura D, et al. In vitro antioxidant and in vivo
photoprotective effects of a lyophilized extract of Capparis spinosa L. buds.
J Cosmet Sci. 2002;53:321–35.
8. Cao YL, Li X, Zheng M. Capparis spinosa protects against oxidative stress in
systemic sclerosis dermal fibroblasts. Arch Dermatol Res. 2010;302:349–55.
9. Darwish RM, Aburjai TA. Effect of ethnomedicinal plants used in folklore
medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli.
BMC Complement Altern Med. 2010;10:9.
Capparis spinosa L. 505

10. Eddouks M, Lemhadri A, Michel JB. Caraway and caper: potential anti-
hyperglycaemic plants in diabetic rats. J Ethnopharmacol. 2004;94:143–8.
11. Eddouks M, Lemhadri A, Michel JB. Hypolipidemic activity of aqueous
extract of Capparis spinosa L. in normal and diabetic rats. J Ethnopharma-
col. 2005;98:345–50.
12. Eddouks M, Lemhadri A, Hebi M, et al. Capparis spinosa L. aqueous
extract evokes antidiabetic effect in streptozotocin-induced diabetic mice.
Avicenna J Phytomed. 2017;7:191–8.
13. Feng X, Lu J, Xin H, et al. Antiarthritic active fraction of Capparis spinosa
L. fruits and its chemical constituents. Yakugaku Zasshi. 2011;131:423–9.
14. Gadgoli C, Mishra SH. Antihepatotoxic activity of p-methoxybenzoic acid
from Capparis spinosa. J Ethnopharmacol. 1999;66:187–92.
15. Germanò MP, De Pasquale R, D’Angelo V, et al. Evaluation of extracts and
isolated fraction from Capparis spinosa L. buds as an antioxidant source.
J Agric Food Chem. 2002;50:1168–71.
16. Goel A, Digvijaya, Garg A, Kumar A. Effect of Capparis spinosa Linn.
extract on lipopolysaccharide-induced cognitive impairment in rats. Indian J
Exp Biol. 2016;54:126–32.
17. Huseini HF, Hasani-Rnjbar S, Nayebi N, et al. Capparis spinosa L. (Caper)
fruit extract in treatment of type 2 diabetic patients: a randomized double-blind
placebo-controlled clinical trial. Complement Ther Med. 2013;21:447–52.
18. Jiang HE, Li X, Ferguson DK, et al. The discovery of Capparis spinosa L.
(Capparidaceae) in the Yanghai Tombs (2800 years b.p.), NW China, and
its medicinal implications. J Ethnopharmacol. 2007;113:409–20.
19. Kazemian M, Abad M, Haeri MR, Ebrahimi M, Heidari R. Antidiabetic
effect of Capparis spinosa L. root extract in diabetic rats. Avicenna J
Phytomed. 2015;5:325–32.
20. Khatib M, Pieraccini G, Innocenti M, Melani F, Mulinacci N. An insight
on the alkaloid content of Capparis spinosa L. root by HPLC-DAD-MS,
MS/MS and (1)H qNMR. J Pharm Biomed Anal. 2016;123:53–62.
21. Mahasneh AM. Screening of some indigenous Qatari medicinal plants for
antimicrobial activity. Phytother Res. 2002;16:751–3.
22. Maldini M, Foddai M, Natella F, et al. Metabolomic study of wild and
cultivated caper (Capparis spinosa L.) from different areas of Sardinia and
their comparative evaluation. J Mass Spectrom. 2016;51:716–28.
23. Maresca M, Micheli L, Di Cesare Mannelli L, et al. Acute effect of
Capparis spinosa root extracts on rat articular pain. J Ethnopharmacol.
2016;193:456–65.
24. Matthäus B, Ozcan M. Glucosinolates and fatty acid, sterol, and tocopherol
composition of seed oils from Capparis spinosa var. spinosa and Capparis ovata
Desf. var. canescens (Coss.) Heywood. J Agric Food Chem. 2005;53:7136–41.
25. Ozcan MM. Investigation on the mineral contents of capers (Capparis spp.)
seed oils growing wild in Turkey. J Med Food. 2008;11:596–9.
26. Panico AM, Cardile V, Garufi F, et al. Protective effect of Capparis spinosa
on chondrocytes. Life Sci. 2005;77:2479–88.
506 Capparis spinosa L.

27. Ramezani Z, Aghel N, Keyghobadi H. Rutin from different parts of Capparis

spinosa growing wild in Khuzestan/Iran. Pak J Biol Sci. 2008;11:768–72.
28. Sharaf M, el-Ansari MA, Saleh NA. Quercetin triglycoside from Capparis
spinosa. Fitoterapia. 2000;71:46–9.
29. Tesoriere L, Butera D, Gentile C, Livrea MA. Bioactive components of
caper (Capparis spinosa L.) from Sicily and antioxidant effects in a red meat
simulated gastric digestion. J Agric Food Chem. 2007;55:8465–71.
30. Tlili N, Feriani A, Saadoui E, Nasri N, Khaldi A. Capparis spinosa leaves
extract: source of bioantioxidants with nephroprotective and hepatoprotec-
tive effects. Biomed Pharmacother. 2017;87:171–9.
31. Tlili N, Khaldi A, Triki S, Munné-Bosch S. Phenolic compounds and
vitamin antioxidants of caper (Capparis spinosa). Plant Foods Hum Nutr.
2010;65:260–5.
32. Tlili N, Nasri N, Saadaoui E, Khaldi A, Triki S. Carotenoid and tocopherol
composition of leaves, buds, and flowers of Capparis spinosa grown wild in
Tunisia. J Agric Food Chem. 2009;57:5381–5.
33. Trombetta D, Occhiuto F, Perri D, et al. Antiallergic and antihistaminic
effect of two extracts of Capparis spinosa L. flowering buds. Phytother Res.
2005;19:29–33.
34. Yang T, Liu YQ, Wang CH, Wang ZT. Advances on investigation of chemical
constituents, pharmacological activities and clinical applications of Capparis
spinosa. Zhongguo Zhong Yao Za Zhi. 2008;33:2453–8 (Chinese).
35. Yaniv Z, Dafni A, Friedman J, Palevitch D. Plants used for the treatment of
diabetes in Israel. J Ethnopharmacol. 1987;19:145–51.
36. Zhou HF, Xie C, Jian R, Kang J, et al. Biflavonoids from Caper (Cap-
paris spinosa L.) fruits and their effects in inhibiting NF-kappa B activa-
tion. J Agric Food Chem. 2011;59:3060–5.
Cardiospermum halicacabum L.
(Sapindaceae)

Abstract
A climbing herbaceous, more or less hairy plant (vine) that is a native of Central
and South America, but also found in tropical and subtropical Asia and Africa. In
Unani medicine, it is described as aphrodisiac and fattening of the body. Aerial
parts are diuretic, stomachic, laxative, alterative and rubefacient. Root and leaves
are used as decoction for rheumatism, nervous diseases, piles, chronic bronchitis,
phthisis and for amenorrhea. Fried leaves are applied to pubis to improve
menstrual flow in amenorrhea. Plant juice is dropped into ear for earache and
discharge from the meatus. Its non-edible oil is used as insect repellent. Leaves
largely contain tannins, saponins and traces of alkaloids. Apigenin, luteolin, and
apigenin-7-O-glucoside were identified as the predominant constituents of aerial
parts and seeds from Italy. Cardiospermin, a cyanogenic glucoside isolated from
root is suggested to be responsible for its anxiolytic activity. Aqueous leaf extract
significantly increased sperm count, sperm motility, and serum testosterone level
in rats. Anti-inflammatory activity of ethanol extract of aerial parts has been
ascribed to the presence of rutin, and berberine, an isoquinoline alkaloid, has
been identified as a competitive inhibitor of phospholipase A2. Luteolin-7-O-
glucuronide, apigenin-7-O-glucuronide and chrysoeriol have also been identified
as anti-inflammatory compounds. Topical application of hexane, ethyl acetate,
benzene, chloroform and methanol extracts offered a safe protection against
mosquito bites.

Keywords





Alfombrilla Balãozinho Ballonrebe Dominicani Hubbul-qilqil Kanphuti






Kapotavalli Laftaf Tao ti ling Winter cherry

Vernaculars: Urd.: Anardana jangli, Gawar chikna, Hubbul-qilqil (Habul qalqal);

Hin.: Kanaphata, Kanphuti; San.: Banu-uchchhe, Indravalli, Jyantisha-mati,
Kãkãdani, Kapotavalli, Karnasphotã, Krsnatandulã, Lataphatki, Paravata-padi,
© Springer Nature Switzerland AG 2020 507
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_54
508 Cardiospermum halicacabum L.

Śakralatã, Triputã; Ben.: Lotaphatakari (seeds), Napatki, Nayaphataki, Shibjhul;

Mal.: Jyotishmati, Karuthakunni, Katabhi, Paluruvan, Ulinja, Uzhinja, Valli-
uzhinja; Mar.: Kakumardamka, Kanphuti, Kapala-phodi, Shibjal; Tam.: Keerai,
Kottavan, Modakanthan, Moddacoatan, Moedakottan, Mooda-cottan, Mudakattan,
Mudakkathaan, Mudulcottan, Samuttiram; Tel.: Buddakakaraeega, Budha-kakara,
Nella gulisi-tenda, Tapaakaayateega, Vekkudutige; Ara.: Bakeeraf, Habbal-kulkul,
Laftaf; Chi.: 倒地铃, Tao ti ling; Dut.: Blaaserwt; Eng.: Balloon vine, Blister
creeper, Chinese cypress, Heart-pea, Heartseed, Love in a puff, Winter cherry; Fin.:
Rakkoköynnös; Fre.: Pois de coeur, Pois de merveille; Ger.: Ballonrebe, Blas-
enerbse, Herzsame; Ita.: Cuore delle indie, Dominicani, Paternostrinie, Vesicaria
del cuore; Jap.: Fûsen-kazura; Nep.: Jyotismati; Pol.: Miłość w obłoku, Winorośl
balonowa; Por.: Balãozinho (Br.); Spa.: Alfombrilla, Ballarina, Bejuco de orinar,
Bejuco tronador, Bobo, Bolsilla, Bombilla, Farolitos, Hierba del chivato, Hierba de
los farolitos, Hierba del golpe, Huevo de gato, Rayó, Revienta caballo, Tronador;
Swe.: Ballongranka; Tag.: Parol-parolan.
Description: It is a native of Central and South America, but also found in tropical
and subtropical Asia and Africa. A climbing herbaceous, more or less hairy plant
(vine) with deeply furrowed, slender stem, 1–3 m high; leaves are trifoliate, 5–9 cm
long, with coarsely toothed or lobed margins; flowers are small, white and about
1.5–2.5 mm long, and the fruit is inflated, obvoid, 1.5–2.5 cm long, somewhat
triangular and three keeled. Seeds are rounded and black, with a prominent, white,
heart-shaped aril at the base (Figs. 1, 2 and 3).CXVII
Actions and Uses: In Greeco-Arab medicine, Ibn-al-Baitar,LXIX quoting Ibn-
Masawaiyh and Masarjawaih (in Arabic, Masarjoya), described it as aphrodisiac
when seeds (temperament, hot and moist) are used after roasting; it is also fattening

Fig. 1 Cardiospermum halicacabum, Unripe Fruits, H. Zell, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cardiospermum_halicacabum_
04.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Cardiospermum halicacabum L. 509

Fig. 2 Cardiospermum halicacabum, Ripe Fruits, H. Zell, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cardiospermum_halicacabum_
06.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Cardiospermum halicacabum, Opened Fruit showing Seeds, H. Zell, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cardiospermum_
halicacabum_08.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

of the body, and is mainly used in compound drugs to improve sexual perfor-
mance.LXXVII Root and leaves are used as decoction for rheumatism, nervous dis-
eases, piles, chronic bronchitis, phthisis and for amenorrhea. Juice of the plant is
dropped into ear for earache and discharge from the meatus.LX,CV Aerial parts are
diuretic, stomachic, laxative, alterative and rubefacient.LXXXI Fried leaves are
applied to pubis to improve menstrual flow in amenorrhea; and boiled in castor oil
applied for rheumatism, swellings, and various kinds of tumors. Seeds are used for
510 Cardiospermum halicacabum L.

fevers and rheumatism,LXXXIV,CV and the whole plant is reportedly used as a remedy
for rhumatism, nervous diseases, orchitis, and dropsy, and as hair wash to remove
scurf [17]. It is one among the “Ten Sacred Flowers” of Kerala State in India,
collectively known as Dasapushpam, and is also utilized as a leafy vegetable in India
[13, 14]. In the Philippines, root decoction is regarded diaphoretic, and is used in the
catarrh of the bladder, and the leaves are considered antirheumatic whether taken
internally or applied externally in oil embrocations.LVI,CXVII Leaves and roots are
used for the treatment of rashes, abscesses and boils in East Africa.LXXV
Phytoconstituents: Leaves of the plant were reported to contain largely tannins,
saponins and traces of alkaloids [10]. Apigenin, kaempferol, luteolin, quercetin,
methyl 3,4-dihydroxybenzoate, p-coumaric acid, 4-hydroxybenzoic acid, hydro-
quinone, protocathehuic acid, gallic acid, chrysoeriol, quercetin-3-O-a-l-rhamnoside,
kaempferol-3-O-a-L-rhamnoside, apigenin-7-O-b-D-glucuronide, apigenin 7-O-b-
D-glucuronide methyl ester, apigenin 7-O-b-D-glucuronide ethyl ester, and indole-
3-carboxylic acid, were isolated from ethanol extract of Taiwanese C. halicacabum
[7]. Apigenin, luteolin, and apigenin-7-O-glucoside were identified as the predomi-
nant constituents of aerial parts and seeds from Italy [19]. Chen et al. [6] identified
eight compounds as pentadecanoie acid, apigenin, protocatechuic acid, protocate-
chualdehyde, hentriacontanol, calycosin, rutin, and quercetin. Major compounds in
ethanol leaves extract from India included benzene acetic acid, caryophyllene, phytol,
neophytadiene and cyclohexane-1,4,5-triol-3-one-1-carboxylic acid [13]. Fatty acids,
including eicosanoic acid, methyl 11-eicosenoate and oleic acid, were major con-
stituents of n-hexane fraction of seed extract which produced significant inhibition of
BChE [19]. Cardiospermin, a cyanogenic glucoside isolated from root is suggested to
be responsible for its anxiolytic activity [18].
Its non-edible oil is used as insect repellent [15]. Air dried seeds contain
moisture 10.71%, ash 3%, total N 2.22%, organic phosphorylates 2.34%, and oil
32.28%; seed oil contained volatile acids 0.75%, arachidic and lignoceric 11%,
stearic 6%, oleic 71% and linoleic acids 1.30%, along with unsaponified fraction
and glycerol. Gedeon and Kincl [9] reported presence of saponins, and b-sitosterol.
Phalobaphene, phlobatannins, Ca, Mg, Al, Fe, Na, K, chloride, sulfate, carbonate
and phosphate ions were reported in roots by Desai and Suresh Sethna [8]. Shukla et al.
[29] isolated alkaloidal fraction from seeds, and cyanolipids from seed oil were
reported by Mikolajczak et al. [20].
Pharmacology: Alcohol leaf extract produced fall in BP and bradycardia, powerful
contraction of isolated guinea pig ileum, mild analgesia, and CNS depression in near
lethal doses; both fall in BP and contractile effect were partially antagonized by atropine
and antihistamine [10]. Ethanol root extract also produced significant anxiolytic effects in
mice [18]. Aqueous leaf extract for 30-days significantly increased sperm count, sperm
motility, and serum testosterone level in rats [23]. Seeds EO produced an immediate fall
in B.P. of anesthetized dog, lasting 1.5 h, whereas water soluble fraction of an ethyl
alcohol seed extract caused a prolonged (2–4 h) hypotensive action [21]. Chandra and
Sadique [5] reported anti-inflammatory activity, and ethanol extract of aerial parts was
effective against carrageenan-induced rat paw edema, decreased NO level in edematous
Cardiospermum halicacabum L. 511

paw tissue and in serum, and diminished serum TNFa level [12]. In cotton pellet gran-
uloma assay, it suppressed transudative, exudative and proliferative components of
chronic inflammation, and lowered lipid peroxide content and c-glutamyl transpeptidase
and phospholipase A2 activity in the exudate. It was suggested that it exerts its
anti-inflammatory activity by inhibition of phospholipase A2 [25]. Ethanol extract also
inhibits mRNA expression of COX-2, TNFa, iNOS, and COX-2 protein expression in
mouse macrophage RAW264.7 cells [28]. Anti-inflammatory activity of ethanol extract
has been ascribed to the presence of rutin [2], and berberine, an isoquinoline alkaloid,
has been identified as a competitive inhibitor of phospholipase A2 [4]. Luteolin-7-
O-glucuronide, apigenin-7-O-glucuronide and chrysoeriol have also been named as
anti-inflammatory compounds [14]. Ethanol and n-hexane extracts of whole plant
powder exhibit potent antipyretic activity, while the aqueous extract was devoid of any
significant antipyretic activity [1].
Ethanol extract inhibited ethanol-induced gastric ulcers in rats, and increased
levels of gastric glutathione and decreased alkaline phosphatase activity [27].
Methanol and petroleum ether extracts significantly protected against APAP-
nephrotoxicity in rats, with methanol extract showing better effect [22]. Ethanol leaf
extract decreased TBARS and LPO levels of diabetic rats. Plasma TC, phospho-
lipids, TGs, and FFAs [32], and the levels of plasma and tissues glycoproteins
containing hexose, hexosamine and fucose [33] of STZ-diabetic rats returned to
near normal in leaf extract-treated animals. Co-treatment with methanol extract
significantly prevented CP-induced immunosuppression in mice, and restored total
WBC count, reduced proinflammatory cytokine TNF-a, and significantly increased
GSH level [24].
Ethanol leaf extract inhibits growth of S. aureus, E. coli, the fish pathogen
A. hydrophila, and C. albicans [13]. Aqueous extract significantly reduces motility
of adult female microfilariae B. pahangi after 24 h of exposure, and adult males
after 3 days in culture medium [16]. Aqueous extract also showed weak antiplas-
modial activity, but was toxic to P. berghei-infected mice, none surviving beyond
day 4 of oral administration [34]. Exposure of S. stercoralis larvae to aqueous and
alcohol extracts immobilized them within 72 and 48 h, respectively, comparative to
up to 4-days for ivermectin, and more than 7-days for piperazine to achieve the
same rate of nonmotility [3].
Clinical Studies: Topical application of hexane, ethyl acetate, benzene, chloro-
form and methanol extracts were concentration dependently protective against
mosquito bites of C. quinquefasciatus, A. aegypti and A. stephensi, without any
allergic reaction [11].
Human A/Es, Allergy and Toxicity: The seeds cause diarrhea, weaken digestion,
and produce headache.LXXVII
Animal Toxicity: Ethanol extract is devoid of any conspicuous acute and short-term
toxicity in rats [27]. Ethyl acetate leaf extract at 40 mg/kg was also nonlethal and
nontoxic to rats [26].
512 Cardiospermum halicacabum L.

Potential Drug-Herb Interactions: Concurrent administration of C. halicacabum

tea with carbamazepine in rats did not have any significant changes in blood levels
of carbamazepine or drug-related toxicity [30]. However, a significant increase in
steady state levels of theophylline (48.2%) occurred when administered concur-
rently with C. halicacabum herbal tea [31].
Commentary: Pharmacological studies verified the potential anti-inflammatory
effects, and improvements in sexual markers, such as sperm count and motility and
serum testosterone level in animals, as mentioned in traditional uses. However,
there are no clinical studies reported in humans.

References
1. Asha VV, Pushpangadan P. Antipyretic activity of Cardiospermum halica-
cabum. Indian J Exp Biol. 1999;37:411–4.
2. Babu KC, Krishnakumari S. Anti-inflammatory and antioxidant compound,
rutin in Cardiospermum halicacabum leaves. Anc Sci Life. 2005;25:47–9.
3. Boonmars T, Khunkitti W, Sithithaworn P, Fujimaki Y. In vitro antiparasitic
activity of extracts of Cardiospermum halicacabum against third-stage
larvae of Strongyloides stercoralis. Parasitol Res. 2005;97:417–9.
4. Chandra DN, Prasanth GK, Singh N, et al. Identification of a novel and
potent inhibitor of phospholipase A(2) in a medicinal plant: crystal structure
at 1.93Å and Surface Plasmon Resonance analysis of phospholipase A(2)
complexed with berberine. Biochim Biophys Acta. 2011;1814:657–63.
5. Chandra T, Sadique J. Anti-inflammatory effect of the medicinal plant,
Cardiospermum halicacabum L, in vitro study. Arogya. 1984;10:57.
6. Chen J, Wei JH, Cai SF, Miao WS, Pan LW. Study on chemical constituents
of Cardiospermum halicacabum. Zhong Yao Cai. 2013;36:228–30 (Article
in Chinese).
7. Cheng HL, Zhang LJ, Liang YH, et al. Anti-inflammatory and antioxidant
flavonoids and phenols from Cardiospermum halicacabum (Dào Dì Líng).
J Tradit Complement Med. 2013;3:33–40.
8. Desai KB, Suresh Sethna. Chemical investigation of the root of the Indian
medicinal plant Cardiospermum halicacabum (Linn). J MS Univ Baroda.
1954;111:33–9.
9. Gedeon J, Kincl FA. Saponins and sapogenins. Arch Pharm. 1956;289:162–5.
10. Gopalakrishnan C, Dhananjayan R, Kameswaran L. Studies on the pharmaco-
logical actions of Cardiospermum helicacabum. Indian J Physiol Pharmacol.
1976;20:203–8.
11. Govindarajan M, Sivakumar R. Repellent properties of Cardiospermum
halicacabum Linn. (Family: Sapindaceae) plant leaf extracts against three
important vector mosquitoes. Asian Pac J Trop Biomed. 2012;2:602–7.
12. Huang MH, Huang SS, Wang BS, et al. Antioxidant and anti-inflammatory
properties of Cardiospermum halicacabum and its reference compounds
ex vivo and in vivo. J Ethnopharmacol. 2011;133:743–50.
Cardiospermum halicacabum L. 513

13. Jeyadevi R, Sivasudha T, Ilavarasi A, Thajuddin N. Chemical constituents

and antimicrobial activity of Indian green vegetable Cardiospermum halica-
cabum. Indian J Microbiol. 2013;53:208–13.
14. Jeyadevi R, Sivasudha T, Rameshkumar A, Dinesh Kumar L. Antiarthritic
activity of the Indian leafy vegetable Cardiospermum halicacabum in
Wistar rats and UPLC-QTOF-MS/MS identification of the putative active
phenolic components. Inflamm Res. 2013;62:115–26.
15. Khan MWY, Ahmad F, Ahmad I, Osman SM. Non-edible seed oils as insect
repellant. J Am Oil Chem Soc. 1983;60:949.
16. Khunkitti W, Fujimaki Y, Aoki Y. In vitro antifilarial activity of extracts of
the medicinal plant Cardiospermum halicacabum against Brugia pahangi.
J Helminthol. 2000;74:241–6.
17. Kraemer H. Materia medica of Ceylon. Am J Pharm. 1894;66:530–9.
18. Kumar R, Murugananthan G, Nandakumar K, Talwar S. Isolation of
anxiolytic principle from ethanolic root extract of Cardiospermum halica-
cabum. Phytomedicine. 2011;18:219–23.
19. Menichini F, Losi L, Bonesi M, et al. Chemical profiling and in vitro
biological effects of Cardiospermum halicacabum L. (Sapindaceae) aerial
parts and seeds for applications in neurodegenerative disorders. J Enzyme
Inhib Med Chem. 2014;29:677–85.
20. Mikolajczak KL, Smith RC Jr, Tjarks LW. Cyanolipids of Cardiospermum
halicacabum and other Sapindaceous seed oils. Lipids. 1970;5:812–7.
21. Modi NT, Deshmankar BS. Some preliminary pharmacological investiga-
tions on Cardiospermum helicacabum. Indian J Pharm. 1972;34:76–7.
22. Parameshappa B, Ali Basha MS, Sen S, et al. Acetaminophen-induced neph-
rotoxicity in rats: protective role of Cardiospermum halicacabum. Pharm
Biol. 2012;50:247–53.
23. Peiris LD, Dhanushka MA, Jayathilake TA. Evaluation of aqueous leaf ex-
tract of Cardiospermum halicacabum (L.) on fertility of male rats. Biomed
Res Int. 2015;2015:175726.
24. Pratheeshkumar P, Kuttan G. Cardiospermum halicacabum inhibits
cyclophosphamide induced immunosupression and oxidative stress in mice
and also regulates iNOS and COX-2 gene expression in LPS stimulated
macrophages. Asian Pac J Cancer Prev. 2010;11:1245–52.
25. Sadique J, Chandra T, Thenmozhi V, Elango V. Biochemical modes of
action of Cassia occidentalis and Cardiospermum halicacabum in inflam-
mation. J Ethnopharmacol. 1987;19:201–12.
26. Shareef H, Rizwani GH, Mahmud S, Perveen R, Khalid L. Histopathologic
changes in liver and kidney of male Sprague Dawley rats treated with extract
of Cardiospermum halicacabum L. Pak J Pharm Sci. 2014;27:2247–50.
27. Sheeba MS, Asha VV. Effect of Cardiospermum halicacabum on ethanol-
induced gastric ulcers in rats. J Ethnopharmacol. 2006;106:105–10.
514 Cardiospermum halicacabum L.

28. Sheeba MS, Asha VV. Cardiospermum halicacabum ethanol extract inhibits
LPS induced COX-2, TNF-alpha and iNOS expression, which is mediated by
NF-kappaB regulation, in RAW 264.7 cells. J Ethnopharmacol. 2009;124:
39–44.
29. Shukla SD, Modi NT, Deshmankar BS. Pharmacological actions of an alka-
loidal fraction from Cardiospermum halicacabum. Indian J Pharm. 1973;
35:40.
30. Thabrew I, Munasinghe J, Chackrewarthi S, Senarath S. The effects of Cassia
auriculata and Cardiospermum halicacabum teas on the steady state blood
level and toxicity of carbamazepine. J Ethnopharmacol. 2004;90:145–50.
31. Thabrew MI, Munasinghe TM, Senarath S, Yapa RM. Effects of Cassia
auriculata and Cardospermum halicacabum teas on the steady state blood
levels of theophylline in rats. Drug Metabol Drug Interact. 2004;20:263–72.
32. Veeramani C, Pushpavalli G, Pugalendi KV. In vivo antioxidant and hypolipi-
demic effect of Cardiospermum halicacabum leaf extract in streptozotocin-
induced diabetic rats. J Basic Clin Physiol Pharmacol. 2010;21:107–25.
33. Veeramani C, Al-Numair KS, Alsaif MA, et al. Protective effect of
Cardiospermum halicacabum leaf extract on glycoprotein components on
STZ-induced hyperglycemic rats. Asian Pac J Trop Med. 2012;5:939–44.
34. Waako PJ, Gumede B, Smith P, Folb PI. The in vitro and in vivo anti-
malarial activity of Cardiospermum halicacabum L. and Momordica foetida
Schumch. Et Thonn. J Ethnopharmacol. 2005;99:137–43.
Carthamus tinctorius L.
(Asteraceae/Compositae)

(Syns.: C. glaber Burm.f., C. inermis Hegi, nom. inval.; Calcitrapa tinctoria Röhl.;
Carduus tinctorius Ehrh.; C. tinctorius (L.) Falk; Centaurea carthamus E.H.L.Krause)

Abstract
An annual, branching herb that is mainly cultivated for its seeds (to obtain edible
oil), throughout India, China, Laos, southern Vietnam, Cambodia and other
countries. Greeks called the seeds Atraktus and Dioscorides called them Knikus.
Pliny called leaves Cuccos, and Greeks used them like rennet to curdle milk to make
cheese. Dioscorides and Galen described the seeds purgative and Masarjoya said it
is carminative and increases production of semen, and Avicenna recommended it
with honey and fig in colic, to expel phlegm and as an aphrodisiac. Jamaicans use
seeds as laxative after beating seeds kernels into an emulsion with honeyed water.
In Unani medicine, seeds are used with honey to expectorate phlegm and clear
chest in cases of cough and asthma, and clear vocal irritation, and also used in
compound drugs to improve sexual performance. In Ayurveda, the leaves are used
in pratiśyãya and netraroga, the seeds in aśmari, and the seed oil in prameha,
aśmari, rãjayaksmã and vrana. In traditional Iranian medicine, seeds are used as
purgative, analgesic, antipyretic, antidote to poisoning, in painful menstruation, in
postpartum hemorrhage, and osteoporosis. Carthamin, known as Natural Red 26, is
the red pigment used as a dye and food coloring, and is also reported exhibiting
estrogenic activity. In Indo-China, the flowers are used in the treatment of
dysmenorrhea and as emmenagogue, and as tonic in paralysis. In China, the flowers
are known as Hung-Hua; which are considered emmenagogue, blood stimulant,
channel deobstruent, stasis discutient, and analgesic, and are mainly used to treat
amenorrhea, dysmenorrhea, dystocia, and postpartum lochiostasis. This drug was
first recorded in Chinese literature in Kai Pao Pen Tsao in 973 A.D. to treat
cerebrovascular and cardiovascular diseases, as analgesic, anti-inflammatory
agent, abdominal lump or obstruction, and injuries due to impact, fractures,
contusions and strains. Over 104 compounds have been isolated and identi-
fied from this plant. Flowers contain flavonoids, flavonol glycosides, quinochal-
cones, tinctormine, carthamin, safflor yellow B, safflomin A and C, isocarthamidin,

© Springer Nature Switzerland AG 2020 515

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_55
516 Carthamus tinctorius L.

isocarthamin, spermidine compounds, triterpenoid saponins, triterpene alcohol,

palmitic acid, 1-O-hexadecanolenin, adenosine, coumaric acid, apigenin, daucos-
terol and kaempferol.

Keywords




Alazor Asfur Azafrán Carthame
Färbersaflor
Hung-hua
Kusumba




Qurtum Safflower Vyãghridala

Vernaculars: Urd.: Asfar, Gul-e-qurtum (flowers), Karad, Khasakdana, Qurtum,

Tukhme kazeera (seeds), Tukhme majeera (seeds); Hin.: Kar, Kusumba, Kusumbar;
San.: Kamalottara, Kantaki, Kantaphala, Kusumbha, Latwãka, Vahniśikham, Vas-
trarañjaka, Vyãghridala; Ben.: Kajireh, Kusukphal, Kusum, Kusumphul; Mal.: Chen-
durakam, Shinduram; Mar.: Kardi, Kardai, Kurdi, Kusumba; Tam.: Kushumba,
Kusumbā puṣpamu, Kusumbavirai, Sendurakam, Sendurukkai, Sethurangam; Tel.:
Agnisikha, Kushumba, Kusumbalu; Ara.: Asfur, Bazar-al-aahris, Habbul-asfar, Jauzar,
Qurtum, Zãfraan; Chi.: 红花, Da hong hua, Hung-hua, Hung lan-hua; Cze.: Azafrán,
Světlice barvířská; Dan.: Falsk safran, Farvetidsel, Safflor, Saflorfroe (seeds); Dut.:
Bastaard saffran, Carthamusbloem, Saffloer, Saffloer-bloem, Verfdistel; Eng.: Bastard
saffron, Dyer’s saffron, False saffron, Parrot seed, Safflower; Fin.: Värisaflori; Fre.:
Carthame, Carthame des teinturiers, Centaurée des teinturiers, Faux safran, Fleur de
carthame, Graine de carthame, Graine deperroquet, Safran batard; Ger.: Falscher safran,
Färberdistel, Färbersaflor, Saflor, Saflorbluete (flower), Saflorsaat (seeds), Wilder
safran; Gre.: Knikos; Ita.: Cartamo, Falso zafferano, Fiore di cartamo (flower), Seme di
cartamo (seeds); Jap.: Benibana, Mogami-benibana; Kor.: Honghwa, Honggwassi,
Sapullaweo; Kor.: Hong hwa; Lao.: Kham nhong; Nor.: Saflor; Per.: Gulrang,
Khasakdana, Tukhme-kaafshah; Pol.: Krokosz barwierski; Por.: Açaflor, Aça-
frão-bastardo, Cártamo, Falso-açafrão; Rus.: Saflor krasil’nyj; Spa.: Alazor, Azafrán
bastardo, Azafran somi, Cártamo; Swe.: Färgtistel, Safflor; Tag.: Biri, Kasubhá,
Kasúmba, Lago; Tha.: Khamfoi; Tur.: Asfur, Aspir, Aspur, Kantawáras, Safran yalancı;
Vie.: Cây rum, Hồng hoa.
Description: An annual, branching herb that is mainly cultivated for its seeds (to
obtain edible oil)LXXVII throughout India, China, Laos, southern Vietnam, Cambodia
and other countries; 0.6–1 m high, glabrous, young stems are greenish and become
whitish on maturity, striate. Leaves sessile, somewhat clasping, lanceolate-oblong,
attenuate at both ends, strongly dentate, faintly spiny; venation pinnate and netted.
Inflorescence a broad corymb, heads 3–5 borne on leafy peduncles. Flowers yellow,
orange or red; fruit a white achene.LXXIX The capsule contains 7–8 somewhat flat,
quadrangular and white seeds, which are medicinally used (Figs. 1, 2 and 3).LXXVII
Actions and Uses: Greeks called the seeds Atraktus and Dioscorides called them
Knikus. Pliny called leaves Cuccos, and Greeks used them like rennet to curdle milk to
make cheese.XL Dioscorides and Galen described the seeds purgative and Masarjoya
said it is carminative and increases production of semen, and Avicenna recommended
it with honey and fig in colic, to expel phlegm and as an aphrodisiac.LXIX Jamaicans
Carthamus tinctorius L. 517

Fig. 1 Carthamus tinctorius, Flower, Paulatz, WikimediaCommons, https://commons.wikimedia.

org/wiki/Carthamus_tinctorius#/media/File:Safflower.jpg

Fig. 2 Carthamus tinctorius, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, Permission granted to use under GFDL by Kurt
Stueber, WikimediaCommons, https://commons.wikimedia.org/wiki/File:Illustration_Carthamus_
tinctorius0.jpg; www.biolib.de
518 Carthamus tinctorius L.

Fig. 3 Carthamus tinctorius, Turkish Safron, Explicitimplicity, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Tuerkischer_safran.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

use seeds as laxative after beating seeds kernels into an emulsion with honeyed
water.XL In Unani medicine, seeds (temperament, hot 2° and dry1°) are used with
honey to expectorate phlegm and clear chest in cases of cough and asthma, and clear
vocal irritation, and also used in compound drugs to improve sexual perfor-
mance.LXXVII Dried flowers taken internally are reported to cure jaundice, and the
whole plant boiled in sesame oil is a valuable remedy for itch, and is locally applied to
rheumatic and painful joints, paralytic limbs and intractable ulcers.XXI,CV Hot infusion
of dried flowers is used as a diaphoretic in jaundice, nasal catarrh, and muscular
rheumatism; whereas a cold infusion is used as laxative and tonic to speed up eruptions
in measles and other exanthemata.LXXXI,CV In Ayurveda, the leaves are used in pra-
tiśyãya and netraroga, the seeds in aśmari, and the seed oil in prameha, aśmari,
rãjayaksmã and vrana.LX In traditional Iranian medicine, seeds are used as purgative,
analgesic, antipyretic, antidote to poisoning, in painful menstruation, in postpartum
hemorrhage, and osteoporosis [5], and its flowers are used as food coloring and
flavoring agent [48]. Carthamin, known as Natural Red 26, is the red pigment used as a
dye and food coloring, and is also reported exhibiting estrogenic activity [9]. In
Indo-China, the flowers are used in the treatment of dysmenorrhea and as emmena-
gogue, and as tonic in paralysis.CXVII In China, the flowers are known as Hung-Hua;
which are acrid and ‘warm’; are considered emmenagogue, blood stimulant, channel
deobstruent, stasis discutient, and analgesic, and are mainly used to treat amenorrhea,
dysmenorrhea, dystocia, and postpartum lochiostasis. This drug was first recorded in
Chinese literature in Kai Pao Pen Tsao in 973 A.D. [78],LXVI to treat cerebrovascular
and cardiovascular diseases [8], as analgesic, anti-inflammatory agent [62], abdominal
lump or obstruction, and injuries due to impact, fractures, contusions and strains.XIX
Fixed seed oil (21.22%), known as Honghuaziyou is a light-yellow transparent
semidrying oil, consisting of palmitic acid, stearic acid, oleic acid, linoleic acid and
linolenic acid. It has a high proportion of polyunsaturated fatty acids which exert an
Carthamus tinctorius L. 519

antilipidemic action in man [2]. However, experiments in rats showed the oil
to markedly increase hepatic lipids and cholesterol, while lowering blood lipids
and cholesterol [50, 68]. KeysLXXIX described its use as a uterine astringent in
dysmenorrhea.
Phytoconstituents: Over 104 compounds from this plant have been isolated and
identified, and quinochalcones and flavonoids are considered the active constituents
of safflower [78]. Flowers contain flavonoids, flavonol glycosides, quinochalcones
(hydroxysafflor yellow A (HSYA) and B), tinctormine, carthamin, safflor yellow B,
safflomin A and C, isocarthamidin, isocarthamin [20, 27, 28, 36, 44, 45, 57, 66, 75,
79, 80], spermidine compounds [26, 77], adenosine [34], triterpenoid saponins [67],
triterpene alcohol [3], palmitic acid, 1-O-hexadecanolenin, coumaric acid, apigenin,
daucosterol and kaempferol [40]. Hydrolysis of carthamin yields carthamidin and
glucose. Flowers also contain lignans and fixed oil. Yellow pigments of carthamin
and its analogues are enzymatically oxidized into the red pigment carthamone.XIX
Phenolic compounds reach their maximum at flower formation stage [52]. Major
phenolic compound in aqueous extract is (−)-epigallocatechin [74]. Seeds contain
flavone glycosides [1], an antiestrogenic lignan glycoside (tracheloside) [73], and
phytosterols (b-sitosterol) [15]. Major fatty acid of safflower oil is linoleic acid, and
various amounts of a-tocopherol, b-tocopherol and c-tocopherol [43].
Pharmacology: Herb decoction strengthened cardiac contractility at low dosage
but inhibited at high dosage in the isolated toad heart and in situ rabbit heart,XIX
causing cardiac arrest of isolated toad and rat hearts in diastolic phase. Intravenous
injection of aqueous flower extract increased coronary blood flow by 60% in in situ
dog heart, and slightly increased myocardial oxygen consumption; while the alcohol
extract produced no significant change. However, both extracts (i.v.) lowered BP in
anesthetized cats and dogs, the aqueous extract being 10 more potent than the
alcohol extract. While the herb decoction produced various degrees of vasocon-
striction, the flower injection produces a vasodilatory effect.XIX Hydroxysafflor
yellow A significantly reduces mean arterial BP and HR in both normotensive and
SHRs [47], lowers plasma renin activity and angiotensin II level in SHRs [38], and
relaxes rat pulmonary artery [8]. Aqueous extract reduced myocardial infarct size
and leakage of myocardial enzyme in rat model of myocardial I/R injury by
increasing level of 6-keto-PGF1a, that inhibits platelet aggregation and prevents
thrombosis [39], and potently inhibited platelet aggregation after incubation with
platelet-rich plasma from healthy Chinese volunteers [69]. Carthamin yellow, the
pigment used as food coloring, significantly decreases whole blood viscosity, plasma
viscosity, and erythrocyte aggregation index in a blood stasis animal model, with
hematocrit and platelet aggregation also reduced, and prothrombin time increased
[35]. Alcohol extract produces a significant prolongation of blood clotting time, and
marked inhibitory action on prothrombin and thrombin [31], and inhibits ADP- or
collagen-induced platelet aggregation.XIX Aqueous decoction had no significant
effect in hypercholesterolemic rabbits, nor did it prevent atherosclerosis in aortic
and coronary vessels.XIX However, studies in rats showed marked increase in
hepatic lipids and cholesterol, while lowering blood lipids and cholesterol [50, 68].
520 Carthamus tinctorius L.

Diabetic animals treated with flower extracts significantly decreased FBG and
increased insulin level [6, 51]. Serotonin derivative compounds (N-p-coumaroyl
serotonin and N-feruloyl serotonin) isolated from safflower seeds also show potent
in vitro a-glucosidase inhibitory activity [56].
Free radical scavenging activity of aqueous extract of safflower petals is propor-
tional to contents of carthamin, the orange color pigment is highest in orange variety,
followed by in yellow and white varieties [11, 16, 22]. N-(p-coumaroyl)serotonin and
N-feruroylserotonin in safflower oil possess antioxidative activity [23], and inhibit
in vitro oxidation of LDL and atherosclerosis in Apo E-deficient mice [32]. Nicoti-
florin, a natural flavonoid of flowers, protects against memory dysfunction, energy
metabolism failure, and oxidative stress in multi-infarct dementia in rats [24]. Alcohol
flower extract and carthamin significantly increase tolerance to hypoxia in mice, and
significantly increased survival of rats in acute hypoxic encephalopathy, reducing
ischemic brain damage, and expediting recovery.XIX HSYA exerts significant neu-
roprotective effects in rats with focal cerebral ischemic injury by reducing infarct area,
significantly reduces infarct size and improves cardiac function in experimental
MI [17, 18] and protects spinal cords from I/R injury in rabbits [53], and in vitro
significantly attenuates I/R injury of cultured rat cardiomyocytes [13], significantly
inhibits glutamate and sodium cyanide induced neuronal damage in cultured fetal
cortical cells [71, 81, 82], and attenuates lymphostatic encephalopathy-induced brain
injury in rats [49].
Hydroalcohol extract shows remarkable antinociceptive and anti-inflammatory
activities in experimental models [62]. Linoleic-acid-rich safflower-seed oil dose-
dependently decreases severity of experimental autoimmune encephalomyelitis in rats
[19]. HSYA pretreatment significantly attenuates LPS-induced inflammatory cell
infiltration and pulmonary edema; and inhibits proinflammatory cytokines TNF-a,
IL-1b and IL-6 mRNA expression and promotes anti-inflammatory cytokine IL-10
gene expression [54, 61], protects against chronic CCl4-induced liver fibrosis [76],
which is due to protection of liver from oxidative stress, and requires stimulation of
PPARc activity [59]. It also effectively protects rat liver from long-term alcohol injury,
by enhancing antioxidant capacity of liver tissues and inhibition of transforming
growth factor b1 expression [21]. Carthamus red treatment lowers serum levels
of ALT, AST, ALP and total protein in CCl4-induced liver damage in rats [64].
C. tinctorius injection attenuates LPS-induced endothelium inflammatory injury [29],
and is cardioprotective against acute MI in rats, which is likely related to decreased
inflammatory response mediated by TNF-a and IL-6 [58]. HSYA also attenuates loss
in body weight, increase of hydroxyproline content, increase of myeloperoxidase
activity in lung tissues and the pathologic changes of bleomycin-induced pulmonary
fibrosis in rats [60, 65], and small airway remodeling of COPD [63].
While toxic effects of aqueous extract on spermatogenesis in mice [46] and
detrimental effects on ovarian histomorphology and female reproductive hormones
[41] were reported, Bahmanpour et al. [7] observed significant improvement in
sperm count, motility and morphology of partially sterile rats. Ethanol extract
also exhibited strong 5a-reductase and hair growth promoting activity [33]. Both
defatted seeds in diet and seed oil protected bone loss in ovariectomized rats, without
Carthamus tinctorius L. 521

substantial effect on the uterus, which is likely mediated through stimulation of

osteoblasts proliferation [4, 25, 30, 31]. Safflor injection significantly prevented I/R
renal injury and dysfunction of rat [14], and inhibited calcium oxalate crystal
deposition in ethylene glycol-fed rats [37]. Polysaccharides isolated from flower
petals inhibited proliferation of breast cancer cells MCF-7, by inducing apoptosis
[42]; whereas HSYA suppressed hepatocellular carcinoma growth in mice by
inhibiting secretion of angiogenesis factors [70]. A mixture of erythroalkane-
6,8-diols from the flowers also markedly suppressed promoting effect of TPA on
skin tumor formation in mice following initiation with DMBA [72].
Clinical Studies: In a double-blind, placebo-controlled clinical trial, 12-weeks
treatment with ethanol defatted seed extract of 46 Japanese patients (with 46 mat-
ched controls) with high blood glucose and high normal blood pressure improved
their arterial stiffness, without any significant change in oxidized LDL and anti-
MDA-LDL [55]. Following results of clinical studies are from China, as reported by
Chang and But. In 40 cases of CAD, use of alcohol extract tablets markedly
improved angina pectoris, increased endurance and improved ECG changes in 18
cases and some improvement in 16 cases. Favorable therapeutic outcomes of
intravenous injection of flower infusion are also reported in 30 cases of cerebral
thrombosis or embolism. Symptomatic improvement was seen in 4 cases of
thromboangitis obliterans and 3 cases of thrombophlebitis. External application of
the tincture (0.5%) to contusions and sprains causes local hyperemia and rapid
subsidence of swelling, and also very effective in cases of subacute tenosynovitis.XIX
Mechanism of Action: Cerebral anti-ischemic effect of HSYA are suggested to be
due to its inhibition of NF-jB activity, and the mRNA expression of cytokines in
inflammatory transduction pathway [10]. The anti-inflammatory effects are due to
inhibition of proinflammatory cytokines TNF-a, IL-1b and IL-6 mRNA expression
and promotion of anti-inflammatory cytokine IL-10 gene expression [54, 61], The
anticancer activity is suggested to be due to apoptosis [42]; and inhibition of
secretion of angiogenesis factors [70].
Human A/Es, Allergy and Toxicity: Chinese writers warn that the drug should be
used with caution in patients with peptic ulcer or hemorrhagic diseases. Although,
various preparations of flowers show no significant adverse reactions in majority of
patients, a minority of patients may develop dizziness, skin eruptions and transient
urticaria. It may also increase menstrual flow in some women and is contraindicated
in pregnant women.XIX It is also regarded harmful in gastric ailments.LXXVII
Animal Toxicity: Mean lethal dose (i.p.) of the decoction in mice is 1,200 mg/kg.
LD50 (i.v.) of alcohol extract in mice was determined to be 5,300 mg (crude drug)/
kg. LD50 (i.v.) of carthamus red (carthamin) in mice was 2,350 mg/kg, whereas its
safe dose by mouth was >8,000 mg/kg.XIX Carthamin was not fatal and/or toxic up
to a dose of 2,000 mg/kg in rats [64]. Young rats fed with carthamin in diet, 0.015–
1.5 g/kg daily for 3-months, did not show significant changes in blood, liver and
kidney functions, nor any morphological abnormalities in heart, liver, kidneys, and
gastrointestinal tract.XIX
522 Carthamus tinctorius L.

Pharmacokinetics: Excretion studies in dogs and cats indicated that intravenously

injected or infused HSYA was rapidly excreted as unchanged drug in the urine [12].
Commentary: Safflower oil is promoted for its beneficial antioxidant effects, and
pharmacological studies show some significant effects. However, there are no RCTs
reported in journals listed on PubMed other than one Japanese study on ethanol
defatted seed extract that showed a trend towards decrease in arterial stiffness in
individuals with higher blood glucose and high normal BP, but not in any defined
disease state. Therefore, clinical studies are needed to establish any beneficial
effects of C. tinctorius.

References
1. Ahmed KM, Marzouk MS, el-Khrisy EA, et al. A new flavone diglycoside
from Carthamus tinctorius seeds. Pharmazie. 2000;55:621–2.
2. Ahrens EH Jr, Insull W Jr, Blomstrand R, et al. The influence of dietary fats
on serum-lipid levels in man. Lancet. 1957;272:943–53.
3. Akihisa T, Yasukawa K, Oinuma H, et al. Triterpene alcohols from the
flowers of compositae and their anti-inflammatory effects. Phytochemistry.
1996;43:1255–60.
4. Alam MR, Kim SM, Lee JI, et al. Effects of Safflower seed oil in osteoporosis
induced-ovariectomized rats. Am J Chin Med. 2006;34:601–12.
5. Asgarpanah J, Kazemivash N. Phytochemistry, pharmacology and medicinal
properties of Carthamus tinctorius L. Chin J Integr Med. 2013;19:153–9.
6. Asgary S, Rahimi P, Mahzouni P, Madani H. Antidiabetic effect of hydro-
alcoholic extract of Carthamus tinctorius L. in alloxan-induced diabetic rats.
J Res Med Sci. 2012;17:386–92.
7. Bahmanpour S, Vojdani Z, Panjehshahin MR, Hoballah H, Kassas H. Effects
of Carthamus tinctorius on semen quality and gonadal hormone levels in
partially sterile male rats. Korean J Urol. 2012;53:705–10.
8. Bai Y, Lu P, Han C, et al. Hydroxysafflor yellow A (HSYA) from flowers
of Carthamus tinctorius L. and its vasodilatation effects on pulmonary
artery. Molecules. 2012;17:14918–27.
9. Booth AN, Bickoff EM, Kohler GO. Estrogen-like activity in vegetable oils
and mill byproducts. Science. 1960;131:1807–8.
10. Chen TT, Du YJ, Liu XL, Zhu HB. Inhibitory action of hydroxysafflor
yellow A on inflammatory signal transduction pathway related factors in rats
with cerebral cortex ischemia. Yao Xue Xue Bao. 2008;43:570–5 (Chinese).
11. Choi EM, Kim GH, Lee YS. Carthamus tinctorius flower extract prevents
H2O2-induced dysfunction and oxidative damage in osteoblastic MC3T3-E1
cells. Phytother Res. 2010;24:1037–41.
12. Chu D, Liu W, Huang Z, et al. Pharmacokinetics and excretion of hydroxy-
safflor yellow A, a potent neuroprotective agent from safflower, in rats and
dogs. Planta Med. 2006;72:418–23.
Carthamus tinctorius L. 523

13. Duan JL, Wang JW, Guan Y, et al. Safflor yellow A protects neonatal rat
cardiomyocytes against anoxia/reoxygenation injury in vitro. Acta Pharmacol
Sin. 2013;34:487–95.
14. Gao F, Wu XH, Luo CL, et al. Effect of saffor (Carthamus tinctorius)
injection on renal ischemia/reperfusion injury in rats. Zhongguo Zhong Yao
Za Zhi. 2006;31:1814–8 (Chinese).
15. Hamrouni-Sellami I, Salah HB, Kchouk ME, Marzouk B. Variations in
phytosterol composition during the ripening of Tunisian safflower (Cartha-
mus tinctorius L.) seeds. Pak J Biol Sci. 207;10:3829–34.
16. Han SY, Li HX, Bai CC, Wang L, Tu PF. Component analysis and free
radical-scavenging potential of Panax notoginseng and Carthamus tincto-
rius extracts. Chem Biodivers. 2010;7:383–91.
17. Han SY, Li HX, Ma X, et al. Evaluation of the antimyocardial ischemia
effect of individual and combined extracts of Panax notoginseng and
Carthamus tinctorius in rats. J Ethnopharmacol. 2013;145:722–7.
18. Han SY, Li HX, Ma X, et al. Protective effects of purified safflower extract on
myocardial ischemia in vivo and in vitro. Phytomedicine. 2009;16:694–702.
19. Harbige LS, Yeatman N, Amor S, Crawford MA. Prevention of experimental
autoimmune encephalomyelitis in Lewis rats by a novel fungal source of
gamma-linolenic acid. Br J Nutr. 1995;74:701–15.
20. He J, Shen Y, Jiang JS, et al. New polyacetylene glucosides from the florets
of Carthamus tinctorius and their weak anti-inflammatory activities. Carbo-
hydr Res. 2011;346:1903–8.
21. He Y, Liu Q, Li Y, et al. Protective effects of hydroxysafflor yellow A (HSYA)
on alcohol-induced liver injury in rats. J Physiol Biochem. 2015;71:69–78.
22. Hiramatsu M, Takahashi T, Komatsu M, et al. Antioxidant and neuropro-
tective activities of Mogami-benibana (safflower, Carthamus tinctorius
Linne). Neurochem Res. 2009;34:795–805.
23. Hotta Y, Nagatsu A, Liu W, et al. Protective effects of antioxidative
serotonin derivatives isolated from safflower against post-ischemic myocar-
dial dysfunction. Mol Cell Biochem. 2002;238:151–62.
24. Huang JL, Fu ST, Jiang YY, et al. Protective effects of nicotiflorin on
reducing memory dysfunction, energy metabolism failure and oxidative stress
in multi-infarct dementia model rats. Pharmacol Biochem Behav. 2007;86:
741–8.
25. Jang HO, Park YS, Lee JH, et al. Effect of extracts from safflower seeds on
osteoblast differentiation and intracellular calcium ion concentration in
MC3T3-E1 cells. Nat Prod Res. 2007;21:787–97.
26. Jiang JS, Lü L, Yang YJ, et al. New spermidines from the florets of
Carthamus tinctorius. J Asian Nat Prod Res. 2008;10:447–51.
27. Jiang JS, Chen Z, Yang YN, Feng ZM, Zhang PC. Two new glycosides from
the florets of Carthamus tinctorius. J Asian Nat Prod Res. 2013;15:427–32.
28. Jiang JS, He J, Feng ZM, Zhang PC. Two new quinochalcones from the
florets of Carthamus tinctorius. Org Lett. 2010;12:1196–9.
524 Carthamus tinctorius L.

29. Jin M, Sun CY, Zang BX. Hydroxysafflor yellow A attenuate lipopolysac-
charide-induced endothelium inflammatory injury. Chin J Integr Med. 2016;
22:36–41.
30. Kim HJ, Bae YC, Park RW, et al. Bone-protecting effect of safflower seeds
in ovariectomized rats. Calcif Tissue Int. 2002;71:88–94.
31. Kim KW, Suh SJ, Lee TK, et al. Effect of safflower seeds supplementation on
stimulation of the proliferation, differentiation and mineralization of
osteoblastic MC3T3-E1 cells. J Ethnopharmacol. 2008;115:42–9.
32. Koyama N, Kuribayashi K, Seki T, et al. Serotonin derivatives, major
safflower (Carthamus tinctorius L.) seed antioxidants, inhibit low-density
lipoprotein (LDL) oxidation and atherosclerosis in apolipoprotein E-deficient
mice. J Agric Food Chem. 2006;54:4970–6.
33. Kumar N, Rungseevijitprapa W, Narkkhong NA, Suttajit M, Chaiyasut C.
5a-reductase inhibition and hair growth promotion of some Thai plants
traditionally used for hair treatment. J Ethnopharmacol. 2012;139:765–71.
34. Kutsuna H, Fujii S, Kitamura K, et al. Identification and determination of
platelet aggregation inhibitor from safflower (Carthamus tinctorius L.).
J Pharmaceut Soc Japan. 1988;108:1101–3 (Japanese).
35. Li HX, Han SY, Wang XW, et al. Effect of the carthamins yellow from
Carthamus tinctorius L. on hemorheological disorders of blood stasis in
rats. Food Chem Toxicol. 2009;47:1797–802.
36. Li Y, Che Q. Studies on chemical components of Carthamus tinctorius
petals. Yao Xue Xue Bao. 1998;33:626–8 (Chinese).
37. Lin WC, Lai MT, Chen HY, et al. Protective effect of Flos carthami extract
against ethylene glycol-induced urolithiasis in rats. Urol Res. 2012;40:655–61.
38. Liu F, Wei Y, Yang XZ, et al. Hypotensive effects of safflower yellow in
spontaneously hypertensive rats and influence on plasma renin activity and
angiotensin II level. Acta Pharmaceut Sinica. 1992;27:785–7 (Chinese).
39. Liu J, Zhang D, Li J, et al. Effects of Salvia miltiorrhiza and Carthamus
tinctorius aqueous extracts and compatibility on rat myocardial ischemic
reperfusion injury. Zhongguo Zhong Yao Za Zhi. 2011;36:189–94 (Chinese).
40. Liu Y, Yang J, Liu Q. Studies on chemical constituents from the flowers of
Carthamus tinctorius L. Zhong Yao Cai. 2005;28:288–9 (Chinese).
41. Louei Monfared A, Salati AP. Effects of Carthamus tinctorius L. on the
ovarian histomorphology and the female reproductive hormones in mice.
Avicenna J Phytomed. 2013;3:171–7.
42. Luo Z, Zeng H, Ye Y, et al. Safflower polysaccharide inhibits the proliferation
and metastasis of MCF-7 breast cancer cell. Mol Med Rep. 2015;11:4611–6.
43. Matthaus B, Özcan MM, Al Juhaimi FY. Fatty acid composition and
tocopherol profiles of safflower (Carthamus tinctorius L.) seed oils. Nat Prod
Res. 2015;29:193–6.
44. Meselhy MR, Kadota S, Momose Y, et al. Tinctormine, a novel Ca2+ anta-
gonist N-containing quinochalcone C-glycoside from Carthamus tinctorius
L. Chem Pharmaceut Bull. 1992;40:3355–7.
Carthamus tinctorius L. 525

45. Meselhy MR, Kadota S, Momose Y, et al. Two new quinochalcone yellow
pigments from Carthamus tinctorius and Ca2+ antagonistic activity of
tinctormine. Chem Pharmaceut Bull. 1993;41:1796–802.
46. Mirhoseini M, Mohamadpour M, Khorsandi L. Toxic effects of Carthamus
tinctorius L. (Safflower) extract on mouse spermatogenesis. J Assist Reprod
Genet. 2012;29:457–61.
47. Nie PH, Zhang L, Zhang WH, Rong WF, Zhi JM. The effects of hydroxysafflor
yellow A on blood pressure and cardiac function. J Ethnopharmacol. 2012;
139:746–50.
48. Nobakht M, Fattahi M, Hoormand M, et al. A study on the teratogenic and
cytotoxic effects of safflower extract. J Ethnopharmacol. 2000;73:453–9.
49. Pan Y, Zheng DY, Liu SM, et al. Hydroxysafflor yellow A attenuates
lymphostatic encephalopathy-induced brain injury in rats. Phytother Res.
2012;26:1500–6.
50. Pawar SS, Tidwell HC. Cholesterol and lipid levels in blood and livers of
rats fed unsaturated fats. Am J Physiol. 1967;213:1350–502.
51. Qazi N, Khan RA, Rizwani GH, Feroz Z. Effect of Carthamus tinctorius
(Safflower) on fasting blood glucose and insulin levels in alloxan induced
diabetic rabbits. Pak J Pharm Sci. 2014;27:377–80.
52. Salem N, Msaada K, Hamdaoui G, Limam F, Marzouk B. Variation in
phenolic composition and antioxidant activity during flower development of
safflower (Carthamus tinctorius L.). J Agric Food Chem. 2011;59:4455–63.
53. Shan LQ, Ma S, Qiu XC, et al. Hydroxysafflor yellow A protects spinal
cords from ischemia/reperfusion injury in rabbits. BMC Neurosci. 2010;
11:98.
54. Sun CY, Pei CQ, Zang BX, Wang L, Jin M. The ability of hydroxysafflor
yellow A to attenuate lipopolysaccharide-induced pulmonary inflammatory
injury in mice. Phytother Res. 2010;24:1788–95.
55. Suzuki K, Tsubaki S, Fujita M, et al. Effects of safflower seed extract on
arterial stiffness. Vasc Health Risk Manag. 2010;6:1007–14.
56. Takahashi T, Miyazawa M. Potent a-glucosidase inhibitors from safflower
(Carthamus tinctorius L.) seed. Phytother Res. 2012;26:722–6.
57. Takahashi Y, Saito K, Yanagiya M, Ikura M, Hikichi K. Chemical
constitution of safflor yellow B, a quinochalcone C-glycoside from the
flower petals of Carthamus tinctorius L. Tetrahedron Lett. 1984;25:2471–4.
58. Wan LH, Chen J, Li L, Xiong WB, Zhou LM. Protective effects of
Carthamus tinctorius injection on isoprenaline-induced myocardial injury in
rats. Pharm Biol. 2011;49:1204–9.
59. Wang CY, Liu Q, Huang QX, et al. Activation of PPARc is required for
hydroxylsafflor yellow A of Carthamus tinctorius to attenuate hepatic
fibrosis induced by oxidative stress. Phytomedicine. 2013;20:592–9.
60. Wang L, Jin M, Zang BX, Wu Y. Inhibitory effect of safflor yellow on
pulmonary fibrosis. Biol Pharm Bull. 2011;34:511–6.
526 Carthamus tinctorius L.

61. Wang XF, Jin M, Tong J, et al. Protective effect of hydroxysafflor yellow A
against acute lung injury induced by oleic acid and lipopolysaccharide in
rats. Yao Xue Xue Bao. 2010;45:940–4 (Article in Chinese).
62. Wang Y, Chen P, Tang C, et al. Antinociceptive and anti-inflammatory
activities of extract and two isolated flavonoids of Carthamus tinctorius L.
J Ethnopharmacol. 2014;151:944–50.
63. Wang Y, Xue C, Dong F, et al. Hydroxysafflor yellow A attenuates small
airway remodeling in a rat model of chronic obstructive pulmonary disease.
Biol Pharm Bull. 2014;37:1591–8.
64. Wu S, Yue Y, Tian Het al. Carthamus red from Carthamus tinctorius L.
exerts antioxidant and hepatoprotective effect against CCl(4)-induced liver
damage in rats via the Nrf2 pathway. J Ethnopharmacol. 2013;148:570–8.
65. Wu Y, Wang L, Jin M, Zang BX. Hydroxysafflor yellow A alleviates early
inflammatory response of bleomycin-induced mice lung injury. Biol Pharm
Bull. 2012;35:515–22.
66. Xie X, Zhou J, Sun L, et al. A new flavonol glycoside from the florets
of Carthamus tinctorius L. Nat Prod Res. 2016;30:150–6.
67. Yadava RN, Chakravarti N. Anti-inflammatory activity of a new triter-
penoid saponin from Carthamus tinctorius linn. J Enzyme Inhib Med Chem.
2008;23:543–8.
68. Yamada K, Kuzuya F, Yokoyama T, et al. Effects of vitamin B6 and
safflower oil on dietarily induced hyperlipemia and fat in the liver of rats.
J Vitaminol (Kyoto). 1965;11:215–9.
69. Yan LG, Ruan JS, Zhang L, et al. Effect of aqueous extracts of several kinds
of herbs on human platelet aggregation and expression of P-selectin in vitro.
Chin J Integr Med. 2015;21:286–90.
70. Yang F, Li J, Zhu J, et al. Hydroxysafflor yellow A inhibits angiogenesis of
hepatocellular carcinoma via blocking ERK/MAPK and NF-jB signaling
pathway in H22 tumor-bearing mice. Eur J Pharmacol. 2015;754:105–14.
71. Yang Q, Yang ZF, Liu SB, et al. Neuroprotective effects of hydroxysafflor
yellow A against excitotoxic neuronal death partially through downregulation
of NR2B-containing NMDA receptors. Neurochem Res. 2010;35:1353–60.
72. Yasukawa K, Akihisa T, Kasahara Y, et al. Inhibitory effect of alkane-6,8-diols,
the components of safflower, on tumor promotion by 12-O-tetradecanoylphorbol-
13-acetate in two-stage carcinogenesis in mouse skin. Oncology. 1996;53:133–6.
73. Yoo HH, Park JH, Kwon SW. An antiestrogenic lignan glycoside, tracheloside,
from seeds of Carthamus tinctorius. Biosci Biotechnol Biochem. 2006;70:
2783–5.
74. Yu SY, Lee YJ, Kim JD, et al. Phenolic composition, antioxidant activity
and antiadipogenic effect of hot water extract from safflower (Carthamus
tinctorius L.) seed. Nutrients. 2013;5:4894–907.
75. Yue S, Tang Y, Xu C, et al. Two new quinochalcone C-glycosides from the
florets of Carthamus tinctorius. Int J Mol Sci. 2014;15:16760–71.
Carthamus tinctorius L. 527

76. Zhang Y, Guo J, Dong H, et al. Hydroxysafflor yellow A protects against

chronic carbon tetrachloride-induced liver fibrosis. Eur J Pharmacol. 2011;
660:438–44.
77. Zhao G, Gai Y, Chu WJ, Qin GW, Guo LH. A novel compound N(1),N(5)-
(Z)-N(10)-(E)-tri-p-coumaroylspermidine isolated from Carthamus tincto-
rius L. and acting by serotonin transporter inhibition. Eur Neuropsychophar-
macol. 2009;19:749–58.
78. Zhou X, Tang L, Xu Y, Zhou G, Wang Z. Towards a better understanding
of medicinal uses of Carthamus tinctorius L. in traditional Chinese
medicine: a phytochemical and pharmacological review. J Ethnopharmacol.
2014;151:27–43.
79. Zhou YZ, Chen H, Qiao L, et al. Two new compounds from Carthamus
tinctorius. J Asian Nat Prod Res. 2008;10:429–33.
80. Zhou YZ, Qiao L, Chen H, et al. New aromatic glucosides from Carthamus
tinctorius. J Asian Nat Prod Res. 2008;10:817–21.
81. Zhu H, Wang Z, Ma C, et al. Neuroprotective effects of hydroxysafflor
yellow A: in vivo and in vitro studies. Planta Med. 2003;69:429–33.
82. Zhu HB, Zhang L, Wang ZH, et al. Therapeutic effects of hydroxysafflor
yellow A on focal cerebral ischemic injury in rats and its primary mecha-
nisms. J Asian Nat Prod Res. 2005;7:607–13.
Carum carvi L.
(Apiaceae/Umbelliferae)

(Syns.: Apium carvi (L.) Crantz; Bunium carum M. Bieb.; B. carvi (L.) M. Bieb.;
Carum officinale S.F. Gray; C. velenovskyi Rohlena; Foeniculum carvi (L.) Link;
Ligusticum carvi (L.) Roth; Sium carvi (L.) Bernh)

Abstract
The plant is native to western Asia, northern Africa and Europe. Fruits erroneously
called seeds (at harvesting fruits split, and are called seeds) are crescent-shaped
achenes. Seeds (fruits) are described in Unani medicine as astringent, coagulant,
expectorant and tonic for lungs, stomachic, eupeptic, digestive, carminative,
antispasmodic, antidiarrheal, diuretic, and galactagogue; used to relieve flatulence
and flatulent colic in infants, and to allay hiccough. In Ayurveda, seeds are used in
agnimãndya, ãdhmãna, jirnajvara, grahaniroga and krmiroga. Vapors from
caraway seeds are reported to relieve pain in patients suffering from lumbago and
rheumatism. In Iranian traditional medicine, caraway is indicated for treatment of
epilepsy. Major constituents of caraway are carvacrol, carvone, a-pinene, limonene,
c-terpinene, carvenone, linalool, and p-cymene. Seeds of annual caraway varieties
have lower EO content than fruits of biennial varieties, and biennial caraway usually
has a higher carvone-to-limonene ratio. Flavonoid constituents of seeds are
quercetin 3-glucuronide, isoquercitrin, quercetin 3-O-caffeylglucoside and kaemp-
ferol 3-glucoside, and monoterpenes: anethofuran, carvone and limonene. Aqueous
fruit extract and EO exhibit significant antiulcerogenic activity in rats. Hydro-
alcohol extract and EO are also significantly protective against TNBS-induced
colitis in rats, regardless of their route of administration. Repeated oral adminis-
tration of aqueous extract significantly reduced FBG, TC, LDL-C, non-HDL-C, and
LDL-C/HDL-C ratio of diabetic rats, without affecting blood glucose levels of
normal rats, and no changes in basal plasma insulin concentrations. In a triple-blind
RCT, administration of aqueous extract to healthy but overweight and obese adult
females for 90-days significantly reduced body weight, BMI, body fat percentage,
and waist-to-hip ratio, with lipid profile, urine specific gravity, and BP remaining
unaffected.

© Springer Nature Switzerland AG 2020 529

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_56
530 Carum carvi L.

Keywords






Black caraway Brotkümmel Carvi Gě lǚ zi Kalazira Karve Karwijzaad




Kimyon Krsnajiraka Kumina

Vernaculars: Urd.: Kala zeera, Kamoon kirmani, Zeera siyah; Hin.: Kalazira,
Siyah jeera, Zira; San.: Jaranah, Kãśmirajiraka, Krsnajiraka, Sugandhah,
Udgãrśodhanaah; Ben.: Jira, Kala jira, Shia-jira; Mal.: Karinjeerakam, Karunjiraka,
Sajirakam; Mar.: Sa-jire, Shahira, Shahajira, Shalajira; Tam.: Karamjiragam,
Pilappushiragam, Shimai-jeerakam, Shimaishiragam, Shimaishombu; Tel.: Jee-
lakarra, Nalla, Shimaisapu, Sima-jilakara; Ara.: Carawiya, Kamun-e-rumi, Kar-
awiya; Bur.: Ziya; Chi.: 葛缕子, Gě lǚ zi; Cze.: Kmin kořenný, Kmín luční; Dan.:
Karve, Kommen; Dut.: Echte karwij, Karwijzaad (seeds), Kummel, Wilde komijn;
Eng.: Black caraway, Caraway seeds; Fin.: Kumina, Saksan kumina, Tavallinen
kumina; Fre.: Anis des vosges, Carvi, Cumin des montagnes, Cumin des prés,
Grains de carvi; Ger.: Brotkümmel, Echter kümmel, Echtkümmel, Feldkümmel,
Gemeiner kümmel, Gewöhnlicher kümmel, Mattenkümmel, Speisekümmel, Wie-
senkümmel; Gre.: Karo, Karvi; Hun.: Kömeny, Köménymag (seeds); Ind.: Jintan;
Ita.: Anice dei vosgi, Caro, Carvi, Comino tedesco, Cumino dei prati; Jap.:
Himeuikyô, Karumu, Kiyarawei; Kor.: Kaerowei; Nor.: Karve; Per.: Zireh-
kirmani, Zireh-siah; Pol.: Kminek zwyczajny; Por.: Alcarávia, Cuminho, Semente
de alcarávia (seeds); Rus.: Tmin obyknovennyj; Spa.: Alcaravea, Carvi, Comino de
prado, Hinojo de prado; Swe.: Brödkummin, Kummin; Tha.: Hom pom, Thiam
takap; Tur.: Hakiki kimyon, Kimyon.
Description: Native to western Asia, northern Africa and Europe, the plant has
finely divided, feathery leaves with thread-like divisions, growing on 20–30 cm
long stems. Main flower stem is 40–60 cm tall, with small white or pink flowers in
umbels. Fruits erroneously called seeds (at harvesting fruits split, and are called
seeds), are crescent-shaped achenes, ovoid, slightly arched, laterally compressed,
crowned by the style. They vary in size but are generally 4 mm long and 1.25 mm
in diameter with five pale ridges; brown in color, but the ribs are of a lighter color
than the furrows.XL They have pungent, anise-like flavor and odor, due to the
presence of essential oils, containing carvone and limonene (Figs. 1, 2 and 3).
Actions and Uses: Seeds (fruits) are aromatic, carminative, astringent, pectoral,
diuretic and anthelmintic. Caraway bath is recommended for painful swellings of the
womb and a poultice for painful and protruding piles.XL Seeds (temperament, hot 2°
and dry 2°) are described as astringent and coagulant in Unani medicine; the water
after soaking seeds in it is used to cleanse face. Internally, it is considered expectorant
and tonic for lungs, stomachic, eupeptic, digestive, carminative, antispasmodic,
antidiarrheal, diuretic, and galactagogue;LXXVII,CV also described as stimulant, and
used to relieve flatulence and flatulent colic in infants, and to allay hiccough.XXI,LXXXI
In Ayurveda, seeds are used in agnimãndya, ãdhmãna, jirnajvara, grahaniroga and
krmiroga.LX Vapors from caraway seeds are reported to relieve pain in patients suf-
fering from lumbago and rheumatism.LXXXIV In Iranian traditional medicine, caraway
Carum carvi L. 531

Fig. 1 Carum carvi, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wikimedia-
Commons, https://commons.wikimedia.org/wiki/File:Carum_carvi_-_K%C3%B6hler%E2%80%93s_
Medizinal-Pflanzen-172.jpg

Fig. 2 Carum carvi, Seeds (close up), Slick, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:K%C3%BCmmel_2012-07-08-9523.jpg

is indicated for treatment of epilepsy [38]. In the Errachidia province of south-eastern

Morocco, it is one of the most commonly used drugs by traditional healers to treat
diabetes and hypertension [39]. It is also regarded stomachic and carminative in the
UK and USA,CXIV and used as a remedy for flatulence, indigestion, lack of appetite
532 Carum carvi L.

Fig. 3 Carum carvi, Seeds (Actual size), Prof. Akbar, Original

and as a galactagogue in Poland. Russians use it in the treatment of pneumonia, and it is

utilized in Indonesia to treat inflamed eczema [34]. The fruits (essential oil) are
employed as flavor and carminative.CXXXXI A number of clinical trials on compound
drugs of which caraway was the main constituents showed significant improvement in
nonulcer dyspepsia [40]. Anethole, generally regarded as a minor product in the EO of
this species, has also been found to be a major component.LXXV
Phytoconstituents: The herb contains (+)-carvone and (+)-limonene as its major
monoterpene components. Johri [15] reported carvacrol, carvone, a-pinene, limo-
nene, c-terpinene, carvenone, linalool, and p-cymene as the major compounds in
caraway. Seeds (fruits) of annual caraway varieties have lower EO content than fruits
of biennial varieties [4], and biennial caraway usually has a higher carvone-
to-limonene ratio [3]. Flavonoid constituents of seeds are quercetin 3-glucuronide,
isoquercitrin, quercetin 3-O-caffeylglucoside and kaempferol 3-glucoside [23], and
monoterpenes: anethofuran, carvone and limonene [41]. Limonene (terpene) and
carvone (ketone) were initially reported as the major constituents of volatile
oil,LXXXVIII but later various authors described different contents of EO as the major
constituents. Furia and BellancaXLVII described 50–76% carvone, d-limonene, car-
veol, diacetyl furfural, methyl alcohol, and acetic aldehyde as the contents of EO.
From Italy, main components of the oil were reported as carvone, limonene, germa-
crene D, and trans-dihydrocarvone [14]. Oil from young fruits from the wildly
growing caraway in meadows of Vienna region of Austria had a high proportion of
limonene (61–83%), and those from inflorescences limonene (39–62%) and germa-
crene D (23–41%) [5], but EOs of fruits obtained from Tunisia and Lithuania showed
high contents of carvone and limonene [2]. Tunisian caraway seeds oil was also
Carum carvi L. 533

reported rich in an unusual fatty acid-petroselinic acid, which varied from 31.53 to
38.36% of the total fatty acids [25].
Pharmacology: Aqueous fruit extract exhibits antiulcerogenic activity against
indomethacin-induced ulcers in rats, associated with a reduced acid output and
increased mucin secretion, an increase in PGE2 release and a decrease in leuko-
trienes [22], while EO, in 200 and 300 mg/kg doses protected against HCl/EtOH-
induced gastric ulcers 81% and 88%, respectively, compared to 95% protection by
omeprazole [2]. Ethanol extract inhibited ACh-induced contractions of dispersed
intestinal smooth muscle cells of guinea pigs; which may explain, in part, the
beneficial effect of caraway in relieving gastrointestinal symptoms associated with
dyspepsia [1]. Both hydroalcohol extract and EO were significantly effective against
TNBSA-induced colitis in rats, regardless of their route of administration by mouth
or i.p [21]. Methanol fruit extract inhibited growth of H. pylori [27], whereas EO
inhibited growth of E. coli and S. aureus [28], C. ramosum [16], and of potential
intestinal pathogenic bacteria (C. albicans, C. difficile, C. perfringens and B. fragilis)
at concentrations that did not affect the beneficial organisms [13]. De Martino et al.
[9] reported predominantly oxygenated monoterpenes in the EO that exhibited
potent antioxidant activity due to the presence of carvacrol, anethole and estragol,
and antibacterial activity against B. cereus and P. aeruginosa. Carvacrol is the most
active against E. coli, and completely inhibits growth of P. citrinum.
Three-weeks dosing of aqueous extract to diabetic rats significantly reduced
FBG, TC, LDL-C, non-HDL-C, and LDL-C/HDL-C ratio, without affecting CRP
[33]. Blood glucose levels were nearly normalized two weeks after daily repeated
oral administration of aqueous extract to STZ-diabetic rats, with no significant
changes in blood glucose levels of normal rats, and no changes in basal plasma
insulin concentrations in either normal or STZ-diabetic rats [11], and also protected
rats against diabetic nephropathy [32]. Oral administration of caraway to
STZ-diabetic rats for three-weeks also significantly decreased blood TC and LDL-C
with no significant change in TGs and HDL-C levels, and attenuated body weight
loss [12], but repeated oral administration of aqueous extract significantly reduced
TGs and TC in both normal and STZ-diabetic rats [26]. In a comparative study,
aqueous extract produced better hypolipidemic effects in diet-induced hyperlipi-
demic rats than simvastatin [35]. Aqueous extract shows strong antioxidant activity
that is superior to ascorbic acid [37]. Aqueous extract and EO increased latency to
the onset of myoclonic and clonic PTZ-seizures, and the oil protected > 70% mice
from death [38]. Caraway oil was protective against sepsis-induced oxidative injury
to kidneys [8], and reduced LPO in CCl4-hepatotoxicity in rats [36]. Aqueous extract
also significantly increased urine output and urinary excretion of Na+ and K+,
without affecting plasma levels of Na+ and K+ [24].
Caraway supplementation in diet for 15-weeks significantly reduced aberrant
cryptic foci development in DMH-induced colon carcinogenesis in rats, and
decreased levels of fecal bile acids, neutral sterols, and tissue ALP activities [10, 17],
and thirty-weeks supplementation diminished levels of intestinal, colonic and caecal
lipoperoxide products, such as conjugated dienes, lipid hydroperoxides and TBARS,
and significantly reversed decrease of antioxidant enzymes [18].
534 Carum carvi L.

Clinical Studies: In a triple-blind RCT, administration of aqueous extract to

healthy but overweight and obese adult Iranian females for 90-days significantly
reduced body weight, BMI, body fat percentage, and waist-to-hip ratio; however,
lipid profile, urine specific gravity, and BP were not affected [20]; RBC counts were
significantly increased, but no other significant changes in HR, and blood chemistry
were noted after 12-weeks of treatment [19].
Mechanism of Action: DMH-induced colon premalignant lesions inhibition is
mediated through hepatic xenobiotic metabolizing (CYP1A1) enzymes [7], that is
known to convert xenobiotics and endogenous compounds to toxic and/or car-
cinogenic metabolites [29].
Human A/Es, Allergy and Toxicity: An Iranian patient with papillary thyroid
carcinoma, being treated with levothyroxine experienced an elevated TSH level after
ingesting caraway; the TSH levels returned to normal after discontinuing caraway.
This prompted one of the researchers with hypothyroidism and maintained on
levothyroxine, to experimentally take caraway 40 mg/kg/day, that resulted in her
TSH level increased after two-weeks, which returned to normal after five months of
discontinuing caraway [30]. It is also regarded harmful for lungs.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interactions: The seed extracts caused
approximately 10-fold suppression of the CYP1A1 enzyme activity, an enzyme
known to convert xenobiotics and endogenous compounds to toxic and/or car-
cinogenic metabolites [29]. A product containing caraway increased bioavailability
of rifampicin, pyrazinamide, and isoniazid in Wistar rats, resulting in enhanced
plasma levels [31], and addition of butanol fruit extract to a fixed dose combination
of isoniazid, rifampicin and pyrazinamide, significantly increased oral bioavail-
ability of these antitubercular drugs in healthy volunteers [6].
Commentary: Caraway fruits (seeds) are generally used as spice in the Indian
subcontinent, and in Ayurveda and Unani polyherbal formulations for their bene-
ficial effects on the GIT. However, their effects on diabetes and lipids, as demon-
strated by pharmacological studies, and positive effects on body weight observed in
Iranian obese, healthy individuals need further exploration in RCTs.

References
1. Al-Essa MK, Shafagoj YA, Mohammed FI, Afifi FU. Relaxant effect of
ethanol extract of Carum carvi on dispersed intestinal smooth muscle cells
of the guinea pig. Pharm Biol. 2010;48:76–80.
2. Baananou S, Bagdonaite E, Marongiu B, et al. Extraction of the volatile oil
from Carum carvi of Tunisia and Lithuania by supercritical carbon dioxide:
chemical composition and antiulcerogenic activity. Nat Prod Res. 2013;27:
2132–6.
Carum carvi L. 535

3. Bouwmeester HJ, Gershenzon J, Konings MCJM, Croteau R. Biosynthesis

of the monoterpenes, limonene and carvone in the fruit of caraway. Plant
Physiol. 1998;117:901–12.
4. Bouwmeester HJ, Kuijpers A-M. Relationship between assimilate supply
and essential oil accumulation in annual and biennial caraway (Carum carvi
L.). J Essent Oil Res. 1993;5:143–52.
5. Chizzola R. Composition of the essential oil of wild grown caraway in
meadows of the Vienna region (Austria). Nat Prod Commun. 2014;9:581–2.
6. Choudhary N, Khajuria V, Gillani ZH, Tandon VR, Arora E. Effect
of Carum carvi, a herbal bioenhancer on pharmacokinetics of antitubercular
drugs: a study in healthy human volunteers. Perspect Clin Res. 2014;5:80–4.
7. Dadkhah A, Allameh A, Khalafi H, Ashrafihelan J. Inhibitory effects of dietary
caraway essential oils on 1,2-dimethylhydrazine-induced colon carcinogen-
esis is mediated by liver xenobiotic metabolizing enzymes. Nutr Cancer.
2011;63:46–54.
8. Dadkhah A, Fatemi F. Heart and kidney oxidative stress status in septic rats
treated with caraway extracts. Pharm Biol. 2011;49:679–86.
9. De Martino L, De Feo V, Fratianni F, Nazzaro F. Chemistry, antioxidant,
antibacterial and antifungal activities of volatile oils and their components.
Nat Prod Commun. 2009;4:1741–50.
10. Deeptha K, Kamaleeswari M, Sengottuvelan M, Nalini N. Dose dependent
inhibitory effect of dietary caraway on 1,2-dimethylhydrazine induced colonic
aberrant crypt foci and bacterial enzyme activity in rats. Invest New Drugs.
2006;24:479–88.
11. Eddouks M, Lemhadri A, Michel JB. Caraway and caper: potential anti-
hyperglycaemic plants in diabetic rats. J Ethnopharmacol. 2004;94:143–8.
12. Haidari F, Seyed-Sadjadi N, Taha-Jalali M, Mohammed-Shahi M. The effect of
oral administration of Carum carvi on weight, serum glucose, and lipid profile
in streptozotocin-induced diabetic rats. Saudi Med J. 2011;32:695–700.
13. Hawrelak JA, Cattley T, Myers SP. Essential oils in the treatment of intestinal
dysbiosis: a preliminary in vitro study. Altern Med Rev. 2009;14:380–4.
14. Iacobellis NS, Lo Cantore P, Capasso F, Senatore F. Antibacterial activity of
Cuminum cyminum L. and Carum carvi L. essential oils. J Agric Food Chem.
2005;53:57–61.
15. Johri RK. Cuminum cyminum and Carum carvi: an update. Pharmacogn
Rev. 2011;5:63–72.
16. Kačániová M, Vukovič N, Horská E, et al. Antibacterial activity against
Clostridium genus and antiradical activity of the essential oils from different
origin. J Environ Sci Health B. 2014;49:505–12.
17. Kamaleeswari M, Deeptha K, Sengottuvelan M, Nalini N. Effect of dietary
caraway (Carum carvi L.) on aberrant crypt foci development, fecal steroids, and
intestinal alkaline phosphatase activities in 1,2-dimethylhydrazine-induced
colon carcinogenesis. Toxicol Appl Pharmacol. 2006;214:290–6.
536 Carum carvi L.

18. Kamaleeswari M, Nalini N. Dose-response efficacy of caraway (Carum

carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon
carcinogenesis. J Pharm Pharmacol. 2006;58:1121–30.
19. Kazemipoor M, Radzi CW, Hajifaraji M, Cordell GA. Preliminary safety
evaluation and biochemical efficacy of a Carum carvi extract: results from a
randomized, triple-blind, and placebo-controlled clinical trial. Phytother
Res. 2014;28:1456–60.
20. Kazemipoor M, Radzi CW, Hajifaraji M, et al. Antiobesity effect of caraway
extract on overweight and obese women: a randomized, triple-blind, placebo-
controlled clinical trial. Evid Based Complement Alternat Med. 2013;2013:
928582.
21. Keshavarz A, Minaiyan M, Ghannadi A, Mahzouni P. Effects of Carum
carvi L. (Caraway) extract and essential oil on TNBS-induced colitis in rats.
Res Pharm Sci. 2013;8:1–8.
22. Khayyal MT, el-Ghazaly MA, Kenawy SA, et al. Antiulcerogenic effect of
some gastrointestinally acting plant extracts and their combination. Arzneimit-
telforschung. 2001;51:545–53.
23. Kunzemann J, Herrmann K. Isolation and identification of flavon(ol)-
O-glycosides in caraway (Carum carvi L.), fennel (Foeniculum vulgare
Mill.), anise (Pimpinella anisum L.), and coriander (Coriandrum sativum L.),
and of flavon-C-glycosides in anise. I. Phenolics of spices (author’s transl).
Z Lebensm Unters Forsch. 1977;164:194–200.
24. Lahlou S, Tahraoui A, Israili Z, Lyoussi B. Diuretic activity of the aqueous
extracts of Carum carvi and Tanacetum vulgare in normal rats. J Ethnophar-
macol. 2007;110:458–63.
25. Laribi B, Kouki K, Mougou A, Marzouk B. Fatty acid and essential oil
composition of three Tunisian caraway (Carum carvi L.) seed ecotypes.
J Sci Food Agric. 2010;90:391–6.
26. Lemhadri A, Hajji L, Michel JB, Eddouks M. Cholesterol and triglycerides
lowering activities of caraway fruits in normal and streptozotocin diabetic
rats. J Ethnopharmacol. 2006;106:321–6.
27. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helico-
bacter pylori to botanical extracts used traditionally for the treatment of gastro-
intestinal disorders. Phytother Res. 2005;19:988–91.
28. Mohsenzadeh M. Evaluation of antibacterial activity of selected Iranian
essential oils against Staphylococcus aureus and Escherichia coli in nutrient
broth medium. Pak J Biol Sci. 2007;10:3693–7.
29. Naderi-Kalali B, Allameh A, Rasaee MJ, et al. Suppressive effects of caraway
(Carum carvi) extracts on 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-dependent
gene expression of cytochrome P450 1A1 in the rat H4IIE cells. Toxicol In
Vitro. 2005;19:373–7.
30. Naghibi SM, Ramezani M, Ayati N, Zakavi SR. Carum induced hypothy-
roidism: an interesting observation and an experiment. Daru. 2015;23:5.
Carum carvi L. 537

31. Sachin BS, Monica P, Sharma SC, et al. Pharmacokinetic interaction of

some antitubercular drugs with caraway: implications in the enhancement of
drug bioavailability. Hum Exp Toxicol. 2009;28:175–84.
32. Sadiq S, Nagi AH, Shahzad M, Zia A. The renoprotective effect of aqueous
extract of Carum carvi (black zeera) seeds in streptozotocin induced diabetic
nephropathy in rodents. Saudi J Kidney Dis Transpl. 2010;21:1058–65.
33. Sadjadi NS, Shahi MM, Jalali MT, Haidari F. Short-term caraway extract
administration improves cardiovascular disease risk markers in streptozotocin-
induced diabetic rats: a dose-response study. J Diet Suppl. 2014;11:30–9.
34. Sadowska A, Obidoska G. Caraway. In: Nemeth E, editor. The genus Carum.
Boca Raton, FL: CRC Press; 2004.
35. Saghir MR, Sadiq S, Nayak S, Tahir MU. Hypolipidemic effect of aqueous
extract of Carum carvi (black Zeera) seeds in diet induced hyperlipidemic
rats. Pak J Pharm Sci. 2012;25:333–7.
36. Samojlik I, Lakić N, Mimica-Dukić N, Daković-Svajcer K, Bozin B.
Antioxidant and hepatoprotective potential of essential oils of coriander
(Coriandrum sativum L.) and caraway (Carum carvi L.) (Apiaceae). J Agric
Food Chem. 2010;58:8848–53.
37. Satyanarayana S, Sushruta K, Sarma GS, et al. Antioxidant activity of the
aqueous extracts of spicy food additives—evaluation and comparison with
ascorbic acid in in-vitro systems. J Herb Pharmacother. 2004;4:1–10.
38. Showraki A, Emamghoreishi M, Oftadegan S. Anticonvulsant effect of the
aqueous extract and essential oil of Carum Carvi L. seeds in a pentylenete-
trazol model of seizure in mice. Iran J Med Sci. 2016;41:200–8.
39. Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B. Ethnopharmacological survey
of plants used in the traditional treatment of hypertension and diabetes in
south-eastern Morocco (Errachidia province). J Ethnopharmacol. 2007;110:
105–17.
40. Thompson Coon J, Ernst E. Systematic review: herbal medicinal products for
nonulcer dyspepsia. Aliment Pharmacol Ther. 2002;16:1689–99 (Review).
41. Zheng GQ, Kenney PM, Lam LK. Anethofuran, carvone, and limonene:
potential cancer chemopreventive agents from dill weed oil and caraway oil.
Planta Med. 1992;58:338–41.
Cassia fistula L.
(Fabaceae/Leguminosae)

(Syns.: C. bonplandiana DC; C. excelsa Kunth; C. fistuloides Collad; C. rhombifolia Roxb.)

Abstract
A moderate-sized erect, deciduous tree of tropical Asia. Arabs are credited for
the discovery of medicinal uses of its pulp, which is mild laxative in small doses
and acts as a purgative in large doses. Greek physicians came to know about the
drug through Arab physicians, and described it as lenitive, useful for relieving
thoracic obstructions and heat of blood, a safe aperient for children and women,
even when pregnant, but slow in action. It is well adapted to febrile and
inflammatory afflictions and is a convenient, palatable purgative for children;
however, external application of pods provokes abortion and expulsion of
placenta. Fruit pulp is also used in Ayurveda for vibandha, udavarta, gulma,
sula, udararoga, hrdroga, and prameha. Externally, it is said to be a good
application in gout and rheumatism. In traditional Iranian medicine, it has been
used for the treatment of IBD. Leaves are used in Panamanian folk medicine for
treatment of diabetes, and in northern Peru, it is traditionally used to treat
bacterial infections, which are referred to by local healers as ‘inflammation.’
Native populations of Tanzania, Zimbabwe, Mozambique and Brazil use the
plant to treat malaria and associated symptoms, and in Brazil, the root is also
used as anthelmintic. Anthraquinone glycosides, the active laxative content, are
concentrated in leaves and flowers during peak flowering, and hydroxy-
anthraquinones reach peak during the months of September and October. Fruit
pulp contains a sterol, clerosterol with antileishmanial activity and significantly
less toxicity than pentamidine, and is rich in mineral nutrients, potassium and
calcium. Seeds and various flower extracts have shown antibacterial, antifungal,
and antioxidant properties. Fluconazole-resistant Candida species isolated from
HIV patients (C. krusei and C. parapsilosis) were most sensitive to ethanol seed
extract. Methanol leaf extract is larvicidal and ovicidal to chikungunya vector,
Aedes aegypti, and filarial and malarial vector mosquitos. Seed powder killed
100% trophozoites of axenically grown E. histolytica and cured experimental

© Springer Nature Switzerland AG 2020 539

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_57
540 Cassia fistula L.

intestinal amoebiasis in rats and hepatic amoebiasis in golden hamsters. In clinical

trials, patients aged 12–60 years old, treated with 150–250 mg dose/day of seed
powder were cured of amoebiasis in seven days.

Keywords






Amaltaas Aragwadha Cañafístula Canéficier Fistelkassie Indian laburnum




Khiyar-shamber La chang shu Nanban saikachi Roerkassia

Vernaculars: Urd.: Amaltaas, Khayar-shamber; Hin.: Amaltaas, Aragvadha,

Bandarlauri, Girimala, Sonhali; San.: Aragbhada, Aragwadha, Ārevata, Caturan-
gula, Dirghaphala, Karnikãra, Krtamala, Nripadruma, Rajataru, Rajavraksha,
Śampãka, Suvarnaka, Vyãdhighãta; Ben.: Amaltas, Amultas, Bundarlati, Sonali,
Sonalu, Sondal, Sondala, Sondhali, Soondali; Guj.: Garmalo; Mal.: Kanikonna,
Konikkonna, Konna, Kritamalam, Svarnaviram; Mar.: Amaltas, Bahava, Bhava,
Boya, Kaniar, Karangal, Kiar; Tam.: Appai, Arakkuvadam, Irjiviruttam, Kay,
Kone, Konnai, Konraikkai, Mambala-konnai, Sarakkonai, Sarakondai, Sarakonrai,
Sharak-konraik-kai; Tel.: Aragvadamu, Aragvadhamu, Koelapenna, Kolaponna,
Kondrakaya, Kondrakayi, Raelachettu, Relagujju, Rela-kayalu; Ara.: Khiyar-
shamber; Bur.: Mai lum, Ngu; Chi.: 腊肠树, A bo le, La chang shu; Dan.:
Roerkassia; Dut.: Indishe goude regen; Eng.: Golden shower tree, Indian laburnum,
Pudding pipe tree, Purging cassia; Fin.: Kultasadekassia; Fre.: Bâton casse,
Canéficier, Cassé, Cassie fistuleuse, Cassier commun; Ger.: Fistelkassie, Indischer
mannabaum, Purgierkassie, Röhrenkassie; Ita.: Cassia fistola, Cassia in bastoni,
Fistola della cassia; Jap.: Nanban saikachi; Lao.: Khoun; Maly.: Bereksa, Kayu
raja, Keyok, Sonawir and Tanggoeli (Java); Nep.: Amaltas, Amaltash; Nor.: Kasja;
Per.: Flous, Khiyar-shamber; Por.: Canafista, Cássia, Cássia-brasiliana, Cássia-
fístula and Cássia-imperial (Br.); Sin.: Aehaela-gaha, Ahalla-gass; Spa.: Cañaflote
(Venezuela), Cañafístola cimarron (Cuba), Cañafístula, Cañafístula de Castilla
(Mexico), Casiafístula, Casiapístola, Casiafístola; Tag.: Ancherhan, Fistula, Kaña-
pístola, Kanya-pistula; Tha.: Chaiyaphruek, Rachapruek; Vie.: Bò cạp nước, Bò
cạp vàng, Muồng hoàng yến.
Description: A moderate-sized erect, deciduous tree of tropical Asia with smooth,
pinnate leaves 30 to 40 cm long. The bright-yellow flowers are borne in long, lax
racemes, 30 to 50 cm long, on 3 to 5 cm long stalks. The dark-brown, smooth,
shining and pendulous pod is cylinderical, 30 to 60 cm long and about 2.5 cm in
diameter; small, ovoid slightly compressed, smooth, shining and yellowish-brown
seeds are numerous, embedded in black, sweet pulp, completely separated by thin,
tranverse segments (Figs. 1, 2, 3 and 4).CXVII
Actions and Uses: Arabs are credited for the discovery of medicinal uses of the
pulp, which is mild laxative in small doses and acts as a purgative in large doses.CX It
is well adapted to febrile and inflammatory afflictions and is a convenient, palatable
purgative for children,CXIII and even for pregnant women; however, external
application of pods provoke abortion and expulsion of placenta.XXXIX In Ayurveda,
Cassia fistula L. 541

Fig. 1 Cassia fistula, Tree, Suniltg, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA
3.0, https://commons.wikimedia.org/wiki/File:Konnamaram.JPG; https://creativecommons.org/
licenses/by-sa/3.0/deed.en

Fig. 2 Cassia fistula, Leaves, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported CC BY-
SA 3.0, https://commons.wikimedia.org/wiki/File:Amaltas_(Cassia_fistula)_leaves_in_Hyderabad,
_AP_W_289.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
542 Cassia fistula L.

Fig. 3 Cassia fistula, Flowers, HFret, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA
3.0, https://commons.wikimedia.org/wiki/File:Cassia.jpg; https://creativecommons.org/licenses/
by-sa/3.0/deed.en

Fig. 4 Cassia fistula, Pods, Didier Descouens, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cassia_fistula_MHNT.BOT.2007.26.
54.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

pulp is used as a cathartic, and root is also sometimes given as a laxative. Fruit pulp
is also used in Ayurveda for vibandha, udavarta, gulma, sula, udararoga, hrdroga,
and prameha.LX Greek physicians came to know about the drug through Arab
physicians, and described it as lenitive, useful for relieving thoracic obstructions and
heat of blood, a safe aperient for children and women, even when pregnant, but slow
in action. Externally, it is said to be a good application in gout and rheumatism. From
5 to 7 of the powdered seeds are prescribed as emetic, and the shell of the pod rubbed
down with saffron, sugar and rose-water in difficult parturition.XL The pulp, root-
bark, seeds and leaves possess purgative property; the root is purgative, tonic and
febrifuge, and the fruit is cathartic.XXI,CV Pulp (temperament, hot 1° and moist 1°) in
Unani medicine is used as purgative and anti-inflammatory; whereas rind (temper-
ament, hot 3° and dry 2°) is mainly used as emmenagogue and oxytocic to help
deliver fetus and expel placenta. It is especially useful to purge excessive phlegm,
black and yellow bile, and to soften chest;LXXVII and is used in the treatment of
Cassia fistula L. 543

tonsilitis, diphtheria, and nephritis; the rind is also a strong diuretic, that may
sometimes cause abortion.1 Bark and leaves, mixed with oil, are applied to pus-
tules.LXXXI In traditional Iranian medicine, it has been used for the treatment of IBD,
probably due to its antimicrobial properties [48]. Leaves are used in Panamanian folk
medicine for treatment of diabetes [17], and in northern Peru, it is traditionally used
to treat bacterial infections, which are referred to by local healers as ‘inflammation’
[12]. Decoction of leaves and pulp are used as purgative in the Philippines;LVI native
populations of Tanzania, Zimbabwe, Mozambique and Brazil use the plant to treat
malaria and associated symptoms [21], and in Brazil, the root is also used as
anthelmintic [58]. Leaves are laxative and purgative, and the juice or ground leaves
are applied to ringworm.XXXIX,CV
Phytoconstituents: Anthraquinone glycosides, the active laxative content, are
concentrated in leaves and flowers during peak flowering, and hydroxyan-
thraquinones reach peak during the months of September and October [2]. Fruit pulp
contains a sterol, clerosterol with antileishmanial activity and significantly less
toxicity than pentamidine [50], and is rich in mineral nutrients, K and Ca being in
sufficient quantity in 100 g of pulp to meet U.S. RDA, and a good source of Fe and
Mn higher than in apple, apricot, peach, pear and orange, and significant amino acids
contents [6]. Methanol extract of fruit pulp showed presence of saponins, steroids,
triterpinoids, flavonoids, tannins, glycosides, anthraquinones, gums, mucilage and
amino acids, and exhibited significant antioxidant activity [10]. Biochanin A, an
isoflavone isolated from fruits, shows antileishmanial and anti-T. cruzi activities
[51]. Seeds contain anthraquinones, saponins, tannins and terpenoids, a compound
roseanone with antiyeast activity [28], and galactomannan [34]. Seeds from Jamaica
were also rich in protein and small quantities of fat, palmitic acid being the pre-
dominant saturated fatty acid, and oleic and linoleic acids in smaller quantities [18].
Pulp and seed oil contain antifungal constituents, b-sitosterol, stigmasterol, ergos-
terol, betulinic acid, lupeol, fucosterol, a-amyrin and friedelin [23]. Three new
anthraquinones with cytotoxic activity, fistulaquinones A-C, were isolated from the
twigs [58], and Amento flavone (biflavonoid) was isolated from leaves, that showed
moderate cytotoxicity to liver carcinoma (HepG2) cells [56]. Fistulains A and B
were isolated from the bark [59].
Pharmacology: Seeds [28] and various flower extracts [16] have shown antibacte-
rial, antifungal, and antioxidant properties [33]. Methanol seed extract at a concen-
tration of 6.25 mg/ml completely inhibited C. albicans growth [29]. Fluconazole-
resistant Candida species isolated from HIV patients (C. krusei and C. parapsilosis)
were most sensitive to ethanol seed extract [55]. Ethanol and methanol flower extracts
were significantly effective against E. coli and K. pneumoniae [53]. Perumal Samy
[42] also reported significant antibacterial activity against E. coli, K. aerogenes,
P. vulgaris, and P. aerogenes. Hydroalcohol and chloroform extracts of fruit pulp
showed dose-dependent moderate to strong antibacterial activity against S. aureus,
S. pyogenes, E. coli and P. aeruginosa, and antifungal activity against A. niger,

1
Tayyab M: Personal Communication.
544 Cassia fistula L.

A. clavatus, and C. albicans [9]. Aqueous pulp extract retained its antidermatophytes
(T. mentagrophytes, T. mentagrophytes, T. rubrum, and M. gypseum) activity after
regular storage for six-months [14]. Hydroalcohol leaf extract was also significantly
active against all these organisms [11, 41], and aqueous and methanol leaf extracts
were moderately active against B. cereus, S. aureus, E. coli, S. typhimurium, Sh.
dysentriae, Sh. flexneri, Sh. sonnei, and V. cholera [40]. A protease inhibitor, fistulin,
isolated from leaves showed activity against B. subtilis, S. aureus, K. pneumoniae,
P. aeruginosa and E. coli, comparable to streptomycin sulfate [5]. Methanol leaf
extract is larvicidal and ovicidal to chikungunya vector, Aedes aegypti [20], and
filarial and malarial vector mosquitos [19]. Seed powder killed 100% trophozoites of
axenically grown E. histolytica at the minimum dose of 15.62 ug/ml; cured experi-
mental intestinal amoebiasis in rats and hepatic amoebiasis in golden hamsters at a
dose of 100 mg/kg/day for 5-days. Monkeys passing E. histolytica and E. coli cysts
were cysts-free after 5-days of treatment with the same dose of seed powder. In vitro
100% cysticidal activity against cysts of E. histolytica was 64 mg/ml which decreased
dose-dependently [54].
Aqueous flower extract showed significant antioxidant activity in alloxan-diabetic
rats, and restored key antioxidant enzymes, such as SOD, CAT, GPx, GR and GSH to
their near normal values [37]. Petroleum ether and ethanol flower extracts and the
water-soluble fraction of ethanol extract exhibited significant antihyperglycemic
activity [26]. Ethanol stem bark extract also produced antidiabetic and antioxidant
effects in alloxan-diabetic rats, with significant decrease in serum creatinine and
increase in serum albumin and total protein [3], and aqueous leaf extract produced
hypoglycemia in normoglycemic mice [17]. Methanol stem extract also exhibited
antihyperglycemic activity in STZ-diabetic rats, due to catechin. Catechin in a dose of
20 mg/kg for 6-weeks significantly increased tissue glycogen and 14C-glucose oxi-
dation without affecting plasma insulin and C-peptide levels, and restored activities of
glucokinase, G-6-Pase, glycogen synthase and glycogen phosphorylase to near
normal [15]. Thirty-days administration of ethanol fruit extract to hyperlipidemic
mice significantly restored levels of serum lipids, MDA and enzymes activities in
liver and heart [1].
In high doses, ethanol leaf extract reduced volume, pH, free acidity, and total
acidity in gastric juice of pylorus-ligated rats, comparable to ranitidine [32], and
significantly protected against CCl4- and DEN-induced hapatic injury [43, 44],
and rats pretreated with ethanol for 15-days were protected against DEN-liver
injury comparable to silymarin [45]. Hydroalcohol fruit extract protected against
bromobenzene-induced liver damage [30], and nephrotoxicity in mice [31].
N-heptane leaves extract was also protective against CCl4- and APAP-hepatotoxicity
in rats [7, 8]. Sugar-free residue from pulp possesses cathartic property which is more
than the effect of the total pulp. When pulp or sugar-free residue is administered to
mice, they pass ‘Senna’ like stools within 4–6 h and the effect continues for 8–10 h;
minimum effective dose of the pulp was 12 mg per 20 g mouse [25]. Aqueous extract
of dried pulp shows maximum anti-inflammatory activity in rats, and a synergistic
Cassia fistula L. 545

anti-inflammatory effect with aqueous extract of Solanum xanthocarpum [4]. Fruits

(pods) have high phenol contents but their extract showed poor antioxidant and free
radical-scavenging activities [47], contradicting Luximon-Ramma [36] who reported
pods with highest total phenolic contents and antioxidant potentials. Extracts of seeds
from Jamaica, however, showed antioxidant and free radical-scavenging activities
due to their phenolic contents [18]. Topical application of an ointment formulated
from alcohol leaf extract to infected wounds in rats improved wound closure, and
tissue regeneration at the wound site [52]. Butanol flower extract did not affect skin
fibroblast cell growth, but significantly increased collagen and hyaluronic acid syn-
thesis, and inhibited collagenase, MMP-2, and tyrosinase activity that causes
hyperpigmentation [35].
Ethanol fruit extract significantly reduced duration of immobility and anxiety, and
increased locomotor activity of mice in chronic fatigue syndrome model [49]. An
aqueous extract of seeds reversibly suppressed fertility in male rats [13], and in a dose
of 500 mg/kg prevented pregnancy in 100% female rats [57]. However, ethanol
(50%) extract of ripe pods showed no anti-implantation activity in rats [46]. Methanol
extract of seeds increased life span of EAC-bearing mice and decreased tumor volume
and viable tumor cell count [22].
Clinical Studies: In a comparative randomized trial of C. fistula emulsion
(CFE) with mineral oil (MO) in pediatric functional constipation, 84% children in
CFE-group and 50% in MO-group improved after 3-weeks of treatment [38]. In
clinical trials, patients aged 12–60 years old, treated with 150–250 mg dose/day of
seed powder were cured of amoebiasis in seven days [54].
Mechanism of Action: Both pulp and seed extracts and the oils produce antifungal
activity by inhibiting ergosterol biosynthesis in Candida cell wall [23, 24].
Human A/Es, Allergy and Toxicity: The pulp is spasmodic and causes dysentery;
the rind may cause abortion.LXXVII
Animal Toxicity: Methanol seed extract, with the highest dose of 5,000 mg/kg for
14-days, was nontoxic to mice [27]. Ethanol stem bark extract was also nontoxic up
to a dose of 2,000 mg/kg in Wistar rats [3]. Anthraquinone glycosides did not
induce any significant chromosomal aberrations in bone marrow cells of mice, but
sennoside B and rhein were weakly genotoxic [39].
Commentary: Wide-spread clinical use of this plant in Indian traditional
medicines is usually limited to as a laxative/purgative, and in pulmonary irritations.
However, there is only one randomized trial in children, and an old antiamoebic
trial reported in English literature. More RCTs are required, and broad-spectrum
antimicrobial effects of various extracts in pharmacological studies deserve further
investigation and exploration in clinical trials.
546 Cassia fistula L.

References
1. Abid R, Mahmood R, Santosh Kumar HS. Hypolipidemic and antioxidant
effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice.
Pharm Biol. 2016;54:2822–9.
2. Abo KA, Adeyemi AA, Sobowale AO. Microscopic evaluation and seasonal
variations of anthraquinone glycosides of cultivated Cassia fistula Linn. Afr J
Med Med Sci. 2001;30:9–12.
3. Agnihotri A, Singh V. Effect of Tamarindus indica Linn. and Cassia
fistula Linn. stem bark extracts on oxidative stress and diabetic conditions.
Acta Pol Pharm. 2013;70:1011–9.
4. Anwikar S, Bhitre M. Study of the synergistic anti-inflammatory activity of
Solanum xanthocarpum Schrad and Wendl and Cassia fistula Linn. Int J
Ayurveda Res. 2010;1:167–71.
5. Arulpandi I, Sangeetha R. Antibacterial activity of fistulin: a protease inhibitor
purified from the leaves of Cassia fistula. ISRN Pharm. 2012;2012:584073.
6. Barthakur NN, Arnold NP, Alli I. The Indian laburnum (Cassia fistula L.)
fruit: an analysis of its chemical constituents. Plant Foods Hum Nutr.
1995;47:55–62.
7. Bhakta T, Banerjee S, Mandal SC, et al. Hepatoprotective activity of Cassia
fistula leaf extract. Phytomedicine. 2001;8:220–4.
8. Bhakta T, Mukherjee PK, Mukherjee K, et al. Evaluation of hepatoprotective
activity of Cassia fistula leaf extract. J Ethnopharmacol. 1999;66:277–82.
9. Bhalodia NR, Nariya PB, Acharya RN, Shukla VJ. In vitro antibacterial and
antifungal activities of Cassia fistula Linn. fruit pulp extracts. Ayu. 2012;33:
123–9.
10. Bhalodia NR, Nariya PB, Acharya RN, Shukla VJ. In vitro antioxidant
activity of hydroalcoholic extract from the fruit pulp of Cassia fistula Linn.
Ayu. 2013;34:209–14.
11. Bhalodia NR, Shukla VJ. Antibacterial and antifungal activities from leaf
extracts of Cassia fistula l.: an ethnomedicinal plant. J Adv Pharm Technol
Res. 2011;2:104–9.
12. Bussmann RW, Malca-García G, Glenn A, et al. Minimum inhibitory
concentrations of medicinal plants used in Northern Peru as antibacterial
remedies. J Ethnopharmacol. 2010;132:101–8.
13. Chauhan A, Agarwal M. Evaluating the antifertility potential of an aqueous
extract from Cassia fistula seeds in male rats. Fertil Steril. 2010;93:1706–10.
14. Chewchinda S, Wuthi-udomlert M, Gritsanapan W. HPLC quantitative
analysis of rhein and antidermatophytic activity of Cassia fistula pod pulp
extracts of various storage conditions. Biomed Res Int. 2013;2013:821295.
15. Daisy P, Balasubramanian K, Rajalakshmi M, Eliza J, Selvaraj J. Insulin
mimetic impact of Catechin isolated from Cassia fistula on the glucose
oxidation and molecular mechanisms of glucose uptake on Streptozotocin-
induced diabetic Wistar rats. Phytomedicine. 2010;17:28–36.
Cassia fistula L. 547

16. Duraipandiyan V, Ignacimuthu S. Antibacterial and antifungal activity

of Cassia fistula L.: an ethnomedicinal plant. J Ethnopharmacol. 2007;112:
590–4.
17. Espósito Avella M, Díaz A, de Gracia I, de Tello R, Gupta MP. Evaluation
of traditional medicine: effects of Cajanus cajan L. and of Cassia fistula L.
on carbohydrate metabolism in mice. Rev Med Panama. 1991;16:39–45
(Article in Spanish).
18. Goldson Barnaby A, Reid R, Rattray V, Williams R, Denny M. Character-
ization of Jamaican Delonix regia and Cassia fistula seed extracts. Biochem
Res Int. 2016;2016:3850102.
19. Govindarajan M, Jebanesan A, Pushpanathan T. Larvicidal and ovicidal
activity of Cassia fistula Linn. leaf extract against filarial and malarial vector
mosquitoes. Parasitol Res. 2008;102:289–92.
20. Govindarajan M. Bioefficacy of Cassia fistula Linn. (Leguminosae) leaf
extract against chikungunya vector, Aedes aegypti (Diptera: Culicidae). Eur
Rev Med Pharmacol Sci. 2009;13:99–103.
21. Grace MH, Lategan C, Graziose R, et al. Antiplasmodial activity of the
ethnobotanical plant Cassia fistula. Nat Prod Commun. 2012;7:1263–6.
22. Gupta M, Mazumder UK, Rath N, Mukhopadhyay DK. Antitumor activity
of methanolic extract of Cassia fistula L. seed against Ehrlich ascites
carcinoma. J Ethnopharmacol. 2000;72:151–6.
23. Irshad M, Ahmad A, Zafaryab M, et al. Composition of Cassia fistula oil
and its antifungal activity by disrupting ergosterol biosynthesis. Nat Prod
Commun. 2013;8:261–4.
24. Irshad, Shreaz S, Manzoor N, Khan LA, Rizvi MM. Anticandidal activity
of Cassia fistula and its effect on ergosterol biosynthesis. Pharm Biol. 2011;
49:727–33.
25. Iyenger MA, Pendse GS, Narayana N. Bioassay of Cassia fistula L.
(Aragvadha). Planta Med. 1966;14:289–301.
26. Jarald EE, Joshi SB, Jain DC, Edwin S. Biochemical evaluation of the
hypoglycemic effects of extract and fraction of Cassia fistula Linn. in
alloxan-induced diabetic rats. Indian J Pharm Sci. 2013;75:427–34.
27. Jothy SL, Zakaria Z, Chen Y, et al. Acute oral toxicity of methanolic seed
extract of Cassia fistula in mice. Molecules. 2011;16:5268–82.
28. Jothy SL, Zakaria Z, Chen Y, et al. Bioassay-directed isolation of active
compounds with antiyeast activity from a Cassia fistula seed extract.
Molecules. 2011;16:7583–92.
29. Jothy SL, Zakariah Z, Chen Y, Sasidharan S. In vitro, in situ and in vivo
studies on the anticandidal activity of Cassia fistula seed extract. Molecules.
2012;17:6997–7009.
30. Kalantari H, Jalali M, Jalali A, et al. Protective effect of Cassia fistula fruit
extract against bromobenzene-induced liver injury in mice. Hum Exp Toxicol.
2011;30:1039–44.
548 Cassia fistula L.

31. Kalantari H, Jalali M, Jalali A, et al. Protective effect of Cassia fistula fruit
extract on bromobenzene-induced nephrotoxicity in mice. Hum Exp Toxicol.
2011;30:1710–5.
32. Karthikeyan S, Gobianand K. Antiulcer activity of ethanol leaf extract
of Cassia fistula. Pharm Biol. 2010;48:869–77.
33. Kumar VP, Chauhan NS, Padh H, Rajani M. Search for antibacterial and
antifungal agents from selected Indian medicinal plants. J Ethnopharmacol.
2006;107:182–8.
34. Lal J, Gupta PC. Galactomannan from the seeds of Cassia fistula. Planta
Med. 1972;22:70–7.
35. Limtrakul P, Yodkeeree S, Thippraphan P, Punfa W, Srisomboon J. Anti-
aging and tyrosinase inhibition effects of Cassia fistula flower butanolic
extract. BMC Complement Altern Med. 2016;16:497.
36. Luximon-Ramma A, Bahorun T, Soobrattee MA, Aruoma OI. Antioxidant
activities of phenolic, proanthocyanidin, and flavonoid components in
extracts of Cassia fistula. J Agric Food Chem. 2002;50:5042–7.
37. Manonmani G, Bhavapriya V, Kalpana S, Govindasamy S, Apparanan-
tham T. Antioxidant activity of Cassia fistula (Linn.) flowers in alloxan
induced diabetic rats. J Ethnopharmacol. 2005;97:39–42.
38. Mozaffarpur SA, Naseri M, Esmaeilidooki MR, Kamalinejad M, Bijani A.
The effect of Cassia fistula emulsion on pediatric functional constipation in
comparison with mineral oil: a randomized, clinical trial. Daru. 2012;20:83.
39. Mukhopadhyay MJ, Saha A, Dutta A, et al. Genotoxicity of sennosides on
the bone marrow cells of mice. Food Chem Toxicol. 1998;36:937–40.
40. Panda SK, Mohanta YK, Padhi L, et al. Large scale screening of ethno-
medicinal plants for identification of potential antibacterial compounds.
Molecules. 2016;21:293.
41. Panda SK, Padhi LP, Mohanty G. Antibacterial activities and phytochemical
analysis of Cassia fistula (Linn.) leaf. J Adv Pharm Technol Res. 2011;2:
62–7.
42. Perumal Samy R, Ignacimuthu S, Sen A. Screening of 34 Indian medicinal
plants for antibacterial properties. J Ethnopharmacol. 1998;62:173–82.
43. Pradeep K, Mohan CV, Gobianand K, Karthikeyan S. Effect of Cassia
fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats.
Chem Biol Interact. 2007;167:12–8.
44. Pradeep K, Mohan CV, Anand KG, Karthikeyan S. Effect of pretreatment
of Cassia fistula Linn. leaf extract against subacute CCl4 induced hepato-
toxicity in rats. Indian J Exp Biol. 2005;43:526–30.
45. Pradeep K, Raj Mohan CV, Gobianand K, Karthikeyan S. Protective effect
of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage
and oxidative stress in ethanol pretreated rats. Biol Res. 2010;43:113–25.
46. Prakash AO. Potentialities of some indigenous plants for antifertility activity.
Int J Crude Drug Res. 1986;24:19–24.
Cassia fistula L. 549

47. Prakash D, Suri S, Upadhyay G, Singh BN. Total phenol, antioxidant and
free radical scavenging activities of some medicinal plants. Int J Food Sci
Nutr. 2007;58:18–28.
48. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J Gastro-
enterol. 2010;16:4504–14.
49. Sarma P, Borah M, Das S. Evaluation of the effect of ethanolic extract of
fruit pulp of Cassia fistula Linn. on forced swimming induced chronic
fatigue syndrome in mice. Res Pharm Sci. 2015;10:206–13.
50. Sartorelli P, Andrade SP, Melhem MS, et al. Isolation of antileishmanial
sterol from the fruits of Cassia fistula using bioguided fractionation.
Phytother Res. 2007;21:644–7.
51. Sartorelli P, Carvalho CS, Reimão JQ, Ferreira MJ, Tempone AG. Anti-
parasitic activity of biochanin A, an isolated isoflavone from fruits of Cassia
fistula (Leguminosae). Parasitol Res. 2009;104:311–4.
52. Senthil Kumar M, Sripriya R, Vijaya Raghavan H, Sehgal PK. Wound
healing potential of Cassia fistula on infected albino rat model. J Surg Res.
2006;131:283–9.
53. Seyyednejad SM, Motamedi H, Vafei M, Bakhtiari A. The antibacterial
activity of Cassia fistula organic extracts. Jundishapur J Microbiol. 2014;7:
e8921.
54. Shukla SC, Das SR. Cure of amoebiasis by seed powder of Cassia fistula.
Int J Crude Drug Res. 1988;26:141–4.
55. Sony P, Kalyani M, Jeyakumari D, Kannan I, Sukumar RG. In vitro antifun-
gal activity of Cassia fistula extracts against fluconazole resistant strains of
Candida species from HIV patients. J Mycol Med. 2017. pii: S1156–5233(17)
30284-6.
56. Srividhya M, Hridya H, Shanthi V, Ramanathan K. Bioactive Amento
flavone isolated from Cassia fistula L. leaves exhibits therapeutic efficacy.
3 Biotech. 2017;7:33.
57. Yadav R, Jain GC. Antifertility effect of aqueous extract of seeds of Cassia
fistula in female rats. Adv Contracept. 1999;15:293–301.
58. Zhou M, Xing HH, Yang Y, et al. Three new anthraquinones from the twigs
of Cassia fistula and their bioactivities. J Asian Nat Prod Res. 2017;1–6.
59. Zhou M, Zhou K, Gao XM, et al. Fistulains A and B, new bischromones
from the bark of Cassia fistula, and their activities. Org Lett. 2015;17:
2638–41.
Catharanthus roseus (L.) G. Don
(Apocynaceae)

(Syns.: Ammocallis rosea (L.) Small; Lochnera rosea (L.) Rchb. ex Endl.; Pervinca
rosea (L.) Gaterau; Vinca rosea L.)

Abstract
Native to Madagascar, periwinkle is an evergreen shrub that is grown/cultivated as
garden plant in the tropics and subtropics, and wildly grows in woods and on
banks. This herb is dear to Venus, and is said that if two lovers eat a sprig of it
together, they will stay in love all their lives. It is a natural tonic and specific for
the treatment of upset digestion (diarrhea, flatulence etc.); other conditions where
it is prescribed include ulcers of throat and mouth, diphtheria, diabetes and
disorders of skin and scalp. In northern Europe it is used by traditional healers
for the treatment of diabetes mellitus, and in the Philippines, leaf decoction is
prescribed for diabetes, and root decoction as emmenagogue, which may cause
abortion. Hot infusion of dried flowers is used as diaphoretic in jaundice, nasal
catarrh, and muscular rheumatism; whereas cold infusion is used as laxative and
tonic in measles and scarlet fever to favor efflorescence of eruptions. In China, it is
known as Changchunhua and is described to have a bitter taste and ‘cool’
property, and being toxic. In Unani medicine, leaves are macerated in water,
filtered, added sugar and used in the treatment of gonorrhea. Despite its clinical
toxicity, it has been used as an important traditional Chinese medicine for different
stages of cancer. Elsewhere in the world, it has been extensively used as an
anticancer agent, and is the source of the modern anticancer agents, vincristine and
vinblastine. In South Africa also, infusion of leaves is used as a remedy for
diabetes and to treat menorrhagia. Leaves contain alkaloids, sterols, flavonoids,
polyphenols and saponins; whereas stems test positive for alkaloids, triterpenes,
sterols, flavonoids, and polyphenols. Phenolic compounds, such as flavonol
glycosides with their antioxidant potential, along with tannins, phlotatannins,
triterpenoids, reducing sugars, anthraquinones and glycosides are present in
leaves. A number of alkaloids have been isolated from root, stem, leaves and
seeds, and more continue to be isolated. Vinca alkaloids comprise a group of about
130 terpenoid indole alkaloids. Leaf extract and powder significantly lower
blood sugar in normal and diabetic rats, and normalize the significant increase in
plasma TC, TGs, LDL-C and VLDL-C, and the atherogenic index of diabetic rats.
© Springer Nature Switzerland AG 2020 551
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_58
552 Catharanthus roseus (L.) G. Don

Keywords




Binka Boa-noite Gul-e-farang Periwinkle Rosafarbenes

Rosensköna





Sadabahar Sadampuspi Sadaphuli Zhangchunhua

Vernaculars: Urd.: Sadabahar; Hin.: Sadabahar, Sadaphuli, Sadasuhagan; San.:

Nityakalyani, Sadam-puspã, Sadampuspi; Ben.: Gulferinghi, Noyontara; Mal.:
Shavam naari, Ushamalari; Mar.: Sadaphuli; Tam.: Nithyakalyani, Sudukadu
mallikai; Tel.: Billaganneru; Chi.: 长春花, Changchunhua, Zhangchunhua; Eng.:
Madagascar periwinkle, Old-maid, Periwinkle, Rosy periwinkle, Vinca; Fin.:
Katara; Fre.: Catharanthe rose, Pervenche de Madagascar; Ger.: Madagaskar-
immergrün, Rosafarbene catharanthe, Rosafarbenes, Zimmerimmergrün; Jap.:
Binka, Nichi-nichi-ka, Nichi-nichi-sô; Per.: Gul-e-farang; Por.: Boa-noite (Br.),
Maria-sem-vergonha, Vinca-de-gato, Vinca-de-Madagáscar; Swe.: Őgonklara,
Rosensköna; Tag.: Amnias, Chichirica, Kantotan, Sitchirika, Tsitsirika.
Description: Native to Madagascar, periwinkle is an evergreen shrub that is
grown/cultivated as garden plant in the tropics and subtropics [8], and wildly grows
in woods and on banks where its pink flowers contrast with its dark evergreen
leaves.XXVI It is an erect, smooth, simple or slightly branched plant, growing up to
50 cm in height; leaves oblong, 4–7 cm long, rounded at the tip, and pointed at the
base; flowers are white, pink or red, or variegated white and red (purple), with a
darker red center, 3–5 cm across, with five petal-like lobes, and borne in the axils of
leaves. Green calyx-lobes are very cylinder and about 4 mm long; fruit is a follicle
and is cylindric, hairy and 2–3 cm long (Figs. 1 and 2).CXVII
Actions and Uses: This herb is dear to Venus, and is said that if two lovers eat a
sprig of it together, they will stay in love all their lives. It is a natural tonic and
specific for the treatment of upset digestion (diarrhea, flatulence etc.); other

Fig. 1 Catharanthus roseus, Plant with Flowers, Venkatx5, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Nithyakalyani_India.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Catharanthus roseus (L.) G. Don 553

Fig. 2 Catharanthus roseus, Flowers, Arun Punnathatta, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Nithyaklalyani.jpg

conditions where it is prescribed include ulcers of throat and mouth, diphtheria,

diabetes and disorders of skin and scalp.XXVI In northern Europe it is used by
traditional healers for the treatment of diabetes mellitus [31], and in the Philippines,
leaf decoction is prescribed for diabetes, and root decoction as emmenagogue, which
may cause abortion.LVI,CXVII Hot infusion of dried flowers is used as diaphoretic in
jaundice, nasal catarrh, and muscular rheumatism; whereas cold infusion is used as
laxative and tonic in measles and scarlet fever to favor efflorescence of eruptions,CV
and in the Indian State of Punjab, seeds are considered diuretic and tonic.LXXXIV
Therapeutic uses in Ayurveda include anidra, raktãrbuda, madhumeha, śūla, gulma,
and raktabhãrãdhikya.LX In China, it is known as Changchunhua and is described to
have a bitter taste and ‘cool’ property, and being toxic.XVIII In Unani medicine,
leaves (temperament, cold 1° and moist 1°) are macerated in water, filtered, added
sugar and used in the treatment of gonorrhea.LXXVII Despite its clinical toxicity, it
has been used as an important traditional Chinese medicine for different stages of
cancer [14]. Elsewhere in the world, it has been extensively used as an anticancer
agent [24], and is the original source of the modern anticancer agents, vincristine and
vinblastine [9]. In South Africa also, infusion of leaves is used as a remedy for
diabetes and to treat menorrhagia [47].CL In the Bapedi culture of Limpopo Province
of South Africa, the plant is extensively used by traditional primary healthcare sector
for treatment of gonorrhea [28]; whereas in a rural community in northern Maputa-
land of South Africa, it is one of the most frequently used antidiarrheal plants [6]. In
Mauritius, infusion of leaves is prescribed for indigestion and dyspepsia.CXV In
Trinidad and Tobago, it is used by traditional healers for treatment of (unspecified)
male problems [12], and to treat diabetes [13]. It is also one of the plants used to treat
diabetes by the Garos, a tribal indigenous community of Bangladesh [23].
554 Catharanthus roseus (L.) G. Don

Phytoconstituents: Leaves contain alkaloids, sterols, flavonoids, polyphenols and

saponins; while stems test positive for alkaloids, triterpenes, sterols, flavonoids, and
polyphenols [40]. Phenolic compounds, such as flavonol glycosides (di- and
trisaccharides of kaempferol, quercetin and isorhamnetin) with their antioxidant
potential [7], along with tannins, phlotatannins, triterpenoids, reducing sugars,
anthraquinones and glycosides are present in leaves [19]. A number of alkaloids
have been isolated from root, stem, leaves and seeds, and more continue to be
isolated [27, 43–46, 51]. Vinca alkaloids comprise a group of about 130 terpenoid
indole alkaloids [2]. Reported indole alkaloids are vinblastine, vincristine, leu-
rosine, vincadioline, leurosidine, catharanthine,XVIII vindolinine B, lochnericine,
horhammericine, vindorosine, coronaridine, vindoline [51], vidolicine, norma-
cusine B N-oxide, lochnerine [46], vindogentianine, vindolidine, vindolicine, vin-
dolinine, perivine and serpentine [33, 34]. Vincristine (or leurocristine) is marketed
as Oncovin® for the treatment of non-Hodgkin’s lymphoma. Vinblastine became a
lead compound for anticancer drug development and has been marketed for more
than 50 years as anticancer drug [38] for the treatment of Hodgkin’s lymphoma and
other cancers. Leaves are the only source of the indolomonoterpenic alkaloids
(vincristine and vinblastine) [22]. Aqueous extract of flower petals is the richest
source of phenolics, namely caffeoylquinic acids and flavonoids derivatives (almost
5 of the leaves), followed by leaves, whereas seeds and stems contain half the
amounts present in leaves; organic acids, such as citric acid, are highest in stems,
followed by leaves; and amino acids, especially arginine, are highest in leaves,
followed by seeds, petals and stems [21]. 15,20-Dehydro-3a-(2-oxopropyl) coro-
naridine, a monoterpenoid indole alkaloid [42], and two new vinblastine-type
N-oxide alkaloids, 17-desacetoxyvinblastine N′b-oxide and 20′-deoxyvinblastine N′
b-oxide were also isolated from leaves [49]. Methanol-soluble fraction of water
extract of aerial parts yielded two triterpenes, ursolic acid and oleanolic acid, and
three alkaloids, vindoline, ajmalicine, and serpentine; ajmalicine and serpentine are
potent CYP2D6 inhibitors [37]. Flavonoid glucosides from seeds, stems, leaves,
petals and roots have been isolated [5], and two anthocyanidin glycosides were
isolated from pale red flowers [32].
Pharmacology: Leaf extract and powder significantly lower blood sugar in normal
and diabetic rats, and normalize the significant increase in plasma TC, TGs, LDL-C
and VLDL-C, and the atherogenic index of diabetic rats [4, 25]. Reduction in blood
glucose by leaf juice and aqueous extract of both normal and diabetic rabbits [16],
and rats is comparable to glibenclamide [1]. Leaf juice with high-fat diet prevented
rise of serum lipids, and decreased fatty changes in tissue, and significantly reduced
serum LDL-C and TC/HDL-C ratio in guinea pigs [20]. Aqueous stem extract and
its alkaloid-free fraction also significantly reduced blood glucose in diabetic mice
[39]. Dichloromethane:methanol extract of leaves and twigs also exhibited signif-
icant hypoglycemic effect, and pretreatment for 30-days provided complete pro-
tection against STZ challenge, and significantly improved activities of glycogen
synthase, G-6-PD, succinate dehydrogenase and malate dehydrogenase enzymes of
STZ-diabetic rats [30]. Aqueous flower extract also significantly lowered blood
Catharanthus roseus (L.) G. Don 555

sugar and lipids levels in alloxan-diabetic rats, and restored antioxidant enzymes,
CAT and GPx to normal [11]. Petroleum ether extract, containing tannins, flavo-
noids and alkaloids, significantly lowered blood sugar in oral glucose-induced
hyperglycemia in rats [10]. However, Swanston-Flatt et al. [31] had reported that
treatment with plant in diet or its decoction/infusion for 28-days did not affect
glucose homeostasis parameters (basal plasma glucose and insulin, glucose toler-
ance, insulin-induced hypoglycemia and HbA1c) in normal and STZ-diabetic mice.
A single dose of vincristine or vinblastine in Rhesus monkeys caused a marked
decrease in plasma LDL-C and a concomitant increase in plasma triacylglycerol
concentrations, which returned to normal within 7–10 days after injection [29].
The herb also possesses significant antioxidant capacity [50].
Leaf extract (i.p.) produced significant hypotensive effect in adrenaline (epi-
nephrine)-induced hypertension in rats [3]. Methanol leaf extract was moderately
active against S. aureus, E. coli, P. aeruginosa, E. aerogenes, E. cloacae, and
K. pnemoniae [40], and ethanol extracts of both leaf and flower enhanced wound
healing [17, 18]. Oral administration of leaf extract caused widespread testicular
necrosis, hyalinization of tubules and Sertoli cell-only-Syndrome, and a notable
reduction in glycogen and fructose levels in reproductive tissues [15]. Aqueous root
extract is a strong AChE inhibitor in in vitro microassay, an effect attributed mainly
to serpentine that inhibits AChE with an IC50 of 0.775 microM compared to IC50
of 6.45 micoM for physostigmine [22]. Leaf extracts demonstrate positive
antiproliferative activity against human cancer cell lines [35, 48].
Clinical Studies: Other than the anticancer studies on the alkaloids, vincristine and
vinblastine, there are no other RCT clinical studies reported.
Mechanism of Action: Ethanol extract is reported to activate human peroxisome
proliferator-activated receptor (PPARc), that could explain its antidiabetic effect
[26].
Human A/Es, Allergy and Toxicity: Skin prick test in 282 individuals with res-
piratory allergy in the suburb of Calcutta city, India, revealed 29.8% being positive
to C. roseus pollen [8]. It should be used with caution in patients with phlegmatic
temperament.LXXVII
Animal Toxicity: Oral LD50 of methanol leaf extract in mice was 2,121 mg/kg [19],
and ethanol leaf extract was nonlethal to rats up to an oral dose of 2,000 mg/kg;
however, doses above 300 mg/kg raised liver enzymes [41].
CYP450 and Potential for Drug-Herb Interactions: Ajmalicine and serpentine
are very potent inhibitors of CYP2D6 [36, 37]; serpentine being an irreversible
inhibitor [37], and methanol leaf extract significantly increases hypoglycemic effect
of metformin in alloxan diabetic rats [19].
Commentary: Although the serendipitous discovery by Noble and colleagues that
the plant extract caused significant leucopenia was the result of their effort to study
antidiabetic effect of the plant in rabbits; it, however, changed the history and
556 Catharanthus roseus (L.) G. Don

diverted all efforts to its anticancer potentials. As a result, all other effects of the
plant, such as its hypotensive, antidiabetic and hypolipidemic potentials have been
ignored, that need a fresh look in light of the recent pharmacological outcomes.

References
1. Ahmed AU, Ferdous AH, Saha SK, et al. Hypoglycemic effect of Catha-
ranthus roseus in normal and streptozotocin-induced diabetic rats. Mymen-
singh Med J. 2007;16:143–8.
2. Almagro L, Fernández-Pérez F, Pedreño MA. Indole alkaloids from
Catharanthus roseus: bioproduction and their effect on human health.
Molecules. 2015;20:2973–3000.
3. Ara N, Rashid M, Amran MS. Comparison of hypotensive and hypolipi-
demic effects of Catharanthus roseus leaves extract with atenolol on
adrenaline induced hypertensive rats. Pak J Pharm Sci. 2009;22:267–71.
4. Chattopadhyay RR. A comparative evaluation of some blood sugar
lowering agents of plant origin. J Ethnopharmacol. 1999;67:367–72.
5. Chung IM, Ahmad A, Ali M, et al. Flavonoid glucosides from the hairy
roots of Catharanthus roseus. J Nat Prod. 2009;72:613–20.
6. de Wet H, Nkwanyana MN, van Vuuren SF. Medicinal plants used for the
treatment of diarrhoea in northern Maputaland, KwaZulu-Natal Province,
South Africa. J Ethnopharmacol. 2010;130:284–9.
7. Ferreres F, Pereira DM, Valentão P, et al. New phenolic compounds and
antioxidant potential of Catharanthus roseus. J Agric Food Chem. 2008;56:
9967–74.
8. Ghosh D, Roy I, Chanda S, Gupta-Bhattacharya S. Allergy to periwinkle
pollen (Catharanthus roseus G. Don.). Ann Agric Environ Med. 2007;14:
39–43.
9. Huxtable RJ. The pharmacology of extinction. J Ethnopharmacol. 1992;37:
1–11.
10. Islam MA, Akhtar MA, Khan MR, et al. Oral glucose tolerance test (OGTT)
in normal control and glucose induced hyperglycemic rats with Coccinia
cordifolia l. and Catharanthus roseus L. Pak J Pharm Sci. 209;22:402–4.
11. Kaleem M, Sheema, Sarmad H, Bano B. Protective effects of Piper nigrum
and Vinca rosea in alloxan induced diabetic rats. Indian J Physiol Pharmacol.
2005;49:65–71.
12. Lans C. Ethnomedicines used in Trinidad and Tobago for reproductive
problems. J Ethnobiol Ethnomed. 2007;3:13.
13. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary problems
and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2:45.
14. Man S, Gao W, Wei C, Liu C. Anticancer drugs from traditional toxic
Chinese medicines. Phytother Res. 2012;26:1449–65.
15. Mathur R, Chaudan S. Antifertility efficacy of Catharanthus roseus Linn: a
biochemical and histological study. Acta Eur Fertil. 1985;16:203–5.
Catharanthus roseus (L.) G. Don 557

16. Nammi S, Boini MK, Lodagala SD, Behara RB. The juice of fresh leaves of
Catharanthus roseus Linn. reduces blood glucose in normal and alloxan
diabetic rabbits. BMC Complement Altern Med. 2003;3:4.
17. Nayak BS, Anderson M, Pinto Pereira LM. Evaluation of wound-healing
potential of Catharanthus roseus leaf extract in rats. Fitoterapia. 2007;78:
540–4.
18. Nayak BS, Pinto Pereira LM. Catharanthus roseus flower extract has wound-
healing activity in Sprague Dawley rats. BMC Complement Altern Med.
2006;6:41.
19. Ohadoma SC, Michael HU. Effects of coadministration of methanol leaf
extract of Catharanthus roseus on the hypoglycemic activity of metformin
and glibenclamide in rats. Asian Pac J Trop Med. 2011;4:475–7.
20. Patel Y, Vadgama V, Baxi S, Chandrabhanu, Tripathi B. Evaluation of
hypolipidemic activity of leaf juice of Catharanthus roseus (Linn.) G. Donn.
in guinea pigs. Acta Pol Pharm. 2011;68:927–35.
21. Pereira DM, Ferreres F, Oliveira J, et al. Targeted metabolite analysis of
Catharanthus roseus and its biological potential. Food Chem Toxicol. 2009;
47:1349–54.
22. Pereira DM, Ferreres F, Oliveira JM, et al. Pharmacological effects of
Catharanthus roseus root alkaloids in acetylcholinesterase inhibition and
cholinergic neurotransmission. Phytomedicine. 2010;17:646–52.
23. Rahmatullah M, Azam MN, Khatun Z, et al. Medicinal plants used for treat-
ment of diabetes by the Marakh sect of the Garo tribe living in Mymensingh
district, Bangladesh. Afr J Tradit Complement Altern Med. 2012;9:380–5.
24. Ram VJ, Kumari S. Natural products of plant origin as anticancer agents.
Drug News Perspect. 2001;14:465–82.
25. Rasineni K, Bellamkonda R, Singareddy SR, Desireddy S. Antihyper-
glycemic activity of Catharanthus roseus leaf powder in streptozotocin-
induced diabetic rats. Pharmacognosy Res. 2010;2:195–201.
26. Rau O, Wurglics M, Dingermann T, et al. Screening of herbal extracts for
activation of the human peroxisome proliferator-activated receptor. Phar-
mazie. 2006;61:952–6.
27. Roepke J, Salim V, Wu M, et al. Vinca drug components accumulate
exclusively in leaf exudates of Madagascar periwinkle. Proc Natl Acad Sci
U.S.A. 2010;107:15287–92.
28. Semenya S, Potgieter M, Tshisikhawe M, Shava S, Maroyi A. Medicinal
utilization of exotic plants by Bapedi traditional healers to treat human ailments
in Limpopo province, South Africa. J Ethnopharmacol. 2012;144:646–55.
29. Sethi VS, Lewis JC, St Clair RW. Vincristine and vinblastine lower plasma
cholesterol concentrations in Rhesus monkeys. Biochim Biophys Acta.
1983;752:482–7.
30. Singh SN, Vats P, Suri S, et al. Effect of an antidiabetic extract of Catha-
ranthus roseus on enzymic activities in streptozotocin induced diabetic rats.
J Ethnopharmacol. 2001;76:269–77.
558 Catharanthus roseus (L.) G. Don

31. Swanston-Flatt SK, Day C, Flatt PR, Gould BJ, Bailey CJ. Glycaemic
effects of traditional European plant treatments for diabetes. Studies in
normal and streptozotocin diabetic mice. Diabetes Res. 1989;10:69–73.
32. Tatsuzawa F. 7-O-methylpelargonidin glycosides from the pale red flowers
of Catharanthus roseus. Nat Prod Commun. 2013;8:1095–7.
33. Tiong SH, Looi CY, Arya A, et al. Vindogentianine, a hypoglycemic alkaloid
from Catharanthus roseus (L.) G. Don (Apocynaceae). Fitoterapia. 2015;102:
182–8.
34. Tiong SH, Looi CY, Hazni H, et al. Antidiabetic and antioxidant properties
of alkaloids from Catharanthus roseus (L.) G. Don. Molecules. 2013;18:
9770–84.
35. Ueda JY, Tezuka Y, Banskota AH, et al. Antiproliferative activity of
Vietnamese medicinal plants. Biol Pharm Bull. 2002;25:753–60.
36. Usia T, Iwata H, Hiratsuka A, et al. CYP3A4 and CYP2D6 inhibitory
activities of Indonesian medicinal plants. Phytomedicine. 2006;13:67–73.
37. Usia T, Watabe T, Kadota S, Tezuka Y. Cytochrome P450 2D6 (CYP2D6)
inhibitory constituents of Catharanthus roseus. Biol Pharm Bull. 2005;28:
1021–4.
38. van Der Heijden R, Jacobs DI, Snoeijer W, Hallard D, Verpoorte R. The
Catharanthus alkaloids: pharmacognosy and biotechnology. Curr Med Chem.
2004;11:607–28.
39. Vega-Ávila E, Cano-Velasco JL, Alarcón-Aguilar FJ, et al. Hypoglycemic
activity of aqueous extracts from Catharanthus roseus. Evid Based
Complement Alternat Med. 2012;2012:934258.
40. Voukeng IK, Beng VP, Kuete V. Antibacterial activity of six medicinal
Cameroonian plants against Gram-positive and Gram-negative multidrug
resistant phenotypes. BMC Complement Altern Med. 2016;16:388.
41. Vutukuri VR, Das MC, Reddy M, Prabodh S, Sunethri P. Evaluation of
acute oral toxicity of ethanol leaves extract of Catharanthus roseus in
Wistar albino rats. J Clin Diagn Res. 2017;11:FF01–4.
42. Wang B, Liu L, Chen YY, et al. Monoterpenoid indole alkaloids from
Catharanthus roseus cultivated in Yunnan. Nat Prod Commun. 2015;10:
2085–6.
43. Wang CH, Wang GC, Wang Y, et al. Cytotoxic dimeric indole alkaloids
from Catharanthus roseus. Fitoterapia. 2012;83:765–9.
44. Wang CH, Wang GC, Wang Y, et al. Three new monomeric indole alkaloids
from the roots of Catharanthus roseus. J Asian Nat Prod Res. 2012;14:249–55.
45. Wang GC, Zhong XZ, Zhang DM, et al. Two pairs of epimeric indole
alkaloids from Catharanthus roseus. Planta Med. 2011;77:1739–41.
46. Wang L, Zhang Y, He HP, et al. Three new terpenoid indole alkaloids from
Catharanthus roseus. Planta Med. 2011;77:754–8.
47. White CT. Vinca rosea—a reported cure for diabetes. Queensland Agr J.
1925;23:143.
Catharanthus roseus (L.) G. Don 559

48. Wong SK, Lim YY, Abdullah NR, Nordin FJ. Antiproliferative and phyto-
chemical analyses of leaf extracts of ten Apocynaceae species. Pharmacognosy
Res. 2011;3:100–6.
49. Zhang WK, Xu JK, Tian HY, et al. Two new vinblastine-type N-oxide
alkaloids from Catharanthus roseus. Nat Prod Res. 2013;27:1911–6.
50. Zheng W, Wang SY. Antioxidant activity and phenolic compounds in
selected herbs. J Agric Food Chem. 2001;49:5165–70.
51. Zhong XZ, Wang GC, Wang Y, Zhang XQ, Ye WC. Monomeric indole
alkaloids from the aerial parts of Catharanthus roseus. Yao Xue Xue Bao.
2010;45:471–4 (Chinese).
Celastrus paniculatus Willd.
(Celastraceae)

Abstract
It is a large deciduous twining shrub, found in South Asia and Australia. In
Ayurveda, seeds are classified as Medhya Rasayana (nervine tonic) and credited
with stimulating intellectual powers and sharpening memory, thence called
Jyotishmati. Its therapeutic uses include vãtavyãdhi, smrtidaurbalya, and śvitra.
The seed oil was used by courts and colleges of India and by a great many pundits
to increase intelligence of their pupils. Seed oil has also been used in Ayurveda for
treatment of intestinal disorders. Muslim practitioners of Unani medicine
describe them as aphrodisiac and stimulating. Seed decoction, with or without
aromatics, is used in the treatment of rheumatism, gout, paralysis and leprosy; the
seed oil is rubefacient and applied to relieve rheumatic pains. Methanol leaf
extract tested positive for steroid, terpenoid, carbohydrate, alkaloid, saponin, and
phenolic compounds, and several sesquiterpenes have been isolated from seeds.
Aqueous seed extract is neuroprotective against oxidative stress due to free
radical damage, and protects neuronal cells against glutamate-toxicity, exhibits
cognition-enhancing and antioxidant properties, and cholinergic activity, which
might be involved in improving memory performance. There are no clinical
studies reported in mainstream literature.

Keywords




Adibaricham Bilogo Ceruppunnari Deng you teng Intellect plant






Jyotishmati Kanuni Malkangni Pãrãvatapadi Staff tree

Vernaculars: Urd.: Malkangni; Hin.: Malkangni, Malkanguni, Malkunki; San.:

Alavanã, Jyotishmati, Kanguni, Kangunikã, Katumbhi, Pãrãvatapadi, Vanhiruchi;
Ben.: Kijri, Kondgaidh, Lataphataki, Malkangni, Sankhu; Mal.: Ceruppunna,
Ceruppunnari, Palulavum, Uzhinja, Valulavum, Valuzhavam; Mar.: Dhimarbel,
Kangani, Kanguni, Kanuni, Malkanguni, Pigavi; Tam.: Adibaricham, Ati-parich-
cham, Kagodagi, Kalambam, Kaligam, Kirumikkundram, Kungiligam, Manjakodi,
© Springer Nature Switzerland AG 2020 561
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_59
562 Celastrus paniculatus Willd.

Siruvaluluvai, Sodiyam, Valuluvai; Tel.: Bavunji, Danti cettu, Gundu-meda,

Gundumida, Kasara-tige, Mala-eri-kata, Malkanguni, Manirteega, Peddamaveru,
Palleru; Chi.: 灯油藤, 小黄果, Deng you teng; Eng.: Black oil plant, Intellect
plant, Staff tree; Tag.: Bilogo, Lagete, Lañgitñgit.
Description: It is a large deciduous twining shrub, found in South Asia and
Australia; with a pale-brown, rough and exfoliating bark; highly regarded in India
for its nootropic (cognition enhancing, neuroprotective) property. Leaves are
elliptic, oblong, ovate, or obovate to sub-orbicular, glabrous, base cuneate, margin
serrate; flowers (greenish) from April thru June. Fruit is a 3-celled, globose, green
capsule, containing 3–6 seeds enclosed in a complete arillus of a rich orange color
and sweet taste; seeds are about the size of millet, of a reddish-brown color, oily and
angular like a section of a sphere; the testa is hard, and the kernel which is white has
an acrid taste. Expressed oil (sometimes called staff-tree oil) has a deep
reddish-yellow color; it deposits a solid fat after it has been kept for a short time
[12] (Figs. 1, 2 and 3).
Actions and Uses: In Ayurveda, seeds are classified as Medhya Rasayana (nervine
tonic) and credited with stimulating intellectual powers and sharpening memory,
thence called Jyotishmati. Its therapeutic uses include vãtavyãdhi, smrtidaurbalya,
and śvitra.LX Seed oil has also been used in Ayurveda for treatment of intestinal

Fig. 1 Celastrus paniculatus, Flowers, Vinayaraj, WikimediaCommons; ShareAlike 4.0 Interna-

tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Celastrus_paniculatus_-_Black_
Oil_Plant_flowers_at_Periya_2014.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
Celastrus paniculatus Willd. 563

Fig. 2 Celastrus paniculatus, Fruits, Vinayaraj, WikimediaCommons; ShareAlike 4.0 Interna-

tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Celastrus_paniculatus_03.JPG;
https://creativecommons.org/licenses/by-sa/4.0/deed.en

Fig. 3 Celastrus paniculatus, Seeds, DrLee, WikimediaCommons, Universal CC0 1.0. https://
commons.wikimedia.org/wiki/File:Celastrus_paniculatus_seeds.jpg; https://creativecommons.org/
publicdomain/zero/1.0/deed.en
564 Celastrus paniculatus Willd.

disorders [6]. Extraction of oil from seeds is supposed to be obtained by placing

seeds on a sword and exposing it to sun or direct heat over a fire. This oil was used
by courts and colleges of India and by a great many pundits to increase intelligence
of their pupils. Muslim practitioners of Unani medicine describe them as aphro-
disiac and stimulating, and useful both externally and internally for treatment of
gout, rheumatism, paralysis, and leprosy. Seeds may be administered in such cases,
starting with one seed and increasing by one seed daily to fifty a day; concurrently,
the oil or the crushed seeds combined with aromatics, may be applied externally.
The latter application is said to be very efficient for the relief of local pain of
rheumatic or malarial nature.XL Seeds (temperament, hot 3° and dry 3°) are also
regarded in Unani medicine as carminative, appetizer, digestive, expel phlegm, and
beneficial for cold diseases, such as rheumatoid arthritis, paralysis, palsy, dementia,
and epilepsy, and used to enhance memory, intellect, sexual power and stomach
functions.L,LXXVII Seed decoction, with or without aromatics, is used in the treat-
ment of rheumatism, gout, paralysis and leprosy; the seed oil is rubefacient and
applied to relieve rheumatic pains.XXI,LXXXI,CV QuisumbingCXVII quotes Guerrero
that the pulverized seeds are used as antirheumatic and in the treatment of paralysis;
whereas, the sap from leaves is used as an antidote to opium poisoning. Bark and
leaves are reported abortifacient, ecbolic and oxytocic [8, 27], and the leaves,
emmenagogue [19, 27].
Phytoconstituents: Methanol leaf extract tested positive for steroid, terpenoid, car-
bohydrate, alkaloid, saponin, and phenolic compounds [10], and several sesquiterpenes
(1a,6b,8b-triacetoxy-9b-benzoyloxydihydro-b-agarofuran, 1a,6b,8a-triacetoxy-9a-
benzoyloxydihydro-b-agarofuran, 1a,6b,8b,14-tetraacetoxy-9a-benzoyloxydihydro-
b-agarofuran, 1a,6b,8b,14-tetraacetoxy-9b-benzoyloxydihydro-b-agarofuran, 1a,8b-
diacetoxy-9b-benzoyloxydihydro-b-agarofuran, 1a,8b, 14-triacetoxy-9b-furoyloxydi-
hydro-b-agarofuran, and angulatueoid C) have been isolated from seeds [5, 6, 30].
Pharmacology: Aqueous seed extract was neuroprotective against oxidative stress
due to free radical damage [12], and protected neuronal cells against glutamate-
toxicity by modulating glutamate receptor function [13], exhibited cognition-
enhancing and antioxidant properties [17], and cholinergic activity, which might be
involved in improving memory performance [3]. Twenty-days oral treatment with
macerated ethanol seed extract significantly ameliorated 3-nitropropionic acid-
induced neuronal deficit, including cognitive dysfunction, and oxidative stress in
rats [20]. Seed oil exhibited significant anxiolytic activity [24], highly efficacious in
reducing stress [18], attenuated stress-induced anxiety behavior and improved
cognitive functions [2], improved retention ability, significantly decreased contents
of NE, DA and 5-HT and their metabolites in rats’ brain [21], completely reversed
scopolamine-induced task performance deficit [11, 25], and prevented onset of
aluminum-induced neural insult and overall systemic oxidative stress [9]. The oil
also exhibited antidepressant-like activity in mice, comparable to fluoxetine, and
inhibited brain MAO-A activity [28]. The oil exhibited the least antioxidant
properties, but was the most effective in preventing neuronal cells against hydrogen
peroxide- and glutamate-induced toxicities [14].
Celastrus paniculatus Willd. 565

Methanol seed extract relaxed isolated rat intestinal preparations [6], which was
blocked by CCB, nifedipine [7]. Seed oil protected against various gastric
ulcerogenic challenges, and improved activities of antioxidant enzymes, SOD and
CAT [22]. Methanol seed extract substantially reduced plasma TC, TGs and
LDL-C, and increased HDL-C of hypercholesterolemic rats [23], and exhibited
significant antioxidant activity [26]. Ethanol seed extract [16] and methanol flower
extract [1] are reported to exhibit moderate analgesic and anti-inflammatory effects.
Antifungal activity was reported against T. mentagrophytes, T. rubrum, T. souda-
nense, Torulopsis glabrata, C. albicans, and C. krusei [29], and saponins isolated
from seeds showed antibacterial activity against oral pathogens, S. salivarius and
L. acidophilus [15].
Clinical Studies: There are no clinical studies reported in journals listed on
PubMed.
Mechanism of Action: Neuroprotective effect could be due to its antioxidant
activity [12, 20], though the oil exhibited least antioxidant property and was most
neuroprotective [14]. Cognition-and memory enhancing effects may involve its
cholinergic activity [3], and brain MAO-A inhibitory activity may be responsible
for its antidepressant-like effect [28].
Human A/Es, Allergy and Toxicity: Unani physicians regard it not suitable for
individuals with hot temperament, and especially for young adults.LXXVII
Animal Toxicity: An oily seed extract inhibited spermatogenesis in rats, and
caused reversible focal necrosis of liver [4].
Commentary: Absence of any reported clinical studies may classify this plant as
virgin for potential clinical exploration for its memory-enhancing and antidepres-
sant effects.

References
1. Ahmad F, Khan RA, Rasheed S. Preliminary screening of methanolic
extracts of Celastrus paniculatus and Tecomella undulata for analgesic and
anti-inflammatory activities. J Ethnopharmacol. 1994;42:193–8.
2. Bhagya V, Christofer T, Shankaranarayana Rao BS. Neuroprotective effect of
Celastrus paniculatus on chronic stress-induced cognitive impairment.
Indian J Pharmacol. 2016;48:687–93.
3. Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G. Nootropic
activity of Celastrus paniculatus seed. Pharm Biol. 2010;48:324–7.
4. Bidwai PP, Wangoo D, Bhullar N. Antispermatogenic action of Celastrus
paniculatus seed extract in the rat with reversible changes in the liver. J
Ethnopharmacol. 1990;28:293–303.
5. Borbone N, Borrelli F, Montesano D, et al. Identification of a new sesquiterpene
polyol ester from Celastrus paniculatus. Planta Med. 2007;73:792–4.
566 Celastrus paniculatus Willd.

6. Borrelli F, Borbone N, Capasso R, et al. New sesquiterpenes with intestinal

relaxant effect from Celastrus paniculatus. Planta Med. 2004;70:652–6.
7. Borrelli F, Borbone N, Capasso R, et al. Potent relaxant effect of a Celastrus
paniculatus extract in the rat and human ileum. J Ethnopharmacol. 2009;122:
434–8.
8. Casey RC. 298 alleged antifertility plants of India. Indian J Med Sci. 1960;
14:590–600.
9. Chakrabarty M, Bhat P, Kumari S, et al. Corticohippocampal salvage in
chronic aluminium induced neurodegeneration by Celastrus paniculatus
seed oil: neurobehavioural, biochemical, histological study. J Pharmacol
Pharmacother. 2012;3:161–71.
10. Debnath M, Biswas M, Shukla VJ, Nishteswar K. Phytochemical and
analytical evaluation of Jyotishmati (Celastrus paniculatus Willd.) leaf
extracts. Ayu. 2014;35:54–7.
11. Gattu M, Boss KL, Terry AV Jr, Buccafusco JJ. Reversal of scopolamine-
induced deficits in navigational memory performance by the seed oil of
Celastrus paniculatus. Pharmacol Biochem Behav. 1997;57:793–9.
12. Godkar P, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus
seed water soluble extracts protect cultured rat forebrain neuronal cells from
hydrogen peroxide-induced oxidative injury. Fitoterapia. 2003;74:658–69.
13. Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus
seed water soluble extracts protect against glutamate toxicity in neuronal
cultures from rat forebrain. J Ethnopharmacol. 2004;93:213–9.
14. Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus
seed oil and organic extracts attenuate hydrogen peroxide- and glutamate-
induced injury in embryonic rat forebrain neuronal cells. Phytomedicine.
2006;13:29–36.
15. Jyothi KS, Seshagiri M. In-vitro activity of saponins of Bauhinia purpurea,
Madhuca longifolia, Celastrus paniculatus and Semecarpus anacardium
on selected oral pathogens. J Dent (Tehran). 2012;9:216–23.
16. Kulkarni YA, Agarwal S, Garud MS. Effect of Jyotishmati (Celastrus
paniculatus) seeds in animal models of pain and inflammation. J Ayurveda
Integr Med. 2015;6:82–8.
17. Kumar MH, Gupta YK. Antioxidant property of Celastrus paniculatus
Willd.: a possible mechanism in enhancing cognition. Phytomedicine. 2002;
9:302–11.
18. Lekha G, Mohan K, Samy IA. Effect of Celastrus paniculatus seed oil
(Jyothismati oil) on acute and chronic immobilization stress induced in
swiss albino mice. Pharmacognosy Res. 2010;2:169–74.
19. Malhi BS, Trivedi VP. Vegetable antifertility drugs of India. Quart J Crude
Drug Res. 1972;12:1922.
20. Malik J, Karan M, Dogra R. Ameliorating effect of Celastrus paniculatus
standardized extract and its fractions on 3-nitropropionic acid induced
neuronal damage in rats: possible antioxidant mechanism. Pharm Biol.
2017;55:980–90.
Celastrus paniculatus Willd. 567

21. Nalini K, Karanth KS, Rao A, Aroor AR. Effects of Celastrus paniculatus
on passive avoidance performance and biogenic amine turnover in albino
rats. J Ethnopharmacol. 1995;47:101–8.
22. Palle S, Kanakalatha A, Kavitha CN. Gastroprotective and antiulcer effects
of Celastrus paniculatus seed oil against several gastric ulcer models in rats.
J Diet Suppl. 2018;15:373–85.
23. Patil RH, Prakash K, Maheshwari VL. Hypolipidemic effect of Celastrus
paniculatus in experimentally induced hypercholesterolemic Wistar rats.
Indian J Clin Biochem. 2010;25:405–10.
24. Rajkumar R, Kumar EP, Sudha S, Suresh B. Evaluation of anxiolytic
potential of Celastrus oil in rat models of behaviour. Fitoterapia. 2007;78:
120–4.
25. Raut SB, Parekar RR, Jadhav KS, Marathe PA, Rege NN. Effect of
Jyotiṣmatī seed oil on spatial and fear memory using scopolamine induced
amnesia in mice. Anc Sci Life. 2015;34:130–3.
26. Russo A, Izzo AA, Cardile V, Borrelli F, Vanella A. Indian medicinal plants
as antiradicals and DNA cleavage protectors. Phytomedicine. 2001;8:125–32.
27. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
28. Valecha R, Dhingra D. Behavioral and biochemical evidences for antide-
pressant-like activity of Celastrus Paniculatus seed oil in mice. Basic Clin
Neurosci. 2016;7:49–56.
29. Vonshak A, Barazani O, Sathiyamoorthy P, et al. Screening of South Indian
medicinal plants for antifungal activity against cutaneous pathogens.
Phytother Res. 2003;17:1123–5.
30. Weng JR, Yen MH, Lin WY. Cytotoxic constituents from Celastrus
paniculatus induce apoptosis and autophagy in breast cancer cells. Phyto-
chemistry. 2013;94:211–9.
Centaurea behen L.
(Asteraceae/Compositae)

(Syns.: C. acuta Vahl ex M.Bieb.; C. alata Lam.; C. brachyptera DC.; Centaurium

behen (L.) K. Koch; Behen album Garsault)

Abstract
The plant grows wild in Persia, Syria, Armenia and Kabul. Arabs became
acquainted with red and white Bahmans through ancient Persians. Bahman is
equivalent to Brahman and means the supreme intelligence. It is also the name
of one of the Persian months. The Persians powdered roots of white Bahman and
drank it with milk to strengthen memory. Muslim physicians practicing Unani
medicine consider the root fattening, powerful aphrodisiac and resolvent of
phlegmatic humours; they also prescribe it in calculous affections and jaundice.
Fat, sugar, gum, ash, and three sesquiterpene lactones, including cynaropicrin,
4b,15-dehydro-3-dehydrosolstitialin A, and aguerin B have been reported from
the root. Cynaropicrin and aguerin B exhibited significant antiangiogenic effects,
and remarkable inhibitory effect on proliferation and migration of human
umbilical vein endothelial cells.

Keywords





Asgand vilayati Bahman safed Behen Behman abiad Centaurea Crupine

vulgaire

Vernaculars: Urd.: Asgand vilayati, Bahman safed; Hin.: Safed behman; Ara.:
Behman abiad; Eng.: Behen, Centaurea; Fre.: Crupine commune, Crupine vulgaire;
Per.: Bahman-e-safed.
Description: The plant grows wild in Persia, Syria, Armenia and Kabul; is less than
a meter high; leaves are relatively large, comparable to spinach leaves; flowers small,
yellow. Roots are of a whitish-brown color and 2.5 or 5 cm in length and about 2 cm
in diameter; twisted, and much shriveled, near the crown it is marked by numerous
circular lines. The interior is white and spongy; when soaked in water it swells and
become mucilaginous.XL Upper end of the root is blunt, where it is marked with

© Springer Nature Switzerland AG 2020 569

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_60
570 Centaurea behen L.

Fig. 1 Centaurea behen, Illustration, E.P. Ventenat, WikimediaCommons, https://commons.wiki

media.org/wiki/File:C.behen-Ventenat-1.jpg

blackish rings which are remnants of sheath-leaves. In some the remains of leaf buds
are seen resembling in shape of a bunch of grapes. Odor is rather aromatic; taste
mucilaginous and sweetish (Fig. 1).LXXXI
Actions and Uses: Arabs became acquainted with red and white Bahmans through
ancient Persians. Bahman is equivalent to Brahman and means the supreme
intelligence. It is also the name of one of the Persian months, of the second day of
each month, and of a plant which flowers in the month of Bahman (January). The
Persians powdered roots of white Bahman and drank it with milk to strengthen
memory. Muslim physicians consider the root (temperament, hot 2° and dry 2°)
fattening, powerful aphrodisiac and resolvent of phlegmatic humours; they also
prescribe it in calculous affections and jaundice.XL It is also deobstruent, increases
sexual desire by increasing semen production, cardiotonic and useful in palpita-
tion,L,LXIX,LXXVII and possesses diuretic and mild aperient properties; a good
substitute for Musli safed and is used in seminal debility.L,LXXVII,LXXXI,CV
Phytoconstituents: Sesquiterpene lactones, including cynaropicrin, 4b,15-dehydro-
3-dehydrosolstitialin A, and aguerin B have been isolated from the root of C. behen
[2].
Pharmacology: Cynaropicrin and aguerin B exhibited strong cytotoxic activity,
comparable to doxorubicin, against A2780 cells, and strongly inhibited prolifera-
tion and migration of HUVECs [2]. The essential oil was also cytotoxic, and
increased total oxidative status in cultured human whole blood cells [1].
Centaurea behen L. 571

Clinical Studies: No clinical studies are reported about this plant.

Human A/Es, Allergy and Toxicity: Not suitable for hot temperament
patients.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: The plant has not been sufficiently investigated pharmacologically,
and there are no clinical studies reported in the literature.

References
1. Çelikezen FÇ, Hayta Ş, Özdemir Ö, Türkez H. Cytotoxic and antioxidant
properties of essential oil of Centaurea behen L. in vitro. Cytotechnology
2019;71:345–50.
2. Shakeri A, Amini E, Asili J, et al. Screening of several biological activities
induced by different sesquiterpene lactones isolated from Centaurea behen L.
and Rhaponticum repens (L.) Hidalgo. Nat Prod Res. 2018;32:1436–40.
Centella asiatica (L.) Urban
(Apiaceae/Umbelliferae)

(Syns.: C. coriacea Nann.; Hydrocotyle asiatica L.; H. erecta L. f.; H. pallida DC.;
Trisanthus cochinchinensis Lour.)

Abstract
It is a prostrate, sparingly hairy or nearly smooth annual herb found in open,
damp grasslands of India, Sri Lanka, China, Japan, Southeast Asian countries,
South Africa, and Australia. The plant has been used in Ayurveda and traditional
Chinese medicine to alleviate symptoms of depression and anxiety. In Ayurveda,
herbal formulations that boost memory, restore cognitive deficits and improve
mental function are called Medhyarasayanas, of which Brahmi is an important
ingredient. Apart from its neuroprotective effects, the herb is used for wound
healing, treatment of various skin conditions such as leprosy, lupus, varicose
ulcers, eczema, and psoriasis, diarrhea, fever, amenorrhea, and diseases of the
female genitourinary tract. In traditional Chinese medicine, it is widely used as
an anti-inflammatory agent, for memory improvement, antitumor activity and for
the treatment of gastric ulcers. Leaves are considered stimulant, and used for
rejuvenation, for liver ailments, leprosy and syphilis in Indonesia. The plant is
also reportedly used in Indonesia and Brazil in the treatment of dermatitis,
hypertension, as blood purifier, and to improve memory. In Malaysia it is used as
a remedy for diabetes, to treat bronchitis, asthma, gastric catarrh, dysentery,
kidney trouble, urethritis, liver complaints, tuberculosis, hematuria, and dropsy.
Root is administered with milk and liquorice in fever and dysentery, and the
powder is dusted over ulcers, and applied externally in chronic skin diseases,
such as eczema, lupus, psoriasis, secondary syphilitic sores and skin eruptions.
Pentacyclic triterpenoid saponins, collectively known as centelloids, are the
major constituents and include asiaticoside, brahmoside, brahminoside, centel-
loside, centellose, madecassoside, thankuniside, sceffoleoside, asiatic-, brahmic-,
centellic- and madecassic acids. It also contains volatile oils, flavonoids, tannins,
phytosterols, amino acids, and sugars. Two flavonoids named castilliferol and
castillicetin, and isochlorogenic acid were isolated from the whole plant.
Aqueous extract improved learning and memory in normal rats and mice,
significantly attenuated colchicine-induced memory impairment and oxidative

© Springer Nature Switzerland AG 2020 573

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_61
574 Centella asiatica (L.) Urban

damage, and reversed increase in forebrain AChE activity, significantly reduced

MPTP-induced LPO and increased antioxidant enzyme levels in corpus striatum
and hippocampus regions of aged Sprague-Dawley rats. Single oral dose of 12 g
of the plant was anxiolytic in healthy volunteers, and hydroethanol extract
to patients with GAD, significantly attenuated anxiety, reduced stress and
depression, and improved patients’ cognition and willingness for adjustment.

Keywords




Artaniya-e-hindi Asiatic pennywort Brahmi booti Centela Gotu kola






Indischer wassernabel Ji xue cao Kulakudi Mandūkaparni Sallatsspikblad

Vernaculars: Urd.: Kula kudi; Hin.: Bengsag, Brahmamanduki, Brahmibooti,1

Khulakhudi, Mandukparni; San.: Brahami, Brahmamanduki, Brãhmibheda, Divyã,
Mandookparni, Mandūkaparni, Mandūki, Tvãstri; Ben.: Bora thulkari, Brahma
manduki, Jholkhuri, Thankuni, Tholkuri; Guj.: Barmi; Mal.: Kodagam, Kudangal,
Kudavan, Kutakan, Muththil, Muyalchevi; Mar.: Brahmi, Karinga, Karivana;
Tam.: Babassa, Ballau, Vallaarai-kire, Vallarai; Tel.: Babassa, Babassailaka,
Bokuddu, Manduka-brummi, Saraswataku, Sarswathi aku, Vauari; Ara.: Artaniya-
e-hindi; Chi.: 积雪草, 崩大碗, Chi-hsueh Ts’ao, Ji xue cao, K’ou-tzu ts’ao; Dan.:
Asiatisk centella; Dut.: Brahmi, Gotu kola; Eng.: Asian coinleaf, Asiatic pennywort,
Centella, Coinwort, Indian pennywort, Sheep-rot, Spadeleaf; Fin.: Rohtosam-
makonputki; Fre.: Centelle asiatique, Écuelle d’eau, Herbe du tigre, Hydrocotyle
asiatique, Hydrocotyle indien; Ger.: Indischer wassernabel; Ind.: Daun kaki kuda;
Ita.: Centella, Erba della tigre e dell’elefante; Jap.: Tsubokusa; Maly.: Gagan-gagan
and Pegaga (Java); Nep.: Brahambuti; Por.: Centela; Sin.: Gotu kola, Hin-gotukola;
Sud.: Antanan; Spa.: Antanan, Brahmi, Gotu kola, Hierba de clavo, Pegaga, Oreja
de ratón, Sombrerito; Swe.: Sallatsspikblad; Tag.: Takip-kohol, Takip-suso, Tapingan-
daga; Tha.: Bai bua bok (leaves); Vie.: Cây rau má, Rau Ma.
Description: It is a prostrate, sparingly hairy or nearly smooth annual herb found
in open, damp grasslands of India, Sri Lanka, China, Japan, Southeast Asian
countries, South Africa, and Australia. Stems are slender, creeping stolons, green to
reddish-green in color, connecting plants to each other; long-stalked, green leaves
are rounded to reniform, 2–5 cm wide, horizontal, more or less cupped, rounded at
the tip, and kidney-shaped or heart-shaped at the base, which have smooth texture
with palmately netted veins; petoles are erect and long. The peduncles occur in pairs
or threes, are less than 1 cm long, and usually bear three sessile flowers; fruits are
clustered at the joints, small laterally compressed and furrowed or ribbed longitu-
dinally; when bruised, the odor is aromatic, taste pungent, nauseous and bitter. The
rootstock consists of rhizomes, creamish in color and covered with root hairs and
growing down vertically (Figs. 1 and 2).LXXXI

1
The name Brahmi also applies to the plant Bacopa monnieri [79].
Centella asiatica (L.) Urban 575

Fig. 1 Centella asiatica, Plant, Vengolis, WikimediaCommons; ShareAlike 4.0 International CC

BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Centella_asiatica_6121.jpg; https://creative
commons.org/licenses/by-sa/4.0/deed.en

Fig. 2 Centella asiatica, Leaves, Shashidhara Halady, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Centella_asiatica_in_
Karnataka.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

Actions and Uses: The plant has been used in Ayurveda and traditional Chinese
medicine to alleviate symptoms of depression and anxiety [8]. In Ayurveda, herbal
formulations that boost memory, restore cognitive deficits and improve mental
function are called Medhyarasayanas, of which Brahmi is an important ingredient
[79]. Apart from its neuroprotective effects, the herb is used for wound healing,
treatment of various skin conditions such as leprosy, lupus, varicose ulcers, eczema
and psoriasis, diarrhea, fever, amenorrhea, and diseases of the female genitourinary
tract [22]; other reported therapeutic uses of the dried plant in Ayurveda include
576 Centella asiatica (L.) Urban

raktapitta, kustha, meha, jvara, śvãsa, kãsa, aruci, pãndu, śotha, kandū, and rak-
tadosa.LX In TCM, it is widely used as an anti-inflammatory agent, for memory
improvement, antitumor activity and for the treatment of gastric ulcers [13]. Tra-
ditional health practitioners of Thanchi upazilla of Bandarban districts in Bangla-
desh use it to treat dysentery [41]. Dymock et al.XL described it as alterative, tonic,
diuretic and local stimulant, especially useful in syphilitic skin diseases, in which it
may be used both externally and internally. In higher doses, it acts as a stupefying
narcotic, producing headache, giddiness, and in some cases, coma. Administration
of powdered drug in lepers first causes sensation of warmth and pricking in skin,
especially of hands and feet, followed after a few days by a general sensation of
warmth, sometimes almost unbearable; capillary circulation is accelerated, and after
about a week appetite improves, and skin becomes soft, throws off the thickened
epidermis, and recovers its transpiratory function. The effectiveness or use in
leprosy or syphilis is considered to be due to its stimulating action on cutaneous
circulation.CXXXXIX Leaves are considered stimulant, and used for rejuvenation, for
liver ailments, leprosy and syphilis in Indonesia [33]. The plant is also reportedly
used in Indonesia and Brazil in the treatment of dermatitis, hypertension, as blood
purifier, and to improve memory. In Malaysia it is used as a remedy for diabetes
[56], to treat bronchitis, asthma, gastric catarrh, dysentery, kidney trouble,
urethritis, liver complaints, tuberculosis, hematuria, and dropsy [75]. Root is
administered with milk and liquorice in fever and dysentery, and the powder is
dusted over ulcers, and applied externally in chronic skin diseases, such as eczema,
lupus, psoriasis, secondary syphilitic sores and skin eruptions.LXXXI The plant is
consumed as a green leafy vegetable in Sri Lanka and in the forms of juice, drink,
and other food products [9]. In the Philippines, leaves are regarded tonic and
stimulant, and used to lower BP;CXVII whereas, the sap of leaves is used to treat
sclerotic wounds, and the decoction of leaves is considered diuretic and useful in
gonorrhea.LVI Titrated extract is a reconstituted mixture of three triterpenes
extracted from the plant, asiatic acid, madecassic acid and asiaticoside, that has
been used in Europe for many years for the treatment of wound healing defects
[53]. Whole plant, including roots and fruits, should be carefully dried and bottled
to preserve volatile oil, as it is more active than leaves only. The plant is sensitive to
biological and chemical water pollutants that may be absorbed into the plant.
Uptake of Zn and Ni by the plant from contaminated soil from various sites in
Peninsular Malaysia, and also potential for lead toxicity from it were determined
high [61].
Phytoconstituents: Aerial parts are a rich source of quercetin [4]. Two dammarane
monodesmosides centellosides A and B, and ginsenosides Mc and Y were isolated
from the whole plant [96]. It also contains volatile oils, flavonoids, tannins, phy-
tosterols, amino acids, and sugars.LXXXVI Two flavonoids named castilliferol
and castillicetin, and isochlorogenic acid were isolated from the whole plant [88].
Pentacyclic triterpenoid saponins, collectively known as centelloids, are the major
constituents and include asiaticoside, brahmoside, brahminoside, centelloside, cen-
tellose, madecassoside, thankuniside, sceffoleoside, asiatic-, brahmic-, centellic-
and madecassic acids [36, 107]; other pentacyclic triterpenic acids and their
Centella asiatica (L.) Urban 577

respective glycosides include, isothankuniside, madasiatic acid, cenellic acid,

indocentic acid, betulinic acid and centic acid [107]. Centellin, asiaticin, and cen-
tellicin [83], oleanane-type triterpene oligoglycosides, centella-saponins B, C, and
D, asiaticoside B, and sceffoleoside A [55], 11,12-dehydroursolic acid lactone,
2a,3a-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, corosolic acid, ursolic
acid, pomolic acid, 8-acetoxy-1,9-pentadecadiene-4,6-diyn-3-ol, b-sitosterol 3-Ob-
glucopyranoside, and rosmarinic acid [102], asiaticoside C, asiaticoside F, 23-O-
acetylmadecassoside, 23-O-acetylasiaticoside B, sitosterol 3-O-b-glucoside, stigmas-
terol 3-O-b-glucoside, and querectin-3-O-b-D-glucuronide [72], 2a,3b,20,23-tetra-
hydroxyurs-28-oic acid [103], docosyl ferulates, bayogenin, 3b-6b-23-trihydroxy-
olean-12-en-28-oic acid, 3b-6b-23-trihydroxyurs-12-en-28-oic acid, and D-gulonic
acid [104], have been reported from aerial parts. An insipissated oil of a pale-
yellowish color (named vellarine and considered the active principle) with a bitter,
pungent and persistent taste and a marked odor of hydrocotyle had been isolated
from the dried herb. However, its presence is subject to variations under
the influence of heat, humidity, and even the climatic conditions, volatilizing at
120 °C; vellarine was principally obtained from the roots.CXXXXIX Australian
C. asiatica collected during different months (seasons) showed that harvesting the
plant in summer gave the highest yield of triterpenoids, kaempferol and chlorogenic
acid [1]. Madecassoside is reported to be the highest amount of triterpene con-
stituent in C. asiatica [49], and Centella from Malaysia contained significant
amounts of madecassoside and asiaticoside, but was low in asiatic and madecassic
acid [31]. Aqueous extract is rich in phenolic compounds, but does not contain
asiatic acid, the known neuroprotective triterpene [86]. Storage of the dried plant
extract over a six-months period showed decline in total phenolic content, asiatic
acid, kaemferol, antioxidant and AChE inhibitory activities [42].
Pharmacology: Aqueous extract improved learning and memory in normal rats and
mice [25, 71, 93], significantly attenuated colchicine-induced memory impairment
and oxidative damage, and reversed increase in forebrain AChE activity [45], sig-
nificantly reduced MPTP-induced LPO and increased antioxidant enzyme levels in
corpus striatum and hippocampus regions of aged Sprague-Dawley rats [30], sig-
nificantly decreased brain levels of MDA and increased levels of GSH [93],
improved STZ-induced cognition impairment and oxidative stress in rats [92], and
decreased PTZ-kindled seizures and improved PTZ kindling-induced learning deficit
in rats [29]. Aqueous extract also attenuated b-amyloid-associated cognitive deficit
in mice, and pretreatment of mice with a standardized aqueous extract was signifi-
cantly protective against 3-nitropropionic acid-induced oxidative stress and mito-
chondrial dysfunction in striatum and other brain regions [78]. Simultaneous
administration of aqueous extract for six-weeks significantly attenuated D-galactose-
induced behavioral alterations, cognition impairment, oxidative damage and mito-
chondrial enzyme complex activities, and reduced AChE level in mice [46], and
protected rats against aluminum-induced memory impairment and oxidative damage
[68]. Ethanol leaf extract improved activities of SOD, CAT and GPx in substantia
nigra of normal and MPTP-treated mice [7], and greatly improved neurobehavioral
578 Centella asiatica (L.) Urban

activity, antioxidant enzymes activity, and diminished infarction size in rats after
right MCA occlusion/reperfusion [91]. Asiatic acid administered orally pre- and
post-ischemia in a mouse model of permanent cerebral ischemia, significantly
reduced the infarct volume and reduced mitochondrial injury [44], and significantly
attenuated glutamate-induced cognitive deficits, and restored LPO and glutathione
and SOD activities in hippocampus and cortex of neonatal mice [100]. Fresh leaf
extract administered to neonatal mice for 6-weeks significantly increased dendrites
length and dendritic branching points along the length of hippocampal CA3 neurons,
the brain regions concerned with learning and memory [58]; similar results were
observed in adult rats [17, 70]. Ethanol extract markedly increased neurite outgrowth
in human SH-SY5Y cells in the presence of nerve growth factor, whereas aqueous
extract was ineffective [85]. Wijeweera et al. [98] reported anxiolytic activity of
methanol and ethyl acetate extracts, and the asiaticoside. Hydroalcohol extract
in vitro inhibited AChE activity by 50% [59].
Pre- and post-treatment with leaf extract and fresh juice significantly inhibited
experimental gastric lesions in rats [11, 12, 26, 73, 108], increased brain GABA
level; pretreatment with bicuculline methiodide (GABAA-specific antagonist)
reversed antiulcerogenic activity [10]. Powdered leaf administration to rats under
oxidative stress for 25-weeks significantly decreased body and liver weights,
lowered serum LDL-C and TGs levels, and increased HDL-C and TC levels [35].
Aqueous infusion of aerial parts also significantly reduced TC, LDL-C and TG
levels, and increased HDL-C and SOD of hyperlipidemic rats [47]. Similarly,
treatment with an extract reversed increased glucose and lipid levels of obese
diabetic rats and increased blood insulin levels [56]. Aqueous and ethanol extracts
were cardioprotective against I/R induced MI [67], and against adriamycin-
cardiomyopathy in rats [20, 21]. Administration of Gotu kola powder to rats alle-
viated DEN—hepatotoxicity, significantly decreased inflammatory mediators, and
increased levels of antioxidant enzymes [13]. Ethanol leaf extract protected against
isoniazid-induced hematological and liver toxicity in rats [19]. Concomitant oral
supplementation with the plant and aqueous extract effectively reduced age-related
brain regional LPO levels and increased antioxidant status of rats and prepubertal
mice [77, 80, 87], and significantly protected against arsenic-induced oxidative
stress in rats [16, 27]. Methanol extract treatment of lymphoma-bearing mice for
14-days significantly increased antioxidant enzymes activity [38], and various
extracts have shown in vitro antioxidant activity [28, 57, 60, 65, 99]. Oral
administration of the extract retarded development of solid and ascites tumors and
increased life-span of tumor bearing mice [3]. Ursolic acid showed significant
in vitro antiproliferative activity against human uterine carcinoma (HeLa), and
murine melanoma (B16F10) cells [102]. A polyacetylene compound induced
apoptosis (63%) independent of cell cycle regimen in mouse lymphoma cells [24].
Both aqueous and ethanol extracts exhibited antiallergic, antipruritic and anti-
inflammatory activities; ethanol extract showing better anti-inflammatory activity in
rats [18]. Antipsoriatic property of the plant is attributed to triterpenoid glycosides,
madecassoside and asiaticoside [74]. Asiatic acid produces anti-inflammatory
activity with concurrent decrease in serum levels of NO, TNF-a, and IL-1b, and an
Centella asiatica (L.) Urban 579

increase in antioxidant enzymes activities [34]. Topical application of titrated

extract ameliorated phthalic anhydride-induced atopic dermatitis in mice, and
inhibited expression of iNOS and COX-2, and NF-jB activity, and release of
TNF-a, IL-1b, IL-6, and IgE [64]. Topical application and oral administration of
aqueous and alcohol extracts augmented epithelialization and the rate of contraction
of rats’ dermal wounds [76, 84, 89, 90]; asiatic acid and asiaticoside were identified
as being responsible for wound healing and antioxidant properties [43, 53, 81, 82].
Oral administration of madecassoside also significantly facilitated complete wound
closure [48]. Aqueous extract possesses anti-HSV-II activity [110], and anti-HSV-1
and HSV-2 activities are attributed to asiaticoside [101]. Methanol leaf extract is
modestly active against S. aureus and MRSA [106], and ethanol leaf extract sig-
nificantly inhibited growth of clinical isolates of H. pylori, and significantly reduced
H. pylori colonization in mice gastric mucosa [109].
Clinical Studies: Single oral dose of 12 g of the plant was anxiolytic in healthy
volunteers [8], and a hydroethanol extract in a dose of 500 mg twice daily after
meal for 60-days to patients with GAD, significantly attenuated anxiety, reduced
stress and depression, and significantly improved patients’ cognition and willing-
ness for adjustment [37]. A 500–750 mg dose of the extract to healthy elderly
participants for 60 to 90-days enhanced working memory, increased lower
extremities strength and improved self-rated mood and quality of life [54, 95].
Patients with poststroke cognitive impairment, treated with 750–1,000 mg/day of
70% ethanol extract for six-weeks significantly improved cognitive function [15].
A recent meta-analysis of RCTs reported no significant differences in cognitive
function domains of treated patients, compared to placebo; however, alertness,
mood and decrease in anger were found significant [69]. Significant improvement
was observed in symptoms of lower limbs heaviness and edema, and improved
venous distensibility after treatment with a titrated extract for two-months of
patients with venous insufficiency [66], and the extract administered in capsule
form to patients with diabetic ulcers promoted wound healing and also suppressed
scar formation [63].
Carotid plaque stability index of asymptomatic Italian subjects (mean age 61.5
years) with high oxidative stress was significantly increased, and the plasma free
radicals significantly decreased after 3-months treatment with a combination of a
commercial leaves extract (Centellicum®) and Pycnogenol® [52]; the combination
also significantly slowed progress of carotid or femoral stenosing plaques, reduced
development of angina events by more than 50%, and significantly lowered chances
of MI and TIAs over a four-year period [6]. Six-months treatment with the com-
bination also significantly increased plaque stability index and regressed the plaque
in asymptomatic subjects with increased oxidative stress, mild hypertension and
hypercholesterolemia [5].
Mechanism of Action: Aqueous and ethanol extracts stimulate in vitro glutamic
acid decarboxylase activity by over 40%, the enzyme that catalyzes conversion of
glutamate to GABA [2]. A combination of asiatic acid and madecassic acid was
most effective in nerve differentiation in vitro through activation of MEK signaling
580 Centella asiatica (L.) Urban

pathway [39]. Pretreatment with various extracts, however, significantly decreased

ACh levels and increased AChE activity in different brain regions during
PTZ-induced seizures in rats [94], which would be contrary to the memory and
cognitive improvement. Wound healing effect appears to be due to production of
type I collagen and decrease in inflammatory reaction and myofibroblast production
[97], and asiaticoside promotes fibroblast proliferation and extracellular matrix
synthesis in wound healing [50, 51].
Human A/Es, Allergy and Toxicity: Although its extract is frequently applied to
damaged skin in the treatment of keloids, leg ulcers, phlebitis, slow-healing
wounds, leprosy, surgical lesions, striae distensae and cellulitis, the risk of contact
sensitization is low [32]. Rare cases of allergic contact dermatitis have been
reported [23]. It causes urinary and ovarian irritation and itching over whole
body.LXXXI Cases of hepatitis after consumption of the plant for 20-days or more in
three middle-aged Argentinian women for weight loss were reported, who fully
recovered after discontinuation, and treatment [40].
Animal Toxicity: A standardized extract was nontoxic and nonlethal to rats in a
single oral dose of 2,000 mg/kg, and 1,000 mg/kg administered for 90-days [14].
Alcohol extract (i.p.) to rats up to a dose of 350 mg/kg caused no adverse effects.XIV
Oral treatment of rats with the (unspecified) extract, in doses of 100–300 mg/kg, for
6-weeks is also reported to cause degeneration of spermatogenic cells and signifi-
cant reduction in the number and motility of spermatozoa [105].
CYP450 and Potential for Drug-Herb Interactions: Aqueous extract does not
significantly inhibit in vitro CYP3A4, CYP2C9 and CYP2D6 isoforms, but ethanol
and dichloromethane extracts moderately inhibited CYP2C9, and negligibly CYP2D6
and CYP3A4; asiatic acid potently inhibits CYP2C9 [62].
Commentary: The drug has shown significant improvement in anxiety, memory
and cognitive impairment in health and disease states in clinical trials. However, a
meta-analysis of these trials has put a question mark on the conclusion which needs
to be resolved by more RCTs in larger number of patients of diverse ethnicity. Its use
in combination with Pycnogenol® to stabilize atherosclerotic plaque, reduce angina
events, and decrease the chances of MI and TIAs are a welcome outcome that should
be further explored. A drug that has been used for thousands of years in Ayurveda
and Unani deserves unbiased objective investigations for its health benefits.

References
1. Alqahtani A, Tongkao-on W, Li KM, et al. Seasonal variation of triterpenes
and phenolic compounds in Australian Centella asiatica (L.) Urb. Phytochem
Anal. 2015;26:436–43.
2. Awad R, Levac D, Cybulska P, et al. Effects of traditionally used anxiolytic
botanicals on enzymes of the gamma-aminobutyric acid (GABA) system.
Can J Physiol Pharmacol. 2007;85:933–42.
Centella asiatica (L.) Urban 581

3. Babu TD, Kuttan G, Padikkala J. Cytotoxic and antitumour properties of

certain taxa of Umbelliferae with special reference to Centella asiatica (L.)
Urban. J Ethnopharmacol. 1995;48:53–7.
4. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and
antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr.
2005;56:287–91.
5. Belcaro G, Cornelli U. Variations in echogenicity in carotid and femoral
atherosclerotic plaques with pycnogenol + Centella asiatica supplementa-
tion. Int J Angiol. 2017;26:95–101.
6. Belcaro G, Dugall M, Ippolito E, et al. Pycnogenol® and Centella asiatica
to prevent asymptomatic atherosclerosis progression in clinical events.
Minerva Cardioangiol. 2017;65:24–31.
7. Bhatnagar M, Goel I, Roy T, Shukla SD, Khurana S. Complete Comparison
Display (CCD) evaluation of ethanol extracts of Centella asiatica and
Withania somnifera shows that they can nonsynergistically ameliorate
biochemical and behavioural damages in MPTP induced Parkinson’s model
of mice. PLoS One. 2017;12:e0177254.
8. Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled
study on the effects of Gotu Kola (Centella asiatica) on acoustic startle
response in healthy subjects. J Clin Psychopharmacol. 2000;20:680–4.
9. Chandrika UG, Prasad Kumarab PA. Gotu kola (Centella asiatica):
nutritional properties and plausible health benefits. Adv Food Nutr Res.
2015;76:125–57.
10. Chatterjee TK, Chakraborty A, Pathak M, Sengupta GC. Effects of plant
extract Centella asiatica (Linn.) on cold restraint stress ulcer in rats. Indian J
Exp Biol. 1992;30:889–91.
11. Cheng CL, Guo JS, Luk J, Koo MW. The healing effects of Centella extract
and asiaticoside on acetic acid induced gastric ulcers in rats. Life Sci.
2004;74:2237–49.
12. Cheng CL, Koo MW. Effects of Centella asiatica on ethanol induced gastric
mucosal lesions in rats. Life Sci. 2000;67:2647–53.
13. Choi MJ, Zheng HM, Kim JM, et al. Protective effects of Centella asiatica
leaf extract on dimethylnitrosamine-induced liver injury in rats. Mol Med
Rep. 2016;14:4521–8.
14. Deshpande PO, Mohan V, Thakurdesai P. Preclinical safety assessment of
standardized extract of Centella asiatica (L.) Urban leaves. Toxicol Int.
2015;22:10–20.
15. Farhana KM, Malueka RG, Wibowo S, Gofir A. Effectiveness of gotu kola
extract 750 mg and 1000 mg compared with folic acid 3 mg in improving
vascular cognitive impairment after stroke. Evid Based Complement
Alternat Med. 2016;2016:2795915.
16. Flora SJ, Gupta R. Beneficial effects of Centella asiatica aqueous extract
against arsenic-induced oxidative stress and essential metal status in rats.
Phytother Res. 2007;21:980–8.
582 Centella asiatica (L.) Urban

17. Gadahad MR, Rao M, Rao G. Enhancement of hippocampal CA3 neuronal

dendritic arborization by Centella asiatica (Linn) fresh leaf extract treatment
in adult rats. J Chin Med Assoc. 2008;71:6–13.
18. George M, Joseph L, Ramaswamy. Antiallergic, antipruritic, and anti-
inflammatory activities of Centella asiatica extracts. Afr J Tradit Comple-
ment Altern Med. 2009;6:554–9.
19. Ghosh K, Indra N, Jagadeesan G. The ameliorating effect of Centella
asiatica ethanolic extract on albino rats treated with isoniazid. J Basic Clin
Physiol Pharmacol. 2017;28:67–77.
20. Gnanapragasam A, Ebenezar KK, Sathish V, Govindaraju P, Devaki T.
Protective effect of Centella asiatica on antioxidant tissue defense system
against adriamycin induced cardiomyopathy in rats. Life Sci. 2004;76:
585–97.
21. Gnanapragasam A, Yogeeta S, Subhashini R, et al. Adriamycin induced
myocardial failure in rats: protective role of Centella asiatica. Mol Cell
Biochem. 2007;294:55–63.
22. Gohil KJ, Patel JA, Gajjar AK. Pharmacological review on Centella
asiatica: a potential herbal cure-all. Indian J Pharm Sci. 2010;72:546–56.
23. Gonzalo Garijo MA, Revenga Arranz F, Bobadilla González P. Allergic
contact dermatitis due to Centella asiatica: a new case. Allergol Immuno-
pathol (Madr). 1996;24:132–4.
24. Govindan G, Sambandan TG, Govindan M, et al. A bioactive polyacetylene
compound isolated from Centella asiatica. Planta Med. 2007;73:597–9.
25. Gray NE, Harris CJ, Quinn JF, Soumyanath A. Centella asiatica modulates
antioxidant and mitochondrial pathways and improves cognitive function in
mice. J Ethnopharmacol. 2016;180:78–86.
26. Guo JS, Cheng CL, Koo MW. Inhibitory effects of Centella asiatica water
extract and asiaticoside on inducible nitric oxide synthase during gastric
ulcer healing in rats. Planta Med. 2004;70:1150–4.
27. Gupta R, Flora SJ. Effect of Centella asiatica on arsenic induced oxidative
stress and metal distribution in rats. J Appl Toxicol. 2006;26:213–22.
28. Gupta S, Prakash J. Studies on Indian green leafy vegetables for their
antioxidant activity. Plant Foods Hum Nutr. 2009;64:39–45.
29. Gupta YK, Veerendra Kumar MH, Srivastava AK. Effect of Centella
asiatica on pentylenetetrazole-induced kindling, cognition and oxidative
stress in rats. Pharmacol Biochem Behav. 2003;74:579–85.
30. Haleagrahara N, Ponnusamy K. Neuroprotective effect of Centella asiatica
extract (CAE) on experimentally induced Parkinsonism in aged Sprague-
Dawley rats. J Toxicol Sci. 2010;35:41–7.
31. Hashim P, Sidek H, Helan MH, et al. Triterpene composition and
bioactivities of Centella asiatica. Molecules. 2011;16:1310–22.
32. Hausen BM. Centella asiatica (Indian pennywort), an effective therapeutic
but a weak sensitizer. Contact Dermatitis. 1993;29:175–9.
Centella asiatica (L.) Urban 583

33. Hirschhorn HH. Constructing a phytotherapeutic concordance based upon

tropical American and Indonesian examples. J Ethnopharmacol. 1983;7:
157–67.
34. Huang SS, Chiu CS, Chen HJ, et al. Antinociceptive activities and the
mechanisms of anti-inflammation of asiatic acid in mice. Evid Based
Complement Alternat Med. 2011;2011:895857.
35. Hussin M, Hamid AA, Mohamad S, et al. Modulation of lipid metabolism
by Centella asiatica in oxidative stress rats. J Food Sci. 2009;74:H72–8.
36. James JT, Dubery IA. Pentacyclic triterpenoids from the medicinal herb,
Centella asiatica (L.) Urban. Molecules. 2009;14:3922–41.
37. Jana U, Sur TK, Maity LN, Debnath PK, Bhattacharyya D. A clinical study
on the management of generalized anxiety disorder with Centella asiatica.
Nepal Med Coll J. 2010;12:8–11.
38. Jayashree G, Kurup Muraleedhara G, Sudarslal S, Jacob VB. Antioxidant
activity of Centella asiatica on lymphoma-bearing mice. Fitoterapia. 2003;
74:431–4.
39. Jiang H, Zheng G, Lv J, et al. Identification of Centella asiatica’s effective
ingredients for inducing the neuronal differentiation. Evid Based Comple-
ment Alternat Med. 2016;2016:9634750.
40. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of
Centella asiatica. Rev Esp Enferm Dig. 2005;97:115–24.
41. Kadir MF, Bin Sayeed MS, Setu NI, Mostafa A, Mia MM. Ethnopharma-
cological survey of medicinal plants used by traditional health practitioners
in Thanchi, Bandarban Hill Tracts. Bangladesh. J Ethnopharmacol. 2014;
155:495–508.
42. Kaur I, Suthar N, Kaur J, Bansal Y, Bansal G. Accelerated stability studies
on dried extracts of Centella asiatica through chemical, HPLC, HPTLC,
and biological activity analyses. J Evid Based Complementary Altern Med.
2016;21:NP127–37.
43. Kimura Y, Sumiyoshi M, Samukawa K, Satake N, Sakanaka M. Facilitating
action of asiaticoside at low doses on burn wound repair and its mechanism.
Eur J Pharmacol. 2008;584:415–23.
44. Krishnamurthy RG, Senut MC, Zemke D, et al. Asiatic acid, a pentacyclic
triterpene from Centella asiatica, is neuroprotective in a mouse model of
focal cerebral ischemia. J Neurosci Res. 2009;87:2541–50.
45. Kumar A, Dogra S, Prakash A. Neuroprotective effects of Centella asiatica
against intracerebroventricular colchicine-induced cognitive impairment and
oxidative stress. Int J Alzheimers Dis 2009;2009.
46. Kumar A, Prakash A, Dogra S. Centella asiatica attenuates D-Galactose-
induced cognitive impairment, oxidative and mitochondrial dysfunction in
mice. Int J Alzheimers Dis. 2011;2011:347569.
47. Kumari S, Deori M, Elancheran R, Kotoky J, Devi R. In vitro and in vivo
antioxidant, antihyperlipidemic properties and chemical characterization of
Centella asiatica (L.) extract. Front Pharmacol. 2016;7:400.
584 Centella asiatica (L.) Urban

48. Liu M, Dai Y, Li Y, et al. Madecassoside isolated from Centella asiatica

herbs facilitates burn wound healing in mice. Planta Med. 2008;74:809–15.
49. Liu M, Dai Y, Yao X, et al. Antirheumatoid arthritic effect of madecassoside
on type II collagen-induced arthritis in mice. Int Immunopharmacol. 2008;8:
1561–6.
50. Lu L, Ying K, Wei S, et al. Asiaticoside induction for cell-cycle
progression, proliferation and collagen synthesis in human dermal fibrob-
lasts. Int J Dermatol. 2004;43:801–7.
51. Lu L, Ying K, Wei S, et al. Dermal fibroblast-associated gene induction by
asiaticoside shown in vitro by DNA microarray analysis. Br J Dermatol.
2004;151:571–8.
52. Luzzi R, Belcaro G, Ippolito E. Carotid plaque stabilization induced by the
supplement association Pycnogenol® and Centella asiatica (Centellicum®).
Minerva Cardioangiol. 2016;64:603–9.
53. Maquart FX, Chastang F, Simeon A, et al. Triterpenes from Centella
asiatica stimulate extracellular matrix accumulation in rat experimental
wounds. Eur J Dermatol. 1999;9:289–96.
54. Mato L, Wattanathorn J, Muchimapura S, et al. Centella asiatica improves
physical performance and health-related quality of life in healthy elderly
volunteer. Evid Based Complement Alternat Med. 2011;2011:579467.
55. Matsuda H, Morikawa T, Ueda H, Yoshikawa M. Medicinal foodstuffs.
XXVII. Saponin constituents of gotu kola (2): structures of new ursane- and
oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D,
from Centella asiatica cultivated in Sri Lanka. Chem Pharm Bull (Tokyo).
2001;49:1368–71.
56. Maulidiani, Abas F, Khatib A et al. Metabolic alteration in obese diabetes
rats upon treatment with Centella asiatica extract. J Ethnopharmacol. 2016;
180:60–9.
57. Meena H, Pandey HK, Pandey P, Arya MC, Ahmed Z. Evaluation of
antioxidant activity of two important memory enhancing medicinal plants
Baccopa monnieri and Centella asiatica. Indian J Pharmacol. 2012;44:114–7.
58. Mohandas Rao KG, Muddanna Rao S, Gurumadhva Rao S. Centella
asiatica (L.) leaf extract treatment during the growth spurt period enhances
hippocampal CA3 neuronal dendritic arborization in rats. Evid Based
Complement Alternat Med. 2006;3:349–57.
59. Mukherjee PK, Kumar V, Houghton PJ. Screening of Indian medicinal
plants for acetylcholinesterase inhibitory activity. Phytother Res. 2007;21:
1142–5.
60. Mukherjee S, Dugad S, Bhandare R, et al. Evaluation of comparative
free-radical quenching potential of Brahmi (Bacopa monnieri) and Man-
dookparni (Centella asiatica). Ayu. 2011;32:258–64.
61. Ong GH, Wong LS, Tan AL, Yap CK. Effects of metal-contaminated soils on
the accumulation of heavy metals in gotu kola (Centella asiatica) and the
potential health risks: a study in Peninsular Malaysia. Environ Monit Assess.
2016;188:40.
Centella asiatica (L.) Urban 585

62. Pan Y, Abd-Rashid BA, Ismail Z, et al. In vitro modulatory effects on three
major human cytochrome P450 enzymes by multiple active constituents and
extracts of Centella asiatica. J Ethnopharmacol. 2010;130:275–83.
63. Paocharoen V. The efficacy and side effects of oral Centella asiatica extract
for wound healing promotion in diabetic wound patients. J Med Assoc Thai.
2010;93 Suppl 7:S166–70.
64. Park JH, Choi JY, Son DJ et al. Anti-inflammatory effect of titrated extract
of Centella asiatica in phthalic anhydride-induced allergic dermatitis animal
model. Int J Mol Sci. 2017;18.
65. Pittella F, Dutra RC, Junior DD, Lopes MT, Barbosa NR. Antioxidant and
cytotoxic activities of Centella asiatica (L) Urb. Int J Mol Sci. 2009;10:
3713–21.
66. Pointel JP, Boccalon H, Cloarec M, Ledevehat C, Joubert M. Titrated
extract of Centella asiatica (TECA) in the treatment of venous insufficiency
of the lower limbs. Angiology. 1987;38:46–50.
67. Pragada RR, Veeravalli KK, Chowdary KP, Routhu KV. Cardioprotective
activity of Hydrocotyle asiatica L. in ischemia-reperfusion induced myocar-
dial infarction in rats. J Ethnopharmacol. 2004;93:105–8.
68. Prakash A, Kumar A. Mitoprotective effect of Centella asiatica against
aluminum-induced neurotoxicity in rats: possible relevance to its antioxidant
and antiapoptosis mechanism. Neurol Sci. 2013;34:1403–9.
69. Puttarak P, Dilokthornsakul P, Saokaew S et al. Effects of Centella asiatica
(L.) Urb. on cognitive function and mood related outcomes: a systematic
review and meta-analysis. Sci Rep. 2017;7:10646.
70. Rao MK, Rao MS, Rao GS. Treatment with Centalla asiatica (Linn) fresh
leaf extract enhances learning ability and memory retention power in rats.
Neurosciences (Riyadh). 2007;12:236–41.
71. Rao SB, Chetana M, Uma Devi P. Centella asiatica treatment during
postnatal period enhances learning and memory in mice. Physiol Behav.
2005;86:449–57.
72. Rumalla CS, Ali Z, Weerasooriya AD, Smillie TJ, Khan IA. Two new
triterpene glycosides from Centella asiatica. Planta Med. 2010;76:1018–21.
73. Sairam K, Rao CV, Goel RK. Effect of Centella asiatica Linn on physical
and chemical factors induced gastric ulceration and secretion in rats. Indian
J Exp Biol. 2001;39:137–42.
74. Sampson JH, Raman A, Karlsen G, Navsaria H, Leigh IM. In vitro
keratinocyte antiproliferant effect of Centella asiatica extract and triter-
penoid saponins. Phytomedicine. 2001;8:230–5.
75. Satake T, Kamiya K, An Y, Oishi Nee Taka T, Yamamoto J. The anti-
thrombotic active constituents from Centella asiatica. Biol Pharm Bull.
2007;30:935–40.
76. Shetty BS, Udupa SL, Udupa AL, Somayaji SN. Effect of Centella asiatica
L (Umbelliferae) on normal and dexamethasone-suppressed wound healing
in Wistar albino rats. Int J Low Extrem Wounds. 2006;5:137–43.
586 Centella asiatica (L.) Urban

77. Shinomol GK, Muralidhara. Effect of Centella asiatica leaf powder on

oxidative markers in brain regions of prepubertal mice in vivo and its in vitro
efficacy to ameliorate 3-NPA-induced oxidative stress in mitochondria.
Phytomedicine. 2008;15:971–84.
78. Shinomol GK, Muralidhara. Prophylactic neuroprotective property of
Centella asiatica against 3-nitropropionic acid induced oxidative stress and
mitochondrial dysfunctions in brain regions of prepubertal mice. Neurotox-
icology. 2008;29:948–57.
79. Shinomol GK, Muralidhara, Bharath MM. Exploring the role of “Brahmi”
(Bocopa monnieri and Centella asiatica) in brain function and therapy.
Recent Pat Endocr Metab Immune Drug Discov. 2011;5:33–49.
80. Shinomol GK, Muralidhara. Prophylaxis with Centella asiatica confers
protection to prepubertal mice against 3-nitropropionic-acid-induced oxida-
tive stress in brain. Phytother Res. 2010;24:885–92.
81. Shukla A, Rasik AM, Dhawan BN. Asiaticoside-induced elevation of
antioxidant levels in healing wounds. Phytother Res. 1999;13:50–4.
82. Shukla A, Rasik AM, Jain GK, et al. In vitro and in vivo wound healing
activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol.
1999;65:1–11.
83. Siddiqui BS, Aslam H, Ali ST, Khan S, Begum S. Chemical constituents of
Centella asiatica. J Asian Nat Prod Res. 2007;9:407–14.
84. Somboonwong J, Kankaisre M, Tantisira B, Tantisira MH. Wound healing
activities of different extracts of Centella asiatica in incision and burn
wound models: an experimental animal study. BMC Complement Altern
Med. 2012;12:103.
85. Soumyanath A, Zhong YP, Gold SA, et al. Centella asiatica accelerates
nerve regeneration upon oral administration and contains multiple active
fractions increasing neurite elongation in-vitro. J Pharm Pharmacol. 2005;
57:1221–9.
86. Soumyanath A, Zhong YP, Henson E, et al. Centella asiatica extract
improves behavioral deficits in a mouse model of Alzheimer’s disease:
investigation of a possible mechanism of action. Int J Alzheimers Dis. 2012;
2012:381974.
87. Subathra M, Shila S, Devi MA, Panneerselvam C. Emerging role of
Centella asiatica in improving age-related neurological antioxidant status.
Exp Gerontol. 2005;40:707–15.
88. Subban R, Veerakumar A, Manimaran R, Hashim KM, Balachandran I.
Two new flavonoids from Centella asiatica (Linn.). J Nat Med (Tokyo).
2008;62:369–73.
89. Suguna L, Sivakumar P, Chandrakasan G. Effects of Centella asiatica extract
on dermal wound healing in rats. Indian J Exp Biol. 1996;34:1208–11.
90. Sunilkumar, Parameshwaraiah S, Shivakumar HG. Evaluation of topical
formulations of aqueous extract of Centella asiatica on open wounds in rats.
Indian J Exp Biol. 1998;36:569–72.
Centella asiatica (L.) Urban 587

91. Tabassum R, Vaibhav K, Shrivastava P, et al. Centella asiatica attenuates

the neurobehavioral, neurochemical and histological changes in transient
focal middle cerebral artery occlusion rats. Neurol Sci. 2013;34:925–33.
92. Veerendra Kumar MH, Gupta YK. Effect of Centella asiatica on cognition
and oxidative stress in an intracerebroventricular streptozotocin model of
Alzheimer’s disease in rats. Clin Exp Pharmacol Physiol. 2003;30:336–42.
93. Veerendra Kumar MH, Gupta YK. Effect of different extracts of Centella
asiatica on cognition and markers of oxidative stress in rats. J Ethnophar-
macol. 2002;79:253–60.
94. Visweswari G, Prasad KS, Chetan PS, Lokanatha V, Rajendra W.
Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in
pentylenetetrazol-induced seizures with respect to cholinergic neurotrans-
mission. Epilepsy Behav. 2010;17:332–5.
95. Wattanathorn J, Mator L, Muchimapura S, et al. Positive modulation of
cognition and mood in the healthy elderly volunteer following the admin-
istration of Centella asiatica. J Ethnopharmacol. 2008;116:325–32.
96. Weng XX, Shao Y, Chen YY, et al. Two new dammarane monodesmosides
from Centella asiatica. J Asian Nat Prod Res. 2011;13:749–55.
97. Widgerow AD, Chait LA, Stals R, Stals PJ. New innovations in scar
management. Aesthetic Plast Surg. 2000;24:227–34.
98. Wijeweera P, Arnason JT, Koszycki D, Merali Z. Evaluation of anxiolytic
properties of Gotukola—(Centella asiatica) extracts and asiaticoside in rat
behavioral models. Phytomedicine. 2006;13:668–76.
99. Wojcikowski K, Wohlmuth H, Johnson DW, Rolfe M, Gobe G. An in vitro
investigation of herbs traditionally used for kidney and urinary system
disorders: potential therapeutic and toxic effects. Nephrology (Carlton).
2009;14:70–9.
100. Xu MF, Xiong YY, Liu JK, et al. Asiatic acid, a pentacyclic triterpene in
Centella asiatica, attenuates glutamate-induced cognitive deficits in mice
and apoptosis in SH-SY5Y cells. Acta Pharmacol Sin. 2012;33:578–87.
101. Yoosook C, Bunyapraphatsara N, Boonyakiat Y, Kantasuk C. Antiherpes
simplex virus activities of crude water extracts of Thai medicinal plants.
Phytomedicine. 2000;6:411–9.
102. Yoshida M, Fuchigami M, Nagao T et al. Antiproliferative constituents
from Umbelliferae plants VII. Active triterpenes and rosmarinic acid from
Centella asiatica. Biol Pharm Bull. 2005;28:173–5.
103. Yu QL, Duan HQ, Takaishi Y, Gao WY. A novel triterpene from Centella
asiatica. Molecules. 2006;11:661–5.
104. Yu QL, Gao WY, Zhang YW, Teng J, Duan HQ. Studies on chemical
constituents in herb of Centella asiatica. Zhongguo Zhong Yao Za Zhi.
2007;32:1182–4 (Chinese)
105. Yunianto I, Das S, Mat Noor M. Antispermatogenic and antifertility effect
of Pegaga (Centella asiatica L) on the testis of male Sprague-Dawley rats.
Clin Ter. 2010;161:235–9.
588 Centella asiatica (L.) Urban

106. Zaidan MR, Noor Rain A, Badrul AR, et al. In vitro screening of five local
medicinal plants for antibacterial activity using disc diffusion method. Trop
Biomed. 2005;22:165–70.
107. Zheng CJ, Qin LP. Chemical components of Centella asiatica and their
bioactivities. Zhong Xi Yi Jie He Xue Bao. 2007;5:348–51.
108. Zheng HM, Choi MJ, Kim JM, et al. Centella asiatica leaf extract protects
against indomethacin-induced gastric mucosal injury in rats. J Med Food.
2016;19:38–46.
109. Zheng HM, Choi MJ, Kim JM, et al. In vitro and in vivo anti-Helicobacter
pylori activities of Centella asiatica leaf extract. Prev Nutr Food Sci.
2016;21:197–201.
110. Zheng MS. An experimental study of the anti-HSV-II action of 500 herbal
drugs. J Tradit Chin Med. 1989;9:113–6.
Chamaecrista absus (L.) H.S. Irwin & Barneby
(Fabaceae/Leguminosae)

(Syns.: Cassia absus L.; C. coccinea Wall.; C. foliolis L.; Senna absus (L.) Roxb.;
S. quadrifolia Burm.)

Abstract
An annual flowering sparsely-branched, erect plant, generally found in North
and South America, tropical Africa, southern Asia, Australasia, India, Iran and
Arab countries. Greeks and Romans learnt about its seeds from Egyptians who
had been using them for years, and Dioscorides called them Akakalis. Seeds are
very bitter, aromatic, attenuant, astringent and mucilaginous, and strengthen
sight when used as collyrium. Ibn-al-Baitar described seeds from Sudan as being
the largest and the best. In Ayurveda, it is used in netraroga, arśa, hikkã, śvãsa,
śula, ãdhmãna, vrana, visphota and medoroga. Roots are used for stomach
troubles and pounded leaves are applied to syphilitic sores in East Africa.
A plaster made from seeds is recommended for wounds and sores, especially of
the penis. Seeds are rich in linoleic acid, followed by palmitic acids; whereas,
palmitic, stearic and arachidic acids are the major fatty acids in aerial parts.
Alkaloids, chaksine and isochaksine have been isolated from seeds; whereas,
chrysophanol, aloe-emodin, chaksine and isochaksine from roots, and quercetin,
rutin, chaksine and isochaksine from leaves have been isolated. Methanol seed
extract contains the highest amount of total phenolics and proanthocyanidins.
Seed extract has been suggested to exert centrally acting/ganglion blocking,
antinicotinic, nonspecific muscle relaxant and curare like effects.

Keywords



Benar Caksusyã Chaksu Chamada

Cheshmak
Chikut
Karunganam




Naguapate Pig’s senna Tashmizaj

Vernaculars: Urd.: Chaksu; Hin.: Banar, Chaksi, Chaksu, Chikut; San.: Āranyaku-
lattha, Caksusyã, Chakshu, Kulatthikã, Vanyakulattha; Ben.: Benar, Chaksi; Mal.:
Karinkilla, Karin-kolla; Mar.: Chamada, Chimar, Chime, Kankuti; Tam.: Avarai-
pattai, Edikkol, Karum, Karunganam, Karunkanam, Kattukkol, Mulaippalavirai,
Mulaippal-virai; Tel.: Chanupalavittulu, Chukuddi-pal; Ara.: Hab-es Sudan, Kushnu
© Springer Nature Switzerland AG 2020 589
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_62
590 Chamaecrista absus (L.) H.S. Irwin & Barneby

zunk, Tashmizaj; Eng.: Pig’s senna, Tropical sensitive pea,; Per.: Chashkhaam,
Chashum, Chastmigah, Cheshmak; Spa.: Naguapate.
Description: An annual flowering sparsely-branched, erect plant of pea family, up
to 1 m tall, generally found in North and South America, tropical Africa, southern
Asia, Australasia, India, Iran and Arab countries. Seeds generally used medicinally,
are triangular ovoid or oblong, black, polished, very shiny, length and breadth
nearly alike, 3–4 mm. The end where the hilum is situated is more pointed than the
other end; taste is bitter (Figs. 1, 2 and 3).XL
Actions and Uses: Greeks and Romans learnt about these seeds from Egyptians
who had been using them for years, and Dioscorides called them Akakalis.XL
Ibn-al-BaitarLXIX described seeds from Sudan as being the largest and the best.
Seeds very bitter, aromatic, attenuant, astringent and mucilaginousXXI,LXXXI;
strengthen sight when used as collyrium; they are prepared by enclosing in a little
dough and placed inside an onion, which is then baked. In prululent conjunctivitis,
a grain of the powdered seed, thus prepared, is introduced beneath the eyelids.XL
Seeds (temperament, hot 2° and dry 4°) are astringent, detergent, anti-inflammatory,
and beneficial for eyesight and eye diseases, such as conjunctivitis, ophthalmalgia,
and cataract. Twenty-one seeds are soaked in water overnight with sandal safed
(5 g) and the infusion is used for renal hematuria.L,LXXVII A plaster made from
seeds is recommended for wounds and sores, especially of the penis.CV In Ayur-
veda, it is used in netraroga, arśa, hikkã, śvãsa, śula, ãdhmãna, vrana, visphota
and medoroga.LX Roots are used for stomach troubles and pounded leaves are
applied to syphilitic sores in East Africa.LXXXV.

Fig. 1 Chamaecrista absus, Plant, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Chamaecrista_absus_W_IMG_3465.
jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Chamaecrista absus (L.) H.S. Irwin & Barneby 591

Fig. 2 Chamaecrista absus, Flower and Stem, J.M. Garg, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Chamaecrista_absus_W2_
IMG_3465.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Chamaecrista absus, Seeds, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://creativecommons.org/licenses/by/3.0/deed.en

Phytoconstituents: Methanol seed extract contains the highest amount of total

phenolics and proanthocyanidins, and seeds are rich in linoleic acid, followed by
palmitic acids; whereas, palmitic, stearic and arachidic acids are the major fatty
acids in aerial parts [9]. Alkaloids, chaksine and isochaksine have been isolated
592 Chamaecrista absus (L.) H.S. Irwin & Barneby

from seeds [5, 7]. Krishna Rao et al. [4] reported isolation of chrysophanol,
aloeemodin, chaksine and isochaksine from roots, and quercetin, rutin, chaksine
and isochaksine from leaves, and Patel et al. [6] isolated a protein from seeds with
trypsine inhibitory activity. Flavonoids have been reported in Cassia species,
including Cassia absus [8].
Pharmacology: A dose-dependent decrease in systemic arterial BP and HR of
anesthetized rats was produced by crude seed extract; pretreatment with atropine,
chlorpheniramine, ranitidine or propranolol did not modify the cardiovascular
effects. The extract was suggested to exert centrally acting/ganglion blocking, antini-
cotinic, nonspecific muscle relaxant and curare like effects [1]. Gupta and Chopra [3]
reported antibacterial properties of chaksine; whereas Ahmad et al. [2] reported
antihypertensive, antifertility, antifungal, anti-inflammatory, antihyperglycemic,
antiglycation, antibacterial, a-amylase inhibitory, and antioxidant activitities.
Human A/Es, Allergy and Toxicity: Not suitable for people of hot tempera-
mentLXXVII.
Animal Toxicity: Seeds are reportedly nontoxic up to a dose of 2,000 mg/kg [2].
Commentary: The plant and its seeds have not been clinically investigated, and
limited pharmacological studies warrant more studies.

References
1. Aftab K, Rahman A-U, Ahmed SI, Usmanghani K. Traditional medicine
Cassia absus L. (chaksu)-pharmacological evaluation. Phytomedicine. 1996;
2:213–9.
2. Ahmad S, Hassan A, Abbasi WM, Rehman T. Phytochemistry and pharma-
cological potential of Cassia absus—a review. J Pharm Pharmacol. 2018;70:
27–41.
3. Gupta KC, Chopra IC. A short note on antibacterial properties of chaksine:
an alkaloid from Cassia absus Linn. Indian J Med Res. 1953;41:459–60.
4. Krishna Rao RV, Seshagiri Rao JVLN, Vimaladevi M. Phytochemical
investigation of Cassia absus (Roots and Leaves). J Nat Prod. 1979;42:299–
300.
5. Lala SD, SenGupta I. Alkaloids from the seeds of Cassia absus. Res Bull
East Punjab Univ. 1952;21:95–8.
6. Patel GK, Gupta AK, Gupta A, et al. Purification and physicochemical
characterization of a trypsin inhibitor from Cassia absus Linn. Protein Pept
Lett. 2014;21:108–14.
7. Puri VN, Sharma VN, Siddiqui S. Studies in the alkaloids of Cassia absus
Linn. J Sci Ind Res. 1946;4:701.
8. Zhao Y, Zhao K, Jiang K, et al. A review of flavonoids from Cassia species
and their biological activity. Curr Pharm Biotechnol. 2016;17:1134–46.
9. Zribi I, Sbai H, Ghezal N, et al. Phytotoxic activity and chemical compo-
sition of Cassia absus seeds and aerial parts. Nat Prod Res. 2017;1–5
Chamaemelum nobile (L.) All.
(Asteraceae/Compositae)

(Syns.: Anthemis nobilis L.; A. odorata Lam.; Chamomilla nobilis (L.) Godr.;
Matricaria nobilis (L.) Baill.)

Abstract
An annual herb, found in waste places in north India, Persia, West Asia, Europe,
and Australia. Whole plant has a distinctive smell, reminiscent of over-ripe
apples. Chamomile has been mentioned by Hippocrates, Galen, and Asclepius,
and is widely recognized in Western culture for its medicinal usage. Dioscorides
effectively used it to treat periodic fevers. It is rubefacient, anti-inflammatory,
analgesic, deobstruent, brain and nerve tonic, aphrodisiac, diuretic, diaphoretic
and galactagogue, and rids body of adust humours. Warm infusion of flowers is
carminative, used as anthelminth in children, and is useful in hysteria and
dysmenorrhea. Its decoction is used as expectorant, emetic and in high fever and
jaundice, and as sitz-bath in amenorrhea, and to expel fetus and placenta. More
than one million cups of chamomile herbal tea are consumed every day in the
world; some people prefer it when it is sweetened with honey. For centuries,
country folks have relied on chamomile to cure children’s complaints, and to
treat many female disorders. This herb has its cosmetic uses too: as a face wash,
the standard infusion clarifies complexion, and as a rinse, lightens fair hair. In
southern Europe, chamomile tea is widely used recreationally; in a dying culture
of medicinal plants, it was still one of the most commonly used plants in
traditional medicine in the northwest of Basque Country (Biscay and Alava) of
Iberian Peninsula. It was also one of the most common traditionally used plants
for the treatment of neurological and mental disorders in Navarra, Spain. Flower
extract, flower oil, flower powder, and flower water are used as fragrance
ingredients, and skin-conditioning agents in cosmetic products, and were
declared safe by an Expert Panel in 2017. Sesquiterpene lactones, hydroper-
oxides, and polyphenolic compounds, the most important being the flavonoid

Both Anthemis nobilis and Matricaria chamomilla are used as Chamomile and share the same
vernacular names.

© Springer Nature Switzerland AG 2020 593

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_63
594 Chamaemelum nobile (L.) All.

glucoside, chamaemeloside, have been identified in the herb. Oral administration

of aqueous extract significantly reduced blood glucose of normal and diabetic
rats, without affecting basal plasma insulin levels.

Keywords
Anthémis noble

Appiolina Babunah
Edelkamille
Jalosauramo






Karpūrapuṣpa Kau-kiuh-hwa Macelão Roman chamomile Romerkamille

Vernaculars: Urd.: Babunah; Hin.: Babune-ke-phul; San.: Karpūrapuṣpa; Mal.:

Shima-jeventi-pushpam; Mar.: Babuna-cha-phula; Tam.: Chaman duppu, Shimai-
chamantippu, Shimaichamanti, Shimedapu; Tel.: Shima chamanti-pushapamu,
Simachamauli pushpamu; Ara.: Babunaj, Shajrat-el-kafur, Tuffah-ul-arz; Chi.:
果香菊, Kau-kiuh-hwa; Dan.: Romerkamille, Romersk kamille; Dut.: Dubbele
kamille, Maagbloempje, Roomse kamille; Eng.: Camomile, Camphor plant (due to
camphor-like odor of flowers), Garden dog-fennel, Noble chamomile, Roman
chamomile; Fin.: Jalosauramo, Roomalainen kamomilla; Fre.: Anthémis noble,
Camomille noble, Camomille romaine; Ger.: Edelkamille, Gartenkamille, Römis-
che kamille; Ita.: Antemide, Appiolina, Camomilla bastarda, Camomilla nobile,
Camomilla odorosa, Camomilla romana; Jap.: Kôyakamitsure, Rômakamitsure,
Rooman kamomiiru; Nor.: Kamille, Kamille romersk; Per.: Babunah; Pol.:
Rumian rzymski, Rumian szlachetny; Por.: Macela, Macelão, Macela-dourada,
Camomilla-verdadeira (Br.); Rus.: Pupavka blagorodnaia, Rimskaja romaška; Spa.:
Camomilla noble, Camomilla de Paris, Manzanilla romana; Swe.: Kamillkulla,
Romersk kamomill; Vie.: Cây cúc cam.
Description: An annual herb, found in many waste places, is a very familiar weed
having daisy-like flowers and feathery grey-green leaves. Whole plant has a dis-
tinctive smell, reminiscent of over-ripe apples. Flowers are yellow in center and
white petals, with strongly aromatic and bitter in taste. Its distribution includes
North India, Persia, West Asia, Europe, and Australia. It is believed to be named
Babunah after the village of Bábunah in Irák-arabi, where it is particularly abun-
dant. However, this description is mentioned about Matricaria chamomilla as
Babunah (Figs. 1 and 2).XL
Actions and Uses: Chamomile has been mentioned by Hippocrates, Galen, and
Asclepius, and is widely recognized in Western culture for its medicinal usage [1].
Dioscorides effectively used it to treat periodic fevers. It is rubefacient, anti-
inflammatory, analgesic, deobstruent, brain and nerve tonic, aphrodisiac, diuretic,
diaphoretic and galactagogue, and rids body of adust humours.L Ibn Jazlah employed
it for epilepsy and Ibn-al-Baitar mentioned it for washing eyes, and soothing mus-
cle.LIII Warm infusion of flowers is carminative, used as anthelminth in children, and
is useful in hysteria and dysmenorrhea. Volatile oil is antispasmodic, and lowers
reflex excitability, and is used in nervous diseases of women.CV In Unani medicine it
(temperament, hot 1° and dry 1°) is considered stomachic, carminative, diuretic,
anti-inflammatory, emmenagogue, antipyretic, and nerve tonic. Its decoction is used
Chamaemelum nobile (L.) All. 595

Fig. 1 Chamaemelum nobile, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Chamaemelum_nobile_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-012.jpg

Fig. 2 Chamaemelum nobile, Chamomile as sold in U.S. Health Food Stores, Prof. Akbar,
Original
596 Chamaemelum nobile (L.) All.

as expectorant, emetic and in high fever and jaundice, and as sitz-bath in amenorrhea,
and to expel fetus and placenta.LXXVII It is commonly used for hay fever, inflam-
mation, muscle spasms, menstrual disorders, insomnia, gastrointestinal disorders,
ulcers, wounds, rheumatic pain, and hemorrhoids. More than one million cups of
chamomile herbal tea are consumed every day in the world [22]. In Palestine,
University students use chamomile tea primarily for treatment of headache, anxiety,
flu, menstrual pain, and sore-throat [19]. In Moroccan traditional medicine, the plant
is used for treatment of diabetes mellitus [6], and the EO of Roman chamomile is used
as aromatherapy agent to relieve anxiety, stress, and depression [20]. An infusion of
the leaves and flowers, fresh or dried, dissolves tumors, heals ulcers, expels worms,
banishes tiredness, and generally revive the system. For centuries, country folks have
relied on chamomile to cure children’s complaints, and to treat many female dis-
orders. This herb has its cosmetic uses too: as a face wash, the standard infusion
clarifies complexion, and as a rinse, lightens fair hair. Chamomile tea is tonic,
digestive and tranquillizing; some people prefer it when it is sweetened with
honey.XXVI In southern Europe, chamomile tea is widely used recreationally [21]; in a
dying culture of medicinal plants, it was still one of the most commonly used plants in
traditional medicine in the northwest of Basque Country (Biscay and Alava) of
Iberian Peninsula [14]. It was also one of the most common traditionally used plants
for the treatment of neurological and mental disorders in Navarra, Spain [2]. Flower
extract, flower oil, flower powder, and flower water are used as fragrance ingredients,
and skin-conditioning agents in cosmetic products, and were declared safe by an
Expert Panel in 2017 [10].
Phytoconstituents: Sesquiterpene lactones [7], hydroperoxides [18], and poly-
phenolic compounds, the most important being the flavonoid glucoside, chamae-
meloside [3], have been identified in the herb. Flavone extract from Roman chamo-
mile (Chamaemelum nobile) grown in China showed eight yellowish antioxidant
spots on TLC; whereas flavones extract of Matricaria chamomile showed seven
spots, both including apigenin and apigenin-7-glucoside. However, antioxidant
activity of EO from M. chamomile was stronger than EO from Roman chamomile [9].
Six octulosonic acid derivatives, that decreased cellular oxidative stress by inhibiting
ROS generation, were isolated from flower-heads of C. nobile grown in China [26].
From the dichloromethane extract of flower-heads grown in Switzerland, 19
sesquiterpene lactones, including 15 germacranolides, two secosesquiterpenes, one
guaianolide sesquiterpene lactone, and one cadinane acid were isolated [4]. Roman
chamomile decoction and infusion from Portugal were found rich in carbohydrates
and proteins, tocopherols, carotenoids and essential fatty acids; the infusion was a
good source of phenolic compounds (flavonoids: flavonols and flavones, phenolic
acids and derivatives) and organic acids (oxalic, quinic, malic, citric and fumaric
acids), with antioxidant and antitumor activities, without hepatotoxicity. 5-O-
caffeoylquinic acid and an apigenin derivative were most abundant compounds in the
plant extract and infusion [8].
Chamaemelum nobile (L.) All. 597

Pharmacology: Both single-dose oral administration of aqueous extract and

treatment for 15 consecutive days of normal and STZ-diabetic rats, significantly
reduced blood glucose without affecting basal plasma insulin levels [6]. Chamae-
meloside has shown in vivo hypoglycemic activity [12]. Aqueous extract produced
in vitro vasorelaxation [24], and significantly reduced SBP in SHR, 24 h after a
single dose. Daily oral administration of the extract for 3-weeks produced a sig-
nificant reduction in SBP and produced significant increase in urinary output and
electrolytes excretion [25]. Essential oil showed antiplatelet activity against ADP-, AA-
and the TXA2 agonist-induced platelet aggregation [23], and was active against
C. albicans, while the ethanol extract was devoid of this activity [5]. Two varieties of
A. nobilis, named “white-headed” or double-flowered and “yellow-headed” show
considerable morphological differences and the composition of their essential oils
vary. Essential oils derived from “white-headed” variety produced anti-inflammatory
and sedative effects [17]. Ointment (5%) of ethanol lyophilized extract in eucerin
effectively accelerated healing of P. aeruginosa-infected wounds in rats, better than
tetracycline ointment [11]. Dichloromethane flower extract showed promising in vitro
antiprotozoal activity against T. brucei rhodesiense and L. donovani [4].
Clinical Studies: All clinical studies on Chamomile have been reported under
Matricaria chamomilla (German chamomile) and none under Anthemis nobilis/
Chamaemelum nobile.
Human A/Es, Allergy and Toxicity: Sesquiterpene lactones are the most
important allergens and may cause sensitization [16]. Idiosyncratic allergic reac-
tions to EO have been reported [13]. A retrospective study of usage of chamomile
tea by pregnant women during last two trimesters of pregnancy, did not show any
risk of low birth weight of the newborn [15].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Despite a shared similarity in therapeutic profile of this plant with
Matricaria chamomilla (German chamomile) clinical studies on this plant must be
delineated, and separately established.

References
1. Anonymous. Matricaria chamomilla (German chamomile)—monograph.
Altern Med Rev. 2008;13:58–62.
2. Calvo MI, Cavero RY. Medicinal plants used for neurological and mental
disorders in Navarra and their validation from official sources. J Ethnophar-
macol. 2015;169:263–8.
3. Carnat A, Carnat AP, Fraisse D, et al. The aromatic and polyphenolic com-
position of Roman camomile tea. Fitoterapia. 2004;75:32–8.
598 Chamaemelum nobile (L.) All.

4. De Mieri M, Monteleone G, Ismajili I, Kaiser M, Hamburger M. Antipro-

tozoal activity-based profiling of a dichloromethane extract from Anthemis
nobilis flowers. J Nat Prod. 2017;80:459–70.
5. Duarte MC, Figueira GM, Sartoratto A, et al. Anti-Candida activity of
Brazilian medicinal plants. J Ethnopharmacol. 2005;97:305–11.
6. Eddouks M, Lemhadri A, Zeggwagh NA, Michel JB. Potent hypoglycaemic
activity of the aqueous extract of Chamaemelum nobile in normal and
streptozotocin-induced diabetic rats. Diabetes Res Clin Pract. 2005;67:
189–95.
7. Grabarczyk H, Drozdz B, Hladoń B, Wojciechowska J. Sesquiterpene
lactones. Part XV. New cytostatic active sesquiterpene lactone from herb of
Anthemis nobilis L. Pol J Pharmacol Pharm. 1977;29:419–23.
8. Guimarães R, Barros L, Dueñas M, et al. Nutrients, phytochemicals and
bioactivity of wild Roman chamomile: a comparison between the herb and
its preparations. Food Chem. 2013;136:718–25.
9. Han SL Li XX, Mian QH, Lan W, Liu Y. Comparison of antioxidant
activity between two species of chamomiles produced in Xinjiang by TLC-
bioautography. Zhongguo Zhong Yao Za Zhi 2013;38:193–8 (Chinese).
10. Johnson W Jr, Heldreth B, Bergfeld WF, et al. Safety assessment of Anthemis
nobilis-derived ingredients as used in cosmetics. Int J Toxicol. 2017;36
(1 suppl):57S–66S.
11. Kazemian H, Ghafourian S, Sadeghifard N, et al. In vivo antibacterial and
wound healing activities of Roman chamomile (Chamaemelum nobile).
Infect Disord Drug Targets. 2018;18:41–5.
12. König GM, Wright AD, Keller WJ, et al. Hypoglycaemic activity of an
HMG-containing flavonoid glucoside, chamaemeloside, from Chamaemelum
nobile. Planta Med. 1998;64:612–4.
13. Maddocks-Jennings W. Critical incident: idiosyncratic allergic reactions to
essential oils. Complement Ther Nurs Midwifery. 2004;10:58–60.
14. Menendez-Baceta G, Aceituno-Mata L, Molina M, et al. Medicinal plants
traditionally used in the northwest of the Basque Country (Biscay and
Alava), Iberian Peninsula. J Ethnopharmacol. 2014;152:113–34.
15. Moussally K, Berard A. Exposure to specific herbal products during
pregnancy and the risk of low birth weight. Altern Ther Health Med. 2012;
18:36–43.
16. Paulsen E. Contact sensitization from Compositae-containing herbal
remedies and cosmetics. Contact Dermatitis. 2002;47:189–98.
17. Rossi T, Melegari M, Bianchi A, et al. Sedative, anti-inflammatory and
antidiuretic effects induced in rats by essential oils of varieties of Anthemis
nobilis: a comparative study. Pharmacol Res Commun. 1988;20 Suppl 5:
71–4.
18. Rücker G, Mayer R, Lee KR. Peroxides as plant constituents. 6. Hydroper-
oxides from the blossoms of Roman camomile, Anthemis nobilis L. Arch
Pharm (Weinheim). 1989;322:821–6 (German).
Chamaemelum nobile (L.) All. 599

19. Sawalha AF, Sweileh WM, Zyoud SH, Jabi SW. Self-therapy practices
among university students in Palestine: focus on herbal remedies. Comple-
ment Ther Med. 2008;16:343–9.
20. Setzer WN. Essential oils and anxiolytic aromatherapy. Nat Prod Commun.
2009;4:1305–16.
21. Sõukand R, Quave CL, Pieroni A, et al. Plants used for making recreational
tea in Europe: a review based on specific research sites. J Ethnobiol
Ethnomed. 2013;9:58.
22. Srivastava JK, Shankar E, Gupta S. Chamomile: a herbal medicine of the
past with bright future. Mol Med Rep. 2010;3:895–901.
23. Tognolini M, Barocelli E, Ballabeni V, et al. Comparative screening of plant
essential oils: phenylpropanoid moiety as basic core for antiplatelet activity.
Life Sci. 2006;78:1419–32.
24. Zeggwagh NA, Michel JB, Eddouks M. Vascular effects of aqueous extract
of Chamaemelum nobile: in vitro pharmacological studies in rats. Clin Exp
Hypertens. 2013;35:200–6.
25. Zeggwagh NA, Moufid A, Michel JB, Eddouks M. Hypotensive effect of
Chamaemelum nobile aqueous extract in spontaneously hypertensive rats.
Clin Exp Hypertens. 2009;31:440–50.
26. Zhao J, Khan SI, Wang M, et al. Octulosonic acid derivatives from Roman
chamomile (Chamaemelum nobile) with activities against inflammation and
metabolic disorder. J Nat Prod. 2014;77:509–15.
Cheilocostus speciosus (J. König) C.D. Specht
(Costaceae)

(Syns.: C. vaginalis Salisb.; Costus speciosus (Retz.) Smith; Banksea speciosa J. König)

Abstract
It is native to India, China, Indonesia, and Australia, and naturalized in
Mauritius, Fiji, Hawaii, Costa Rica, Belize, and the West Indies. In Unani
medicine, four types of Qust have been described. One is yellowish-white in
color, lighter, sweet and aromatic, called Qust Bahri or Qust Arabi, and mostly
used therapeutically. Second type is thicker, and strongly aromatic, called Qust
Suri, because it is found in Syria; the third type is darker outside and yellowish
inside and lighter in weight, lesser aromatic, and called Qust Hindi, and the
fourth type is reddish, heavy and aromatic, and is not used medicinally due to
being poisonous. Therapeutically, the first type is used to treat asthma, cough,
paralysis, tetanus, tremors, arthritis, gout, sciatica, and as analgesic. The second
type is mainly used externally as paste for paralysis, palsy, tetanus, tremors,
arthritis, gout, sciatica and pleurisy. In Ayurveda, it is used to subdue vata and
kapha, to treat cough and other respiratory disorders, to improve complexion,
and to cure dyspepsia. It is one of the four plants commonly used as leaf
decoction as alternative and complementary treatment of diabetes in southeast
Puerto Rico, and is referred to by locals as ‘insulin.’ In the Philippines, the stem
juice is used in dysentery, and in Malaya, juice of fresh rhizome is considered
purgative, and in Java, rhizomes are used for treatment of syphilis and the stem
juice for dysentery. Rhizomes contain alkaloids, flavonoids, cardiac glycosides,
saponins, sterols, tannins, EO, coumarin, phenols, and anthraquinones. Freeze-
dried juice administered simultaneously with glucose to nondiabetic rats had no
significant effect on fasting or postprandial glucose levels; however, the juice
administered 30-min before glucose load, produced hypoglycemic effect.
Ethanol root extract normalized diabetic changes, significantly decreased blood
glucose, plasma total lipid, TC and TGs levels, increased glycogenesis and
improved hepatic antioxidant enzyme activities. Nasal drops of lyophilized
aqueous extract of rhizomes relieved symptoms within 24 h in nine out of 15
adult and pediatric patients suffering from acute pharyngitis and tonsillitis.

© Springer Nature Switzerland AG 2020 601

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_64
602 Cheilocostus speciosus (J. König) C.D. Specht

Keywords



Bramhatirtha Crepe ginger Kemuk Koshta

Kostus
Koth
Practige




kostwur Qust White costus Zhang liu tou

Vernaculars: Urd.: Koth, Qust; Hin.: Kebu, Kemuk, Kemuaa, Kenaa, Keu, Kust;
San.: Bramhatirtha, Kashmeera, Kebuka, Kembuka, Kemu, Kemuka, Kevuka,
Pushkara, Pushkarmula, Shivasari, Subandhu; Ben.: Keu, Kevu, Kura, Kust; Mal.:
Anakkuva, Anappu, Canna, Cannakkilannu, Channakkilannu, Channakkuvva,
Narunchana, Onapoovu, Patimukam; Mar.: Naagaali, Penva, Pevaa, Pushkaramoola,
Pushkarmula; Tam.: Catikostam, Cikarappati, Koeshtam, Kostam, Koshtam,
Kottam, Kuruvam; Tel.: Bhangalkoshta, Bogakhikadumpalu, Bommakachika,
Cengalva, Changalvakoshtu, Chenglavaa-koshtu, Kashmeeramu, Kostamu, Kostu;
Chi.: 水蕉花, Zhang liu tou; Eng.: Cane-reed, Costus elegant, Crepe ginger, Malay
ginger, Spiral ginger, White costus, Wild ginger; Fre.: Fleur de mai; Ger.: Practige
kostwur; Gre.: Kostus; Per.: Koshta; Tag.: Setawar, Tabubungiau; Vie.: Cây cu chóc.
Description: It is native to India, China, Indonesia, and Australia, and naturalized
in Mauritius, Fiji, Hawaii, Costa Rica, Belize, and the West Indies; found in
roadside ditches and low lying areas in the forest. Flowering season in India starts
after rainy season, October to December. The rhizome resembles great galangal in
growth and structure, but has no aromatic properties, the taste being mucilaginous
and feebly astringent (Figs. 1, 2 and 3).XL
Actions and Uses: In Unani medicine, four types of Qust have been described.
One is yellowish-white in color, lighter, sweet and aromatic, called Qust Bahri or
Qust Arabi, and mostly used therapeutically. Second type is thicker, and strongly
aromatic, called Qust Suri, because it is found in Syria; the third type is darker

Fig. 1 Cheilocostus speciosus, Plants in Guadeloupe, Jayen466, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Costus_speciosus_Guadeloupe.JPG
Cheilocostus speciosus (J. König) C.D. Specht 603

Fig. 2 Cheilocostus speciosus, Flowers and Leaves in Costa Rica, Hans Hillewaert, Wikime-
diaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/
File:Cheilocostus_speciosus.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Cheilocostus speciosus, Flowers, Vengolis, WikimediaCommons, https://commons.wiki

media.org/wiki/File:Cheilocostus_speciosus_9191.jpg
604 Cheilocostus speciosus (J. König) C.D. Specht

outside and yellowish inside and lighter in weight, lesser aromatic, and called
Qust Hindi, and the fourth type is reddish, heavy and aromatic, and is not used
medicinally due to being poisonous.L Externally, Qust (temperament, hot 3° and
dry 3°) is astringent, coagulant, and anti-inflammatory; internally, it is nerve tonic,
expectorant, carminative, anthelmintic, diuretic, aphrodisiac, and emmenagogue;
relieves uterine pain and provides energy to vital organs. Therapeutically, the first
type is used to treat asthma, cough, paralysis, tetanus, tremors, arthritis, gout,
sciatica, and as analgesic. The second type is mainly used externally as paste
for paralysis, palsy, tetanus, tremors, arthritis, gout, sciatica and pleurisy.LXXVII
In India, rhizomes have been used as famine food, bitter, stimulant, purgative, and
in the treatment of catarrhal fever, coughs, dyspepsia, worms, skin diseases,CV and
for snake bite.XXI In Ayurveda, it is used to subdue vata and kapha, to treat cough
and other respiratory disorders, to improve complexion, and to cure dyspepsia [26].
Dried rhizomes are prescribed in the treatment of kaphapittaja vikara, agnimandya,
grahani, krmiroga, raktavikara, prameha, svitra, kustha, jvara, kasa, kamala, arsa,
kaphaja, and mutrakrcchra;LVIII and rhizome extract to treat pneumonia, rheuma-
tism, and diabetes, and rhizomes and leaves extracts in the treatment regimens of
malignancies and mental illnesses [20]. It is one of the four plants commonly used as
leaf decoction as alternative and complementary treatment of diabetes in southeast
Puerto Rico, and is referred to by locals as ‘insulin’ [12]. In the Philippines, the stem
juice is used in dysentery,CXVII and in Malaya, juice of fresh rhizome is considered
purgative, and in Java, rhizomes are used for treatment of syphilis and the stem
juice for dysentery.XVI In Jamaica, the root was used as a substitute for ginger, but
considered very inferior to it.XL
Phytoconstituents: Alkaloids, flavonoids, cardiac glycosides, saponins, sterols,
tannins, EO, coumarin, phenols, and anthraquinones are present in rhizomes [8, 28].
Methanol leaves extract also showed the presence of alkaloids, phenolics, saponins,
sterols, cardiac glycosides, tannins, and terpenoids; the aqueous extract lacked
the presence of alkaloids, tannins, terpenoids, and cardiac glycosides, but showed
the presence of flavonoids [12]. Diosgenin and glucono-1,5-lactone, a typical
b-glucosidase inhibitor [14], 5a-stigmasten-3b-ol, sitosterol-b-D-glucoside, dioscin,
prosapogenins A and B of dioscin, gracillin and quinines [17], tetradecyl 13-
methylpentadecanoate, tetradecyl 11-methyltridecanoate, 14-oxotricosanoic acid,
14-oxoheptacosanoic acid and 15-oxooctacosanoic acid [16], diosgenone, cycloar-
tanol, 25-en-cycloartenol and octacosanoic acid [25], 22-ketocholesteryl palmi-
tate, 24-methylenecycloartanol, stigmasterol and linoleic acid [15], 22,23-
dihydrospinasterone, dehydrodihydrocostus lactone, specioic acid (mokko lac-
tone), dehydrocostus lactone, arbusculin A, santamarine (douglanin), and reynosin
[1], gracillin and zingibernsis newsaponin [35], and costunolide and eremanthin [9,
10] have been isolated from rhizomes. Diosgenin, the steroidal sapogenin, serves as a
precursor for the synthesis of steroidal drugs, such as corticosteroids, sex hormones,
oral contraceptives, and anabolic agents [13]. Diosgenin content vary in different
parts of the same rhizome, being highest in the nodal region and least in the tip [29];
its seeds are also a good source of diosgenin [32]. Seed oil mainly contains palmitic
Cheilocostus speciosus (J. König) C.D. Specht 605

acid (55.97%), oleic acid (23.75%), linoleic, stearic, myristic and lauric acids [27].
From leaves, a-amyrinsterate, b-amyrin and lupeolpalmitates were reported [23].
Pharmacology: When freeze-dried juice was administered simultaneously with
glucose to nondiabetic rats, it had no significant effect on fasting or postprandial
glucose levels. However, if the juice was given 30-min before glucose load, hypo-
glycemic effect was observed [19]. Ethanol root extract normalized alloxan-induced
diabetic changes, significantly decreased blood glucose, plasma total lipid, TC and
TGs levels, increased glycogenesis and improved hepatic antioxidant enzyme
activities [4], increased serum insulin levels, glucokinase, aldolase, pyruvate kinase,
succinate dehydrogenase, and glycogen synthase activities [2]. Methanol leaves
extract potently inhibited a-glucosidase with lower IC50 value than acarbose [24].
Costunolide and eremanthin, the sesquiterpenoids, also significantly reduced
plasma glucose, HbA1c, serum TC, TGs, LDL-C, and increased plasma insulin,
tissue glycogen, HDL-C and serum protein [9, 10], and significantly increased
activities of antioxidant enzymes of diabetic rats [11]. Benzene extract showed
maximum phenolic content and antioxidant activity compared to other extracts [21];
methanol leaf extract also exhibited significant antioxidant activity [22].
Aqueous and ethanol extracts possess significant analgesic activity [5]; the latter
also anti-inflammatory and antipyretic activities [6]. Methanol extract of aerial parts
also showed significant anti-inflammatory [34], analgesic and antipyretic effects [33].
Methanol leaf extract significantly reduces cell viability of HepG2 cells, perturbes
cell cycle progression and induces apoptosis [20]. Diosgenin exhibited in vitro
anti-inflammatory, antioxidant and antiangiogenic activities [31], and cytotoxicity
to HepG2 and MCF-7 cells [30]. Aqueous rhizome extract inhibited growth of
S. aureus, but was inactive against K. pneumoniae, E. coli and P. aeruginosa [28],
whereas, methanol extracts of stem and flower inhibited M. tuberculosis [18]. Cos-
tunolide and eremanthin exhibited antifungal activity; costunolide being significantly
more potent against T. mentagrophytes, T. simii, T. rubrum, E. floccosum, Scopu-
lariopsis sp, A. niger, C. lunata, and M. grisea [7].
Clinical Studies: Nasal drops of lyophilized aqueous extract of rhizomes relieved
symptoms within 24 hours in nine out of 15 adult and pediatric patients suffering
from acute pharyngitis and tonsillitis [3].
Mechanism of Action: Upregulation of cellular apoptotic molecules, caspases,
ROS generation and downregulation of antiapoptotic agents are suggested mech-
anisms for its anticancer activity [8]. Insulinomimetic, increased activities of car-
bohydrate metabolism [2], increased glycogenesis and antioxidant activity [4] and
inhibition of a-glucosidase [24] may contribute to its antidiabetic effect.
Human A/Es, Allergy and Toxicity: It is considered harmful for urinary bladder
and in the presence of pulmonay diseases.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
606 Cheilocostus speciosus (J. König) C.D. Specht

Commentary: Other than a small study on acute pharyngitis and tonsillitis patients,
there are no clinical studies published in mainstream journals. Its antidiabetic and
hypolipidemic effects in pharmacological studies need further clinical investigations.

References
1. Al-Attas AA, El-Shaer NS, Mohamed GA, Ibrahim SR, Esmat A. Anti-
inflammatory sesquiterpenes from Costus speciosus rhizomes. J Ethnophar-
macol. 2015;176:365–74.
2. Ali HA, Almaghrabi OA, Afifi ME. Molecular mechanisms of antihyper-
glycemic effects of Costus speciosus extract in streptozotocin-induced
diabetic rats. Saudi Med J. 2014;35:1501–6.
3. Bakhsh ZA, Al-Khatib TA, Al-Muhayawi SM, et al. Evaluating the
therapeutic efficacy, tolerability, and safety of an aqueous extract of Costus
speciosus rhizome in acute pharyngitis and acute tonsillitis. A pilot study.
Saudi Med J. 2015;36:997–1000.
4. Bavarva JH, Narasimhacharya AV. Antihyperglycemic and hypolipidemic
effects of Costus speciosus in alloxan induced diabetic rats. Phytother Res.
2008;22:620–6.
5. Bhattacharya S, Nagaich U. Assessment of antinociceptive efficacy of Costus
speciosus rhizome in swiss albino mice. J Adv Pharm Technol Res. 2010;1:
34–40.
6. Binny K, Kumar SG, Dennis T. Anti-inflammatory and antipyretic properties
of the rhizome of Costus speciosus (Koen.) Sm. J Basic Clin Pharm. 2010;1:
177–81.
7. Duraipandiyan V, Al-Harbi NA, Ignacimuthu S, Muthukumar C. Antimi-
crobial activity of sesquiterpene lactones isolated from traditional medicinal
plant, Costus speciosus (Koen ex. Retz.) Sm. BMC Complement Altern
Med. 2012;12:13.
8. El-Far AH, Badria FA, Shaheen HM. Possible anticancer mechanisms of
some Costus speciosus active ingredients concerning drug discovery. Curr
Drug Discov Technol. 2016;13:123–43.
9. Eliza J, Daisy P, Ignacimuthu S, Duraipandiyan V. Antidiabetic and
antilipidemic effect of eremanthin from Costus speciosus (Koen.) Sm., in
STZ-induced diabetic rats. Chem Biol Interact. 2009;182:67–72.
10. Eliza J, Daisy P, Ignacimuthu S, Duraipandiyan V. Normoglycemic and
hypolipidemic effect of costunolide isolated from Costus speciosus (Koen
ex. Retz.) Sm. in streptozotocin-induced diabetic rats. Chem Biol Interact.
2009;179:329–34.
11. Eliza J, Daisy P, Ignacimuthu S. Antioxidant activity of costunolide and
eremanthin isolated from Costus speciosus (Koen ex. Retz) Sm. Chem Biol
Interact. 2010;188:467–72.
Cheilocostus speciosus (J. König) C.D. Specht 607

12. Gavillán-Suárez J, Aguilar-Perez A, Rivera-Ortiz N, et al. Chemical profile

and in vivo hypoglycemic effects of Syzygium jambos, Costus speciosus and
Tapeinochilos ananassae plant extracts used as diabetes adjuvants in Puerto
Rico. BMC Complement Altern Med. 2015;15:244.
13. Gupta MM, Farooqui SU, Lal RN. Distribution and variation of diosgenin in
different parts of Costus speciosus. J Nat Prod. 1981;44:486–9.
14. Inoue K, Ebizuka Y. Purification and characterization of furostanol glycoside
26-O-beta-glucosidase from Costus speciosus rhizomes. FEBS Lett. 1996;
378:157–60.
15. Kumar A, Chand G, Agnihotri VK. A new oxosterol derivative from the
rhizomes of Costus speciosus. Nat Prod Res. 2018;32:18–22.
16. Madan Gupta M, Ram Lal N, Yogendra Shukla N. 5a-stigmast-9(11)-en-
3b-ol, a sterol from Costus speciosus roots. Phytochemisry. 1981;20:2257–9.
17. Mahato SB, Sahu NP, Ganguly AN. Carbon-13 NMR spectra of dioscin and
gracillin isolated from Costus speciosus. Indian J Chem. 1980;19B:817–9.
18. Mohamad S, Zin NM, Wahab HA, et al. Antituberculosis potential of some
ethnobotanically selected Malaysian plants. J Ethnopharmacol. 2011;133:
1021–6.
19. Mosihuzzaman M, Nahar N, Ali L, et al. Hypoglycemic effects of three
plants from eastern Himalayan belt. Diabetes Res. 1994;26:127–38.
20. Nair SV, Hettihewa M, Rupasinghe HP. Apoptotic and inhibitory effects on
cell proliferation of hepatocellular carcinoma HepG2 cells by methanol leaf
extract of Costus speciosus. Biomed Res Int. 2014;2014:637098.
21. Nehete J, Bhatia M, Narkhede M. In-vitro evaluation of antioxidant activity
and phenolic content of Costus speciosus (Koen) J.E. Sm. Iran J Pharm Res.
2010;9:271–7.
22. Pai Kotebagilu N, Reddy Palvai V, Urooj A. Protective effect of selected
medicinal plants against hydrogen peroxide induced oxidative damage on
biological substrates. Int J Med Chem. 2014;2014:861084.
23. Pai PP, Kulkarni GH. Isolation of a-amyrinsterate, b-amyrin and lupeol-
palmitates from the Costus leaves. Curr Sci. 1997;46:261–2.
24. Perera HK, Premadasa WK, Poongunran J. a-glucosidase and glycation
inhibitory effects of Costus speciosus leaves. BMC Complement Altern Med.
2016;16:2.
25. Qiao CF, Li QW, Dong H, Xu LS, Wang ZT. Studies on chemical con-
stituents of two plants from Costus. Zhongguo Zhong Yao Za Zhi. 2002;27:
123–5 (Article in Chinese).
26. Rani AS, Sulakshana G, Patnaik S. Costus speciosus, an antidiabetic plant—
review. FS J Pharm Res. 2012;1:52–3.
27. Rastogi RP, Mehrotra BN. Compendium of Indian Medicinal Plants, vol. 3.
New Delhi: CDRI, Lucknow and Institute of Science Communication;
1999, p. 215.
28. Saraf A. Phytochemical and antimicrobial studies of medicinal plant Costus
speciosus (Koen.). E-J Chem. 2010;7(S1):S405–13.
608 Cheilocostus speciosus (J. König) C.D. Specht

29. Sarin YK, Kapahi BK, Kapur SK, Atal CK. Studies on Costus speciosus
Sims. Part I. Variability in diosgenin content. Curr Sci. 1976;45:688–90.
30. Selim S, Al Jaouni S. Anticancer and apoptotic effects on cell proliferation
of diosgenin isolated from Costus speciosus (Koen.) Sm. BMC Complement
Altern Med. 2015;15:301.
31. Selim S, Al Jaouni S. Anti-inflammatory, antioxidant and antiangiogenic
activities of diosgenin isolated from traditional medicinal plant, Costus
speciosus (Koen ex.Retz.) Sm. Nat Prod Res. 2016;30:1830–3.
32. Singh SB, Thakur RS. Saponins from the seeds of Costus speciosus. J Nat
Prod. 1982;45:667–71.
33. Srivastava S, Singh P, Jha KK, et al. Anti-inflammatory, analgesic and
antipyretic activities of aerial parts of Costus speciosus Koen. Indian J
Pharm Sci. 2013;75:83–8.
34. Srivastava S, Singh P, Jha KK, et al. Evaluation of antiarthritic potential of
the methanolic extract of the aerial parts of Costus speciosus. J Ayurveda
Integr Med. 2012;3:204–8.
35. Zheng W, Yan CM, Zhang YB, et al. Antiparasitic efficacy of gracillin and
zingibernsis newsaponin from Costus speciosus (Koen ex. Retz) Sm. against
Ichthyophthirius multifiliis. Parasitology. 2015;142:473–9.
Cichorium intybus L.
(Asteraceae/Compositae)

(Syns.: C. balearicum Porta; C. byzantinum Clementi; C. cicorea Dumort.; C. glabratum

C. Presl; C. glaucum Hoffmanns. & Link; C. officinale Gueldenst. ex Ledeb.)

Abstract
An erect fairly woody perennial herb, native to Europe, it is now naturalized all
over the world, and found in India, China, Iran, North and South Africa, North
America, and Australia. The plant has been used since earlier times as it was
known to ancient Egyptians, Greeks and Romans. It is a typical Mediterranean
vegetable, and widely used medicinally to treat various ailments ranging from
wounds to diabetes in Europe and Asia, and used as a winter vegetable in Chile.
Aqueous root extract contains large amounts of carbohydrates and is safe for
human consumption. Dioscorides described two kinds of it, the wild and the
cultivated, and described both as astringent, cooling and stomachic, and stated
that due to its cooling property, it is also applied externally in inflammatory
affections. Chicory root dried, roasted and powdered was extensively used as a
substitute for coffee, and is now added to certain brands of coffee. From roots,
triterpenic constituents, an aliphatic d-lactone, 11–15% polysaccharide, 10–22%
of fructose, bitter principles lactucin and lactucopicrin, tannin, both a fatty and a
volatile oil, and small amounts of several other compounds have been isolated.
Ethanol and aqueous root extracts produced significant anti-inflammatory effect
in carrageenan-induced paw edema, increased CAT and GPx activities in paw
tissue and decreased serum TNF-a, IL-6, and IL-1 levels; however, one report
stated that ethanol root extract increased (59%) carrageenan-induced inflamma-
tion in rats. Ethanol extract of whole plant lowered serum glucose by 20%, TGs
by 91% and TC by 16% of diabetic rats with no change in serum insulin levels.
Intestinal absorption of glucose is reduced in chicory water extract or inulin
perfused rat gut. A proprietary bioactive extract of chicory root showed potential
role in the management of osteoarthritis in a phase I placebo-controlled trial.

Keywords
Almeirão

Bazarula

Chicorei

Cichorienkraut
Cikorie
Hindiba




Horseweed Kasni Kãsani Ku-tsai

© Springer Nature Switzerland AG 2020 609
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_65
610 Cichorium intybus L.

Vernaculars: Urd.: Hindiba, Kasni; Hin.: Hinduba, Kasni; San.: Kãsani; Ben.:
Hinduba, Kasni; Mal.: Cikkari, Munnchattikizhangu; Mar.: Kachani; Tam.:
Kashini-virai; Tel.: Kasini-vittulu; Ara.: Bazarula, Hindiba, Shikoriah, Siris; Chi.:
菊苣, Ku-tsai, Kuku; Cze.: Čekanka obecná; Dan.: Cikorie; Dut.: Brusselsche
kooltjes, Chicorei, Suikerij, Wilde cichorei; Eng.: Blue daisy, Blue dandelion, Blue
weed, Chicory, Horseweed, Wild endive; Fin.: Juurisikuri, Punasikuri, Radicchio,
Salaattisikuri, Sikuri; Fre.: Barbe de capucin, Chicorée amère, Chicorée sauvage,
Witloof; Ger.: Bittere cichorie, Chicorée, Cichorienkraut, Gemeine wegwarte,
Zichorie; Hun.: Cikória; Ita.: Cicoria amara. Cicoria selvatica, Radicchio; Jap.:
Kikunigana, Kio, Tsisa; Nor.: Sikori; Per.: Ambuboia, Kasni (potherb), Tarkashkun
(wild), Tukhme-kasni (seeds); Pol.: Cykoria; Por.: Almeirão; Rus.: Cikorij; Spa.:
Achicoria amarga, Achicoria silvestre, Almirón amargo, Masteguera borda, Radi-
cheta; Swe.: Cikoria, Vägvårda; Tur.: Hindiba, Korla; Vie.: Diê’p xoân, Rau di’êp
dâng.
Description: Native to Europe, it is now naturalized all over the world, and found
in India, China, Iran, North and South Africa, North America, and Australia. An
erect fairly woody perennial herb, around 1 m in height with hollow stems, a fleshy
taproot of up to 75 cm in length and large basal leaves [7]. Achenes are about the
same size as those of lettuce, angled, of a pale, mottled gray color. Fleshy taproot,
somewhat branched, longitudinally wrinkled, light-brown externally and whitish
internally; bark is rather thin, radially striate from the dark colored milk-vessels,
and separated by a brown cambium-line from the finely porous yellow wood; taste
is bitter and mucilaginous.XL Seeds are small, light or dark-brown in color, angular,
furrowed, and rather cuneate or narrow at the base, apex crowned with numerous
torn calyces or teeth. Sides of the seeds rather curved, taste slightly bitter (Figs. 1, 2
and 3).LXXVII,LXXXI
Actions and Uses: The plant has been used since earlier times as it was known to
ancient Egyptians, Greeks and Romans. It is a typical Mediterranean vegetable [39,
63, 66], and widely used medicinally to treat various ailments ranging from wounds
to diabetes in Europe and Asia [67], and used as a winter vegetable in Chile [18].
Aqueous root extract contains large amounts of carbohydrates and is safe for human
consumption. Dioscorides described two kinds of it, the wild and the cultivated
type, and described both as astringent, cooling and stomachic, and stated that due to
its cooling property, it is also applied externally in inflammatory affections. Pliny
said: ‘… persons who rub themselves with the juice of the entire plant, mixed with
oil, are sure to find more favor with others, and to obtain with greater facility
anything they may desire.’ Chicory root dried, roasted and powdered was exten-
sively used as a substitute for coffee, and is now added to certain brands of cof-
fee.XL Ibn Jazlah employed it in obstructions of the liver, and as a remedy for gout,
quartan fever, and bees and scorpion stings.LIII Leaves are deobstruent, diuretic,
cooling, liver tonic and blood purifier, and beneficial in hot liver and spleen
inflammations. Roots are diuretic, emmenagogue, deobstruent, anti-inflammatory,
and emetic, and used for the treatment of phlegmatic fevers and arthritis. Juice
squeezed from fresh leaves is boiled and when green foam is removed, the clear
Cichorium intybus L. 611

Fig. 1 Cichorium intybus, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons; https://commons.wiki
media.org/wiki/File:Illustration_Cichorium_intybus0_clean.jpg; www.biolib.de.

water is filtered and used for liver, stomach and spleen inflammation.LXXVII Ibn
Jazlah mentioned that good seeds are blackish, thick and bitter; are deobstruent,
diuretic, and beneficial in ascites, headache and palpitation; being bitter, they may
cause nausea and emesis, and they are harmful for kidneys; the root is diuretic,
blood purifier and anti-inflammatory.L In Ayurveda, seeds are considered carmi-
native and cooling, increase bile secretion, promote digestion, and promote secre-
tions in bowels and kidneys. Decoction of seeds is used mainly in hypo- or
inactivity of the liver, enlargement of spleen and general dropsy.LXXXI,CV Gupta
and SharmaLVIII reported its uses as a tonic, curative in acne, ophthalmia and
inflamed throat, and reported seeds as carminative and cordial, brain tonic, and
useful in headache and asthma. In folk medicine, chicory root is valued primarily as
a mild nonirritating tonic with associated diuretic and particularly laxative effect-
s.CLIV In Afghanistan, aqueous root extract is used for treatment of malaria; lactucin
and lactucopicrin were identified as the antimalarial compounds [10]. It protects
liver from, and acts as a counterstimulant to the effects of excess coffee drinking.LV
In Egypt it is valued as a remedy for tachycardia, and bruised leaves make a good
612 Cichorium intybus L.

Fig. 2 Cichorium intybus, Inflorescence, Blue Variety, Darkone, WikimediaCommons; ShareA-

like 2.0 Generic CC BY-SA 2.0, https://commons.wikimedia.org/wiki/File:Wegwarte_Cichorium_
intybus.jpg; https://creativecommons.org/licenses/by-sa/2.0/deed.en

poultice, and are applied locally for relief of swellings and inflammations.CXXXXIII
In Turkish folk remedies it is used to treat stomachache [20], and in Iranian culture
parental consumption of chicory leaves is believed to affect the gender of the
newborn [9]. Chicory fructooligosaccharides are recognized as natural food
ingredients, and improve bioavailability of essential minerals and reduce serum
triglyceridemia by lowering hepatic lipogenesis [13, 60].
Phytoconstituents: Leaves contain higher values of total flavonoids, total phenolic
acids, tannins, saponins, and high amount of Mg2+ and Zn2+ [1]; a favorable Ca2+ to
Mg2+ ratio and Mn, iron, and copper [69]; the predominant phenolic compounds
are hydroxycinnamic acids, including chlorogenic and cichoric acid [66]. Cichorin
A, B and C, oleanolic acid, and b-sitosterol [25, 26], cichoriin-6′-p-hydroxyphenyl
acetate [32], 2,6-di[but-3(E)-en-2-onyl] naphthalene, 3,3′,4,4′-tetrahydroxychalcone,
scopoletin, 4-hydroxyphenylacetic acid, 3-hydroxy-4-methoxybenzoic acid,
4,4′-dihydroxychalcone, 6,7-dihydroxycoumarine, 1-triacontanol, lupeol and
b-sitosterol-3-O-b-glucopyranoside [61] have been isolated from aerial parts. From
Cichorium intybus L. 613

Fig. 3 Cichorium intybus, Roots, Rasbak, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Witlof_en_wortel.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

roots, triterpenic constituents, an aliphatic d-lactone [36, 75], 11–15% polysaccharide

inulin (up to 58% in cultivated plants), 10–22% of fructose, bitter principles lactucin
and lactucopicrin, tannin, both a fatty and a volatile oil, and small amounts of several
other compounds have been isolated.XC Methanol extract contains alkaloids and/or
nitrogenous bases, carbohydrates and/or glycosides, tannins, flavonoids, saponins
and unsaturated sterols and/or triterpenes [5].
Pharmacology: Ethanol and aqueous root extracts produced significant anti-
inflammatory effect in carrageenan-induced paw edema, increased CAT and GPx
activities in paw tissue and decreased serum TNF-a, IL-6, and IL-1 levels [58];
whereas, Mascolo et al. [43] reported that ethanol root extract increased (59%)
carrageenan-induced inflammation in rats. Ethyl acetate root extract markedly
inhibited PGE2 production by inhibiting COX-2 expression in human colon car-
cinoma HT29 cells treated with TNF-a [12]. Aesculin, chlorogenic acid, chicoric
acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3a-ol are
suggested as the major constituents responsible for its uric acid lowering activity
[76]. Kim et al. [29] reported that aqueous extract inhibits mast cell-mediated
immediate-type allergic reactions in vitro and in mice.
Intestinal absorption of glucose is reduced in chicory water extract or inulin
perfused rat gut [31]. Ethanol extract of whole plant lowered serum glucose by
20%, TGs by 91% and TC by 16% of diabetic rats with no change in serum insulin
614 Cichorium intybus L.

levels, but a marked reduction in hepatic G-6-Pase activity [52]. However, chicoric
acid and chlorogenic acid stimulate insulin secretion from insulin-secreting cell line
and rat islets of Langerhans [70]. Aqueous seed extract prevented body weight loss
and decreased FBG, lowered ALT enzyme activity and levels of TGs, TC, and
HbA1c of diabetic rats [19]; whereas the ethanol extract significantly reduced blood
glucose, TGs, TC and LDL-C, and significantly increased HDL-C as well as
increased body weight, GSH, SOD, GST and CAT, and reduced MDA level in
diabetic rats [62]. Rats fed chicory extract and inulin diets had significantly greater
ratios of HDL/LDL-C and significantly greater fecal lipid, cholesterol and bile acid
excretions [30]. Caffeoylquinic acid-rich ethanol extract with high cholesterol diet
to rats improved glycemia, decreased atherogenic index and increased blood
antioxidant status [27], and chicory consumption by ApoE-deficient mice sup-
pressed aortic cholesterol accumulation and expression of intercellular adhesion
molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant
protein-1 [39]. Feeding dried leaf powder to diabetic rats for 10-days resulted in an
increase in AChE activity in cerebrum, cerebellum and medulla oblongata [2].
Bitter sesquiterpene lactones, lactucin and its derivatives lactucopicrin and
11b,13-dihydrolactucin showed analgesic activity; lactucin and lactucopicrin also
showed sedative properties [71]. A scientific report stated that lactucin and, to a
lesser extent, lactucopicrin antagonized stimulant properties of caffeine beverages
due to their CNS sedative effect [16].
Lavelli [37] reported a relationship between polyphenol contents and the
antioxidant activity of different extracts of C. intybus, but Schaffer et al. [63] found
substantial differences in polyphenol content of nutritionally used part, and diverse
specific antioxidant effects, ranging from no activity to almost complete protection,
with no clear correlations between polyphenol content and antioxidant activity in
samples collected from Greece (Crete), southern Italy, and southern Spain. D’evoli
et al. [14] also described whole leaf of Italian red chicory as a good source of total
phenolics and anthocyanins and their antioxidant and cytoprotective effects; the red
part of leaf having a significantly higher content of both total phenolics and
anthocyanins. Interestingly, Yook et al. [73] reported that antioxidant activity of
chicory was affected by the presence or absence of pesticides, and chicory grown
using ecodeveloped or organic fertilizer was more effective in suppressing the
proliferation of HepG2 cells when compared to chicory grown with chemical fer-
tilizer. Chicory-supplemented diet protected against nitrosamine-induced oxidative
stress and hepatotoxicity in rats [21]. Ethanol extracts of root and aerial parts
normalized CCl4-induced alterations in liver, and blood [5, 15, 34, 38]; root callus
extract exhibited better protection against CCl4-hepatotoxicity in rats than the
natural root extract [74], and effectively protected against cerulein-induced acute
pancreatitis in mice, more significant after parenteral administration [44]. Ethanol
extract pretreatment partially prevented cisplatin-induced electrolytes imbalances
and Na+K+-ATPase activity [46].
Methanol extract moderately inhibited growth of MDR S. typhi [53]. Various
extracts inhibited growth of plant pathogens A. radiobacter sp. tumefaciens,
E. carotovora, P. fluorescens and P. aeruginosa; ethyl acetate extract being the
Cichorium intybus L. 615

most active [50], B. thuringiensis, B. subtilis, and S. typhi [40], and against MDR
bacteria, MRSA and ESbetaL-producing enteric bacteria [4]. Extraction of seeds in
sodium phosphate citrate buffer, and sodium acetate buffer exhibited moderate
antibacterial activity against P. vulgaris, E. coli and S. aureus [3]. Antifungal
activity of root extracts has also been reported [41].
Aqueous decoction and methanol root extract significantly protect against
experimental gastric ulcerogenesis [20], exhibit antisecretory activity and stimula-
tion of defense barrier function of gastric mucosa in rats [35]. Chicory inulin
enhanced calcium absorption from cecocolon and improved femur and tibia mineral
contents in gastrectomized or ovariectomized rats [59]. Oligofructose and inulin,
the fermentable chicory fructans, stimulate growth of bifidobacteria that are bene-
ficial strains in the colon and inhibit colon carcinogenesis in laboratory animals [55,
56], by stimulating apoptosis at an early stage in the onset of cancer [24]. Ethanol
root extract is significantly effective against Ehrlich ascites carcinoma in mice [22].
Methanol root extract also exhibited potent wound healing activity [68]. Aqueous
leaf extract reportedly increased sex ratio of male to female offspring in experi-
mental rats [9], and ethanol seed extract was effective as postcoital contraceptive in
female rats [28]. Egyptian scientists reported its usefulness in tachycardia, showed
the presence of a digitalis-like principle in both the dried and roasted root [8]. The
active principle was not isolated, and the significance of this finding was difficult to
assess.CXXXXIII
Clinical Studies: A proprietary bioactive extract of chicory root showed potential
role in the management of osteoarthritis in a phase I placebo-controlled trial [47].
Consumption of snack bars containing chicory inulin by healthy individuals resulted
in a slight increase in stool frequency, and increased counts of bifidobacteria [33]. In
a clinical trial of elderly patients with constipation, daily supplementation with 15 g
inulin improved constipation and quality of life with slight gastrointestinal symp-
toms, such as flatulence [42]. Consumption of morning coffee containing 7.8 g
of inulin for one-week caused a slight but significant increase in overall abdomi-
nal discomfort of healthy subjects in a double-blind crossover study, but 5 g inulin
was better tolerated [57]. Caffeine-free chicory coffee consumption for a week
decreased platelet aggregation and significantly decreased whole blood and plasma
viscosity [65]. In a double-blind RCT, ingestion of roasted chicory root extract by
healthy adult participants did not significantly affect fasting plasma glucose or
insulin but reduced HgA1c level [45], and a double-blind trial showed that con-
sumption of oligofructose-enriched inulin for 6-weeks by postmenopausal women
increased the intestinal absorption of Ca2+ and Mg2+ [23]. Massage of inflamed
gums twice daily with dried alcohol extract for three-weeks, significantly reduced
gingival inflammation index, relieving inflammation and bleeding in 40 dental
patients with pyorrhea [49].
Mechanism of Action: Caffeic acid promotes decrease in hepatic glycogenolysis,
while ferulic acid increases insulin release and causes a reduction in hepatic
glycogenolysis, but chicoric acid extract increased insulin release and glucose
uptake without any effect on hepatic glycolgenolysis [6].
616 Cichorium intybus L.

Human A/Es, Allergy and Toxicity: Occupational contact dermatitis [17, 72],
inhalation occupational and ingestive immediate-type allergy [11], rhinoconjunc-
tivitis and asthma [51], have been reported.
Animal Toxicity: Mean lethal dose (i.p.) in mice is 8,900 and 9,300 mg/kg for
aqueous and alcohol extracts, respectively [48]. A sesquiterpene lactones-rich chic-
ory root extract did not show any mutagenic activity in Ames test, and was nontoxic
to Sprague-Dawley rats up to an oral dose of 1,000 mg/kg/day for 4-weeks [64].
CYP450 and Potential for Drug-Herb Interactions: Chicory root administration
to pigs increased activities of CYP1A2 and CYP2A [54].
Commentary: Clinical studies are mostly conducted on inulin, that has shown
favorable effects on constipation, increased counts of bifidobacteria, and enhanced
absorption of Ca2+ and Mg2+ in postmenopausal women. However, these are isolated
studies that do not allow to make a definitive opinion about these effects. Pharma-
cological results about blood glucose and lipids, especially TGs lowering effects
should be clinically explored individually for seeds, roots and the whole plant.

References
1. Abbas ZK, Saggu S, Sakeran MI, et al. Phytochemical, antioxidant and
mineral composition of hydroalcoholic extract of chicory (Cichorium
intybus L.) leaves. Saudi J Biol Sci. 2015;22:322–6.
2. Ahmed N, Tarannum S. Acetylcholinesterase activity in the brain of alloxan
diabetic albino rats: presence of an inhibitor of this enzyme activity in the
cerebral extract. Int J Diabetes Dev Ctries. 2009;29:174–7.
3. Al Akeel R, Al-Sheikh Y, Mateen A, et al. Evaluation of antibacterial
activity of crude protein extracts from seeds of six different medical plants
against standard bacterial strains. Saudi J Biol Sci. 2014;21:147–51.
4. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian
medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
5. Atta AH, Elkoly TA, Mouneir SM, et al. Hepatoprotective effect of
methanol extracts of Zingiber officinale and Cichorium intybus. Indian J
Pharm Sci. 2010;72:564–70.
6. Azay-Milhau J, Ferrare K, Leroy J, et al. Antihyperglycemic effect of a
natural chicoric acid extract of chicory (Cichorium intybus L.): a comparative
in vitro study with the effects of caffeic and ferulic acids. J Ethnopharmacol.
2013;150:755–60.
7. Bais HP, Ravishankar GA. Cichorium intybus L.—cultivation, processing,
utility, value addition and biotechnology, with an emphasis on current status
and future prospects. J Sci Food Agri. 2001;81:467–84.
8. Balbaa SI, Zaki AY, Abdel-Wahab SM, el-Denshary ES, Motazz-Bellah M.
Preliminary phytochemical and pharmacological investigations of the roots
of different varieties of Cichorium intybus. Planta Med. 1973;24:133–44.
Cichorium intybus L. 617

9. Behnam-Rassouli M, Aliakbarpour A, Hosseinzadeh H, et al. Investigating

the effect of aqueous extract of Chicorium intybus L. leaves on offspring
sex ratio in rat. Phytother Res. 2010;24:1417–21.
10. Bischoff TA, Kelley CJ, Karchesy Y, et al. Antimalarial activity of lactucin
and lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus
L. J Ethnopharmacol. 2004;95:455–7.
11. Cadot P, Kochuyt AM, Deman R, Stevens EA. Inhalative occupational and
ingestive immediate-type allergy caused by chicory (Cichorium intybus).
Clin Exp Allergy. 1996;26:940–4.
12. Cavin C, Delannoy M, Malnoe A, et al. Inhibition of the expression and
activity of cyclooxygenase-2 by chicory extract. Biochem Biophys Res
Commun. 2005;327:742–9.
13. Chow J. Probiotics and prebiotics: a brief overview. J Ren Nutr. 2002;
12:76–86.
14. D’evoli L, Morroni F, Lombardi-Boccia G, et al. Red chicory (Cichorium
intybus L. cultivar) as a potential source of antioxidant anthocyanins for
intestinal health. Oxid Med Cell Longev. 2013;704310.
15. El-Sayed YS, Lebda MA, Hassinin M, Neoman SA. Chicory (Cichorium
intybus L.) root extract regulates the oxidative status and antioxidant gene
transcripts in CCl4-induced hepatotoxicity. PLoS One. 2015;10:e0121549.
16. Forst AW. Naunyn-schmiedebergs Archiv fur experimentelle Pathologie
und Pharmakologie. 1940;195:1–25.
17. Friis B, Hjorth N, Vail JT Jr, Mitchell JC. Occupational contact dermatitis
from Cichorium (chicory, endive) and Lactuca (lettuce). Contact Dermatitis.
1975;1:311–3.
18. García J, Atalah E, Urteaga C, et al. Dietary carotene intake and lung cancer
among men from Santiago. Rev Med Chil. 1995;123:51–60 (Spanish).
19. Ghamarian A, Abdollahi M, Su X, et al. Effect of chicory seed extract on
glucose tolerance test (GTT) and metabolic profile in early and late stage
diabetic rats. Daru. 2012;20:56.
20. Gürbüz I, Ustün O, Yeşilada E, et al. In vivo gastroprotective effects of five
Turkish folk remedies against ethanol-induced lesions. J Ethnopharmacol.
2002;83:241–4.
21. Hassan HA, Yousef MI. Ameliorating effect of chicory (Cichorium
intybus L.)-supplemented diet against nitrosamine precursors-induced liver
injury and oxidative stress in male rats. Food Chem Toxicol. 2010;48:
2163–9.
22. Hazra B, Sarkar R, Bhattacharyya S, Roy P. Tumour inhibitory activity of
chicory root extract against Ehrlich ascites carcinoma in mice. Fitoterapia.
2002;73:730–3.
23. Holloway L, Moynihan S, Abrams SA, et al. Effects of oligofructose-
enriched inulin on intestinal absorption of calcium and magnesium and bone
turnover markers in postmenopausal women. Br J Nutr. 2007;97:365–72.
618 Cichorium intybus L.

24. Hughes R, Rowland IR. Stimulation of apoptosis by two prebiotic chicory

fructans in the rat colon. Carcinogenesis. 2001;22:43–7.
25. Hussain H, Hussain J, Ali S, et al. Cichorins B and C: two new benzo-
isochromenes from Cichorium intybus. J Asian Nat Prod Res. 2012;14:
297–300.
26. Hussain H, Hussain J, Saleem M, et al. Cichorin A: a new benzo-
isochromene from Cichorium intybus. J Asian Nat Prod Res. 2011;13:566–9.
27. Jurgoński A, Juśkiewicz J, Zduńczyk Z, Król B. Caffeoylquinic acid-rich
extract from chicory seeds improves glycemia, atherogenic index, and
antioxidant status in rats. Nutrition. 2012;28:300–6.
28. Keshri G, Lakshmi V, Singh MM. Postcoital contraceptive activity of some
indigenous plants in rats. Contraception. 1998;57:357–60.
29. Kim HM, Kim HW, Lyu YS, et al. Inhibitory effect of mast cell-mediated
immediate-type allergic reactions by Cichorium intybus. Pharmacol Res.
1999;40:61–5.
30. Kim M, Shin HK. The water-soluble extract of chicory influences serum and
liver lipid concentrations, cecal short-chain fatty acid concentrations and
fecal lipid excretion in rats. J Nutr. 1998;128:1731–6.
31. Kim M, Shin HK. The water-soluble extract of chicory reduces glucose
uptake from the perfused jejunum in rats. J Nutr. 1996;126:2236–42.
32. Kisiel W, Michalska K. A new coumarin glucoside ester from Cichorium
intybus. Fitoterapia. 2002;73:544–6.
33. Kleessen B, Schwarz S, Boehm A, et al. Jerusalem artichoke and chicory
inulin in bakery products affect faecal microbiota of healthy volunteers. Br J
Nutr. 2007;98:540–9.
34. Krylova SG, Efimova LA, Vymiatina ZK, Zueva EP. The effect of cichorium
root extract on the morphofunctional state of liver in rats with carbon
tetrachloride induced hepatitis model. Eksp Klin Farmakol. 2006;69:34–6
(Russian).
35. Krylova SG, Vymyatnina ZK, Zueva EP, et al. Effects of Cichorium intybus
L. root extract on secretory activity of the stomach in health and ulcer
disease. Bull Exp Biol Med. 2015;159:638–41.
36. Kumari R, Ali M, Aeri V. Two new triterpenoids from Cichorium intybus L.
roots. J Asian Nat Prod Res. 2012;14:7–13.
37. Lavelli V. Antioxidant activity of minimally processed red chicory (Cicho-
rium intybus L.) evaluated in xanthine oxidase-, myeloperoxidase-, and
diaphorase-catalyzed reactions. J Agric Food Chem. 2008;56:7194–200.
38. Li GY, Gao HY, Huang J, et al. Hepatoprotective effect of Cichorium
intybus L., a traditional Uighur medicine, against carbon tetrachloride-
induced hepatic fibrosis in rats. World J Gastroenterol. 2014;20:4753–60.
39. Lin W, Liu C, Yang H, et al. Chicory, a typical vegetable in Mediterranean
diet, exerts a therapeutic role in established atherosclerosis in apolipoprotein
E-deficient mice. Mol Nutr Food Res. 2015;59:1803–13.
Cichorium intybus L. 619

40. Liu H, Wang Q, Liu Y, Chen G, Cui J. Antimicrobial and antioxidant

activities of Cichorium intybus root extract using orthogonal matrix design.
J Food Sci. 2013;78:M258–63.
41. Mares D, Romagnoli C, Tosi B, et al. Chicory extracts from Cichorium
intybus L. as potential antifungals. Mycopathologia. 2005;160:85–91.
42. Marteau P, Jacobs H, Cazaubiel M, et al. Effects of chicory inulin in
constipated elderly people: a double-blind controlled trial. Int J Food Sci
Nutr. 2011;62:164–70.
43. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal
plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
44. Minaiyan M, Ghannadi AR, Mahzouni P, Abed AR. Preventive effect of
Cichorium Intybus L. Two extracts on cerulein-induced acute pancreatitis in
mice. Int J Prev Med. 2012;3:351–7.
45. Nishimura M, Ohkawara T, Kanayama T, et al. Effects of the extract from
roasted chicory (Cichorium intybus L.) root containing inulin-type fructans
on blood glucose, lipid metabolism, and fecal properties. J Tradit Comple-
ment Med. 2015;5:161–7.
46. Noori S, Mahboob T. Role of electrolytes disturbances and Na(+)-K(+)-
ATPase in cisplatin-induced renal toxicity and effects of ethanolic extract
of Cichorium intybus. Pak J Pharm Sci. 2012;25:857–62.
47. Olsen NJ, Branch VK, Jonnala G, et al. Phase 1, placebo-controlled, dose
escalation trial of chicory root extract in patients with osteoarthritis of the
hip or knee. BMC Musculoskelet Disord. 2010;11:156.
48. Patel VK, Venkatakrishna-Bhatt H. Anti-inflammatory effects of chicory
(Cichorium intybus L.) in pyorrhoea. Proc Indian Pharmacol Soc Annual
Conf. 1983;50 (Abstr. 112).
49. Patel VK, Venkatakrishna-Bhatt H. Cichorium intibus Linn.: a novel herbal
preparation as a gum massage, dentrifice, anti-inflammatory and antiplaque
agent (review & applied study). Therapie (France). 1983;38:405–15.
50. Petrovic J, Stanojkovic A, Comic LJ, Curcic S. Antibacterial activity of
Cichorium intybus. Fitoterapia. 2004;75:737–9.
51. Pirson F, Detry B, Pilette C. Occupational rhinoconjunctivitis and asthma
caused by chicory and oral allergy syndrome associated with bet v 1-related
protein. J Investig Allergol Clin Immunol. 2009;19:306–10.
52. Pushparaj PN, Low HK, Manikandan J, et al. Antidiabetic effects of
Cichorium intybus in streptozotocin-induced diabetic rats. J Ethnopharmacol.
2007;111:430–4.
53. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
54. Rasmussen MK, Zamaratskaia G, Ekstrand B. In vivo effect of dried
chicory root (Cichorium intybus L.) on xenobiotica metabolising cyto-
chrome P450 enzymes in porcine liver. Toxicol Lett. 2011;200:88–91.
620 Cichorium intybus L.

55. Reddy BS, Hamid R, Rao CV. Effect of dietary oligofructose and inulin on
colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis. 1997;18:
1371–4.
56. Reddy BS. Prevention of colon cancer by pre- and probiotics: evidence from
laboratory studies. Br J Nutr. 1998;80:S219–23.
57. Ripoll C, Flourié B, Megnien S, et al. Gastrointestinal tolerance to an inulin-
rich soluble roasted chicory extract after consumption in healthy subjects.
Nutrition. 2010;26:799–803.
58. Rizvi W, Fayazuddin M, Shariq S, et al. Anti-inflammatory activity of roots
of Cichorium intybus due to its inhibitory effect on various cytokines and
antioxidant activity. Anc Sci Life. 2014;34:44–9.
59. Roberfroid MB, Cumps J, Devogelaer JP. Dietary chicory inulin increases
whole-body bone mineral density in growing male rats. J Nutr. 2002;132:
3599–602.
60. Roberfroid MB. Health benefits of nondigestible oligosaccharides. Adv Exp
Med Biol. 1997;427: 211–19 (Review).
61. Saied S, Shah S, Ali Z, et al. Chemical constituents of Cichorium intybus
and their inhibitory effects against urease and alpha-chymotrypsin enzymes.
Nat Prod Commun. 2011;6:1117–20.
62. Samarghandian S, Borji A, Tabasi SH. Effects of Cichorium intybus Linn
on blood glucose, lipid constituents and selected oxidative stress parameters
in streptozotocin-induced diabetic rats. Cardiovasc Hematol Disord Drug
Targets. 2013;13:231–6.
63. Schaffer S, Schmitt-Schillig S, Müller WE, Eckert GP. Antioxidant prop-
erties of Mediterranean food plant extracts: geographical differences.
J Physiol Pharmacol. 2005;56 Suppl 1:115–24.
64. Schmidt BM, Ilic N, Poulev A, Raskin I. Toxicological evaluation of a
chicory root extract. Food Chem Toxicol. 2007;45:1131–9.
65. Schumacher E, Vigh E, Molnár V, et al. Thrombosis preventive potential
of chicory coffee consumption: a clinical study. Phytother Res. 2011;25:
744–8.
66. Sinkovič L, Demšar L, Žnidarčič D, et al. Phenolic profiles in leaves
of chicory cultivars (Cichorium intybus L.) as influenced by organic and
mineral fertilizers. Food Chem. 2015;166:507–13.
67. Street RA, Sidana J, Prinsloo G. Cichorium intybus: traditional uses,
phytochemistry, pharmacology, and toxicology. Evid Based Complement
Alternat Med. 2013;2013:579319.
68. Süntar I, Küpeli Akkol E, Keles H, et al. Comparative evaluation of
traditional prescriptions from Cichorium intybus L. for wound healing:
stepwise isolation of an active component by in vivo bioassay and its mode
of activity. J Ethnopharmacol. 2012;143:299–309.
69. Szentmihályi K, May Z, Süle K, Then M. Mineral content of some herbs
and plant extracts with anti-inflammatory effect used in gastrointestinal
diseases. Orv Hetil. 2013;154:538–43 (Hungarian).
Cichorium intybus L. 621

70. Tousch D, Lajoix AD, Hosy E, et al. Chicoric acid, a new compound able to
enhance insulin release and glucose uptake. Biochem Biophys Res Commun.
2008;377:131–5.
71. Wesołowska A, Nikiforuk A, Michalska K, Kisiel W, Chojnacka-Wójcik E.
Analgesic and sedative activities of lactucin and some lactucin-like guaiano-
lides in mice. J Ethnopharmacol. 2006;107:254–8.
72. Willi R, Pfab F, Huss-Marp J, et al. Contact anaphylaxis and protein contact
dermatitis in a cook handling chicory leaves. Contact Dermatitis. 2009;60:
226–7.
73. Yook JS, Kim M, Pichiah PB, et al. The antioxidant properties and
inhibitory effects on HepG2 cells of Chicory cultivated using three different
kinds of fertilizers in the absence and presence of pesticides. Molecules.
2015;20:12061–75.
74. Zafar R, Mujahid Ali S. Antihepatotoxic effects of root and root callus
extracts of Cichorium intybus L. J Ethnopharmacol. 1998;63:227–31.
75. Zhou CX, Zou L, Zhao ZZ, et al. Terpenoids from Cichorium intybus. Nat
Prod Commun. 2012;7:971–2.
76. Zhu CS, Zhang B, Lin ZJ, et al. Relationship between high-performance
liquid chromatography fingerprints and uric acid-lowering activities of
Cichorium intybus L. Molecules. 2015;20:9455–67.
Cinnamomum camphora (L.) J. Presl.
(Lauraceae)

(Syns.: Laurus camphora L.; Camphora officinarum Nees; Camphora camphora (L.)
H. Karst.)

Abstract
The tree is native to south China, Taiwan, south Japan, Korea, Vietnam,
Formosa and Tonkin, India, Sri Lanka, Europe, Malaya, the Philippines, Eastern
and Southern Africa, Central America, and the United States. Camphor, freely
soluble in water, is chiefly distilled from the root trunk and branches, and is
purified by sublimation and condensed into balls, tablets or sublime powder.
D-camphor is highest in bark and lowest in fruits. Externally, camphor is rube-
facient, resolvent, disinfectant, antipruritic, analgesic and anesthetic; internally,
it is cardiostimulant, cardiorefrigerant, antipyretic, stomach tonic, carminative
and constipative. In therapeutic doses, it stimulates heart, respiration, and the
vasomotor ganglia, and stimulates and increases sexual desire, after a while it
depresses sexual functions. It stimulates uterus and increases menstrual flow. As
an anodyne it relieves pain, moderates sexual excitement and other neurotic
affections. Different chemotypes of C. camphora demonstrate anti-inflammatory
effect on Freund’s adjuvant-induced arthritis in rats. Essential oil possesses
significant anticandidal activity, arrests growth of toxigenic strains of A. flavus,
A. niger, and is also toxic to human breast tumor cells. Daily topical application
of 1/3 diluted camphor oil with glycerol, and metronidazole orally for fifteen-
days to females suffering from erythema to telangiectatic rosacea, due to
Demodex folliculorum infestation, produced good results without any apparent
side effect. Safrole is a component of essential oil that induces hepatomas in rats
in concentration of 0.5–1% of diet.

Keywords


Alcanfor Alcanforeira Camphor

Camphrier
Kafoor
Kamferipuu




Karpūra Kusu-no-ki Laurocanfora
Zhang

© Springer Nature Switzerland AG 2020 623

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_66
624 Cinnamomum camphora (L.) J. Presl.

Vernaculars: Urd.: Kafoor; Hin.: Kaphur, Kapur; San.: Apakva, Chandra, Ghana-
sãra, Hima, Karpūra, Karpuroh, Pakva, Sitabhra; Ben.: Kaphur, Kapur; Mal.:
Cutakkarpuram, Karppuram; Mar.: Kaphur, Kapoora, Kapur; Tam.: Indu,
Karpuram, Shudan karuppuram; Tel.: Karpuram, Karpuramu, Pacca; Ara.: Kafur;
Bur.: Payok, Payuk; Chi.: 樟, Xiang zhang shu, Zhang, Zhang shu; Dut.:
Japaansche kamferboom; Eng.: Camphor, Japanese camphor tree, Camphor laurel,
Gum campho; Fin.: Kamferipuu; Fre.: Camphre, Camphrier, Laurier du Japon;
Ger.: Campher, Kampferbaum; Ita.: Albero confora, Allopo canforato, Lauro-
canfora; Jap.: Kusu-no-ki; Kor.: Nok na mu; Nep.: Kapuur; Per.: Kafur; Por.:
Alcanforeira, Arvore da camphora, Cânfora; Rus.: Kamfarnoe derevo, Kamfornii
lavr; Spa.: Alcanfor, Alcanforero; Swe.: Kamferträd; Tag.: Camphor; Tha.: Karabun,
Op choei yuan; Vie.: Cây-long não.
Description: The tree is native to south China, Taiwan, south Japan, Korea,
Vietnam [5], Formosa and Tonkin, India, Sri Lanka, Europe, Malaya, the Philippines,
Eastern and Southern Africa, Central America, and the United States. Usually it is
12 m high but may attain a height of 25–30 m; it has a short trunk and dense crown,
aromatic, dark-gray or dark-brown, rough, fissured bark; leaves are semievergreen,
alternate, aromatic, long-stalked, ovate to oblong-lanceolate, pointed at both ends,
5–11 cm long and up to 5 cm wide, with 3–5 prominent nerves beginning a little
above the base; leathery, dark-green, glossy above, whitish or glaucous beneath.
Flowers, in short axillary clusters, are sweetly fragrant, yellowish-white, 3 mm long
and 5 mm wide. Fruit, seated on a brownish perianth tube, is round-oval, 10–12 mm
wide, fleshy, with a single seed.C Camphor, freely soluble in water, is chiefly distilled
from the root trunk and branches, and is purified by sublimation and condensed into
balls, tablets or sublime powder. Camphor odor is intense, taste pungent and bitter,
followed by a sensation of cold (Figs. 1 and 2).LXXXI

Fig. 1 Cinnamomum camphora, Tree in Adelaide, Australia, Peripitus, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cinnamomum_
camphora_-_Botanic_Gardens.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Cinnamomum camphora (L.) J. Presl. 625

Fig. 2 Cinnamomum camphora, Leaves and Fruits, Poyt448 Peter Woodard, WikimediaCom-
mons; Universal CC0 1.0, https://commons.wikimedia.org/wiki/File:Cinnamomum_camphora_
Turramurra_railway.jpg; https://creativecommons.org/publicdomain/zero/1.0/deed.en

Actions and Uses: In Asia and Europe, camphor is applied to sprains, inflammations,
gout and rheumatic joints and taken internally to calm hysteria, abate convulsions and
epileptic attacks; also as a carminative, and as a respiratory and cardiac stimulant.XXI,
LXXII,CLIV
Externally, camphor (temperament, cold 3° and dry 3°) is rubefacient,
resolvent, disinfectant, antipruritic, analgesic and anesthetic; internally, it is car-
diostimulant, cardiorefrigerant, antipyretic, stomach tonic, carminative and consti-
pative. In therapeutic doses, it stimulates heart, respiration, and the vasomotor ganglia,
and stimulates and increases sexual desire, after a while it depresses sexual functions.
It stimulates uterus and increases menstrual flow. As an anodyne it relieves pain,
moderates sexual excitement and other neurotic affections. In large doses, it produces
gastroenteritis, depresses heart, produces excitement, cold sweats, cold hands and
feet, and delirium with dilated pupil, ultimately coma, convulsions and death.
Externally, the liniment is useful for sprains, bruises, rheumatic joint pain, and in
spasmodic muscle pain.XL,L,LXXXI Razi is quoted to have said that it is beneficial for
headaches and all ‘hot inflammations’.LXIX In Cuba, camphor is employed as an
antiseptic, antispasmodic, anaphrodisiac, antiasthmatic and anthelmintic; and also
given in nervous and eruptive fevers. For rheumatic pains, camphor leaves are crushed
and steeped in alcohol, which are then applied as a rub.CXXI In Mexico and South
America, camphor in olive oil is applied on bruises, contusions and neuralgia, and also
used to treat rhinitis, asthma, pulmonary congestion, chronic bronchitis and emphy-
sema.XCV In the United States, camphor is used only in preparations for external use as
an antipruritic, rubefacient or counterirritant, or as an anesthetic in lotions to coun-
teract pain and itching.CXI
626 Cinnamomum camphora (L.) J. Presl.

Phytoconstituents: Two types of toxic, irreversibly ribosome-inactivating proteins,

camphorin and cinnamomin were isolated from seeds [6, 9]. Essential oil yield was
highest from leaves, followed by from fruits, and least in the stem bark. Twenty-seven
components were reported in bark oil, while only 17 constituents were identified in
fruit oil. D-camphor was highest in bark and lowest in fruits. Some unique con-
stituents in bark EO include c-terpinene, isoterpinolene, 1,3,8-p-menthatriene,
terpinen-4-ol, a-terpineol, eugenol, b-cadinene, and a-cubebene, in addition to
D-camphor, 1,8-cineole, and 3-methyl-2-butenoic acid, oct-3-en-2-yl ester; main
constituents of fruit oil are safrole, D-camphor, linalool, and 1,8-cineole [5].
Pharmacology: Seed kernel oil significantly decreased body mass, TC, TGs, FFA,
fasting insulin and insulin-resistance in diet-induced obese rats [3], reduced oxida-
tive stress and improved activities of antioxidant enzymes [4]. Different chemotypes
of C. camphora demonstrate anti-inflammatory effect on Freund’s adjuvant-induced
arthritis in rats [8]. Methanol extract and its fractions (hexane and ethyl acetate)
significantly blocked production of IL-1b, IL-6 and TNF-a from LPS-stimulated
RAW264.7 cells, and also inhibited NO production in LPS/IFN-c-activated macro-
phages [7]. Essential oil possesses significant anticandidal activity [1], arrested
growth of toxigenic strains of A. flavus [12], A. niger, and was also toxic to human
breast tumor cells [11]. Cinnamomin and camphorin from the seeds produce inhi-
bitory effects in cultured human hepatocarcinoma and the melanoma cell-lines.
Cinnamomin also exhibits remarkable inhibitory effect on growth of solid skin
melanoma of nude mice [10].
Clinical Studies: Daily topical application of 1/3 diluted camphor oil with glyc-
erol, and 500 mg metronidazole orally for fifteen-days to 15 females suffering from
erythema to telangiectatic rosacea, due to Demodex folliculorum infestation, pro-
duced good results without any apparent side effect [2].
Human A/Es, Allergy and Toxicity: Not suitable for people with cold tempera-
ment, causes bladder stones and harmful to sexual functions. Rhazes says it dries up
semen.LXIX Camphor may be toxic to children and, in large dosage, to adults. Signs
and symptoms of poisoning include feeling of warmth, N/V, headache, confusion,
excitement or occasionally depression, restlessness, delirium, hallucianations, uncon-
sciousness and convulsions; respiratory failure may result in death.CL
Animal Toxicity: Safrole (p-allylyn ethylenediozybenzene) is a component of
many essential oils including C. camphora, that induces hepatomas in rats in
concentration of 0.5–1% of diet; casein supplements aggravate safrole-induced
adenomatosis, and biotin supplements inhibit hepatocarcinogenic activity of
safrole.LXXXVIII
Commentary: Camphor is mainly used externally, and other than one clinical
study on erythema to telangiectatic rosacea due to Demodex folliculorum infestation
in females, no other studies are reported. It has essentially been relegated for use
only as antiseptic and disinfectant.
Cinnamomum camphora (L.) J. Presl. 627

References
1. Dutta BK, Karmakar S, Naglot A, Aich JC, Begam M. Anticandidial activity
of some essential oils of a mega biodiversity hotspot in India. Mycoses.
2007;50:121–4.
2. El-Shazly AM, Hassan AA, Soliman M, et al. Treatment of human
Demodex folliculorum by camphor oil and metronidazole. J Egypt Soc
Parasitol. 2004;34:107–16.
3. Fu J, Zeng C, Zeng Z, et al. Cinnamomum camphora seed kernel oil
improves lipid metabolism and enhances b3-adrenergic receptor expression
in diet-induced obese rats. Lipids. 2016;51:693–702.
4. Fu J, Zeng C, Zeng Z, Wang B, Gong D. Cinnamomum camphora seed
kernel oil ameliorates oxidative stress and inflammation in diet-induced
obese rats. J Food Sci. 2016;81:H1295–300.
5. Guo S, Geng Z, Zhang W, et al. The chemical composition of essential oils
from Cinnamomum camphora and their insecticidal activity against the
stored product pests. Int J Mol Sci. 2016;17.
6. Hou FJ, Xu H, Liu WY. Simultaneous existence of cinnamomin (a type II
RIP) and small amount of its free A- and B-chain in mature seeds of
camphor tree. Int J Biochem Cell Biol. 2003;35:455–64.
7. Lee HJ, Hyun EA, Yoon WJ, et al. In vitro anti-inflammatory and anti-
oxidative effects of Cinnamomum camphora extracts. J Ethnopharmacol.
2006;103:208–16.
8. Li H, Huang L, Zhou A, Li X, Sun J. Study on anti-inflammatory effect
of different chemotype of Cinnamomum camphora on rat arthritis model
induced by Freund’s adjuvant. Zhongguo Zhong Yao Za Zhi. 2009;34:
3251–4 (Article in Chinese).
9. Ling J, Liu WY, Wang TP. Simultaneous existence of two types of
ribosome-inactivating proteins in the seeds of Cinnamonum camphora—
characterization of the enzymatic activities of these cytotoxic proteins.
Biochim Biophys Acta. 1995;1252:15–22.
10. Ling J, Liu WY. Cytotoxicity of two new ribosome-inactivating proteins,
cinnamomin and camphorin, to carcinoma cells. Cell Biochem Funct.
1996;14:157–61.
11. Satyal P, Paudel P, Poudel A, et al. Bioactivities and compositional analyses
of Cinnamomum essential oils from Nepal: C. camphora, C. tamala, and
C. glaucescens. Nat Prod Commun. 2013;8:1777–84.
12. Singh P, Srivastava B, Kumar A, Dubey NK. Fungal contamination of raw
materials of some herbal drugs and recommendation of Cinnamomum
camphora oil as herbal fungitoxicant. Microb Ecol. 2008;56:555–60.
Cinnamomum cassia (L.) J. Presl
(Lauraceae)

(Syns.: Camphorina cassia (Nees & T. Nees) Farw.; C. aromaticum Nees; C. longifolium
Lukman; C. medium Lukman; C. nitidum Nees ex. Bojer.; Laurus cassia L.; Persea cassia (L.)
Spreng.)

Abstract
A tree, native to southern China, Laos, Vietnam, and Sumatra, that was known to
ancient Greeks, Chinese and Indians. Theophrastus, Galen and Dioscorides
described more than one variety of it, and it was mentioned in Chinese Herbals
written in 2700 B.C.; in India, it was known as Tvach and Guda-tvach. Arabs
knew it as Kirfat-ed-darsini or simply Kirfah, through whom it reached Europe.
Dioscorides and Avicenna described it as anti-inflammatory and astringent, and
recommended it for all internal inflammatory conditions. It is a general stimulant
to the nervous and vascular systems. In China, it is known as Rougui or Yugui
and is considered hot and slightly toxic; said to be able to warm and tone up
‘spleen and kidney’, and is cold-discutient, analgesic and vascular-deobstruent.
It is effective in abdominal and gastric pain, diarrhea due to asthenia and
pathogenic cold, hypofunction of kidney, rheumatic backache, cough due to
pathogenic cold in lungs, amenorrhea, and abdominal mass. It is one of the 50
fundamental herbs of TCM, and is used in the treatment of fever, inflammation,
chronic bronchitis, and to improve blood circulation. Dried bark is the main part
used, but Cinnamomi (Kuei) Ramulus (Chih), the dried tender twigs are also
used for the same purpose, and to treat menstrual disorders and hypertension.
Immature fruits are also widely consumed in China as a food spice, dietary
supplements, flavoring agents, and preservatives. In Unani medicine, the oil is
externally used alone or in combination with other oils for sexual weakness. The
oil has no astringency and in therapeutic doses is also good for flatulence,
paralysis of tongue, enteralgia, stomach cramps, and nausea and vomiting.
Cinnamon bark contains volatile oil, mainly composed of cinnamaldehyde with
strong odor (oxidizing rapidly and forming cinnamic acid), eugenol, phellan-
drene, orthomethylcoumaric aldehyde, cinnamyl acetate, phenylpropyl alcohol,
cinnamic alcohol and traces of coumarin. Aqueous bark extract inhibits gastric
secretion, promots gastric mucosal blood flow, and prevents formation of stress-
and serotonin-induced gastric ulcers in rats and mice, and inhibits H. pylori and

© Springer Nature Switzerland AG 2020 629

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_67
630 Cinnamomum cassia (L.) J. Presl

TNF-a stimulated IL-8 secretion from gastric epithelial cells. Cinnamon powder
protects rats from dimethylnitrosamine-induced liver injury.

Keywords






Bastaardkaneel Cassia Kashia Kassie Kirfah Rougui Saleekha Saliha





Taj Tvach

Vernaculars: Urd.: Saleekha, Taj; Hin.: Taj, Tvach, Tvaksara, Tvak-svadvi; San.:
Tvach; Ben.: Dalachini, Taja; Mal.: Lavanga-pattai; Mar.: Dalchini, Daruchini;
Tam.: Karuvap-pattai, Lavanga-pattai, Lawunga; Tel.: Lavanga-pattai; Ara.:
Darsini, Darsoos, Kirfah, Kirfat-ed-darsini, Rehan-al-jamal, Salikha; Chi.: 肉桂,
Guan gui, Gui xin, Gun gwai, Gwai sam, Jih gwai, Kicei, Mauh gwai, Rou-gui,
Yugui, Yuhk gwai, Yuk gwai; Cze.: Skořice čínská; Dan.: Kassiakanel, Kinesisk
kanel, Kinesisk kaneltræ; Dut.: Bastaardkaneel, Chinese kaneel, Valse kaneel;
Eng.: Cassia, Cassia lignea, Chinese cassia, Chinese cinnamon; Fin.: Kassiakaneli,
Kiinankaneli, Talouskaneli; Fre.: Arbre à cannelle, Canéfice, Cannellier casse,
Cannelle de Chine; Ger.: Kassie, China-zimtbaum, Chinesischer zimt, Zimtkassie;
Gre.: Kasia; Ind.: Kayu manis cina; Ita.: Canella del coromandel, Cassia; Jap.:
Kashia, Tonkin nikkei; Kor.: Kasia; Lao.: Sa chouang; Maly.: Kayu manis cina;
Nor.: Kassia; Per.: Ashtargyah, Darchini, Saila myah; Pol.: Cynamon chiński,
Kasja; Por.: Canela-da-china, Cássia-aromática; Rus.: Korichnik aromatnyi,
Korichnoje derevo; Spa.: Canela de la China, Casia; Swe.: Kassia; Tha.: Ob choey
chin; Tur.: Çin tarçını, Saliha; Vie.: Quế dơn, Quế quảng, Quế thanh.
Description: A 10 m high tree, native to southern China, Laos, Vietnam, and
Sumatra; leaves alternate, petiolate, elliptical-oval, 8–15 cm long and 3–4 cm wide,
tip acuminate, base rounded, entire, coriaceous, underside lightly pubescent; petiole
10 mm long, lightly pubescent. Inflorescence densely hairy panicle as long as the
leaves; flowers in May, flowers small, yellowish-white, no petals; fruit a globular
drupe, 8 mm long; red bark is sold as rolled tubes, reddish-brown externally and
brown internally, strongly aromatic, taste is warm and piquant.LXXIX The plant
was known to ancient Greeks, Chinese and Indians. Theophrastus, Galen and
Dioscorides described more than one variety of it, and it was mentioned in Chinese
Herbals written in 2700 B.C.; in India, it was known as Tvach and Guda-tvach.
Arabs knew it as Kirfat-ed-darsini or simply Kirfah, through whom it reached
Europe. In Greco-Arab medicine, Darchini and Saleekha (Salikheh) are barks from
two different trees. Salikheh is of reddish color, thick, and a little bitter to taste,
astringent, and when broken it has a fracture like Chinese rhubarb; it comes in long
folded sticks with a small central hollow like kirfah. Kirfah or darchini does not
have the sweetness, and tastes like cloves. Taj or Kalfah is Indian cassia or
cinnamon, which is chiefly the bark of Cinnamomum tamala, C. iners and C. nitidum
and is available in flat or slightly quilled pieces, is thicker than the Chinese bark and
of a deeper color; it has a strong cinnamon odor and taste but is devoid of
sweetness. In India, leaves of C. cassia are called Sazaj-i-Hindi (in Urdu language)
Cinnamomum cassia (L.) J. Presl 631

Fig. 1 Cinnamomum cassia, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Cinnamomum_aromaticum_-_K%
C3%B6hler%E2%80%93s_Medizinal-Pflanzen-039_cropped.jpg

Fig. 2 Cinnamomum cassia, Cinnamon Sticks, Jan Luca and Magnus Manske, WikimediaCom-
mons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cassia_
bark.jpg#filehistory; https://creativecommons.org/licenses/by-sa/3.0/deed.en
632 Cinnamomum cassia (L.) J. Presl

and Tejpat, Tamalpatra or Talisha-pattiri (in Hindi language) and immature

fruits are called Kala Nagkesar.XL Bark of Saleekha is thicker than Darchini
(Figs. 1 and 2).LXIX
Actions and Uses: It is a general stimulant to the nervous and vascular sys-
tems.LXXIX In China, it is known as Rougui or Yugui and is considered hot and
slightly toxic; said to be able to warm and tone up ‘spleen and kidney,’ and is cold-
discutient, analgesic and vascular-deobstruent. It is effective in abdominal and
gastric pain, diarrhea due to asthenia and pathogenic cold, hypofunction of kidney,
rheumatic backache, cough due to pathogenic cold in lungs, amenorrhea, and
abdominal mass.XVIII It is one of the 50 fundamental herbs of TCM [72], and is
used in the treatment of fever, inflammation, chronic bronchitis, and to improve
blood circulation [29, 38]. HsuLXVI mentioned its Chinese names as Kuei-Pi and
Kui-Chih, and described it as a superior drug recorded in The Herbal by Shen Nung.
Dried bark is the main part used, but Cinnamomi (Kuei) Ramulus (Chih), the dried
tender twigs are also used for the same purpose, and to treat menstrual disorders and
hypertension [75]. Other uses include, to regulate pulse, promote sweating, relieve
muscle tension, reduce anxiety, decrease expectoration, as a carminative, to
improve appetite,LXV and to treat diseases resulting from kidney yang deficiency,
including diabetic nephropathy [83]. Bark oil has a specific hyperemic effect on
uterus and has been used since ancient times to induce abortion [30]. Immature
fruits are also widely consumed in China as a food spice, dietary supplements,
flavoring agents, and preservatives [22]. In Unani medicine, aromatic bark (tem-
perament, hot 3° and dry 3°) is considered antiseptic, astringent, analgesic, diuretic,
emmenagogue, expectorant, stomachic, liver tonic, and aphrodisiac; its oil is
externally used alone or in combination with other oils for sexual weakness.LXXVII
Dioscorides and Avicenna described it as anti-inflammatory and astringent, and
recommended it for all internal inflammatory conditions. It is also reported to cause
complete abortion and expel fetus and placenta.LXIX Bark is also an agreeable
carminative, antispasmodic, aromatic stimulant, and germicide, and is used as
adjunct to other medicines. It is hemostatic and has a specific action on uterus, and
is given with other uterine stimulants to promote parturition, and to check uterine
hemorrhage; also used as a remedy for flatulence, nausea, vomiting, diarrhea and
abdominal gripes caused by other drugs. The oil has no astringency and in thera-
peutic doses is good for flatulence, paralysis of tongue, enteralgia, stomach cramps,
and nausea and vomiting.LXXXI
Phytoconstituents: Cinnamon bark contains 1–2% volatile oil, mainly composed of
cinnamaldehyde (also called cinnamic aldehyde) (80–85%) with strong odor (oxi-
dizing rapidly and forming cinnamic acid), eugenol, phellandrene, orthomethyl-
coumaric aldehyde, cinnamyl acetate, phenylpropyl alcohol, cinnamic alcohol
and traces of coumarin,XVIII amygdalactone, 2′-hydroxycinnamaldehyde (2-CNA),
2-methoxycinnamaldehyde, coniferaldehyde, icariside DC, dihydrocinnacasside
[38]; coumacasia, 2-hydroxycinnamic acid [62], diterpenoids, cinncassiols F and G,
16-O-b-D-glucopyranosyl-19-deoxycinncassiol G, and 18-hydroxyperseanol [90],
(E)-2-hydroxyphenylpropionic acid cinnamoyl ester, 3,3′,4,4′-tetrahydroxybiphenyl,
Cinnamomum cassia (L.) J. Presl 633

methylstictic acid, epi-boscialin, (1R,2S,3S,4S)-2,3-epoxy-1,4-dihydroxy-5-methyl-

5-cyelohexene, 4,5-dihydroxy-3-methylcyclohex-2-enone, cis-4-hydroxymellein,
and 2-hydroxy-4-methoxyl-cinnamaldehyde [25], epianhydrocinnzeylanol and
cinnacasiol H [26], phenolic glycoside, methyl 2-phenylpropanoate-2-O-b-
D-apiofuranosyl-(1!6)-O-b-D-glucopyranoside [89], antiulcerogenic compounds,
3-(2-hydroxyphenyl)-propanoic acid and its O-glucoside [80], proanthocyanidins,
cinnamtannin B-1, cinnamtannin D-1, parameritannin A-1 and cassiatannin A [34].
2-CNA is a farnesyl-protein transferase inhibitor [44], and 3-(2-hydroxyphenyl)-
propanoic acid is a very potent antiulcerogenic compound that produces its effect
without reducing gastric acid secretion [80]. Two diterpenoids with unique diterpene
carbon skeleton, cinnamomols A and B were reported from the leaves [93]. Two new
sesquiterpenoids were isolated from Cassia buds [22]. Essential oil contains cin-
namaldehyde, a C. cassia-specific diterpene [50] and major component of essential
oil, 2-CNA [40, 63], coumarin and cinnamyl acetate; 2-CNA is responsible for the
volatile oil flavor [14]. Essential oil extracted from ultramicropowder shows 34 peaks
and the regular powder 19 peaks on GC-MS [55].
Pharmacology: Aqueous bark extract inhibited gastric secretion, promoted gastric
mucosal blood flow, and prevented formation of stress- and serotonin-induced gastric
ulcers in rats and mice [3, 79], and markedly inhibited H. pylori and TNF-a stimu-
lated IL-8 secretion from gastric epithelial cells [88]. Cinnamon powder protected rats
from dimethylnitrosamine-induced liver injury [52]. Twigs EO exhibits significant
analgesic and anti-inflammatory activities, and decreases levels of proinflammatory
cytokines [75]. E-cinnamaldehyde and O-methoxycinnamaldehyde were identified
as the most potent anti-inflammatory constituents in dichloromethane bark extract
[21]. Aqueous extract also exhibited marked antiallergic activity in guinea pigs [41],
anticomplement action and inhibited complement dependent allergic reaction [60],
and markedly stimulated in vitro human lymphocytes proliferation [68].
Insulin-sensitizing effect of cinnamon has been established in in vitro studies with
adipocytes [5, 10, 31], and in vivo animal studies [67]. Aqueous extract lowered
blood glucose of diabetic mice [12, 24, 46], mediated through suppression of iNOS
expression [46]. Cinnamon extract treatment of diabetic mice significantly decreased
blood glucose, TC, and TGs, and increased levels of GSH and activities of liver GR,
GST, GPx, CAT and SOD enzymes, and significantly reduced LPO [36, 37],
decreased body weight, food intake, serum levels of glucose, insulin, and TC, and
prevented oral glucose tolerance and insulin-resistance by increasing energy
expenditure in obese mice [73]. Verspohl et al. [82] reported decrease in blood
glucose only in glucose tolerance test by cinnamon extract and the powder, and
increased plasma insulin in rats. Methanol extract showed very potent a-amylase
inhibitory activity [8], and sesquiterpenoids prevented diabetic nephropathy [83].
However, the decoction showed no effect on elevated serum TC and b-lipoproteins
of hyperlipidemic rats [13].
Aqueous extract significantly inhibited in vitro glutamate-induced calcium influx
and protected against neuronal cell death [71], prevented hippocampal b-amyloid
accumulation and enhanced hippocampal insulin signaling in rats infused with
634 Cinnamomum cassia (L.) J. Presl

b-amyloid into hippocampal CA1 regions [64], and aqueous methanol extract also
protected neuronal cells from b-amyloid protein toxicity [35]. Ethanol extract
produced anxiolytic-like effects in mice through serotonergic and GABA-ergic
systems [85], by region specific change of 5-HT1A receptors in the dorsal raphe
nucleus [33], and a standardized methanol extract exhibited antidepressant activity
with a rise in brain 5-HT levels [87].
Ethanol bark extract improved survival of mice after LPS-induced septic shock,
and inhibited inflammasome activation [72]. Cinnamaldehyde showed significant
anti-inflammatory activity, and increased activities of CAT, SOD, and GPx in the
inflamed paw tissue [51], Methanol extract strongly inhibited COX-2 activity in
LPS-induced mouse macrophages [27]. Oral administration of cassia oil signifi-
cantly reduced serum and hepatic urate levels in hyperuricemic mice, and in a
relatively high dose was as effective as allopurinol, with significant reductions in
liver XDH and XO activities [91]. Methanol extract of the twigs also exhibited
highly significant in vitro XO inhibiting activity [42]. Fractionation revealed cin-
namaldehyde derivatives possessing the XO inhibiting property [61]. Essential oil
inhibited spontaneous, oxytocin-, PGF2a-, and ACh-induced contractions of isolated
mouse uterus [74]. Dichloromethane, ethanol and water extracts exhibited strong
antioxidant activity [9], the activity of ethanol extract was greater than a-tocopherol
[53]; ethanol extract also potently inhibited in vitro AChE and BChE, the dichloro-
methane extract inhibiting the latter by more than 90% [9]. Aqueous extract pro-
tected normal kidney Vero cells from cisplatin toxicity [17], and cinnamic acid was
protective against CP-induced myelosuppression and oxidative stress in mice [65].
Eugenol, amygdalactone, 2-methoxycinnamaldehyde, and coniferaldehyde are
stronger inhibitor of in vitro platelet aggregation than ASA; eugenol and coni-
feraldehyde being the most active [38]. 2-Methoxycinnamaldehyde significantly
improved myocardial dysfunction and decreased infarct size in rats with MI [29].
Oral administration of C. cassia powder to mice significantly increased plasma level
of ANF [92]. Both C. cassia extracts and cinnamaldehyde inhibit adhesion of
TNFa-induced monocytes to human endothelial cells [50].
Ethanol extract significantly inhibited growth of E. coli, P. aeruginosa and
E. faecalis, while acetone extract was inhibitory to K. pneumoniae [69]. Both the EO
and cinnamaldehyde effectively inhibited growth of S. aureus, E. coli, E. aerogenes,
P. vulgaris, P. aeruginosa, V. cholerae, V. parahaemolyticus, S. typhymurium, and
C. albicans, C. tropicalis, C. glabrata, and C. krusei, and Aspergillus spp., Fusarium
sp., and dermatophytes, M. gypseum, T. rubrum and T. mentagraphytes [63].
Essential oil was also active against A. flavus and A. oryzae [40], potentiated in vitro
antifungal effect of amphotericin B against C. albicans [18], and the hyphal growth
and spore formation of A. niger [66]. Oral administration of aqueous hot infusion
improved symptoms and reduced number of viable Candida cells in the oral
cavity of mice [78], due to fungistatic and fungicidal activity of cinnmaldehyde
[77]. Cinnamaldehyde potently inhibited in vitro growth of intestinal bacteria,
C. perfringens and B. fragilis [49]. Sesquiterpenoids isolated from Cassia buds
exhibited potent activity against C. albicans [22]. Buffered methanol and acetone
extracts moderately inhibit growth of B. cereus [4], and an unidentified extract
Cinnamomum cassia (L.) J. Presl 635

completely inhibited growth of epimastigote form of T. cruzi [54]. Hot water extract
was also active against human RSV [84].
Methanol extract in a dose of 100 mg/kg for 28 days, significantly improved sexual
function in aged rats without any significant effect on sperm count and morphology
[20], and of young male rats with an increase in smooth muscle and decrease in
collagen level in rat penile tissue [19]. Aqueous extract, cinnamaldehyde and its
derivatives are also reported to possess in vitro and in vivo anticancer activity [28, 43,
45, 48, 59].
Clinical Studies: Cinnamon supplementation in healthy humans facilitates glucose
utilization [32], and a single 5 g dose of powdered bark significantly lowered peak
blood glucose level in response to a glucose challenge in young, sedentary, obese
women [23]. Cinnamon powder, in a dose of 1–6 g daily for 40-days to type-2
diabetic patients in Pakistan, reduced mean FBG (18–29%), TGs (23–30%), TC
(12–26%) and LDL-C (7–27%) levels [7]. Aqueous extract (high in type A
polyphenols) treatment of women with insulin-resistance associated with the PCOS,
produced improvements in fasting glucose, glucose tolerance and insulin sensitivity.
Individuals with metabolic syndrome also showed improvement in their FBG and
systolic BP [6]. Review of RCTs on type-2 diabetes reported that two trials provided
strong scientific evidence that cassia cinnamon therapeutically reduced FBG
by 10.3–29%, without lowering HbA1c, but one trial did not observe this effect
[16, 39]. Another review and meta-analysis of RCTs, however, reported a significant
decrease in mean HbA1c [2]. A Cochrane Database Systemic Review of 10 RCTs
involving 577 patients with type-1 or type-2 diabetes, where cinnamon was
administered at a mean dose of 2 g daily for a period ranging from 4 to 16-weeks
reported no statistically significant difference in HbA1c, serum insulin or post-
prandial glucose levels compared to control groups [47]. However, a more recent
review of 8 RCTs of patients with type-2 diabetes and treatment-naïve patients with
prediabetes and those with high pretreatment HbA1c, treated with aqueous extract or
powder, in doses ranging from 500 mg to 6 g per day for a duration of 40-days to
4-months, reported improvement in glycemic control in patients receiving cinnamon
as the sole therapy [58]. A modest effect on FBG and HbA1c was reported after
analysis of 11 RCTs where cinnamon was added to standard therapy and other
lifestyle changes [15]. However, twenty-five postmenopausal patients with type-2
diabetes supplemented with cinnamon (1.5 g/d) or placebo for 6-weeks did not show
any significant difference in whole-body insulin sensitivity, oral glucose tolerance or
blood lipid profile [81]. In another study, sixty type-2 diabetic patients randomized
either to 1.5 g/d of cinnamon powder or placebo, along with their standard treatment
(metformin or sulfonylurea) for 12-weeks, did not show any significant difference in
two groups in reducing FBG, HbA1c and serum lipid profile, although the pro-
portion of patients achieving HbA1c < or = 7% was greater in patients receiving
cinnamon [76]. An herbal tea, marketed as Smooth MoveR, was found to signifi-
cantly increase number of bowel movements in nursing home residents with chronic
constipation, during a 28-day study period [11].
636 Cinnamomum cassia (L.) J. Presl

Mechanism of Action: Insulin receptor autophosphorlylation and dephosphoryla-

tion, GLUT-4 receptor synthesis and translocation, modulation of hepatic glucose
metabolism, alteration in PPARc expression, and inhibition of intestinal glucosidases
are all cited mechanisms for the hypoglycemic effect [58]. Choleretic and analgesic
effects have been cited as the pharmacologic basis of spleen-stomach warming, and
analgesic action [94], and the antigout effect is due to XO inhibitory activity. Reduced
production of NO, TNFa, PGE2, and mRNA expression of iNOS, COX-2, and TNF-a
due to suppression of activation of NF-jB in LPS-activated RAW264.7 cells and
peritoneal macrophages by ethanol extract could be the basis for its anti-inflammatory
effect [86]. Cinnamaldehyde exerts its anti-inflammatory effect by blocking degrada-
tion of the inhibitory protein IkappaB-a [50].
Human A/Es, Allergy and Toxicity: Cinnamon is described as a health hazard,
because coumarin in cinnamon is known to cause liver and kidney damage in rats
and mice. Some European health agencies cautioned against consuming high
amounts of cassia due to its high coumarin contents. Cinnamon-containing foods
collected from Italian markets exceeded the maximum allowable level of 2 mg/kg,
fixed in the European Flavorings Directive [56]. In a four-way crossover study, a
dose of 12 mg coumarin was administered in different formulations to 24 healthy
volunteers, coumarin was fast absorbed from cinnamon tea leading to the highest
peak concentrations, followed by coumarin from cinnamon powder that was only
slightly lower than that of isolated coumarin [1].
Animal Toxicity: Intravenous LD50 of the decoction in mice was 18,480 ± 1,800
mg (crude drug)/kg [13].
CYP450 and Potential for Drug-Herb Interactions: Animals treated with the
plant extract have CYP450 content decreased, and levels of glutathione and activity
of glutathione-dependent antioxidant enzymes, GST, GR and GPx increased [70].
Concurrent administration of cinnamon with pioglitazone decreased metabolism of
pioglitazone due to CYP3A4 inhibition, and potentiated its effect [57].
Commentary: Blood glucose and lipids lowering effects are inconsistent and were
achieved, if at all, at relatively high doses; comparatively high animal doses have
been reported to cause liver and kidney damage in rats and mice. Nevertheless, its
use as an adjunct to conventional therapies in patients not achieving their targeted
levels could be considered, that will also require further studies.

References
1. Abraham K, Pfister M, Wöhrlin F, Lampen A. Relative bioavailability of
coumarin from cinnamon and cinnamon-containing foods compared to
isolated coumarin: a four-way crossover study in human volunteers. Mol
Nutr Food Res. 2011;55:644–53.
2. Akilen R, Tsiami A, Devendra D, Robinson N. Cinnamon in glycaemic
control: systematic review and meta analysis. Clin Nutr. 2012;31:609–15.
Cinnamomum cassia (L.) J. Presl 637

3. Akira T, Tanaka S, Tabata M. Pharmacological studies on the antiulcero-

genic activity of Chinese cinnamon. Planta Med. 1986;52:440–3.
4. Alzoreky NS, Nakahara K. Antibacterial activity of extracts from some edible
plants commonly consumed in Asia. Int J Food Microbiol. 2003;80:223–30.
5. Anderson RA, Broadhurst CL, Polansky MM, et al. Isolation and character-
ization of polyphenol type-A polymers from cinnamon with insulin-like
biological activity. J Agric Food Chem. 2004;52:65–70.
6. Anderson RA. Chromium and polyphenols from cinnamon improve insulin
sensitivity. Proc Nutr Soc. 2008;67:48–53.
7. Blevins SM, Leyva MJ, Brown J, et al. Effect of cinnamon on glucose and
lipid levels in noninsulin-dependent type 2 diabetes. Diabetes Care. 2007;
30:2236–7.
8. Boaduo NK, Katerere D, Eloff JN, Naidoo V. Evaluation of six plant species
used traditionally in the treatment and control of diabetes mellitus in South
Africa using in vitro methods. Pharm Biol. 2014;52:756–61.
9. Boğa M, Hacıbekiroğlu I, Kolak U. Antioxidant and anticholinesterase
activities of eleven edible plants. Pharm Biol. 2011;49:290–5.
10. Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological
activity of culinary and medicinal plant aqueous extracts in vitro. J Agric
Food Chem. 2000;48:849–52.
11. Bub S, Brinckmann J, Cicconetti G, Valentine B. Efficacy of an herbal
dietary supplement (Smooth Move) in the management of constipation in
nursing home residents: a randomized, double-blind, placebo-controlled
study. J Am Med Dir Assoc. 2006;7:556–61.
12. Chen L, Sun P, Wang T, et al. Diverse mechanisms of antidiabetic effects of
the different procyanidin oligomer types of two different cinnamon species
on db/db mice. J Agric Food Chem. 2012;60:9144–50.
13. Chen Y et al. Information on medical science and technology, vol 15. Zhuang
Autonomous Region Institute of Materia Medica, Guangxi, p 39;1979
(cited by Chang and But).XVIII
14. Choi J, Lee KT, Ka H, et al. Constituents of the essential oil of the Cinna-
momum cassia stem bark and the biological properties. Arch Pharm Res. 2001;
24:418–23.
15. Costello RB, Dwyer JT, Saldanha L, et al. Do cinnamon supplements have a
role in glycemic control in type 2 diabetes? A narrative review. J Acad Nutr
Diet. 2016;116:1794–802.
16. Dugoua JJ, Seely D, Perri D, et al. From type 2 diabetes to antioxidant
activity: a systematic review of the safety and efficacy of common and
cassia cinnamon bark. Can J Physiol Pharmacol. 2007;85:837–47 (Review)
17. ElKady AI, Ramadan WS. The aqueous extract of cinnamon bark amelio-
rated cisplatin-induced cytotoxicity in vero cells without compromising the
anticancer efficiency of cisplatin. Biomed Pap Med Fac Univ Palacky
Olomouc Czech Repub. 2016;160:363–71.
638 Cinnamomum cassia (L.) J. Presl

18. Giordani R, Regli P, Kaloustian J, Portugal H. Potentiation of antifungal

activity of amphotericin B by essential oil from Cinnamomum cassia. Phyto-
ther Res. 2006;20:58–61.
19. Goswami SK, Inamdar MN, Jamwal R, Dethe S. Effect of Cinnamomum
cassia methanol extract and sildenafil on arginase and sexual function of
young male Wistar rats. J Sex Med. 2014;11:1475–83.
20. Goswami SK, Inamdar MN, Jamwal R, Dethe S. Efficacy of Cinnamomum
cassia Blume. in age induced sexual dysfunction of rats. J Young Pharm.
2013;5:148–53.
21. Gunawardena D, Karunaweera N, Lee S, et al. Anti-inflammatory activity of
cinnamon (C. zeylanicum and C. cassia) extracts—identification of E-cinnam-
aldehyde and o-methoxy cinnamaldehyde as the most potent bioactive
compounds. Food Funct. 2015;6:910–9.
22. Guoruoluo Y, Zhou H, Zhou J, et al. Isolation and characterization of sesqui-
terpenoids from Cassia buds and their antimicrobial activities. J Agric Food
Chem. 2017;65:5614–9.
23. Gutierrez JL, Bowden RG, Willoughby DS. Cassia cinnamon supplemen-
tation reduces peak blood glucose responses but does not improve insulin
resistance and sensitivity in young, sedentary, obese women. J Diet Suppl.
2016;13:461–71.
24. He K, Li X, Chen X, et al. Evaluation of antidiabetic potential of selected
traditional Chinese medicines in STZ-induced diabetic mice. J Ethnophar-
macol. 2011;137:1135–42.
25. He S, Jiang Y, Tu PF. Chemical constituents from Cinnamomum cassia.
Zhongguo Zhong Yao Za Zhi. 2015;40:3598–602 (Chinese).
26. He S, Jiang Y, Tu PF. Three new compounds from Cinnamomum cassia.
J Asian Nat Prod Res. 2016;18:134–40.
27. Hong CH, Hur SK, Oh OJ, et al. Evaluation of natural products on
inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase
(iNOS) in cultured mouse macrophage cells. J Ethnopharmacol. 2002;83:
153–9.
28. Hong SH, Kim J, Kim JM, et al. Apoptosis induction of 2′-hydroxycinnam-
aldehyde as a proteasome inhibitor is associated with ER stress and mitochondrial
perturbation in cancer cells. Biochem Pharmacol. 2007;74:557–65.
29. Hwa JS, Jin YC, Lee YS, et al. 2-Methoxycinnamaldehyde from Cinnamo-
mum cassia reduces rat myocardial ischemia and reperfusion injury in vivo
due to HO-1 induction. J Ethnopharmacol. 2012;139:605–15.
30. Ito H. Folia Pharmacol Japon. 1957;53:627–32.
31. Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived
from cinnamon functions as a mimetic for insulin in 3T3–L1 adipocytes.
J Am Coll Nutr. 2001;20:327–36.
32. Jitomir J, Willoughby DS. Cassia cinnamon for the attenuation of glucose
intolerance and insulin resistance resulting from sleep loss. J Med Food. 2009;
12:467–72.
Cinnamomum cassia (L.) J. Presl 639

33. Jung YH, Kwon SH, Hong SI, et al. 5-HT(1A) receptor binding in the dorsal
raphe nucleus is implicated in the anxiolytic-like effects of Cinnamomum
cassia. Pharmacol Biochem Behav. 2012;103:367–72.
34. Killday KB, Davey MH, Glinski JA, et al. Bioactive A-type proantho-
cyanidins from Cinnamomum cassia. J Nat Prod. 2011;74:1833–41.
35. Kim DS, Kim JY, Han YS. Alzheimer’s disease drug discovery from herbs:
neuroprotectivity from beta-amyloid (1-42) insult. J Altern Complement Med.
2007;13:333–40.
36. Kim SH, Hyun SH, Choung SY. Antioxidative effects of Cinnamomi
cassiae and Rhodiola rosea extracts in liver of diabetic mice. Biofactors.
2006;26:209–19.
37. Kim SH, Hyun SH, Choung SY. Antidiabetic effect of cinnamon extract on
blood glucose in db/db mice. J Ethnopharmacol. 2006;104:119–23.
38. Kim SY, Koo YK, Koo JY, et al. Platelet antiaggregation activities of
compounds from Cinnamomum cassia. J Med Food. 2010;13:1069–74.
39. Kirkham S, Akilen R, Sharma S, Tsiami A. The potential of cinnamon to
reduce blood glucose levels in patients with type 2 diabetes and insulin
resistance. Diabetes Obes Metab. 2009;11:1100–13.
40. Kocevski D, Du M, Kan J, et al. Antifungal effect of Allium tuberosum,
Cinnamomum cassia, and Pogostemon cablin essential oils and their compo-
nents against population of Aspergillus species. J Food Sci. 2013;78:M731–7.
41. Koda A, Katsuda E, Watanabe S, Mizuno T. Antiallergic effect of Chinese
drugs. Folia Pharmacol Jpn. 1970;66:366–78 (Japanese).
42. Kong LD, Cai Y, Huang WW, et al. Inhibition of xanthine oxidase by some
Chinese medicinal plants used to treat gout. J Ethnopharmacol. 2000;73:
199–207.
43. Koppikar SJ, Choudhari AS, Suryavanshi SA, et al. Aqueous cinnamon
extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in
human cervical cancer cell line (SiHa) through loss of mitochondrial mem-
brane potential. BMC Cancer. 2010;10:210.
44. Kwon BM, Cho YK, Lee SH, et al. 2′-Hydroxycinnamaldehyde from stem
bark of Cinnamomum cassia. Planta Med. 1996;62:183–4.
45. Kwon HK, Hwang JS, So JS, et al. Cinnamon extract induces tumor cell
death through inhibition of NFkappaB and AP1. BMC Cancer. 2010;10:392.
46. Kwon KB, Kim EK, Jeong ES, et al. Cortex cinnamomi extract prevents
streptozotocin- and cytokine-induced beta-cell damage by inhibiting NF-
kappaB. World J Gastroenterol. 2006;12:4331–7.
47. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database
Syst Rev. 2012; 9:CD007170.
48. Lee CW, Lee SH, Lee JW, et al. 2-Hydroxycinnamaldehyde inhibits SW620
colon cancer cell growth through AP-1 inactivation. J Pharmacol Sci. 2007;
104:19–28.
640 Cinnamomum cassia (L.) J. Presl

49. Lee HS, Ahn YJ. Growth-inhibiting effects of Cinnamomum cassia bark-
derived materials on human intestinal bacteria. J Agric Food Chem. 1998;
46:8–12.
50. Liao BC, Hsieh CW, Liu YC, et al. Cinnamaldehyde inhibits the tumor
necrosis factor-alpha-induced expression of cell adhesion molecules in endo-
thelial cells by suppressing NF-kappaB activation: effects upon IkappaB and
Nrf2. Toxicol Appl Pharmacol. 2008;229:161–71.
51. Liao JC, Deng JS, Chiu CS, et al. Anti-inflammatory activities of Cinna-
momum cassia constituents in vitro and in vivo. Evid Based Complement
Alternat Med. 2012;2012:429320.
52. Lim CS, Kim EY, Lee HS, et al. Protective effects of Cinnamomum
cassia Blume in the fibrogenesis of activated HSC-T6 cells and dimethyl-
nitrosamine-induced acute liver injury in SD rats. Biosci Biotechnol Bio-
chem. 2010;74:477–83.
53. Lin CC, Wu SJ, Chang CH, Ng LT. Antioxidant activity of Cinnamomum
cassia. Phytother Res. 2003;17:726–30.
54. Lirussi D, Li J, Prieto JM, et al. Inhibition of Trypanosoma cruzi by plant
extracts used in Chinese medicine. Fitoterapia. 2004;75:718–23.
55. Liu L, Liu NY, Liu Q. Analysis on the chemical compositions of the volatile
oil from ultramicro-powder and common grinding powder of Cinnamomum
cassia. Zhong Yao Cai. 2008;31:379–81 (Chinese).
56. Lungarini S, Aureli F, Coni E. Coumarin and cinnamaldehyde in cinnamon
marketed in Italy: a natural chemical hazard? Food Addit Contam Part A
Chem Anal Control Expo Risk Assess. 2008;25:1297–305.
57. Mamindla S, Koganti VSRGP, Ravouru N, Koganti B. Effect of Cinna-
momum cassia on the pharmacokinetics and pharmacodynamics of pioglita-
zone. Curr Clin Pharmacol. 2017;12:41–9.
58. Medagama AB. The glycaemic outcomes of Cinnamon, a review of the
experimental evidence and clinical trials. Nutr J. 2015;14:108.
59. Moon EY, Lee MR, Wang AG, et al. Delayed occurrence of H-ras12V-
induced hepatocellular carcinoma with long-term treatment with cinnamalde-
hydes. Eur J Pharmacol. 2006;530:270–5.
60. Nagai H, Shimazawa T, Matsuura N, Koda A. Immunopharmacological studies
of the aqueous extract of Cinnamomum cassia (CCAq). I. Antiallergic action.
Jpn J Pharmacol. 1982;32:813–22.
61. Ngoc TM, Khoi NM, Ha do T, et al. Xanthine oxidase inhibitory activity of
constituents of Cinnamomum cassia twigs. Bioorg Med Chem Lett. 2012;22:
4625–8.
62. Ngoc TM, Nhiem NX, Khoi NM, et al. A new coumarin and cytotoxic
activities of constituents from Cinnamomum cassia. Nat Prod Commun. 2014;
9:487–8.
63. Ooi LS, Li Y, Kam SL, et al. Antimicrobial activities of cinnamon oil and
cinnamaldehyde from the Chinese medicinal herb Cinnamomum cassia
Blume. Am J Chin Med. 2006;34:511–22.
Cinnamomum cassia (L.) J. Presl 641

64. Park S, Kang S, Kim DS, Moon BR. Agrimonia pilosa Ledeb., Cinna-
momum cassia Blume, and Lonicera japonica Thunb. protect against
cognitive dysfunction and energy and glucose dysregulation by reducing
neuroinflammation and hippocampal insulin resistance in b-amyloid-infused
rats. Nutr Neurosci. 2017;20:77–88.
65. Patra K, Bose S, Sarkar S, et al. Amelioration of cyclophosphamide induced
myelosuppression and oxidative stress by cinnamic acid. Chem Biol Interact.
2012;195:231–9.
66. Pawar VC, Thaker VS. In vitro efficacy of 75 essential oils against Aspergillus
niger. Mycoses. 2006;49:316–23.
67. Qin B, Nagasaki M, Ren M, et al. Cinnamon extract (traditional herb)
potentiates in vivo insulin-regulated glucose utilization via enhancing insulin
signaling in rats. Diabetes Res Clin Pract. 2003;62:139–48.
68. Shan BE, Yoshida Y, Sugiura T, Yamashita U. Stimulating activity of
Chinese medicinal herbs on human lymphocytes in vitro. Int J Immuno-
pharmacol. 1999;21:149–59.
69. Sharma A, Chandraker S, Patel VK, Ramteke P. Antibacterial activity of medi-
cinal plants against pathogens causing complicated urinary tract infections.
Indian J Pharm Sci. 2009;71:136–9.
70. Sharma N, Trikha P, Athar M, Raisuddin S. Inhibition of benzo[a]pyrene-
and cyclophosphamide-induced mutagenicity by Cinnamomum cassia.
Mutat Res. 2001;480–481:179–88.
71. Shimada Y, Goto H, Kogure T, et al. Extract prepared from the bark of
Cinnamomum cassia Blume prevents glutamate-induced neuronal death in
cultured cerebellar granule cells. Phytother Res. 2000;14:466–8.
72. Shin WY, Shim DW, Kim MK, et al. Protective effects of Cinnamomum
cassia (Lamaceae) against gout and septic responses via attenuation of
inflammasome activation in experimental models. J Ethnopharmacol. 2017;
205:173–7.
73. Song MY, Kang SY, Kang A, et al. Cinnamomum cassia prevents high-fat
diet-induced obesity in mice through the increase of muscle energy. Am J
Chin Med. 2017;45:1017–31.
74. Sun L, Liu LN, Li JC, et al. The essential oil from the twigs of Cinna-
momum cassia Presl inhibits oxytocin-induced uterine contraction in vitro
and in vivo. J Ethnopharmacol. 2017;206:107–14.
75. Sun L, Zong SB, Li JC, et al. The essential oil from the twigs of Cinnamomum
cassia Presl alleviates pain and inflammation in mice. J Ethnopharmacol.
2016;194:904–12.
76. Suppapitiporn S, Kanpaksi N, Suppapitiporn S. The effect of Cinnamon
cassia powder in type 2 diabetes mellitus. J Med Assoc Thai. 2006;89
Suppl 3:S200–5.
77. Taguchi Y, Hasumi Y, Abe S, Nishiyama Y. The effect of cinnamaldehyde
on the growth and the morphology of Candida albicans. Med Mol Morphol.
2013;46:8–13.
642 Cinnamomum cassia (L.) J. Presl

78. Taguchi Y, Takizawa T, Ishibashi H, et al. Therapeutic effects on murine

oral candidiasis by oral administration of cassia (Cinnamomum cassia)
preparation. Nihon Ishinkin Gakkai Zasshi. 2010;51:13–21.
79. Tanaka S, Akira T, Tabata M. Pharmacological analysis of the tradi-
tional Chinese prescription “goreisan-ryo”. Yakugakuzasshi. 1984;104:
601–6 (Japanese).
80. Tanaka S, Yoon YH, Fukui H, et al. Antiulcerogenic compounds isolated
from Chinese cinnamon. Planta Med. 1989;55:245–8.
81. Vanschoonbeek K, Thomassen BJ, Senden JM, et al. Cinnamon supple-
mentation does not improve glycemic control in postmenopausal type 2
diabetes patients. J Nutr. 2006;136:977–80.
82. Verspohl EJ, Bauer K, Neddermann E. Antidiabetic effect of Cinnamomum
cassia and Cinnamomum zeylanicum in vivo and in vitro. Phytother Res.
2005;19:203–6.
83. Yan YM, Fang P, Yang MT, et al. Antidiabetic nephropathy compounds
from Cinnamomum cassia. J Ethnopharmacol. 2015;165:141–7.
84. Yeh CF, Chang JS, Wang KC, et al. Water extract of Cinnamomum
cassia Blume inhibited human respiratory syncytial virus by preventing
viral attachment, internalization, and syncytium formation. J Ethnopharma-
col. 2013;147:321–6.
85. Yu HS, Lee SY, Jang CG. Involvement of 5-HT1A and GABAA receptors
in the anxiolytic-like effects of Cinnamomum cassia in mice. Pharmacol
Biochem Behav. 2007;87:164–70.
86. Yu T, Lee S, Yang WS, et al. The ability of an ethanol extract of Cinna-
momum cassia to inhibit Src and spleen tyrosine kinase activity contributes to
its anti-inflammatory action. J Ethnopharmacol. 2012;139:566–73.
87. Zada W, Zeeshan S, Bhatti HA, et al. Cinnamomum cassia: an implication
of serotonin reuptake inhibition in animal models of depression. Nat Prod
Res. 2016;30:1212–4.
88. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and cyto-
protective effects of selected Pakistani medicinal plants in Helicobacter
pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
89. Zeng J, Xue Y, Lai Y, et al. A new phenolic glycoside from the barks
of Cinnamomum cassia. Molecules. 2014;19:17727–34.
90. Zeng J, Xue Y, Shu P, et al. Diterpenoids with immunosuppressive activities
from Cinnamomum cassia. J Nat Prod. 2014;77:1948–54.
91. Zhao X, Zhu JX, Mo SF, et al. Effects of cassia oil on serum and hepatic uric acid
levels in oxonate-induced mice and xanthine dehydrogenase and xanthine
oxidase activities in mouse liver. J Ethnopharmacol. 2006;103:357–65.
92. Zhou L, Chen ZX, Chen JY. Effect of wu lin powder and its ingredients on
atrial natriuretic factor level in mice. Zhongguo Zhong Xi Yi Jie He Za Zhi.
1995;15:36–7 (Chinese).
Cinnamomum cassia (L.) J. Presl 643

93. Zhou L, Tuo Y, Hao Y, et al. Cinnamomols A and B, immunostimulative

diterpenoids with a new carbon skeleton from the leaves of Cinna-
momum cassia. Org Lett. 2017;19:3029–32.
94. Zhu ZP, Zhang MF, Shen YQ, Chen GJ. Pharmacological study on
spleen-stomach warming and analgesic action of Cinnamomum cassia Presl.
Zhongguo Zhong Yao Za Zhi. 1993;18:553–7, 514–5 (Chinese).
Cinnamomum verum J. Presl.
(Lauraceae)

(Syns.: C. zeylanicum Nees.; Laurus cinnamomum L.)

Abstract
The tree is native to Sri Lanka, south India, Seychelles, Martinique, Cayenne,
Jamaica, Brazil and Malagasy Republic. Traditionally the infusion, decoction or
powder of bark is used in India to treat digestive complaints, such as dyspepsia,
flatulency, mild spasms, cramps, diarrhea, and vomiting. In Unani medicine,
leaves are called Tezpaat or Sazaj Hindi, and the bark is called Darchini, and is
regarded cardiorefrigerant, cardiotonic, cardiostimulant, carminative, antiseptic,
antidote and phlegm liquefier (mucolytic). Therapeutic uses in Ayurveda include
mukhasosa, trsna, kanthamukhroga, pinasa, krmiroga, vastiroga, arsa, and
hrdroga. The bark is considered hot and irritating, and is a constituent of many
prescriptions in TCM, and is used as abortifacient and oxytocic, and for the
treatment of dysmenorrhea, adenopathy, rheumatism, dermatosis, dyspepsia,
stroke, tumors, elephantiasis, and trichomonas, yeast, and viral infections; and in
traditional Korean medicine, to improve blood circulation and Yang Qi. In
southern Mexico state of Oaxaca, it is used by the indigenous community to treat
women’s reproductive health problems, and is said to be effective as uteroactive at
level II, also an emmenagogue, and tonic for stomach, intestine and liver; used
externally in neuralgia, toothache and scorpion sting. In Austria, 85% of patients
with type-1 diabetes and 70% with type-2 diabetes are aware of the positive effects
of cinnamon on blood glucose. In Palestine, cinnamon is one of the most
commonly used herbal products used by diabetic patients, especially the
middle-aged and elderly. Cinnamomum contains eugenol, pinene, myristicine,
cinnamaldehyde and camphor; also contains volatile oil, phlobatannins, mucilage,
calcium oxalate and starch. Animal studies showed that cinnamon reduced FBG,
LDL-C and HbA1c, increased HDL-C and circulating insulin levels, and
attenuated diabetes associated weight loss and metabolic derangements, with

Both Cinnamomum cassia and C. zeylanicum have identical properties, and share the same Indian
vernacular names.

© Springer Nature Switzerland AG 2020 645

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_68
646 Cinnamomum verum J. Presl.

beneficial effects on diabetic neuropathy and nephropathy. Six-gram cinnamon

with rice pudding reduced postprandial blood glucose and delayed gastric
emptying without affecting satiety in healthy Swedish volunteers, and ingestion of
3 g cinnamon by healthy subjects reduced postprandial serum insulin and
increased GLP-1 concentrations, without significantly affecting blood glucose,
ghrelin, satiety, or gastric emptying rate.

Keywords



Caneleira Ceylonzimtbaum Cū mài guì
Dalchini
Darchini
Kanel




Qarfah Skořice True cinnamon Tvak

Vernaculars: Urd.: Darchini; Hin.: Dalchini, Dalcini; San.: Darusita, Gudatvak,

Tanutvak, Tvak, Varanga, Utkata; Ben.: Dalchini, Darchini, Daruchini, Qalami-
darchini; Guj.: Tuj; Mal.: Elavangam, Erikkoloam, Ilavarngathely, Kauva, Karu-
vapatta, Llavangam, Vayana, Vazhana; Mar.: Dalchini; Tam.: Cannalavanagpattai,
Ilayangam, Karuva, Karuvapattai, Lavangapattai, Llavangam; Tel.: Aakerpatri,
Dalchini, Dalchini chekka, Dalcini, Dasini chekka, Lavangapatta, Sanna lavanga;
Ara.: Darseeni, Qarfah, Qirfah, Qurfa; Bur.: Thit-ja-bo-gauk; Chi.: 锡兰肉桂, Cū
mài guì, Xi lan rou gui; Cze.: Skořice; Dan.: Kanel; Dut.: Kaneel, Kaneelboom;
Eng.: Ceylon cinnamon, True cinnamon; Fin.: Aitokaneli, Ceyloninkaneli, Kaneli,
Kanelipuu; Fre.: Arbre à cannelle, Cannelle, Cannelle de Ceylan; Ger.:
Ceylon-zimt, Ceylonzimtbaum, Echter zimt, Kaneelbaum, Zimt; Gre.: Kanela,
Keÿlanes, Kinnamomom; Ind.: Kayu manis; Ita.: Albero della cannella, Canella di
Ceylon; Jap.: Nikkei, Seiron-nikkei; Kor.: Gye, Kyepi; Maly.: Kayu manis; Nor.:
Kanel; Pol.: Cynamon cejloński; Por.: Canela, Caneleira, Caneleira-da-índia; Rus.:
Cejlonskaâ korica, Korichnik tsyelonskii; Sin.: Curruva pattai, Kurundu; Spa.:
Canelero, Palo de la canela; Swe.: Äkta kanel, Ceylonkanel; Tag.: Kanela,
Kaliñgag, Kaliñgak, Makaliñgag, Samiling, Similing; Tha.: Op choei thet; Tur.:
Darçın, Tarcin, Tarçın ağacı; Vie.: Quế rành.
Description: It is native to Sri Lanka, south India, Seychelles, Martinique, Cayenne,
Jamaica, Brazil and Malagasy Republic. The tree is propagated from seeds which are
sown in bed and later transplanted. It reaches a height of 12–20 m. Leaves are leathery,
shining, oval or oval-lanceolate, 8–15 cm long and pointed at both ends; flowers are
numerous, pale-yellow, small and covered outside with grayish hairs.CXVII In the
second or third year after planting, the trees are coppiced to induce formation of
shoots, of which only 5 or 6 are allowed to grow for about two years or until the bark
begins to turn brown by formation of corky layer. The shoots will then be 2–2.5 m
high and 1–5 cm in diameter and are ready for harvesting. It is also referred to as
Ceylon cinnamon or true cinnamon (Figs. 1 and 2).
Actions and Uses: Bark is carminative, antispasmodic, aromatic, stimulant, hemo-
static, astringent, antiseptic and antibacterial. Traditionally the infusion, decoction or
powder of bark is used in India to treat digestive complaints, such as dyspepsia,
flatulency, mild spasms, cramps, diarrhea, and vomiting [74].CV In Unani medicine,
Cinnamomum verum J. Presl. 647

Fig. 1 Cinnamomum verum, Cinnamon Leaves, Germany, H. Zell, WikimediaCommons; Share-

Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cinnamomum_verum_
002.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Cinnamomum verum, Cinnamon Bark, Prof. Akbar, Original

648 Cinnamomum verum J. Presl.

leaves are called Tezpaat or Sazaj Hindi, and the bark is called Darchini (tempera-
ment, hot 3° and dry 3°), and is regarded cardiorefrigerant, cardiotonic, cardiostim-
ulant, carminative, antiseptic, antidote and phlegm liquefier (mucolytic). Darchini
(3 g) boiled in water and administered with honey relieves acute coryza, and the oil,
combined with other oils, is used for external massage.1 Therapeutic uses in Ayurveda
include mukhasosa, trsna, kanthamukhroga, pinasa, krmiroga, vastiroga, arsa, and
hrdroga.LVIII The bark is considered hot and irritating, and is a constituent of many
prescriptions in TCM [50], and is used as abortifacient and oxytocic, and for the
treatment of dysmenorrhea, adenopathy, rheumatism, dermatosis, dyspepsia, stroke,
tumors, elephantiasis, and trichomonas, yeast, and viral infections [21]; and in tra-
ditional Korean medicine, to improve blood circulation and Yang Qi [24]. Cinnamon
is also used in traditional medicines for nervous stress, as nervine tonic and a stimulant
[57]. In southern Mexico state of Oaxaca, it is used by the indigenous community to
treat women’s reproductive health problems, and is said to be effective as uteroactive
at level II [73], also an emmenagogue, and tonic for stomach, intestine and liver; used
externally in neuralgia, toothache and scorpion sting. Oil distilled from leaves and
twigs is employed as stomachic, carminative and germicide.XXIV,CXXXXI In the
Philippines, bark is used to help digestion, relieve flatulence, and as expectorant; its
rubefacient property is utilized as a remedy for headache and rheumatism.CXVII In Sri
Lankan traditional medicine, cinnamon is used as a remedy for respiratory, digestive
and gynecological ailments [88]. In Austria, 85% of patients with type-1 diabetes and
70% with type-2 diabetes are aware of the positive effects of cinnamon on blood
glucose [31]. In Palestine, cinnamon is one of the most commonly used herbal
products used by diabetic patients, especially the middle-aged and elderly [2].
Phytoconstituents: Cinnamomum contains eugenol, pinene, myristicine, cinnam-
aldehyde and camphor;XI,XXIV,LXI also contains 0.8–1.4% volatile oil, phlobatan-
nins, mucilage, calcium oxalate and starch. Oil of cinnamon contains 60–75%
(w/w) cinnamaldehyde, small amounts of cinnamic acid, and cinnamyl acetate;
genuine oil also contains 4 to 10% phenols (chiefly eugenol), hydrocarbons, pinene,
phellandrene and caryophyllene, and small quantities of ketones, alcohols and
esters.CXI Bark oil from India was reported to contain 13 components accounting
for 100% of the total amount; E-cinnamaldehyde being the major component along
with d-cadinene (0.9%) [101]; whereas, eugenol, E-cinnamaldehyde and linalool,
constituting 82.5% of the oil were main components of bark EO from Italy [23].
Oil from Turkey contained nine constituents representing 99.24% of the oil;
major compounds being E-cinnamaldehyde (68.95%), benzaldehyde (9.94%) and
E-cinnamyl acetate (7.44%) [113]. Trans-cinnamaldehyde (72.81%), benzyl alcohol
(12.5%) and eugenol (6.57%) were major compounds of oil from Malaysia [123].
Cinnamon extracts yields in petroleum ether, chloroform and ethanol were reported
to be 4%, 1.474% and 14.21%, respectively [112].
Pharmacology: Animal studies showed that cinnamon reduced FBG, LDL-C and
HbA1c, increased HDL-C and circulating insulin levels, and attenuated diabetes

1
Tayyab M: Personal communication.
Cinnamomum verum J. Presl. 649

associated weight loss and metabolic derangements, with beneficial effects on

diabetic neuropathy and nephropathy [15, 86], decreased gene expression of PEPCK
and G-6-Pase, two major regulators of hepatic gluconeogenesis [22], reduced food
intake, and improved lipid parameters [48, 52, 87], effectively inhibited in vitro
pancreatic a-amylase [9, 16], BChE [9], and intestinal a-glucosidase of diabetic rats
[67], upregulated uncoupling protein-1 and GLUT4 in brown adipose tissues and
muscles [99], and prevented dexamethasone-induced dyslipidemia, atherogenicity
and aortic thickening [69]. Cinnamon added to high-fat/high-fructose diet highly
significantly increased liver glycogen in rats [26], and cinnamon extract supple-
mented in water greatly improved FBG, glucose tolerance, brain insulin sensitivity,
brain activity, and insulin-stimulated locomotor activity in obese and insulin-
resistant mice [96]. Cinnamon oil supplementation also significantly decreased FBG,
plasma C-peptide, TGs, TC and BUN levels, and significantly increased serum
HDL-C of diabetic mice [79]. Essential oil from India, that contained more than 98%
cinnamaldehyde, significantly reduced FBG and protected against diabetic
nephropathy [66]. Cinnamaldehyde significantly decreased blood glucose, HbA1c,
TC, and TGs, and markedly increased plasma insulin, hepatic glycogen and HDL-C
of diabetic rats [108].
While cinnamon in diet of normal and hypercholesterolemic rats did not show
any cholesterol lowering effect [94], methanol extract markedly lowered TC (32%),
LDL-C (75%) and TGs (38%), and increased HDL-C (58%) of L-NAME-induced
hypertensive rats [72]. Highly significant decrease was observed in total lipids,
TGs, TC and LDL-C, and a significant increase in HDL-C by bark powder and
equivalent dose of methanol extract in rabbits [43]. Cinnamon supplementation
significantly reduced systolic BP of SHR on normal and sucrose containing diets,
lowered circulating insulin without affecting blood glucose [81]. Intravenous
injection of aqueous and methanol extracts also produced significant fall in MAP in
normotensive rats, salt-loaded hypertensive, L-NAME hypertensive and SHRs;
pretreatment with L-NAME, propranolol or atropine inhibited BP lowering effect
[71, 72]. Ethanol extract significantly reduced acute alcohol-induced hepatic lipid
accumulation [45], and protected liver against CC14-induced LPO and hepatic
injury, and elevated antioxidant enzymes activities in rats [68].
Pretreatment of rats with cinnamon extract significantly reversed scopolamine-,
diabetes- and monosodium glutamate-induced memory impairment, improved
cognitive performance, reversed alteration in AChE, decreased oxidative stress and
brain MDA level, and increased glutathione level of rats [42, 56, 57, 63]. Ethanol
extract exhibited antinociceptive effect in mice [11], and aqueous extract to mice
significantly prevented increase in serum levels of LPS-induced TNF-a and IL-6,
which was attributed to the presence of high levels of polyphenols in the extract
[40]. Polyphenolic fraction demonstrated prominent action in animal models of
inflammation and arthritis [91]. Ethanol extract also significantly enhanced wound
healing in rats [44]. Anti-inflammatory activity and 100% inhibitory activity
of COX-2 by cinnamon is maintained in uncooked, cooked or digested forms
[13]. E-cinnamaldehyde and O-methoxycinnamaldehyde were identified as the
most active anti-inflammatory compounds [35]. Cinnamon extract also decreased
650 Cinnamomum verum J. Presl.

expression of mast cell-specific mediators of allergy and inflammatory reactions

in vitro and in vivo [37]. Ether, methanol and water extracts sequentially extracted
showed significant antioxidant activity [58]. Essential oil and eugenol were also
powerful antioxidant, but E-cinnamaldehyde and linalool were reported completely
inactive [23].
Cuminaldehyde and 2-methoxycinnamaldehyde suppressed proliferation, and
induced apoptosis of human lung adenocarcinoma and hepatocellular carcinoma
cells, suppressed nuclear transcription factors NF-jB, COX-2, PGE2, and down-
regulated both topoisomerase I & II, as well as telomerase activities [21, 77, 122].
Both petroleum ether and chloroform extracts showed cytotoxic effects on L1210
system [25], and methanol extract demonstrated moderate in vitro antioxidant
activity [109]. Leaf and bark EOs in vitro inhibited hyphal growth and spore for-
mation of A. niger [76], exhibited strong bactericidal activity against P. acnes, and
also strong cytotoxicity to human lung carcinoma, prostate carcinoma and breast
cancer cells [126]. Ethyl acetate, acetone and methanol bark extracts exhibit
various degrees of growth inhibitory activity against K. pneumonia, P. aeroginosa,
S. aureus, E. coil, C. xerosis, and S. faecalis [46], Ethanol extract was bactericidal to
clinical isolates of MRSA [59], and to E. faecalis [36], strongly active against
gentamicin-resistant clinical isolates of enterococcal strains [92], against P. acne and
S. epidermidis [20]. Alcohol extract also showed good anthelmintic activity against
A. lumbricoides [85], and clinical isolates of M. catarrhalis [90]. Cinnamon powder
exhibited significant activity against fluconazole-resistant and -susceptible Candida
isolates [83], against food-borne pathogens, such as S. enterica serovar typhimurium,
E. coli, L. monocytogenes, S. aureus and B. cereus [41], but fluconazole-resistant
C. albicans and Candida nonalbicans were less susceptible to EO than fluconazole-
susceptible organisms [80]. Methanol extract was bactericidal to E. coli [117], and
methylene chloride extract inhibited growth of H. pylori at concentration range of
common antibiotics, while ethanol extract counteracted its urease activity [110].
Essential oil also possesses strong antibacterial and antifungal activities [113],
against isolates belonging to Staphylococcus, Enterococcus, Enterobacter and
Acinetobacter genera [115], against S. aureus, E. coli, S. mutans, L. acidophilus, and
C. albicans [65], K. pneumoniae, and Y. enterocolitica [5], bactericidal to E. coli [97,
123], synergistic with piperacillin against MDR E. coli [123], and with amikacin
against Acinetobacter species [34], enhanced bactericidal activity of clindamycin for
a toxicogenic strain of C. difficile [98], against sensitive and antibiotic-resistant
strains of H. ducreyi [54]. Essential oil also exhibited strong antifungal activity
against food poisoning, spoilage fungi, plant and animal pathogens [100], bacte-
riostatic activity for A. flavus, A. parasiticus, A. ochraceus and F. moniliforme [105],
dermatophytes [53], and bactericidal against M. hominis clinical isolates [104].
Cinnamaldehyde was fungicidal to A. niger, A. fumigatus, A. nidulans, A. flavus, C.
albicans, C. tropicalis, C. pseudotropicalis and H. capsulatum [102].
Aqueous extract normalized testosterone-induced changes in prostate gland of
rats [24]. Cinnamon bark oil for ten-weeks significantly improved testicular
Cinnamomum verum J. Presl. 651

oxidant-antioxidant balance and sperm quality [124], and protected male repro-
ductive organs against CCl4-[125] and taxanes-induced damage in rats [95].
Clinical Studies: Six-gram cinnamon with rice pudding reduced postprandial
blood glucose and delayed gastric emptying without affecting satiety in healthy
Swedish volunteers, and ingestion of 3 g cinnamon by healthy subjects reduced
postprandial serum insulin and increased GLP-1 concentrations, without signifi-
cantly affecting blood glucose, ghrelin, satiety, or gastric emptying rate [38, 39].
A single 3 g dose also did not change gastric emptying, postprandial triacylglycerol,
glucose, or appetite after a high fat meal in healthy young volunteers [61], but
supplementation of 3 g/day to eight male volunteers for 14-days reduced response
to OGTT and improved insulin sensitivity; the response was lost after cessation of
cinnamon intake [107]. At University of Birmingham, single dose of 5 g to seven
lean healthy male volunteers, showed reduced total plasma glucose responses to
oral glucose ingestion and improved insulin sensitivity [106]. Aqueous extract, 500
mg daily for 12-weeks to individuals with impaired FBG and BMI ranging from
25 to 45, improved their antioxidant status [93]. Eight-weeks intake of cinnamon
(3 g/d) by Iranian T2DM patients had no significant effect on blood glucose or BP
[12]; even three-months intake of 1 g/d by T2DM patients in the US showed no
significant difference in blood glucose, lipids, HbA1c or insulin from placebo [17].
However, daily consumption of 1–6 g cinnamon for forty-days reduced mean FBG
(18–29%), TG (23–30%), TC (12–26%) and LDL-C (7–27%) in Pakistani T2DM
patients, compared to 30 patients treated with placebo [47]. Another double-blind
RCT from Germany reported significant reduction in FBG, but no significant
change in HbA1c and lipid profiles of 79 T2DM patients, after supplementation of
their oral antidiabetics with cinnamon aqueous extract (equivalent of 3 g cinnamon)
daily for 4-months; patients with higher initial plasma glucose had more reduction
[60]. Crawford [27], however, reported that cinnamon 1 g daily for 90-days to
adults with T2DM at a US military base lowered HbA1c 0.83% compared with
0.37% reduction with usual care alone. In Chinese T2DM patients, cinnamon
extract at 120 and 360 mg/d significantly reduced both HbA1c and FBG levels; and
blood TGs were significantly decreased only in the low-dose group [55]. Daily
cinnamon (1,500 mg) to Iranian patients with nonalcoholic fatty liver for 12-weeks
significantly decreased FBG, TC, LDL-C, TGs, serum transaminases, and CRP
[10]. Systolic BP also declined of diabetic adults after 12-weeks of treatment with
1,200 mg/day cinnamon [119]. In a double-blinded RCT, supplementation with
cinnamon (1 g/day) of 72 adolescents with T1DM for 90-days did not significantly
affect HbA1c or total daily intake of insulin [6]. In a Netherland study, 25 post-
menopausal T2DM patients with BMI of >30, treated with 1.5 g cinnamon or
placebo daily for 6-weeks showed no significant difference in whole-body insulin
sensitivity, glucose tolerance or lipid profile of the two groups [116]. However,
fifteen women with PCOS randomized to daily oral cinnamon or placebo for
8-weeks at Columbia University showed significant reductions in insulin resistance
in cinnamon group [120]. Meta-analysis of eight RCTs showed that cinnamon
powder or cinnamon extract intake significantly lowers FBG [28], and another
652 Cinnamomum verum J. Presl.

meta-analysis of RCTs involving 543 patients with T2DM also reported significant
reduction in FBG, TC, LDL-C, and TGs, increased levels of HDL-C, but no signi-
ficant effect on HbA1c [4]. RCTs reporting negative beneficial effects of cinnamon
are suggested to involve patients with controlled blood glucose on adequate amount
of antidiabetic drugs and normal or near normal HbA1c levels; a meta-analysis of
these studies would likely show no additional benefits of cinnamon, such as
reported by Baker et al. [14] and Blevins et al. [17].
A commercially available cinnamon preparation used for one week improved
oral candidiasis in three out of five HIV patients [83]. Cinnamon alcohol extract in a
dose of 80 mg/day for 4-weeks to patients infected with H. pylori was ineffective in
eradicating H. pylori [70].
Mechanism of Action: Cinnamon improves insulin-resistance by preventing and
reversing impairment in insulin signaling in skeletal muscles; in adipose tissue,
cinnamon increases expression of PPARc, comparable to PPAR agonists, thiazo-
lidinediones [84]. Aqueous cinnamon extract potentiates in vitro insulin activity
more than 20-fold [18], which is not dependent on cinnamaldehyde [82], and
cinnamon oil and its major components, cinnamaldehyde, cinnamic acid, eugenol,
and coumarin do not possess in vitro insulin-enhancing activity [7], but chromium
and polyphenols in cinnamon are reported to improve insulin sensitivity [8].
Uterine stimulant activity is due to the presence of camphor [32]. Both eugenol and
myristicin are potentially active either as MAO inhibitors or via conversion to NE
analogs, and inhibit PG synthesis [89], which is probably responsible for their
effectiveness in dysmenorrhea, as inhibitors of PGs biosynthesis are used for the
treatment of dysmenorrhea.LII Cinnamaldehyde and myristicin are also spasmolytic
[1, 118], and its astringent property is due to the presence of tannins.CXXXIX
Abuse Potential: Young males aged 11–16 years abuse cinnamon oil by sucking
on toothpicks or fingers dipped in cinnamon oil, experiencing a rush or sensation of
warmth, facial flushing, and oral burning. Nausea or abdominal pain was felt by
some users, but no systemic effects were reported [78].
Human A/Es, Allergy and Toxicity: Workers in Sri Lanka exposed to cinnamon
dust containing cinnamaldehyde, developed skin irritation, loss of hair, smarting of
eyes at work and pulmonary asthma; loss of weight was found in 65% of the
workers examined [114]. Some patients were reported sensitive to cinnamonalde-
hyde in toothpaste [49, 51], others developed oral mucosal reactions and orofacial
granulomatosis due to the presence of cinnamaldehyde in food or flavorings [3, 29,
30, 64, 75, 103, 111]. A 24-year-old American woman developed a squamous cell
carcinoma of the tongue following persistent and prolonged use of cinnamon-
flavored gum [121]. Skin allergies [27, 33], and generalized systemic allergic
dermatitis in a Belgian person after using a herbal tea containing cinnamon [62]
have been reported; it may also exacerbate rosacea [19].
Animal toxicity: Oral LD50 of ethanol bark extract in rats was reported as
2,000 mg/kg [44].
Cinnamomum verum J. Presl. 653

Commentary: Despite inconsistencies in the blood and lipid lowering effects of

cinnamon, and the high doses to achieve any significant results, these generally
positive findings in individuals of various ethnicities deserve more investigations on
cinnamon to find the causes of variations. In most of these studies, chemical
constituents of the products used were either not determined or not reported.
Chemical constituents of herbal drugs could vary significantly due to various fac-
tors, which, in turn, can cause discrepencies in the results obtained. These variables
must be identified to establish causes for variations. Also, the influence of initial
blood glucose, HbA1c, and lipid levels, and any simultaneous use of conventional
medicines be determined to draw a conclusion.

References
1. Achterrath-Tuckermann U, Kunde R, Flaskamp E, Isaac O, Thiemer K.
Pharmacological investigations with compounds of chamomile. V. Inves-
tigations on the spasmolytic effect of compounds of chamomile and
Kamillosan on the isolated guinea pig ileum. Planta Med. 1980;39:38–50
(German).
2. Ali-Shtayeh MS, Jamous RM, Jamous RM. Complementary and alterna-
tive medicine use amongst Palestinian diabetic patients. Complement Ther
Clin Pract. 2012;18:16–21.
3. Allen CM, Blozis GG. Oral mucosal reactions to cinnamon-flavored
chewing gum. J Am Dent Assoc. 1988;116:664–7.
4. Allen RW, Schwartzman E, Baker WL, Coleman CI, Phung OJ. Cinnamon
use in type 2 diabetes: an updated systematic review and meta-analysis.
Ann Fam Med. 2013;11:452–9.
5. Al-Mariri A, Safi M. In vitro antibacterial activity of several plant extracts and
oils against some Gram-negative bacteria. Iran J Med Sci. 2014;39:36–43.
6. Altschuler JA, Casella SJ, MacKenzie TA, Curtis KM. The effect of
cinnamon on A1C among adolescents with type 1 diabetes. Diabetes Care.
2007;30:813–6.
7. Anderson RA, Broadhurst CL, Polansky MM, et al. Isolation and charac-
terization of polyphenol type-A polymers from cinnamon with insulin-like
biological activity. J Agric Food Chem. 2004;52:65–70.
8. Anderson RA. Chromium and polyphenols from cinnamon improve
insulin sensitivity. Proc Nutr Soc. 2008;67:48–53.
9. Arachchige SPG, Abeysekera WPKM, Ratnasooriya WD. Antiamylase,
anticholinesterases, antiglycation, and glycation reversing potential of bark
and leaf of Ceylon cinnamon (Cinnamomum zeylanicum Blume) in vitro.
Evid Based Complement Alternat Med. 2017;2017:5076029.
10. Askari F, Rashidkhani B, Hekmatdoost A. Cinnamon may have therapeutic
benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity
C-reactive protein in nonalcoholic fatty liver disease patients. Nutr Res.
2014;34:143–8.
654 Cinnamomum verum J. Presl.

11. Atta AH, Alkofahi A. Antinociceptive and anti-inflammatory effects of

some Jordanian medicinal plant extracts. J Ethnopharmacol. 1998;60:
117–24.
12. Azimi P, Ghiasvand R, Feizi A, et al. Effect of cinnamon, cardamom,
saffron and ginger consumption on blood pressure and a marker of
endothelial function in patients with type 2 diabetes mellitus: a randomized
controlled clinical trial. Blood Press. 2016;25:133–40.
13. Baker I, Chohan M, Opara EI. Impact of cooking and digestion, in vitro,
on the antioxidant capacity and anti-inflammatory activity of cinnamon,
clove and nutmeg. Plant Foods Hum Nutr. 2013;68:364–9.
14. Baker WL, Gutierrez-Williams G, White CM, Kluger J, Coleman CI.
Effect of cinnamon on glucose control and lipid parameters. Diabetes Care.
2008;31:41–3.
15. Bandara T, Uluwaduge I, Jansz ER. Bioactivity of cinnamon with special
emphasis on diabetes mellitus: a review. Int J Food Sci Nutr. 2012;63:380–6.
16. Beejmohun V, Peytavy-Izard M, Mignon C, et al. Acute effect of Ceylon
cinnamon extract on postprandial glycemia: alpha-amylase inhibition,
starch tolerance test in rats, and randomized crossover clinical trial in
healthy volunteers. BMC Complement Altern Med;14:351.
17. Blevins SM, Leyva MJ, Brown J, et al. Effect of cinnamon on glucose and
lipid levels in non insulin-dependent type 2 diabetes. Diabetes Care. 2007;30:
2236–7.
18. Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological
activity of culinary and medicinal plant aqueous extracts in vitro. J Agric
Food Chem. 2000;48:849–52.
19. Campbell TM, Neems R, Moore J. Severe exacerbation of rosacea induced
by cinnamon supplements. J Drugs Dermatol. 2008;7:586–7.
20. Chaudhary SS, Tariq M, Zaman R, Imtiyaz S. The in vitro antiacne activity
of two Unani drugs. Anc Sci Life. 2013;33:35–8.
21. Chen TW, Tsai KD, Yang SM, et al. Discovery of a novel anticancer agent
targeting both topoisomerase I & II as well as telomerase activities in
human lung adenocarcinoma A549 cells in vitro and in vivo: Cinnamo-
mum verum component cuminaldehyde. Curr Cancer Drug Targets. 2016;16:
796–806.
22. Cheng DM, Kuhn P, Poulev A, et al. In vivo and in vitro antidiabetic
effects of aqueous cinnamon extract and cinnamon polyphenol-enhanced
food matrix. Food Chem. 2012;135:2994–3002.
23. Chericoni S, Prieto JM, Iacopini P, et al. In vitro activity of the essential oil
of Cinnamomum zeylanicum and eugenol in peroxynitrite-induced oxida-
tive processes. J Agric Food Chem. 2005;53:4762–5.
24. Choi HM, Jung Y, Park J, et al. Cinnamomi cortex (Cinnamomum verum)
suppresses testosterone-induced benign prostatic hyperplasia by regulating
5a-reductase. Sci Rep. 2016;6:31906.
Cinnamomum verum J. Presl. 655

25. Chulasiri MU, Picha P, Rienkijkan M, Preechanukool K. The cytotoxic

effect of petroleum ether and chloroform extracts from Ceylon cinnamon
(Cinnamomum zeylanicum Ness) barks on tumor cells in vitro. Int J Crude
Drug Res. 1984;22:177–80.
26. Couturier K, Qin B, Batandier C, et al. Cinnamon increases liver glycogen
in an animal model of insulin resistance. Metabolism. 2011;60:1590–7.
27. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1c in
patients with type 2 diabetes: a randomized, controlled trial. J Am Board
Fam Med. 2009;22:507–12.
28. Davis PA, Yokoyama W. Cinnamon intake lowers fasting blood glucose:
meta-analysis. J Med Food. 2011;14:884–9.
29. Endo H, Rees TD. Cinnamon products as a possible etiologic factor in
orofacial granulomatosis. Med Oral Patol Oral Cir Bucal. 2007;12:E440–4.
30. Endo H, Rees TD. Clinical features of cinnamon-induced contact stomatitis.
Compend Contin Educ Dent. 2006;27:403–9.
31. Fabian E, Töscher S, Elmadfa I, Pieber TR. Use of complementary and
alternative medicine supplements in patients with diabetes mellitus. Ann
Nutr Metab. 2011;58:101–8.
32. Farnsworth NR, Bingel AS, Cordell GA, Crane FA, Fong HS. Potential
value of plants as sources of new antifertility agents I & II. J Pharmaceut
Sci. 1975;64:717–54.
33. Goh CL, Ng SK. Bullous contact allergy from cinnamon. Derm Beruf
Umwelt. 1988;36:186–7.
34. Guerra FQ, Mendes JM, Sousa JP, et al. Increasing antibiotic activity
against a multidrug-resistant Acinetobacter spp. by essential oils of Citrus
limon and Cinnamomum zeylanicum. Nat Prod Res. 2012;26:2235–8.
35. Gunawardena D, Karunaweera N, Lee S, et al. Anti-inflammatory activity
of cinnamon (C. zeylanicum and C. cassia) extracts—identification of
E-cinnamaldehyde and O-methoxycinnamaldehyde as the most potent
bioactive compounds. Food Funct. 2015;6:910–9.
36. Gupta A, Duhan J, Tewari S, et al. Comparative evaluation of antimicrobial
efficacy of Syzygium aromaticum, Ocimum sanctum and Cinnamomum
zeylanicum plant extracts against Enterococcus faecalis: a preliminary
study. Int Endod J. 2013;46:775–83.
37. Hagenlocher Y, Bergheim I, Zacheja S, et al. Cinnamon extract inhibits
degranulation and de novo synthesis of inflammatory mediators in mast
cells. Allergy. 2013;68:490–7.
38. Hlebowicz J, Darwiche G, Björgell O, Almér LO. Effect of cinnamon on
postprandial blood glucose, gastric emptying, and satiety in healthy subjects.
Am J Clin Nutr. 2007;85:1552–6.
39. Hlebowicz J, Hlebowicz A, Lindstedt S, et al. Effects of 1 and 3 g cinnamon
on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-
dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin
concentrations in healthy subjects. Am J Clin Nutr. 2009;89:815–21.
656 Cinnamomum verum J. Presl.

40. Hong JW, Yang GE, Kim YB, et al. Anti-inflammatory activity of cinnamon
water extract in vivo and in vitro LPS-induced models. BMC Complement
Altern Med. 2012;12:237.
41. Hong YJ, Bae YM, Moon B, Lee SY. Inhibitory effect of cinnamon
powder on pathogen growth in laboratory media and oriental-style rice
cakes (sulgidduk). J Food Prot. 2013;76:133–8.
42. Jain S, Sangma T, Shukla SK, Mediratta PK. Effect of Cinnamomum
zeylanicum extract on scopolamine-induced cognitive impairment and
oxidative stress in rats. Nutr Neurosci. 2015;18:210–6.
43. Javed I, Faisal I, Rahman Z, et al. Lipid lowering effect of Cinnamomum
zeylanicum in hyperlipidaemic albino rabbits. Pak J Pharm Sci. 2012;25:141–7.
44. Kamath JV, Rana AC, Chowdhury AR. Prohealing effect of Cinnamomum
zeylanicum bark. Phytother Res. 2003;17:970–2.
45. Kanuri G, Weber S, Volynets V, et al. Cinnamon extract protects against
acute alcohol-induced liver steatosis in mice. J Nutr. 2009;139:482–7.
46. Keskin D, Toroglu S. Studies on antimicrobial activities of solvent extracts
of different spices. J Environ Biol. 2011;32:251–6.
47. Khan A, Safdar M, Ali Khan MM, et al. Cinnamon improves glucose and
lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215–8.
48. Kim SH, Hyun SH, Choung SY. Antidiabetic effect of cinnamon extract on
blood glucose in db/db mice. J Ethnopharmacol. 2006;104:119–23.
49. Kirton V, Wilkinson DS. Sensitivity to cinnamic aldehyde in a toothpaste.
2. Further studies. Contact Dermatitis. 1975;1:77–80.
50. Kong YC, Hu SY, Lau FK, et al. Potential antifertility plants from Chinese
medicine. Am J Chinese Med. 1976;3:105–28.
51. Lamey PJ, Lewis MA, Rees TD, et al. Sensitivity reaction to the
cinnamonaldehyde component of toothpaste. Br Dent J. 1990;168:115–8.
52. Li J, Liu T, Wang L, et al. Antihyperglycemic and antihyperlipidemic
action of cinnamaldehyde in C57BLKS/J db/db mice. J Tradit Chin Med.
2012;32:446–52.
53. Lima EO, Gompertz OF, Giesbrecht AM, Paulo MQ. In vitro antifungal
activity of essential oils obtained from officinal plants against dermato-
phytes. Mycoses. 1993;36:333–6.
54. Lindeman Z, Waggoner M, Batdorff A, Humphreys TL. Assessing the
antibiotic potential of essential oils against Haemophilus ducreyi. BMC
Complement Altern Med. 2014;14:172.
55. Lu T, Sheng H, Wu J, et al. Cinnamon extract improves fasting blood
glucose and glycosylated hemoglobin level in Chinese patients with type 2
diabetes. Nutr Res. 2012;32:408–12.
56. Madhavadas S, Subramanian S. Cognition enhancing effect of the aqueous
extract of Cinnamomum zeylanicum on nontransgenic Alzheimer’s disease
rat model: biochemical, histological, and behavioural studies. Nutr Neurosci.
2017;20:526–37.
Cinnamomum verum J. Presl. 657

57. Malik J, Munjal K, Deshmukh R. Attenuating effect of standardized lyo-

philized Cinnamomum zeylanicum bark extract against streptozotocin-
induced experimental dementia of Alzheimer’s type. J Basic Clin Physiol
Pharmacol. 2015;26:275–85.
58. Mancini-Filho J, Van-Koiij A, Mancini DA, et al. Antioxidant activity of
cinnamon (Cinnamomum zeylanicum, Breyne) extracts. Boll Chim Farm.
1998;137:443–7.
59. Mandal S, Manisha Deb Mandal, Saha K, Pal NK. In vitro antibacterial
activity of three Indian spices against methicillin-resistant Staphylococcus
aureus. Oman Med J. 2011;26:319–23.
60. Mang B, Wolters M, Schmitt B, et al. Effects of a cinnamon extract on
plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J
Clin Invest. 2006;36:340–4.
61. Markey O, McClean CM, Medlow P, et al. Effect of cinnamon on gastric
emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite
responses to high-fat breakfast. Cardiovasc Diabetol. 2011;10:78.
62. Mertens M, Gilissen L, Goossens A, et al. Generalized systemic allergic
dermatitis caused by Cinnamomum zeylanicum in a herbal tea. Contact
Dermatitis. 2017;77:259–61.
63. Mesripour A, Moghimi F, Rafieian-Kopaie M. The effect of Cinnamomum
zeylanicum bark water extract on memory performance in alloxan-induced
diabetic mice. Res Pharm Sci. 2016;11:318–23.
64. Mihail RC. Oral leukoplakia caused by cinnamon food allergy. J Oto-
laryngol. 1992;21:366–7.
65. Miller AB, Cates RG, Lawrence M, et al. The antibacterial and antifungal
activity of essential oils extracted from Guatemalan medicinal plants.
Pharm Biol. 2015;53:548–54.
66. Mishra A, Bhatti R, Singh A, Singh Ishar MP. Ameliorative effect of the
cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic
nephropathy. Planta Med. 2010;76:412–7.
67. Mohamed Sham Shihabudeen H, Hansi Priscilla D, Thirumurugan K.
Cinnamon extract inhibits a-glucosidase activity and dampens postprandial
glucose excursion in diabetic rats. Nutr Metab (Lond). 2011;8:46.
68. Moselhy SS, Ali HK. Hepatoprotective effect of cinnamon extracts against
carbon tetrachloride induced oxidative stress and liver injury in rats. Biol
Res. 2009;42:93–8.
69. Nayak IN, Chinta R, Jetti R. Antiatherosclerotic potential of aqueous extract
of Cinnamomum zeylanicum bark against glucocorticoid induced athero-
sclerosis in Wistar rats. J Clin Diagn Res. 2017;11:FC19–23.
70. Nir Y, Potasman I, Stermer E, et al. Controlled trial of the effect of
cinnamon extract on Helicobacter pylori. Helicobacter. 2000;5:94–7.
71. Nyadjeu P, Dongmo A, Nguelefack TB, Kamanyi A. Antihypertensive and
vasorelaxant effects of Cinnamomum zeylanicum stem bark aqueous extract
in rats. J Complement Integr Med. 2011;8.
658 Cinnamomum verum J. Presl.

72. Nyadjeu P, Nguelefack-Mbuyo EP, Atsamo AD, et al. Acute and chronic
antihypertensive effects of Cinnamomum zeylanicum stem bark methanol
extract in L-NAME-induced hypertensive rats. BMC Complement Altern
Med. 2013;13:27.
73. Ortiz de Montellano BR. Browner CH. Chemical bases for medicinal plant
use in Oaxaca. Mexico. J Ethnopharmacol. 1985;13:57–88.
74. Pandey M, Chandra DR. Evaluation of ethanol and aqueous extracts of Cinna-
momum verum leaf galls for potential antioxidant and analgesic activity.
Indian J Pharm Sci. 2015;77:243–7.
75. Patton DW, Ferguson MM, Forsyth A, James J. Orofacial granulomatosis:
a possible allergic basis. Br J Oral Maxillofac Surg. 1985;23:235–42.
76. Pawar VC, Thaker VS. In vitro efficacy of 75 essential oils against
Aspergillus niger. Mycoses. 2006;49:316–23.
77. Perng DS, Tsai YH, Cherng J, et al. Discovery of a novel anticancer agent
with both antitopoisomerase I and II activities in hepatocellular carcinoma
SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component
2-methoxycinnamaldehyde. Drug Des Devel Ther. 2016;10:141–53.
78. Perry PA, Dean BS, Krenzelok EP. Cinnamon oil abuse by adolescents.
Vet Hum Toxicol. 1990;32:162–4.
79. Ping H, Zhang G, Ren G. Antidiabetic effects of cinnamon oil in diabetic
KK-Ay mice. Food Chem Toxicol. 2010;48:2344–9.
80. Pozzatti P, Scheid LA, Spader TB, et al. In vitro activity of essential oils
extracted from plants used as spices against fluconazole-resistant and
fluconazole-susceptible Candida spp. Can J Microbiol. 2008;54:950–6.
81. Preuss HG, Echard B, Polansky MM, Anderson R. Whole cinnamon and
aqueous extracts ameliorate sucrose-induced blood pressure elevations in
spontaneously hypertensive rats. J Am Coll Nutr. 2006;25:144–50.
82. Qin B, Panickar KS, Anderson RA. Cinnamon: potential role in the
prevention of insulin resistance, metabolic syndrome, and type 2 diabetes.
J Diabetes Sci Technol. 2010;4:685–93.
83. Quale JM, Landman D, Zaman MM, et al. In vitro activity of Cinnamomum
zeylanicum against azole resistant and sensitive Candida species and a pilot
study of cinnamon for oral candidiasis. Am J Chin Med. 1996;24:103–9.
84. Rafehi H, Ververis K, Karagiannis TC. Controversies surrounding the
clinical potential of cinnamon for the management of diabetes. Diabetes
Obes Metab. 2012;14:493–9.
85. Raj RK. Screening of indigenous plants for anthelmintic action against
human Ascaris lumbricoides: Part–II. Indian J Physiol Pharmacol. 1975;
19:H53.
86. Ranasinghe P, Jayawardana R, Galappaththy P, et al. Efficacy and safety of
‘true’ cinnamon (Cinnamomum zeylanicum) as a pharmaceutical agent in
diabetes: a systematic review and meta-analysis. Diabet Med. 2012;29:
1480–92.
Cinnamomum verum J. Presl. 659

87. Ranasinghe P, Perera S, Gunatilake M, et al. Effects of Cinnamomum

zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic
and healthy rat model. Pharmacognosy Res. 2012;4:73–9.
88. Ranasinghe P, Pigera S, Premakumara GA, et al. Medicinal properties of
‘true’ cinnamon (Cinnamomum zeylanicum): a systematic review. BMC
Complement Altern Med. 2013;13:275.
89. Rasheed A, Laekman G, Tottle J, et al. Eugenol and prostaglandin
biosynthesis. New Eng J Med. 1984;310:50–1.
90. Rasheed MU, Thajuddin N. Effect of medicinal plants on Moraxella
catarrhalis. Asian Pac J Trop Med. 2011;4:133–6.
91. Rathi B, Bodhankar S, Mohan V, Thakurdesai P. Ameliorative effects of a
polyphenolic fraction of Cinnamomum zeylanicum l. Bark in animal
models of inflammation and arthritis. Sci Pharm. 2013;81:567–89.
92. Revati S, Bipin C, Chitra PB, Minakshi B. In vitro antibacterial activity of
seven Indian spices against high level gentamicin resistant strains of
enterococci. Arch Med Sci. 2015;11:863–8.
93. Roussel AM, Hininger I, Benaraba R, et al. Antioxidant effects of a
cinnamon extract in people with impaired fasting glucose that are over-
weight or obese. J Am Coll Nutr. 2009;28:16–21.
94. Sambaiah K, Srinivasan K. Effect of cumin, cinnamon, ginger, mustard and
tamarind in induced hypercholesterolemic rats. Nahrung. 1991;35:47–51.
95. Sariözkan S, Türk G, Güvenç M, et al. Effects of cinnamon (C. zeylan-
icum) bark oil against taxanes-induced damages in sperm quality, testicular
and epididymal oxidant/antioxidant balance, testicular apoptosis, and
sperm dna integrity. Nutr Cancer. 2016;68:481–94.
96. Sartorius T, Peter A, Schulz N, et al. Cinnamon extract improves insulin
sensitivity in the brain and lowers liver fat in mouse models of obesity.
PLoS One. 2014;9:e92358.
97. Senhaji O, Faid M, Kalalou I. Inactivation of Escherichia coli O157:H7 by
essential oil from Cinnamomum zeylanicum. Braz J Infect Dis. 2007;11:
234–6.
98. Shahverdi AR, Monsef-Esfahani HR, Tavasoli F, et al. Trans-cinnamaldehyde
from Cinnamomum zeylanicum bark essential oil reduces the clindamycin
resistance of Clostridium difficile in vitro. J Food Sci. 2007;72:S055–8.
99. Shen Y, Fukushima M, Ito Y, et al. Verification of the antidiabetic effects of
cinnamon (Cinnamomum zeylanicum) using insulin-uncontrolled type 1
diabetic rats and cultured adipocytes. Biosci Biotechnol Biochem. 2010;74:
2418–25.
100. Simić A, Soković MD, Ristić M, et al. The chemical composition of some
Lauraceae essential oils and their antifungal activities. Phytother Res.
2004;18:713–7.
101. Singh G, Maurya S, DeLampasona MP, Catalan CA. A comparison of
chemical, antioxidant and antimicrobial studies of cinnamon leaf and bark
volatile oils, oleoresins and their constituents. Food Chem Toxicol. 2007;45:
1650–61.
660 Cinnamomum verum J. Presl.

102. Singh HB, Srivastava M, Singh AB, Srivastava AK. Cinnamon bark oil, a
potent fungitoxicant against fungi causing respiratory tract mycoses.
Allergy. 1995;50:995–9.
103. Siqueira AS, Santos CC, Cristino MR, et al. Intraoral contact mucositis
induced by cinnamon-flavored chewing gum—a case report. Quintessence
Int. 2009;40:719–21.
104. Sleha R, Mosio P, Vydrzalova M, et al. In vitro antimicrobial activities of
cinnamon bark oil, anethole, carvacrol, eugenol and guaiazulene against
Mycoplasma hominis clinical isolates. Biomed Pap Med Fac Univ Palacky
Olomouc Czech Repub. 2014;158:208–11.
105. Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants
on different mycotoxigenic fungi. Food Chem Toxicol. 2002;40:1669–75.
106. Solomon TP, Blannin AK. Effects of short-term cinnamon ingestion on
in vivo glucose tolerance. Diabetes Obes Metab. 2007;9:895–901.
107. Solomon TP, Blannin AK. Changes in glucose tolerance and insulin
sensitivity following 2 weeks of daily cinnamon ingestion in healthy
humans. Eur J Appl Physiol. 2009;105:969–76.
108. Subash Babu P, Prabuseenivasan S, Ignacimuthu S. Cinnamaldehyde—a
potential antidiabetic agent. Phytomedicine. 2007;14:15–22.
109. Sultana S, Ripa FA, Hamid K. Comparative antioxidant activity study of
some commonly used spices in Bangladesh. Pak J Biol Sci. 2010;13:340–3.
110. Tabak M, Armon R, Neeman I. Cinnamon extracts’ inhibitory effect on
Helicobacter pylori. J Ethnopharmacol. 1999;67:269–77.
111. Tremblay S, Avon SL. Contact allergy to cinnamon: case report. J Can
Dent Assoc. 2008;74:445–61.
112. Ungsurungsie M, Paovalo C, Noonai A. Mutagenicity of extracts from
Ceylon cinnamon in the rec assay (Cinnamomum zeylanicum). Food Chem
Toxicol. 1984;22:109–12.
113. Unlu M, Ergene E, Unlu GV, et al. Composition, antimicrobial activity and
in vitro cytotoxicity of essential oil from Cinnamomum zeylanicum Blume
(Lauraceae). Food Chem Toxicol. 2010;48:3274–80.
114. Uragoda CG. Asthma and other symptoms in cinnamon workers. Br J Ind
Med. 1984;41:224–7.
115. Urbaniak A, Głowacka A, Kowalczyk E, Lysakowska M, Sienkiewicz M.
The antibacterial activity of cinnamon oil on the selected gram-positive and
gram-negative bacteria. Med Dosw Mikrobiol. 2014;66:131–41 (Article in
Polish).
116. Vanschoonbeek K, Thomassen BJ, Senden JM, et al. Cinnamon supple-
mentation does not improve glycemic control in postmenopausal type 2
diabetes patients. J Nutr. 2006;136:977–80.
117. Voukeng IK, Kuete V, Dzoyem JP, et al. Antibacterial and antibiotic-
potentiation activities of the methanol extract of some Cameroonian spices
against Gram-negative multidrug resistant phenotypes. BMC Res Notes.
2012;5:299.
Cinnamomum verum J. Presl. 661

118. Wagner H. Phenolic compounds in plants of pharmaceutical interest.

In: Swain T, Harborne JB, VanSumere CF, editors. Biochemistry of plant
phenolics. New York: Plenum Press; 1978. p. 605, 608.
119. Wainstein J, Stern N, Heller S, Boaz M. Dietary cinnamon supplemen-
tation and changes in systolic blood pressure in subjects with type 2
diabetes. J Med Food. 2011;14:1505–10.
120. Wang JG, Anderson RA, Graham GM 3rd, et al. The effect of cinnamon
extract on insulin resistance parameters in polycystic ovary syndrome: a
pilot study. Fertil Steril. 2007;88:240–3.
121. Westra WH, McMurray JS, Califano J, et al. Squamous cell carcinoma of
the tongue associated with cinnamon gum use: a case report. Head Neck.
1998;20:430–3.
122. Wong HY, Tsai KD, Liu YH, et al. Cinnamomum verum component
2-methoxycinnamaldehyde: a novel anticancer agent with both antitopo-
isomerase I and II activities in human lung adenocarcinoma A549 cells
in vitro and in vivo. Phytother Res. 2016;30:331–40.
123. Yap PS, Krishnan T, Chan KG, Lim SH. Some evidences on the mode of
action of Cinnamomum verum bark essential oil, alone and in combination
with piperacillin against a multidrug resistant Escherichia coli strain.
J Microbiol Biotechnol. 2015;25:1299–306.
124. Yüce A, Türk G, Çeribaşi S, et al. Effects of cinnamon (Cinnamomum
zeylanicum) bark oil on testicular antioxidant values, apoptotic germ cell
and sperm quality. Andrologia. 2013;45:248–55.
125. Yüce A, Türk G, Ceribaşı S, et al. Effectiveness of cinnamon (Cinnamomum
zeylanicum) bark oil in the prevention of carbon tetrachloride-induced
damages on the male reproductive system. Andrologia. 2014;46:263–72.
126. Zu Y, Yu H, Liang L, et al. Activities of ten essential oils towards Propioni-
bacterium acnes and PC-3, A-549 and MCF-7 cancer cells. Molecules.
2010;15:3200–10.
Citrullus colocynthis (L.) Schrad.
(Cucurbitaceae)

(Syns.: C. vulgaris L.; Cucumis colocynthis L.)

Abstract
A perennial desert vine plant that grows in sandy arid soils, found in Mediter-
ranean countries, Asia, North Africa, and southern Europe. Colocynth was
known to Greeks, Romans and Arab physicians. Ibn Jazlah used it for elephan-
tiasis, nervous pain, gout, eye diseases and as antidote for snakebites. Dried and
powdered fruit pulp is a powerful hydragogue, cathartic and toxic in large doses.
Pulp is known to cause miscarriage when administered to pregnant women. Ibn
al-Baitar stated that fruit pulp excretes yellow bile, black bile and phlegm
through diarrhea, and is beneficial in headache, epilepsy, paralysis, palsy,
dyspnea, chronic cough, pneumonia (or pleurisy), arthritis, sciatica, and kidney
and bladder diseases; he quotes Galen and Dioscorides that massaging with juice
of green fruits relieves hip and sciatica pain. Infusion of fruits is used to treat
diabetes in Mediterranean countries. Traditional Iranian herbalists also use fruit
for the treatment of diabetes, and as purgative, anti-inflammatory, analgesic, hair
growth-promoting, abortifacient, and antiepileptic. From fruits, glycosides,
flavonoids, alkaloids, fatty acids, essential oils, curcurbitacins and colocyntho-
sides A, and B have been isolated. Major constituents of the pulp are pectin,
colocynthin, colocynthein, colocynthetin, and gum, while fixed oil and albu-
minoids have been isolated from its seeds. Ethanol fruit extract normalized
cholesterol levels and significantly reduced phospholipids and TGs of hyper-
lipidemic rabbits. Diabetic rats fed with colocynth oil-enriched diet for 2-months
had significantly lower hyperglycemia, reduced insulin-resistance, and partly
restored pancreatic b-cell mass. In RCTs, supplementation with 100 mg fruits
thrice daily for 2-months, significantly decreased HbA1c and FBG of diabetic
Iranian patients maintained on standard antidiabetic treatment, and 1 g daily
for 30-days significantly lowered blood glucose on its own in Chinese diabetic
patients.

© Springer Nature Switzerland AG 2020 663

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_69
664 Citrullus colocynthis (L.) Schrad.

Keywords




Arbuse Colocynth Coloquinda Coloquíntida Coloquinthe

Hanzal




Indravãruni Indarayan Kharbuzahe-rubah Kolokvint

Vernaculars: Urd.: Hanzal; Hin.: Indarayan, Makhal, Pharphendwa; San.: Citra,

Citrãphalã, Gavãkshi, Indrãhvã, Indravãruni, Mrgadani, Vishala; Ben.: Indrayan,
Makal, Makhal, Rakhal, Rakhal sasa mul; Mal.: Kattuvellari (Valutu), Kattu
vellarikkai, Peykomatti, Peykommuti, Valiya pekkummatti; Mar.: Indravana,
Indrayana, Kuruvrandawan; Tam.: Attutummatti, Indarvaruni, Kommaṭṭi, Paedikari,
Paycumuti, Peykomatti, Peyt-tumatti, Tumatti, Vasi-tummatti; Tel.: Chedupuchcha,
Chittipapara, Etipucchala, Eti-puchcha, Paperabudama, Patsakaia, Peikummatti,
Verripuccha; Ara.: Aulqam, Handal, Hanzal, Shari; Dan.: Kolokvint; Dut.: Bitter-
appel, Kolokwint, Kolokwintappel, Kwintappel; Eng.: Bitter Apple, Colocynth,
Indian or Wild Gourd, Vine of Sodom; Fin.: Kolokvintti; Fre.: Coloquinthe Ger.:
Arbuse, Bitter-Apfel, Koloquinte, Purgiergurke, Teufelsapfel, Wassermelone; Gre.:
Kolokunthis; Ita.: Cocomero amaro, Coloquinda, Coloquintide, Pomo amaro,
Popone amaro; Nor.: Kolokvint; Per.: Abu Jahl watermelon, Kabiste talkh,
Kharbuzahe-rubah; Por.: Colocíntida (Br.), Coloquíntida (Portugal); Rus.: Kolocint;
Spa.: Coloquintida, Naranja purgante, Tuera; Swe.: Kolokvint; Tur.: Acı karpuz.
Description: A perennial desert vine plant that grows in sandy arid soils, found in
Mediterranean countries (Cyprus, Greece, etc.), Asia, North Africa, and southern
Europe. Leaves are palmed, angular with 3–7 divided lobes, similar to watermelon
leaves; flowers yellow, solitary in the axes of leaves. Fruits are of a small orange size,
thick and globular, greenish, mottled, containing whitish, light and spongy pulp, that
has numerous small, ovate, oblong, compressed, smooth, brown seeds embedded in
it, which should be discarded before the pulp is used. When dry, the external surface
of the fruit is smooth, yellowish brown and tubercled. Rind is brittle and breaks into
three wedge-shaped pieces; inner surface of the rind is covered with a soft, spongy,
white substance that tastes intensely bitter. All parts of the plant are odorless, but
very bitter, the pulp more so than the seeds (Figs. 1, 2, 3 and 4).LXXXI
Actions and Uses: Colocynth was known to Greeks, Romans and Arab physicians.
Ibn Jazlah used it for elephantiasis, nervous pain, gout, eye diseases and as antidote
for snake-bites.LIII Dried and powdered fruit pulp is a powerful hydragogue,
cathartic and toxic in large doses.XX,CXXXII Pulp is known to cause miscarriage when
administered to pregnant women.XXI Root is also reported abortifacient [45], and
emmenagogue.CL Seeds are purgative and are used for preserving hair from turning
grey. Fruit or root with or without nux vomica is rubbed into a paste with water and
applied to boils and pimples. In rheumatism, equal parts of the root and long pepper
are given as pills.XL Ibn al-BaitarLXIX stated that fruit pulp excretes yellow bile,
black bile and phlegm through diarrhea, and is beneficial in headache, epilepsy,
paralysis, palsy, dyspnea, chronic cough, pneumonia (or pleurisy), arthritis, sciatica,
and kidney and bladder diseases; he quotes Galen and Dioscorides that massaging
with juice of green fruits relieves hip and sciatica pain. Muslim physicians of the
Citrullus colocynthis (L.) Schrad. 665

Fig. 1 Citrullus colocynthis, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Citrullus_colocynthis_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-040.jpg

Fig. 2 Citrullus colocynthis, Plant with Unripe Fruits, H. Zell, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Citrullus_colocynthis_
004.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en
666 Citrullus colocynthis (L.) Schrad.

Fig. 3 Citrullus colocynthis, Female Flower, H. Zell, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Citrullus_colocynthis_002.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 4 Citrullus colocynthis, Ripe Fruits, Jacopo188, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Hanzal_001.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Unani medicine in India extensively use pulp (temperament, hot 3° and dry 2°) as a
drastic purgative of phlegm and black bile in ascites and jaundice, as laxative for
chronic constipation due to liver disease, as anti-inflammatory, abortifacient, in
leprosy, and various uterine conditions, especially in amenorrhea; since its use
causes abdominal cramps, it is used with almond oil.LXXVII,CV Therapeutic uses of
fruit in Ayurveda include krmiroga, kãmalã, kãsa, śvãsa, kustha, gulma, and
udararoga; while the dried root is also used for treatment of pliharoga, prameha,
viśavikãra, vrana, apaci and gandamalã.LVIII
Citrullus colocynthis (L.) Schrad. 667

Infusion of fruits is used to treat diabetes in Mediterranean countries [41, 46].

Traditional Iranian herbalists also use fruit for the treatment of diabetes [28], and as
purgative, anti-inflammatory, analgesic, hair growth-promoting, abortifacient, and
antiepileptic [36, 44], and for a wide range of other medical conditions including,
leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer,
toothache, wound, mastitis, gastrointestinal disorders, and different microbial infec-
tions [29]. In southern Tunisia, it is used in folk medicine against dermatological,
gynecological and pulmonary infections [33], and inflammatory diseases [34, 35]. It is
one of the most commonly used wild toxic medicinal plants in many parts of Jordan [2,
6], and Morocco [49], for treatment of various diseases, such as diabetes [53], that
must be used only by practitioners and herbalists of traditional medicine rather than the
local healers. It is also one of the commonly used plants by herdsmen in Pakistan, as
anthelmintic in ruminants [30].
Phytoconstituents: Major constituents of the pulp are pectin, colocynthin, colo-
cynthein, colocynthetin, and gum, while fixed oil and albuminoids have been isolated
from its seeds [8]. From fruits, glycosides, flavonoids, alkaloids, fatty acids, essential
oils, curcurbitacins A, B, C, D, E, I, J, K, and L and colocynthosides A, and B have been
isolated [29, 52]. Two cucurbitacins from ethyl acetate fruit extract [48], a cucur-
bitacin glucoside 2-O-b-D-glucopyranosyl-16a-20R-dihydroxycucurbita-1,5,23E,25
(26)-tetraen-3,11,22-trione from methanol fruit extract [40], and elaterin-2-D-glucuo-
pyranoside (coloside A) is the glycoside isolated from pulp [11]. Two tetracyclic
cucurbitane-type triterpene glycosides were reported from ethyl acetate leaves extract
[17]. The oil content of seeds are 17–19%, consisting mainly of linoleic acid (67–73%),
oleic acid (10–16%), palmitic acid (9–12%), and stearic acid (5–8%). Aqueous rind
extract contains tertiary and quaternary alkaloids, glycoside and saponin components
[1], and aqueous seed extract contains catechic tannins, terpenoids and flavonoids [15].
Pharmacology: Aqueous rind extract significantly reduced plasma glucose in
normal rabbits for up to 6 h. Alkaloidal extract did not significantly affect blood
glucose, but the glycosidic and saponin extracts highly significantly lowered FBG
of alloxan-diabetic rabbits [1]. Compared to chloroform and ethanol extracts,
aqueous root extract showed highly significant antihyperglycemic effect in diabetic
rats [3]. Ethanol fruit extract normalized cholesterol levels and significantly reduced
phospholipids and TGs of hyperlipidemic rabbits [18]. Diabetic rats fed with
colocynth oil-enriched diet for 2-months had significantly lower hyperglycemia,
reduced insulin-resistance, and partly restored pancreatic b-cell mass [46]. Aqueous
seed extract for 2-weeks significantly reduced plasma levels of AST and LDH,
without significantly affecting increased blood levels of c-glutamyl transferase,
ALP, and BUN in diabetic rats [5]. Methanol extracts of both defatted seeds and
pulp significantly increased accumulation of glycogen stores in hepatocytes of
diabetic rabbits [47]. Crude and hydroalcohol seed extracts significantly stimulate
insulin secretion from isolated rat pancreas and isolated rat islets [41].
668 Citrullus colocynthis (L.) Schrad.

Aqueous and organic solvent extracts of ripe and immature fruits and seeds
display significant analgesic and anti-inflammatory activities [34, 35]. Methanol
fruit extract possesses significant protective and antioxidant activity against APAP-
hepatotoxicity [51]; however, a standardized extract failed to prevent or alleviate
CCl4-hepatotoxicity in rats [13]. Hydroalcohol fruit extract also exhibited signifi-
cant anticonvulsant effect in PTZ-induced seizures in mice [36]. Female rats treated
with fruit for 12-weeks had reduced percentage of pregnancies and number of
implantation sites, with decrease in ovarian weight and decreased viable fetus’s
number [42]. Ethanol (50%) fruit extract administered to male rats for 60-days
showed reversible antiandrogenic effects, significantly reduced cauda epididymis
sperm motility and density, fertility, and blood testosterone levels [16]. Coloside A
failed to stimulate uterus but elicited purgative property, and also exhibited anti-
histaminic and antimuscarinic-like activity on intestinal musculature and exhibited
negative chronotropic and inotropic activity in isolated mammalian and amphibian
hearts [11]. Topical application of petroleum ether fruit extract exhibited promising
hair growth-promoting activity in androgen-induced alopecia [19].
Aqueous fruit extract exhibited high antifungal activity against C. albicans and
C. glabrata, and against Gram-negative E. coli and P. aeruginosa [33], while
methanol extract of ripe deseeded fruit was significantly active against drug sensi-
tive and drug resistant M. tuberculosis [37]. Ethanol extracts of fruits, leaves, stems
and roots were active against B. pumilus and S. aureus, and the fruit and root
extracts were also active against B. subtilis at higher concentrations [38]. Crude
acetone leaf extract exhibited activity against P. aeruginosa, whereas chloroform
extract was active against E. coli [24].
Cucurbitacin E from fruits shows antiproliferation effects [39]; cucurbitacin E
glucoside and cucurbitacin I glucoside also show potent inhibitory activity against
hepatoma cells (HepG2), and prolong survival time, life-span and normalize bio-
chemical parameters of EAC-infected mice [10]. Cucurbitacin B/E glucosides
extracted from leaves also exhibit pleiotropic effects on cells, causing both cell
cycle arrest and apoptosis of human breast cancer cells [50]. It was also reported
active against Ehrlich carcinoma, 37 sarcoma, 180 sarcoma and Black SBL-1
sarcoma [14, 21, 22].
Clinical Studies: In RCTs, supplementation with 100 mg fruits thrice daily for
2-months, significantly decreased HbA1c and FBG of diabetic Iranian patients main-
tained on standard antidiabetic treatment [28], and 1 g daily for 30-days significantly
lowered blood glucose on its own in Chinese diabetic patients [32]. Powdered seeds,
300 mg daily to dyslipidemic patients for 6-weeks significantly decreased TGs and TC
[43]. Application of a topical formulation of fruit extract significantly decreased pain in
Iranian patients with painful diabetic polyneuropathy [26].
Mechanism of Action: Administration of antihistamine drug, dimethylaminoethyl
benzylaniline, to rats slowed down the purgative action of colocynth, indicating the
purgative action due at least, in part, to the involvement of histamine [20]. Antag-
onism of its anticonvulsion effect by pretreatment with flumezanil and naloxone
indicate the involvement of GABA-ergic and opioid receptors [36]. Abortive activity
Citrullus colocynthis (L.) Schrad. 669

was suggested to be due to an indirect action, a manifestation of cathartic activity of

the drug and congestion of the pelvic region. However, possibility of some direct
action on uterus could not be completely ruled out, as cucurbitacins are cytotoxic
that may contribute to its antifertility and abortifacient activities [14, 22, 25].
Human A/Es, Allergy and Toxicity: It causes intestinal gripping,LXXVII and toxic
acute colitis has occurred after ingestion of colocynth, resulting in mucosal diarrhea
followed by acute rectorrhagia [4, 23, 31].
Animal Toxicity: Feeding diet containing 10% of ripe fruits to rats for 6-weeks
decreased body weight gain and food intake, and caused enterohepatonephropathy
[7], and administration of C. colocynthis in doses of 0.5–10 g/kg/day killed goats after
dosing for 1-day to 2-weeks [12]. LD50 (i.p.) in mice was determined as 681 mg/kg
[9]. Condensate from seeds contain a large number of polycyclic hydrocarbons,
including known carcinogens (B(a)P, benz(a)anthracene, benzo(b) fluoranthene, and
benzo(j)luoranthene). Dose related carcinogenic activity of this condensate was
established after chronic epicutaneous application to mouse skin [27].
Commentary: Antidiabetic activity of this plant is recognized and traditionally
utilized in various cultures. Limited clinical trials have also verified this activity
with added effect on lipids, but more extensive studies are needed to firmly establish
the plant part/extract used, and the dose for practical clinical application as a safe
antidiabetic agent.

References
1. Abdel-Hassan IA, Abdel-Barry JA, Tariq Mohammeda S. The hypogly-
caemic and antihyperglycaemic effect of Citrullus colocynthis fruit aqueous
extract in normal and alloxan diabetic rabbits. J Ethnopharmacol. 2000;71:
325–30.
2. Aburjai T, Hudaib M, Tayyem R, et al. Ethnopharmacological survey of
medicinal herbs in Jordan, the Ajloun Heights region. J Ethnopharmacol.
2007;110:294–304.
3. Agarwal V, Sharma AK, Upadhyay A, Singh G, Gupta R. Hypoglycemic
effects of Citrullus colocynthis roots. Acta Pol Pharm. 2012;69:75–9.
4. Al Faraj S. Haemorrhagic colitis induced by Citrullus colocynthis. Ann
Trop Med Parasitol. 1995;89:695–6.
5. Al-Ghaithi F, El-Ridi MR, Adeghate E, Amiri MH. Biochemical effects of
Citrullus colocynthis in normal and diabetic rats. Mol Cell Biochem. 2004;
261:143–9.
6. Al-Qura’n S. Ethnopharmacological survey of wild medicinal plants in
Showbak, Jordan. J Ethnopharmacol. 2009;123:45–50.
7. Al-Yahya MA. AL-Farhan AH, Adam SE. Preliminary toxicity study on the
individual and combined effects of Citrullus colocynthis and Nerium
oleander in rats. Fitoterapia. 2000;71:385–91.
670 Citrullus colocynthis (L.) Schrad.

8. Ardekani MRS, Rahimi R, Javadi B. Relationship between temperaments of

medicinal plants and their major chemical compounds. J Trad Chin Med.
2011;31:27–31.
9. Aswal BS, Bhakuni DS, Goel AK, et al. Screening of Indian plants for
biological activity: Part X. Indian J Exp Biol. 1984;22:312–32.
10. Ayyad SE, Abdel-Lateff A, Alarif WM, et al. In vitro and in vivo study of
cucurbitacins-type triterpene glucoside from Citrullus colocynthis growing
in Saudi Arabia against hepatocellular carcinoma. Environ Toxicol Phar-
macol. 2012;33:245–51.
11. Banerjee SP, Dandiya PC. Smooth muscle and cardiovascular pharma-
cology of alpha-elaterin-2-D-glucopyranoside glycoside of Citrullus colo-
cynthis. J Pharm Sci. 1967;56:1665–7.
12. Barri ME, Onsa TO, Elawad AA, et al. Toxicity of five Sudanese plants to
young ruminants. J Compar Pathol. 1983;93:559–75.
13. Barth A, Müller D, Dürrling K. In vitro investigation of a standardized dried
extract of Citrullus colocynthis on liver toxicity in adult rats. Exp Toxicol
Pathol. 2002;54:223–30.
14. Belkin M, Fitzgerald DB. Tumor-damaging capacity of plant materials.
I. Plants used as cathartics. J Natl Cancer Inst. 1952;13:139–55.
15. Benariba N, Djaziri R, Bellakhdar W, et al. Phytochemical screening and
free radical scavenging activity of Citrullus colocynthis seeds extracts.
Asian Pac J Trop Biomed. 2013;3:35–40.
16. Chaturvedi M, Mali PC, Ansari AS. Induction of reversible antifertility with
a crude ethanol extract of Citrullus colocynthis Schrad. fruit in male rats.
Pharmacology. 2003;68:38–48.
17. Chawech R, Jarraya R, Girardi C, et al. Cucurbitacins from the leaves
of Citrullus colocynthis (L.) Schrad. Molecules. 2015;20:18001–15.
18. Daradka H, Almasad MM, Qazan WSh, El-Banna NM, Samara OH. Hypo-
lipidaemic effects of Citrullus colocynthis L. in rabbits. Pak J Biol Sci. 2007;
10:2768–71.
19. Dhanotia R, Chauhan NS, Saraf DK, Dixit VK. Effect of Citrullus colo-
cynthis Schrad. fruits on testosterone-induced alopecia. Nat Prod Res. 2011;
25:1432–43.
20. Erspamer V, Paolini A. Histamine a positive conditioner of the purgative
action of some drastic agents. Experientia. 1946;2:455–8.
21. Faust RE, Cwalina GR, Ramstad E. The antineoplastic action of chemical
fractions of the fruit of Citrulius colocynthis on sarcoma-37. J Am Pharm
Assoc, Sci Ed. 1958;47:1–5.
22. Gitter S, Gallily R, Shohat B, Lavie D. Studies on the antitumor effect of
cucurbitacins. Cancer Res. 1961;21:516–21.
23. Goldfain D, Lavergne A, Galian A, et al. Peculiar acute toxic colitis after
ingestion of colocynth: a clinicopathological study of three cases. Gut.
1989;30:1412–8.
24. Gowri SS, Priyavardhini S, Vasantha K, Umadevi M. Antibacterial activity
on Citrullus colocynthis leaf extract. Anc Sci Life. 2009;29:12–3.
Citrullus colocynthis (L.) Schrad. 671

25. Hartwell JL, Abbott BJ. Antineoplastic principles in plants: recent develop-
ments in the field. Adv Pharmacol. 1969;7:117–209.
26. Heydari M, Homayouni K, Hashempur MH, Shams M. Topical Citrullus
colocynthis (bitter apple) extract oil in painful diabetic neuropathy: a double-
blind randomized placebo-controlled clinical trial. J Diabetes. 2016;8:
246–52.
27. Hobs M, John SA, Schmahl D. Carcinogenic activity of condensate from
coloquint seeds (Citrullus colocynthis) after chronic epicutaneous admin-
istration to mice. J Cancer Res Clin Onco (W.Ger.). 1984;108:154–6.
28. Huseini HF, Darvishzadeh F, Heshmat R, et al. The clinical investigation of
Citrullus colocynthis (L.) Schrad. fruit in treatment of Type II diabetic
patients: a randomized, double blind, placebo-controlled clinical trial.
Phytother Res. 2009;23:1186–9.
29. Hussain AI, Rathore HA, Sattar MZ, et al. Citrullus colocynthis (L.) Schrad.
(bitter apple fruit): a review of its phytochemistry, pharmacology, traditional
uses and nutritional potential. J Ethnopharmacol. 2014;155:54–66.
30. Jabbar A, Raza MA, Iqbal Z, Khan MN. An inventory of the ethnobotani-
cals used as anthelmintics in the southern Punjab (Pakistan). J Ethnophar-
macol. 2006;108:152–4.
31. Javadzadeh HR, Davoudi A, Davoudi F, et al. Citrullus colocynthis as the
cause of acute rectorrhagia. Case Rep Emerg Med. 2013;2013:652192.
32. Li Y, Zheng M, Zhai X, et al. Effect of Gymnema sylvestre, Citrullus
colocynthis and Artemisia absinthium on blood glucose and lipid profile in
diabetic human. Acta Pol Pharm. 2015;72:981–5.
33. Marzouk B, Marzouk Z, Décor R, et al. Antibacterial and anticandidal
screening of Tunisian Citrullus colocynthis Schrad. from Medenine. J Ethno-
pharmacol. 2009;125:344–9.
34. Marzouk B, Marzouk Z, Fenina N, et al. Anti-inflammatory and analgesic
activities of Tunisian Citrullus colocynthis Schrad. immature fruit and seed
organic extracts. Eur Rev Med Pharmacol Sci. 2011;15:665–72.
35. Marzouk B, Marzouk Z, Haloui E, et al. Screening of analgesic and anti-
inflammatory activities of Citrullus colocynthis from southern Tunisia. J Ethno-
pharmacol. 2010;128:15–9.
36. Mehrzadi S, Shojaii A, Pur SA, Motevalian M. Anticonvulsant activity of
hydroalcoholic extract of Citrullus colocynthis fruit: involvement of
benzodiazepine and opioid receptors. J Evid Based Complementary Altern
Med. 2016;21:NP31–5.
37. Mehta A, Srivastva G, Kachhwaha S, Sharma M, Kothari SL. Antimyco-
bacterial activity of Citrullus colocynthis (L.) Schrad. against drug sensitive
and drug resistant Mycobacterium tuberculosis and MOTT clinical isolates.
J Ethnopharmacol. 2013;149:195–200.
38. Memon U, Brohi AH, Ahmed SW, et al. Antibacterial screening of Citrullus
colocynthis. Pak J Pharm Sci. 2003;16:1–6.
672 Citrullus colocynthis (L.) Schrad.

39. Nakamura S. Search for biofunctional constituents from medicinal foods-

elucidation of constituents with antiproliferation effects and the target mole-
cule from Citrullus colocynthis. Yakugaku Zasshi. 2012;132:1063–7 (Japanese).
40. Nayab D, Ali D, Arshad N, et al. Cucurbitacin glucosides from Citrullus
colocynthis. Nat Prod Res. 2006;20:409–13.
41. Nmila R, Gross R, Rchid H, et al. Insulinotropic effect of Citrullus
colocynthis fruit extracts. Planta Med. 2000;66:418–23.
42. Qazan WSh, Almasad MM, Daradka H. Short and long effects of Citrullus
colocynthis L. on reproductive system and fertility in female Spague-Dawley
rats. Pak J Biol Sci. 2007;10:2699–703.
43. Rahbar AR, Nabipour I. The hypolipidemic effect of Citrullus colocyn-
this on patients with hyperlipidemia. Pak J Biol Sci. 2010;13:1202–7.
44. Rahimi R, Amin G, Ardekani MR. A review on Citrullus colocynthis
Schrad.: from traditional Iranian medicine to modern phytotherapy. J Altern
Complement Med. 2012;18:551–4.
45. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
46. Sebbagh N, Cruciani-Guglielmacci C, Ouali F, et al. Comparative effects of
Citrullus colocynthis, sunflower and olive oil-enriched diet in streptozotocin-
induced diabetes in rats. Diabetes Metab. 2009;35:178–84.
47. Shafaei H, Rad JS, Delazar A, Behjati M. The effect of pulp and seed extract
of Citrullus colocynthis, as an antidiabetic medicinal herb, on hepatocytes
glycogen stores in diabetic rabbits. Adv Biomed Res. 2014;3:258.
48. Song F, Dai B, Zhang HY, et al. Two new cucurbitane-type triterpenoid
saponins isolated from ethyl acetate extract of Citrullus colocynthis fruit.
J Asian Nat Prod Res. 2015;17:813–8.
49. Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B. Ethnopharmacological survey
of plants used in the traditional treatment of hypertension and diabetes in
south-eastern Morocco (Errachidia province). J Ethnopharmacol. 2007;110:
105–17.
50. Tannin-Spitz T, Grossman S, Dovrat S, et al. Growth inhibitory activity of
cucurbitacin glucosides isolated from Citrullus colocynthis on human breast
cancer cells. Biochem Pharmacol. 2007;73:56–67.
51. Vakiloddin S, Fuloria N, Fuloria S, et al. Evidences of hepatoprotective and
antioxidant effect of Citrullus colocynthis fruits in paracetamol induced
hepatotoxicity. Pak J Pharm Sci. 2015;28:951–7.
52. Yoshikawa M, Morikawa T, Kobayashi H, et al. Bioactive saponins and
glycosides. XXVII. Structures of new cucurbitane-type triterpene glycosides
and antiallergic constituents from Citrullus colocynthis. Chem Pharm Bull
(Tokyo). 2007;55:428–34.
53. Ziyyat A, Legssyer A, Mekhfi H, et al. Phytotherapy of hypertension and
diabetes in oriental Morocco. J Ethnopharmacol. 1997;58:45–54.
Clitoria ternatea L.
(Fabaceae/Leguminosae)

(Syns.: C. albiflora Mattei; C. bracteata Poir.; C. parviflora Raf.; C. philippensis Perr.)

Abstract
A vine native to India, Sri Lanka, and introduced to Africa, Australia and North
America. Sanskrit writers of Ayurveda described root as aperient and diuretic,
and used it with other diuretics and laxatives in ascites, and enlargement of
abdominal viscera. Root infusion is also used to relieve irritation of bladder and
urethra due to its demulcent and diuretic properties. According to Ayurvedic
pharmacopeia, dried roots are used in mutraroga, kustha, sotha, vrana, and sula;
whereas dried leaves are used in kustha, mutradosa, sotha, vrana, visa, unmada,
ardhavabhedaka, sula, grahabadha, amadosa, raktatisara, bhrama, svasa, kasa,
jvara, daha and vamana. Some texts described additional clinical uses in
Ayurveda as antidote to snake poison, antitubercular, to relieve inflammation, in
rheumatism, ear diseases, fever, eye ailments, sore throat and bodyache, and also
reportedly used to enhance memory, as a nootropic, antistress, anxiolytic,
antidepressant, tranquilizing, sedative and anticonvulsant agent. In TCM, it is
used to treat infertility, gonorrhea, as emmenagogue and aphrodisiac. Seeds are
known as Samsampin in the Philippines, and are used as purgative and aperient.
Ternatins (polyacylated delphinidin glucosides) are anthocyanins found in blue
petals of flowers; white petal flowers do not contain anthocyanins. Aqueous root
extract fed to 7-days old rat pups for 30-days improved retention and spatial
learning performance. Memory enhancing, anxiolytic, antidepressant, antistress
and anticonvulsant activities of aqueous methanol extract have been reproduced.
Alcohol extract of aerial parts and root significantly ameliorated MES-induced
amnesia in rats, root extract being more effective. Methanol extracts of leaf and
root also exhibit significant analgesic activity in various antinociceptive models.
Aqueous extract demonstrated antioxidative, a-glucosidase and pancreatic
a-amylase inhibitory activities, justifying its use as antidiabetic plant. Lipid
lowering effect is suggested to be due to increased biliary excretion, and
decreased absorption of dietary cholesterol.

© Springer Nature Switzerland AG 2020 673

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_70
674 Clitoria ternatea L.

Keywords




Aprajita Blaue schmetterlingswicke Butterfly bean Campanilla Dié dòu






Fagiolo indiano Mazaryun Pukiñggan Shankpushpi Siniherne

Vernaculars: Urd.: Mazaryun, Mazeriyun-i-hindi; Hin.: Aprajita, Gokarana,

Kambu malini, Kambu puspi smritihita, Kavathenthi, Kiriti, Medhya vana vilasini,
Sankhanamni, Sankhaphuli, Shankpushpi; San.: Aprajita, Ashphota, Gokarna, Gir-
ikarnikã, Radha, Sankapushpi, Vishnu-kranta; Ben.: Aprajita, Nila aprajita; Mal.:
Aral, Malayamukki, Samkhupuspam, Shankhpushpam; Mar.: Aparajita, Gokaran,
Gokarna, Gokurna-mula (root), Kajali, Vishnukranta; Tam.: Girikanni, Kakkanan,
Kakkanan-kodi, Kakkatankodi, Kannikkoti, Kavachhi, Kuruvilai, Sangpuspi; Tel.:
Dintana, Gentana, Gilarnika, Sankham poolu, Sankhu-pushpamu; Ara.: Buzrula,
Mazaryun-e-hindi; Chi.: 蝶豆, Dié dòu, Hu die hua dou; Eng.: Asian pigeon wings,
Blue pea, Butterfly bean, Butterfly pea, Conch flower, Mazerion, Mussel shell-
creeper, Winged leaved clitoria; Fin.: Siniherne; Fre.: Clitore de ternate; Ger.: Blaue
schmetterlingswicke; Haw.: Thoua keo; Ita.: Fagiolo indiano, Fior celeste; Per.:
Mazaryun, Nabat-bikh-e-hayat; Spa.: Bejuco de conchitas, Campanilla, Chorreque
azul, Conchita de mar, Conchitas, Papito, Zapatillo de la reina (Mexico); Tag.:
Kolokánting, Pukiñggan, Samsampin.
Description: A vine with cylindrical and slender stems; native to India, Sri Lanka;
introduced to Africa, Australia and North America. Leaflets are 5–7, elliptic to
oblong in shape and 3–7 cm long; flowers are single or multilayer of deep-blue color
with a white or yellowish center. Root white, tapering, branched and fleshy; taste
acrid and bitter; root bark soft and thick; seeds generally black or greyish-brown,
minutely mottled-green and black, oblong, round or nearly reniform with a white
scar at one margin, slightly compressed near the edges. The ends of some seeds are
smooth as if cut off with a knife; testa brittle, containing two cotyledons which are
full of granular starch, thus resembling senna-seeds; taste oily, acrid, bitter and

Fig. 1 Clitoria ternatea, Flower from Margarita Island, The Photographer, WikimediaCommons;
Universal CC0 1.0, https://commons.wikimedia.org/wiki/File:Clitoria_ternatea.jpg; https://creative
commons.org/publicdomain/zero/1.0/deed.en
Clitoria ternatea L. 675

Fig. 2 Clitoria ternatea, Pods in Various Stages of Ripeness, Tux the penquin, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Clitoria_ternatea_
beans.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Clitoria ternatea, White Variety used as Sankupuzhpam, Vijayakumarblathur, WikimediaCom-

mons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/Clitoria_
ternatea#/media/File:Sankupuzhpam.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

disagreeable. Its latex is a strong poison. In Kerala, C. ternatea is used as

Shankapushpi, while the Bengali Ayurveda practitioners believe it to be C. decussata
and in some areas of central, western and northern India, C. pluricaulis and Evolvu-
lus alsinoides are marketed as Shankapushpi [3] (Figs. 1, 2 and 3).
Actions and Uses: Root is acrid bitter in taste, laxative and diuretic, seeds are
powerful cathartic and the root bark is demulcent, diuretic and laxative.CV Sanskrit
writers of Ayurveda described root as aperient and diuretic, and used it with other
diuretics and laxatives in ascites, and enlargement of abdominal viscera.XL Root
infusion is also used to relieve irritation of bladder and urethra due to its demulcent and
diuretic properties.LXXXI,CXXII According to Ayurvedic pharmacopeia, dried roots are
676 Clitoria ternatea L.

used in mutraroga, kustha, sotha, vrana, and sula; whereas dried leaves are used in
kustha, mutradosa, sotha, vrana, visa, unmada, ardhavabhedaka, sula, grahabadha,
amadosa, raktatisara, bhrama, svasa, kasa, jvara, daha and vamana.LVIII Some texts
described additional clinical uses in Ayurveda as antidote to snake poison, antitu-
bercular,XXI to relieve inflammation, in rheumatism, ear diseases, fever, eye ailments,
sorethroat and bodyache [11], and also reportedly used to enhance memory, as a
nootropic, antistress, anxiolytic, antidepressant, tranquilizing, sedative and anticon-
vulsant agent [20]. Root, bark, seeds and leaves (temperament, hot 3° and dry 3°) are
described in Unani medicine as purgative of phlegm, yellow bile and black bile,L
detergent, anthelmintic, diuretic, anti-inflammatory, antiitch and emmenagogue, and
used for the treatment of ascites, jaundice, and weakness of liver function, also
beneficial externally for vitiligo, ringworm, leucoderma, eczema and other skin
diseases.L,LXXVII Unani physicians internally use root after a purification process, in
which it is soaked in vinegar for 3-days and nights, dried, and after roasting in almond
oil it is lightly pounded for future use in stomachache and intestinal worms.1 In TCM, it
is used to treat infertility, gonorrhea, as emmenagogue and aphrodisiac [7]. Seeds are
known as Samsampin in the Philippines [27], are purgative, aperient,LXXXIV contain
high contents of oligosaccharides (4.79%), and have high flatulence potential. Leaves
are used in the Philippines in poultices for swollen joints.CXVII
Phytoconstituents: Ternatins (polyacylated delphinidin glucosides) are antho-
cyanins found in blue petals of flowers [13, 30, 33, 34]; white petal flowers do not
contain anthocyanins [14]. Three closely related anthocyanins namely malvidin-
3-b-glucoside, delphinidin-3-b-glucoside and 3 methyl derivative of delphinidin-
3-b-glucoside [30], and several other flavonol glycosides, including kaempferol,
quercetin, myricetin 3-neohesperidosides, and 3-rutinosides have been isolated from
flowers [15]. Roots contain steroids, saponin, flavonoids and glycosides [32], tannins
and resins [23]. Root-bark contains starch, tannin and resin, and seeds contain
p-hydroxycinnamic acid [16], a fixed oil, a bitter resin (the active principle), tannic
acid, glucose, a light-brown resin and ash (6%). From root, taraxerol and taraxerone
have also been isolated [4, 5].
Pharmacology: Aqueous root extract fed to 7-days old rat pups for 30-days
improved retention and spatial learning performance [26]. Memory enhancing,
anxiolytic, antidepressant, antistress and anticonvulsant activities of aqueous
methanol extract have been reproduced [9, 17]. Alcohol extract of aerial parts and
root significantly ameliorated MES-induced amnesia in rats, root extract being more
effective [31], and hydroalcohol extract of aerial parts also prevented STZ-induced
cognitive impairment by reducing oxidative stress, cholinesterase activity, and rho
kinase (ROCK II) expression [19]. Aqueous flower extract possesses stronger
antioxidant activity than ethanol extract [12], and blue flowers being better antiox-
idants [28]. Aqueous blue flower extract protected rats from ketoconazole-induced
testicular damage, and alleviated reduction of reproductive organ weight parameters,
testosterone levels, and sperm counts [8]. Methanol extracts of leaf and root also

1
Tayyab M: Personal Communication.
Clitoria ternatea L. 677

exhibit significant analgesic activity in various antinociceptive models [11].

Methanol extracts of flower and leaf are cytotoxic against two breast cancer cell lines
(MCF-7 and MDA-MB-231) [2]. Hydroalcohol extract of seeds and roots signifi-
cantly lowered TC, TGs, VLDL-C and LDL-C in diet-induced hyperlipidemic rats.
Hepatoprotective and antioxidant activity of methanol leaf extract [21], and anti-
pyretic, analgesic and anti-inflammatory activities of methanol root extract [6, 22]
have also been reported. Aqueous flower extract also exhibited significant anti-
microbial efficacy against three oral cavity pathogenic microorganisms, S. mutans,
L. casei, and S. aureus [24], and leaf extract was significantly active against A. niger
and other filamentous fungi [10].
Mechanism of Action: Aqueous extract demonstrated antioxidative [12], a-gluco-
sidase and pancreatic a-amylase inhibitory activities, justifying its use as antidiabetic
plant [1]. Lipid lowering effect is suggested to be due to increased biliary excretion, and
decreased absorption of dietary cholesterol [29]. Aqueous root extract significantly
increased hippocampal ACh content [25], alcohol extract of aerial parts and root also
increased brain ACh content [19, 31], contributing to its learning and memory-enhancing
effects.
Human A/Es, Allergy and Toxicity: Not suitable for hot temperament people and
harmful in the presence of liver affections.LXXVII
Animal Toxicity: LD50 of ethanol root extract in mice is more than 1,300 mg/kg
[32], and aqueous fruit extract, in the dose of 0.05–0.2 ml (s.c.) twice daily for
5-days to mice decreased number of litters [18].
Commentary: There are no clinical studies reported on any parts of the plant.

References
1. Adisakwattana S, Ruengsamran T, Kampa P, Sompong W. In vitro inhibi-
tory effects of plant-based foods and their combinations on intestinal a-gluco-
sidase and pancreatic a-amylase. BMC Complement Altern Med. 2012;
12:110.
2. Akter R, Uddin SJ, Grice ID, Tiralongo E. Cytotoxic activity screening of
Bangladeshi medicinal plant extracts. J Nat Med. 2014;68:246–52.
3. Aulakh GS, Narayanan S, Mahadevan G. Phytochemistry and pharmacology
of shankapushpi—four varieties. Anc Sci Life. 1988;7:149–56.
4. Banerjee SK, Chakravarti RN. Taraxerol from Clitoria ternata Linn. Bull
Calcutta Sch Trop Med. 1963;11:106–7.
5. Banerjee SK, Chakravarti RN. Taraxerone from Clitoria ternata Linn. Bull
Calcutta Sch Trop Med. 1964;12:23.
6. Devi BP, Boominathan R, Mandal SC. Anti-inflammatory, analgesic and
antipyretic properties of Clitoria ternatea root. Fitoterapia. 2003;74:345–9.
7. Fantz PR. Ethnobotany of Clitoria (Leguminosae). Economic Botany (New
York Botanical Garden Press). 1991;45:511–20.
678 Clitoria ternatea L.

8. Iamsaard S, Burawat J, Kanla P, et al. Antioxidant activity and protective

effect of Clitoria ternatea flower extract on testicular damage induced by
ketoconazole in rats. J Zhejiang Univ Sci B. 2014;15:548–55.
9. Jain NN, Ohal CC, Shroff SK, et al. Clitoria ternatea and the CNS.
Pharmacol Biochem Behav. 2003;75:529–36.
10. Kamilla L, Mansor SM, Ramanathan S, Sasidharan S. Effects of Clitoria
ternatea leaf extract on growth and morphogenesis of Aspergillus niger.
Microsc Microanal. 2009;15:366–72.
11. Kamilla L, Ramanathan S, Sasidharan S, Mansor SM. Evaluation of anti-
nociceptive effect of methanolic leaf and root extracts of Clitoria ter-
natea Linn. in rats. Indian J Pharmacol. 2014;46:515–20.
12. Kamkaen N, Wilkinson JM. The antioxidant activity of Clitoria ternatea
flower petal extracts and eye gel. Phytother Res. 2009;23:1624–5.
13. Kazuma K, Kogawa K, Noda N, et al. Identification of delphinidin 3-O-(6″-
O-malonyl)-beta-glucoside-3′-O-beta-glucoside, a postulated intermediate
in the biosynthesis of ternatin C5 in the blue petals of Clitoria ternatea
(butterfly pea). Chem Biodivers. 2004;1:1762–70.
14. Kazuma K, Noda N, Suzuki M. Flavonoid composition related to petal color
in different lines of Clitoria ternatea. Phytochemistry. 2003;64:1133–9.
15. Kazuma K, Noda N, Suzuki M. Malonylated flavonol glycosides from the
petals of Clitoria ternatea. Phytochemistry. 2003;62:229–37.
16. Kulshreshtha DK, Khane MP. Chemical investigation of the seeds of Clitoria
ternatea Linn. Curr Sci. 1967;36:124.
17. Malik J, Karan M, Vasisht K. Nootropic, anxiolytic and CNS-depressant studies
on different plant sources of shankhpushpi. Pharm Biol. 2011;49:1234–42.
18. Matsui AS, Rogers J, Woo YK, Cutting WC. Effects of some natural products
on fertility in mice. Med Pharmacol Exp Int J Exp Med. 1967;16:414–24.
19. Mehla J, Pahuja M, Gupta P, et al. Clitoria ternatea ameliorated the intra-
cerebroventricularly injected streptozotocin induced cognitive impairment
in rats: behavioral and biochemical evidence. Psychopharmacology (Berl).
2013;230:589–605.
20. Mukherjee PK, Kumar V, Kumar NS, Heinrich M. The Ayurvedic medicine
Clitoria ternatea—from traditional use to scientific assessment. J Ethnophar-
macol. 2008;120:291–301.
21. Nithianantham K, Shyamala M, Chen Y, et al. Hepatoprotective potential of
Clitoria ternatea leaf extract against paracetamol induced damage in mice.
Molecules. 2011;16:10134–45.
22. Parimaladevi B, Boominathan R, Mandal SC. Evaluation of antipyretic potential
of Clitoria ternatea L. extract in rats. Phytomedicine. 2004;11:323–6.
23. Prasad M, Tiwari SK, Chaturvedic GN. Certain studies on Aparajita (Clitoria
ternatea Linn.). J Natl Integ Assoc. 1980;22:140.
24. Pratap GM, Manoj KM, Sai SA, Sujatha B, Sreedevi E. Evaluation of three
medicinal plants for antimicrobial activity. Ayu. 2012;33:423–8.
25. Rai KS, Murthy KD, Karanth KS, et al. Clitoria ternatea root extract enhances
acetylcholine content in rat hippocampus. Fitoterapia. 2002;73:685–9.
Clitoria ternatea L. 679

26. Rai KS, Murthy KD, Karanth KS, Rao MS. Clitoria ternatea (Linn.) root
extract treatment during growth spurt period enhances learning and memory
in rats. Indian J Physiol Pharmacol. 2001;45:305–13.
27. Revilleza MJ, Mendoza EM, Raymundo LC. Oligosaccharides in several
Philippine indigenous food legumes: determination, localization and removal.
Plant Foods Hum Nutr. 1990;40:83–93.
28. Sivaprabha J, Supriya J, Sumathi S, et al. A study on the levels of non-
enzymic antioxidants in the leaves and flowers of Clitoria ternatea. Anc Sci
Life. 2008;27:28–32.
29. Solanki YB, Jain SM. Antihyperlipidemic activity of Clitoria ternatea and
Vigna mungo in rats. Pharm Biol. 2010;48:915–23.
30. Srivastava BK, Pande CS. Anthocyonins from the flowers of Clitoria ternata.
Planta Med. 1977;32:138–40.
31. Taranalli AD, Cheeramkuzhy TC. Influence of Clitoria ternatea extracts on
memory and central cholinergic activity in rats. Pharm Biol. 2000;38:51–6.
32. Taur DJ, Patil RY. Evaluation of antiasthmatic activity of Clitoria ternatea
L. roots. J Ethnopharmacol. 2011;136:374–6.
33. Terahara N, Oda M, Matsui T, et al. Five new anthocyanins, ternatins A3,
B4, B3, B2, and D2, from Clitoria ternatea flowers. J Nat Prod. 1996;59:
139–44.
34. Terahara N, Toki K, Saito N, et al. Eight new anthocyanins, ternatins C1-C5
and D3 and preternatins A3 and C4 from young Clitoria ternatea flowers.
J Nat Prod. 1998;61:1361–7.
Colchicum autumnale L.
(Colchicaceae)

(Syns.: C. borisii Stef.; C. bulgaricum Velen.; C. crociflorum Sims; C. orientale Friv.

ex Kunth)

Abstract
Autumn crocus is native to grassy meadows and woods and river banks in
southeastern Ireland, England, the Netherlands and Denmark, and at altitudes
between 400 and 1,200 m ranges east to Poland and south to Spain and central
Italy and North Africa. Corm and seeds were well known to ancient Greeks and
Romans for their remedial property in gout, rheumatism, arthritis, dropsy,
gonorrhea and enlarged prostate. Dioscorides and Galen described corms toxic
and lethal, as they taste delicious and increase the desire to eat more; its leaves,
corm and seeds are all poisonous. In Babylonia, it was used for swelling poison
of the limbs, scorpion sting, head and eye diseases, as well as for breast pain.
The plant was called by different names through the ages: ephemera, finger of
Hermes, pater noster, and tue-chiens. Modern phytonyms refer to the land of
Colchis, a mythical place close to Armenia. According to Byzantine historians,
first use of C. autumnale in the treatment of gout was by the 5th century
physician, Jacob Psychristus. The disease (podagra) was common at the time, its
main causes being overconsumption of alcoholic drinks and food, and thus
referred to as the ‘disease of kings,’ though the disease was recognized by
Hippocrates in the fifth-century B.C., who called it ‘the unwalkable disease.’
Some refer to Byzantine Christian physician, Alexander of Tralles in the 6th
century A.D. as the first user for the selective and specific treatment of gout.
Besides the main active principle colchicine present in amounts up to 0.6%, the
corm contains several other alkaloids. In modern practice, the alkaloid colchicine
is only used as a specific treatment for gouty arthritis. Colchicine was approved
by the FDA for the treatment and prophylaxis of gout flares, and has also been
used with varying success in the treatment of familial Mediterranean fever,
alcoholic, posthepatitic and primary biliary cirrhosis, psoriasis, Behçet’s disease,
aphthous stomatitis, linear IgA dermatosis, relapsing polychondritis, Sweet’s
syndrome, scleroderma, amyloidosis, leukocytoclastic vasculitis, epidermolysis

© Springer Nature Switzerland AG 2020 681

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_71
682 Colchicum autumnale L.

bullosa, and dermatomyositis. In the early 1950s, demecolcine (substance F) was

used for the treatment of leukemia, lymphoid hemoblastoses and Hodgkin’s
disease.

Keywords




Açafrão-bastardo Aci çiğdem Autumn crocus Chicolquicos Hirantutiya







Hiranyatuttha Høsttidløs Qatel el-kelb Qiū shuǐxiān Suranjaan shireen

Vernaculars: Urd.: Suranjaan shireen; Hin.: Hirantutiya; San.: Hiranyatuttha,

Suranjana; Ben.: Kōlakisāma śarṭamēla; Mar.: Kŏlīkśama śarada rtūtīla; Tam.:
Curincan, Curinacanmiciri; Tel.: Konceṁ śaradrtuvu; Ara.: Akna, Hafer el-mohar,
Qatel el-kelb, Shameera, Surinjan; Chi.: 秋水仙, Qiū shuǐxiān; Cze.: Ocún jesenní,
Ocún podzimní; Dan.: Høsttidløs; Dut.: Herfsttijdloos, Wilde herfsttijloos; Eng.:
Autumn crocus, Meadow saffron, Naked ladies; Fin.: Syysmyrkkylilja; Fre.: Ché-
narde, Colchique d’automne, Dame sans chemise, Faux safran, Femme nue, Lis vert,
Oignon de loup, Poulotte, Safran bâtard, Safran des prés, Tue-chien, Tue-loup,
Vachotte, Veilleuse, Veillote; Ger.: Herbsttulpe, Herbstzeitlose; Gre.: Kolchikó to
fthinoporinó; Ita.: Colchico d’autunno, Freddoline, Narciso autumnale, Strozza-
cane, Zafferano bastardo; Jap.: Inusafuran, Koruchikamu; Nor.: Tidlaus, Tidløyse;
Per.: Suranjaan, Zafran alfazar; Pol.: Zimowit jesienny; Por.: Açafrão-bastardo,
Açafrão-dos-prados, Cebola venenosa, Colquico, Narciso de outono; Rus.: Bezvre-
mennik osennij; Spa.: Azafrán bastardo, Azafrán silvestre, Cebolla montés, Chi-
colquicos, Colchico común, Colchico de otoño, Colchico oficinal, Colchico que mata,
Cólquico, Despacha pastores, Flor de otoño, Matacán, Quita meriendas, Quitame-
riendas de otoño, Villorita; Swe.: Hösttidlösa, Nakna jungfrun, Tidlösa; Tur.: Aci
çiğdem, Güz çiğdemi, Itboğan, Sonbahar çiğdemi; Vie.: Bả chó, Cây bả chó.
Description: Autumn crocus is native to grassy meadows and woods and river
banks in southeastern Ireland, England, the Netherlands and Denmark, and at
altitudes between 400 and 1,200 m ranges east to Poland and south to Spain and
central Italy and North Africa. It is the only species of its genus native to the United
Kingdom, and occurs across mainland Europe from Portugal to Ukraine. They are
generally found in periodically wet to moderately moist grasslands [20]. A peren-
nial herb 30 cm tall, having a fleshy, conical or ovate corm 3–5 cm long when
mature, with dark-brown, membranous coat, an inner coat of lighter-brown, and
producing at the base numerous fibrous roots. Internally it is white, firm, with a
milky juice, very bitter and acrid and with a radish-like odor. It is generally found
15–20 cm beneath the surface of the soil. From August to October, 1–6 flowers
arise in succession, directly from the immature corm; they are tubular and enclosed
at the base by a membranous sheath. The blooms are lavender to light-pink, with 6
flaring segments 3–4.5 cm long, and 6 stamens tipped with oblong yellow anthers,
and they wither and die down quickly.XII,C However, GhaniL described it as a root
of a plant that has yellow and white flowers, and it is white both inside and outside,
with a sweet taste; its potency is maintained for 3 years (Figs. 1, 2, 3 and 4).
Colchicum autumnale L. 683

Fig. 1 Colchicum autumnale, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://commons.
wikimedia.org/wiki/File:Illustration_Colchicum_autumnale0.jpg; www.biolib.de

Fig. 2 Colchicum autumnale, Flowers, Luc Viatour, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Colchicum_autumnale_Luc_
Viatour.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
684 Colchicum autumnale L.

Fig. 3 Colchicum autumnale, Seed Capsule, BerndH, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Colchicum_autumnale_
050505.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 4 Colchicum autumnale, Seeds, Danny S., WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Semen_Colchici_by_Danny_S._-_001.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Actions and Uses: Corm and seeds were well known to ancient Greeks and Romans
for their remedial property in gout, rheumatism, arthritis, dropsy, gonorrhea and
enlarged prostate.CXXIV Dioscorides and Galen described corms toxic and lethal, as they
Colchicum autumnale L. 685

taste delicious and increase the desire to eat more; its leaves, corm and seeds are all
poisonous. In Babylonia, it was used for swelling poison of the limbs, scorpion sting,
head and eye diseases, as well as for breast pain.LIII The plant was called by different
names through the ages: ephemera, finger of Hermes, pater noster, and tue-chiens.
Modern phytonyms refer to the land of Colchis, a mythical place close to Armenia
[12].XL According to Byzantine historians, first use of C. autumnale in the treatment of
gout was by the 5th century physician, Jacob Psychristus. The disease (podagra) was
common at the time, its main causes being overconsumption of alcoholic drinks and
food, and thus referred to as the ‘disease of kings,’ though the disease was recognized by
Hippocrates in the fifth-century B.C., who called it ‘the unwalkable disease’ [29];
anxiety and heredity were also considered among the etiological factors of the disease
[21]. Some refer to Byzantine Christian physician, Alexander of Tralles in the 6th
century A.D. as the first user for the selective and specific treatment of gout [29]. In
Unani medicine, the root (temperament, hot 3° and dry 2°) is considered as deobstruent,
purgative of phlegm, analgesic, anti-inflammatory, and aphrodisiac, and is mostly used
internally for the treatment of gout, rheumatism, sciatica, and seminal weakness. To
reduce inflammation and for the relief of pain, its paste, along with saffron, is applied
externally.LXXVII It is also described as diaphoretic and diuretic, increases secretions of
skin, kidneys and liver and the flow of bile; in large doses, it is gastrointestinal irritant
producing vomiting, purging and extreme prostration, cardiac depression, convulsions,
collapse and death. It is used in gout with an alkali; in ascites due to liver disease it is a
very efficacious remedy, and in cerebral and hepatic congestions its purgative action
benefits. Good results also follow its use in gonorrhea and chordee.LXXXI Homeopathic
preparation has also been reported beneficial in improving clinical symptoms and
hormone metabolism in patients with subclinical hyperthyroidism [34]. Corm was
included in London Pharmacopoeia from 1618 to 1639, was eliminated, but again
restored in 1788. Seeds were made official in England in 1824, as being safer than the
corms.CXXXXI
In modern practice, the alkaloid colchicine is only used as a specific treatment for
gouty arthritis.CXI Colchicine was approved by the FDA for the treatment and pro-
phylaxis of gout flares, but has also been used with varying success in the treatment of
familial Mediterranean fever, alcoholic, posthepatitic and primary biliary cirrhosis,
psoriasis, Behçet’s disease, aphthous stomatitis, linear IgA dermatosis, relapsing
polychondritis, Sweet’s syndrome, scleroderma, amyloidosis, leukocytoclastic vas-
culitis, epidermolysis bullosa, and dermatomyositis [4, 17]. Its anti-inflammatory
action was attributed to the drug’s interference with protoplasmic gelation [23],
inhibition of intracellular mobilization and extracellular release of granular enzymes
by phagocytizing leukocytes [40]. It is also successfully employed in the treatment of
familial Mediterranean fever prevalent in Egypt [14, 24, 30], and a seed decoction is
said to remedy leukemia [13]. Pernice, a sicilian pathologist first observed, more than
one-hundred years ago in 1889, mitotic changes in two dogs injected with a large dose
of tincture of colchicum, the well-known effect of a spindle poison. The finding was,
however, ignored until 1949 [11]. Colchicine, is now used in manipulating genetic
structure of plants and animals. Other uses of colchicine include plant breeding to
double the chromosomes and develop new strains of garden flowers (large blooms) or
other crops (“super” fruits and vegetables).C
686 Colchicum autumnale L.

Phytoconstituents: Besides the main active principle colchicine present in amounts

up to 0.6%,XXIV the corm contains several other alkaloids: colchiceine, colchicerine,
colchamine, 3-methylcolchicine, 2-demethylcolchicine, lumicolchicines, O-demethyl-
N-methylcolchicine, N-deacetyl-N-methylcolchicine, N-formyl-N-deacetyl-colchicine
[38],CLI and demicolcine.XXXVIII Colchicine is a pale-yellow powder soluble in water,
alcohol and chloroform,XXIV but only slightly soluble in ether or petroleumCXXXXI and
is not destroyed by drying, storage or boiling.XLVI Demecolcine is another alkaloid
with strong antimitotic activity [33]. Seeds contain 0.6–1.2% colchicine,CXXXXI also
colchicerine, 2-demethylcolchicine, N-deacetyl-N-methyl-colchicine, a- and b-lumi-
colchicine [38],CLI plus a resin, fixed oil and sugars.CXXXXI Colchicine and other
alkaloids are found throughout the plant with the highest concentrations in seeds and
corms. From bulbs collected during the course of an entire year, highest percentage of
colchicine-like compounds was found in old bulbs in the beginning of spring. It is of
advantage to collect bulbs in the fall [32]. Active anticancer alkaloidal compounds are
demecolcine and colchicine, and their contents in raw and dried leaves, stems, mother
and daughter corms decrease with drying [37].
Pharmacology: There are no pharmacological studies reported on corms or seeds.
Clinical Studies: In the early 1950s, demecolcine (substance F) was used for the
treatment of leukemia, lymphoid hemoblastoses and Hodgkin’s disease [5, 22, 35].
Mechanism of Action: Uric acid is deposited in the form of monosodium urate
crystals in joint tissues and in subcutaneous nodules called tophi. The associated
inflammation is related to the injury of leucocytes that have phagocytized these
crystals, causing release of lysosomes. Colchicine breaks the chain reaction that
leads to inflammation in joints by inhibiting phagocytic activity of leucocytes for
urate crystals.LXXXVIII Antifertility activity may be due to the presence of cytotoxic
agents, colchicine and demecolcine.XLII Colchicine is cytotoxic and acts by dis-
rupting spindle mechanism during mitosis, thereby blocking cell division [11].
Human A/Es, Allergy and Toxicity: Internal human use is considered harmful in
Unani medicine for stomach and liver.LXXVII All parts of the plant are poisonous;
fatalities have occurred following administration of this plant for gout and rheuma-
tism as well as after eating corms in place of onions and by children who have eaten
the flowers.LXXIV Toxins can pass in milk of animals that have eaten Colchicum and
can accumulate during slow ingestion to reach a toxic level.XLVI As little as 7 mg
colchicine has proved fatal, but the usual lethal dose is closer to 65 mg.CXI Lowest
human lethal dose has been reported as 186 µg in 4-days [10]. Main symptoms
of poisoning are burning of the throat and stomach, abdominal pain, violent vomit-
ing, purging, flatulence, weak quick pulse, chills, gritting of teeth, pain in the
extremities, loss of muscular power, sometimes paralysis, kidney failure and respi-
ratory failure, generally resulting in death after several days;XLVI,CVIII,CXXV,CXXXV
autopsy reveals kidney and vascular damage.CXI People might confuse this highly
poisonous plant with wild garlic (Allium ursinum), a popular spice in central
European cuisines, and the consumption results in continuing cases of accidental
poisoning [3, 26]. Most common cause of death is multiorgan failure within two to
Colchicum autumnale L. 687

four days of the ingestion [6–8, 15, 19, 31, 36, 39]. In Switzerland, there were ten
cases of accidental poisoning with C. autumnale in 29 years, resulting in diarrhea,
liver necrosis, and two cases of fatal multiorgan failure [16]. Colchicine and the plant
have also been used to commit suicide [1, 18, 28]. Prolonged therapeutic use
of colchicine may cause agranulocytosis, aplastic anemia, peripheral neuritis,
azoospermia or oligospermia, sometimes loss of hairs [9, 25],CXI and muscu-
loskeletal adverse effects ranging from myopathy to rhabdomyolysis [2]. Colchicine
is also a mutagen and teratogen, and a mitotic poison that selectively kills fetuses,
but is not necessarily teratogenic for survivors.
Animal Toxicity: Autumn crocus leaves cause toxicity in cattle, producing diar-
rhea. Administration of bulb colchicine to guinea pigs caused severe diarrhea, and
histopathological findings were consistent with those in autumn crocus-poisoned
cattle. However, mice administered with the bulb or colchicine did not develop
diarrhea, indicating a species-specific enterotoxicity [41]. Demecolcine given to
rabbits in a dose of 0.1–5 mg/kg (s.c.) was toxic to fetus when administered after
implantation, causing death within 2–4 h [27]. Colchicine, when instilled into one
uterine horn of rat in a dose of 0.1 mg resulted in decrease in fetuses in both horns
[42].
Commentary: There are no pharmacological or clinical studies reported on this
plant, probably due to its toxicity. Most of the newer published reports about this
plant are cases of accidental or intentional poisonings. However, a fresh look at the
effects of this toxic plant may be rewarding.

References
1. Allender WJ. Colchicine poisoning as a mode of suicide. J Forensic Sci.
1982;27:944–7.
2. Arslan MN, Özgün A, Daş T, et al. Colchicine-induced rhabdomyolysis: an
autopsy case. Am J Forensic Med Pathol. 2016;37:57–9.
3. Bajramović-Omeragić L, Čalkić L, Hadžić E, Aličkovič I. Accidental
poisoning with a plant Colchicum autumnale: report of two cases. Lijec
Vjesn. 2015;137:288–91.
4. Bhat A, Naguwa SM, Cheema GS, Gershwin ME. Colchicine revisited.
Ann N Y Acad Sci. 2009;1173:766–73.
5. Bock HE, Gross R. Leukemia and cancer treatment with a new alkaloid
from Colchicum autumnale; demecolcin. Acta Haematol. 1954;11:280–300.
6. Brncić N, Visković I, Perić R, et al. Accidental plant poisoning with
Colchicum autumnale: report of two cases. Croat Med J. 2001;42:673–5.
7. Brvar M, Kozelj G, Mozina M, Bunc M. Acute poisoning with autumn crocus
(Colchicum autumnale L.). Wien Klin Wochenschr. 2004;116:205–8.
8. Brvar M, Ploj T, Kozelj G, et al. Case report: fatal poisoning with Colchicum
autumnale. Crit Care. 2004;8:R56–9.
688 Colchicum autumnale L.

9. Crabie P, Pollet J, Pebay-Peyroula F. Study of hemostasis during acute

colchicine intoxication. J Eur Toxicol. 1970;3:373–85.
10. Duke JA. Phytotoxin tables. CRC. Crit Rev Toxicol. 1977;5:189–237.
11. Dustin P. The centennial of the discovery of the antimitotic properties of
colchicine. Rev Med Brux. 1989;10:385–90 (French).
12. Fabre AJ. The autumn crocus: two millenniums of actuality. Hist Sci Med.
2005;39:143–54 (French).
13. Hartwell JL. Plants used against cancer. A survey. Lloydia. 1967–71.
14. Hassan A, Trabolsi B, Frid Z. Colchicine for familial Mediterranean fever
(periodic peritonitis). Concl N Eng J Med. 1974;290:973.
15. Hermanns-Clausen M, Schindler F, Stedtler U, et al. Poisoning by the
autumn crocus plant. MMW Fortschr Med. 2006;148:45–7 (German).
16. Jaspersen-Schib R, Theus L, Guirguis-Oeschger M, Gossweiler B,
Meier-Abt PJ. Serious plant poisonings in Switzerland 1966–1994. Case
analysis from the Swiss Toxicology Information Center. Schweiz Med
Wochenschr. 1996;126:1085–98 (German).
17. Kershenobich D, Borovoy J, Guevara RL. Colchicine: rationale for its use in
liver disease. Rev Invest Clin. 1990;42(Suppl):97–100 (Spanish).
18. Kicka M, Olszowy Z, Jankowski Z, et al. Fatal colchicine poisoning—case
report and review of literature. Przegl Lek. 2010;67:630–2 (Polish).
19. Klintschar M, Beham-Schmidt C, Radner H, et al. Colchicine poisoning by
accidental ingestion of meadow saffron (Colchicum autumnale): patholog-
ical and medicolegal aspects. Forensic Sci Int. 1999;106:191–200.
20. Lambert J. La prairie a colchiques: une des plus interessantes formations
vegetales d’Ardenne, en voie de disparition. Neth J Agr Sci. 1965;13:129–42.
21. Lascaratos J. ‘Arthritis’ in Byzantium (AD 324-1453): unknown informa-
tion from nonmedical literary sources. Ann Rheum Dis. 1995;54:951–7.
22. Leonardi P, D’Agnolo B. Deacetyl-N-methylcolchicine, an antimitotic
alkaloid of Colchicum autumnale, in therapy of leukemia and Hodgkin’s
disease. Acta Med Patav. 1954;14:69–109.
23. Malawista SE, Bensch KG. Human polymorphonuclear leukocytes: demon-
stration of microtubes and effect of colchicine. Science. 1967;156:521–2.
24. Manialawi M. Colchicine for familial Mediterranean fever. New Eng J Med.
1973;289:752.
25. Merlin HE. Azoospermia caused by colchicine: a case report. Fert Steril.
1972;23:180–1.
26. Mestrallet S, Lebrun D, Zucchini L, et al. Abdominal pain, vomiting, diarrhea
in a 36-year-old man. Rev Med Intern. 2016;37:854–6 (Article in French).
27. Morris JM, Van Wagenen G, Herteau GD, Johnston DW, Carlson RA.
Compounds interfering with ovum implantation and development. I. Alka-
loids and antimetabolites. Fert Sterl. 1967;18:7–17.
28. Nagesh KR, Menezes RG, Rastogi P, et al. Suicidal plant poisoning
with Colchicum autumnale. J Forensic Leg Med. 2011;18:285–7.
29. Nuki G, Simkin PA. A concise history of gout and hyperuricemia and their
treatment. Arthritis Res. 2006;Ther 8 Suppl 1:S1 (Review).
Colchicum autumnale L. 689

30. Poffenbarger PL, Brinkley BR. Colchicine for familial Mediterranean fever:
possible adverse effects. New Eng J Med. 1974;290:56.
31. Sannohe S, Makino Y, Kita T, et al. Colchicine poisoning resulting from
accidental ingestion of meadow saffron (Colchicum autumnale). J Forensic
Sci. 2002;47:1391–6.
32. Santavy F, Reichstein T. The alkaloids of Colchicum autumnale during its
development. Pharm Acta Helv. 1952;27:71–6.
33. Schar B, Loustalot P, Gross F. Demecolcin (substance F) a new alkaloid
with strong antimitotic effect isolated from Colchicum autumnale. Klin
Wochenschr. 1954;32:49–57.
34. Scheffer C, Debus M, Heckmann C, Cysarz D, Girke M. Colchicum au-
tumnale in patients with goitre with euthyroidism or mild hyperthyroidism:
indications for a therapeutic regulative effect-results of an observational
study. Evid Based Complement Alternat Med. 2016;2016:2541912.
35. Storti E, Gallinelli R. Results of treatment of lymphoid hemoblastoses with
substance F extracted from Colchicum autumnale. G Ital Chemioter. 1954;
1:82–7 (Italian).
36. Sundov Z, Nincevic Z, Definis-Gojanovic M, et al. Fatal colchicine poisoning
by accidental ingestion of meadow saffron-case report. Forensic Sci Int. 2005;
149:253–6.
37. Vicar J, Klusáková L, Simánek V. Changes in colchicine and demecolcine
content during vegetation period of Colchicum autumnale L. Acta Univ
Palacki Olomuc Fac Med. 1993;136:5–7.
38. Willaman JJ, Li HL. Alkaloid-bearing plants and their contained alkaloids.
1957-68. Lloydia. 1970;33(3A) (Suppl):1–286.
39. Wollersen H, Erdmann F, Risse M, Dettmeyer R. Accidental fatal ingestion
of colchicine-containing leaves—toxicological and histological findings.
Leg Med (Tokyo). 2009;11 Suppl 1:S498–9.
40. Wright DG, Malawista SE. Mobilization and extracellular release of granular
enzymes from human leukocytes during phagocytosis. Inhibition by colchicine
and cortisol but not by salicylate. Arthritis Rheum. 1973;16:749–58. BA 58:
9542.
41. Yamada M, Kobayashi Y, Furuoka H, Matsui T. Comparison of entero-
toxicity between autumn crocus (Colchicum autumnale L.) and colchicine in
the guinea pig and mouse: enterotoxicity in the guinea pig differs from that
in the mouse. J Vet Med Sci. 2000;62:809–13.
42. Zipper J, Medel M, Prager R. Alterations in fertility induced by unilateral
intrauterine instillation of cytotoxic compounds in rats. Am J Obstet Gynecol.
1968;101:971–8.
Colchicum luteum Baker
(Colchicaceae)

Abstract
C. luteum is the bitter variety, whereas C. autumnale is the sweet one which is
found in meadows throughout Europe but not in India. C. luteum is found in
Afghanistan, Turkey and grassy slopes or margins of forests of the Western
Himalayas. C. luteum is distinguished from C. autumnale by its bitter taste,
smaller size, darker color and a reticulated appearance of the corms. Corms are
considered by Muslim physicians of Unani medicine as deobstruent, alterative,
analgesic, anti-inflammatory and aperient, and especially useful in gout, and
rheumatism. A paste made with saffron and eggs is applied to rheumatic and other
swellings to relieve pain and inflammation; powdered root is sprinkled on
wounds to promote healing. In gout, it is combined with aloes; with ginger and
pepper it is used as an aphrodisiac. In Indian Pharmacopoeia, the artificially dried
corms are regarded as carminative, laxative, aphrodisiac, alterative and aperient.
Corms contain a large amount of starch, a small quantity of oily resinous matter
and the bitter alkaloid, colchicine. Methanol extract and its fractions exhibited
significant inhibition of LOX enzyme, low to significant inhibitory activity of
BChE and AChE. Hydroalcohol extract produced significant and dose-dependent
inhibition of joint swelling of arthritis in rats, and significantly reduced serum
levels of TNF-a, and expression of proinflammatory mediators TNF-R1, IL-6 and
IL-1b. Dried corm powder also significantly reduced uric acid in fructose-induced
hyperuricemic rabbits, comparable to allopurinol.

Keywords
Bezvremennik želtyj
Colchique
Gelbe zeitlose
Hirantuliya
Keltamyrk-


kylilja Qalb al-‘ard
Suranjan-talkh
Tutham
Tuthanjana
Yellow saffron

Vernaculars: Urd.: Suranjan-talkh; Hin.: Haran tutiya, Hirantuliya, Surinjan; San.:

Hiranya-tuttha, Surañjãna, Tutham, Tuthanjana; Mal.: Hiranyatutham; Mar.: Mothi,
Pimpli, Suranja; Tam.: Curinacanmiciri; Tel.: Charumamidi, Priyaluvu, Raj-adanamu;
© Springer Nature Switzerland AG 2020 691
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_72
692 Colchicum luteum Baker

Ara.: Alhalah, Assabi hurmas, Haafir al-muhr, Qalb al-‘ard, Suranjan; Eng.: Golden
collyrium, Kashmir hermodactyls, Yellow autumn crocus, Yellow saffron; Fin.:
Keltamyrkkylilja; Fre.: Colchique; Ger.: Gelbe herbstzeitlose, Gelbe zeitlose; Per.:
Suranjan talkh; Rus.: Bezvremennik želtyj.
Description: C. luteum is the bitter variety, whereas C. autumnale is the sweet one
which is found in meadows throughout Europe but not in India. C. luteum is found in
Afghanistan, Turkey and grassy slopes or margins of forests of the Western Hima-
layas from Kashmir to Chamba at elevations between 2,000 and 9,000 ft in temperate
climate. C. luteum is distinguished from C. autumnale by its bitter taste, smaller size,
darker color and a reticulated appearance of the corms. C. luteum bears yellow
flowers, and contains colchicine alkaloid in fairly large proportions, and hence
externally used as a substitute for C. autumnale for the treatment of gout. Corms are
somewhat conical or broadly ovoid or elongated, and plainoconvex in section,
brownish to brownish-grey in color, dark-brown when dry, and are either translucent
or opaque. The surface is marked by indefinite and irregular longitudinal striations.
Fresh corm usually measures 15–35 mm in length and 10–20 mm in diameter; dried
corm breaks easily with a mealy fracture and the broken surface is white and starchy.
The corm is odorless and possesses bitter and acrid taste (Figs. 1 and 2).LXXXI,CV
Actions and Uses: Corms (temperament, hot 3° and dry 3°) are considered by
Muslim physicians of Unani medicine as deobstruent, alterative, analgesic, anti-
inflammatory and aperient, and especially useful in gout, and rheumatism.L,LXXVII A
paste made with saffron and eggs is applied to rheumatic and other swellings to relieve
pain and inflammation; powdered root is sprinkled on wounds to promote heal-
ing.LXXXI,C,CV In gout, it is combined with aloes; with ginger and pepper it is used as an
aphrodisiac.XXI In Indian Pharmacopoeia, the artificially dried corms are regarded as
carminative, laxative, aphrodisiac, alterative and aperient.IV,LVIII

Fig. 1 Colchicum luteum, Plant with Flowers, Gothenburg Botanical Garden, Averater, Wikimedia-
Commons; 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Colchicum_
luteum_001_GotBot_2016.jpg; https://creativecommons.org/licenses/by/4.0/deed.en
Colchicum luteum Baker 693

Fig. 2 Colchicum luteum, Flower, Gothenburg Botanical Garden, Averater, WikimediaCommons,

https://commons.wikimedia.org/wiki/File:Colchicum_luteum_002_GotBot_2016.jpg

Phytoconstituents: Corms contain a large amount of starch, a small quantity of oily

resinous matter and the bitter alkaloid, colchicine. In air-dried corms the alkaloid
present is 0.21–0.25% and in seeds 0.41–0.43%.XXI
Pharmacology: Methanol extract and its fractions exhibited significant inhibition
of LOX enzyme, low to significant inhibitory activity of BChE and AChE [1].
Hydroalcohol extract produced significant and dose-dependent inhibition of joint
swelling against formaldehyde and Freund’s adjuvant-induced arthritis in rats, and
significantly reduced serum levels of TNF-a, and expression of proinflammatory
mediators TNF-R1, IL-6 and IL-1b [4, 5]. Dried corm powder also significantly
reduced uric acid in fructose-induced hyperuricemic rabbits, comparable to allop-
urinol [3]. Methanol corms extract inhibited growth of B. subtilis, T. longifusus and
M. canis [2].
Human A/Es, Allergy and Toxicity: All A/Es and toxicity are similar to
C. autumnale, but cases of accidental poisoning are less likely due to its bitter taste.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Like C. autumnale there are no formal clinical trials reported about
this plant.

References
1. Ahmad B, Khan H, Bashir S, Ali M. Antimicrobial bioassay of Colchicum
luteum Baker. J Enzyme Inhib Med Chem. 2006;21:765–9.
2. Ahmad B, Khan H, Bashir S, et al. Inhibition activities of Colchicum luteum
Baker on lipoxygenase and other enzymes. J Enzyme Inhib Med Chem. 2006;
21:449–52.
694 Colchicum luteum Baker

3. Mohammad IS, Latif S, Yar M, et al. Comparatve uric acid lowering studies
of allopurinol with an indigenous medicinal plant in rabbits. Acta Pol Pharm.
2014;71:855–9.
4. Nair V, Kumar R, Singh S, Gupta YK. Investigation into the anti-inflammatory
and antigranuloma activity of Colchicum luteum Baker in experimental models.
Inflammation. 2012;35:881–8.
5. Nair V, Singh S, Gupta YK. Evaluation of the disease modifying activity of
Colchicum luteum Baker in experimental arthritis. J Ethnopharmacol. 2011;
133:303–7.
Commiphora gileadensis (L.) C.Chr
(Burseraceae)

(Syn.: C. opobalsamum (L.) Engl.)

Abstract
It is a deciduous shrub or small tree, native of Saudi Arabia, Yemen, southern
Oman, Sudan, Eritrea, Djibouti, Ethiopia, Somalia, and southeast Egypt. Ancient
records indicate it growing in the Dead Sea area at the time of King Solomon. The
fruit (seed) is called Habb-e-balsan; the wood is Oud, and the oil is Roghan-e-
balsa’n. The oil is obtained by a cut through the bark up to the wood; the best is
fresh, strongly fragrant, liquid, a little astringent, and is readily soluble in water;
after a while it becomes a yellowish, sticky, thick exudate. Purity of the oil is
tested by dropping few drops on a cloth, after washing it should not leave any
marks; or dropping in water quickly forms a milky liquid. Dioscorides described
the Roghan-e-balsa’n as the strongest in qualities, followed by seeds and then
wood. In traditional Arabic medicine, flower and leaf decoctions are used as
analgesic and to increase bowel movements and diuresis. Resin is astringent and
demulcent, and is used in the treatment of diseases with profuse mucous dis-
charge, such as gonorrhea, gleet, leucorrhea and chronic catarrh in elderly
patients. Fruits are also beneficial in pleurisy, hot inflammations of lungs, sciatica,
epilepsy, intestinal colic and oliguria. The oil, mixed with other oils, is used to
massage arthritic joints, it is lithotriptic and its massage of the penis cures loose-
ness. Oil is also brain and nerve tonic, resolvent, expectorant, aphrodisiac, and
promotes wound healing; used for the treatment of cold phlegmatic diseases, such
as paralysis, palsy, tetanus, epilepsy, and gonorrhea. Ethanol resin extract exhi-
bited significant protective effect against hepatotoxicity in mice, and prevented
prolongation of barbiturate-induced sleeping time associated with liver damage.
Pretreatment with ethanol extract also completely protected gastric mucosa
against various necrotizing agents.

Keywords



Balsam makkah Balsa’n Baumier de la mecque Guggulu

Mecca myrrh



Mekanmirhapuu Mekka-myrrhenstrauch Murr makki

© Springer Nature Switzerland AG 2020 695
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_73
696 Commiphora gileadensis (L.) C.Chr

Vernaculars: Urd.: Balsa’n, Murr makki; Hin.: Balsa’n, Roghan-e-balsan; San.:

Guggulu; Ara.: Akulla-balsan, Balsam, Balsa’n, Habb-el-balsana; Eng.: Arabian bal-
sam tree, Balm of Giliad, Balm of Mecca, Mecca myrrh; Fin.: Arabialainen mirhami,
Mekanmirhapuu, Mekka-palsami; Fre.: Baumier de la Mecque; Ger.: Mekka-
myrrhenstrauch; Ita.: Balsamo della Mecca; Per.: Balasãn; Tur.: Balsam Makkah.
Description: It is a deciduous shrub or small tree growing up to 5 m tall; native of
Saudi Arabia, Yemen, southern Oman, Sudan, Eritrea, Djibouti, Ethiopia, Somalia,
and southeast Egypt. Ancient records indicate it growing in the Dead Sea area at the
time of King Solomon [11]. The fruit (seed) is called Habb-e-balsan; the wood is
Oud, and the oil is Roghan-e-balsa’n. The oil is obtained by a cut through the bark
up to the wood; the best is fresh, strongly fragrant, liquid, a little astringent, and is
readily soluble in water; after a while it becomes a yellowish, sticky, thick exudate.
Purity of the oil is tested by dropping few drops on a cloth, after washing it should
not leave any marks; or dropping in water quickly forms a milky liquid. Volatile oil
is colorless and has fragrant odor, and soluble in alcohol and ether. Best wood is
thin, rough, heavy, red in color, covered with papery bark, and fragrant. Fruit is
most commonly used and the best is big yellowish-red blackish, filled with liquid,
heavy, smells like Roghan-e-balsa’n, and causes burning sensation on tongue.LXIX
Dioscorides described the Roghan-e-balsa’n as the strongest in qualities, followed
by seeds and then wood (Fig. 1).
Actions and Uses: In traditional Arabic medicine, flower and leaf decoctions are
used as analgesic and to increase bowel movements and diuresis [2]. Resin is astrin-
gent and demulcent, and is used in the treatment of diseases with profuse mucous
discharge, such as gonorrhea, gleet, leucorrhea and chronic catarrh in elderly
patients.LXXXI,CV Fruits are also beneficial in pleurisy, hot inflammations of lungs,
sciatica, epilepsy, intestinal colic and oliguria; the oil is lithotriptic and its massage
of the penis cures looseness.LXIX Unani physicians in Indian subcontinent consider
the wood as brain tonic, expectorant, diuretic and abortifacient; and the fruit, expec-
torant, emmenagogue, nerve tonic and stomachic.1 Oil (temperament, hot and
moist) is brain and nerve tonic, resolvent, expectorant, aphrodisiac, and promotes
wound healing; used for the treatment of cold phlegmatic diseases, such as paral-
ysis, palsy, tetanus, epilepsy, and gonorrhea. Oil, mixed with other oils, is used to
massage arthritic joints. Fruits and wood (temperament, hot 2° and dry 2°) are
carminative, stomachic, expectorant, and stimulant, and decoction of wood and
fruits is used in combination with gum acacia in chronic coughs, dysentery and
diarrhea; and a paste of fruits is applied to indolent ulcers, recent cuts and bleeding
wounds. It causes expulsion of the fetus and placenta.LXXVII In TCM, it is used to
treat traumatic injury, and is considered to mainly act by relaxing blood vessels [8].
Phytoconstituents: From the aerial parts, triterpenes: friedelin, canophyllal, and
oleanonic acid; the flavonols: mearnsetin and quercetin; and syringic acid have been
isolated [1]. Two diterpenes, dehydroabietic acid and sandaracopimaric acid [8], and

1
Tayyab M: Personal Communication.
Commiphora gileadensis (L.) C.Chr 697

Fig. 1 Commiphora gileadensis, Illustration, Petronella J.M. Pas, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Balsamodendron_ehrenbergianum00.jpg

three cycloartane-type triterpenoids, and seven sesquiterpenoids [10, 12], and sec-
ondary metabolites were isolated from the resin [9]. Phytochemical screening of
stem bark yielded eleven flavonoids, including six prenylated congeners, como-
phorin A–E, and comophoroside A [7]. Major components of EOs of stem bark,
leaves and fruits from Israel were reported to be the monoterpenes: a-pinene
(11–18%), sabinene (16–36%), b-pinene (6–18%), p-cymene (5–8%), limonene
(1.3–6%), c-terpinene (0.7–8%), and terpinen-4-ol (5–18%) [6]. An apoptosis-
inducing agent, b-caryophyllene (trans-(1R,9S)-8-methylene-4,11,11-trimethyl-
bicyclo[7.2.0]undec-4-ene) was isolated from EO of the stem [5].
Pharmacology: Ethanol resin extract exhibited significant protective effect against
CCl4-hepatotoxicity in mice, and prevented prolongation of barbiturate-induced
sleeping time associated with liver damage [4]. Pretreatment with ethanol extract
also completely protected gastric mucosa against various necrotizing agents [3].
Intravenous administration of aqueous extract of branches significantly lowered
systemic arterial BP and reduced HR of anesthetized rats; both effects were inhi-
bited by pretreatment with atropine [2]. Dehydroabietic acid (DA) and sandara-
copimaric acid reduced contractions of phenylephrine-induced pulmonary arteries,
and endothelium contributed to the vasodilatory effect of DA, as the effect was
698 Commiphora gileadensis (L.) C.Chr

attenuated by L-NAME, an eNOS inhibitor [8]. A cycloartane-type triterpenoid and

an aliphatic alcohol glycoside showed moderate antiproliferative effects on human
prostate cancer cell lines PC3, and inhibited expression of androgen receptor in
LNCaP cells [9], and comophoroside A was strongly cytotoxic against MCF-7 and
HepG-2 cell lines [7]. Ethanol fresh sap (oil) extract significantly reduced viability
of both immortalized and transformed epidermal cells, without affecting normal
fibroblasts and human skin organ cultures; the extract showed only traces of
b-caryophyllene, reported to be cytotoxic [11].
Human A/Es, Allergy and Toxicity: The oil should not be used in pregnant women
for fear of causing abortion, and wood decoction is harmful for intestines.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported on any of its therapeutically
used parts.

References
1. Abbas FA, Al-Massarany SM, Khan S, et al. Phytochemical and biological
studies on Saudi Commiphora opobalsamum L. Nat Prod Res. 2007;21:383–91.
2. Abdul-Ghani AS, Amin R. Effect of aqueous extract of Commiphora
opobalsamum on blood pressure and heart rate in rats. J Ethnopharmacol.
1997;57:219–22.
3. Al-Howiriny T, Al-Sohaibani M, Al-Said M, et al. Effect of Commiphora
opobalsamum (L.) Engl. (Balessan) on experimental gastric ulcers and
secretion in rats. J Ethnopharmacol. 2005;98:287–94.
4. Al-Howiriny TA, Al-Sohaibani MO, Al-Said MS, et al. Hepatoprotective
properties of Commiphora opobalsamum (“Balessan”), a traditional
medicinal plant of Saudi Arabia. Drugs Exp Clin Res. 2004;30:213–20.
5. Amiel E, Ofir R, Dudai N, et al. b-Caryophyllene, a compound isolated
from the Biblical Balm of Gilead (Commiphora gileadensis), is a selective
apoptosis inducer for tumor cell lines. Evid Based Complement Alternat
Med. 2012;2012:872394.
6. Dudai N, Shachter A, Satyal P, Setzer WN. Chemical composition and
monoterpenoid enantiomeric distribution of the essential oils from apharse-
mon (Commiphora gileadensis). Medicines. 2017;4:66.
7. El-Gamal AA, Al-Massarani SM, Abdel-Mageed WM, et al. Prenylated
flavonoids from Commiphora opobalsamum stem bark. Phytochemistry.
2017;141:80–5.
8. Gao W, Dong X, Xie N, et al. Dehydroabietic acid isolated from Commiphora
opobalsamum causes endothelium-dependent relaxation of pulmonary artery
via PI3 K/Akt-eNOS signaling pathway. Molecules. 2014;19:8503–17.
Commiphora gileadensis (L.) C.Chr 699

9. Shen T, Wan W, Yuan H, et al. Secondary metabolites from Commiphora

opobalsamum and their antiproliferative effect on human prostate cancer
cells. Phytochemistry. 2007;68:1331–7.
10. Shen T, Yuan HQ, Wan WZ, et al. Cycloartane-type triterpenoids from the
resinous exudates of Commiphora opobalsamum. J Nat Prod. 2008;71:81–6.
11. Wineman E, Douglas I, Wineman V, et al. Commiphora gileadensis sap
extract induces cell cycle-dependent death in immortalized keratinocytes
and human dermoid carcinoma cells. J Herbal Med. 2015;5:199–206.
12. Yang JL, Shi YP. Cycloartane-type triterpenoids and sesquiterpenoids from
the resinous exudates of Commiphora opobalsamum. Phytochemistry. 2012;
76:124–32.
Commiphora myrrha (Nees) Engl.
(Burseraceae)

(Syn.: C. molmol (Engl.) Engl. ex Tschirch)

Abstract
It is a resinous exudate (gum) of a tree, which is indigenous to northeastern Africa,
Oman and Saudi Arabia, but also grows in Persia and western India. In Ayurveda, it
is regarded astringent and stimulating expectorant, and is used in the treatment of
chronic bronchitis, phthisis, dyspepsia, chlorosis, and menstrual disorders. In
Unani medicine, the gum is considered astringent, antiseptic, carminative,
stomachic, anthelmintic, emmenagogue, and expectorant; and is used with other
drugs as prophylactic for epidemic diseases, also applied topically to gouty and
painful joints, and to heal wounds. Several sesquiterpenes with various biological
activities have been isolated from its resin. Furanoeudesma 1,3-diene and
menthofuran are the main constituents of myrrh oil. Aqueous suspension of myrrh
protects gastric mucosa against various ulcerogenic agents in rats, and ethanol
extract exhibited anti-inflammatory activity against acute and chronic inflammation
in mice. Myrrh treatment for six to eight successive days significantly improved
Egyptian patients suffering from metronidazole and tinidazole-resistant T. vaginalis
infection, and cured more than 85% patients suffering from fascioliasis after 6
consecutive days treatment with 600 mg dose in the morning on an empty stomach.
Several studies reported cure rates of more than 90% in Egyptian patients with
Schistosomiasis. In an RCT of Italian patients with pain of various etiologies, such
as headache, fever-associated pain, joint pain, muscle aches, lower back pain, and
menstrual cramps, myrrh extract significantly alleviated pain.

Keywords





Arbol de mirra Arbre à myrrhe Bol Echter myrrhenbaum Hirabol Mo yao





Murr Myrrh Rasagandha Saindhava

Vernaculars: Urd.: Murr; Hin.: Bol, Boli, Hirabol; San.: Bola, Gandharasa,
Goparasa, Pinda, Prana, Rasagandha, Saindhava, Samudraguggul, Vola; Ben.:
Gandharash, Gandhbol; Mal.: Narumpasa, Narumpasamaram; Mar.: Hirabol;
© Springer Nature Switzerland AG 2020 701
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_74
702 Commiphora myrrha (Nees) Engl.

Tam.: Vellaip-polam, Vellaippa-polam; Tel.: Balin tabolu, Balintra-polam; Ara.:

Murr; Chi.: Mo yao; Eng.: Myrrh; Fin.: Afrikanmirhapuu, Mirhami; Fre.: Arbre à
myrrhe; Ger.: Echter myrrhenbaum; Per.: Bol; Spa.: Arbol de mirra; Swe.: Myrra.
Description: It is a resinous exudate (gum) of a tree, which is indigenous to
northeastern Africa, Oman and Saudi Arabia, but also grows in Persia and western
India. The resin is smooth, reddish-yellow, light, soft and aromatically bitter. It is
expensive, widely used in India, and is often found adulterated with gum mukul
(also known as ‘false myrrh’) (Figs. 1 and 2).CV
Actions and Uses: In Ayurveda, it is regarded astringent and stimulating expectorant,
and is used in the treatment of chronic bronchitis, phthisis, dyspepsia, chlorosis, and
menstrual disorders.LVIII In Unani medicine, the gum (temperament, hot 2° and dry 2°)
is considered astringent, antiseptic, carminative, stomachic, anthelmintic, emmena-
gogue, and expectorant; and is used with other drugs as prophylactic for epidemic
diseases, also applied topically to gouty and painful joints, and to heal wounds,LXXVII

Fig. 1 Commiphora myrrha, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Commiphora_myrrha_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-019.jpg
Commiphora myrrha (Nees) Engl. 703

Fig. 2 Commiphora myrrha, Gum, Sjschen, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Commiphora-myrrha-resin-myrrh.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

especially dusting with its powder heals deep ulcers on head,LXIX and to resolve cold
and phlegmatic inflammations.L It kills intestinal worms and the fetus, and expels
them.LXIX
Phytoconstituents: Several sesquiterpenes with various biological activities have
been isolated from its resin [25, 29–31]. Furanoeudesma 1,3-diene and menthofuran
are the main constituents of myrrh oil, and the ethanol extract mainly contains
2-tert-butyl-1,4-naphthoquinone, benzenemethanol,3-methoxy-a-phenyl, and cur-
zerene [17].
Pharmacology: Aqueous suspension of myrrh protects gastric mucosa against var-
ious ulcerogenic agents in rats [4], and ethanol extract exhibits anti-inflammatory
activity against acute and chronic inflammation in mice [8]. Mirazid, a purified
oleo-resin extract, caused 100% reduction in both intestinal and fecal parasitic counts
in G. lamblia-infected rats [13]. Myrrh EO and ethanol extract inhibited growth
of dermatophytes, T. mentagrophytes, T. rubrum, T. verrucosum, M. canis, and
M. gypseum; oil being more potent [17]. Inhibition of E. faecalis growth inside tooth
cavity by aqueous resin extract was equal to 2% chlorhexidine [6]. Myrrh prevented
changes in hepatocytes and markedly reduced granulomas in the portal areas, and
ameliorated intercellular fibrosis in bilharzia-infected mice [21]. A similar protection
was reported against an Egyptian strain of S. mansoni in mice [22]. Myrrh oil, at
subtoxic doses, significantly reduced IL-1b-stimulated IL-6 and IL-8 production by
human gingival fibroblasts, but not by epithelial cells [28]. Myrrh was highly cytotoxic
704 Commiphora myrrha (Nees) Engl.

in the EAC cell-bearing mice and its antitumor activity was equivalent to CP [2, 3, 24].
Myrrh emulsion is a potent antioxidant, and protects against lead acetate-induced
hepatic oxidative damage and immunotoxicity by reducing LPO and enhancing
antioxidant and immune defense mechanisms [7]. Supplementation with resin sig-
nificantly attenuated ammonia-induced liver injury, decreased circulating ammonia,
and TNF-a in hyperammonemic rats [18]. The resin extract significantly decreased
circulating markers of inflammation, tumor proliferation, angiogenesis, and liver LPO
and NO in DEN-induced hepatocarcinogenesis in rats [19], but El-Shahat et al. [10]
reported no improvement in biochemical parameters or delay in DEN-induced hepa-
tocarcinogenesis in rats. Myrrh extract is also reported to exhibit strong antithrombotic
activity [23].
Clinical Studies: Myrrh treatment for six to eight successive days significantly
improved Egyptian patients suffering from metronidazole and tinidazole-resistant
T. vaginalis infection [11, 12], and cured more than 85% patients suffering from
fascioliasis after 6 consecutive days treatment with 600 mg dose in the morning on
an empty stomach [1, 16, 20, 27]. Several studies reported cure rates of more than
90% in Egyptian patients with Schistosomiasis, when the resin was orally admin-
istered at a dose of 10 mg/kg body weight/day for three days [9, 15, 26]. In an RCT
of Italian patients with pain of various etiologies, such as headache, fever-
associated pain, joint pain, muscle aches, lower back pain, and menstrual cramps,
myrrh extract (MyrLiq®) with high total furanodiene contents, and standardized
contents of curzerene, furanoeudesma-1,3-diene, and lindestrene, significantly
alleviated pain [14].
Human A/Es, Allergy and Toxicity: It is not suitable for patients with hot
temperament.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Potential Drug-Herb Interaction: Bioavailability of cyclosporine was signifi-
cantly decreased when coadministered with myrrh in rats [5].
Commentary: It is an important agent in the Arab folk medicines, especially
useful, safe and effective for parasitic infections, like Schistosomiasis, which has
been established through several formal clinical studies. Its effectiveness as anal-
gesic could be further explored.

References
1. Abo-Madyan AA, Morsy TA, Motawea SM, Morsy AT. Clinical trial of
Mirazid in treatment of human fascioliasis, Ezbet El-Bakly (Tamyia Center)
Al-Fayoum Governorate. J Egypt Soc Parasitol. 2004;34:807–18.
2. al-Harbi MM, Qureshi S, Ahmed MM, et al. Effect of Commiphora molmol
(oleo-gum-resin) on the cytological and biochemical changes induced by
cyclophosphamide in mice. Am J Chin Med. 1994;22:77–82.
Commiphora myrrha (Nees) Engl. 705

3. al-Harbi MM, Qureshi S, Raza M, et al. Anticarcinogenic effect of Commi-

phora molmol on solid tumors induced by Ehrlich carcinoma cells in mice.
Chemotherapy. 1994;40:337–47.
4. al-Harbi MM, Qureshi S, Raza M, et al. Gastric antiulcer and cytoprotective
effect of Commiphora molmol in rats. J Ethnopharmacol. 1997;55:141–50.
5. Al-Jenoobi FI, Alam MA, Al-Mohizea AM, Ahad A, Raish M. Orally coad-
ministrated oleogum resin of Commiphora myrrha decreases the bioavail-
ability of cyclosporine A in rats. Pharmazie. 2015;70:549–52.
6. Anand S, Rajan M, Venkateshbabu N, et al. Evaluation of the antibacterial
efficacy of Azadirachta indica, Commiphora myrrha, Glycyrrhiza glabra
against Enterococcus faecalis using real time PCR. Open Dent J. 2016; 10:
160–5.
7. Ashry KM, El-Sayed YS, Khamiss RM, El-Ashmawy IM. Oxidative stress
and immunotoxic effects of lead and their amelioration with myrrh
(Commiphora molmol) emulsion. Food Chem Toxicol. 2010;48:236–41.
8. Atta AH, Alkofahi A. Antinociceptive and anti-inflammatory effects of some
Jordanian medicinal plant extracts. J Ethnopharmacol. 1998;60:117–24.
9. El Baz MA, Morsy TA, El Bandary MM, Motawea SM. Clinical and
parasitological studies on the efficacy of Mirazid in treatment of Schisto-
somiasis haematobium in Tatoon, Etsa Center, El Fayoum Governorate.
J Egypt Soc Parasitol. 2003;33:761–76.
10. El-Shahat M, El-Abd S, Alkafafy M, El-Khatib G. Potential chemopreven-
tion of diethylnitrosamine-induced hepatocarcinogenesis in rats: myrrh
(Commiphora molmol) versus turmeric (Curcuma longa). Acta Histochem.
2012;114:421–8.
11. El-Sherbini GT, El Gozamy BR, Abdel-Hady NM, Morsy TA. Efficacy of two
plant extracts against vaginal trichomoniasis. J Egypt Soc Parasitol. 2009;
39:47–58.
12. El-Sherbiny GM, El Sherbiny ET. The effect of Commiphora molmol
(Myrrh) in treatment of Trichomoniasis vaginalis infection. Iran Red Cres-
cent Med J. 2011;13:480–6.
13. Fathy FM. Effect of mirazid (Commiphora molmol) on experimental
giardiasis. J Egypt Soc Parasitol. 2011;41:155–77.
14. Germano A, Occhipinti A, Barbero F, Maffei ME. A pilot study on bioactive
constituents and analgesic effects of MyrLiq®, a Commiphora myrrha extract
with a high furanodiene content. Biomed Res Int. 2017;2017:3804356.
15. Hamed MA, Hetta MH. Efficacy of Citrus reticulata and Mirazid in treatment
of Schistosoma mansoni. Mem Inst Oswaldo Cruz. 2005;100:771–8.
16. Hassan MM, Abbaza BE, El-Karamany I, et al. Detection of anti-Fasciola
isotypes among patients with fascioliasis before and after treatment with
Mirazid. J Egypt Soc Parasitol. 2004;34:857–64.
17. Mahboubi M, Kashani LM. The antidermatophyte activity of Commiphora
molmol. Pharm Biol. 2016;54:720–5.
18. Mahmoud AM, Alqahtani S, Othman SI, et al. Commiphora molmol modulates
glutamate-nitric oxide-cGMP and Nrf2/ARE/HO-1 pathways and attenuates
706 Commiphora myrrha (Nees) Engl.

oxidative stress and hematological alterations in hyperammonemic rats. Oxid

Med Cell Longev. 2017;2017:7369671.
19. Mahmoud AM, Zaki AR, Hassan ME, Mostafa-Hedeab G. Commiphora
molmol resin attenuates diethylnitrosamine/phenobarbital-induced hepato-
carcinogenesis by modulating oxidative stress, inflammation, angiogenesis
and Nrf2/ARE/HO-1 signaling. Chem Biol Interact. 2017;270:41–50.
20. Massoud A, El Sisi S, Salama O, Massoud A. Preliminary study of thera-
peutic efficacy of a new fasciolicidal drug derived from Commiphora
molmol (myrrh). Am J Trop Med Hyg. 2001;65:96–9.
21. Massoud AM, El Ebiary FH, Abd El Salam NF. Effect of myrrh extract on
the liver of normal and bilharzially infected mice. An ultrastructural study.
J Egypt Soc Parasitol 34:1–21.
22. Massoud AM, el Ebiary FH, Ibrahim SH. Light microscopic study of the
effect of new antischistosmal drug (myrrh extract) on the liver of mice.
J Egypt Soc Parasitol. 2005;35:971–88.
23. Olajide OA. Investigation of the effects of selected medicinal plants on
experimental thrombosis. Phytother Res. 1999;13:231–2.
24. Qureshi S, al-Harbi MM, Ahmed MM, et al. Evaluation of the genotoxic,
cytotoxic, and antitumor properties of Commiphora molmol using normal
and Ehrlich ascites carcinoma cell-bearing Swiss albino mice. Cancer
Chemother Pharmacol. 1993;33:130–8.
25. Rahman MM, Garvey M, Piddock LJ, Gibbons S. Antibacterial terpenes
from the oleoresin of Commiphora molmol (Engl.). Phytother Res. 2008;22:
1356–60.
26. Sheir Z, Nasr AA, Massoud A, et al. A safe, effective, herbal antischis-
tosomal therapy derived from myrrh. Am J Trop Med Hyg. 2001;65:700–4.
27. Soliman OE, El-Arman M, Abdul-Samie ER, et al. Evaluation of myrrh
(Mirazid) therapy in fascioliasis and intestinal Schistosomiasis in children:
immunological and parasitological study. J Egypt Soc Parasitol. 2004;34:
941–66.
28. Tipton DA, Lyle B, Babich H, Dabbous MKh. In vitro cytotoxic and anti-
inflammatory effects of myrrh oil on human gingival fibroblasts and epithelial
cells. Toxicol In Vitro. 2003;17:301–10.
29. Xu J, Guo Y, Li Y, et al. Sesquiterpenoids from the resinous exudates of
Commiphora myrrha and their neuroprotective effects. Planta Med. 2011;77:
2023–8.
30. Xu J, Guo Y, Zhao P, et al. Four new sesquiterpenes from Commiphora myrrha
and their neuroprotective effects. Fitoterapia. 2012;83:801–5.
31. Xu J, Guo Y, Zhao P, et al. Neuroprotective cadinane sesquiterpenes from the
resinous exudates of Commiphora myrrha. Fitoterapia. 2011;82:1198–201.
Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl.
(Burseraceae)

(Syns.: Balsamea mukul Baill.; Balsamodendrum mukul Hook. Ex Stocks;

B. roxburghii Stocks)

Abstract
A low bush or small tree with a very large trunk, native of Arabia, Somalia, Africa,
Sacotra and Yemen. Gum resin is found in the bark and pith and exudes
spontaneously as a juice. It is soft, oily, yellowish (golden color), fragrant at first and
then becomes roundish, irregular tears or hard masses of a brownish or
reddish-brown color, waxy looking; odor balsamic; taste bitter, acrid and aromatic.
It burns in fire, melts in the sun and with water it gives a brownish yellow emulsion,
and with nitric acid a purple color. Myrrh is detergent, astringent, and aperient; a
disperser of cold tumors and one of the most important of medicines as it preserves
humours from corruption. It is much used externally as a stimulant and as
disinfectant of ulcers and sores. Dissolved in women’s or ass’s milk it is dropped
into the eye in purulent ophthalmia. As an internal remedy it is given in coughs, in
atonic dyspepsia, diarrhea, amenorrhea, and worms, and is also thought to keep
away fever and prevent hair from falling off. When taken internally, it produces a
sensation of warmth in the stomach and is quickly absorbed, and acts as a bitter,
stomachic and carminative, stimulating appetite and improving digestion. It is
excreted via skin, mucous membranes and the kidneys, stimulating and disinfecting
their secretions during excretion. In Ayurveda, the gum resin has been used for
centuries to treat internal tumors, obesity, liver disorders, malignant sores and
ulcers, urinary complaints, intestinal worms, vitiligo, sinuses, edema and sudden
paralytic seizures. In TCM it is used for the treatment of trauma, arthritis, fractures
and diseases caused by blood stagnation. The gum resin known as “Moghl” in
Iranian medicine is used for the treatment of IBD. The resin is soluble in alcohol,
chloroform and ether. The gum is soluble in water and is partially precipitated by
acetate of lead and hence differs from gum Arabic. Guggulsterone, a steroid, has
been identified as one of the major active components of this gum resin, with
hypolipidemic, antioxidant, anti-inflammatory and anticancer activities.

© Springer Nature Switzerland AG 2020 707

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_75
708 Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl.

Keywords





Baijahundana Bole False myrrh Guggula Indian bedellium Kou-shikaha





Mo yao Moql Muqul Salai-gogil

Vernaculars: Urd.: Muqul; Hin.: Bol, Gubdee, Gugal, Gugala, Mukul, Salai-gogil;
San.: Drava-sihla-i-guggula, Guggalaha-sallake, Guggula, Kou-shikaha; Ben.:
Goobdee, Gugala, Guggul, Mukul; Mal.: Guggulu; Mar.: Guggula; Tam.: Gukkal,
Gukkulu, Kukkulu, Maisatchi kungiliyam; Tel.: Googula, Gukkulu, Maishakshi;
Ara.: Moql, Mukala, Murr; Chi.: Mo yao; Eng.: Bole, False myrrh, Gum-gugul,
Indian bedellium, Salai tree; Per.: Baijahundana, Boe-jahudan, Bola, Moghl.
Description: A low bush or small tree about 0.6–1.8 m high with a very large trunk,
native of Arabia, Somalia, Africa, Sacotra and Yemen. Branches many, knotty,
irregular and at right angles, terminating in sharp spines; leaves simple (or trifoliate)
and long; leaflets sessile, obovate; flowers small, brownish and fruit long and pyriform.
Gum resin is found in the bark and pith and exudes spontaneously as a juice. It is soft,
oily, yellowish (golden color), fragrant at first and then becomes roundish, irregular
tears or hard masses of a brownish or reddish-brown color, waxy looking; odor bal-
samic; taste bitter, acrid and aromatic. It burns in fire, melts in the sun and with water it
gives a brownish yellow emulsion and with nitric acid a purple color. The best Myrrh is
of a reddish-yellow color, and the surface covered with pale dust. When broken it
should show white marks like those on the finger nails. Turkish variety is the best and
the Indian one is very impure (Figs. 1 and 2).XL
Actions and Uses: Myrrh is detergent, astringent, and aperient; a disperser of cold
tumors and one of the most important of medicines as it preserves humours from
corruption. It is much used externally as a stimulant and as disinfectant of ulcers and

Fig. 1 Commiphora wightii, Plant, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Commiphora_wightii_06.JPG; https://creati
vecommons.org/licenses/by-sa/3.0/deed.en
Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl. 709

Fig. 2 Commiphora wightii, Gum, Vinayaraj, WikimediaCommons; ShareAlike 2.5 Generic CC

BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Commiphora-wightii-resin.jpg; https://crea
tivecommons.org/licenses/by-sa/2.5/deed.en

sores. Dissolved in women’s or ass’s milk it is dropped into the eye in purulent
ophthalmia. As an internal remedy it is given in coughs, in atonic dyspepsia, diarrhea,
amenorrhea, and worms, and is also thought to keep away fever and prevent hair from
falling off. Leaves, fruit, and wood are said to partake the same properties as the gum
resin.XL GhaniL describes the gum (temperament, hot 3° and dry 2°) as diuretic,
astringent, and lithotriptic, and used as a demulcent, aperient, carminative, alterative,
antispasmodic, uterine stimulant, and emmenagogue to regulate menstruation. It is
also resolvent, emollient, purgative of phlegm, expectorant, rubefacient, detergent,
aphrodisiac and antihemorrhoidal, and used in chronic ulcers and inflammation of
organs, asthma, cough, hemoptysis, facial paralysis, paralysis, rheumatism, gout,
sciatica, and specifically in bleeding piles.LXIX,LXXVII When taken internally, it pro-
duces a sensation of warmth in the stomach and is quickly absorbed, and acts as a bitter,
stomachic and carminative, stimulating appetite and improving digestion. It is excreted
via skin, mucous membranes and the kidneys, stimulating and disinfecting their
secretions during excretion.CV The oleoresin has no action on unbroken skin but on the
abraded skin and on the mucous membranes it acts as an astringent and antiseptic. It is
also useful in leprosy, syphilitic disorders, scrofulous affections, nervous and skin
diseases and in urinary disorders.XXI In Ayurveda, the gum resin has been used for
centuries to treat internal tumors, obesity, liver disorders, malignant sores and ulcers,
urinary complaints, intestinal worms, leucoderma (vitiligo), sinuses, edema and sud-
den paralytic seizures [9, 39, 51]. In TCM it is used for the treatment of trauma,
arthritis, fractures and diseases caused by blood stagnation [37]. The gum resin known
as “Moghl” in Iranian medicine is used for the treatment of IBD [29].
710 Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl.

Phytoconstituents: The resin is soluble in alcohol, chloroform and ether. The

bitter principle, obtained by exhausting the resin with warm water is an amorphous
brittle brown substance, sparingly soluble in water, and of an intensely bitter taste.
The gum is soluble in water and is partially precipitated by acetate of lead and
hence differs from gum Arabic.XXI Phytochemical investigation of this genus
identifies more than 300 secondary metabolites [37]. Guggulsterone (stereoisomers
Z-guggulsterone and E-guggulsterone), a steroid, has been identified as one of the
major active components of this gum resin, with hypolipidemic, antioxidant,
anti-inflammatory and anticancer activities [9, 39]. Other constituents reported from
the resin are triterpenes: myrrhanol A and B, myrrhanone A, and myrrhanones
B and A acetate, and epimansumbinol [16, 19, 20], cembrenoids, bicyclic diter-
pene, guggulusterone derivatives, myrrhanone derivatives, myrrhanol derivative,
a lignan [11], stigmastane-type steroids, stigmasta-5,22E-diene-3b,11a-diol and
stigmasta-5,22E-diene-3b,7a,11a-triol [38]. Z-guggulsterone is a strong thyroid
stimulatory compound in rats; it increases iodine-uptake by thyroid and enhances
activities of thyroid peroxidase and protease [49]. A volatile oil, also called myr-
rhenol or myrrhol; an oxygenated etherial volatile oil (2%); resin myrrhin (25–40%),
which by fusion becomes converted into myrrhic acid; gum 40–60%; bitter
principle—a glucoside; salts as calcium phosphate and carbonate etc. have also
been isolated.
Pharmacology: Ethanol resin extract to diabetic rats significantly lowered blood
sugar, lipids, hyperinsulinemia, LPO, protein oxidation, and improved insulin-
sensitivity, antioxidant status and delayed development of insulin-resistance [3, 30,
31]. Hypolipidemic effects of the resin have been observed in normal animals [10], in
experimental hyperlipemic animals [2, 15, 35, 36], and of resin extracts in experi-
mental hyperlipidemia [17, 41]. Fresh resin is reported to have better serum choles-
terol, TGs, and VLDL lowering effects than old samples [52]. The resin and its extracts
significantly improve cardiac function and prevent isoproterenol-induced MI and
preserve structural integrity of myocardium in rats [1, 25, 26]. Guggulsterone is pro-
tective against doxorubicin-cardiotoxicity [56].
Myrrhanol A produced more potent anti-inflammatory effect than hydrocortisone in
adjuvant-induced air pouch granuloma of mice [16]. A fraction of the gum resin was as
effective as phenylbutazone and ibuprofen in experimental arthritis [34]. Crude ethyl
acetate extract and a purified compound from the resin downregulated inflammatory
mediators such as IFN-c, IL-12, TNF-a, IL-1b and NO from peripheral blood
mononuclear cells [18]. Oral administration of resin significantly modulates neuro-
pathic pain in animals [21], and guggulipid, the neutral fraction of ethyl acetate extract,
significantly reduced spontaneous and induced pain in rats [12]. Guggulsterone pro-
tected mice against development of sign and symptoms of TNBSA- and
oxazolone-induced colon inflammation, and effectively attenuated severity of the
wasting disease [22].
Guggulsterone inhibited proliferation of various human tumor cell types including
leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma,
breast carcinoma, and ovarian carcinoma; and also inhibited proliferation of drug-
resistant cancer cells [40], induced apoptosis in human prostate cancer cells [45],
Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl. 711

and inhibited angiogenesis [55]. Topical application of guggulsterone significantly

reduced tumor incidence, lowered tumor body burden and significantly delayed
latency period of DMBA-initiated skin carcinogenesis in mice [32]. The resin and its
petroleum ether extract significantly improved thyroid structure and function in
hypothyroidism of rats [27, 42]. Administration of the extract enhanced T3 concen-
tration and T3/T4 ratio [28]. Methanol resin extract also significantly increased bone
strength and restored the bone microarchitecture of ovariectomized rats [14].
Clinical Studies: In a multicenter, double-blind, crossover study of dyslipidemic
Indian patients, guggulipid (500 mg tid) for 12-weeks significantly lowered TC,
LDL-C and TGs in 70–80% patients, and increased HDL-C in 60% patients [23].
Similar results were reported after treatment with only 50 mg guggulipid twice
daily for 24-weeks as an adjunct to a fruit- and vegetable-enriched diet in patients
with hypercholesterolemia [44]. Contrarily, in a double-blind, RCT of ambulatory,
community-dwelling, healthy adults with hypercholesterolemia in Philadelphia on
typical Western diet, treatment with guggulipid (1,000 mg or 2,000 mg), thrice
daily for 8-weeks, raised LDL-C levels by 4% and 5%, respectively, with no
significant changes in TC, HDL-C, TGs, or VLDL-C levels [47]. Another double-
blind, RCT of 34 Norwegian women and men, age 27–70 years with moderate
hypercholesterolemia, guggul 2,160 mg daily for 12-weeks, caused a significant fall
in TC and HDL-C, with no significant changes in LDL-C, TGs, and TC/HDL-C
ratio. Ten out of 18 guggul users vs 4 out of 16 placebo patients reported adverse
effects [24].
Concentrated resin extract (500 mg TID) for 2-months, significantly improved both
subjective and objective measures in 30 male and female Indian participants with knee
osteoarthritis [43]. In an RCT, 20 patients with nodulocystic acne treated with either
tetracycline 500 mg or guggulipid (equivalent to 25 mg guggulsterone) twice daily for
3-months, had progressive reduction in inflammatory lesions in 65% vs 68% in
tetracycline and gugulipid groups, respectively; patients with oily skin responded
remarkably better to guggulipid. Relapse in 4 cases on tetracyline and 2 cases on
guggulipid occurred after 3-months [48]. Treatment with the resin 3 g/d for 4-weeks of
patients with noncomplicated hemorrhoids of grade 1 and 2, significantly reduced
flatulence, dyspepsia, GER, colonoscopic grading scores, rate of constipation, and
proctorrhagia [57].
Mechanism of Action: Its effectiveness in IBD is due to its immunomodulatory,
antioxidant, and antibacterial properties as it decreases NF-jB, NO and Cox-2 [29],
and guggulsterone attenuates generation of IL-2 and IL-4 and IFNc as well as T cell
proliferation [22]. Guggulipid and commipheric acid activate human PPARa and
PPARc, and guggulipid also activates liver X receptor a [6], and guggulsterone sig-
nificantly improves PPARc expression [33] for antidiabetic effect. Guggulsterone is a
highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone
receptor activated by bile acids [5, 7, 50, 54, 58], and a key transcriptional regulator for
the maintenance of cholesterol and bile acid homeostasis [9]; and enhances liver
uptake of LDL-C through receptor mediated endocytosis to lower serum cholesterol
and liver membrane lipids [46], and also significantly inhibits LDL oxidation [53].
712 Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl.

Guggulsterone exerts its anticancer effect by modulating gene expression through

regulation of various transcription factors, including NF-jB, STAT-3 and C/EBPa,
and various steroid receptors such as androgen receptor and glucocorticoid receptors,
that leads to inhibition of cell proliferation, induction of apoptosis [45], downregu-
lation of antiapoptotic gene [40], suppression of invasion and inhibition of angio-
genesis [39, 55]. It also increases number of leucocytes in the blood and stimulates
phagocytosis.XXI
Human A/Es, Allergy and Toxicity: It is considered quite harmless and can be
taken for a long period without any harmful effects; rarely erythematous rash
and symptoms of kidney irritation may appear which disappear rapidly after the
drug is discontinued.XXI It has been described harmful for lungs and liver in Unani
medicine.LXXVII Use of guggulipid in dyslipidemic Indian patients for 24-weeks
produced only headache, mild nausea, eructation, and hiccup as side effects in a few
patients [44]. Six out of 67 American patients treated with 1,000 and 2,000 mg doses
of guggulipid for 8-weeks developed hypersensitive skin rash [47]. Ten out of eighteen
Norwegian women with moderate hypercholesterolemia, who used guggul 2,160 mg
daily for 12-weeks, reported mild GIT discomfort (7), possible thyroid problems (2),
and generalized skin rash (1) as side effects [24]. A 55-year-old Italian man developed
rhabdomyolysis with hemoglobinuria after two-weeks treatment with C. mukul extract
300 mg three times daily [4]; and a 63-year old Italian woman suffered from severe
lobular necroinflammatory changes of liver after using Equisterol®, containing gug-
gulsterol for six-months that resolved after discontinuing the medication, this patient
had earlier developed hepatitis on lovastatin [13].
Animal Toxicity: Oral LD50 of methanol extract in mice was reported to be
>2,500 mg/kg [19], and LD50 of guggulipid in rats was reported as 1,600 mg/kg [15].
Potential for Drug-Herb Interactions: Simultaneous oral administration of gug-
gulipid significantly reduced Cmax and AUCs of propranolol and diltiazem in normal
healthy volunteers [8].
Commentary: Guggulipid is heavily marketed as a natural lipid-lowering herbal
substitute of conventional drugs, despite inconsistent results reported from RCTs.
Unless, favorable results from further formal studies in the form of double-blinded
RCTs are achieved in large number of dyslipidemic patients of various ethnicity, its
lipids-lowering effects remain questionable in scientific terms.

References
1. Arora RB, Das D, Kapoor SC, Sharma RC. Effect of some fractions of Commi-
phora mukul on various serum lipid levels in hypercholesterolemic chicks and
their effectiveness in myocardial infarction in rats. Indian J Exp Biol. 1973;
11:166–8.
2. Baldwa VS, Bhasin V, Ranka PC, Mathur KM. Effects of Commiphora
mukul (Guggul) in experimentally induced hyperlipemia and atherosclero-
sis. J Assoc Physicians India. 1981;29:13–7.
Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl. 713

3. Bellamkonda R, Rasineni K, Singareddy SR, et al. Antihyperglycemic and

antioxidant activities of alcoholic extract of Commiphora mukul gum resin
in streptozotocin induced diabetic rats. Pathophysiology. 2011;18:255–61.
4. Bianchi A, Cantù P, Firenzuoli F, et al. Rhabdomyolysis caused by
Commiphora mukul, a natural lipid-lowering agent. Ann Pharmacother.
2004;38:1222–5.
5. Burris TP, Montrose C, Houck KA, et al. The hypolipidemic natural product
guggulsterone is a promiscuous steroid receptor ligand. Mol Pharmacol.
2005;67:948–54.
6. Cornick CL, Strongitharm BH, Sassano G, et al. Identification of a novel
agonist of peroxisome proliferator-activated receptors alpha and gamma that
may contribute to the antidiabetic activity of guggulipid in Lep(ob)/Lep(ob)
mice. J Nutr Biochem. 2009;20:806–15.
7. Cui J, Huang L, Zhao A, et al. Guggulsterone is a farnesoid X receptor
antagonist in coactivator association assays but acts to enhance transcription
of bile salt export pump. J Biol Chem. 2003;278:10214–20.
8. Dalvi SS, Nayak VK, Pohujani SM, et al. Effect of gugulipid on bioavailability
of diltiazem and propranolol. J Assoc Physicians India. 1994;42:454–5.
9. Deng R. Therapeutic effects of guggul and its constituent guggulsterone:
cardiovascular benefits. Cardiovasc Drug Rev. 2007;25:375–90 (Review).
10. Dixit VP, Joshi S, Sinha R, Bharvava SK, Varma M. Hypolipidemic activity
of guggal resin (Commiphora mukul) and garlic (Alium sativum Linn.) in
dogs (Canis familiaris) and monkeys (Presbytis entellus entellus Dufresne).
Biochem Exp Biol. 1980;16:421–4.
11. Francis JA, Raja SN, Nair MG. Bioactive terpenoids and guggulusteroids
from Commiphora mukul gum resin of potential anti-inflammatory interest.
Chem Biodivers. 2004;1:1842–53.
12. Goyal S, Khilnani G, Singhvi I, Singla S, Khilnani AK. Guggulipid of
Commiphora mukul, with antiallodynic and antihyperalgesic activities in
both sciatic nerve and spinal nerve ligation models of neuropathic pain.
Pharm Biol. 2013;51:1487–98.
13. Grieco A, Miele L, Pompili M, et al. Acute hepatitis caused by a natural
lipid-lowering product: when “alternative” medicine is no “alternative” at all.
J Hepatol. 2009;50:1273–7.
14. Khan S, Dwivedi C, Parmar V, et al. Methanol extract of dried exudate of
Commiphora mukul prevents bone resorption in ovariectomized rats. Pharm
Biol. 2012;50:1330–6.
15. Khanna N, Arora D, Halder S, et al. Comparative effect of Ocimum sanctum,
Commiphora mukul, folic acid and ramipril on lipid peroxidation in
experimentally-induced hyperlipidemia. Indian J Exp Biol. 2010;48:299–305.
16. Kimura I, Yoshikawa M, Kobayashi S, et al. New triterpenes, myrrhanol A and
myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory
effect on adjuvant-induced air pouch granuloma of mice. Bioorg Med Chem
Lett. 2001;11:985–9.
714 Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl.

17. Lata S, Saxena KK, Bhasin V, et al. Beneficial effects of Allium sativum,
Allium cepa and Commiphora mukul on experimental hyperlipidemia and
atherosclerosis—a comparative evaluation. J Postgrad Med. 1991;37:132–5.
18. Manjula N, Gayathri B, Vinaykumar KS, et al. Inhibition of MAP kinases
by crude extract and pure compound isolated from Commiphora mukul
leads to down regulation of TNF-alpha, IL-1beta and IL-2. Int Immunophar-
macol. 2006;6:122–32.
19. Matsuda H, Morikawa T, Ando S, et al. Absolute stereostructures of poly-
podane-type triterpenes, myrrhanol A and myrrhanone A, from guggul-gum
resin (the resin of Balsamodendron mukul). Chem Pharm Bull (Tokyo).
2004;52:1200–3.
20. Matsuda H, Morikawa T, Ando S, et al. Absolute stereostructures of poly-
podane- and octanordammarane-type triterpenes with nitric oxide production
inhibitory activity from guggul gum resins. Bioorg Med Chem. 2004;12:
3037–46.
21. Mehta AK, Tripathi CD. Commiphora mukul attenuates peripheral neuro-
pathic pain induced by chronic constriction injury of sciatic nerve in rats.
Nutr Neurosci. 2015;18:97–102.
22. Mencarelli A, Renga B, Palladino G, Distrutti E, Fiorucci S. The plant sterol
guggulsterone attenuates inflammation and immune dysfunction in murine
models of inflammatory bowel disease. Biochem Pharmacol. 2009;78:1214–23.
23. Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid.
A new hypolipidaemic agent. J Assoc Physicians India. 1989;37:323–8.
24. Nohr LA, Rasmussen LB, Straand J. Resin from the mukul myrrh tree,
guggul, can it be used for treating hypercholesterolemia? A randomized,
controlled study. Complement Ther Med. 2009;17:16–22.
25. Ojha S, Bhatia J, Arora S, et al. Cardioprotective effects of Commiphora
mukul against isoprenaline-induced cardiotoxicity: a biochemical and
histopathological evaluation. J Environ Biol. 2011;32:731–8.
26. Ojha SK, Nandave M, Arora S, et al. Effect of Commiphora mukul extract
on cardiac dysfunction and ventricular function in isoproterenol-induced
myocardial infarction. Indian J Exp Biol. 2008;46:646–52.
27. Panda S, Kar A. Guggulu (Commiphora mukul) potentially ameliorates
hypothyroidism in female mice. Phytother Res. 2005;19:78–80.
28. Panda S, Kar A. Gugulu (Commiphora mukul) induces triiodothyronine
production: possible involvement of lipid peroxidation. Life Sci 1999;65:
PL137–41.
29. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J Gastro-
enterol. 2010;16:4504–14.
30. Ramesh B, Karuna R, Sreenivasa RS, et al. Effect of Commiphora mukul
gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants
status in pancreas and heart of streptozotocin induced diabetic rats. Asian
Pac J Trop Biomed. 2012;2:895–900.
Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl. 715

31. Ramesh B, Saralakumari D. Antihyperglycemic, hypolipidemic and antioxi-

dant activities of ethanolic extract of Commiphora mukul gum resin in
fructose-fed male Wistar rats. J Physiol Biochem. 2012;68:573–82.
32. Sarfaraz S, Siddiqui IA, Syed DN, et al. Guggulsterone modulates MAPK
and NF-kappaB pathways and inhibits skin tumorigenesis in SENCAR
mice. Carcinogenesis. 2008;29:2011–8.
33. Sharma B, Salunke R, Srivastava S, Majumder C, Roy P. Effects of guggul-
sterone isolated from Commiphora mukul in high fat diet induced diabetic
rats. Food Chem Toxicol. 2009;47:2631–9.
34. Sharma JN, Sharma JN. Comparison of the anti-inflammatory activity of
Commiphora mukul (an indigenous drug) with those of phenylbutazone and
ibuprofen in experimental arthritis induced by mycobacterial adjuvant.
ArzneimForsch. 1977;27:1455–7.
35. Sheela CG, Augusti KT. Antiperoxide effects of S-allyl cysteine sulphoxide
isolated from Allium sativum Linn. and gugulipid in cholesterol diet fed rats.
Indian J Exp Biol. 1995;33:337–41.
36. Sheela CG, Augusti KT. Effects of S-allyl cysteine sulfoxide isolated from
Allium sativum Linn. and gugulipid on some enzymes and fecal excretions
of bile acids and sterols in cholesterol fed rats. Indian J Exp Biol. 1995;33:
749–51.
37. Shen T, Li GH, Wang XN, Lou HX. The genus Commiphora: a review of
its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol.
2012;142:319–30.
38. Shen T, Zhang L, Wang YY, et al. Steroids from Commiphora mukul
display antiproliferative effect against human prostate cancer PC3 cells via
induction of apoptosis. Bioorg Med Chem Lett. 2012;22:4801–6.
39. Shishodia S, Harikumar KB, Dass S, et al. The guggul for chronic diseases:
ancient medicine, modern targets. Anticancer Res. 2008;28:3647–64 (Review).
40. Shishodia S, Sethi G, Ahn KS, Aggarwal BB. Guggulsterone inhibits tumor
cell proliferation, induces S-phase arrest, and promotes apoptosis through
activation of c-Jun N-terminal kinase, suppression of Akt pathway, and
downregulation of antiapoptotic gene products. Biochem Pharmacol. 2007;
74:118–30.
41. Siddiqui MZ, Mazumder PM. Comparative study of hypolipidemic profile
of resinoids of Commiphora mukul/Commiphora wightii from different geo-
graphical locations. Indian J Pharm Sci. 2012;74:422–7.
42. Singh AK, Tripathi SN, Prasad GC. Response of Commiphora mukul
(guggulu) on melatonin induced hypothyroidism. Anc Sci Life. 1983;3:85–90.
43. Singh BB, Mishra LC, Vinjamury SP, et al. The effectiveness of Commi-
phora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther
Health Med. 2003;9:74–9.
44. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of
Commiphora mukul as an adjunct to dietary therapy in patients with hyper-
cholesterolemia. Cardiovasc Drugs Ther. 1994;8:659–64.
716 Commiphora wightii (Arn.) Bhandari/C. mukul (Hook. ex Stocks) Engl.

45. Singh SV, Choi S, Zeng Y, et al. Guggulsterone-induced apoptosis in human

prostate cancer cells is caused by reactive oxygen intermediate depen-
dent activation of c-Jun NH2-terminal kinase. Cancer Res. 2007;67:
7439–49.
46. Singh V, Kaul S, Chander R, Kapoor NK. Stimulation of low density
lipoprotein receptor activity in liver membrane of guggulsterone treated rats.
Pharmacol Res. 1990;22:37–44.
47. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of
hypercholesterolemia: a randomized controlled trial. JAMA. 2003;290:
765–72.
48. Thappa DM, Dogra J. Nodulocystic acne: oral gugulipid versus tetracycline.
J Dermatol. 1994;21:729–31.
49. Tripathi YB, Malhotra OP, Tripathi SN. Thyroid stimulating action of
Z-guggulsterone obtained from Commiphora mukul. Planta Med. 1984;50:
78–80.
50. Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers
cholesterol as an antagonist ligand for FXR. Science. 2002;296:1703–6.
51. Urizar NL, Moore DD. GUGULIPID: a natural cholesterol-lowering agent.
Annu Rev Nutr. 2003;23:303–13.
52. Vyas KY, Bedarkar P, Galib R, Prajapati PK. Comparative antihyperlip-
idaemic activity of navīna (fresh) and purāṇa (old) Guggulu. Anc Sci Life.
2015;35:101–9.
53. Wang X, Greilberger J, Ledinski G, et al. The hypolipidemic natural product
Commiphora mukul and its component guggulsterone inhibit oxidative
modification of LDL. Atherosclerosis. 2004;172:239–46.
54. Wu J, Xia C, Meier J, et al. The hypolipidemic natural product guggulsterone
acts as an antagonist of the bile acid receptor. Mol Endocrinol. 2002;16:1590–7.
55. Xiao D, Singh SV. z-Guggulsterone, a constituent of ayurvedic medicinal
plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo. Mol
Cancer Ther. 2008;7:171–80.
56. Xu HB, Shen ZL, Fu J, Xu LZ. Reversal of doxorubicin resistance by
guggulsterone of Commiphora mukul in vivo. Phytomedicine. 2014;21:
1221–9.
57. Yousefi M, Mahdavi MR, Hosseini SM, et al. Clinical evaluation of
Commiphora Mukul, a botanical resin, in the management of hemorrhoids: a
randomized controlled trial. Pharmacogn Mag. 2013;9:350–6.
58. Yu BZ, Kaimal R, Bai S, et al. Effect of guggulsterone and cembranoids
of Commiphora mukul on pancreatic phospholipase A(2): role in hypo-
cholesterolemia. J Nat Prod. 2009;72:24–8.
Convolvulus scammonia B.P.
(Convolvulaceae)

Abstract
A perennial, twining, very small, shrubby and diffuse plant, that is native of
eastern Mediterranean basin, Syria, western Asia, and Greek Islands; also grows
in India. The gum resin (scammony resin), obtained by incising the fresh root,
occurs in flattened cakes or irregular pieces of a brown, dark-grey or nearly black
color, and often covered with a greyish-black powder, brittle and glossy. It is a
hydrogogue or cholagogue cathartic and anthelmintic; more active than Jalap,
acts very promptly, causes severe gripping, colic and watery stool. It is largely
used in dropsy, anasarca, cerebral affections, torpid liver and in intestinal catarrh
with shiny intestinal mucous. Also used for tapeworms, and due to its insipid
taste can be given to children in constipation and as vermifuge for roundworms
and tapeworms. In Unani medicine, it is used after a purification process to avoid
gastrointestinal adverse effects. The sap contains resin, gum, sugar, and starch.
Root contains an active principle jalapin—identical with convolvulin of
Jalap. Scammony is inert by itself, until it combines with bile in small intestine
and forms a strong purgative complex that stimulates liver and intestinal glands
secretion.

Keywords




Alepponkierto Bingözotu Ipomea purgativa Mahmooda Purgierwinde






Sakamunia Saqmunia Scammonéa d’alep Scammonium Virgin scammony

Vernaculars: Urd.: Saqmunia; Hin.: Sakamunia; Ben.: Sakmoniya; Tam.: Caka-

moni, Cakamuniya, Mamuda; Tel.: Shakmuniya; Ara.: Mahmooda, Saqmunia; Dut.:
Scammonium; Eng.: Aleppo scammony, Virgin scammony; Fin.: Alepponkierto;
Fre.: Liseron scammonée, Scammonéa d’Alep; Ger.: Purgierwinde, Syrische winde;
Ita.: Ipomea purgativa, Scammonea d’Aleppo; Per.: Mahmudah, Saqmonia; Tur.:
Bingözotu.

© Springer Nature Switzerland AG 2020 717

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_76
718 Convolvulus scammonia B.P.

Description: A native of eastern Mediterranean Basin, Syria, western Asia, and

Greek Islands; also grows in India (Gujarat State). A perennial, twining, very small,
shrubby and diffuse plant, growing up to 0.8 m; leaves ovate, sessile, very small and
acute, of an ash color; flowers numerous, small, subsessile, and of a white or pink color.
Roots are contorted or cylindrical and tapering, brown outside and white inside;
surface longitudinally furrowed, having a particular smell and bitter taste. The gum
resin (scammony resin), obtained by incising the fresh root, occurs in flattened cakes or
irregular pieces of a brown, dark-grey or nearly black color, and often covered with a
greyish-black powder, brittle and glossy. When broken, the surface is resinous, porous
and dark brown. Ash-grey when reduced to powder, triturated with water yields
greenish emulsion; odor characteristic and taste acrid, soluble in ether.LXXXI Best
scammony is clean, light and spongy, easily breakable, and turns white when placed on
the tongue without causing any irritation (Figs. 1 and 2).LXIX
Actions and Uses: It is a hydrogogue or cholagogue cathartic and anthelmintic;
more active than Jalap, acts very promptly, causes severe gripping, colic and watery
stool. It is largely used in dropsy, anasarca, cerebral affections, torpid liver and in
intestinal catarrh with shiny intestinal mucous.XXI,CV Also, used for tapeworms, and
due to its insipid taste can be given to children in constipation and as vermifuge for

Fig. 1 Convolvulus scammonia, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Convolvulus_scammonia_-_K%
C3%B6hler%E2%80%93s_Medizinal-Pflanzen-046.jpg
Convolvulus scammonia B.P. 719

Fig. 2 Convolvulus scammonia, Scammony, Steve Hurst, USDA, https://plants.usda.gov/java/

largeImage?imageID=cosc10_001_ahp.tif

roundworms and tapeworms; its use should be avoided if there is any irritability of
the stomach or bowels.LXXXI In Unani medicine, it (temperament, hot 3° and dry
3°) is used after a purification process to avoid gastrointestinal adverse effects. For
purification, the drug is placed inside hollowed out apple or quince, covered with
dough like a dumpling and baked in an oven; the dried scammony is powdered and
clinically used.LXIX Internally, a strong purgative, slightly gastric and liver tonic,
abortifacient (both internally and as a douche), and is used in ascites, coma, chronic
constipation and to expel worms; particularly used as phlegm and bile purgative and
as abortifacient. Externally it is detergent, and used in the treatment of vitiligo,
eczema, dermatitis, and other skin diseases, rheumatism, sciatica, and chronic
headache.LXXVII It is also described as anti-inflammatory, carminative, diuretic, and
deobstruent, and enhances effects of other purgatives.L
Phytoconstituents: The sap contains resin 75–90%, gum 3–8%, sugar, and
starch.LXXXI Root contains an active principle jalapin—identical with convolvulin
of Jalap. Ether-soluble resin glycoside (‘jalapin’) and two resin glycosides, named
scammonin I and II were obtained from scammony roots [2]. Scammonins VII and
VIII, two minor ether-soluble resin glycosides, and (2S)-2-methylbutyric acid and
tiglic acid are also reported from the roots [3]. This drug was also described as
another source for ergot alkaloids besides the fungus Clavicips purpurea, although
no such chemical compounds were ever isolated [1].
Pharmacology: One report is quoted as showing that an ether extract of scam-
mony resin stimulated isolated guinea pig uterus [1].
Mechanism of Action: Scammony is inert by itself, until it combines with bile in
small intestine and forms a strong purgative complex that stimulates liver and
intestinal glands secretion.
720 Convolvulus scammonia B.P.

Human A/Es, Allergy and Toxicity: Nausea, vomiting, cramps, abdominal dis-
comfort, anorexia and palpitation are commonly reported A/Es.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no formal clinical studies, and this drug is only used by
traditional herbal medicine practitioners as purgative, especially of Indian
subcontinent.

References
1. Alberto-Puleo M. The obstetrical use in ancient and early modern times of
Convolvulus scammonia or Scammony: another nonfungal source of ergot
alkaloids? J Ethnopharmacol. 1979;1:193–5.
2. Noda N, Kogetsu H, Kawasaki T, Miyahara K. Scammonins I and II, the
resin glycosides of radix scammoniae from Convolvulus scammonia. Phyto-
chemistry. 1990;29:3565–9.
3. Noda N, Kogetsu H, Kawasaki T, Miyahara K. Scammonins VII and VIII, two
resin glycosides from Convolvulus scammonia. Phytochemistry. 1992;31:
2761–6.
Cotoneaster nummularius Fisch. & C.A.Mey.
(Rosaceae)

Abstract
An exudation of a tree called Kashira; a mountainous winter deciduous woody
shrub or small tree with yellow and white mottled wood. It is found in northwest
India, Pakistan, China, Iran, Afghanistan, Central Asia, and Mediterranean
countries. The manna exudes or oozes out of the leaves, bark of the trunk and
large branches; sometimes it bursts through large pores spontaneously. Manna is
aperient and expectorant, and strengthens liver, stomach and intestines, and
counteracts hot humours that are generated by those organs. As a laxative it is
used for delicate persons, females and children, in fevers, torpid liver, deranged
stomach and intestines; as pectoral emollient and expectorant, used for chronic
bronchitis and coughs; and as detergent, used to remove pigmentation of skin.
Manna is used for the treatment of diabetes mellitus and hemorrhoids and as an
expectorant in Anatolia (Turkey) folk medicine. Total phenolic and flavonoid
contents of water extract of twigs are the highest, followed by methanol and
ethyl acetate extracts. Major phenolic compounds in extracts are ferulic acid,
chlorogenic acid, (−)-epicatechin and catechin. High concentration of ferulic
acid is considered to be responsible for the biological activities.

Keywords


Asian cotoneaster Black wool tree
Dağmuşmulası
Kashiru
Shirkhisht



Siah chob Sira khista

Vernaculars: Urd.: Shirkhisht; Hin.: Sira khista; Eng.: Asian cotoneaster, Black
wool tree; Per.: Bhaklu (Manna), Kashiru, Shirkhisht, Shirkhushk, Siah chob; Tur.:
Dağmuşmulası, Tavs¸an elması.
Description: An exudation of a tree called Kashira; a mountainous winter deciduous
woody shrub or small tree with yellow and white mottled wood. It is found in
northwest India, Pakistan, China, Iran, Afghanistan, Central Asia, and Mediterranean

© Springer Nature Switzerland AG 2020 721

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_77
722 Cotoneaster nummularius Fisch. & C.A.Mey.

Fig. 1 Cotoneaster nummularius, Plant, Elie Plus, WikimediaCommons; ShareAlike 4.0 Interna-
tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Cotoneaster_nummularius_5.jpg;
https://creativecommons.org/licenses/by-sa/4.0/deed.en

Fig. 2 Cotoneaster nummularius, Flowers, Gideaon Pisanty, WikimediaCommons, https://commo

ns.wikimedia.org/wiki/File:Cotoneaster_nummularius_3.jpg
Cotoneaster nummularius Fisch. & C.A.Mey. 723

countries. It flowers from April to June; blooms in clusters of 3–5 white hermaphrodite
flowers. The manna exudes or oozes out of the leaves, bark of the trunk and large
branches; sometimes it bursts through large pores spontaneously. However, making
incisions in the bark increases the oozing of the substance.L It occurs in flat viscid
pieces or yellowish-white, granules of the size of millet seeds. Each piece is 5–10 cm
long and 2.5–4 cm wide and resembles ordinary camphor; odor sugary, and easily
melts in mouth leaving a sweet cool taste (Figs. 1 and 2).XL
Actions and Uses: Manna (temperament, hot 1° and moist 1°) is aperient and
expectorant, and strengthens liver, stomach and intestines, and counteracts hot
humours that are generated by those organs.XL As a laxative it is used for delicate
persons, females and children, in fevers, torpid liver, deranged stomach and intestines;
as pectoral emollient and expectorant, used for chronic bronchitis and coughs; and as
detergent, used to remove pigmentation of skin.LXXVII,CV It is given to newborn to
bring out the muconium.LXXXI Manna is used for the treatment of diabetes mellitus and
hemorrhoids and as an expectorant in Anatolia (Turkey) folk medicine [1, 3, 4].
Phytoconstituents: Glucose 8.3%, sucrose 4.1% and a sugar, called chirkhestite,
50% of which belongs to mannite group and is nearly related to sorbit. Total
phenolic and flavonoid contents of water extract of twigs are the highest, followed
by methanol and ethyl acetate extracts. Major phenolic compounds in extracts are
ferulic acid, chlorogenic acid, (−)-epicatechin and catechin. High concentration of
ferulic acid is considered to be responsible for the biological activities [5].
Pharmacology: Ethyl acetate, methanol and aqueous extracts of twigs possess
significant antioxidant, a-glucosidase and a-amylase inhibitory activities. Water
extract inhibited growth of S. aureus (MSSA), S. aureus (MRSA), S. lutea and
E. faecalis [5]. Methanol and water extract exhibited remarkable AChE inhibitory
activity, and methanol extract significantly inhibited a-glucosidase and a-amylase
[5]. Pretreatment of mice with aqueous and alcohol extracts for 5-days was sig-
nificantly protective against gamma irradiation [2].
Human A/Es, Allergy and Toxicity: It causes gaseous distension and thins semen,
decreases ejaculation time, and is contraindicated in colics, as it exacerbates colic.L
Animal Toxicity: LD50 (i.p.) of aqueous and alcohol extracts in mice were
reported to be 2,890 mg/kg and 17,500 mg/kg, respectively [2].
Commentary: Its use is very limited by traditional folk medicine practitioners, and
no formal clinical trials are reported. It might hold promise as antidiabetic and
memory-enhancing agent, as it possesses significant antioxidant, a-glucosidase and
a-amylase inhibitory activities, and remarkable AChE inhibitory activity.
724 Cotoneaster nummularius Fisch. & C.A.Mey.

References
1. Cakilcioglu U, Khatun S, Turkoglu I, Hayta S. Ethnopharmacological survey
of medicinal plants in Maden (Elazig-Turkey). J Ethnopharmocol. 2011;137:
469–86.
2. Haddad F, Moghimi A, Salmani A, Rahimi MF, Gawam-Nasiri MR. Analysing
the radioprotective effect of Cotoneaster nummularia in mouse bone marrow
cells using micronucleus assay. J Cell Mol Res. 2009;1:77–83.
3. Ozgen U, Kaya Y, Houghton P. Folk medicines in the villages of Ilıca
District (Erzurum-Turkey). Turk J Biol. 2012;36:93–106.
4. Polat R, Cakilcioglu U, Satil F. Traditional uses of medicinal plants in Solhan
(Bingöl-Turkey). J Ethnopharmocol. 2013;148:951–63.
5. Zengin G, Uysal A, Gunes E, Aktumsek A. Survey of phytochemical
composition and biological effects of three extracts from a wild plant
(Cotoneaster nummularia Fisch. et Mey.): a potential source for functional
food ingredients and drug formulations. PLoS One. 2014;9:e113527.
Crocus sativus L.
(Iridaceae)

(Syns.: C. officinalis (L.) Honck.; C. orsinii Parl.; C. pendulus Stokes; C. setifolius

Stokes)

Abstract
Crocus sativus is a small, perennial stemless plant, mainly cultivated in Iran,
Greece, Spain, India and France. Saffron consists of a small portion of the style and
three long tubular stigmas of a rich orange color. Saffron is the most expensive spice
by weight in the world. Saffron has a rich ancient history of use from the East (India,
Persia, China, Arabia) to the West (Rome, Greece, Spain), in various forms.
Cultivation and human use of saffron for medicinal purposes spans more than
3500 years, including its use against cancer and depression. Mesopotamians used
it in religious celebrations and for health benefits, Phoenicians used it as dye,
and Romans used it as dye, in perfumes, and in healthcare. It was considered
diuretic, astringent, deobstruent, and emmenagogue, and used as cardiac stimulant,
aphrodisiac, improving skin complexion, increasing brilliancy of eyes, and
promoting childbirth. Razi, the great Persian physician, said ‘it is a diuretic and a
stimulant of sexual desire, and is a digestive drug with astringent properties; it
cleanses the stomach.’ Saffron is also antispasmodic, and is used in cases of
amenorrhea, chlorosis, seminal debility, leucorrhea, dysmenorrhea, flatulent colic,
spasmodic asthma and cough, rheumatism and neuralgic pain. In traditional
Chinese medicine it has been used as an anodyne or tranquilizer, antipyretic and to
improve circulation. Chemical analysis of saffron stigmas has shown the presence
of more than 150 volatile, non-volatile and aroma yielding compounds, including
safranal, zeaxanthin, lycopene, a- and b-carotenes and carotenoids; they also
include fat, minerals, protein, crude fiber, and sugars, including starch, reducing
sugars, pentosans, gums, pectin, and dextrins. Saffron extracts and crocins
ameliorate experimentally-induced impairment of learning and memory processes
in animals, and pretreatment with aqueous extract significantly attenuated cerebral
ischemia-induced neurobehavioral and neurochemical changes in rats. Saffron, its
hydroalcohol extract, and the petals treatment was effective in patients with mild to

© Springer Nature Switzerland AG 2020 725

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_78
726 Crocus sativus L.

moderate depression, comparable to fluoxetine and imipramine, and also amelio-

rated some of the fluoxetine-induced sexual dysfunction in women, including
arousal, lubrication, and pain.

Keywords



Açafrão Kesara Krokos Kunkuma

Kurkum
Sa-fa-lang
Safran




Saffron Za’afran Zağferan

Vernaculars: Urd.: Za’afran; Hin.: Kangan-mundi, Karkum, Kesara, Zaffran;

San.: Agnishikha, Bãhlika, Bhavarakta, Ghusrna, Kashmirajanma, Kãśmira,
Kunkuma, Kurikuma, Kusrunam, Mangalya, Nagakeshara, Rudhira, Saurab, Sau-
rapha kesara; Ben.: Jafran, Kangan-mundi, Kesara; Guj.: Keshar; Mal.: Kunkuma-
pavva, Piwva konger, Kunkumam, Kunkumappu; Mar.: Kesara, Keshar; Tam.:
Kungumappu, Kungumapuvu, Kunkumappu, Kunlumappu; Tel.: Kunkumapave,
Kunkumma-purru, Kunkuma puvva; Ara.: Krûkû, Kurkum, Zaffran; Chi.: 番红花,
Fan-hung-hwa, Sa-fa-lang; Cze.: Šafrán; Dan.: Safran; Dut.: Safraan, Saffraankrokus;
Eng.: Saffron; Fin.: Maustesahrami, Sahrami; Fre.: Safran; Ger.: Safran, Safrankro-
kus; Gre.: Krokos, Safrani, Zafora; Ind.: Kunyit kering; Ita.: Zaffarano, Zafferano;
Jap.: Bankoka, Safuran; Kor.: Sapuran, Syapuran; Maly.: Kuma-kuma; Nep.: Kesari;
Nor.: Safran; Per.: Abir, Karkum, Za’afran, Zipharana; Pol.: Krokus uprawny; Por.:
Açafrão; Rus.: Šhafran; Sin.: Kūmkūma, Kūmkūmappū; Spa.: Azafrán; Swe.: Saf-
fran; Tag.: Kashubha, Saffron; Tha.: Ya faran; Tur.: Çiğdem, Safran, Zağferan; Vie.:
Màu vàng nghệ, Nghệ tây.
Description: Crocus sativus is a small, perennial stemless plant, mainly cultivated
in Iran, Greece, Spain, India and France. The plant grows to a height of 10–30 cm;
has 5–11 true leaves that are covered by 5–11 nonphotosynthetic white leaves. In
October, the plant blooms striped purple, with a honey-like smell [79]; inside is a
3-branched stigma, which are the distal ends of the plant’s carpels; the color of the
stigma depends on the level of carotenoid and lycopene [62]. Saffron consists of a
small portion of the style and these, three long (1.25–2.5 cm) tubular stigmas of a
rich orange color. The upper extremity of each stigma spreads out to form a flat
lamina with a dentate border;XL peculiar and highly aromatic odor, taste
mucilaginous, slightly bitter and pungent. Saffron is the most expensive spice by
weight in the world, and its world’s annual production is estimated around 300 tons
per year (Iran accounts for about 76% of world production) [41] (Figs. 1, 2 and 3).
Actions and Uses: Saffron has a rich ancient history of use from the East (India,
Persia, China, Arabia) to the West (Rome, Greece, Spain), in various forms. Culti-
vation and human use of saffron for medicinal purposes spans more than 3500 years
[17], including its use against cancer and depression [108]. Mesopotamians used it in
religious celebrations and for health benefits, Phoenicians used it as dye, and Romans
used it as dye, in perfumes, and in healthcare [66]. It was considered diuretic, astrin-
gent, deobstruent, and emmenagogue, and used as cardiac stimulant, aphrodisiac,
improving skin complexion, increasing brilliancy of eyes, and promoting childbirth.XL
Crocus sativus L. 727

Fig. 1 Crocus sativus, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wikimedia-
Commons, https://commons.wikimedia.org/wiki/File:Crocus_sativus_-_K%C3%B6hler%E2%80
%93s_Medizinal-Pflanzen-194.jpg

Fig. 2 Crocus sativus, Flowers, KENPEI, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Crocus_sativus2.jpg; https://creativecomm
ons.org/licenses/by-sa/3.0/deed.en
728 Crocus sativus L.

Fig. 3 Crocus sativus, Stigmas, Prof. Akbar, Original

Razi [99], the great Persian physician in his book Al-Hawi mentioned saffron as
diuretic, analgesic, anti-inflammatory, hepatoprotective, appetite suppressant,
antidepressant, hypnotic, and bronchodilator [77]. Razi said…‘it is a diuretic and a
stimulant of sexual desire, and is a digestive drug with astringent properties; it cleanses
the stomach [55].’ Jorjani [56] stated in his book Zakhireh Kharazmshahi, that:
“saffron is astringent and resolvent and its fragrance can strengthen these two effects.
Hence, its action on enlivening the essence of the spirit and inducing happiness is
great.” In Iranian folk medicine, saffron is used in the treatment of bronchitis,
cephalalgia, pharyngoplasty, vomiting, epilepsy, inflammations, skin diseases, septic
inflammations, fever, and for stimulation of circulation [77, 110]. Saffron is also
antispasmodic, and is used in cases of amenorrhea, chlorosis, seminal debility, leuc-
orrhea, dysmenorrhea, flatulent colic, spasmodic asthma and cough, rheumatism and
neuralgic pain [102].LXXXI In Unani medicine, it (temperament, hot 2° and dry 1°) is
also described as cardiac, nerve and liver tonic, detergent, and antiseptic, but it
weakens kidney functions.LXXVII Aphrodisiac virtue of saffron has been ascribed to its
essential oil contents.CV In Ayurveda, it is used in vyañga, vrana, ŝiroroga, drstiroga,
chardi, kãsa, kantharoga, sidhma, udavarta, mūtrãghãta, suryavarta and ardhavb-
hedaka.CXXVII In traditional Chinese medicine it has been used as an anodyne or
tranquilizer [87], antipyretic and to improve circulation.LXVI
Phytoconstituents: Chemical analysis of saffron stigmas has shown the presence
of more than 150 volatile, non-volatile and aroma yielding compounds, including
safranal, zeaxanthin, lycopene, a- and b-carotenes and carotenoids [106]; they also
include 5% fat, 10% moisture, 5% minerals, 12% protein, 5% crude fiber, and 63%
sugars, including starch, reducing sugars, pentosans, gums, pectin, and dextrins
(% w/w) [1]. Aqueous and ethanol stigma extracts show the presence of alkaloids
and saponins; while the aqueous and ethanol extracts of petals contain flavonoids,
Crocus sativus L. 729

tannins and anthocyanins [51]; fresh flower petals contain kaempferol [64]. Major
bioactive volatile compounds include terpenes, terpenes alcohol, and their esters,
crocin (the water soluble carotenoid), picrocrocin (bitter principle) and safranal
(volatile agent), responsible for saffron’s exclusive color, taste and odor, respec-
tively, and also its medicinal properties [8, 20, 72, 100]. Crocin is not absorbed
from GIT, crocin hydrolysis after saffron digestion in the GIT results in the for-
mation of crocetin esters [34], only crocetin is absorbed from GIT both in animals
[14], and in humans [112]. Crocetin esters are the compounds responsible for
saffron’s color [25]. Safranal, crocin and crocetin, also possess antioxidant activity
[23]. Heating adversely affects the concentrations of crocins and safranal, but the
concentration of picrocrocin remains unaffected [100]. Other active ingredients
include zeaxanthin, lycopene, carotene, and vitamins particularly riboflavin and
thiamine [20]. Eight new minor glycosides were also reported [111]. Crocusatins F,
G, H, and I are also reported in saffron; crocusatin H, crocin-1, and crocin-3 possess
significant tyrosinase inhibitory activity [65].
Pharmacology: Pretreatment with aqueous extract significantly attenuated cerebral
ischemia-induced neurobehavioral and neurochemical changes in rats [103]. Saffron
extracts and crocins ameliorate experimentally-induced impairment of learning and
memory processes in animals, by modulating storage and/or retrieval of information
and significantly improving CNS antioxidant status [3, 36–38, 81, 82, 91, 92, 116], and
exhibit sedative and anxiolytic effects [90, 116]. Crocin exhibits antioxidant, anti-
tumor, memory enhancing, antidepressant, anxiolytic and aphrodisiac activities,
without any major toxicity in experimental models [8]. Saffron extract does not
improve aluminum-induced impairment of cognitive performance of mice, but sig-
nificantly reverses Al-induced changes in MAO activity and levels of LPO and GSH,
indicating its neuroprotective potential [67]. Saffron and crocin prevent chronic
stress-induced oxidative stress damage of the brain, liver and kidneys [18], and crocin
protects I/R injury and cerebral edema in a rat model of stroke, primarily by sup-
pressing free radicals formation and increased antioxidant enzymes activity [113, 117].
Saffron and crocetin protected dopaminergic neurons in the substantia nigra from
deleterious effects of 6-OHDA and MPTP [5, 96]. Both aqueous and ethanol extracts,
and low dose of safranal, also protected against and suppressed harmaline-induced
tremors [12]. Safranal exhibits anticonvulsant effect in PTZ-induced convulsions and
protects mice from death [50], and antiabsence seizure [101], and also significantly
reduces kainic acid-induced increase in extracellular concentrations of glutamate and
aspartate in the rat hippocampus [47].
Administration of aqueous extract for 30-days inhibited 20-MCA-induced soft tissue
sarcomas incidence by 90%, and topical application reduced DMBA-induced skin
carcinogenesis by 67% [27, 104], delayed growth of transplanted sarcoma-180, EAC
and Dalton’s lymphoma ascites tumors in mice [83], significantly protected against
cisplatin-toxicity and prolonged life-span of mice [30, 84, 94, 95]. Aqueous saffron
extract also showed anticancer effects in lung cancer cells [105], 1-nitrosoguanidine
(MNNG)-induced gastric adenomas in rats [19], and DMBA-induced hamster buccal
730 Crocus sativus L.

pouch carcinoma [69]. Saffron and crocin promote cell cycle arrest in prostate cancer
(PCa) cells [26], and affect in vivo tumor growth of two aggressive PCa cell lines [34].
Crocin, picrocrocin and safranal are also significantly cytotoxic to HeLa cells [31];
crocetin is approximately 5- to 18-fold higher cytotoxic than crocin in HeLa cells, and
acts by different mechanism than crocin [63]. Long-term treatment with crocin selec-
tively enhances survival of female rats with colon adenocarcinoma [35].
Chronic administration of saffron aqueous extract and crocin lowers mean SBP
of desoxycorticosterone acetate-induced hypertension in rats [53, 54], without
affecting BP of normotensive rats; conversely crocin improves diazinon-induced
reduction of SBP and increased HR in rats [98]. Single dose aqueous extract also
caused diuresis in rats [110], and both saffron aqueous extract and safranal pre-
treatment significantly protected rats against isoproterenol-induced MI [71]. Aqu-
eous extract significantly reduced hyperglycemia and hyperlipidemia risk and the
oxidative stress in diabetic encephalopathy of rats [107], and significantly decreased
serum levels of TGs and VLDL [43]. Crocin substantially lowered TC, TGs and
LDL, and increased HDL in hyperlipidemic rats [115], and exerted antioxidative
effect, lowered LPO, and blood sugar in STZ-diabetic rats [97]. Aqueous extract
and crocin prevented renal I/R-induced oxidative injury in rats [48]. Methanol
extract, crocin and safranal also exhibit high radical scavenging activity [15, 89].
Aqueous and ethanol stigma extracts showed antinociceptive activity and weak
to moderate effect against acute inflammation [51], and alleviated neuropathic pain,
partly through attenuation of proinflammatory cytokines, and antioxidant activity
[10]. Crocin also relieved chronic pain induced by spinal cord injury, by decreasing
calcitonin gene related peptide, an important mediator of inflammation and pain
[58], and revitalized arthritis-induced cartilage and bone deterioration, and neu-
tralized the augmented serum levels of enzymatic mediators and inflammatory
cytokines, and improved antioxidant status [28, 44]. Aqueous saffron extract pro-
tected against ethylene glycol-induced calcium oxalate nephrolithiasis in rats [11],
and hydroalcohol extract was protective against APAP-hepatotoxicity in rats [88].
While aqueous saffron extract and crocin produced aphrodiasic effects in male rats,
mediated via an increase in cyclic GMP [9], and the extract protected against
Cd-induced testicular toxicity [13], safranal was devoid of such activity [52].
Ethanol extract and safranal produced modest antitussive effect in guines pigs
[45], though both aqueous-ethanol extract and safranal produced a significant
relaxant effect on isolated precontracted tracheal chains of guinea-pig [21]; the
extract potently stimulated b2-adrenoceptors which was partially due to safranal
[85], and significantly reduced serum levels of inflammatory markers, ET-1, and total
protein [40]. Pretreatment of ovalbumin-sensitized rats with the extract produced a
significant reduction in WBC and eosinophil counts [68, 114]. Safranal significantly
decreased levels of serum IL-4, total NO and nitrite in sensitized rats [22], and
significantly reduced oxidative stress in bronchial epithelial cells [24].
Clinical Studies: Saffron [7, 109], its hydroalcohol extract [86], and the petals
treatment was effective in Iranian patients with mild to moderate depression,
comparable to fluoxetine and imipramine [6, 78], and also ameliorated some of the
Crocus sativus L. 731

fluoxetine-induced sexual dysfunction in women, including arousal, lubrication,

and pain [59]. A meta-analysis of clinical trials revealed that supplementation with
saffron can improve symptoms of major depressive disorder in adults [42]. Sup-
plementation of aqueous saffron extract in patients with schizophrenia prevented
olanzapine-induced metabolic syndrome [33], and was safe and well tolerated [80].
One-year administration of saffron extract, in a double-blind RCT, reduced cog-
nitive decline in Iranian patients with moderate to severe Alzheimer’s disease,
comparable to memantine [32]. Saffron tablets (30 mg/day) were significantly
effective in relieving symptoms of premenstrual syndrome of at least 6 months
duration [4], and a topical gel of saffron significantly improved erectile dysfunction
in diabetic patients [75]. Saffron supplementation was also found useful in early
age-related macular degeneration [70], and in a dose of 100 mg daily to 45 healthy
men aged 21.4 ± 0.8 years, showed temporary immunomodulatory effects,
increasing IgG level and monocytes, and decreasing IgM, percentage of basophils
and platelets count after 3-weeks treatment, but all parameter returned to baseline
after 6-weeks of administration [61].
Mechanism of Action: Antidepressant effects of saffron aqueous extract are sug-
gested to be due to increased levels of brain-derived neurotrophic factor, VGF neu-
ropeptide, CREB and phospho-CREB (p-CREB) in rat hippocampus [39]. For its
antihyperglycemic effect, saffron increases glucose uptake and insulin sensitivity in
skeletal muscle cells through AMP-activated PK [57]. Smooth muscle relaxing
activity of saffron is due to activation of ß2-adrenoceptors, inhibition of histamine H1
and muscarinic receptors and calcium channels and/or modulation of NO [76]. Anti-
convulsant effect against PTZ-induced convulsions [50], and antiabsence seizures
[101], may be mediated, at least partly, through GABAA-BDZ receptor complex [49].
Human A/Es, Allergy and Toxicity: Administration of saffron tablets to healthy
volunteers of both sexes for 7-days did not cause any significant clinical changes
except lowering standing and MABP at a higher dose of 400 mg/day [74], and no
significant effects on blood coagulation or platelet aggregation [16]. Saffron in
doses between 1.2 and 2 g induced nausea, vomiting, diarrhea and bleeding [108],
and is toxic in doses above 5 g. Razi [99] said “three mithqal (13.5 g) of saffron
makes a man so overjoyed that, as a result, high consumption of saffron does not
have a good effect on the brain and may be fatal. Abuse of it might cause insane
behavior.” Accumulation of saffron in sclera, skin, or mucosa can produce yel-
lowish coloration that mimics jaundice [77]. It is suggested not to be used at more
than 5 g/day during pregnancy due to its uterine stimulation activity [93], which is
ridiculously a very high and unlikely dose to be used.
Animal Toxicity: Oral LD50 of saffron in mice is 20,700 mg/kg and i.p. injection
up to a dose of 5,000 mg/kg was nonlethal [2, 60]. Oral LD50 of aqueous saffron
extract in mice was 4,120 mg/kg [17], and oral administration of aqueous extract in
doses of 500, 1,000 or 2,000 mg/kg/day for three weeks to lactating mice, starting
soon after delivery, was practically safe for both the mother and pups [17]. LD50
(i.p.) values of the aqueous and ethanol petal extracts in mice were 6,670 mg/kg
732 Crocus sativus L.

and 9,990 mg/kg, respectively [51]. Safranal was nonlethal up to a dose of

0.75 mL/kg, and LD50s (i.p.) as 1.48 mL/kg and 1.88 mL/kg in male and female
mice, respectively, and 1.50 mL/kg (i.p.) in male rats. Oral administration of
safranal to male rats once daily for 21-days, significantly decreased body weight,
food consumption, RBC counts, hematocrit, Hb, platelets, TC, TGs and ALP,
increased LDH and BUN. Oral LD50 values of safranal were 21.42 mL/kg and
11.42 mL/kg in male and female mice, respectively; and 5.53 mL/kg in male rats
[46]. However, co-treatment of lethal dose of safranal with saffron aqueous extract
(10 mg/kg i.p.) significantly reduced mortality, and increased survival of rats [118].
Teratogenic studies on crocin and safranal revealed minor skeletal malformations
and growth retardation of fetuses [73].
CYP450 and Potential for Drug-Herb Interactions: Crocin significantly
decreases metabolic activity of CYP2A, CYP2B, CYP2C11, and CYP3A enzymes,
while safranal significantly increases metabolic activity of CYP2B and CYP2C11
enzymes in rats [29].
Commentary: Antidepressant, and cognition and memory-enhancing effects of
saffron have been observed in limited clinical studies. More extensive studies for these
effects are probably constrained due to the high cost of saffron. Its anticancer effects in
animal studies are an important area for clinical studies. Two important observations,
decrease in lethal dose mortality of safranol by addition of aqueous saffron extract, and
opposite CYP450 activities of crocin and safranol on CYP2B and CYP2C11, reinforce
the concept of differences in effects of the whole versus the constituents.

References
1. Abdullaev FI. Biological effects of saffron. BioFactors. 1993;4:83–6.
2. Abdullaev FI. Cancer chemopreventive and tumoricidal properties of saffron
(Crocus sativus L.). Exp Biol Med. 2008;247:20–5.
3. Abe K, Sugiura M, Yamaguchi S, et al. Saffron extract prevents acetaldehyde-
induced inhibition of long-term potentiation in the rat dentate gyrus in vivo.
Brain Res. 1999;851:287–9.
4. Agha-Hosseini M, Kashani L, Aleyaseen A, et al. Crocus sativus L. (saffron)
in the treatment of premenstrual syndrome: a double-blind, randomised and
placebo-controlled trial. BJOG. 2008;115:515–9.
5. Ahmad AS, Ansari MA, Ahmad M, et al. Neuroprotection by crocetin in a
hemiparkinsonian rat model. Pharmacol Biochem Behav. 2005;81:805–13.
6. Akhondzadeh Basti A, Moshiri E, Noorbala AA, et al. Comparison of petal
of Crocus sativus L. and fluoxetine in the treatment of depressed out-
patients: a pilot double-blind randomized trial. Prog Neuropsychopharma-
col Biol Psychiatry. 2007;31:439–42.
7. Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L.
in the treatment of mild to moderate depression: a double-blind, randomized
and placebo-controlled trial. Phytother Res. 2005;19:148–51.
Crocus sativus L. 733

8. Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of

crocin: a comprehensive review. Food Chem Toxicol. 2014;64:65–80.
9. Al-Rehaily AJ, Alhowiriny TA, El-Tahir KE, Al-Taweel AM, Perveen S.
Molecular mechanisms that underlie the sexual stimulant actions of
Avicennia marina (Forssk.) Vierh. and Crocus sativus L. Pak J Pharm Sci.
2015;28:49–58.
10. Amin B, Abnous K, Motamedshariaty V, Hosseinzadeh H. Attenuation of
oxidative stress, inflammation and apoptosis by ethanolic and aqueous
extracts of Crocus sativus L. stigma after chronic constriction injury of
rats. An Acad Bras Cienc. 2014;86:1821–32.
11. Amin B, Feriz HM, Hariri AT, Meybodi NT, Hosseinzadeh H. Protective
effects of the aqueous extract of Crocus sativus against ethylene glycol-
induced nephrolithiasis in rats. EXCLI J. 2015;14:411–22.
12. Amin B, Malekzadeh M, Heidari MR, Hosseinzadeh H. Effect of Crocus
sativus extracts and its active constituent safranal on the harmaline-induced
tremor in mice. Iran J Basic Med Sci. 2015;18:449–58.
13. Asadi MH, Zafari F, Sarveazad A, et al. Saffron improves epididymal sperm
parameters in rats exposed to cadmium. Nephrourol Mon. 2013;6:e12125.
14. Asai A, Nakano T, Takahashi M, et al. Orally administered crocetin and
crocins are absorbed into blood plasma as crocetin and its glucuronide
conjugates in mice. J Agric Food Chem. 2005;53:7302–6.
15. Assimopoulou AN, Sinakos Z, Papageorgiou VP Radical scavenging
activity of Crocus sativus L. extract and its bioactive constituents. Phyto-
ther Res. 2005;19:997–1000.
16. Ayatollahi H, Javan AO, Khajedaluee M, Shahroodian M, Hosseinzadeh H.
Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation
systems in healthy volunteers. Phytother Res. 2014;28:539–43.
17. Bahmani M, Rafieian M, Baradaran A, Rafieian S, Rafieian-Kopaei M.
Nephrotoxicity and hepatotoxicity evaluation of Crocus sativus stigmas in
neonates of nursing mice. J Nephropathol. 2014;3:81–5.
18. Bandegi AR, Rashidy-Pour A, Vafaei AA, Ghadrdoost B. Protective effects
of Crocus sativus L. extract and crocin against chronic-stress induced
oxidative damage of brain, liver and kidneys in rats. Adv Pharm Bull. 2014;4
Suppl 2:493–9.
19. Bathaie SZ, Miri H, Mohagheghi MA, et al. Saffron aqueous extract
inhibits the chemically-induced gastric cancer progression in the Wistar
albino rat. Iran J Basic Med Sci. 2013;16:27–38.
20. Bathaie SZ, Mousavi SZ. New applications and mechanisms of action of
saffron and its important ingredients. Crit Rev Food Sci Nutr. 2010;50:761–86.
21. Boskabady MH, Aslani MR. Relaxant effect of Crocus sativus (saffron) on
guinea-pig tracheal chains and its possible mechanisms. J Pharm Pharmacol.
2006;58:1385–90.
734 Crocus sativus L.

22. Boskabady MH, Byrami G, Feizpour A. The effect of safranal, a constituent

of Crocus sativus (saffron), on tracheal responsiveness, serum levels of
cytokines, total NO and nitrite in sensitized guinea pigs. Pharmacol Rep.
2014;66:56–61.
23. Broadhead GK, Chang A, Grigg J, McCluskey P. Efficacy and safety of
saffron supplementation: current clinical findings. Crit Rev Food Sci Nutr.
2016;56:2767–76.
24. Bukhari SI, Pattnaik B, Rayees S, Kaul S, Dhar MK. Safranal of Crocus
sativus L. inhibits inducible nitric oxide synthase and attenuates asthma in
a mouse model of asthma. Phytother Res. 2015;29:617–27.
25. Carmona M, Zalacain A, Sánchez AM, et al. Crocetin esters, picrocrocin
and its related compounds present in Crocus sativus stigmas and Gardenia
jasminoides fruits. Tentative identification of seven new compounds by
LC-ESI-MS. J Agric Food Chem. 2006;54:973–9.
26. D’Alessandro AM, Mancini A, Lizzi AR, et al. Crocus sativus stigma
extract and its major constituent crocin possess significant antiproliferative
properties against human prostate cancer. Nutr Cancer. 2013;65:930–42.
27. Das I, Chakrabarty RN, Das S. Saffron can prevent chemically induced skin
carcinogenesis in Swiss albino mice. Asian Pac J Cancer Prev. 2004;5:70–6.
28. Ding Q, Zhong H, Qi Y, et al. Antiarthritic effects of crocin in interleukin-
1b-treated articular chondrocytes and cartilage in a rabbit osteoarthritic
model. Inflamm Res. 2013;62:17–25.
29. Dovrtělová G, Nosková K, Juřica J, Turjap M, Zendulka O. Can bioactive
compounds of Crocus sativus L. influence the metabolic activity of
selected CYP enzymes in the rat? Physiol Res. 2015;64 Suppl 4: S453–8.
30. el Daly ES. Protective effect of cysteine and vitamin E, Crocus sativus and
Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Belg.
1998;53:87–93; discussion 93–5.
31. Escribano J, Alonso GL, Coca-Prados M, Fernandez JA. Crocin, safranal
and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of
human cancer cells in vitro. Cancer Lett. 1996;100:23–30.
32. Farokhnia M, Shafiee Sabet M, Iranpour N, et al. Comparing the efficacy
and safety of Crocus sativus L. with memantine in patients with moderate
to severe Alzheimer’s disease: a double-blind randomized clinical trial.
Hum Psychopharmacol. 2014;29:351–9.
33. Fadai F, Mousavi B, Ashtari Z, et al. Saffron aqueous extract prevents
metabolic syndrome in patients with schizophrenia on olanzapine treat-
ment: a randomized triple blind placebo controlled study. Pharmaco-
psychiatry. 2014;47:156–61.
34. Festuccia C, Mancini A, Gravina GL, et al. Antitumor effects of saffron-
derived carotenoids in prostate cancer cell models. Biomed Res Int. 2014;
2014:135048.
35. García-Olmo DC, Riese HH, Escribano J, et al. Effects of long-term treatment
of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus
sativus L.): an experimental study in the rat. Nutr Cancer. 1999;35:120–6.
Crocus sativus L. 735

36. Georgiadou G, Grivas V, Tarantilis PA, Pitsikas N. Crocins, the active

constituents of Crocus sativus L., counteracted ketamine-induced behavioural
deficits in rats. Psychopharmacology (Berl). 2014;231:717–26.
37. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, et al. Protective effects of
saffron extract and its active constituent crocin against oxidative stress and
spatial learning and memory deficits induced by chronic stress in rats. Eur J
Pharmacol. 2011;667:222–9.
38. Ghaffari Sh, Hatami H, Dehghan G. Saffron ethanolic extract attenuates
oxidative stress, spatial learning, and memory impairments induced by
local injection of ethidium bromide. Res Pharm Sci. 2015;10:222–32.
39. Ghasemi T, Abnous K, Vahdati F, et al. Antidepressant effect of Crocus
sativus aqueous extract and its effect on CREB, BDNF, and VGF Transcript
and protein levels in rat hippocampus. Drug Res (Stuttg). 2015;65:337–43.
40. Gholamnezhad Z, Koushyar H, Byrami G, Boskabady MH. The extract of
Crocus sativus and its constituent safranal, affect serum levels of endothelin
and total protein in sensitized guinea pigs. Iran J Basic Med Sci. 2013;16:
1022–6.
41. Gohari AR, Saeidnia S, Mahmoodabadi MK. An overview on saffron,
phytochemicals, and medicinal properties. Pharmacogn Rev. 2013;7:61–6.
42. Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus
L.) and major depressive disorder: a meta-analysis of randomized clinical
trials. J Integr Med. 2013;11:377–83.
43. Hemmati M, Asghari S, Zohoori E, Karamian M. Hypoglycemic effects of
three Iranian edible plants; jujube, barberry and saffron: correlation with
serum adiponectin level. Pak J Pharm Sci. 2015;28:2095–9.
44. Hemshekhar M, Sebastin Santhosh M, Sunitha K, et al. A dietary colorant
crocin mitigates arthritis and associated secondary complications by
modulating cartilage deteriorating enzymes, inflammatory mediators and
antioxidant status. Biochimie. 2012;94:2723–33.
45. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of stigma
and petals of saffron (Crocus sativus) and its components, safranal and
crocin in guinea pigs. Fitoterapia. 2006;77:446–8.
46. Hosseinzadeh H, Sadeghi Shakib S, Khadem Sameni A, Taghiabadi E.
Acute and subacute toxicity of safranal, a constituent of saffron, in mice
and rats. Iran J Pharm Res. 2013;12:93–9.
47. Hosseinzadeh H, Sadeghnia HR, Rahimi A. Effect of safranal on extra-
cellular hippocampal levels of glutamate and aspartate during kainic acid
treatment in anesthetized rats. Planta Med. 2008;74:1441–5.
48. Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of
aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent,
on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm
Pharm Sci. 2005;8:387–93.
49. Hosseinzadeh H, Sadeghnia HR. Protective effect of safranal on pentylene-
tetrazol-induced seizures in the rat: involvement of GABAergic and
opioids systems. Phytomedicine. 2007;14:256–62.
736 Crocus sativus L.

50. Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and

crocin from Crocus sativus in mice. Fitoterapia. 2005;76:722–4.
51. Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory
effects of Crocus sativus L. stigma and petal extracts in mice. BMC Phar-
macol. 2002;2:7.
52. Hosseinzadeh H, Ziaee T, Sadeghi A. The effect of saffron, Crocus sativus
stigma, extract and its constituents, safranal and crocin on sexual behaviors
in normal male rats. Phytomedicine. 2008;15:491–5.
53. Imenshahidi M, Razavi BM, Faal A, et al. Effects of chronic crocin
treatment on desoxycorticosterone acetate (doca)-salt hypertensive rats.
Iran J Basic Med Sci. 2014;17:9–13.
54. Imenshahidi M, Razavi BM, Faal A, et al. The effect of chronic administration
of saffron (Crocus sativus) stigma aqueous extract on systolic blood pressure
in rats. Jundishapur J Nat Pharm Prod. 2013;8:175–9.
55. Javadi B, Sahebkar A, Emami SA. A survey on saffron in major Islamic
traditional medicine books. Iran J Basic Med Sci. 2013;16:1–11.
56. Jorjani SE. Zakhireh Kharazmshahi (Treasure of Kharazmshahi). In:
Saeedi Sirjani AA, editors. Photo print of the manuscript dated 1206 A.D
Tehran: The lranian Culture Foundation. 1976, p. 664.
57. Kang C, Lee H, Jung ES, et al. Saffron (Crocus sativus L.) increases
glucose uptake and insulin sensitivity in muscle cells via multipathway
mechanisms. Food Chem. 2012;135:2350–8.
58. Karami M, Bathaie SZ, Tiraihi T, et al. Crocin improved locomotor
function and mechanical behavior in the rat model of contused spinal cord
injury through decreasing calcitonin gene related peptide (CGRP). Phyto-
medicine. 2013;21:62–7.
59. Kashani L, Raisi F, Saroukhani S, et al. Saffron for treatment of fluoxetine-
induced sexual dysfunction in women: randomized double-blind placebo-
controlled study. Hum Psychopharmacol. 2013;28:54–60.
60. Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, M Tsatsakis A. The
effects of Crocus sativus (saffron) and its constituents on nervous system: a
review. Avicenna J Phytomed. 2015;5:376–91.
61. Kianbakht S, Ghazavi A. Immunomodulatory effects of saffron: a random-
ized double-blind placebo-controlled clinical trial. Phytother Res. 2011;
25:1801–5.
62. Kianbakht S. Systematic review of pharmacological properties of saffron
and active ingredients of it. Med Plants. 2008;28:1–23.
63. Kim SH, Lee JM, Kim SC, Park CB, Lee PC. Proposed cytotoxic
mechanisms of the saffron carotenoids crocin and crocetin on cancer cell
lines. Biochem Cell Biol. 2014;92:105–11.
64. Kubo I, Kinst-Hori I. Flavonols from saffron flower: tyrosinase inhibitory
activity and inhibition mechanism. J Agric Food Chem. 1999;47:4121–5.
65. Li CY, Wu TS. Constituents of the stigmas of Crocus sativus and their
tyrosinase inhibitory activity. J Nat Prod. 2002;65:1452–6.
Crocus sativus L. 737

66. Lićon C, Carmona M, Llorens S, Berruga MI, Alonso GL. Potential

healthy effects of saffron spice (Crocus sativus L. stigmas) consumption.
Func Plant Sci Biotech. 2010;4(Special Issue 2):64–73.
67. Linardaki ZI, Orkoula MG, Kokkosis AG, Lamari FN, Margarity M.
Investigation of the neuroprotective action of saffron (Crocus sativus L.) in
aluminum-exposed adult mice through behavioral and neurobiochemical
assessment. Food Chem Toxicol. 2013;52:163–70.
68. Mahmoudabady M, Neamati A, Vosooghi S, Aghababa H. Hydroalcoholic
extract of Crocus sativus effects on bronchial inflammatory cells in
ovalbumin sensitized rats. Avicenna J Phytomed. 2013;3:356–63.
69. Manoharan S, Wani SA, Vasudevan K, et al. Saffron reduction of 7,12-
dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis.
Asian Pac J Cancer Prev. 2013;14:951–7.
70. Marangoni D, Falsini B, Piccardi M, et al. Functional effect of saffron
supplementation and risk genotypes in early age-related macular degene-
ration: a preliminary report. J Transl Med. 2013;11:228.
71. Mehdizadeh R, Parizadeh MR, Khooei AR, Mehri S, Hosseinzadeh H.
Cardioprotective effect of saffron extract and safranal in isoproterenol-
induced myocardial infarction in wistar rats. Iran J Basic Med Sci. 2013;
16:56–63.
72. Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of
the world’s most expensive spice: Saffron. Food Res Int. 2010;43:1981–9.
73. Moallem SA, Afshar M, Etemad L, Razavi BM, Hosseinzadeh H.
Evaluation of teratogenic effects of crocin and safranal, active ingredients
of saffron, in mice. Toxicol Ind Health. 2016;32:285–91.
74. Modaghegh MH, Shahabian M, Esmaeili HA, et al. Safety evaluation of
saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine.
2008;15:1032–7.
75. Mohammadzadeh-Moghadam H, Nazari SM, Shamsa A, et al. Effects of a
topical saffron (Crocus sativus L.) gel on erectile dysfunction in diabetics:
a randomized, parallel-group, double-blind, placebo-controlled trial. J Evid
Based Complementary Altern Med. 2015;20:283–6.
76. Mokhtari-Zaer A, Khazdair MR, Boskabady MH. Smooth muscle relaxant
activity of Crocus sativus (saffron) and its constituents: possible mecha-
nisms. Avicenna J Phytomed. 2015;5:365–75.
77. Mollazadeh H, Emami SA, Hosseinzadeh H. Razi’s Al-Hawi and saffron
(Crocus sativus): a review. Iran J Basic Med Sci. 2015;18:1153–66.
78. Moshiri E, Basti AA, Noorbala AA, et al. Crocus sativus L. (petal) in the
treatment of mild-to-moderate depression: a double-blind, randomized and
placebo-controlled trial. Phytomedicine. 2006;13:607–11.
79. Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical applications of
saffron (Crocus sativus) and its constituents: a review. Drug Res (Stuttg).
2015;65:287–95.
738 Crocus sativus L.

80. Mousavi B, Bathaie SZ, Fadai F, et al. Safety evaluation of saffron stigma
(Crocus sativus L.) aqueous extract and crocin in patients with schizo-
phrenia. Avicenna J Phytomed. 2015;5:413–9.
81. Naghibi SM, Hosseini M, Khani F, et al. Effect of aqueous extract of Crocus
sativus L. on morphine-induced memory impairment. Adv Pharmacol Sci.
2012;2012:494367.
82. Naghizadeh B, Mansouri MT, Ghorbanzadeh B, Farbood Y, Sarkaki A.
Protective effects of oral crocin against intracerebroventricular streptozotocin-
induced spatial memory deficit and oxidative stress in rats. Phytomedicine.
2013;20:537–42.
83. Nair SC, Pannikar B, Panikkar KR. Antitumour activity of saffron (Crocus
sativus). Cancer Lett. 1991;57:109–14.
84. Nair SC, Salomi MJ, Panikkar B, Panikkar KR. Modulatory effects of
Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in
mice. J Ethnopharmacol. 1991;31:75–83.
85. Nemati H, Boskabady MH, Ahmadzadef, Vostakolaei HA. Stimulatory
effect of Crocus sativus (saffron) on beta2-adrenoceptors of guinea pig
tracheal chains. Phytomedicine. 2008;15:1038–45.
86. Noorbala AA, Akhondzadeh S, Tahmacebi-Pour N, Jamshidi AH. Hydro-
alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment
of mild to moderate depression: a double-blind, randomized pilot trial.
J Ethnopharmacol. 2005;97:281–4.
87. Ochiai T, Shimeno H, Mishima K, et al. Protective effects of carotenoids
from saffron on neuronal injury in vitro and in vivo. Biochim Biophys
Acta. 2007;1770:578–84.
88. Omidi A, Riahinia N, Montazer Torbati MB, Behdani MA. Hepato-
protective effect of Crocus sativus (saffron) petals extract against aceta-
minophen toxicity in male Wistar rats. Avicenna J Phytomed. 2014;4:
330–6.
89. Papandreou MA, Kanakis CD, Polissiou MG, et al. Inhibitory activity on
amyloid-beta aggregation and antioxidant properties of Crocus sativus
stigmas extract and its crocin constituents. J Agric Food Chem. 2006;54:
8762–8.
90. Pitsikas N, Boultadakis A, Georgiadou G, et al. Effects of the active consti-
tuents of Crocus sativus L., crocins, in an animal model of anxiety. Phyto-
medicine. 2008;15:1135–9.
91. Pitsikas N, Sakellaridis N. Crocus sativus L. extracts antagonize memory
impairments in different behavioural tasks in the rat. Behav Brain Res.
173:112–5.
92. Pitsikas N, Zisopoulou S, Tarantilis PA, et al. Effects of the active cons-
tituents of Crocus sativus L., crocins on recognition and spatial rats’
memory. Behav Brain Res. 2007;183:141–6.
93. Poma A, Fontecchio G, Carlucci G, Chichiriccò G. Anti-inflammatory
properties of drugs from saffron crocus. Anti-inflamm Antiallergy Agents
Med Chem. 2012;11:37–51.
Crocus sativus L. 739

94. Premkumar K, Abraham SK, Santhiya ST, Ramesh A. Inhibitory effects of

aqueous crude extract of saffron (Crocus sativus L.) on chemical-induced
genotoxicity in mice. Asia Pac J Clin Nutr. 2003;12:474–6.
95. Premkumar K, Thirunavukkarasu C, Abraham SK, et al. Protective effect
of saffron (Crocus sativus L.) aqueous extract against genetic damage
induced by antitumor agents in mice. Hum Exp Toxicol. 2006;25:79–84.
96. Purushothuman S, Nandasena C, Peoples CL, et al. Saffron pretreatment
offers neuroprotection to nigral and retinal dopaminergic cells of MPTP-
treated mice. J Parkinsons Dis. 2013;3:77–83.
97. Rajaei Z, Hadjzadeh MA, Nemati H, et al. Antihyperglycemic and antioxi-
dant activity of crocin in streptozotocin-induced diabetic rats. J Med Food.
2013;16:206–10.
98. Razavi M, Hosseinzadeh H, Abnous K, Motamedshariaty VS, Imenshahidi M.
Crocin restores hypotensive effect of subchronic administration of diazinon in
rats. Iran J Basic Med Sci. 2013;16:64–72.
99. Razi MZ. Al-Hawi fi’l-Tibb (Comprehensive Book of Medicine). In:
Khan A, editor. Hyderabad: Osmania Oriental Publications Bureau; 1968,
vol. 20. p. 548–53.
100. Rodríguez-Neira L, Lage-Yusty MA, López-Hernández J. Influence of
culinary processing time on saffron’s bioactive compounds (Crocus sativus
L.). Plant Foods Hum Nutr. 2014;69:291–6.
101. Sadeghnia HR, Cortez MA, Liu D, et al. Antiabsence effects of safranal in
acute experimental seizure models: EEG and autoradiography. J Pharm
Pharm Sci. 2008;11:1–14.
102. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
103. Saleem S, Ahmad M, Ahmad AS, et al. Effect of saffron (Crocus sativus)
on neurobehavioral and neurochemical changes in cerebral ischemia in
rats. J Med Food. 2006;9:246–53.
104. Salomi MJ, Nair SC, Panikkar KR. Inhibitory effects of Nigella sativa and
saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr Cancer.
1991;16:67–72.
105. Samarghandian S, Borji A, Farahmand SK, Afshari R, Davoodi S. Crocus
sativus L. (saffron) stigma aqueous extract induces apoptosis in alveolar
human lung cancer cells through caspase-dependent pathways activation.
Biomed Res Int. 2013;417928.
106. Samarghandian S, Borji A. Anticarcinogenic effect of saffron (Crocus
sativus L.) and its ingredients. Pharmacognosy Res. 2014;6:99–107.
107. Samarghandian S, Azimi-Nezhad M, Samini F. Ameliorative effect of
saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative
stress on diabetic encephalopathy in streptozotocin induced experimental
diabetes mellitus. Biomed Res Int. 2014;2014:920857.
108. Schmidt M, Betti G, Hensel A. Saffron in phytotherapy: pharmacology and
clinical uses. Wien Med Wochenschr. 2007;157:315–9.
740 Crocus sativus L.

109. Shahmansouri N, Farokhnia M, Abbasi SH, et al. A randomized, double-

blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with
fluoxetine for improving mild to moderate depression in post percutaneous
coronary intervention patients. J Affect Disord. 2014;155:216–22.
110. Shariatifar N, Shoeibi S, Sani MJ, et al. Study on diuretic activity of
saffron (stigma of Crocus sativus L.) aqueous extract in rat. J Adv Pharm
Technol Res. 2014;5:17–20.
111. Tung NH, Shoyama Y. New minor glycoside components from saffron.
J Nat Med. 2013;67:672–6.
112. Umigai N, Murakami K, Ulit MV, et al. The pharmacokinetic profile of
crocetin in healthy adult human volunteers after a single oral administra-
tion. Phytomedicine. 2011;18:575–8.
113. Vakili A, Einali MR, Bandegi AR. Protective effect of crocin against
cerebral ischemia in a dose-dependent manner in a rat model of ischemic
stroke. J Stroke Cerebrovasc Dis. 2014;23:106–13.
114. Vosooghi S, Mahmoudabady M, Neamati A, Aghababa H. Preventive
effects of hydroalcoholic extract of saffron on hematological parameters of
experimental asthmatic rats. Avicenna J Phytomed. 2013;3:279–87.
115. Xu GL, Yu SQ, Gong ZN, Zhang SQ. Study of the effect of crocin on rat
experimental hyperlipemia and the underlying mechanisms. Zhongguo
Zhong Yao Za Zhi. 2005;30:369–72 (Chinese).
116. Zhang Y, Shoyama Y, Sugiura M, Saito H. Effects of Crocus sativus L. on
the ethanol-induced impairment of passive avoidance performances in
mice. Biol Pharm Bull. 1994;17:217–21.
117. Zheng YQ, Liu JX, Wang JN, Xu L. Effects of crocin on reperfusion-
induced oxidative/nitrative injury to cerebral microvessels after global
cerebral ischemia. Brain Res. 2007;1138:86–94.
118. Ziaee T, Razavi BM, Hosseinzadeh H. Saffron reduced toxic effects of its
constituent, safranal, in acute and subacute toxicities in rats. Jundishapur J
Nat Pharm Prod. 2014;9:3–8.
Croton tiglium L.
(Euphorbiaceae)

Abstract
A small evergreen tree, native of India, Sri Lanka, southwest China, Myanmar,
Laos, Vietnam, Malaysia, and the Philippines. Croton seeds were not known to
ancient Hindu physicians, but Persians were familiar with them from earlier times
having been introduced from China; they were first introduced to India through
Nepal. Muslim physicians described seeds as detergent, purgative of phlegm, black
bile and adust humours; and recommend their use in dropsy, calculus, gout, and
other diseases arising from cold humours, and beneficial in ascites, backache and
colic. In Ayurveda, seeds and seed oil are used in the treatment of constipation, fever,
intestinal worms, anasarca, ascites, enlargement of abdominal viscera, tympanites,
calculous affections, colic, and gout. In China they are used to treat gastrointestinal
disorders, intestinal inflammation, rheumatism, headache, peptic ulcer and visceral
pain. Croton oil is the most violent of all cathartics, half to one drop produces
burning in the mouth and stomach, often emesis, several extensive fluid evacuations
with colic and tenesmus; toxic doses produce gastroenteritis and collapse. The
kernel contains croton oil that contains glyceryl crotonate, croton resin, a mixture of
phorbol formate, phorbol butyrate and phorbol crotonate, crotin, crotonoside, and an
alkaloid similar to ricinine in structure. Croton oil has been used since the mid 1960s
as a promoter in a two-stage experimental skin carcinogenesis model. Ethanol seed
extract at a dose of 0.06 mL/30 g was effective as laxative in 100% mice, with an
ED50 of 0.027 mL; the laxative effect was partially blocked by atropine. In contrast
to the tumor promoting activity of topical croton oil, intralesional administration of
emulsified croton oil into established transplants of murine fibrosarcoma caused
complete regression of the tumors in mice without any recurrence.

Keywords
Croton seeds
Croton révulsif
Habb-el-salátin
Hazu
Jamalgota
Jaypál

Kanakaphala
Kroton
Pa-tou
Purgierkroton

© Springer Nature Switzerland AG 2020 741

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_79
742 Croton tiglium L.

Vernaculars: Urd.: Jamalgota; Hin.: Jamalgota, Jaypál; San.: Dunti, Jayapála,

Kanakaphala, Naepala, Napal, Tittiriphala; Ben.: Jaipal, Jaypál, Rechuk; Guj.:
Nepal; Mal.: Chiduram, Kadal-avanaku, Nirválam, Valam; Mar.: Arabi-erand,
Jaipaala, Jamálgota, Mogli-erand, Nepalcha-bi; Tam.: Chiduram, Nervalam,
Valam; Tel.: Naepalvaema, Nepalam, Nepala-vithalu, Nepalavitua; Ara.: Batu,
Dand, Habb-el-khatsi, Habb-el-salátin, Habb-ul-malook, Wandsini; Bur.: Kanako;
Chi.: 巴豆, Ba-dou, Pa-tou; Cze.: Kroton počistivý; Dan.: Kroton, Oliekroton,
Purgerkroton; Dut.: Crotonolie, Purgeerkorrels; Eng.: Cathay castor seeds, Croton
seeds, Purging croton; Fre.: Bois de moluques, Bois de pavane, Croton cathartique,
Croton révulsif, Huile-dectiglium, Petit pignon d’Inde; Ger.: Krotonol, Kro-
tonölbaum, Purgierkroton, Tiglibaum; Hun.: Hashajtó kroton; Ita.: Crotone, Tiglio
drastico; Jap.: Hazu; Kor.: Keuloton; Lao.: Kok mak tong; Maly.: Bori, Cheng-
kiang, Cheraken and Penchahar (Java); Per.: Dund (oil), Mahudana, Shabab,
Tukhm baid injeer khatai; Pol.: Kroton przeczyszczający; Por.: Cróton (Br.),
Crotone; Rus.: Kroton rvotnyj; Spa.: Crotoncillo, Piñón de Indias (seeds); Swe.:
Krotonoljeträd; Tag.: Kamaisa, Kamausa, Makaisa, Túba, Tubang-kamaisa,
Tubang-makaisa; Tha.: Sà lòt (Salood); Vie.: Ba dâu.
Description: A small evergreen tree, 5–6 m tall; native of India, Sri Lanka,
southwest China, Myanmar, Laos, Vietnam, Malaysia, and the Philippines. Leaves
alternate, petiolate in length, stipulate, obovate, entire, acuminate, rounded base,
9–16 cm long by 4–7 cm wide. Fruit is a capsule of the size of a hazel nut,
externally smooth and brownish yellow, tricoccous, dehiscent, each cell containing
one seed. Seeds are brownish-black, 12–15 mm long by 8 mm wide, oblong,
rounded at the two extremities, with two faces, dorsal face more convex than the
ventral; the taste is oily, at first sweet and then burning. Seeds contain 35–55%
fixed oil; pale yellow or brownish-yellow, viscid, slightly disagreeable (rancid) odor
and poisonous.LXXIX,LXXXI,CXVII Between the two halves of the albumen are two
foliaceous cotyledons, and a short thick radical; the structure of these parts closely
resembles to the albumen and embryo of Ricinus communis (Figs. 1, 2 and 3).XL
Actions and Uses: Croton seeds were not known to ancient Hindu physicians, but
Persians were familiar with them from earlier times having been introduced from
China; they were first introduced to India through Nepal. They are described as heavy,
mucilaginous, purgative that expel bile and phlegm, and useful in fever, constipation,
enlargement of abdominal viscera, ascites, anasarca, and cough.XL Muslim physicians
described seeds as detergent, purgative of phlegm, black bile and adust humours; and
recommend their use in dropsy, calculus, gout, and other diseases arising from cold
humours,XL and beneficial in ascites, backache and colic.LXIX Seeds (temperament,
hot 4° and dry 4°) are considered very strong purgative, and poisonous in Unani
medicine, and used as a purgative of phlegm and black bile in diseases such as arthritis,
ascites, and mental shock. They are always used internally after a detoxification
process; to detoxify, the testa and embryo are removed and the kernel is boiled in
milk.LXXVII In Ayurveda, seeds and seed oil are used in the treatment of constipation
[11], fever, intestinal worms, anasarca, ascites, enlargement of abdominal viscera,
tympanites, calculous affections, colic, and gout.LXXXI,CV In China they are used to
Croton tiglium L. 743

Fig. 1 Croton tiglium, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wikime-
diaCommons, https://commons.wikimedia.org/wiki/File:Croton_tiglium_-_K%C3%B6hler%E2%
80%93s_Medizinal-Pflanzen-197.jpg

treat gastrointestinal disorders, intestinal inflammation, rheumatism, headache, peptic

ulcer and visceral pain [8]. Croton oil is the most violent of all cathartics, half to one
drop produces burning in the mouth and stomach, often emesis, several extensive fluid
evacuations with colic and tenesmus; toxic doses produce gastroenteritis and collapse.
Externally, it is an irritant leading to pustulation, and even sloughing.LXXIX A liniment
acts as a useful stimulant in chronic rheumatism, neuralgia, glandular and other
indolent swellings, chronic bronchitis and other pulmonary affections.CXVII In Ayur-
veda, the detoxification (purification) process is called Śodhana; the process involves
soaking seeds in water overnight, the testa (outer cover) and cotyledon are removed
and the endosperm is ground to coarse powder. The coarse powder is wrapped in a
cotton cloth (sack), tied and hung in an iron pot of boiling cow’s milk, completely
immersed in milk but not touching the pot, and heated for 3 h. The sack is removed,
washed thrice with hot water, dried and the whole process is repeated three times.
Chemical analysis shows that phorbol esters equivalent to phorbol-12-myristate-
13-acetate contents were reduced from 5.2 mg/100 g before the detoxification process
to 1.8 mg/100 g of dried seeds; while the crotonic acid content became negligible from
0.102 mg/100 g in unpurified seeds [10]. In a simple Chinese process of detoxifica-
tion, seeds are stacked in a 3 cm thick layer and baked at 180 °C for 90 min [23].
744 Croton tiglium L.

Fig. 2 Croton tiglium, Fruit, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Croton_tiglium_08.JPG; https://creativeco
mmons.org/licenses/by-sa/3.0/deed.en

Phytoconstituents: The kernel contains 34–57% croton oil that contains glyceryl
crotonate, croton resin, a mixture of phorbol formate, phorbol butyrate and phorbol
crotonate, crotin, crotonoside, and an alkaloid similar to ricinine in structure.XVIII
Croton oil has been used since the mid 1960s as a promoter in a two-stage
experimental skin carcinogenesis model [2, 12, 17, 18], and the active constituents,
i.e. phorbol esters were isolated from it in 1967 and their role as promoters of
carcinogenesis was established [3, 4, 16]. El-Mekkawy [1] isolated five phorbol
esters from the seeds, of which 12-O-tetradecanoylphorbol-13-acetate (TPA) was a
highly potent activator of protein kinase C, and eight phorbol diesters from the
seeds were reported by Zhang et al. [24] Croton oil, obtained by extraction of
Chinese seeds in petroleum ether, contains linoleic acid, oleic acid, and eicosenoic
acid as the main components, accounting for 77.3%, and aromatic compounds, such
as isoborneol and fenchyl alcohol, but no phorbol esters [6]. Isoguanosine is a
cytotoxic agent isolated from seeds that inhibits growth of S-180 ascitic tumor and
Ehrlich solid tumor in mice [5]. A protein with strong and broad-spectrum
antimicrobial activity has also been isolated from seeds [14]. Crotonine, isolated
from leaves is a remarkable inhibitor of acetic acid-induced writhing in mice [21],
and a number of phorbol esters have also been isolated from the leaves [19].
Croton tiglium L. 745

Fig. 3 Croton tiglium, Leaves, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Croton_tiglium_07.JPG; https://creativeco
mmons.org/licenses/by-sa/3.0/deed.en

Pharmacology: Ethanol seed extract at a dose of 0.06 mL/30 g was effective as

laxative in 100% mice, with an ED50 of 0.027 mL [13]; the laxative effect
was partially blocked by atropine [11]. Low dose of seed EO increases gastroin-
testinal transit of charcoal and barium meal and the production of fecal pellets in
mice, whereas, high dose exerts an inhibitory effect [20]. Seed decoction
showed antibacterial activity against S. aureus, H. influenzae, C. diphtheriae, and
P. aeruginosa.XVIII Ethanol extracts of stem, leaves and seeds exhibit antifungal
activities against T. mentagrophytes, T. rubrum, and E. floccosum. The ethanol stem
extract shows the greatest inhibitory activity against T. mentagrophytes and
E. floccosum. Oleic acid and hexadecanoic acid are the major constituents in the
stem extract responsible for the antidermatophytic activity [7]. Hydroalcohol seed
extract shows anticonvulsant activity in both electrically-induced and chemically-
induced convulsions in rats and mice; however, it increases mortality in chemically-
induced convulsive animals [9]. In contrast to the tumor promoting activity of
topical croton oil, intralesional administration of emulsified croton oil into estab-
lished transplants of murine fibrosarcoma caused complete regression of the tumors
in C3H mice without any recurrence. TPA incorporated in mineral oil droplets in
aqueous suspension also caused regression of murine tumors when injected
746 Croton tiglium L.

intralesionally. The explanation offered is that TPA emulsions-induced tumor

regression is due to indiscriminate destruction of the tissue [22]. Topical application
of croton oil to the ears of mice induces an edema that maximizes 6–7 h after
application; while application of croton oil to the shaved back skin induces
inflammation characterized by epidermal hyperplasia and PMNL infiltration of the
dermis [15].
Mechanism of Action: Spasmogenic and spasmolytic properties of croton oil and its
regulatory effects on gastrointestinal motility are suggested to be mediated via acti-
vation of M3 muscarinic receptors and Ca2+ influx through L-type Ca2+ channel [8].
Human A/Es, Allergy and Toxicity: Croton seeds may cause abortion in pregnant
women, and are contraindicated in weak patients. It is very irritating to skin and
mucous membranes; worker coming in contact with shelled seeds, the defatted
kernel or their vapors developed contact dermatitis, vesicles, pustules, burning in
the eyes and nose, lacrimation, conjunctivitis and rhinitis. Twenty drops of croton
oil by mouth is lethal to humans.XVIII It may cause nausea, and is harmful to pyloric
sphincter.LXIX
Animal Toxicity: Oral LD50 of ethanol seed extract in mice was 0.0707 ml [13].
Commentary: There are no formal clinical studies on croton seeds or croton oil,
though they continue to be used in traditional medicines, mostly as laxative/
purgative. Croton oil or its constituent, TPA, are generally used as tumor promoters
in pharmacology experiments.

References
1. El-Mekkawy S, Meselhy MR, Nakamura N, et al. Anti-HIV-1 phorbol
esters from the seeds of Croton tiglium. Phytochemistry. 2000;53:457–64.
2. Frei JV. Features of tumor enhancement by croton oil. Cancer Res. 1968;
28:947–9.
3. Hecker E. Cocarcinogenic principles from the seed oil of Croton tiglium and
from other Euphorbiaceae. Cancer Res. 1968;28:2338–49.
4. Hecker E. Phorbol esters from croton oil. Chemical nature and biological
activities. Naturwissenschaften. 1967;54:282–4.
5. Kim JH, Lee SJ, Han YB, Moon JJ, Kim JB. Isolation of isoguanosine from
Croton tiglium and its antitumor activity. Arch Pharm Res. 1994;17:115–8.
6. Lan M, Wan P, Wang ZY, Huang XL. GC-MS analysis of chemical compo-
nents in seeds oil from Croton tiglium. Zhong Yao Cai. 2012;35:1105–8
(Chinese).
7. Lin HC, Kuo YL, Lee WJ, Yap HY, Wang SH. Antidermatophytic activity of
ethanolic extract from Croton tiglium. Biomed Res Int. 2016;2016:3237586.
8. Liu Z, Gao W, Zhang J, Hu J. Antinociceptive and smooth muscle relaxant
activity of Croton tiglium L seed: an in-vitro and in-vivo study. Iran J Pharm
Res. 2012;11:611–20.
Croton tiglium L. 747

9. Mudium R, Kolasani B. Anticonvulsant effect of hydroalcoholic seed

extract of Croton tiglium in rats and mice. J Clin Diagn Res. 2014;8:24–6.
10. Pal PK, Nandi MK, Singh NK. Detoxification of Croton tiglium L. seeds by
Ayurvedic process of Śodhana. Anc Sci Life. 2014;33:157–61.
11. Pillai NR. Gastrointestinal effects of Croton tiglium in experimental animals.
Anc Sci Life. 1999;18:205–9.
12. Pound AW. Further observations concerning the influence of preliminary
stimulation by croton oil and acetic acid on the initiation of skin tumours in
mice by urethane. Br J Cancer. 1966;20:385–98.
13. Saputera, Mangunwidjaja D, Raharja S, Kardono LB, Iswantini D. Charac-
teristics, efficacy and safety testing of standardized extract of Croton tiglium
seed from Indonesia as laxative material. Pak J Biol Sci. 2008;11:618–22.
14. Shahid M, Tayyab M, Naz F, et al. Activity-guided isolation of a novel
protein from Croton tiglium with antifungal and antibacterial activities.
Phytother Res. 2008;22:1646–9.
15. Shwaireb M. Inflammatory effects of the tumor promoter croton-oil in
BALB/c mice skin. Oncol Rep. 1995;2:133–5.
16. Sivak A, Ray F, Van Duuren BL. Phorbol ester tumor-promoting agents and
membrane stability. Cancer Res. 1969;29:624–30.
17. Van Duuren BL, Langseth L, Sivak A, Orris L. The tumor-enhancing prin-
ciples of Croton tiglium L. II. A comparative study. Cancer Res. 1966;26:
1729–33.
18. Van Duuren BL, Orris L. The tumor-enhancing principles of Croton tiglium
L. Cancer Res. 1965;25:1871–5.
19. Wang JF, Yang SH, Liu YQ, et al. Five new phorbol esters with cytotoxic
and selective anti-inflammatory activities from Croton tiglium. Bioorg Med
Chem Lett. 2015;25:1986–9.
20. Wang X, Zhang F, Liu Z, et al. Effects of essential oil from Croton tiglium
L. on intestinal transit in mice. J Ethnopharmacol. 2008;117:102–7.
21. Wu XA, Zhao YM, Yu NJ. A novel analgesic pyrazine derivative from the
leaves of Croton tiglium L. J Asian Nat Prod Res. 2007;9:437–41.
22. Yarkoni E, Rapp HJ. Local tumor regression after intralesional injection of
croton oil. J Natl Cancer Inst. 1979;63:503–5.
23. Zeng B, Huang MQ, Tang JP, et al. New processing procedure for Croton
tiglium with study on comparison of Croton tiglium and processed product.
Zhong Yao Cai. 2012;35:371–5 (Chinese).
24. Zhang XL, Wang L, Li F, Yu K, Wang MK. Cytotoxic phorbol esters of
Croton tiglium. J Nat Prod. 2013;76:858–64.
Cullen corylifolium (L.) Medicus
(Fabaceae/Leguminosae)

(Syns.: C. corylifolius (L.) Medik; Lotodes corylifolia (L.) Kuntze; Psoralea corylifolia L.;
P. patersoniae Schonl.; Trifolium unifolium Forssk)

Abstract
An annual plant found throughout plains of India, especially in the semiarid regions
of Rajasthan, Punjab, and Uttar Pradesh, and Iran. The seeds are considered
lenitive, fragrant, stimulant and aphrodisiac, and are recommended in the treatment
of leprosy, and other chronic skin diseases caused by a vitiated state of blood. In
Unani medicine, seeds are classified as blood purifier, anthelmintic, carminative,
laxative and to tonify stomach. Due to its blood purifying properties, it is used in
skin diseases, such as leprosy, leucoderma, eczema and itching. However, the seeds
are required to be used after purification by soaking them in ginger water for a week.
In China, ripe fruits are known as Buguzhi, Heiguzi and Poguzhi, and described as
acrid and bitter in taste, warm in property, and their actions are kidney-tonyfying,
“Yang (vital function)-invigorative,” “stomach and spleen-warming” and antidiar-
rheal. Mature, dried fruits are officially listed in the Pharmacopoeia of the Peoples’
Republic of China of 2000 (vol II) for the treatment of enuresis, urinary frequency
(pollakiuria), waist and knee psychalgia and kidney weakness. The herb is mainly
used in China to treat impotence due to “kidney” asthenia, premature ejaculation,
nocturnal emissions, enuresis, backache and knee pain, and pollakiuria; exter-
nally, it is used for vitiligo, callus, psoriasis, and alopecia. A number of chemical
compounds including psoralen, isopsoralen, psoralidin, bakuchiol, bakuchalcone,
bavachinin, flavones, volatile oils, and lipids have been reported from different
parts of the plant. Aqueous seed extract significantly improved hyperglycemia and
glucose tolerance, and increased serum insulin levels in diabetic mice; also signif-
icantly reduced body weight, blood glucose levels, improved glucose tolerance and
insulin-sensitivity in high fat diet-induced nonalcoholic fatty liver in mice.
Inhibition of oxidative stress, and inhibition of a-glucosidase activity by psoralidin,
coryfolin, and daidzein may contribute to the antidiabetic activity.

© Springer Nature Switzerland AG 2020 749

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_80
750 Cullen corylifolium (L.)

Keywords






Babchi Bakuchi Bokoshi Buguzhi Bukchi Lata-kasturi Loelab el abid





Psoraléa Trébol hediondo Waghchi

Vernaculars: Urd.: Babchi; Hin.: Babachi, Bakuci, Bavanchiyan, Bemchi, Bhavaj,

Buguchi, Bukchi; San.: Aindavi, Avalguja, Bākucī, Chanderlekha, Chanderprabha,
Krishnaphala, Kushthahantri, Lata-kasturi, Sitavari, Somaraji, Sugandha-kantak,
Vākucī; Ben.: Bakuchi, Barachi, Bavachi, Hakuchi, Kakuchi, Latakasturi, Somraji;
Mal.: Karkal, Karkokil, Karkokilari, Kaurkoalari; Mar.: Babachi, Bavachi, Bavachya,
Bavanchi; Tam.: Kaarboka-arisi, Karpogalarisi, Karpokarishi, Karpuva-arishi,
Karpuvanshi; Tel.: Bavanchalu, Bhavanchi-vittulu, Kala-ginja, Karu-bogi,
Karu-bogi-vittulu; Ara.: Bakuci, Loelab el abid, Mahalep; Chi.: 破故纸, Bu-gu-zhi,
Bu ku zi, Heiguzi, Malaytea scurfpea, Poguzhi; Eng.: Babchi seeds, Fountain bush,
Indian bread root, Malayan scurf-pea, Malaysian scurfpea, Psoralea seeds, West Indian
satinwood; Fre.: Psoraléa; Jap.: Bokoshi, Bokotsushi, Hokotsushi, Oranda biyu;
Kor.: Boh-gol-zhee, Gaeampul, Pagodzi; Per.: Ba bakhi, Vabkuchi, Waghchi; Rus.:
Bakuchi, Psoraleia; Sin.: Bodi; Spa.: Trébol hediondo.
Description: An annual plant found throughout plains of India, especially in the
semiarid regions of Rajasthan, Punjab, and Uttar Pradesh, and Iran; 90 cm high with
blackish glands; leaves petiolate, roundish-oval, dentate 2.5–7.5 cm long with black
spots on both surfaces. Inflorescence, axillary, pedunculate head; corolla yellow;
stamens 10 and ovary sessile. Fruit, an oval pod, short, dry, indehiscent, black,
glabrous, surrounded with persistent calyx. Seeds are oval or reniform, compressed,
blackish-yellow, 4 mm long by 3 mm in diameter. The taste is pungent and bitter-
sweet.LXXIX Dymock et al.XL described seeds as oblong and flattened, rough, dark
brown, 2 or 2.5 lines in length; they are unctuous (slippery) to touch, and have an
agreeable aromatic odor exactly resembling that of a bael fruit and very similar to elemi
(oleoresin from a tree native to the Philippines); the taste is aromatic and bitterish
(Figs. 1 and 2).
Actions and Uses: The seeds are considered lenitive, fragrant, stimulant and
aphrodisiac, and are recommended in the treatment of leprosy, and other chronic
skin diseases caused by a vitiated state of blood. They are also useful in febrile
bilious affections, and as anthelmintic and diuretic. They are used both internally
and applied externally as a plaster. Dymock et al.XL quoted Dr. Kenny Loll Dey
who recommended the oleoresinous extract of seeds diluted with simple ointment
base as an application in leucoderma; and states… “after application for some days
the white patches appear to become red or vascular; sometimes a slightly painful
sensation is felt. Occasionally, some small vesicles or pimples appear, and if these
be allowed to remain undisturbed, they dry up, leaving a dark spot of pigmentary
matter, which forms as it were a nucleus. From this point, as well as from the
margins of the patch, pigmentary matter gradually develops, which ultimately
Cullen corylifolium (L.) 751

Fig. 1 Cullen corylifolium, Plant, Biswarup Ganguly, WikimediaCommons; 3.0 Unported CC BY

3.0, https://commons.wikimedia.org/wiki/File:Psoralea_corylifolia_-_Agri-Horticultural_Society_
of_India_-_Alipore_-_Kolkata_2013-01-05_2280.JPG; https://creativecommons.org/licenses/by-sa/
3.0/deed.en

Fig. 2 Cullen corylifolium, Twig, Biswarup Ganguly, WikimediaCommons; 3.0 Unported CC

BY 3.0, https://commons.wikimedia.org/wiki/File:Psoralea_corylifolia_-_Agri-Horticultural_Soci
ety_of_India_-_Alipore_-_Kolkata_2013-01-05_2282.JPG; https://creativecommons.org/licenses/
by-sa/3.0/deed.en
752 Cullen corylifolium (L.)

coalesce with each other, and thus the whole patch disappears. It is also remarkable
that the appearance of fresh patches is also arrested by its application” (Phar Jour
Sept. 1881). In Unani medicine, seeds (temperament, hot 2–3° and dry 2–3°) are
classified as blood purifier, anthelmintic, carminative, laxative and to tonify
stomach. Due to its blood purifying properties, it is used in skin diseases, such as
leprosy, leucoderma, eczema and itching.LXXVII GhaniL also described seeds as
stomachic, appetizer, refrigerant, useful for phlegmatic fevers, and for the treatment
of skin diseases, such as vitiligo, leprosy and dermatitis. However, the seeds are
required to be used after purification by soaking them in ginger water for a week.
Other authors have described seeds as antibacterial, anti-inflammatory/antipyretic
and adaptogenic [1, 11]. Seeds are also used internally as tonic and stimulant in
impotence, nocturnal emissions and leucorrhea.LXXIX NadkarniCV described seeds
having an agreeable odor and a pungent bitterish taste, and classified in Ayurveda as
hot and dry and by some as cold and dry possessing laxative, fragrant, stimulant
and aphrodisiac properties; they are useful in bilious affections, and their powder is
especially used by Vaids for leprosy and leucoderma. In China, ripe fruits are
known as Buguzhi, Heiguzi and Poguzhi, and described as acrid and bitter in taste,
warm in property, and their actions are kidney-tonyfying, “Yang (vital function)-
invigorative,” “stomach and spleen-warming” and antidiarrheal. Mature, dried fruits
are officially listed in the Pharmacopoeia of the Peoples’ Republic of China of 2000
(vol II) for the treatment of enuresis, urinary frequency (pollakiuria), waist and
knee psychalgia and kidney weakness [68]. The herb is mainly used in China to
treat impotence due to “kidney” asthenia, premature ejaculation, nocturnal emis-
sions, enuresis, backache and knee pain, and pollakiuria; externally, it is used for
vitiligo, callus, psoriasis, and alopecia.XVIII Seeds are also used as tonic or an
aphrodisiac agent, and commonly employed as a remedy for bone fracture,
osteomalacia and osteoporosis in the TCM [56].
Phytoconstituents: A number of chemical compounds including psoralen, isop-
soralen, psoralidin, bakuchiol, bakuchalcone, bavachinin, flavones, volatile oils,
and lipids have been reported from different parts of the plant [8]. Ripe fruits
contain flavonoids: corylifolin (bavachin), corylifolinin (isobavachalcone), bava-
chromene and neobavachalcone; coumarins: psoralen, angelicin (isopsoralen),
psoralidin, isopsoralidin and corylidin; and monoterpene phenol, bakuchiol; volatile
oil, fixed oil, and resin [27, 47, 54, 69], bavachalcone, and bavadin [60], benzofuran
glycosides: psoralenoside and isopsoralenoside [31], isoflavonoids: corylinin,
sophoracoumestan A, neobavaisoflavone, daidzin and uracil [34], biochanin A [46],
genistein [13]; coryfolia D and bavarigenin [61]; meroterpenes, psoracorylifol F
[55], 8-methoxypsoralen, bavachinin, and astragalin [48]. Two flavonoids, bakui-
soflavone and bakuflavanone were isolated from fruits [9], and six unnamed fla-
vonoids and a meroterpenoid were also reported from dried fruits [52]. Flavonoids
and coumarins are identified as the major bioactive constituents [40]. Angelicin and
psoralidin, isobavachalcone, neobavaisoflavone, bavachin [45], bavachinin and
isobavachin [12], cyclobakuchiol C [66], 12,13-dihydro-12,13-dihydroxybakuchiol
and (12′S)-bisbakuchiol C [54], neocorylin [7], furano (2″, 3″, 7, 6)-4′-hydroxy-
flavanone, genistein, psoralen [26], have been isolated from the seeds. Leaves
contain high concentrations (>2 g/kg dry weight) of the anticancer metabolite,
Cullen corylifolium (L.) 753

genistein [17]. Corylifolin, bakuchiol and neobavaisoflavone are DNA polymerase

inhibitors, daidzein, a DNA polymerase and topoisomerase II inhibitor, and
bakuchicin is a topoisomerase II inhibitor [39].
Pharmacology: Aqueous seed extract significantly improved hyperglycemia and
glucose tolerance, and increased serum insulin levels in diabetic mice [35]; also
significantly reduced body weight, blood glucose levels, improved glucose toler-
ance and insulin-sensitivity in high fat diet-induced nonalcoholic fatty liver in mice
[36], and inhibited ROS production and protected hepatocytes against oxidative
stress and mitochondrial dysfunction [37]; bakuchiol was identified as the hepato-
protective agent in the extract [6, 30]. A combination of aqueous seed extracts of
P. corylifolia and Trigonella foenum-graecum (100 mg/kg each) to diabetic rats
produced significant synergistic effect on FBG, HbA1c and serum lipid profiles [2].
Total furocoumarins, psoralen and psoralidin from seeds exhibited potent antide-
pressant effect, mediated via inhibition of MAO activity, the HPA axis and
oxidative systems in mice [4, 5, 57, 64].
Aqueous-ethanol seed extract exhibits strong anti-H. pylori activity [67], and
methanol seed extract and bakuchiol have significant antimycobacterial activity against
M. aurum [29]. Bakuchiol was also bactericidal to oral bacteria including, S. mutans,
S. sanguis, S. salivarius, S. sobrinus, E. faecalis, E. faecium, L. acidophilus, L. casei,
L. plantarum, A. viscosus, and P. gingivalis [16]. Psoralidin, bakuchicin, psoralin and
angelicin, isolated from seeds, exhibited significant antibacterial activities against a
number of Gram-positive and Gram-negative bacteria [18], whereas, corylifolinin and
neobavaisoflavone significantly inhibited growth of S. aureus, MRSA and ESbetaL-
producing S. aureus [48]. Prenylflavonoids, corylifols A–C were also significantly
active against S. aureus and S. epidermidis [65]. A flavonol glycoside showed sig-
nificant antibacterial and antifungal activities [58], and methanol seed extract showed
antifungal activity against T. rubrum, T. mentagrophytes, E. floccosum and M. gyp-
seum, which was identified to be due to the flavonoid, 4′-methoxy flavones [33].
Ethanol fruit extract was cytotoxic in cell cultures [21], and bakuchiol was
identified as the active component for this activity [14], and psoralidin from seeds
was active against stomach carcinoma cell lines [62]. Isoflavonoid, corylifol A
shows significant anticancer activity against HepG2 and Hep3B hepatocellular
carcinoma cell lines [38]. A mixture of glycerides of fatty acids from seeds inhibited
growth and delayed the onset of papilloma formation in mice on topical application,
and on oral administration significantly inhibited growth of 20-MCA-induced soft
tissue fibrosarcomas in mice [23]. Ethanol extract showed antineoplastic activity
against Hep-2 cell and lung carcinoma cells [51], and the seed extract was active in
a human breast cancer cell line [32], and also stimulated immune system in mice
[22]. Psoralen and isopsoralen are suggested to contribute to the anticancer effect
[15, 49]. Szliszka et al. [40] found neobavaisoflavone and psoralidin cytotoxic to
prostate cancer cells, while psoralidin was identified to augment anticancer effects
of tumor necrosis factor-related apoptosis-inducing ligand [3]. A P. corylifolia
extract is reported to decrease urinary calcium excretion and serum osteocalcin [44],
and psoralen promoted bone mass in ovariectomized rats [63], and ethanol fruit
754 Cullen corylifolium (L.)

extract and bakuchiol [25] and bavachin treatments of ovariectomized rats also
reduced bone loss, with no uterotrophic activity [50]. The fruit extract in collagen
matrix graft also increased in vivo local new bone formation [53].
Mechanism of Action: Inhibition of oxidative stress, and inhibition of a-glucosidase
activity by psoralidin, coryfolin, and daidzein [48] may contribute to the antidiabetic
activity [35]. Also, psoralidin and bakuchiol are significant inhibitors of protein tyr-
osine phosphatase 1B [19]; protein tyrosine phosphatase 1B plays a major role in the
negative regulation of insulin signaling. Antidepressant effect is mediated via inhibi-
tion of MAO activity, the HPA axis and oxidative systems in mice [4, 5, 57, 64];
psoralen and isopsoralen also inhibit MAO-A in vitro [20]. Psoralen and isopsoralen
cause significant in vitro apoptosis of tumor cells and may contribute to its anticancer
effect [49]. Neobavaisoflavone significantly inhibits ROS, reactive nitrogen species
and cytokines: ILs and TNF-a in stimulated macrophages [41], and psoralidin is a dual
inhibitor of COX-2 and 5-LOX, suppresses radiation-induced expression of
proinflammatory cytokines (TNF-a, TGF-b, IL-6 and IL-1 a/b), and ICAM-1 in mice
lung [59]. Bakuchiol, bavachinin, neobavaisoflavone, corylifol A, corylin,
isobavachalcon, and bavachin inhibit IL-6-induced STAT3 activation and phospho-
rylation, that may also contribute to its anti-inflammatory effects [24]. Upregulation of
primary human osteoblast differentiation, via Wnt signalling pathway by bakuchiol
and bavachin [50], and stimulation of osteoblastic differentiation from bone
mesochymal cells [63] are the suggested mechanisms for protection against bone loss
in ovariectomized rats.
Human A/Es, Allergy and Toxicity: Flatulence is a common A/E of treatment
with seeds and fruits.LXXVII A Korean woman who used over 10 times the usual
dose of Psoralea seeds to self-treat postmenopausal osteoporosis, developed acute
cholestatic hepatitis [28]. Another 64-year old female patient in Germany treated
herself for 9-months with various Indian Ayurvedic herbal products for her vitiligo
and experienced a severe hepatotoxicity [43].
Animal Toxicity: Oral LD50 of the crude drug, total herb oil, and isopsoralen in
mice were 38,000 mg/kg, 2.3 ml/kg, and 180 mg/kg, respectively. LD50 (i.p.) of
isopsoralen in mice was 138 mg/kg.XVIII Ethanol seed extract in diet to rats for
90-days lowered body weight gain, food consumption and food conversion effi-
ciency, testes weights in male rats and ovaries in female rats, suggesting a dis-
ruption of hypothalamus-pituitary-gonadal axis [42].
Pharmacokinetics: Elimination half-lives of psoralen and isopsoralen after intra-
venous administration in rats were 4.88 and 5.35 h, and after oral administration,
4.13 and 5.56 h, respectively [10].
Commentary: Despite significant use of herbal preparations involving this plant,
both in Unani and Ayurveda, no formal clinical studies published in scientific
journals listed on PubMed are available.
Cullen corylifolium (L.) 755

References
1. Anand KK, Sharma ML, Singh B, Ray Ghatak BJ. Anti-inflamatory, antipyretic
& analgesic properties of bavachinin—a flavanone isolated from seeds of
Psoralea corylifolia Linn. (Babchi). Indian J Exp Biol. 1978;16:1216–7.
2. Bera TK, Ali KM, Jana K, Ghosh A, Ghosh D. Protective effect of aqueous
extract of seed of Psoralea corylifolia (Somraji) and seed of Trigonella
foenum-graecum L. (Methi) in streptozotocin-induced diabetic rat: a
comparative evaluation. Pharmacognosy Res. 2013;5:277–85.
3. Bronikowska J, Szliszka E, Jaworska D, et al. The coumarin psoralidin
enhances anticancer effect of tumor necrosis factor-related apoptosis-
inducing ligand (TRAIL). Molecules. 2012;17:6449–64.
4. Chen Y, Kong LD, Xia X, et al. Behavioral and biochemical studies of total
furocoumarins from seeds of Psoralea corylifolia in the forced swimming
test in mice. J Ethnopharmacol. 2005;96:451–9.
5. Chen Y, Wang HD, Xia X, et al. Behavioral and biochemical studies of total
furocoumarins from seeds of Psoralea corylifolia in the chronic mild stress
model of depression in mice. Phytomedicine. 2007;14:523–9.
6. Cho H, Jun JY, Song EK, et al. Bakuchiol: a hepatoprotective compound of
Psoralea corylifolia on tacrine-induced cytotoxicity in HepG2 cells. Planta
Med. 2001;67:750–1.
7. Choi YH, Yon GH, Hong KS, et al. In vitro BACE-1 inhibitory phenolic
components from the seeds of Psoralea corylifolia. Planta Med. 2008;
74:1405–8.
8. Chopra B, Dhingra AK, Dhar KL. Psoralea corylifolia L. (Buguchi)—
folklore to modern evidence: review. Fitoterapia. 2013;90:44–56.
9. Cui Y, Taniguchi S, Kuroda T, Hatano T. Constituents of Psoralea coryli-
folia fruits and their effects on methicillin-resistant Staphylococcus aureus.
Molecules. 2015;20:12500–11.
10. Feng L, Wang L, Jiang X. Pharmacokinetics, tissue distribution and excretion
of coumarin components from Psoralea corylifolia L. in rats. Arch Pharm Res.
2010;33:225–30.
11. Gaind KN, Dar RN, Kaul RN. Antistaphylococcal activity of seeds of
Psoralea corylifolia. J Pharm Sci. 1965;53:1428–9.
12. Haraguchi H, Inoue J, Tamura Y, Mizutani K. Antioxidative components of
Psoralea corylifolia (Leguminosae). Phytother Res. 2002;16:539–44.
13. Hsu YT, Wu CJ, Chen JM, et al. The presence of three isoflavonoid
compounds in Psoralea corylifolia. J Chromatogr Sci. 2001;39:441–4.
14. Iwamura J, Dohi T, Tanaka H, et al. Cytotoxicity of corylifoliae fructus. II.
Cytotoxicity of bakuchiol and the analogues. Yakugaku Zasshi. 1989;109:
962–5 (Japanese).
15. Jiang Z, Xiong J. Induction of apoptosis in human hepatocarcinoma
SMMC-7721 cells in vitro by psoralen from Psoralea corylifolia. Cell
Biochem Biophys. 2014;70:1075–81.
756 Cullen corylifolium (L.)

16. Katsura H, Tsukiyama RI, Suzuki A, Kobayashi M. In vitro antimicrobial

activities of bakuchiol against oral microorganisms. Antimicrob Agents
Chemother. 2001;45:3009–13.
17. Kaufman PB, Duke JA, Brielmann H, et al. A comparative survey of
leguminous plants as sources of the isoflavones, genistein and daidzein:
implications for human nutrition and health. J Altern Complement Med.
1997;3:7–12.
18. Khatune NA, Islam ME, Haque ME, et al. Antibacterial compounds from
the seeds of Psoralea corylifolia. Fitoterapia. 2004;75:228–30.
19. Kim YC, Oh H, Kim BS, et al. In vitro protein tyrosine phosphatase 1B
inhibitory phenols from the seeds of Psoralea corylifolia. Planta Med. 2005;
71:87–9.
20. Kong LD, Tan RX, Woo AY, Cheng CH. Inhibition of rat brain monoamine
oxidase activities by psoralen and isopsoralen: implications for the treatment
of affective disorders. Pharmacol Toxicol. 2001;88:75–80.
21. Kubo M, Dohi T, Odani T, et al. Cytotoxicity of corylifoliae fructus.
I. Isolation of the effective compound and the cytotoxicity. Yakugaku
Zasshi. 1989;109:926–31 (Japanese).
22. Latha PG, Evans DA, Panikkar KR, Jayavardhanan KK. Immunomodula-
tory and antitumour properties of Psoralea corylifolia seeds. Fitoterapia.
2000;71:223–31.
23. Latha PG, Panikkar KR. Inhibition of chemical carcinogenesis by Psoralea
corylifolia seeds. J Ethnopharmacol. 1999;68:295–8.
24. Lee SW, Yun BR, Kim MH, et al. Phenolic compounds isolated from
Psoralea corylifolia inhibit IL-6-induced STAT3 activation. Planta Med.
2012;78:903–6.
25. Lim SH, Ha TY, Kim SR, et al. Ethanol extract of Psoralea corylifolia L.
and its main constituent, bakuchiol, reduce bone loss in ovariectomised
Sprague-Dawley rats. Br J Nutr. 2008;19:1–9.
26. Liu H, Bai YJ, Chen YY, Zhao YY. Studies on chemical constituents from
seed of Psoralea corylifolia. Zhongguo Zhong Yao Za Zhi. 2008;33:1410–2
(Chinese).
27. Mar W, Je KH, Seo EK. Cytotoxic constituents of Psoralea corylifolia.
Arch Pharm Res. 2001;24:211–3.
28. Nam SW, Baek JT, Lee DS, et al. A case of acute cholestatic hepatitis
associated with the seeds of Psoralea corylifolia (Boh-Gol-Zhee). Clin
Toxicol (Phila). 2005;43:589–91.
29. Newton SM, Lau C, Gurcha SS, et al. The evaluation of forty-three plant
species for in vitro antimycobacterial activities; isolation of active con-
stituents from Psoralea corylifolia and Sanguinaria canadensis. J Ethnophar-
macol. 2002;79:57–67.
30. Park EJ, Zhao YZ, Kim YC, Sohn DH. Protective effect of (S)-bakuchiol
from Psoralea corylifolia on rat liver injury in vitro and in vivo. Planta Med.
2005;71:508–13.
Cullen corylifolium (L.) 757

31. Qiao CF, Han QB, Mo SF, et al. Psoralenoside and isopsoralenoside, two
new benzofuran glycosides from Psoralea corylifolia. Chem Pharm Bull
(Tokyo). 2006;54:714–6.
32. Rajan V, Tripathi J, Variyar P, Pandey BN. Mechanism of cytotoxicity by
Psoralea corylifolia extract in human breast carcinoma cells. J Environ
Pathol Toxicol Oncol. 2014;33:265–77.
33. Rajendra Prasad N, Anandi C, Balasubramanian S, Pugalendi KV. Anti-
dermatophytic activity of extracts from Psoralea corylifolia (Fabaceae)
correlated with the presence of a flavonoid compound. J Ethnopharmacol.
2004;91:21–4.
34. Ruan B, Kong LY, Takaya Y, Niwa M. Studies on the chemical constituents
of Psoralea corylifolia L. J Asian Nat Prod Res. 2007;9:41–4.
35. Seo E, Lee EK, Lee CS, et al. Psoralea corylifolia L. seed extract ame-
liorates streptozotocin-induced diabetes in mice by inhibition of oxidative
stress. Oxid Med Cell Longev. 2014;897296.
36. Seo E, Oh YS, Jun HS. Psoralea corylifolia L. seed extract attenuates
nonalcoholic fatty liver disease in high-fat diet-induced obese mice. Nutrients.
2016;8:83.
37. Seo E, Oh YS, Kim D, et al. Protective role of Psoralea corylifolia L. seed
extract against hepatic mitochondrial dysfunction induced by oxidative
stress or aging. Evid Based Complement Alternat Med. 2013;678028.
38. Song P, Yang XZ, Yuan JQ. Cytotoxic constituents from Psoralea
corylifolia. J Asian Nat Prod Res. 2013;15:624–30.
39. Sun NJ, Woo SH, Cassady JM, Snapka RM. DNA polymerase and
topoisomerase II inhibitors from Psoralea corylifolia. J Nat Prod. 1998;61:
362–6.
40. Szliszka E, Czuba ZP, Sędek Ł, et al. Enhanced TRAIL-mediated apoptosis in
prostate cancer cells by the bioactive compounds neobavaisoflavone and
psoralidin isolated from Psoralea corylifolia. Pharmacol Rep. 2011;63:139–48.
41. Szliszka E, Skaba D, Czuba ZP, Krol W. Inhibition of inflammatory
mediators by neobavaisoflavone in activated RAW264.7 macrophages.
Molecules. 2011;16:3701–12.
42. Takizawa T, Imai T, Mitsumori K, et al. Gonadal toxicity of an ethanol
extract of Psoralea corylifolia in a rat 90-day repeated dose study. J Toxicol
Sci. 2002;27:97–105.
43. Teschke R, Bahre R. Severe hepatotoxicity by Indian Ayurvedic herbal
products: a structured causality assessment. Ann Hepatol. 2009;8:258–66.
44. Tsai MH, Huang GS, Hung YC, et al. Psoralea corylifolia extract ameliorates
experimental osteoporosis in ovariectomized rats. Am J Chin Med. 2007;35:
669–80.
45. Tsai WJ, Hsin WC, Chen CC. Antiplatelet flavonoids from seeds of
Psoralea corylifolia. J Nat Prod. 1996;59:671–2.
46. Wall ME, Wani MC, Manikumar G, et al. Plant antimutagenic agents, 2.
Flavonoids. J Nat Prod. 1988;51:1084–91.
758 Cullen corylifolium (L.)

47. Wall ME, Wani MC, Manikumar G, et al. Plant antimutagenic agents, 3.
Coumarins. J Nat Prod. 1988;51:1148–52.
48. Wang TX, Yin ZH, Zhang W, Peng T, Kang WY. Chemical constituents
from Psoralea corylifolia and their antioxidant alpha-glucosidase inhibitory
and antimicrobial activities. Zhongguo Zhong Yao Za Zhi. 2013;38:2328–
33 (Chinese).
49. Wang Y, Hong C, Zhou C, et al. Screening antitumor compounds psoralen
and isopsoralen from Psoralea corylifolia L. seeds. Evid Based Comple-
ment Alternat Med. 2011;363052.
50. Weng ZB, Gao QQ, Wang F, et al. Positive skeletal effect of two ingredients
of Psoralea corylifolia L. on estrogen deficiency-induced osteoporosis and
the possible mechanisms of action. Mol Cell Endocrinol. 2015;417:103–13.
51. Whelan LC, Ryan MF. Ethanolic extracts of Euphorbia and other ethnob-
otanical species as inhibitors of human tumour cell growth. Phytomedicine.
2003;10:53–8.
52. Won TH, Song IH, Kim KH, et al. Bioactive metabolites from the fruits of
Psoralea corylifolia. J Nat Prod. 2015;78:666–73.
53. Wong RW, Rabie AB. Effect of Buguzhi (Psoralea corylifolia fruit) extract
on bone formation. Phytother Res. 2010;24 Suppl 2:S155–60.
54. Wu CZ, Hong SS, Cai XF, et al. Hypoxia-inducible factor-1 and nuclear
factor-kappaB inhibitory meroterpene analogues of bakuchiol, a constituent of
the seeds of Psoralea corylifolia. Bioorg Med Chem Lett. 2008;18:2619–23.
55. Xiao G, Li X, Wu T, et al. Isolation of a new meroterpene and inhibitors of
nitric oxide production from Psoralea corylifolia fruits guided by TLC
bioautography. Fitoterapia. 2012;83:1553–7.
56. Xin D, Wang H, Yang J, et al. Phytoestrogens from Psoralea corylifolia reveal
estrogen receptor-subtype selectivity. Phytomedicine. 2010;17:126–31.
57. Xu Q, Pan Y, Yi LT, et al. Antidepressant-like effects of psoralen isolated
from the seeds of Psoralea corylifolia in the mouse forced swimming test.
Biol Pharm Bull. 2008;31:1109–14.
58. Yadava RN, Verma V. A new biologically active flavonol glycoside from
Psoralea corylifolia (Linn.). J Asian Nat Prod Res. 2005;7:671–5.
59. Yang HJ, Youn H, Seong KM, et al. Psoralidin, a dual inhibitor of COX-2
and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflam-
mation. Biochem Pharmacol. 2011;82:524–34.
60. Yang TT, Qin MJ. Isolation and structure identification of a new isoflavone
from Psoralea corylifolias. Yao Xue Xue Bao. 2006;41:76–9 (Chinese).
61. Yang TT, Li J, Qin MJ, et al. Two new compounds from Psoralea
corylifolia L. Yao Xue Xue Bao. 2009;44:1387–90 (Chinese).
62. Yang YM, Hyun JW, Sung MS, et al. The cytotoxicity of psoralidin from
Psoralea corylifolia. Planta Med. 1996;62:353–4.
63. Yang Z, Huang JH, Liu SF, et al. The osteoprotective effect of psoralen in
ovariectomy-induced osteoporotic rats via stimulating the osteoblastic differ-
entiation from bone mesenchymal stem cells. Menopause. 2012;19:1156–64.
Cullen corylifolium (L.) 759

64. Yi LT, Li YC, Pan Y, et al. Antidepressant-like effects of psoralidin isolated

from the seeds of Psoralea corylifolia in the forced swimming test in mice.
Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:510–9.
65. Yin S, Fan CQ, Wang Y, et al. Antibacterial prenylflavone derivatives from
Psoralea corylifolia, and their structure-activity relationship study. Bioorg
Med Chem. 2004;12:4387–92.
66. Yin S, Fan CQ, Yue JM. Cyclobakuchiol C, a new bakuchiol derivative
from Psoralea coryllfolia. J Asian Nat Prod Res. 2007;9:29–33.
67. Zaidi SF, Yamada K, Kadowaki M, et al. Bactericidal activity of medicinal
plants, employed for the treatment of gastrointestinal ailments, against
Helicobacter pylori. J Ethnopharmacol. 2009;121:286–91.
68. Zhao LH, Wu MH, Xiang BR. Analysis of Psoralea corylifolia L. fruits in
different regions. Chem Pharm Bull (Tokyo). 2005;53:1054–7.
69. Zhu DU, Chen ZX, Zhou BN, et al. Studies on the chemical costituents of
Bu-Gu-Zhi, the seeds of Psoralea corylifolia L. Yao Hsueh Hsueh Pao.
1979;14:605–11.
Cuminum cyminum L.
(Apiaceae/Umbelliferae)

(Syns.: C. odorum Salisb.; C. hispanicum Bunge; Ligusticum cuminum (L.) Crantz)

Abstract
A flowering plant that has been cultivated since antiquity, and is now mainly
cultivated in North Africa, Iran, India, Indonesia, China, and the East Mediter-
ranean. The fruit (inaccurately referred to as seeds) consists of two mericarps which
remain united together when dry. Use of cumin dates back to centuries since ancient
civilizations. It is mentioned in the writings of Greeks, Romans and Egyptians;
Dioscorides considered it good for stomach and inflammation, and used it as
stomachic, emmenagogue and for arthritis. Ibn Sina, Arabs and Persians, following
Dioscorides, described four kinds of cumin, which they named Kirmani or black,
Farsi or yellow, Shami (Syrian) and Nabti (Egyptian). The Kirmani or black cumin
is identified in India as Siyah Zira, a species of caraway, peculiar to Central Asia, the
Nabti or Egyptian kind is considered the true cumin. Galen described it as diuretic,
carminative and antiflatulence, whereas Dioscorides said that it is useful in chronic
leucorrhea, and smelling the powdered seeds mixed with vinegar cures epistaxis. In
Ayurveda also, it is regarded aromatic, stomachic, and stimulant, and used in the
treatment of dyspepsia, hoarseness of voice, agnimãndya, atisãra, krmiroga, and
kãmalã. Fully ripe seeds (fruits) are richer in polyphenols and condensed tannins
than unripe ones, and exhibit higher antioxidant activity. Unripe fruits have higher
total flavonoid content compared to the half-ripe and fully ripe fruits; rosmarinic
acid being the major phenolic acid for the unripe fruits and p-coumaric acid in
half-ripe and fully ripe fruits. Essential oil yield and its chemical constituents vary in
samples from various locations. Oral administration of cumin to diabetic rats
significantly reduced blood glucose (better than glibenclamide), plasma and tissue
cholesterol, phospholipids, FFAs and TGs, but did not lower cholesterol level of
hypercholesterolemic rats. Pretreatment of rats with cumin extract protected against
stress-induced biochemical changes, inhibited LPO, and corrected scopolamine-
induced memory deficit. In an RCT, overweight/obese women who took 3 g/d
cumin powder with yogurt at two meals for 3-months, had reduced serum levels of
fasting TC, TGs, and LDL, and increased HDL, but no effect on FBG.

© Springer Nature Switzerland AG 2020 761

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_81
762 Cuminum cyminum L.

Keywords



Cominho Cumijn Cumin Haferkümmel

Jiraka
Jirana
Kammun




Ma qin Safed jira Spidskommen

Vernaculars: Urd.: Zeera safed; Hin.: Safed jira, Zira; San.: Ajaji, Dipyaka,
Dirghajiraka, Gaurajaji, Hrasvanga, Jira, Jiraka, Jirakaha, Jirana, Kunchika; Ben.: Jira,
Sadajira, Safed jira, Zira; Guj.: Jiru; Mal.: Cheerakam, Jintan, Jirakam, Jorekam;
Mar.: Jire, Jiregire, Jiru, Pandhare jire; Tam.: Cheerakam, Jeerakam, Shimai-shombu,
Shiragam; Tel.: Jeelatsara, Jilakara, Jilakarra, Jilakhrah, Jiraka, Jirana, Tella jilakarra;
Ara.: Kammun, Sannût; Bur.: Ziya; Chi.: 孜然芹, Ma qin (Ma ch’in), Xian hao,
Xiang han qin, Zi ran; Cze.: Římský kmín, Šabrej kmínovitý; Dan.: Kloeftsvoeb,
Spidskommen; Dut.: Cumijn, Komijn; Eng.: Cumin, Cumin seeds; Fin.: Juustoku-
mina, Kumina, Maustekumina, Roomankumina; Fre.: Anisacre, Cumin, Cumin blanc,
Cumin du maroc, Faux anis; Ger.: Aegypischer kümmel, Haferkümmel, Italienischer
kümmel, Kreuzkümmel, Linsenkümmel, Mohrenkümmel, Mutterkümmel, Pfaf-
fenkümmel, Spießkümmel, Römischer kümmel, Weißer kreuzkümmel; Gre.: Kimino;
Ind.: Jinten; Ita.: Comino bianco, Cumino; Jap.: Hime unikyoo, Kumin; Kor.:
Kumin; Lao.: Thien khaw; Maly.: Jintan, Jintan putih; Nep.: Jiiraa; Nor.: Spis-
skummen; Per.: Zeera, Zhireh, Zira safed, Zireh; Pol.: Kmin rzymski; Por.: Cominho;
Rus.: Kmin tminovyj; Sin.: Duru, Suduru; Spa.: Alcamonia, Comino, Comino blanco,
Comino fino; Swe.: Romersk kummin, Spiskummin; Tha.: Thian-khao, Yee raa;
Tur.: Acem kimyonu, Kimyon.
Description: A flowering plant that has been cultivated since antiquity, and is now
mainly cultivated in North Africa, Iran, India, Indonesia, China, and the East
Mediterranean [17]. The fruit (inaccurately referred to as seeds) consists of two
mericarps which remain united together when dry, and form an elongated ovoid body
about 6 mm long and 2.5 mm wide in the middle. Each mericarp has five primary
ridges and four secondary, the vittae are six in number, two of them situated on the
commissural side; the seeds are pentangular with rounded angles (Figs. 1, 2 and 3).XL
Actions and Uses: Use of cumin dates back to centuries since ancient civilizations. It
is mentioned in the writings of Greeks, Romans and Egyptians; Dioscorides consid-
ered it good for stomach and inflammation, and used it as stomachic, emmenagogue
and for arthritis.LIII Ibn Sina, Arabs and Persians, following Dioscorides, described
four kinds of cumin, which they named Kirmani or black, Farsi or yellow, Shami
(Syrian) and Nabti (Egyptian). The Kirmani or black cumin is identified in India as
Siyah Zira, a species of caraway, peculiar to Central Asia, the Nabti or Egyptian kind is
considered the true cumin.XL Galen described it as diuretic, carminative and antiflat-
ulence, whereas Dioscorides said that it is useful in chronic leucorrhea, and smelling
the powdered seeds (temperament, hot 2° and dry 3°) mixed with vinegar cures
epistaxis.LXIX In Indian traditional systems of medicine, cumin is considered carmi-
native, eupeptic, antispasmodic and astringent, and is used in the treatment of mild
digestive disorders, diarrhea, dyspepsia, flatulence, morning sickness, colic, dyspeptic
headaches and bloating, as an analgesic, in bronchopulmonary disorders, and to
Cuminum cyminum L. 763

Fig. 1 Cuminum cyminum, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Cuminum_cyminum_-_K%C3%B6hl
er%E2%80%93s_Medizinal-Pflanzen-198.jpg

Fig. 2 Cuminum cyminum, Fruits/Seeds, Prof. Akbar, Original

764 Cuminum cyminum L.

Fig. 3 Carum carvi (for comparison), Prof. Akbar, Original

promote assimilation of other herbs and to improve liver function [19]. In Ayurveda
also, it is regarded aromatic, stomachic, and stimulant, and used in the treatment of
dyspepsia, hoarseness of voice,LXXXI,CV agnimãndya, atisãra, krmiroga,CXXVII and
kãmalã [8]. In Iranian traditional medicine, fruits are also used as a remedy for diar-
rhea, flatulence, indigestion,CVII and as stimulant, and astringent [1]. In Thai traditional
medicine, cumin is used to treat colds, asthma and fever; and is thought to be cooling,
and applied in the form of a plaster to allay pain and irritation [30].
Phytoconstituents: Fully ripe seeds (fruits) are richer in polyphenols and condensed
tannins than unripe ones, and exhibit higher antioxidant activity. Unripe fruits have
higher total flavonoid content compared to the half-ripe and fully ripe fruits; rosmarinic
acid being the major phenolic acid for the unripe fruits and p-coumaric acid in half-ripe
and fully ripe fruits [45]. Essential oil yield and its chemical constituents vary in
samples from various locations. Essential oil is rich in cuminaldehyde (35–60%);
a and b-pinene, d-3-carene, 1,8-cineole, a- and b-phellandrene, p-cymene, limonene,
a- and c-terpinene, a-terpineol, terpinene-4-ol cuminyl alcohol, myrcene, trans-
dihydrocarvone, linalool, b-caryophyllene, b-farnesene, b-elemene, luteolin, and
7-O-b-D-glucopyranosides of apigenin, being the minor constituents. Twelve
monoterpenoid glucosides were isolated from water-soluble portion of methanol
extract [17]. Forty-nine compounds were identified in volatile oil from China; cuminal
and safranal accounting for 32.26% and 24.46%, respectively. Contents more than 1%
were monterpenes, sesquiterpenes, aromatic aldehydes and aromatic oxides; terpenes,
terpenols, terpenals, terpenones, terpene esters and aromatic compounds were present
in relatively small amounts [67]. Essential oil yields of Indian and Tunisian cumin
Cuminum cyminum L. 765

fruits were 1.21 and 1.62%, respectively, and a total of 40 compounds were identified,
34 of which were common in both essential oils [5], whereas Hajlaoui et al. [13]
reported twenty-one components from EO of a Tunisian variety with cuminlaldehyde
(39.48%), c-terpinene (15.21%), O-cymene (11.82%), b-pinene (11.13%),
2-caren-10-al (7.93%), trans-carveol (4.49%) and myrtenal (3.5%) as the major
components. Major components in cumin EO from India were cuminaldehyde,
pinenes, and p-cymene [47]. Monoterpenes: b-pinene, p-cymene and c-terpinene and
the terpenoid aldehydes, cuminic aldehyde were the major compounds in cumin oils
collected from four different geographical locations in Morocco [66]. Iranian cumin
EO had cuminaldehyde (29.02%) and a-terpinen-7-al (20.70%) as the highest amounts
of the EO [40]. Another Iranian oil from Alborz Mountain was reported to have
a-pinene (29.2%), limonene (21.7%), 1,8-cineole (18.1%), linalool (10.5%), linalyl
acetate (4.8%), and a-terpineole (3.17%) as the major components [32]. Essential oil
yield of cumin fruits from Pakistan by hydrodistillation was reported as
2.52 ± 0.11%, with cuminal, c-terpinene and pinocarveol as the major components
[9], while the major components in oil from Italy were reported to be p-mentha-1,
4-dien-7-al, cumin aldehyde, c-terpinene, and b-pinene [15]. Two sesquiterpenoid
glucosides, cuminoside A and B, and two alkyl glycosides were isolated from the polar
portion of methanolic extract [61], and two flavone glucosides were isolated from the
alcoholic extract of fruits [24].
Pharmacology: Ethanol extract exhibits significant antimicrobial activity against H.
pylori [38], a moderate activity against clinical isolates of MRSA [31], and against
gentamicin-resistant clinical isolates of enterococcal strains [46]. Ethyl acetate, ace-
tone and methanol extracts exhibited various degrees of modest antibacterial activity
against K. pneumoniae, P. aeruginosa, S. aureus, E. coil, C. xerosis, and S. faecalis
[23]. Chloroform and isoamyl alcohol extracts were significantly active against
P. aeruginosa, S. marcescens and S. pyogenes [4]. Essential oil showed significant
antibacterial activity against a number of human pathogenic bacteria [57, 66], against
B. cereus [40], highly effective against Vibrio spp. strains [13], E. coli, S. aureus, and
S. faecalis [1], moderately active against S. typhi and E. coli [36], C. albicans [16, 33,
39, 66], against dermatophytes, especially T. rubrum [7, 47], showed a strong fungal
growth inhibitory effect on A. flavus, A. parasiticus and A. niger [21, 32, 55], and
inhibited aflatoxins production by A. parasiticus [26].
Oral administration of cumin to diabetic rats significantly reduced blood glucose
(better than glibenclamide), plasma and tissue cholesterol, phospholipids, FFAs and
TGs [8] but did not lower cholesterol level of hypercholesterolemic rats [52]. Dietary
supplementation of cumin significantly increased pancreatic lipase, trypsine, and
chymotrypsine of rats [42], prevented ethanol and thermally oxidized sunflower
oil-induced changes in the liver phospholipid fatty acid composition [2, 27], and
decreased levels of intestinal phosphatases and sucrase [43]. Methanol extract to
diabetic rats for 28-days reduced blood glucose, HbA1c, creatinine and BUN, sig-
nificantly reduced renal oxidative stress and advanced glycated end products,
improved serum insulin, liver and muscle glycogen content [18], and lowered
cholesterol in ovariectomized rats [56]. Petroleum ether extract to diabetic rats for
766 Cuminum cyminum L.

45-days also lowered blood glucose and improved lipid profile; cuminaldehyde and
cuminol were identified as potent insulinotrophic components; an inhibitor of insulin
secretion with potent b-cell protective action was also isolated from the same pet-
roleum ether fraction, so cumin can lower blood glucose without causing hypo-
glycemia [41]. Cumin extract also significantly decreased area under the glucose
tolerance curve and hyperglycemic peak in healthy rabbits [48]. Cuminaldehyde also
shows in vitro aldose reductase and a-glucosidase inhibitory activity [29]. Essential
oil reduced LDL/HDL ratio by half, significantly increased Hb concentration,
hematocrit, and platelet count, and decreased WBCs count [1]. Cumin also improved
plasma NO and decreased SBP in hypertensive rats [20]. Ether extract inhibited
arachidonate-induced platelet aggregation, and inhibited AA-induced TXB2 pro-
duction [58].
Pretreatment of rats with cumin extract protected against stress-induced bio-
chemical changes, inhibited LPO, and corrected scopolamine-induced memory def-
icit [28]. The EO reduced acquisition and expression of morphine-induced
conditioned place preference [22, 25], and at a higher dose of 2% significantly
attenuated development of morphine tolerance and dependence in mice [12]. Aqu-
eous, ethanol and methanol cumin extracts show strong in vitro antioxidant activity
[6, 37, 53, 59], which is correlated with the presence of flavonoid contents [37].
Methanol fruit extract reduced blood glucose, and gastric ulcer score, significantly
increased gastric mucus content, antioxidant status and cellular ATPase enzyme
levels of diabetic rats [64], whereas aqueous extract increased gastric acid secretion
and significantly inhibited castor oil-induced diarrhea in rats [49, 65]. Methanol fruit
extract also inhibited in vitro LOX activity, which was ascribed mainly to cumi-
naldehyde [62]. Essential oil shows better antioxidant activity [1, 9, 13], and oil
obtained by supercritical carbon dioxide extraction showed higher activity than
steam-distilled oil [63]. Ethanol fruit extract potently inhibited LPS-induced NO
production in RAW 264.7 cells [30].
Cumin seeds significantly decreased incidence of B(a)P-induced stomach neo-
plasia, 3′-methyl-4-dimethylaminoazobenzene-induced hepatomas, colon carcinoma
and MCA-induced uterine cervix tumors in rats [3, 10, 34, 35]. Methanol cumin
extract to male rats for 60-days inhibited spermatogenesis and fertility without pro-
ducing any apparent toxic effects [11], and an isolated fraction inhibited spermato-
genesis and significantly lowered testosterone levels [54]. Essential oil, however,
significantly improved copper-induced decrease in sperm count, motility and via-
bility, and normal architecture [50]. Ethanol seeds extract did not show any
anti-implantation activity in rats [44].
Clinical Studies: Addition of 3–5 drops of a cumin extract thrice daily to healthy
volunteers for 45-days significantly reduced FBG and oxidized LDL levels [51]. In
an RCT, overweight/obese Iranian women who took 3 g/d cumin powder with
yogurt at two meals for 3-months, had reduced serum levels of fasting TC, TGs, and
LDL, and increased HDL, but no effect on FBG [68]. Consumption of cumin
powder and Orlistat120 by overweight individuals for 8-weeks produced a similar
Cuminum cyminum L. 767

significant decrease in weight and BMI. Cumin group also had a significant
reduction in serum insulin levels [60].
Mechanism of Action: Cumin seeds significantly elevate activities of antioxidant
enzymes: SOD and CAT [10], cuminaldehyde and cuminol were identified as
potent insulinotrophic [41], and cuminaldehyde also possesses in vitro aldose
reductase and a-glucosidase inhibitory activity [29]; they all can contribute to its
antidiabetic activity. Cumin protects colon from carcinogenic effects of DMH by
decrease in colonic activity of b-glucuronidase and mucinase [35].
Human A/Es, Allergy and Toxicity: It may cause constipation.LXXVII
Animal Toxicity: Cumin fruits (2%) fed to rats in diet for 6-weeks were nontoxic.
However, diet containing 10% cumin fruits, impaired growth and caused entero-
hepatonephropathy [14].
Commentary: In small quantities, cumin seeds and their powder are used in cooking
of many countries, that might be beneficial for digestive health, if used on a regular
basis. However, as a medicinal agent, quite high dose (3 g/d) was used to achieve
lipid-lowering effects in obese/overweight women. While cumin-extract lowered FBG
in healthy volunteers [51], and cumin lowered blood glucose better than glibenclamide
in diabetic rats [8], blood glucose was not reduced in obese/overweight women [68].
Further clinical studies in large number of patients, and diverse populations will be
needed to establish any clinical benefits of this common spice. Also, wide variations in
chemical constituents of cumin from various geographical locations must be taken into
consideration when evaluating its benefits.

References
1. Allahghadri T, Rasooli I, Owlia P, et al. Antimicrobial property, antioxidant
capacity, and cytotoxicity of essential oil from cumin produced in Iran. J Food
Sci. 2010;75:H54–61.
2. Aruna K, Rukkumani R, Varma PS, Menon VP. Therapeutic role of
Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced
toxicity. Phytother Res. 2005;19:416–21.
3. Aruna K, Sivaramakrishnan VM. Anticarcinogenic effects of some Indian
plant products. Food Chem Toxicol. 1992;30:953–6.
4. Awan UA, Andleeb S, Kiyani A, et al. Antibacterial screening of traditional
herbal plants and standard antibiotics against some human bacterial
pathogens. Pak J Pharm Sci. 2013;26:1109–16.
5. Bettaieb I, Bourgou S, Sriti J, et al. Essential oils and fatty acids
composition of Tunisian and Indian cumin (Cuminum cyminum L.) seeds: a
comparative study. J Sci Food Agric. 2011;91:2100–7.
6. Birjees Bukhari S, Iqbal S, Bhanger MI. Antioxidant potential of
commercially available cumin (Cuminum cyminum Linn.) in Pakistan.
Int J Food Sci Nutr. 2008;1–8.
768 Cuminum cyminum L.

7. Deshmukh SK, Indra, Chile SK. Sensitivity of some dermatophytes to

essential oils of Aracus hypogea, Chenopodium album and Cuminum
cyminum. Indian Drugs. 1982;19:404–7.
8. Dhandapani S, Subramanian VR, Rajagopal S, Namasivayam N. Hypolipi-
demic effect of Cuminum cyminum L. on alloxan-induced diabetic rats.
Pharmacol Res. 2002;46:251–5.
9. El-Ghorab AH, Nauman M, Anjum FM, et al. A comparative study on
chemical composition and antioxidant activity of ginger (Zingiber officinale)
and cumin (Cuminum cyminum). J Agric Food Chem. 2010;58:8231–7.
10. Gagandeep, Dhanalakshmi S, Méndiz E, et al. Chemopreventive effects of
Cuminum cyminum in chemically induced forestomach and uterine cervix
tumors in murine model systems. Nutr Cancer. 47:171–80.
11. Gupta RS, Saxena P, Gupta R, Kachhawa JB. Evaluation of reversible
contraceptive activities of Cuminum cyminum in male albino rats. Contra-
ception. 2011;84:98–107.
12. Haghparast A, Shams J, Khatibi A, et al. Effects of the fruit essential oil of
Cuminum cyminum Linn. (Apiaceae) on acquisition and expression of
morphine tolerance and dependence in mice. Neurosci Lett. 2008;440:
134–9.
13. Hajlaoui H, Mighri H, Noumi E, et al. Chemical composition and biological
activities of Tunisian Cuminum cyminum L. essential oil: a high effective-
ness against Vibrio spp. strains. Food Chem Toxicol. 2010;48:2186–92.
14. Haroun EM, Mahmoud OM, Adam SE. Effect of feeding Cuminum
cyminum fruits, Thymus vulgaris leaves or their mixture to rats. Vet Hum
Toxicol. 2002;44:67–9.
15. Iacobellis NS, Lo Cantore P, Capasso F, Senatore F. Antibacterial activity
of Cuminum cyminum L. and Carum carvi L. essential oils. J Agric Food
Chem. 2005;53:57–61.
16. Irkin R, Korukluoglu M. Growth inhibition of pathogenic bacteria and
some yeasts by selected essential oils and survival of L. monocytogenes and
C. albicans in apple-carrot juice. Foodborne Pathog Dis. 2009;6:387–94.
17. Ishikawa T, Takayanagi T, Kitajima J. Water-soluble constituents of cumin:
monoterpenoid glucosides. Chem Pharm Bull (Tokyo). 2002;50:1471–8.
18. Jagtap AG, Patil PB. Antihyperglycemic activity and inhibition of advanced
glycation end product formation by Cuminum cyminum in streptozotocin
induced diabetic rats. Food Chem Toxicol. 2010;48:2030–6.
19. Johri RK. Cuminum cyminum and Carum carvi: an update. Pharmacogn
Rev. 2011;5:63–72.
20. Kalaivani P, Saranya RB, Ramakrishnan G, et al. Cuminum cyminum, a
dietary spice, attenuates hypertension via endothelial nitric oxide synthase
and NO pathway in renovascular hypertensive rats. Clin Exp Hypertens.
2013;35:534–42.
Cuminum cyminum L. 769

21. Kedia A, Prakash B, Mishra PK, Dubey NK. Antifungal and antiaflatox-
igenic properties of Cuminum cyminum (L.) seed essential oil and its
efficacy as a preservative in stored commodities. Int J Food Microbiol.
2014;168–169:1–7.
22. Kermani M, Azizi P, Haghparast A. The role of nitric oxide in the effects of
cumin (Cuminum cyminum L.) fruit essential oil on the acquisition of
morphine-induced conditioned place preference in adult male mice. Chin J
Integr Med. 2012 Jan 12 (Epub ahead of print).
23. Keskin D, Toroglu S. Studies on antimicrobial activities of solvent extracts
of different spices. J Environ Biol. 2011;32:251–6.
24. Khafagy SM, Sorg TM, Abdel-Salam NA, Gaber O. Isolation of two
flavone glycosides from the fruits of Cuminum cyminum L. grown in Egypt.
Pharmazie. 1978;33:296–7.
25. Khatibi A, Haghparast A, Shams J, et al. Effects of the fruit essential oil of
Cuminum cyminum L. on the acquisition and expression of morphine-induced
conditioned place preference in mice. Neurosci Lett. 2008;448:94–8.
26. Khosravi AR, Shokri H, Minooeianhaghighi M. Inhibition of aflatoxin
production and growth of Aspergillus parasiticus by Cuminum cyminum,
Ziziphora clinopodioides, and Nigella sativa essential oils. Foodborne Pathog
Dis. 2011;8:1275–80.
27. Kode A, Rajagopalan R, Penumathsa SV, Menon VP. Effect of ethanol and
thermally oxidized sunflower oil ingestion on phospholipid fatty acid compo-
sition of rat liver: protective role of Cuminum cyminum L. Ann Nutr Metab.
2005;49:300–3.
28. Koppula S, Choi DK. Cuminum cyminum extract attenuates scopolamine-
induced memory loss and stress-induced urinary biochemical changes in
rats: a noninvasive biochemical approach. Pharm Biol. 2011;49:702–8.
29. Lee HS. Cuminaldehyde: Aldose reductase and alpha-glucosidase inhibitor
derived from Cuminum cyminum L. seeds. J Agric Food Chem. 2005;53:
2446–50.
30. Makchuchit S, Itharat A, Tewtrakul S. Antioxidant and nitric oxide
inhibition activities of Thai medicinal plants. J Med Assoc Thai. 2010;93
Suppl 7:S227–35.
31. Mandal S, DebMandal M, Saha K, Pal NK. In vitro antibacterial activity of
three Indian spices against methicillin-resistant Staphylococcus aureus.
Oman Med J. 2011;26:319–23.
32. Mohammadpour H, Moghimipour E, Rasooli I, et al. Chemical composition
and antifungal activity of Cuminum cyminum L. essential oil from Alborz
Mountain against Aspergillus species. Jundishapur J Nat Pharm Prod.
2012;7:50–5.
33. Naeini A, Naderi NJ, Shokri H. Analysis and in vitro anti-Candida
antifungal activity of Cuminum cyminum and Salvadora persica herbs
extracts against pathogenic Candida strains. J Mycol Med. 2014;24:13–8.
770 Cuminum cyminum L.

34. Nalini N, Manju V, Menon VP. Effect of spices on lipid metabolism in

1,2-dimethylhydrazine-induced rat colon carcinogenesis. J Med Food.
2006;9:237–45.
35. Nalini N, Sabitha K, Viswanathan P, Menon VP. Influence of spices on the
bacterial (enzyme) activity in experimental colon cancer. J Ethnopharmacol.
1998;62:15–24.
36. Naveed R, Hussain I, Tawab A, et al. Antimicrobial activity of the bioactive
components of essential oils from Pakistani spices against Salmonella and
other multidrug resistant bacteria. BMC Complement Altern Med. 2013;13:
265.
37. Nickavar B, Abolhasani FA. Screening of antioxidant properties of seven
Umbelliferae fruits from Iran. Pak J Pharm Sci. 2009;22:30–5.
38. Nostro A, Cellini L, Di Bartolomeo S, et al. Antibacterial effect of plant
extracts against Helicobacter pylori. Phytother Res. 2005;19:198–202.
39. Pai MB, Prashant GM, Murlikrishna KS, et al. Antifungal efficacy of Punica
granatum, Acacia nilotica, Cuminum cyminum and Foeniculum vulgare on
Candida albicans: an in vitro study. Indian J Dent Res. 2010;21:334–6.
40. Pajohi MR, Tajik H, Farshid AA, Hadian M. Synergistic antibacterial
activity of the essential oil of Cuminum cyminum L. seed and nisin in a food
model. J Appl Microbiol. 2011;110:943–51.
41. Patil SB, Takalikar SS, Joglekar MM, et al. Insulinotropic and b-cell
protective action of cuminaldehyde, cuminol and an inhibitor isolated from
Cuminum cyminum in streptozotocin-induced diabetic rats. Br J Nutr. 2013;
1–10.
42. Platel K, Srinivasan K. Influence of dietary spices and their active principles
on pancreatic digestive enzymes in albino rats. Nahrung. 2000;44:42–6.
43. Platel K, Srinivasan K. Influence of dietary spices or their active principles
on digestive enzymes of small intestinal mucosa in rats. Int J Food Sci Nutr.
1996;47:55–9.
44. Prakash AO. Potentialities of some indigenous plants for antifertility
activity. Int J Crude Drug Res. 1986;24:19–24.
45. Rebey IB, Kefi S, Bourgou S, et al. Ripening stage and extraction method
effects on physical properties, polyphenol composition and antioxidant
activities of cumin (Cuminum cyminum L.) seeds. Plant Foods Hum Nutr.
2014;69:358–64.
46. Revati S, Bipin C, Chitra PB, Minakshi B. In vitro antibacterial activity of
seven Indian spices against high level gentamicin resistant strains of
enterococci. Arch Med Sci. 2015;11:863–8.
47. Romagnoli C, Andreotti E, Maietti S, et al. Antifungal activity of essential
oil from fruits of Indian Cuminum cyminum. Pharm Biol. 2010;48:834–8.
48. Roman-Ramos R, Flores-Saenz JL, Alarcon-Aguilar FJ. Antihyperglycemic
effect of some edible plants. J Ethnopharmacol. 1995;48:25–32.
49. Sahoo HB, Sahoo SK, Sarangi SP, Sagar R, Kori ML. Antidiarrhoeal
investigation from aqueous extract of Cuminum cyminum Linn. seed in
albino rats. Pharmacognosy Res. 2014;6:204–9.
Cuminum cyminum L. 771

50. Sakhaee E, Emadi L, Azari O, et al. Effects of Cuminum cyminum L.

essential oil on some epididymal sperm parameters and histopathology of
testes following experimentally induced copper poisoning in mice.
Andrologia. 2016;48:542–7.
51. Samani KG, Farrokhi E. Effects of cumin extract on oxLDL, paraoxanase 1
activity, FBS, total cholesterol, triglycerides, HDL-C, LDL-C, Apo A1, and
Apo B in the patients with hypercholesterolemia. Int J Health Sci. 2014;8:39–43.
52. Sambaiah K, Srinivasan K. Effect of cumin, cinnamon, ginger, mustard and
tamarind in induced hypercholesterolemic rats. Nahrung. 1991;35:47–51.
53. Satyanarayana S, Sushruta K, Sarma GS, et al. Antioxidant activity of the
aqueous extracts of spicy food additives—evaluation and comparison with
ascorbic acid in in vitro systems. J Herb Pharmacother. 2004;4:1–10.
54. Saxena P, Gupta R, Gupta RS. Contraceptive studies of isolated fractions of
Cuminum cyminum in male albino rats. Nat Prod Res. 2015;29:2328–31.
55. Sharifzadeh A, Jebeli Javan A, Shokri H, Abbaszadeh S, Keykhosravy K.
Evaluation of antioxidant and antifungal properties of the traditional plants
against foodborne fungal pathogens. J Mycol Med. 2016;26:e11–7.
56. Shirke SS, Jagtap AG. Effects of methanolic extract of Cuminum cyminum
on total serum cholesterol in ovariectomized rats. Indian J Pharmacol.
2009;41:92–3.
57. Singh G, Kapoor IP, Pandey SK, et al. Studies on essential oils: part 10;
antibacterial activity of volatile oils of some spices. Phytother Res.
2002;16:680–2.
58. Srivastava KC. Extracts from two frequently consumed spices—cumin
(Cuminum cyminum) and turmeric (Curcuma longa)—inhibit platelet
aggregation and alter eicosanoid biosynthesis in human blood platelets.
Prostaglandins Leukot Essent Fatty Acids. 1989;37:57–64.
59. Sultana S, Ripa FA, Hamid K. Comparative antioxidant activity study of
some commonly used spices in Bangladesh. Pak J Biol Sci. 2010;13:340–3.
60. Taghizadeh M, Memarzadeh MR, Asemi Z, Esmaillzadeh A. Effect of the
Cumin cyminum L. intake on weight loss, metabolic profiles and biomarkers
of oxidative stress in overweight subjects: a randomized double-blind
placebo-controlled clinical trial. Ann Nutr Metab. 2015;66:117–24.
61. Takayanagi T, Ishikawa T, Kitajima J. Sesquiterpene lactone glucosides and
alkyl glycosides from the fruit of cumin. Phytochemistry. 2003;63:479–84.
62. Tomy MJ, Dileep KV, Prasanth S, et al. Cuminaldehyde as a lipoxygenase
inhibitor: in vitro and in silico validation. Appl Biochem Biotechnol. 2014;
174:388–97.
63. Topal U, Sasaki M, Goto M, Otles S. Chemical compositions and antioxi-
dant properties of essential oils from nine species of Turkish plants obtained
by supercritical carbon dioxide extraction and steam distillation. Int J Food
Sci Nutr. 2007;59:619–34.
64. Vador N, Jagtap AG, Damle A. Vulnerability of gastric mucosa in diabetic
rats, its pathogenesis and amelioration by Cuminum cyminum. Indian J Pharm
Sci. 2012;74:387–96.
772 Cuminum cyminum L.

65. Vasudevan K, Vembar S, Veeraraghavan K, Haranath PS. Influence of

intragastric perfusion of aqueous spice extracts on acid secretion in
anesthetized albino rats. Indian J Gastroenterol. 2000;19:53–6.
66. Wanner J, Bail S, Jirovetz L, et al. Chemical composition and antimicrobial
activity of cumin oil (Cuminum cyminum, Apiaceae). Nat Prod Commun.
2010;5:1355–8.
67. Yan JH, Tang KW, Zhong M, Deng NH. Determination of chemical
components of volatile oil from Cuminum cyminum L. by gas chromatography-
mass spectrometry. Se Pu. 2002;20:569–72 (Chinese).
68. Zare R, Heshmati F, Fallahzadeh H, Nadjarzadeh A. Effect of cumin powder
on body composition and lipid profile in overweight and obese women.
Complement Ther Clin Pract. 2014;20:297–301.
Curcuma aromatica Salisb.
(Zingiberaceae)

(Syn.: C. wenyujin Y.H. Chen & C. Ling)

Abstract
The plant is grown and cultivated in India, Bhutan, Myanmar, Nepal and Sri Lanka.
Its medicinal properties are very similar to turmeric, but its flavor being bitter,
pungent, and camphoraceous is not so agreeable. It is the Vana-haridra of Sanskrit
writers, and considered in Ayurveda as stomachic, stimulant, carminative and
tonic, and is topically applied in skin diseases and to promote eruptions in
exanthematous fevers. It is seldom used alone, but is generally combined with
other astringents when applied to bruises. In southern India, it is a valuable remedy
for snakebite, administered in conjunction with golden orpiment (a mineral),
costus and ajwain (carom) seeds. In Unani medicine, it is externally applied to the
forehead as a hot paste to relieve nerve headache; the paste is also applied to itching
and small pox eruptions. Dried rhizome is used as an aromatic adjunct with other
drugs for the treatment of skin diseases and impurities of blood. In Chinese
medicine, it was first recorded in Tang Pen Tsao in 659 A.D. and is used for pain in
the chest and abdomen, gallstones, jaundice, hemoptysis, epistaxis, hematuria,
epilepsy, menstrual cramps, and fever with sweating. Curcuminoids and bisabolane-
type sesquiterpenes are the main constituents of Curcuma species. Curcumin is the
major yellow pigment, and the most important constituent among natural
curcuminoids; curdione is the main ingredient of essential oils. Aqueous rhizome
extract significantly protected gastric mucosa of rats against ethanol-induced
gastritis. Methanol rhizome extract showed no significant inhibitory effects on
adjuvant-induced paw swelling, but the volatile oil is reported to possess
anti-inflammatory activity. Hepatic arterial infusion with embolized Curcuma aro-
matic oil in Chinese patients with primary liver cancer showed similar favorable but
superior effect, with longer survival time and milder myelosuppression, as
transcatheter artery chemoembolization.

© Springer Nature Switzerland AG 2020 773

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_82
774 Curcuma aromatica Salisb.

Keywords


Aranyaharidra Ganghoang Haruukon

Jangli haldi
Kurkum
Round



zedoary Wild turmeric Yu-chin

Vernaculars: Urd.: Jangli haldi; Hin.: Ban-haridra, Jangli haldi; San.: Aranya-
haridra, Shati, Vana-haridra; Ben.: Ban-halad, Ban-halod, Shati; Mal.: Anakuva,
Dantmanjal, Kasthurimanjal, Kattumanjal, Kattumanna, Pullakizhangu; Mar.:
Ambe-haldi, Ran-halad, Ran-halada, Vedi-halad; Tam.: Kasturi arishina, Kasturi-
manjal, Kattumanjal; Tel.: Adavipasupu, Kasturi-pasupa, Kattu-mannal; Ara.:
Kurkum; Bur.: Kiyasanoin; Chi.: 姜黄, 温郁金, 郁金, Yu-chin, Yu jin, Wenezhu;
Eng.: Cochin turmeric, Round zedoary, Wild turmeric, Yellow Zedoary; Fre.:
Safran des Indes; Kor.: Ganghoang; Jap.: Haruukon; Nep.: Van dhaale, Van
haledo; Tha.: Wan nang kham; Vie.: Nghê rùng, Nghê trang.
Description: The plant is 1 m in height, grown and cultivated in India (Bengal),
Bhutan, Myanmar, Nepal and Sri Lanka. Leaves, when young have a central purple
stain, which almost disappears when they attain their full size; flowers appear in
May or June, with the first leaves just before the rainy season (in India). Central
rhizomes are oblong or conical, often more than 5 cm in diameter, external surface
dark-grey, marked with circular rings and giving off many thick rootlets; at the end
of some of them are orange-yellow tubers about the size and shape of an almond in
its shell; lateral rhizomes about as thick as a finger, with a few fleshy rootlets.
Internally, both central and lateral rhizomes are of a deep orange color like turmeric;
the odor of the root is strongly camphoraceous (Figs. 1, 2 and 3).XL
Actions and Uses: Its medicinal properties are very similar to turmeric, but its flavor
being bitter, pungent, and camphoraceous is not so agreeable. It is the Vana-haridra of
Sanskrit writers, and considered in Ayurveda as stomachic, stimulant, carminative and
tonic, and is topically applied in skin diseases and to promote eruptions in exanthe-
matous fevers. It is seldom used alone, but is generally combined with other astringents
when applied to bruises.XL,LXXXI In southern India, it is a valuable remedy for sna-
kebite, administered in conjunction with golden orpiment (a mineral), costus and
ajwain (carom) seeds.XL In Unani medicine, it (temperament, hot 3° and dry 3°) is
externally applied to the forehead as a hot paste to relieve nerve headache; the paste is
also applied to itching and small pox eruptions.L Dried rhizome is used as an aromatic
adjunct with other drugs for the treatment of skin diseases and impurities of blood.CV It
is known as Yu-Chin in Chinese medicine, and is described as the dried, cylindrical root
of C. aromatica Salisb., or C. longa L. or other Curcuma sp. of Zingiberaceae family. It
was first recorded in Tang Pen Tsao in 659 A.D. and is used for pain in the chest and
abdomen, gallstones, jaundice, hemoptysis, epistaxis, hematuria, epilepsy, menstrual
cramps, and fever with sweating. However, the same author also mentioned its name as
Chiang-huang, that dispels effused blood, and is analgesic and emmenagogue.LXVI
Curcuma aromatica Salisb. 775

Fig. 1 Curcuma aromatica, Wildly-growing Plant, Nandhupuniyam, WikimediaCommons;

ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Curcuma_
aromatica_plant.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

Fig. 2 Curcuma aromatica, Plant, Shijan Kaakkara, WikimediaCommons; ShareAlike 4.0 Inter-
national CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Curcuma_Aromatica_-_%E0%
B4%95%E0%B4%B8%E0%B5%8D%E0%B4%A4%E0%B5%81%E0%B4%B0%E0%B4%BF_
%E0%B4%AE%E0%B4%9E%E0%B5%8D%E0%B4%9E%E0%B5%BE.jpg; https://creativecom
mons.org/licenses/by-sa/4.0/deed.en
776 Curcuma aromatica Salisb.

Fig. 3 Curcuma aromatica, Flower, Goldentakin, WikimediaCommons; 2.0 Generic CC BY 2.0,

https://commons.wikimedia.org/wiki/File:Curcuma_aromatica.jpg; https://creativecommons.org/
licenses/by/2.0/deed.en

Phytoconstituents: Curcuminoids and bisabolane-type sesquiterpenes are the

main constituents of Curcuma species. Curcumin is the major yellow pigment, and
the most important constituent among natural curcuminoids [10]; curdione is the
main ingredient of essential oils [7]. Curdione, neocurdione, curcumol, tetram-
ethylpyrazine and (R)-(+)-1,2-hexadecanediol have been isolated from Chinese
C. aromatica [9]. Chemical compositions of EOs from rhizomes cultivated in Japan
and India are extremely different. Major constituents in Japanese oil are curdione,
germacrone, 1,8-cineole, (45,5S)-germacrone-4,5-epoxide, b-elemene, and linalool;
whereas the Indian oil contains b-curcumene, ar-curcumene, xanthorrhizol, ger-
macrone, camphor, and curzerenone [17]. Oil obtained from Chinese rhizomes
contained eucalyptol (53.86%), neocurdione (9.89%), linalool (4.24%), camphor
(3.14%), a-terpineol (2.94%) and germacrone (2.89%) as the main components,
comprising 93.11% out of a total of 50 constituents [3]. However, another report
listed curdione as the major constituent, which was relatively constant in samples of
rhizomes from different regions of China, and at different stages of growth [6].
Chemical composition of the hydrodistilled EO of leaves from Korea reported the
presence of twenty-three compounds representing 94.29% of the total oil [1].
Ethanol (70%) extract contained higher content of total phenols than the 30%, 50%
and 90% extracts [19].
Curcuma aromatica Salisb. 777

Pharmacology: Aqueous rhizome extract significantly protected gastric mucosa of

rats against ethanol-induced gastritis [12]. Hydroalcohol extract improved antioxidant
status, reduced LPO and exhibited remarkable cardioprotective effects against
isoproterenol-induced acute MI in rats [19], and ethanol rhizome extract exhibited
significant antitussive effect on sulfur dioxide-induced cough in mice [20]. Methanol
rhizome extract showed no significant inhibitory effects on adjuvant-induced paw
swelling [25], but the volatile oil is reported to possess anti-inflammatory activity [18].
Aqueous-methanol extract, though, protected neuronal cells from b-amyloid protein
toxicity [15]. The oil exhibits significant protection on renal interstitial fibrosis in rats,
induced by unilateral ureteral obstruction [29]; and the leaf extract also protected
against arsenic trioxide-induced nephrotoxicity in rats [24]. Curcumin is an effective
antiplatelet compound that inhibits AA-, collagen- and ADP-induced platelet aggre-
gation [11]. Essential oil and methanol extract of leaves and aqueous extract of rhi-
zomes possess significant antioxidant activity [1, 2, 14]. Aqueous extract showed
antiproliferative effect for colon carcinoma, through both extrinsic and intrinsic
apoptosis, and induced G2/M phase arrest via downregulation of cyclin B1 and CDK1
and without the participation of p53 [8]. The oil inhibited growth of hepatoma in mice
[28], and microsphere-entrapped oil infused via hepatic artery against transplanted
hepatoma in rats [27].
Alcohol rhizomes extract showed moderate activity against human A. lumbri-
coides [22]. Hexane extract was significantly active against several standard and
clinical isolates of S. aureus, S. epidermidis, E. faecalis, Streptococcus sp., and
MRSA, but no activity against Gram-negative strains, E. coli, Pseudomonas sp. and
Klebshiella sp [23]. It also showed strong estrogenic activity [13, 16], and afforded
significant protection as mosquito repellent [5, 21]. Curcuminoids from the rhi-
zomes inhibited IgE-antigen complex-induced passive cutaneous anaphylaxis
reaction, and inhibited degranulation, protein expression of TNF-a and IL-4, and
transcription factor NF-kappaB activation in IgE-antigen complex-induced
RBL-2H3 cells [26].
Clinical Studies: Hepatic arterial infusion with embolized Curcuma aromatic oil in
32 Chinese patients with primary liver cancer showed similar favorable but superior
effect with longer survival time and milder myelosuppression, as transcatheter
artery chemoembolization [4].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interactions: Curdione is the major
component responsible for CYP3A4 inhibitory activity and a drug-drug interaction
potential [7].
778 Curcuma aromatica Salisb.

Commentary: It is generally confined to external uses in traditional Indian

medicines, but the Chinese study in patients with a primary hepatic cancer, and a
favorable clinical response opens new avenues for future research. However, the
variations in its chemical constituents should be kept in mind when evaluating a
pharmacological or clinical effect.

References
1. Al-Reza SM, Rahman A, Sattar MA, et al. Essential oil composition and
antioxidant activities of Curcuma aromatica Salisb. Food Chem Toxicol.
2010;48:1757–60.
2. Baliga MS, Jagetia GC, Rao SK, Babu K. Evaluation of nitric oxide
scavenging activity of certain spices in vitro: a preliminary study. Nahrung.
2003;47:261–4.
3. Chai L, Liu BM, Lin X, Li QX, Lai MX. Analysis of compositions of the
essential oil from Curcuma aromatica by gas chromatography-mass
spectrometry. Zhong Yao Cai. 2012;35:1102–4 (Chinese).
4. Cheng JH, Chang G, Wu WY. A controlled clinical study between hepatic
arterial infusion with embolized curcuma aromatic oil and chemical drugs in
treating primary liver cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi.
2001;21:165–7 (Chinese).
5. Das NG, Nath DR, Baruah I, et al. Field evaluation of herbal mosquito
repellents. J Commun Dis. 1999;31:241–5.
6. Feng J, Xu MM, Huang XL, et al. GC-MS analysis of essential oil from
Curcuma aromatica rhizome of different growth periods. Zhong Yao Cai.
2013;36:1926–9 (Chinese).
7. Hou XL, Hayashi-Nakamura E, Takatani-Nakase T, et al. Curdione plays an
important role in the inhibitory effect of Curcuma aromatica on CYP3A4 in
Caco-2 cells. Evid Based Complement Alternat Med. 2011;2011:913898.
8. Hu B, Shen KP, An HM, Wu Y, Du Q. Aqueous extract of Curcuma aromatica
induces apoptosis and G2/M arrest in human colon carcinoma LS-174-T cells
independent of p53. Cancer Biother Radiopharm. 2011;26:97–104.
9. Huang KX, Tao ZM, Zhang AJ, et al. Studies on chemical constituents of
Curcuma aromatica Salisb. Zhongguo Zhong Yao Za Zhi. 2000;25:163–5
(Chinese).
10. Itokawa H, Shi Q, Akiyama T, et al. Recent advances in the investigation of
curcuminoids. Chin Med. 2008;3:11.
11. Jantan I, Raweh SM, Sirat HM, et al. Inhibitory effect of compounds from
Zingiberaceae species on human platelet aggregation. Phytomedicine.
2008;15:306–9.
12. Jeon WY, Lee MY, Shin IS, Jin SE, Ha H. Curcuma aromatica water
extract attenuates ethanol-induced gastritis via enhancement of antioxidant
status. Evid Based Complement Alternat Med. 2015;2015:582496.
Curcuma aromatica Salisb. 779

13. Kang SC, Lee CM, Choi H, et al. Evaluation of oriental medicinal herbs for
estrogenic and antiproliferative activities. Phytother Res. 2006;20:1017–9.
14. Kim BJ, Kim JH, Kim HP, Heo MY. Biological screening of 100 plant
extracts for cosmetic use (II): antioxidative activity and free radical
scavenging activity. Int J Cosmet Sci. 1997;19:299–307.
15. Kim DS, Kim JY, Han YS. Alzheimer’s disease drug discovery from herbs:
neuroprotectivity from beta-amyloid (1-42) insult. J Altern Complement
Med. 2007;13:333–40.
16. Kim IG, Kang SC, Kim KC, et al. Screening of estrogenic and antiestrogenic
activities from medicinal plants. Environ Toxicol Pharmacol. 2008;25:75–82.
17. Kojima H, Yanai T, Toyota A. Essential oil constituents from Japanese and
Indian Curcuma aromatica rhizomes. Planta Med. 1998;64:380–1.
18. Li CZ. Anti-inflammatory effect of the volatile oil from Curcuma aromatica.
Chung Yao Tung Pao. 1985;10:38–40 (Chinese).
19. Li Y, Feng J, Mo Y, Liu H, Yang B. Concordance between cardioprotective
effect on isoproterenol-induced acute myocardial ischemia and phenolic
content of different extracts of Curcuma aromatica. Pharm Biol. 2016;54:
3226–31.
20. Marina GD, Kekuda TR, Sudarshan SJ. Antitussive activity of ethanolic
extract of Curcuma aromatica rhizomes on sulfur dioxide induced cough in
mice. Anc Sci Life. 2008;27:36–40.
21. Pitasawat B, Choochote W, Tuetun B, et al. Repellency of aromatic turmeric
Curcuma aromatica under laboratory and field conditions. J Vector Ecol.
2003;28:234–40.
22. Raj RK. Screening of indigenous plants for anthelmintic action against
human Ascaris lumbricoides: Part–II. Indian J Physiol Pharmacol. 1975;19.
23. Revathi S, Malathy NS. Antibacterial activity of rhizome of Curcuma
aromatica and partial purification of active compounds. Indian J Pharm Sci.
2013;75:732–5.
24. Saxena PN, Anand S, Saxena N, Bajaj P. Effect of arsenic trioxide on renal
functions and its modulation by Curcuma aromatica leaf extract in albino
rat. J Environ Biol. 2009;30:527–31.
25. Tohda C, Nakayama N, Hatanaka F, Komatsu K. Comparison of anti-
inflammatory activities of six Curcuma rhizomes: a possible curcuminoid-
independent pathway mediated by Curcuma phaeocaulis extract. Evid
Based Complement Alternat Med. 2006;3:255–60.
26. Trinh HT, Bae EA, Lee JJ, Kim DH. Inhibitory effects of curcuminoids on
passive cutaneous anaphylaxis reaction and scratching behavior in mice.
Arch Pharm Res. 2009;32:1783–7.
27. Wu W, Deng R, Ou Y. Therapeutic efficacy of microsphere-entrapped
Curcuma aromatica oil infused via hepatic artery against transplanted
hepatoma in rats. Zhonghua Gan Zang Bing Za Zhi. 2000;8:24–6 (Chinese).
780 Curcuma aromatica Salisb.

28. Wu WY, Xu Q, Shi LC, Zhang WB. Inhibitory effects of Curcuma

aromatica oil on proliferation of hepatoma in mice. World J Gastroenterol.
2000;6:216–9.
29. Zhao L, Zhang H, Yang Y, et al. Serum metabonomic analysis of protective
effects of Curcuma aromatica oil on renal fibrosis rats. PLoS ONE. 2014;9:
e108678.
Curcuma longa L.
(Zingiberaceae)

(Syns.: C. domestica Valeton; Amomum curcuma Jacq.)

Abstract
An aromatic, herbaceous perennial herb, widely cultivated in southeast Asian
countries like India, Pakistan, Bangladesh, Sri Lanka, Myanmar, Indonesia,
Madagascar, Laos, Vietnam, Cambodia, and Taiwan. In Ayurveda, the rhizome is
considered hot, bitter, pungent, astringent and drying; it corroborates the humours,
prevents skin diseases, and is a useful application on swellings and boils.
A decoction is used as a cooling lotion in conjunctivitis, and boiled in milk and
sweetened with sugar is a popular remedy for cold, and is also used in jaundice and
other liver ailments. Other uses in Ayurveda include visavikãra, kustha, tvagroga,
prameha, pãndu, ŝitapitta, and pinasa. In Unani medicine, the rhizome is regarded
expectorant, vasodilator, vulnerary, anthelmintic, analgesic, anti-inflammatory,
blood purifier, detergent and to improve complexion. Its most common use is as a
condiment and a household remedy for intermittent fevers, flatulence, dyspepsia,
and to tone-up stomach, and externally for sprains, strains, bruises and wounds. It is
approved for use in GI disorders in Europe since Nov. 2005 by the HMPC of the
European Medicines Agency. In China, it is known as Jianghuang and is often
used interchangeably with C. aromatica to treat distension of the chest and
abdomen, obstruction or lump in the abdomen, frozen shoulder, amenorrhea due to
blood stasis, postpartum abdominal pain due to stasis, wounds and injuries,
carbuncle and jaundice. Major alkaloids are curcuminoids, that include curcumin
(also described as curcumin I), demethoxycurcumin (curcumin II) and bis-
demethoxycurcumin (curcumin III). Turmeric powder suspension significantly
alleviated metabolic syndrome-associated hyperglycemia and dyslipidemia, and
elevation of atherogenic indices, by increasing insulin level, enhancing antioxidant
defense system and decreasing LPO of diabetic rats. Orally ethanol and ether
extracts, curcumin and the volatile oil lowered serum TC, TGs and b-lipoprotein
levels in hyperlipidemic rats, and ethanol extract elevated HDL-C/TC ratio in
hyperlipidemic rats. A single dose of 6 g turmeric increased postprandial serum
insulin, without affecting plasma glucose levels in healthy Swedish volunteers, and

© Springer Nature Switzerland AG 2020 781

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_83
782 Curcuma longa L.

daily intake of turmeric for sixty-days decreased peroxidation of both HDL and
LDL, in healthy volunteers with high baseline values.

Keywords



Açafrão da índia Geelwortel Gelbwurz Gurkemeje

Haldi
Haridrã




Maustekurkuma Turmeric Uqdah-safra Yu-chin

Vernaculars: Urd.: Haldi; Hin.: Halada, Haldar, Haldi, Halja; San.: Gauri,
Haridrã, Kãñcani, Krmighnã, Niŝã, Nisha, Rajani, Yositpriyã; Ben.: Halad, Halada,
Halud, Pitras; Mal.: Manjal, Marinalu, Monjella-kua; Mar.: Halad, Halada, Halede,
Halkund, Kunhet; Tam.: Manjal, Mancal; Tel.: Haridra, Pampi, Pasupu; Ara.:
Hard, Kurkum, Uqdah-safra, Uruk-es-sabaghin, Uruq-es-sufr, Zirsud; Bur.:
Hsanwen, Sanwin; Chi.: 姜黄, Jianghuang, Yu-chin; Cze.: Kurkuma, Žlutý kořen,
Žlutý zázvor; Dan.: Gurkemeje; Dut.: Geelwortel, Indaansche saffraan, Kurkuma;
Eng.: Indian Saffron, Turmeric; Fin.: Maustekurkuma; Fre.: Curcuma, Safran des
Indes; Ger.: Gelbwurz, Gelbwurzel, Gilber ingwer, Indischer safran, Kurkuma;
Ind.: Kunir, Kunyit, Kunyit basah; Ita.: Croco indiano, Curcuma di levante,
Curcuma lunga, Radice gialla, Safferano dell Indie; Jap.: Taamerikku, Ukon; Kor.:
Kang-hwang; Lao.: Khi min khun; Maly.: Kooneit, Kunyit betul; Nor.: Gurke-
meie; Per.: Daraserda, Kurkum, Zard chubah; Por.: Açafrão da Índia, Curcuma;
Rus.: Kurkuma dlinnaia; Sin.: Kaha; Spa.: Azafrán arabe, Cúrcuma, Turmérico;
Swe.: Gurkmeja, Guskmeja; Tag.: Dilau; Tha.: Kha min chan, Khamin luang, Kha
mi: Tur.: Hint safranı, Safran kökü, Zerdali, Zerdeçal; Vie.: Bột nghệ, Củ nghệ,
Khương hoàng, Nghệ, Uất kim.
Description: An aromatic, herbaceous perennial herb (0.6–1 m tall) is widely
cultivated in southeast Asian countries like India, Pakistan, Bangladesh, Sri Lanka,
Myanmar, Indonesia, Madagascar, Laos, Vietnam, Cambodia, and Taiwan. Leaves
oblong or elliptical, shortly acuminate, base narrow, both faces glabrous, 45 cm
long and 18 cm wide. Inflorescence cylindrical or lengthily ovoid, 12–15 cm long
and 4–6 cm wide; flowers pale-yellow; calyx tubular; corolla 2–3 times longer,
tubular, lobes 10 mm long.LXXIX Rhizome consists of a central ovoid portion and
several lateral elongated portions, all of a deep-orange color; from these proceed a
number of radicles, at the ends of some of which colorless oval tubers are produced.
Central rhizome vary in size and shape, may be pyriform, ovoid or almost round,
and are generally cut up into pieces. Fresh rhizomes are boiled and dried, which are
then marketed for use as a spice (Figs. 1 and 2).XL
Actions and Uses: In Ayurveda, the rhizome is considered hot, bitter, pungent,
astringent and drying; it corroborates the humours, prevents skin diseases, and is a
useful application on swellings and boils. A decoction is used as a cooling lotion in
conjunctivitis, and boiled in milk and sweetened with sugar is a popular remedy for
cold, and is also used in jaundice and other liver ailments.XL,LXXXI Other uses in
Ayurveda include visavikãra, kustha, tvagroga, prameha, pãndu, ŝitapitta, and
pinasa.CXXVII In Unani medicine, the rhizome is assigned a temperament of hot 3°
Curcuma longa L. 783

Fig. 1 Curcuma longa, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons; https://commons.wikimedia.org/wiki/File:Curcuma_longa_-_K%C3%B6hler%E2%
80%93s_Medizinal-Pflanzen-199.jpg

Fig. 2 Curcuma longa, Rhizomes, Prof. Akbar, Original

784 Curcuma longa L.

and dry 3°, while Galen considered it hot 4° and dry 4°,LXIX and is regarded
expectorant, vasodilator, vulnerary, anthelmintic, analgesic, anti-inflammatory,
blood purifier, detergent and to improve complexion.LXXVII Its most common use is
as a condiment and a household remedy for intermittent fevers, flatulence, dys-
pepsia, and to tone-up stomach, and externally for sprains, strains, bruises and
wounds.CV It is approved for use in GI disorders in Europe since Nov. 2005 by the
HMPC of the European Medicines Agency. In China, it is known as Jianghuang
and is often used interchangeably with C. aromatica. It is described having a
pungent and bitter taste, a ‘warm’ property, and as blood- and vital-energy-
stimulant, analgesic and emmenagogue, and mainly used to treat distension of the
chest and abdomen, obstruction or lump in the abdomen, frozen shoulder, amenorrhea
due to blood stasis, postpartum abdominal pain due to stasis, wounds and injuries,
carbuncle and jaundice.XVIII Turmeric extract is a major constituent of the ancient
Chinese herbal medicine, Jiawei-Xiaoyao-san, that has been used for the treatment
of dyspepsia, stress, and mood disorders [207, 215]. In the Philippines, the rhizome
with coconut oil is considered stomachic and vulnerary,CXVII and Malays use it to
treat abdominal spasm, flatulence, diarrhea and dysentery [29]. In Thai traditional
medicine, fresh and dried rhizomes are used as carminatives, anti-inflammatory, and
to treat peptic ulcer and wounds [210]. In African traditional medicine, turmeric is
used to treat palpitation, hypertension, and blood circulation disorders [1]. Turmeric
was also used as a dye for dyeing silk, wool and cotton. A U.S. patent for the use of
turmeric in wound healing was awarded to the University of Mississippi Medical
Center in 1995, which was abrogated two years later due to objections from the
Indian Council of Scientific and Industrial Research, because it has been medi-
cinally used for thousands of years in India.
Phytoconstituents: Major alkaloids are curcuminoids, that include curcumin (also
described as curcumin I), demethoxycurcumin (curcumin II) and bisdemethoxy-
curcumin (curcumin III) [184]. Bisabolane sesquiterpenes: 5-hydroxyl-ar-turmerone,
bisabolone, bisabolone-4-one, turmeronol A and B [221], bisacurone, bisacurone A,
B, and C, zingerone and dehydrozingerone [113, 201], curcuminoid, cyclocurcumin
[93], and water-soluble, antioxidant peptide, turmerin [185] are other constituents.
Curcumin, which gives the yellow color to turmeric was first isolated more than two
centuries ago in 1815, and its structure as diferuloylmethane was determined in
1910 [6]; it is the most biologically active constituent of turmeric and comprises
2–8% of most turmeric preparations [178]. Curcuminoids and EO contents of turmeric
rhizomes increase with the progress of plant development, and maximum contents
of curcuminoids reach in early September and early October; and longer storage years
decrease contents of curcuminoids and essential oil [111]. Curcuminoids and EO
contents also decrease with increased fertilizer application, though the rhizome yield
increases [112]. The volatile oil (4.5–6%) is composed of turmerone (58%),
zingiberene (20%), and small amounts of phellandrene, sesquiterpene alcohols, and
borneol.XVIII Aromatic (Ar)-turmerone, a-turmerone and b-turmerone were the major
constituents of fresh rhizome oil, whereas dry rhizome oil had Ar-turmerone,
a-santalene and Ar-curcumene as the major constituents [182]. Due to its poor water
Curcuma longa L. 785

solubility and poor intestinal absorption, oral curcumin is far less active than
i.p. administration, and a challenge for its therapeutic applications [12, 97].
C. aromatica and C. xanthorrhiza are the other important Curcuma species that
contain curcuminoids (esp. curcumin) and bisabolane-type sesquiterpenes as their
major constituents [73].
Pharmacology: Turmeric powder suspension significantly alleviated metabolic
syndrome-associated hyperglycemia and dyslipidemia, and elevation of atherogenic
indices, by increasing insulin level, enhancing antioxidant defense system and
decreasing LPO of diabetic rats [118]. However, turmeric extract with 1% of
curcuminoids, administered for ten-weeks to high fructose and saturated fatty acid
diet-fed rats, did not prevent increase in glucose, TGs, TC and insulin levels [195].
Orally ethanol and ether extracts, curcumin and the volatile oil lowered serum TC,
TGs and b-lipoprotein levels in hyperlipidemic rats [152], and ethanol extract
elevated HDL-C/TC ratio in hyperlipidemic rats [48], decreased LDL oxidation
susceptibility and plasma lipids in atherosclerotic rabbits [164], and significantly
reduced fatty streak lesions in thoracic and abdominal aorta of hypercholesterolemic
rabbits [155]. High-cholesterol diet supplemented with turmeric extract significantly
decreased TC, LDL-C, and HMG-CoA reductase levels, but increased HDL-C, and
prevented formation of fatty liver [217]. Curcuminoids supplemented high-fat diet fed
to rats for twelve-weeks significantly reduced plasma FFA and glucose levels,
and ameliorated cardiac autonomic imbalance [148]. Curcumin significantly lowered
TC, LDL-C, TGs and phospholipids in diabetic [18, 92], hyperlipidemic rats [170],
and with high-fat diet lowered serum TC, FBG, insulin, and body weight and
adipose tissue weight of mice [197], reduced liver TGs and serum fetuin-A levels of
rats [141]. Increased antioxidant enzymes activities by a turmeric extract improved
vasorelaxation of isolated aorta from hypercholesterolemic rats [78]. Due to its
antiproliferative activity curcumin-coated stents prevent restenosis in hypercholes-
terolemic rabbits [75].
Single oral doses up to 250 mg/kg of freeze-dried powder in milk significantly
lowered FBG after glucose loading in normoglycemic rats. Treatment of severely
hyperglycemic rats with daily dose of freeze-dried powder in milk for fourteen-days
significantly lowered FBG, TC and TGs, and increased HDL-C [157]. Aqueous
extract stimulated in vitro insulin secretion from mouse pancreatic tissues under basal
and hyperglycemic conditions [128], and ethanol extract significantly suppressed
increase in blood glucose of diabetic mice [137]. Both turmeric and curcumin sig-
nificantly reduced blood sugar, Hb and HbA1c levels, and oxidative stress in diabetic
rats [14], and ameliorated hyperglycemia-induced oxidative stress and delayed pro-
gression and maturation of cataract in diabetic rats [191]. Aqueous extract is also an
effective in vitro aldose reductase inhibitor, potentially able to reduce cataractogenic
effect of diabetes [65]. Oral administration of curcumin prevented and reduced
high-fat diet-induced insulin-resistance and hyperglycemia, and attenuated TNF-a
levels in rats [55] and significantly improved diabetes-induced endothelial dysfunc-
tion [171]. Curcumin significantly increases in vitro glucose transport from jejunal
and upper ileal portion of small intestine [53]. Tetrahydrocurcumin, a major colorless
786 Curcuma longa L.

metabolite of curcumin, also lowers blood glucose and plasma glycoproteins, and
increases plasma insulin levels in diabetic rats [144].
Aqueous and ethanol extracts, and curcumin are effective antioxidants [177,
194], improved antioxidant enzyme activities in diabetes-induced oxidative stress,
without altering hyperglycemic status [190], and dietary turmeric significantly
improved activities of antioxidant enzymes in iron-induced LPO in rats [167].
However, only aqueous extract protected against doxorubicin-cardiotoxicity [205].
Curcumin pretreatment significantly prevented sleep deprivation-induced behav-
ioral alterations and oxidative damage in mice [100], and protected against
LPS-induced vascular dysfunction and oxidative stress, as it restored arterial BP,
modulated HR, and suppressed aortic LPO [183]. The EO of fresh rhizomes showed
higher in vitro antioxidant activity than the oil from dry rhizomes [182]. Turmeric
induces endothelium-independent vasodilatory effect [62]. The ethanol extract
significantly inhibits AChE, BChE and LOX enzymes [86]. Turmeric administered
to mice 3 g/kg/day for 3-weeks protected against benzene-hematotoxicity [204].
Aqueous extract potently inhibited platelet aggregation after incubation with
platelet-rich plasma from healthy Chinese volunteers [216], and ether extract
inhibited in vitro platelet aggregation and reduced production of TXB2 in platelets
[187], so did curcumin [186], which preferentially inhibited PAF- and AA-induced
aggregation [176]. Curcuma oil also efficiently reversed ADP-induced platelet
aggregation and protected against intravascular thrombosis in rats [149]. Turmeric
aqueous extract for thirty-days protected against I/R-induced MI, and restored
myocardial antioxidant status and hemodynamic parameters in rats [129, 130];
curcumin also offered similar protection [37, 202]. Turmeric extract also protected
against doxorubicin-induced cardio-hepato-renal toxicity [127], and dietary tur-
meric supplementation (3%) of SHRs for twelve-weeks significantly decreased
blood viscosity and BP [62]. Intravenous injection of methanol extract in nor-
motensive rats significantly reduced BP and produced pronounced bradycardia [1].
Aqueous extract exhibited better antidepressant effect than fluoxetine, and also
significantly inhibited MAO-A and MAO-B in mice brains [220], and ethanol
extract exhibited antidepressant-like activity in chronic mildly stressed rats,
decreased serum cortisol, IL-6 and TNF-a levels [212], and increased 5-HT,
5-HIAA, NE and DA concentrations [211]. Oral curcumin also produced anti-
depressant activity, and markedly increased 5-HT and NE levels in both the frontal
cortex and hippocampus in mice [214, 215], whereas an i.p. dose of 20 mg/kg,
produced antidepression-like effects, and significantly reversed chronic
unpredictable stress-induced behavioral, biochemical, and neurochemical alter-
ations in rats [24, 96, 213]. Treatment of aged rats with turmeric extract for two-
months enhanced learning and spatial memory, lowered plasma corticosterone
level, and increased 5-HT level in the prefrontal cortex [153], significantly
increased recognition memory, and increased dendritic spine density and length in
pyramidal neurons of the prefrontal cortex, the CA1 and CA3 regions of the dorsal
hippocampus [199], and chronic aqueous suspension supplementation protected
brain against neurotoxic insults [133]. Curcumin supplemented-diet impaired fear
memory consolidation and reconsolidation processes, such as that observed in
Curcuma longa L. 787

traumatic memory formation in PTSD [131], and improved age-related cognitive

functions in rats [21], and significantly improved cognitive tasks, locomotor
activity, oxidative defense, and attenuated D-galactose-induced increased AChE
activity in mice [99]. Curcumin also protected against acute ethanol-induced
memory deficit [218], significantly reversed brain oxidative damage [159], and
methanol intoxication-induced retinopathy in rats [38]. Curcumin (20 mg/kg, i.p.)
produced a significant antianxiety-like effect in stressed mice without any signifi-
cant change in brain GABA contents, whereas diazepam produces anxiolytic-like
effect only in unstressed mice by increasing brain GABA contents [61], but oral
curcumin in a dose of 100 mg/kg produced an anxiogenic effect, while significantly
increasing MES seizure threshold in mice [22]. Curcumin treatment protected
against aluminium (a potent neurotoxin implicated in the etiology of Alzheimer’s
and Parkinson’s diseases)-induced cognitive dysfunction and oxidative damage,
and reduced AChE activity [98, 175], and also protected against a fungal neuro-
toxin, 3-nitropropionic acid [102]. Curcuminoids pretreatment was also neuropro-
tective against MPTP-induced dopaminergic neurodegeneration in mice [139].
Post-ischemia treatments with turmeric oil and curcumin ameliorated ischemia-
induced neurological functional deficit and the cerebral infarct size and edema
volume [49–51], and pretreatment with curcumin reversed the chronic haloperidol-
induced behavioral changes (experimental tardive dyskinesia) in rats, and the
oxidative damage in subcortical regions of the brain [25].
Dietary turmeric supplementation improved DEN-induced biochemical changes
and delayed initiation of hepatocarcinogenesis [56], B(a)P-induced forestomach
tumors [16, 43], DMBA-induced mammary tumor incidence and tumor burden [23,
42], and significantly reduced DMBA-induced hamster buccal pouch tumor num-
bers, burden and growth [95, 101]. Dietary turmeric to rats, at doses of 0.5% and
above, for three-months inhibited B(a)P- and 3-MC-mediated mutagenicity [147].
Pretreatment with aqueous extract, curcumin-free aqueous extract and curcumin
also significantly inhibited B(a)P-induced genotoxicity; the aqueous extract
showing the weakest activity [17]. Curcumin-free aqueous turmeric extract sig-
nificantly reduced B(a)P-induced forestomach tumors multiplicity and tumor
incidence more than turmeric powder or ethanol extract [43]. Feeding major
curcuminoids (77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxy-
curcumin) in diet inhibited forestomach tumors, duodenal tumors, and colon tumors
[70]; curcumin also significantly inhibited number of DMBA-induced skin tumor
per mouse, tumor volume, and percentage of tumor-bearing mice, without affecting
tumor growth [116]. Synthetic curcumin exhibited chemopreventive activity whether
administered prior to, during, or after carcinogen treatment [82].
Turmeric was very efficient bactericidal against clinical isolates of MDR
S. aureus, P. aeruginosa, K. pneumoniae, E. coli, B. subtilis and P. mirabilis [33].
However, a commercial turmeric extract standardized to 60% curcumin was mod-
estly active against clinical isolates of H. influenzae, S. pneumoniae, S. pyrogene
and S. aureus [136]. Crude turmeric paste incorporated into growth media inhibited
growth of S. aureus and E. coli; MIC of aqueous extract was 800 lg/ml for
S. aureus and 2,000 lg/ml for E. coli, compared to MIC of Amikacin for both
788 Curcuma longa L.

bacteria being 10 lg/ml [4]. Ethanol extract exhibited potent antibacterial activity
against S. pyogenes and E. fecalis [120], but was inactive against L. monocytogenes,
and S. typhimurium [193]. Both methanol extract and curcumin inhibited growth of
19 strains of H. pylori [119], whereas curcumin exhibited remarkable activity
against ten strains of MRSA, and markedly reduced MICs of oxacillin, ampicillin,
ciprofloxacin, and norfloxacin against MRSA [132], and an ethyl acetate extract
exhibited significant activity against MRSA, and markedly lowered MICs of
ampicillin and oxacillin against MRSA [91]. Curcumin also restored sensitivity of
resistant C. albicans to fluconazole [60]. Freshly distilled and 18-month-old volatile
oil was significantly active against a number of clinical isolates of dermatophytes,
comparable to ketoconazole [13, 210]. Essential oil and curcumin also exhibited
potent in vitro antiaflatoxigenic activities [57]. An aqueous extract also repressed
HBV replication [90], and curcumin inhibited HIV-1 integrase [121].
Turmeric powder supplementation protected against antituberculosis drugs-
hepatotoxicity in guinea pigs [3], and pretreatment with turmeric extracts and
curcumin ameliorated CCl4- [44, 107, 108, 173], D-galactosamine- [2, 45],
methotrexate- [126], and thioacetamide-induced liver damage [172]. Curcumin was
protective against CCl4- [209], APAP- [27, 87], chloroquin- [143], and ethanol-
induced oxidative stress and liver damage [154, 160, 169], and significantly
stimulated bile flow and reduced cyclosporin-induced cholestasis [46, 47]. Cur-
cumin was also beneficial in ameliorating diabetic nephropathy in rats [39, 179,
189], and prevented ferric nitrilotriacetate (a renal carcinogen)-induced oxidative
damage to the kidneys [140], but was not protective against glycerol-induced acute
renal failure in rats [200].
Turmeric extract arrested degenerative changes in collagen-induced [192], and
adjuvant-induced [162] arthritis in rats; the three major curcuminoids are mainly
responsible for the antiarthritic effect [59]. Aqueous extract protected against
radiation-induced oxidative stress in male rats [134], and topical application of alcohol
extract incorporated in cream was beneficial in ultraviolet-induced skin damage [81].
Topical application of aqueous extract exhibited potent anti-inflammatory activity
against endotoxin-induced uveitis in rabbits [63], and LPS-induced uveitis in rats
[5]. Application offresh turmeric paste significantly enhanced healing offull-thickness
wounds in rabbits [103], and application of turmeric powder mixed with ghee (purified
butter) obtained from sheep butterfat, enhanced surgical gingival wound healing in
dogs [64]. Curcumin enhanced cutaneous wound healing in rats and guinea pigs,
and improved impaired wound healing in diabetic rats [180, 181]. Pretreatment with
curcumin also significantly improved healing of protracted irradiated wound [74].
However, application of aqueous and alcoholic turmeric extract drops delayed healing
of both superficial and penetrating corneal wounds in rabbits [122]. Methanol turmric
extract significantly inhibited iNOS activity (>70% at a concentration of 10 lg/ml)
in LPS-induced mouse macrophages [67]. Turmeric oil produced significant reduction
in both acute and chronic inflammation, and exhibited potent antinociceptive activity
[115], whereas Funk et al. [58] found orally administered oil modestly active against
streptococcal cell wall-induced arthritis, but highly active when used intraperitoneally,
Curcuma longa L. 789

however, associated with significant morbidity and mortality in female rats. Chronic
curcumin treatment alleviated neuropathic pain [222].
Oral curcumin significantly attenuated TNBSA-induced chronic colitis in rats,
substantially reduced rise in myeloperoxidase activity and TNF-a, and induced
downregulation of COX-2 and iNOS expression [30]. Dietary supplementation of
turmeric extract (a patented formulation with 18–22% curcuminoids content) [9],
and curcumin [41] significantly attenuated DSS-induced colitis in mice, and the
extract also exerted direct and indirect myorelaxant effect on isolated mouse ileum
and colon [9], via noncompetitive inhibition of cholinergic, histaminergic and
serotoninergic receptors [124], but curcumin did not show histamine H2 receptors
blocking effect [89]. Pretreatment of mice with aqueous extract and curcumin
significantly protects against cerulein-induced acute pancreatitis, and pancreatitis-
associated lung injury [174, 219].
Ethanol and aqueous extracts exhibit antispermatogenic and antiandrogenic
effects in male rats [15, 152]; the antifertility effect of twelve-weeks of aqueous
extract administration in mice was reversible after eight-weeks of withdrawal [125].
Conversely, curcumin was reported to significantly ameliorate dexamethasone-
induced spermatogenesis defects in mice [88]. Adding curcumin in diet did not
affect mortality but protected rats against other effects of radiation exposure [71].
Curcumin also significantly attenuated OVA-induced airway constriction and air-
way hyperreactivity in guinea pigs [161], and mice [138].
Clinical Studies: A single dose of 6 g turmeric increased postprandial serum
insulin, without affecting plasma glucose levels in healthy Swedish volunteers
[206], and daily intake of turmeric for sixty-days decreased peroxidation of both
HDL and LDL, in healthy volunteers with high baseline values [163], and intake of
curcuminoids 4 g/day, beginning three-days before CABG surgery and continued
for five-days after surgery, significantly reduced in-hospital incidence of post
CABG surgery MI in Thai patients [208]. Curcumin also improved age-related
decline in endothelial function in postmenopausal Japanese women [8].
Six-weeks treatment of patients with painful knee osteoarthritis with a curcuma
extract (NR-INF-02) significantly decreased use of rescue medication, and
improved clinical and subjective symptoms [117]; another RCT reported similar
results after treatment of Indian patients with knee osteoarthritis with a curcuma
extract for four-months, that also significantly reduced serum levels of inflamma-
tory biomarkers, IL-1b, ROS, and MDA [188]. A 30 mg thrice daily dose of
curcuminoids for four-weeks significantly reduced COX-2 secretion by synovial
fluid’s monocytes, comparable to diclofenac, in Indonesian patients with knee
osteoarthritis [83]. A meta-analysis of the RCTs concluded that turmeric extract
providing about 1,000 mg/day of curcumin was efficacious in the treatment of
arthritis [40].
In an RCT, 6 g daily dose of turmeric for eight-weeks was not superior to
placebo in healing duodenal ulcers in Vietnamese and Swedish patients [198].
However, turmeric powder (600 mg five times daily) reportedly healed peptic
790 Curcuma longa L.

ulcers in Thai patients after twelve-weeks of treatment, and relieved abdominal pain
and discomfort in patients with erosions, gastritis and dyspepsia [151]. Curcumin
was ineffective to significantly eradicate H. pylori in infected gastritis patients [94],
but produced a cholinokinetic effect in healthy volunteers [166]. In a randomized,
pilot study of healthy English adults with IBS symptoms, a standardized turmeric
extract daily for 8-weeks significantly improved symptoms in two-thirds of the
individuals [28]. Efficacy of oral treatment with curcumin of patients suffering from
chronic anterior uveitis at a dose of 375 mg three times daily for twelve-weeks was
comparable to corticosteroid therapy, without the adverse effects of corticosteroids
[105].
An RCT, using up to 4 g/day of oral curcumin (Curcumin C3 Complex®) for
24-weeks, in U.S. patients with mild to moderate Alzheimer’s Disease, did not
show any significant clinical or biochemical evidence of efficacy [168]. In another
RCT, there was no significant difference in cognitive functions of community-
dwelling older adults in Australia who received 1,500 mg/d of a commercial for-
mulation of curcumin (Biocurcumax®) or placebo for 12-months [158]. However,
curry consumption was associated with significantly better cognitive functions in
nondemented elderly Asian subjects, aged 60–93 years, who consumed curry often
or very often [135].
A 500 mg turmeric capsule with each meal for two-months significantly reduced
proteinuria and serum levels of TGF-b and IL-8 in Iranian patients with ESRD due
to type-2 diabetic nephropathy [84]. Turmeric supplementation also reduced uremic
pruritus, and serum levels of hs-CRP in ESRD patients [142]. Turmeric, in a dose of
1,500 mg/day for 30-days, significantly reduced urinary excretion of mutagens in
chronic smokers, signifying its antimutagenic effects [146]. Oral curcuma-extract
significantly improved more Spanish patients with moderate to severe plaque
psoriasis when used along with RVLP than treatment with RVLP alone [31], and
topical application of ethanol extract and a curcumin ointment produced remarkable
symptomatic relief in external cancerous lesions, reducing smell and itching, and
drying of lesions in most of the sixty-two Indian patients [104].
Mechanism of Action: Curcumin is suggested to act chemically as a scavenger of
free radicals and/or influences signal transduction and modulates activity of specific
transcription factors that regulate expression of genes involved in free radicals
scavenging and lipid homeostasis [223]. Turmeric volatile oils inhibit glucosidase
enzyme more effectively than acarbose, and drying of the rhizomes enhances
a-glucosidase and a-amylase inhibitory activities; ar-turmerone, the major volatile
component is mainly responsible for these activities [109]. Turmerin, the water-
soluble peptide in turmeric rhizomes, also significantly inhibits a-amylase and
a-glucosidase activities [110]. Of the main curcuminoids, bisdemethoxycurcumin is
the most potent in vitro a-glucosidase inhibitor [52]. It regulates numerous tran-
scription factors, cytokines, protein kinases, adhesion molecules, redox status and
other mediators of inflammation [7], including phospholipase, LOX, COX2, LTs,
TX, PGs, NO, collagenase, elastase, hyaluronidase, MCP-1, interferon-inducible
protein, TNF, and IL-12 [32]. Curcumin encompasses inhibitory activities of some
Curcuma longa L. 791

of the most successful modern drugs, such as TNF blockers (Adalimumab,

Infliximab, and Etanercept), VEGF blocker (Bevacizumab), human EGFR blockers
(Cetuximab, Erlotinib, and Geftinib), and HER2 blocker (Trastuzumab) [6]. It is
thus beneficial in autoimmune diseases, such as MS, RA, psoriasis, and IBD [26].
Curcumin also downregulates some of the cyclins and cyclin-dependent kinases
(Cdk), upregulates Cdk inhibitors, and inhibits DNA synthesis [80]. Strong NF-jB
inhibitory activity of curcumin acts synergistically with anticancer drugs that often
leads to cellular apoptotic response [196]. Aqueous extract and curcumin signifi-
cantly inhibit 5-LOX activity [150]. Curcumin I and curcumin II potently inhibit
COX-2 than curcumin III, and all curcuminoids modestly and equally inhibit
COX-1 [165]. Curcumin also inhibits 5-LOX, and 12-LOX activities [11],
LPS-induced production of TNF-a, IL-1, activation of NF-jB [34], and formation
of PGE2, and COX-2 expression [106, 145] for its anti-inflammatory effects.
A marked increase in hepatic cholesterol-7a-hydroxylase activity (CYP7A1), a
rate-limiting enzyme in the biosynthesis of bile acid from cholesterol suggests a
higher rate of cholesterol catabolism, may in part be responsible for cholesterol
lowering effect [18, 92]. Turmeric oil and curcumin ameliorate brain oxidative
damage via NO modulation [49–51, 100], as curcumin significantly inhibits iNOS
in cultured astrocytes [76]. Antidepressant-like effect of curcumin is suggested to be
mediated, in part, via serotonergic system involving 5-HT(1A/1B) and 5-HT2C
receptors [203]; aqueous extract also significantly inhibits MAO-A and MAO-B in
mice brain [220]. Antioxidant and AChE-inhibiting activities may in part, con-
tribute for neuroprotective, memory and cognition-enhancing effects [98, 99, 175].
Antiproliferative effects of curcumin against several breast tumor cell lines showed
that it preferentially arrested cells in the G2/S phase of the cell cycle, and did not
involve apoptosis or any significant change in the expression of apoptosis-related
genes [66, 123]. However, synthetic curcumin administration during initiation and
post-initiation stages and throughout promotion/progression stage increased apop-
tosis in colon tumors of rats [82]; apoptotic process was also determined the
mechanism mediating in vitro AK-5 tumor cell death [85].
Human A/Es, Allergy and Toxicity: Curcumin, up to a dose of 8,000 mg per day
for 3-months was found safe in humans [32], and produced no treatment-related
toxicity in Taiwanese patients with high risk of premalignant lesions [36]. Turmeric
oil intake (one ml daily) by healthy Indian volunteers for twelve-weeks did not
affect body weight, pulse, and BP, and no other clinical, haematological, renal or
hepatic-toxicity signs were observed [77].
Animal Toxicity: Single oral dose up to 3,000 mg/kg of freeze-dried powder in
milk was nonlethal and nontoxic to rats [157], and turmeric EO in a single dose of
up to 5,000 mg/kg, and up to 500 mg/kg daily for thirteen-weeks to Wistar rats,
caused no mortality or any clinical or microscopic organ toxicity [114]. Mice
treated with ethanol extract in a single dose of up to 3,000 mg/kg and
100 mg/kg/day for ninety-days had no mortality, but increased weights of sexual
organs, sperm motility and sperm counts in male mice [156]. Mice are susceptible
to turmeric powder and ethanol extract-induced hepatotoxicity [79]. Curcumin also
792 Curcuma longa L.

caused dose-dependent hepatotoxicity [19]. Out of two hundred compounds from

the turmeric, 184 compounds were predicted as toxigenic, 136 compounds as
mutagenic, 153 compounds as carcinogenic and 64 compounds as hepatotoxic in
in vitro studies [20].
CYP450 and Potential for Drug-Herb Interactions: The rhizome ethanol extract
significantly inhibited activities of CYP2D6 and CYP3A4 in healthy human sub-
jects [10]. Methanol extract of C. longa of Japanese origin, significantly decreased
in vitro activity of CYP3A4 by about 85–98%, and curcumin caused a 30–40%
decrease in CYP3A4 catalytic activity [69]. Curcumin also inhibited CYP1A2, but
enhanced the activity of CYP2A6 in healthy male Chinese volunteers [35]. Dietary
supplementation of curcumin to mice for 30-days significantly increased activities
of antioxidant and phase II-metabolizing enzymes in liver and kidneys [72].
Methanol extract significantly increased activity of P-gp in Caco-2 cells, whereas
curcumin inhibited the activity of P-gp [68]. Pretreatment of rats with turmeric juice
significantly increased blood concentration of tacrolimus [54].
Commentary: Turmeric, its purported active constituent, curcumin I, and turmeric
oil have shown a number of beneficial effects, both pharmacologically and in
clinical trials, especially the anti-inflammatory effects. Nevertheless, inconsistent
results on other clinical benefits need to be verified by more extensive clinical
studies. Clinical results with oral curcumin should require special attention, as
curcumin has poor water solubility and intestinal absorption. Also, turmeric or
curcumin use with conventional drugs be monitored, because of their significant
effects on CYP450 enzymes and the potential for drug-herb interactions.

References
1. Adaramoye OA, Anjos RM, Almeida MM, et al. Hypotensive and
endothelium-independent vasorelaxant effects of methanolic extract from
Curcuma longa L. in rats. J Ethnopharmacol. 2009;124:457–62.
2. Adaramoye OA, Odunewu AO, Farombi EO. Hepatoprotective effect of
Curcuma longa L. in D-galactosamine induced liver injury in mice:
evidence of antioxidant activity. Afr J Med Med Sci. 2010;39(Suppl):
27–34.
3. Adhvaryu MR, Reddy N, Parabia MH. Effects of four Indian medicinal
herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury
and immunosuppression in guinea pigs. World J Gastroenterol. 2007;13:
3199–205.
4. Afrose R, Saha SK, Banu LA, et al. Antibacterial effect of Curcuma longa
(Turmeric) against Staphylococcus aureus and Escherichia coli. Mymen-
singh Med J. 2015;24:506–15.
Curcuma longa L. 793

5. Agarwal R, Gupta SK, Agarwal P, Srivastava S. Topically applied standard-

ized aqueous extract of Curcuma longa Linn. suppresses endotoxin-induced
uveal inflammation in rats. Indian J Exp Biol. 2013;51:797–803.
6. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian
solid gold. Adv Exp Med Biol. 2007;595:1–75.
7. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin,
the anti-inflammatory agent, against neurodegenerative, cardiovascular,
pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem
Cell Biol. 2009;41:40–59.
8. Akazawa N, Choi Y, Miyaki A, et al. Curcumin ingestion and exercise
training improve vascular endothelial function in postmenopausal women.
Nutr Res. 2012;32:795–9.
9. Aldini R, Budriesi R, Roda G, et al. Curcuma longa extract exerts a
myorelaxant effect on the ileum and colon in a mouse experimental colitis
model, independent of the anti-inflammatory effect. PLoS ONE. 2012;7:
e44650.
10. Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. Effect of Curcuma longa
on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in
human liver microsomes and healthy human subjects. Eur J Drug Metab
Pharmacokinet. 2015;40:61–6.
11. Ammon HP, Safayhi H, Mack T, Sabieraj J. Mechanism of anti-inflammatory
actions of curcumine and boswellic acids. J Ethnopharmacol. 1993;38:113–9.
12. Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med.
1991;57:1–7.
13. Apisariyakul A, Vanittanakom N, Buddhasukh D. Antifungal activity of
turmeric oil extracted from Curcuma longa (Zingiberaceae). J Ethnophar-
macol. 1995;49:163–9.
14. Arun N, Nalini N. Efficacy of turmeric on blood sugar and polyol pathway
in diabetic albino rats. Plant Foods Hum Nutr. 2002;57:41–52.
15. Ashok P, Meenakshi B. Contraceptive effect of Curcuma longa (L.) in
male albino rat. Asian J Androl. 2004;6:71–4.
16. Azuine MA, Bhide SV. Adjuvant chemoprevention of experimental cancer:
catechin and dietary turmeric in forestomach and oral cancer models. J
Ethnopharmacol. 1994;44:211–7.
17. Azuine MA, Kayal JJ, Bhide SV. Protective role of aqueous turmeric
extract against mutagenicity of direct-acting carcinogens as well as benzo
[alpha] pyrene-induced genotoxicity and carcinogenicity. J Cancer Res
Clin Oncol. 1992;118:447–52.
18. Babu PS, Srinivasan K. Hypolipidemic action of curcumin, the active
principle of turmeric (Curcuma longa) in streptozotocin induced diabetic
rats. Mol Cell Biochem. 1997;166:169–75.
19. Balaji S, Chempakam B. Pharmacokinetics prediction and drugability
assessment of diphenylheptanoids from turmeric (Curcuma longa L). Med
Chem. 2009;5:130–8.
794 Curcuma longa L.

20. Balaji S, Chempakam B. Toxicity prediction of compounds from turmeric

(Curcuma longa L). Food Chem Toxicol. 2010;48:2951–9.
21. Belviranlı M, Okudan N, Atalık KE, Oz M. Curcumin improves spatial
memory and decreases oxidative damage in aged female rats. Biogeron-
tology. 2013;14:187–96.
22. Bharal N, Sahaya K, Jain S, et al. Curcumin has anticonvulsant activity on
increasing current electroshock seizures in mice. Phytother Res. 2008;22:
1660–4.
23. Bhide SV, Azuine MA, Lahiri M, Telang NT. Chemoprevention of
mammary tumor virus-induced and chemical carcinogen-induced rodent
mammary tumors by natural plant products. Breast Cancer Res Treat.
1994;30:233–42.
24. Bhutani MK, Bishnoi M, Kulkarni SK. Antidepressant like effect of
curcumin and its combination with piperine in unpredictable chronic
stress-induced behavioral, biochemical and neurochemical changes. Phar-
macol Biochem Behav. 2009;92:39–43.
25. Bishnoi M, Chopra K, Kulkarni SK. Protective effect of Curcumin, the
active principle of turmeric (Curcuma longa) in haloperidol-induced
orofacial dyskinesia and associated behavioural, biochemical and neuro-
chemical changes in rat brain. Pharmacol Biochem Behav. 2008;88:
511–22.
26. Bright JJ. Curcumin and autoimmune disease. Adv Exp Med Biol. 2007;
595:425–51 (Review).
27. Bulku E, Stohs SJ, Cicero L, et al. Curcumin exposure modulates
multiple proapoptotic and antiapoptotic signaling pathways to antagonize
acetaminophen-induced toxicity. Curr Neurovasc Res. 2012;9:58–71.
28. Bundy R, Walker AF, Middleton RW, Booth J. Turmeric extract may
improve irritable bowel syndrome symptomology in otherwise healthy
adults: a pilot study. J Altern Complement Med. 2004;10:1015–8.
29. Burkill IH. A dictionary of the economic products of the Malaya
Peninsula. London; 1935.
30. Camacho-Barquero L, Villegas I, Sánchez-Calvo JM, et al. Curcumin, a
Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2
and iNOS expression in chronic experimental colitis. Int Immunopharmacol.
2007;7:333–42.
31. Carrion-Gutierrez M, Ramirez-Bosca A, Navarro-Lopez V, et al. Effects of
Curcuma extract and visible light on adults with plaque psoriasis. Eur J
Dermatol. 2015;25:240–6.
32. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a
component of tumeric (Curcuma longa). J Altern Complement Med. 2003;
9:161–8.
33. Chakraborty B, Nath A, Saikia H, Sengupta M. Bactericidal activity of
selected medicinal plants against multidrug resistant bacterial strains from
clinical isolates. Asian Pac J Trop Med. 2014;7S1:S435–41.
Curcuma longa L. 795

34. Chan MM. Inhibition of tumor necrosis factor by curcumin, a phytochem-

ical. Biochem Pharmacol. 1995;49:1551–6.
35. Chen Y, Liu WH, Chen BL, et al. Plant polyphenol curcumin significantly
affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volun-
teers. Ann Pharmacother. 2010;44:1038–45.
36. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a
chemopreventive agent, in patients with high-risk or premalignant lesions.
Anticancer Res. 2001;21:2895–900.
37. Cheng H, Liu W, Ai X. Protective effect of curcumin on myocardial ischemia
reperfusion injury in rats. Zhong Yao Cai. 2005;28:920–2 (Article in
Chinese).
38. Chirapapaisan N, Uiprasertkul M, Chuncharunee A. The effect of
coenzyme Q10 and curcumin on chronic methanol intoxication induced
retinopathy in rats. J Med Assoc Thai. 2012;95 Suppl 4:S76–81.
39. Chiu J, Khan ZA, Farhangkhoee H, Chakrabarti S. Curcumin prevents
diabetes-associated abnormalities in the kidneys by inhibiting p300 and
nuclear factor-kappaB. Nutrition. 2009;25:964–72.
40. Daily JW, Yang M, Park S. Efficacy of turmeric extracts and curcumin for
alleviating the symptoms of joint arthritis: a systematic review and
meta-analysis of randomized clinical trials. J Med Food. 2016;19:717–29.
41. Deguchi Y, Andoh A, Inatomi O, et al. Curcumin prevents the develop-
ment of dextran sulfate sodium (DSS)-induced experimental colitis. Dig
Dis Sci. 2007;52:2993–8.
42. Deshpande SS, Ingle AD, Maru GB. Chemopreventive efficacy of curcumin-
free aqueous turmeric extract in 7,12-dimethylbenz[a]anthracene-induced rat
mammary tumorigenesis. Cancer Lett. 1998;123:35–40.
43. Deshpande SS, Ingle AD, Maru GB. Inhibitory effects of curcumin-free
aqueous turmeric extract on benzo[a]pyrene-induced forestomach papillo-
mas in mice. Cancer Lett. 1997;118:79–85.
44. Deshpande UR, Gadre SG, Raste AS, et al. Protective effect of turmeric
(Curcuma longa L.) extract on carbon tetrachloride-induced liver damage
in rats. Indian J Exp Biol. 1998;36:573–7.
45. Deshpande UR, Joseph LJ, Samuel AM. Hepatobiliary clearance of
labelled mebrofenin in normal and D-galactosamine HCl-induced hepatitis
rats and the protective effect of turmeric extract. Indian J Physiol Pharmacol.
2003;47:332–6.
46. Deters M, Siegers C, Muhl P, Hänsel W. Choleretic effects of curcum-
inoids on an acute cyclosporin-induced cholestasis in the rat. Planta Med.
1999;65:610–3.
47. Deters M, Siegers C, Hänsel W, et al. Influence of curcumin on cyclosporin-
induced reduction of biliary bilirubin and cholesterol excretion and on
biliary excretion of cyclosporin and its metabolites. Planta Med. 2000;66:
429–34.
796 Curcuma longa L.

48. Dixit VP, Jain P, Joshi SC. Hypolipidaemic effects of Curcuma longa L
and Nardostachys jatamansi, DC in triton-induced hyperlipidaemic rats.
Indian J Physiol Pharmacol. 1988;32:299–304.
49. Dohare P, Garg P, Jain V, et al. Dose dependence and therapeutic window
for the neuroprotective effects of curcumin in thromboembolic model of
rat. Behav Brain Res. 2008;193:289–97.
50. Dohare P, Garg P, Sharma U, et al. Neuroprotective efficacy and
therapeutic window of curcuma oil: in rat embolic stroke model. BMC
Complement Altern Med. 2008;8:55.
51. Dohare P, Varma S, Ray M. Curcuma oil modulates the nitric oxide system
response to cerebral ischemia/reperfusion injury. Nitric Oxide. 2008;19:1–11.
52. Du ZY, Liu RR, Shao WY, et al. Alpha-glucosidase inhibition of natural
curcuminoids and curcumin analogs. Eur J Med Chem. 2006;41:213–8.
53. Dvivedi J, Pandey S, Gupta R. Effect of curcumin on glucose absorption:
an experimental study on albino rats. Indian J Physiol Pharmacol.
2011;55:207–12.
54. Egashira K, Sasaki H, Higuchi S, Ieiri I. Food-drug interaction of tacrolimus
with pomelo, ginger, and turmeric juice in rats. Drug Metab Pharmacokinet.
2012;27:242–7.
55. El-Moselhy MA, Taye A, Sharkawi SS, El-Sisi SF, Ahmed AF. The
antihyperglycemic effect of curcumin in high fat diet fed rats. Role of
TNF-a and free fatty acids. Food Chem Toxicol. 2011;49:1129–40.
56. El-Shahat M, El-Abd S, Alkafafy M, El-Khatib G. Potential chemopre-
vention of diethylnitrosamine-induced hepatocarcinogenesis in rats: myrrh
(Commiphora molmol) versus turmeric (Curcuma longa). Acta Histochem.
2012;114:421–8.
57. Ferreira FD, Kemmelmeier C, Arrotéia CC, et al. Inhibitory effect of the
essential oil of Curcuma longa L. and curcumin on aflatoxin production by
Aspergillus flavus Link. Food Chem. 2013;136:789–93.
58. Funk JL, Frye JB, Oyarzo JN, et al. Antiarthritic effects and toxicity of the
essential oils of turmeric (Curcuma longa L). J Agric Food Chem. 2010;
58:842–9.
59. Funk JL, Oyarzo JN, Frye JB, et al. Turmeric extracts containing curcuminoids
prevent experimental rheumatoid arthritis. J Nat Prod. 2006;69:351–5.
60. Garcia-Gomes AS, Curvelo JA, Soares RM, Ferreira-Pereira A. Curcumin
acts synergistically with fluconazole to sensitize a clinical isolate of Candida
albicans showing a MDR phenotype. Med Mycol. 2012;50:26–32.
61. Gilhotra N, Dhingra D. GABAergic and nitriergic modulation by curcumin
for its antianxiety-like activity in mice. Brain Res. 2010;1352:167–75.
62. Goto H, Sasaki Y, Fushimi H, et al. Effect of curcuma herbs on
vasomotion and hemorheology in spontaneously hypertensive rat. Am J
Chin Med. 2005;33:449–57.
Curcuma longa L. 797

63. Gupta SK, Agarwal R, Srivastava S, et al. The anti-inflammatory effects of

Curcuma longa and Berberis aristata in endotoxin-induced uveitis in
rabbits. Invest Ophthalmol Vis Sci. 2008;49:4036–40.
64. Habiboallah G, Nasroallah S, Mahdi Z, et al. Histological evaluation of
Curcuma longa-ghee formulation and hyaluronic acid on gingival healing
in dog. J Ethnopharmacol. 2008;120:335–41.
65. Halder N, Joshi S, Gupta SK. Lens aldose reductase inhibiting potential of
some indigenous plants. J Ethnopharmacol. 2003;86:113–6.
66. Hanif R, Qiao L, Shiff SJ, Rigas B. Curcumin, a natural plant phenolic
food additive, inhibits cell proliferation and induces cell cycle changes in
colon adenocarcinoma cell lines by a prostaglandin-independent pathway.
J Lab Clin Med. 1997;130:576–84.
67. Hong CH, Hur SK, Oh OJ, et al. Evaluation of natural products on
inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase
(iNOS) in cultured mouse macrophage cells. J Ethnopharmacol. 2002;83:
153–9.
68. Hou XL, Takahashi K, Tanaka K, et al. Curcuma drugs and curcumin
regulate the expression and function of P-gp in Caco-2 cells in completely
opposite ways. Int J Pharm. 2008;358:224–9.
69. Hou XL, Takahashi K, Kinoshita N, et al. Possible inhibitory mechanism
of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated
Caco-2 cells. Int J Pharm. 2007;337:169–77.
70. Huang MT, Lou YR, Ma W, et al. Inhibitory effects of dietary curcumin on
forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res.
1994;54:5841–7.
71. Inano H, Onoda M. Radioprotective action of curcumin extracted from
Curcuma longa Linn.: inhibitory effect on formation of urinary 8-hydroxy-
2′-deoxyguanosine, tumorigenesis, but not mortality, induced by gamma-
ray irradiation. Int J Radiat Oncol Biol Phys. 2002;53:735–43.
72. Iqbal M, Sharma SD, Okazaki Y, et al. Dietary supplementation of
curcumin enhances antioxidant and phase II metabolizing enzymes in ddY
male mice: possible role in protection against chemical carcinogenesis and
toxicity. Pharmacol Toxicol. 2003;92:33–8.
73. Itokawa H, Shi Q, Akiyama T, et al. Recent advances in the investigation
of curcuminoids. Chin Med. 2008;3:11.
74. Jagetia GC, Rajanikant GK. Role of curcumin, a naturally occurring
phenolic compound of turmeric in accelerating the repair of excision
wound, in mice whole-body exposed to various doses of gamma-radiation.
J Surg Res. 2004;120:127–38.
75. Jang HS, Nam HY, Kim JM, et al. Effects of curcumin for preventing
restenosis in a hypercholesterolemic rabbit iliac artery stent model.
Catheter Cardiovasc Interv. 2009;74:881–8.
76. Jiang J, Wang W, Sun YJ, et al. Neuroprotective effect of curcumin on
focal cerebral ischemic rats by preventing blood-brain barrier damage.
Eur J Pharmacol. 2007;561:54–62.
798 Curcuma longa L.

77. Joshi J, Ghaisas S, Vaidya A, et al. Early human safety study of turmeric
oil (Curcuma longa oil) administered orally in healthy volunteers. J Assoc
Physicians India. 2003;51:1055–60.
78. Kam TS, Wong CY, Kwan PL, et al. Effects and mechanism of turmeric
vasorelaxation of the thoracic aorta in hypercholesterolemic rats. J Med
Food. 2012;15:190–9.
79. Kandarkar SV, Sawant SS, Ingle AD, et al. Subchronic oral hepatotoxicity
of turmeric in mice—histopathological and ultrastructural studies. Indian J
Exp Biol. 1998;36:675–9.
80. Karunagaran D, Joseph J, Kumar TR. Cell growth regulation. Adv Exp
Med Biol. 2007;595:245–68 (Review).
81. Kaur CD, Saraf S. Topical vesicular formulations of Curcuma longa
extract on recuperating the ultraviolet radiation-damaged skin. J Cosmet
Dermatol. 2011;10:260–5.
82. Kawamori T, Lubet R, Steele VE, et al. Chemopreventive effect of curcumin,
a naturally occurring anti-inflammatory agent, during the promotion/
progression stages of colon cancer. Cancer Res. 1999;59:597–601.
83. Kertia N, Asdie AH, Rochmah W, Marsetyawan. Ability of curcuminoid
compared to diclofenac sodium in reducing the secretion of cycloxyge-
nase-2 enzyme by synovial fluid’s monocytes of patients with osteoarthritis.
Acta Med Indones. 2012;44:105–13.
84. Khajehdehi P, Pakfetrat M, Javidnia K, et al. Oral supplementation of
turmeric attenuates proteinuria, transforming growth factor-b and interleukin-
8 levels in patients with overt type 2 diabetic nephropathy: a randomized,
double-blind and placebo-controlled study. Scand J Urol Nephrol. 2011;
45:365–70.
85. Khar A, Ali AM, Pardhasaradhi BV, et al. Antitumor activity of curcumin
is mediated through the induction of apoptosis in AK-5 tumor cells. FEBS
Lett. 1999;445:165–8.
86. Khattak S, Saeed-Ur-Rehman, Shah HU et al. In vitro enzyme inhibition
activities of crude ethanolic extracts derived from medicinal plants of
Pakistan. Nat Prod Res. 2005;19:567–71.
87. Kheradpezhouh E, Panjehshahin MR, Miri R, et al. Curcumin protects rats
against acetaminophen-induced hepatorenal damages and shows synergis-
tic activity with N-acetyl cysteine. Eur J Pharmacol. 2010;628:274–81.
88. Khorsandi L, Mirhoseini M, Mohamadpour M, et al. Effect of curcumin on
dexamethasone-induced testicular toxicity in mice. Pharm Biol. 2013;51:
206–12.
89. Kim DC, Kim SH, Choi BH, et al. Curcuma longa extract protects against
gastric ulcers by blocking H2 histamine receptors. Biol Pharm Bull. 2005;
28:2220–4.
90. Kim HJ, Yoo HS, Kim JC, et al. Antiviral effect of Curcuma longa Linn.
extract against hepatitis B virus replication. J Ethnopharmacol. 2009;124:
189–96.
Curcuma longa L. 799

91. Kim KJ, Yu HH, Cha JD, et al. Antibacterial activity of Curcuma longa L.
against methicillin-resistant Staphylococcus aureus. Phytother Res. 2005;
19:599–604.
92. Kim M, Kim Y. Hypocholesterolemic effects of curcumin via up-regulation
of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr Res Pract.
2010;4:191–5.
93. Kiuchi F, Goto Y, Sugimoto N, et al. Nematocidal activity of turmeric:
synergistic action of curcuminoids. Chem Pharm Bull (Tokyo). 1993;41:
1640–3.
94. Koosirirat C, Linpisarn S, Changsom D, Chawansuntati K, Wipasa J. Inves-
tigation of the anti-inflammatory effect of Curcuma longa in Helicobacter
pylori-infected patients. Int Immunopharmacol. 2010;10:815–8.
95. Krishnaswamy K, Goud VK, Sesikeran B, et al. Retardation of experi-
mental tumorigenesis and reduction in DNA adducts by turmeric and
curcumin. Nutr Cancer. 1998;30:163–6.
96. Kulkarni SK, Bhutani MK, Bishnoi M. Antidepressant activity of curcumin:
involvement of serotonin and dopamine system. Psychopharmacology.
2008;201:435–42.
97. Kulkarni SK, Akula KK, Deshpande J. Evaluation of antidepressant-like
activity of novel water-soluble curcumin formulations and St. John’s wort
in behavioral paradigms of despair. Pharmacology. 2012;89:83–90.
98. Kumar A, Dogra S, Prakash A. Protective effect of curcumin (Curcuma
longa), against aluminium toxicity: possible behavioral and biochemical
alterations in rats. Behav Brain Res. 2009;205:384–90.
99. Kumar A, Prakash A, Dogra S. Protective effect of curcumin (Curcuma
longa) against D-galactose-induced senescence in mice. J Asian Nat Prod
Res. 2011;13:42–55.
100. Kumar A, Singh A. Possible nitric oxide modulation in protective effect of
(Curcuma longa, Zingiberaceae) against sleep deprivation-induced behav-
ioral alterations and oxidative damage in mice. Phytomedicine. 2008;15:
577–86.
101. Kumar G, Tajpara P, Maru G. Dietary turmeric post-treatment decreases
DMBA-induced hamster buccal pouch tumor growth by altering cell pro-
liferation and apoptosis-related markers. J Environ Pathol Toxicol Oncol.
2012;31:295–312.
102. Kumar P, Padi SS, Naidu PS, Kumar A. Possible neuroprotective
mechanisms of curcumin in attenuating 3-nitropropionic acid-induced
neurotoxicity. Methods Find Exp Clin Pharmacol. 2007;29:19–25.
103. Kundu S, Biswas TK, Das P, et al. Turmeric (Curcuma longa) rhizome
paste and honey show similar wound healing potential: a preclinical study
in rabbits. Int J Low Extrem Wounds. 2005;4:205–13.
104. Kuttan R, Sudheeran PC, Josph CD. Turmeric and curcumin as topical
agents in cancer therapy. Tumori. 1987;73:29–31.
105. Lal B, Kapoor AK, Asthana OP, et al. Efficacy of curcumin in the management
of chronic anterior uveitis. Phytother Res. 1999;13:318–22.
800 Curcuma longa L.

106. Lantz RC, Chen GJ, Solyom AM, et al. The effect of turmeric extracts on
inflammatory mediator production. Phytomedicine. 2005;12:445–52.
107. Lee GH, Lee HY, Choi MK, et al. Protective effect of Curcuma longa L.
extract on CCl4-induced acute hepatic stress. BMC Res Notes. 2017;10:77.
108. Lee HS, Li L, Kim HK, et al. The protective effects of Curcuma longa
Linn. extract on carbon tetrachloride-induced hepatotoxicity in rats via
upregulation of Nrf2. J Microbiol Biotechnol. 2010;20:1331–8.
109. Lekshmi PC, Arimboor R, Indulekha PS, Menon AN. Turmeric (Curcuma
longa L.) volatile oil inhibits key enzymes linked to type 2 diabetes. Int J
Food Sci Nutr. 2012;63:832–4.
110. Lekshmi PC, Arimboor R, Raghu KG, Menon AN. Turmerin, the
antioxidant protein from turmeric (Curcuma longa) exhibits antihypergly-
caemic effects. Nat Prod Res. 2012;26:1654–8.
111. Li L, Fu S, Qing S. Effect of growth period, storage time and varieties on
the contents of main active constituents of Curcuma longa L. in rhizome.
Zhongguo Zhong Yao Za Zhi. 1999;24:589–90, 637 (Chinese).
112. Li L, Zhang Y. Effects of cultivating measures on rhizome yield and some
main active constituents of Curcuma longa L. Zhongguo Zhong Yao Za
Zhi. 1999;24:531–3, 574 (Chinese).
113. Li W, Feng JT, Xiao YS, et al. Three novel terpenoids from the rhizomes
of Curcuma longa. J Asian Nat Prod Res. 2009;11:569–75.
114. Liju VB, Jeena K, Kuttan R. Acute and subchronic toxicity as well as
mutagenic evaluation of essential oil from turmeric (Curcuma longa L.).
Food Chem Toxicol. 2013;53:52–61.
115. Liju VB, Jeena K, Kuttan R. An evaluation of antioxidant, anti-inflammatory,
and antinociceptive activities of essential oil from Curcuma longa. L. Indian J
Pharmacol. 2011;43:526–31.
116. Limtrakul P, Lipigorngoson S, Namwong O, et al. Inhibitory effect of dietary
curcumin on skin carcinogenesis in mice. Cancer Lett. 1997;116:197–203.
117. Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa
extract in the treatment of painful knee osteoarthritis: a randomized
placebo-controlled trial. Inflammopharmacology. 2013;21:129–36.
118. Madkor HR, Mansour SW, Ramadan G. Modulatory effects of garlic, ginger,
turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative
stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr. 2011;105:
1210–7.
119. Mahady GB, Pendland SL, Yun G, Lu ZZ. Turmeric (Curcuma longa) and
curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen.
Anticancer Res. 2002;22:4179–81.
120. Marasini BP, Baral P, Aryal P, et al. Evaluation of antibacterial activity of
some traditionally used medicinal plants against human pathogenic
bacteria. Biomed Res Int. 2015;2015:265425.
121. Mazumder A, Raghavan K, Weinstein J, et al. Inhibition of human
immunodeficiency virus type-1 integrase by curcumin. Biochem Pharmacol.
1995;49:1165–70.
Curcuma longa L. 801

122. Mehra KS, Mikuni I, Gupta U, Gode KD. Curcuma longa (Linn.) drops in
corneal wound healing. Tokai J Exp Clin Med. 1984;9:27–31.
123. Mehta K, Pantazis P, McQueen T, Aggarwal BB. Antiproliferative effect
of curcumin (diferuloylmethane) against human breast tumor cell lines.
Anticancer Drugs. 1997;8:470–81.
124. Micucci M, Aldini R, Cevenini M et al. Curcuma longa L. as a therapeutic
agent in intestinal motility disorders. 2: Safety profile in mouse. PLoS One.
2013;8:e80925.
125. Mishra RK, Singh SK. Reversible antifertility effect of aqueous rhizome
extract of Curcuma longa L. in male laboratory mice. Contraception.
2009;79:479–87.
126. Moghadam AR, Tutunchi S, Namvaran-Abbas-Abad A, et al. Preadmin-
istration of turmeric prevents methotrexate-induced liver toxicity and
oxidative stress. BMC Complement Altern Med. 2015;15:246.
127. Mohamad RH, El-Bastawesy AM, Zekry ZK, et al. The role of Curcuma
longa against doxorubicin (adriamycin)-induced toxicity in rats. J Med
Food. 2009;12:394–402.
128. Mohankumar S, McFarlane JR. An aqueous extract of Curcuma longa
(turmeric) rhizomes stimulates insulin release and mimics insulin action on
tissues involved in glucose homeostasis in vitro. Phytother Res. 2011;25:
396–401.
129. Mohanty I, Arya DS, Gupta SK. Effect of Curcuma longa and Ocimum
sanctum on myocardial apoptosis in experimentally induced myocardial
ischemic-reperfusion injury. BMC Complement Altern Med. 2006;6:3.
130. Mohanty I, Singh Arya D, Dinda A, et al. Protective effects of Curcuma
longa on ischemia-reperfusion induced myocardial injuries and their
mechanisms. Life Sci. 2004;75:1701–11.
131. Monsey MS, Gerhard DM, Boyle LM, et al. A diet enriched with curcumin
impairs newly acquired and reactivated fear memories. Neuropsychophar-
macology. 2015;40:1278–88.
132. Mun SH, Joung DK, Kim YS, et al. Synergistic antibacterial effect of curcumin
against methicillin-resistant Staphylococcus aureus. Phytomedicine. 2013;
20:714–8.
133. Mythri RB, Veena J, Harish G, et al. Chronic dietary supplementation with
turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-
mediated neurotoxicity in vivo: implications for Parkinson’s disease. Br J
Nutr. 2011;106:63–72.
134. Nada AS, Hawas AM, Amin Nel-D, et al. Radioprotective effect of
Curcuma longa extract on c-irradiation-induced oxidative stress in rats.
Can J Physiol Pharmacol. 2012;90:415–23.
135. Ng TP, Chiam PC, Lee T, et al. Curry consumption and cognitive function
in the elderly. Am J Epidemiol. 2006;164:898–906.
802 Curcuma longa L.

136. Nilani P, Duraisamy B, Dhamodaran P, et al. Effect of selected

antiasthmatic plant constituents against microorganism causing upper
respiratory tract infection. Anc Sci Life. 2010;29:30–2.
137. Nishiyama T, Mae T, Kishida H, et al. Curcuminoids and sesquiterpenoids
in turmeric (Curcuma longa L.) suppress an increase in blood glucose level
in type 2 diabetic KK-Ay mice. J Agric Food Chem. 2005;53:959–63.
138. Oh SW, Cha JY, Jung JE, et al. Curcumin attenuates allergic airway
inflammation and hyperresponsiveness in mice through NF-jB inhibition.
J Ethnopharmacol. 2011;136:414–21.
139. Ojha RP, Rastogi M, Devi BP, et al. Neuroprotective effect of curcuminoids
against inflammation-mediated dopaminergic neurodegeneration in the
MPTP model of Parkinson’s disease. J Neuroimmune Pharmacol. 2012;
7:609–18.
140. Okazaki Y, Iqbal M, Okada S. Suppressive effects of dietary curcumin on
the increased activity of renal ornithine decarboxylase in mice treated with
a renal carcinogen, ferric nitrilotriacetate. Biochim Biophys Acta. 2005;
1740:357–66.
141. Oner-İyidoğan Y, Koçak H, Seyidhanoğlu M, et al. Curcumin prevents
liver fat accumulation and serum fetuin-A increase in rats fed a high-fat
diet. J Physiol Biochem. 2013;69:677–86.
142. Pakfetrat M, Basiri F, Malekmakan L, Roozbeh J. Effects of turmeric on
uremic pruritus in end stage renal disease patients: a double-blind
randomized clinical trial. J Nephrol. 2014;27:203–7.
143. Pari L, Amali DR. Protective role of tetrahydrocurcumin (THC) an active
principle of turmeric on chloroquine induced hepatotoxicity in rats.
J Pharm Pharm Sci. 2005;8:115–23.
144. Pari L, Murugan P. Changes in glycoprotein components in streptozo-
tocin–nicotinamide induced type 2 diabetes: influence of tetrahydrocur-
cumin from Curcuma longa. Plant Foods Hum Nutr. 2007;62:25–9.
145. Park C, Moon DO, Choi IW, et al. Curcumin induces apoptosis and
inhibits prostaglandin E(2) production in synovial fibroblasts of patients
with rheumatoid arthritis. Int J Mol Med. 2007;20:365–72.
146. Polasa K, Raghuram TC, Krishna TP, Krishnaswamy K. Effect of turmeric
on urinary mutagens in smokers. Mutagenesis. 1992;7:107–9.
147. Polasa K, Sesikaran B, Krishna TP, Krishnaswamy K. Turmeric (Curcuma
longa)-induced reduction in urinary mutagens. Food Chem Toxicol. 1991;
29:699–706.
148. Pongchaidecha A, Lailerd N, Boonprasert W, Chattipakorn N. Effects of
curcuminoid supplement on cardiac autonomic status in high-fat-induced
obese rats. Nutrition. 2009;25:870–8.
149. Prakash P, Misra A, Surin WR, et al. Antiplatelet effects of Curcuma oil in
experimental models of myocardial ischemia-reperfusion and thrombosis.
Thromb Res. 2011;127:111–8.
Curcuma longa L. 803

150. Prasad NS, Raghavendra R, Lokesh BR, Naidu KA. Spice phenolics
inhibit human PMNL 5-lipoxygenase. Prostaglandins Leukot Essent Fatty
Acids. 2004;70:521–8.
151. Prucksunand C, Indrasukhsri B, Leethochawalit M, Hungspreugs K.
Phase II clinical trial on effect of the long turmeric (Curcuma longa Linn.)
on healing of peptic ulcer. Southeast Asian J Trop Med Public Health.
2001;32:208–15.
152. Purohit A. Antifertility efficacy of Curcuma longa (50% EtOH extract)
with special reference to serum biochemistry and fertility test. Anc Sci
Life. 1999;18:192–4.
153. Pyrzanowska J, Piechal A, Blecharz-Klin K, et al. The influence of the long-term
administration of Curcuma longa extract on learning and spatial memory as
well as the concentration of brain neurotransmitters and level of plasma
corticosterone in aged rats. Pharmacol Biochem Behav. 2010;95:351–8.
154. Pyun CW, Han KH, Hong GE, Lee CH. Effect of curcumin on the increase
in hepatic or brain phosphatidylcholine hydroperoxide levels in mice after
consumption of excessive alcohol. Biomed Res Int. 2013;2013:242671.
155. Quiles JL, Mesa MD, Ramírez-Tortosa CL, et al. Curcuma longa extract
supplementation reduces oxidative stress and attenuates aortic fatty streak
development in rabbits. Arterioscler Thromb Vasc Biol. 2002;22:1225–31.
156. Qureshi S, Shah AH, Ageel AM. Toxicity studies on Alpinia galanga and
Curcuma longa. Planta Med. 1992;58:124–7.
157. Rai PK, Jaiswal D, Mehta S, et al. Effect of Curcuma longa freeze dried
rhizome powder with milk in STZ induced diabetic rats. Indian J Clin
Biochem. 2010;25:175–81.
158. Rainey-Smith SR, Brown BM, Sohrabi HR, et al. Curcumin and cognition: a
randomised, placebo-controlled, double-blind study of community-dwelling
older adults. Br J Nutr. 2016;115:2106–13.
159. Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VP. Neuropro-
tective role of curcumin from Curcuma longa on ethanol-induced brain
damage. Phytother Res. 1999;13:571–4.
160. Rajakrishnan V, Jayadeep A, Arun OS, et al. Changes in the prostaglandin
levels in alcohol toxicity: effect of curcumin and N-acetylcysteine. J Nutr
Biochem. 2000;11:509–14.
161. Ram A, Das M, Ghosh B. Curcumin attenuates allergen-induced airway
hyperresponsiveness in sensitized guinea pigs. Biol Pharm Bull. 2003;26:
1021–4.
162. Ramadan G, Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and anti-
oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale
(ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation. 2011;
34:291–301.
163. Ramirez Bosca A, Carrión Gutierrez MA, Soler A, et al. Effects of the
antioxidant turmeric on lipoprotein peroxides: implications for the
prevention of atherosclerosis. Age (Omaha). 1997;20:165–8.
164. Ramírez-Tortosa MC, Mesa MD, Aguilera MC, et al. Oral administration of a
turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects
in rabbits with experimental atherosclerosis. Atherosclerosis. 1999;147:371–8.
804 Curcuma longa L.

165. Ramsewak RS, DeWitt DL, Nair MG. Cytotoxicity, antioxidant and
anti-inflammatory activities of curcumins I-III from Curcuma longa.
Phytomedicine. 2000;7:303–8.
166. Rasyid A, Rahman AR, Jaalam K, Lelo A. Effect of different curcumin
dosages on human gall bladder. Asia Pac J Clin Nutr. 2002;11:314–8.
167. Reddy AC, Lokesh BR. Effect of dietary turmeric (Curcuma longa) on
iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol. 1994;
32:279–83.
168. Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimer’s
disease: tolerability and efficacy in a 24-week randomized, double blind,
placebo-controlled study. Alzheimers Res Ther. 2012;4:43.
169. Rong S, Zhao Y, Bao W, et al. Curcumin prevents chronic alcohol-induced
liver disease involving decreasing ROS generation and enhancing
antioxidative capacity. Phytomedicine. 2012;19:545–50.
170. Rukkumani R, Aruna K, Varma PS, et al. Comparative effects of curcumin
and its analog on alcohol- and polyunsaturated fatty acid-induced
alterations in circulatory lipid profiles. J Med Food. 2005;8:256–60.
171. Rungseesantivanon S, Thenchaisri N, Ruangvejvorachai P, Patumraj S.
Curcumin supplementation could improve diabetes-induced endothelial
dysfunction associated with decreased vascular superoxide production and
PKC inhibition. BMC Complement Altern Med. 2010;10:57.
172. Salama SM, Abdulla MA, AlRashdi AS, et al. Hepatoprotective effect of
ethanolic extract of Curcuma longa on thioacetamide induced liver
cirrhosis in rats. BMC Complement Altern Med. 2013;13:56.
173. Sengupta M, Sharma GD, Chakraborty B. Hepatoprotective and
immunomodulatory properties of aqueous extract of Curcuma longa in
carbon tetrachloride intoxicated Swiss albino mice. Asian Pac J Trop
Biomed. 2011;1:193–9.
174. Seo SW, Bae GS, Kim SG, et al. Protective effects of Curcuma longa
against cerulein-induced acute pancreatitis and pancreatitis-associated lung
injury. Int J Mol Med. 2011;27:53–61.
175. Sethi P, Jyoti A, Hussain E, Sharma D. Curcumin attenuates aluminium-
induced functional neurotoxicity in rats. Pharmacol Biochem Behav.
2009;93:31–9.
176. Shah BH, Nawaz Z, Pertani SA, et al. Inhibitory effect of curcumin, a food
spice from turmeric, on platelet-activating factor- and arachidonic
acid-mediated platelet aggregation through inhibition of thromboxane
formation and Ca2+ signaling. Biochem Pharmacol. 1999;58:1167–72.
177. Shalini VK, Srinivas L. Lipid peroxide induced DNA damage: protection
by turmeric (Curcuma longa). Mol Cell Biochem. 1987;77:3–10.
178. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmaco-
dynamics of curcumin. Adv Exp Med Biol. 2007;595:453–70 (Review).
179. Sharma S, Kulkarni SK, Chopra K. Curcumin, the active principle of
turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clin
Exp Pharmacol Physiol. 2006;33:940–5.
Curcuma longa L. 805

180. Sidhu GS, Mani H, Gaddipati JP, et al. Curcumin enhances wound healing
in streptozotocin induced diabetic rats and genetically diabetic mice.
Wound Repair Regen. 1999;7:362–74.
181. Sidhu GS, Singh AK, Thaloor D, et al. Enhancement of wound healing by
curcumin in animals. Wound Repair Regen. 1998;6:167–77.
182. Singh G, Kapoor IP, Singh P, et al. Comparative study of chemical
composition and antioxidant activity of fresh and dry rhizomes of turmeric
(Curcuma longa Linn.). Food Chem Toxicol. 2010;48:1026–31.
183. Sompamit K, Kukongviriyapan U, Nakmareong S, et al. Curcumin
improves vascular function and alleviates oxidative stress in nonlethal
lipopolysaccharide-induced endotoxaemia in mice. Eur J Pharmacol. 2009;
616:192–9.
184. Song EK, Cho H, Kim JS, et al. Diarylheptanoids with free radical
scavenging and hepatoprotective activity in vitro from Curcuma longa.
Planta Med. 2001;67:876–7.
185. Srinivas L, Shalini VK, Shylaja M. Turmerin: a water soluble antioxidant
peptide from turmeric [Curcuma longa]. Arch Biochem Biophys 1992;292:
617–23.
186. Srivastava KC, Bordia A, Verma SK. Curcumin, a major component of
food spice turmeric (Curcuma longa) inhibits aggregation and alters
eicosanoid metabolism in human blood platelets. Prostaglandins Leukot
Essent Fatty Acids. 1995;52:223–7.
187. Srivastava KC. Extracts from two frequently consumed spices—cumin
(Cuminum cyminum) and turmeric (Curcuma longa)—inhibit platelet
aggregation and alter eicosanoid biosynthesis in human blood platelets.
Prostaglandins Leukot Essent Fatty Acids. 1989;37:57–64.
188. Srivastava S, Saksena AK, Khattri S, Kumar S, Dagur RS. Curcuma longa
extract reduces inflammatory and oxidative stress biomarkers in osteoarthri-
tis of knee: a four-month, double-blind, randomized, placebo-controlled
trial. Inflammopharmacology. 2016;24:377–88.
189. Suresh Babu P, Srinivasan K. Amelioration of renal lesions associated with
diabetes by dietary curcumin in streptozotocin diabetic rats. Mol Cell
Biochem. 1998;181:87–96.
190. Suryanarayana P, Satyanarayana A, Balakrishna N, et al. Effect of turmeric
and curcumin on oxidative stress and antioxidant enzymes in streptozotocin-
induced diabetic rat. Med Sci Monit. 2007;13:BR286–92.
191. Suryanarayana P, Saraswat M, Mrudula T, et al. Curcumin and turmeric
delay streptozotocin-induced diabetic cataract in rats. Invest Ophthalmol
Vis Sci. 2005;46:2092–9.
192. Taty Anna K, Elvy Suhana MR, Das S, et al. Anti-inflammatory effect of
Curcuma longa (turmeric) on collagen-induced arthritis: an anatomico-
radiological study. Clin Ter. 2011;162:201–7.
193. Thongson C, Davidson PM, Mahakarnchanakul W, Vibulsresth P. Antimi-
crobial effect of Thai spices against Listeria monocytogenes and Salmonella
typhimurium DT104. J Food Prot. 2005;68:2054–8.
806 Curcuma longa L.

194. Tilak JC, Banerjee M, Mohan H, Devasagayam TP. Antioxidant avail-

ability of turmeric in relation to its medicinal and culinary uses. Phytother
Res. 2004;18:798–804.
195. Tranchida F, Shintu L, Rakotoniaina Z, et al. Metabolomic and lipidomic
analysis of serum samples following Curcuma longa extract supplementation
in high-fructose and saturated fat fed rats. PLoS One. 2015;10:e0135948.
196. Troselj KG, Kujundzic RN. Curcumin in combined cancer therapy. Curr
Pharm Des. 2014;20:6682–96.
197. Um MY, Hwang KH, Ahn J, Ha TY. Curcumin attenuates diet-induced
hepatic steatosis by activating AMPK. Basic Clin Pharmacol Toxicol.
2013;113:152–7.
198. Van Dau N, Ham NN, Khac DH, et al. The effects of a traditional drug,
turmeric (Curcuma longa), and placebo on the healing of duodenal ulcer.
Phytomedicine. 1998;5:29–34.
199. Vidal B, Vázquez-Roque RA, Gnecco D, et al. Curcuma treatment
prevents cognitive deficit and alteration of neuronal morphology in the
limbic system of aging rats. Synapse. 2017;71.
200. Vlahović P, Cvetković T, Savić V, Stefanović V. Dietary curcumin does
not protect kidney in glycerol-induced acute renal failure. Food Chem
Toxicol. 2007;45:1777–82.
201. Wang LY, Zhang M, Zhang CF, Wang ZT. Alkaloid and sesquiterpenes
from the root tuber of Curcuma longa. Yao Xue Xue Bao. 2008;43:724–7.
202. Wang NP, Wang ZF, Tootle S, et al. Curcumin promotes cardiac repair and
ameliorates cardiac dysfunction following myocardial infarction. Br J
Pharmacol. 2012;167:1550–62.
203. Wang R, Xu Y, Wu HL, et al. The antidepressant effects of curcumin in the
forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol.
2008;578:43–50.
204. Wang SY, Xue J, Zhou J. Preliminary effects of alcohol and Curcuma
longa upon CYP2E1 and hematotoxicity in benzene-induced mice.
Zhonghua Yi Xue Za Zhi. 2009;89:2429–31 (Chinese).
205. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, et al. Screening of
antioxidants from medicinal plants for cardioprotective effect against
doxorubicin toxicity. Basic Clin Pharmacol Toxicol. 2005;96:80–7.
206. Wickenberg J, Ingemansson SL, Hlebowicz J. Effects of Curcuma longa
(turmeric) on postprandial plasma glucose and insulin in healthy subjects.
Nutr J. 2010;9:43.
207. Witkin JM, Li X. Curcumin, an active constiuent of the ancient medicinal herb
Curcuma Longa L.: some uses and the establishment and biological basis of
medical efficacy. CNS Neurol Disord Drug Targets. 2013;12:487–97.
208. Wongcharoen W, Jai-Aue S, Phrommintikul A, et al. Effects of curcum-
inoids on frequency of acute myocardial infarction after coronary artery
bypass grafting. Am J Cardiol. 2012;110:40–4.
209. Wu SJ, Tam KW, Tsai YH, et al. Curcumin and saikosaponin A inhibit
chemical-induced liver inflammation and fibrosis in rats. Am J Chin Med.
2010;38:99–111.
Curcuma longa L. 807

210. Wuthi-udomlert M, Grisanapan W, Luanratana O, Caichompoo W.

Antifungal activity of Curcuma longa grown in Thailand. Southeast
Asian J Trop Med Public Health. 2000;31 Suppl 1:178–82.
211. Xia X, Cheng G, Pan Y, et al. Behavioral, neurochemical and neuroen-
docrine effects of the ethanolic extract from Curcuma longa L. in the
mouse forced swimming test. J Ethnopharmacol. 2007;110:356–63.
212. Xia X, Pan Y, Zhang WY, et al. Ethanolic extracts from Curcuma longa
attenuates behavioral, immune, and neuroendocrine alterations in a rat
chronic mild stress model. Biol Pharm Bull. 2006;29:938–44.
213. Xu Y, Ku B, Tie L, et al. Curcumin reverses the effects of chronic stress on
behavior, the HPA axis, BDNF expression and phosphorylation of CREB.
Brain Res. 2006;1122:56–64.
214. Xu Y, Ku BS, Yao HY, et al. Antidepressant effects of curcumin in the
forced swim test and olfactory bulbectomy models of depression in rats.
Pharmacol Biochem Behav. 2005;82:200–6.
215. Xu Y, Ku BS, Yao HY, et al. The effects of curcumin on depressive-like
behaviors in mice. Eur J Pharmacol. 2005;518:40–6.
216. Yan LG, Ruan JS, Zhang L, et al. Effect of aqueous extracts of several
kinds of herbs on human platelet aggregation and expression of P-selectin
in vitro. Chin J Integr Med. 2015;21:286–90.
217. Yiu WF, Kwan PL, Wong CY, et al. Attenuation of fatty liver and
prevention of hypercholesterolemia by extract of Curcuma longa through
regulating the expression of CYP7A1, LDL-receptor, HO-1, and HMG-CoA
reductase. J Food Sci. 2011;76:H80–9.
218. Yu SY, Gao R, Zhang L, et al. Curcumin ameliorates ethanol-induced
memory deficits and enhanced brain nitric oxide synthase activity in mice.
Prog Neuropsychopharmacol Biol Psychiatry. 2013;44C:210–6.
219. Yu WG, Xu G, Ren GJ, et al. Preventive action of curcumin in experimental
acute pancreatitis in mouse. Indian J Med Res. 2011;134:717–24.
220. Yu ZF, Kong LD, Chen Y. Antidepressant activity of aqueous extracts of
Curcuma longa in mice. J Ethnopharmacol. 2002;83:161–5.
221. Zeng Y, Qiu F, Takahashi K, et al. New sesquiterpenes and calebin derivatives
from Curcuma longa. Chem Pharm Bull (Tokyo). 2007;55:940–3.
222. Zhao X, Xu Y, Zhao Q, et al. Curcumin exerts antinociceptive effects in a
mouse model of neuropathic pain: descending monoamine system and opioid
receptors are differentially involved. Neuropharmacology. 2012;62:843–54.
223. Zingg JM, Hasan ST, Meydani M. Molecular mechanisms of hypolipi-
demic effects of curcumin. Biofactors. 2013;39:101–21.
Curcuma zedoaria (Christm.) Roscoe.
(Zingiberaceae)

(Syns.: C. malabarica Velay. Amalraj & Mural.; C. pallida Lour.; C. raktakanta

Mangaly & M. Sabu; Amomum latifolium Lam.; A. zedoaria Christm.; Costus luteus
Blanco; C. nigricans Blanco; Erndlia zerumbet Giseke; Roscoea nigrociliata Hassk.)

Abstract
It is a perennial herb, that grows in East Indies, India, China, Indonesia and other
countries. It could be the 4th type of Jadwár of Ibn Sina (Avicenna) that Dymock
et al. referred to in their book Pharmacographia Indica. They also described it as
“the Sati and Krachura of Sanskrit writers, and the Zerumbád and Urúk-el-káfúr,
“camphor root” of the Arabians.” Fresh rhizome is considered cooling and diuretic,
and a remedy for leucorrheal and gonorrheal discharges, and as a blood purifier. In
Sri Lanka, the rhizome is used as tonic and carminative, while the Arabs considered
it a tonic and aphrodisiac.XXXVI At one time, the Dispensatory of the United States
mentioned it as a gastrointestinal stimulant in flatulent colic and other digestive
disorders. In China, it is known as E’Zhu but the rhizomes from C. aromatica are
also called E’Zhu. It is considered pungent, bitter and “warm;” and is credited with
‘vital-energy-stimulant,’ ‘stasis-deobstruent,’ digestant and analgesic properties,
and mainly used in the treatment of distention and abdominal pain associated with
dyspepsia, abdominal pain due to blood stasis, hepatomegaly, splenomegaly,
amenorrhea due to blood stasis, and wounds and injuries. Hsu named it O-chu, a
digestant that dispels stagnant blood and smooth the “Qi.” However, despite its
widespread traditional use, it is contraindicated during pregnancy. In Japan, it has
traditionally been used to treat gastrointestinal diseases as an aromatic and
stomachic drug, and is currently used to treat alcohol-induced loss of appetite and
nausea. In Bulacan Province of the Philippines, fresh rhizomes are burnt and the
ash is applied to wounds, ulcers and sprains. Also, the juice of fresh rhizomes is
used effectively for certain forms of dermatitis and topically applied to stomach as
stomachic. Major components isolated from the rhizomes include zedoarone,
curdione, neocurdione, curzeone, aerugidiol, epicurcumol, curzerene, pyrocur-
cuzerenone, curcumin, curcumenol, curcumenone, zedoaronediol, dehydrocur-
dione, furanodienone, furanodiene, zederone, comosone II, zerumin A,

© Springer Nature Switzerland AG 2020 809

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_84
810 Curcuma zedoaria (Christm.) Roscoe.

curcumanolide A, curcuzedoalide, and calcaratarin A. Consumption of an herbal

tea by low to moderately hypercholesterolemic Pakistani patients for two months
lowered body weight, BMI, TC, LDL-C, and TGs, and increased HDL-C.

Keywords
Cedoaria
Çevdar
E’zhu
Gadwâr
Jadwar khatta
Kachoor
Shati

Zedoária
Zedoary
Zitwer

Vernaculars: Urd.: Jadwar khatta, Kachoor; Hin.: Gantamasti, Kachura, Kacura,

Kakhur, Kalihaldi, Shoti; San.: Dravida, Kalpaka, Krachura, Sati, Shati, Ved-
hamukhya; Ben.: Aam aadaa (Mango ginger), Ekangi, Kachura, Sali, Sari, Sati,
Shori, Sutha, Suthi; Mal.: Adavikachhola, Kacholam, Kachuri-kizhanna, Pula-
kizhanna; Mar.: Kachora, Kachura; Tam.: Kastori-manjal, karppurakkiccilikki-
langku, Kichili, Kichilic-kizhanga, Kichilick-kizhangu, Kichiliki, Kizhangu, Nir-
visham, Poolankilangu, Pulan-kizhanga; Tel.: Kachoeramu, Kachoram, Kachoramu,
Kacōramu, Kichili-gadda, Kichili-gaddalu, Kushthuri pasupu; Ara.: Gadwâr, Sat-
wâl, Uruk-el-kafur, Zadwâr, Zerumbad, Zerumbet; Bur.: Thanu-wen; Chi.: E’shu,
E’zhu, Yu jin; Dan.: Zedoar; Dut.: Zedoar, Zedoarwortel; Eng.: Indian arrowroot,
Round zedoary, White turmeric, Zedoary; Fre.: Gingembre bâtard, Rhizome de
Zédoaire, Zédoaire; Ger.: Zedoarwurzel, Zittwer kurkume Zitwer; Ind.: Kunir putih,
Temu; Ita.: Radice di curcuma, Zedoaria, Zedoaria lunga; Maly.: Temu kuning,
Temu putih; Nep.: Kacur; Per.: Jadvar khatta, Kazhur; Por.: Zedoária; Rus.:
Kurkuma zedoarskaia; Spa.: Cedoaria, Cetoal; Tag.: Barak, Bolon, Luya-luyahan,
Tamahiba, Tamo, Tamokansi; Tha.: Khamin hua khuen, Khamin khao, Khamin
khun, Khamin oi; Tur.: Çevdar, Gulpa hamar; Vie.: Bông truât, Ngái tim, Nga truât,
Tam nai.
Description: It is a perennial herb, that grows in East Indies, India, China,
Indonesia and other countries. The rhizome is tuberous like that of Curcuma longa,
fleshy, aromatic, and of pale-yellow color, and has been described as: “The round
Zedoary is externally greyish-white, heavy, compact, grey, and often horny inter-
nally, having a bitter and strongly camphoraceous taste, like that of the long
Zedoary, which it also resembles in odor. The plant blossoms in the hot weather,
just before the rains, when the first leaves begin to appear.”XL It should not be
confused with real Jadwar, the Delphinium denudatum (Figs. 1 and 2).
Actions and Uses: It could be the 4th type of Jadwár of Ibn Sina (Avicenna) that
Dymock et al.XL referred to in their book Pharmacographia Indica. They also
described it as “the Sati and Krachura of Sanskrit writers, and the Zerumbád and
Urúk-el-káfúr, “camphor root” of the Arabians.” Fresh rhizome is considered
cooling and diuretic, and a remedy for leucorrheal and gonorrheal discharges, and
as a blood purifier.LXXXIV Khory and KatrakLXXXI described it as carminative,
rubefacient, diuretic, and stimulant, and its use in gonorrhea, menorrhagia and
kidney complaints; and NadkarniCV mentioned the root useful in flatulence and
dyspepsia, and as a corrector of purgatives. In Ayurveda, dried rhizome is used in
Curcuma zedoaria (Christm.) Roscoe. 811

Fig. 1 Curcuma zedoaria, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Curcuma_zedoaria_-_K%C3%B6hler
%E2%80%93s_Medizinal-Pflanzen-048.jpg

Fig. 2 Curcuma zedoaria, Plant, David J. Stang, WikimediaCommons; ShareAlike 4.0 Interna-
tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Curcuma_zedoaria_15zz.jpg;
https://creativecommons.org/licenses/by-sa/4.0/deed.en
812 Curcuma zedoaria (Christm.) Roscoe.

the treatment of arsa, gulma, hikka, svasa, kasa, kustha, jvara, vrana, pliharoga,
glaganda, and krmi.CXXVII GhaniL mentions it (temperament, hot 2° and dry 2°) as
anthelmintic, appetizer, relieves dyspnea and is beneficial for cough. He also ref-
erenced Vaids that it disinfects urine, and relieves burning of palms and soles of
feet. In Sri Lanka, the rhizome is used as tonic and carminative, while the Arabs
considered it a tonic and aphrodisiac.XXXVI At one time, the Dispensatory of the
United States mentioned it as a gastrointestinal stimulant in flatulent colic and other
digestive disorders (The Dispensatory, 1926). In China, it is known as E’Zhu but
the rhizomes from C. aromatica are also called E’Zhu. It is considered pungent,
bitter and “warm;” and is credited with ‘vital-energy-stimulant,’ ‘stasis-
deobstruent,’ digestant and analgesic properties, and mainly used in the treatment
of distention and abdominal pain associated with dyspepsia, abdominal pain due to
blood stasis, hepatomegaly, splenomegaly, amenorrhea due to blood stasis, and
wounds and injuries.XVIII HsuLXVI named it O-chu, a digestant that dispels stagnant
blood and smooth the “Qi.” However, despite its widespread traditional use, it is
contraindicated during pregnancy [4]. In Japan, it has traditionally been used to
treat gastrointestinal diseases as an aromatic and stomachic drug, and is currently
used to treat alcohol-induced loss of appetite and nausea [20]. In Bulacan Province
of the Philippines, fresh rhizomes are burnt and the ash is applied to wounds, ulcers
and sprains. Also, the juice of fresh rhizomes is used effectively for certain forms of
dermatitis and topically applied to stomach as stomachic.CXVII
Phytoconstituents: It contains 1–2.5% volatile oil, mainly composed of sesquiter-
penes; the oil contains more than 30 components. Major components isolated from the
rhizomes include curzerenone (zedoarone), curdione (PGE2 and COX-2 inhibitor),
neocurdione, curzeone, aerugidiol, epicurcumol, curzerene, pyrocurcuzerenone,
curcumin, curcumol (curcumenol), isocurcuminol, curcumenone, zedoaronediol,
procurcumenol, dehydrocurdione, furanodienone, isofuranodienone, furanodiene,
zederone, comosone II, zerumin A, isoprocurcumenol, curcumanolide A, curcuze-
doalide, calcaratarin A, 13-hydroxygermacrone, labda-8(17),12 diene-15,16dial,
curcolone, ermanin, zerumbone epoxide, stigmast-4-en-3,6-dione, stigmasta-4,22-
dien-3,6-dione, 9-isopropylidene-2,6-dimethyl-11-oxatricyclo [6.2.1.0(1,5)] undec-6-
en-8-ol, germacrone-4,5-epoxide, germacrone-1,10-epoxide, germacrone, and gwei-
curculactone [1, 3, 24, 25], strong PGE2 and NO synthesis inhibitors: ar-turmerone
and b-turmerone [10, 11], and a strong antifungal agent, ethyl p-methoxycinnamate
[8]. Two sesquiterpenoids: 13-hydroxycurzerenone and 1-oxocurzerenone were iso-
lated by Chen et al. [3]. However, Hou et al. [13] reported that curcumin is isolated
from rhizomes of many Curcuma species except C. zedoaria. The amount of ter-
penoids with analgesic property, curcumenol and dihydrocurdione, vary with seasons,
and is three times higher in the mother rhizome in autumn samples than in other
seasons [28]. The amount of major antioxidants b-carotene, ascorbic acid, and total
polyphenols is similar in both methanol and aqueous extracts; however, the cucumi-
noids content are far higher in methanol extract than in the aqueous extract [29].
Curdione and curcumol are antineoplastic agents; whereas furanodiene and
Curcuma zedoaria (Christm.) Roscoe. 813

furanodienone show significant anti-inflammatory activity [24]. Curcolone, ermanin,

13-hydroxycurzerenone, and curcumin potently inhibit AA-induced platelet
aggregation [3]. Curdione is reported as a major component in Chinese traditional herb
E’Zhu, but no curdione was found in the herb collected from Guangdong province
[37].
Pharmacology: Supplementation of diet with 3% rhizomes significantly decreased
systolic BP, increased ACh-induced endothelium-dependent vasorelaxation, and
significantly reduced blood viscosity of SHRs [7]. The rhizomes contain EO,
curcuminoid and other effective constituents with antiplatelet aggregation, blood
lipids-lowering, antioxidation and anti-inflammatory activities. Due to its effects on
vascular endothelial cells and smooth muscle cells, it has been applied in
drug-eluting stents to prevent in-stent restenosis and thrombogenesis [5]. The
Zedoary Turmeric Oil-eluting stent significantly inhibited growth of neointimal in
canine coronary, and prevented restenosis [36]. Ethanol rhizome extract exhibited
highly significant analgesic and anti-inflammatory activities [33]; and crude
methanol extract significantly inhibited TNF-a [17], NO synthesis in activated
macrophages [16], and potently inhibited COX-2 and iNOS activities [9, 23, 27].
Curcumenol has been identified as the active constituent exhibiting analgesic
activity [26]. Furanodiene, germacrone, curdione, neocurdione, curcumenol, isocur-
cumenol, aerugidiol, zedoarondiol, curcumenone and curcumin are reported as
potent hepatoprotective against D-galactosamine/lipopolysaccharide-induced acute
liver toxicity in mice [25].
Various extracts of rhizomes exhibited antitumor, genotoxic, anticlastogenic,
anticancer, cytotoxic, antimutagenic [12, 19, 22], and antimicrobial [15, 21, 34]
activities. Petroleum ether extract inhibited proliferation of human triple nega-
tive breast cancer cells [6]. Essential oil acted synergistically with paclitaxel to
induce apoptosis in human ovarian cancer cells [38]. Curcuminoids, curcumin,
demethoxycurcumin and bisdemethoxycurcumin were cytotoxic to human ovarian
cancer cells [31], and a-curcumene inhibited proliferation of human ovarian cancer
cells [30]. Curcumenone and curcumenol induced apoptotic cell death of MCF-7
cells [1]. The EO shows in vitro and in vivo antiangiogenic activity, and suppresses
melanoma growth and lung metastasis [2, 4].
Petroleum ether and chloroform extracts exhibited antistress and antianxiety
effects, and improved mobility of arthritic rats [18]. The rhizome extracts decrease
alcohol-induced drunkenness and blood alcohol concentrations in mice, which has
been identified due to curcumenone, that decreases elevation of blood alcohol
concentrations through increased liver alcohol dehydrogenase activity [20].
Decoction of the rhizomes significantly increases duration and number of bursts of
action potentials of uterine smooth muscle, that are partially attenuated by atropine
and phentolamine [35].
Ethyl p-methoxycinnamate showed highly significant antifungal activity against
T. rubrum, A. niger, S. cerevisiae, E. floccosum, A. fumigatus, P. purpurogenum,
M. gypseum, C. miyabeanus (formerly H. oryzale, a fungus that causes brown spot
disease in rice), and F. oxysporum [8].
814 Curcuma zedoaria (Christm.) Roscoe.

Clinical Studies: Consumption of an herbal tea (prepared by boiling 1.5 g

powdered rhizome in 200 ml water for 5 min.) by low to moderately hyperc-
holesterolemic Pakistani patients for two months lowered body weight, BMI, TC,
LDL-C, and TGs, and increased HDL-C [32].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Petroleum ether, chloroform, and methanol extracts of roots,
obtained by successive extraction, were orally nontoxic to rats up to a single dose of
5,000 mg/kg [18].
CYP450 and Potential for Drug-Herb Interaction: Methanol extract of rhi-
zomes of Japanese origin significantly decreased in vitro activity of CYP3A4 by
about 85–98%, without any effect on CYP3A4 mRNA expression [14].
Commentary: Only one clinical study on its antidyslipidemic effect is reported.
However, the analgesic and anti-inflammatory activities, and preventive effect on
restenosis with Zedoary Turmeric Oil-eluting stent are of clinical interest for future
investigations.

References
1. Ahmed Hamdi OA, Syed Abdul Rahman SN, Awang K, et al. Cytotoxic
constituents from the rhizomes of Curcuma zedoaria. ScientificWorldJour-
nal. 2014;321943.
2. Chen CC, Chen Y, Hsi YT, et al. Chemical constituents and anticancer activity
of Curcuma zedoaria Roscoe essential oil against nonsmall cell lung
carcinoma cells in vitro and in vivo. J Agric Food Chem. 2013;61:11418–27.
3. Chen JJ, Tsai TH, Liao HR, et al. New sesquiterpenoids and antiplatelet
aggregation constituents from the rhizomes of Curcuma zedoaria. Molecules.
2016;21.
4. Chen W, Lu Y, Gao M, et al. Antiangiogenesis effect of essential oil from
Curcuma zedoaria in vitro and in vivo. J Ethnopharmacol. 2011;133:220–6.
5. Cui YY, Liu JG, Zhao FH, Shi DZ. Advances in studies on pharmacological
action of main chemical constituent of Curcuma Zedoary in preventing
in-stent restenosis. Zhongguo Zhong Yao Za Zhi. 2015;40:1230–4
(Chinese).
6. Gao XF, Li QL, Li HL, et al. Extracts from Curcuma zedoaria inhibit
proliferation of human breast cancer cell MDA-MB-231 in vitro. Evid
Based Complement Alternat Med. 2014;2014:730678.
7. Goto H, Sasaki Y, Fushimi H, et al. Effect of curcuma herbs on vasomotion
and hemorheology in spontaneously hypertensive rat. Am J Chin Med. 2005;
33:449–57.
8. Gupta SK, Banerjee AB, Achari B. Isolation of ethyl p-methoxycinnamate,
the major antifungal principle of Curcumba zedoaria. Lloydia. 1976;39:
218–22.
Curcuma zedoaria (Christm.) Roscoe. 815

9. Hong CH, Hur SK, Oh OJ, et al. Evaluation of natural products on

inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase
(iNOS) in cultured mouse macrophage cells. J Ethnopharmacol. 2002;83:
153–9.
10. Hong CH, Kim Y, Lee SK. Sesquiterpenoids from the rhizome of Curcuma
zedoaria. Arch Pharm Res. 2001;24:424–6.
11. Hong CH, Noh MS, Lee WY, Lee SK. Inhibitory effects of natural sesqui-
terpenoids isolated from the rhizomes of Curcuma zedoaria on prostag-
landin E2 and nitric oxide production. Planta Med. 2002;68:545–7.
12. Hossain S, Kader G, Nikkon F, Yeasmin T. Cytotoxicity of the rhizome of
medicinal plants. Asian Pac J Trop Biomed. 2012;2:125–7.
13. Hou XL, Takahashi K, Tanaka K, et al. Curcuma drugs and curcumin
regulate the expression and function of P-gp in Caco-2 cells in completely
opposite ways. Int J Pharm. 2008;358:224–9.
14. Hou XL, Takahashi K, Kinoshita N, et al. Possible inhibitory mechanism of
Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated
Caco-2 cells. Int J Pharm. 2007;337:169–77.
15. Israr F, Hassan F, Naqvi BS, et al. Report: studies on antibacterial activity of
some traditional medicinal plants used in folk medicine. Pak J Pharm Sci.
2012;25:669–74.
16. Jang MK, Lee HJ, Kim JS, Ryu JH. A curcuminoid and two sesquiter-
penoids from Curcuma zedoaria as inhibitors of nitric oxide synthesis in
activated macrophages. Arch Pharm Res. 2004;27:1220–5.
17. Jang MK, Sohn DH, Ryu JH. A curcuminoid and sesquiterpenes as
inhibitors of macrophage TNF-alpha release from Curcuma zedoaria. Planta
Med. 2001;67:550–2.
18. Kaushik ML, Jalalpure SS. Effect of Curcuma zedoaria Rosc root extracts
on behavioral and radiology changes in arthritic rats. J Adv Pharm Technol
Res. 2011;2:170–6.
19. Kim KI, Kim JW, Hong BS, et al. Antitumor, genotoxicity and anticlasto-
genic activities of polysaccharide from Curcuma zedoaria. Mol Cells. 2000;
10:392–8.
20. Kimura Y, Sumiyoshi M, Tamaki T. Effects of the extracts and an active
compound curcumenone isolated from Curcuma zedoaria rhizomes on
alcohol-induced drunkenness in mice. Fitoterapia. 2013;84:163–9.
21. Lai EY, Chyau CC, Mau JL, et al. Antimicrobial activity and cytotoxicity of
the essential oil of Curcuma zedoaria. Am J Chin Med. 2004;32:281–90.
22. Lee H, Lin JY. Antimutagenic activity of extracts from anticancer drugs in
Chinese medicine. Mut Res. 1988;204:229–34.
23. Lee SK, Hong CH, Huh SK, et al. Suppressive effect of natural sesquiter-
penoids on inducible cyclooxygenase (COX-2) and nitric oxide synthase
(iNOS) activity in mouse macrophage cells. J Environ Pathol Toxicol Oncol.
2002;21:141–8.
24. Makabe H, Maru N, Kuwabara A, et al. Anti-inflammatory sesquiterpenes
from Curcuma zedoaria. Nat Prod Res. 2006;20:680–5.
816 Curcuma zedoaria (Christm.) Roscoe.

25. Matsuda H, Ninomiya K, Morikawa T, Yoshikawa M. Inhibitory effect

and action mechanism of sesquiterpenes from Zedoariae Rhizoma on
D-galactosamine/lipopolysaccharide-induced liver injury. Bioorg Med Chem
Lett. 1998;8:339–44.
26. Navarro Dde F, de Souza MM, Neto RA, et al. Phytochemical analysis and
analgesic properties of Curcuma zedoaria grown in Brazil. Phytomedicine.
2002;9:427–32.
27. Oh OJ, Min HY, Lee SK. Inhibition of inducible prostaglandin E2 produc-
tion and cyclooxygenase-2 expression by curdione from Curcuma zedoaria.
Arch Pharm Res. 2007;30:1236–9.
28. Pamplona CR, de Souza MM, Machado Mda S, et al. Seasonal variation and
analgesic properties of different parts from Curcuma zedoaria Roscoe
(Zingiberaceae) grown in Brazil. Z Naturforsch C. 2006;61:6–10.
29. Peng CH, Chiu WT, Juan CW, et al. Pivotal role of curcuminoids on the
antimutagenic activity of Curcuma zedoaria extracts. Drug Chem Toxicol.
2010;33:64–76.
30. Shin Y, Lee Y. Cytotoxic activity from Curcuma zedoaria through
mitochondrial activation on ovarian cancer cells. Toxicol Res. 2013;
29:257–61.
31. Syu WJ, Shen CC, Don MJ, et al. Cytotoxicity of curcuminoids and some
novel compounds from Curcuma zedoaria. J Nat Prod. 1998;61:1531–4.
32. Tariq S, Imran M, Mushtaq Z, Asghar N. Phytopreventive antihypercholes-
terolmic and antilipidemic perspectives of zedoary (Curcuma Zedoaria
Roscoe.) herbal tea. Lipids Health Dis. 2016;15:39.
33. Ullah HM, Zaman S, Juhara F, et al. Evaluation of antinociceptive, in vivo
& in vitro anti-inflammatory activity of ethanolic extract of Curcuma
zedoaria rhizome. BMC Complement Altern Med. 2014;14:346.
34. Wilson B, Abraham G, Manju VS, et al. Antimicrobial activity of Curcuma
zedoaria and Curcuma malabarica tubers. J Ethnopharmacol. 2005;99:147–51.
35. Xu XB, Qin XM, Xu JD, Pang JJ. Effect of Curcuma zedoaria (Berg.) Bosc
on the myoelectric activity of uterus in rats and study of its mechanisms.
Zhongguo Zhong Yao Za Zhi. 2001;26:334–7 (Chinese).
36. Zhao JL, Sun BG, Wen QZ. Effect of zedoary turmeric oil-eluting stents for
post-stenting restenosis prevention and treatment. Zhongguo Zhong Xi Yi
Jie He Za Zhi. 2008;28:326–9 (Chinese).
37. Zhao R, Chen C, Wu Y. Isolation and structure determination of furan
sesquiterpene from Chinese traditional herb ezhu (rhizome of Curcuma
zedoaria Rosc.). Zhongguo Zhong Yao Za Zhi. 1991;16:291–2, 319 (Chinese).
38. Zhou Y, Shen J, Xia L, Wang Y. Curcuma zedoaria (Berg.) Rosc. essential
oil and paclitaxel synergistically enhance the apoptosis of SKOV3 cells.
Mol Med Rep. 2015;12:1253–7.
Cuscuta chinensis Lam. (or C. epithymum L.)
(Convovulaceae)

(Syns.: C. carinata R.Br.; C. chinensis var. carinata (R. Br.) Engelm.; C. martiana Mak.)

Abstract
A yellowish, rootless, apparently leafless, thread-like perennial parasitic vine,
often found on many trees in temperate and tropical regions, especially China
and India. Cuscuta species known as dodder, have been used in traditional
medicines of eastern and south Asian countries as liver and kidney tonic.
C. chinensis is used in the traditional medicines of China, Korea, Pakistan,
Vietnam, India, Thailand and other countries as an antiaging, anti-inflammatory
and analgesic agent, and aphrodisiac. Ibn al-Baitar described Aftimun as flowers
of a hard plant citing Dioscorides. He says the best is the one that is strongly
aromatic and reddish in color. Referencing to Avicenna, he mentioned it
beneficial for epilepsy, provided it is not boiled for long, and also for the
treatment of abnormal uterine bleeding. In Unani medicine, it is regarded
anti-inflammatory, carminative, anthelmintic, emolient, and purgative of phlegm
and black bile; and is used in the treatment of insanity, melancholy, and
epilepsy. It was one of the most commonly used drugs in ancient times in China,
and is classified as a superior drug in Chinese medicine. Dried ripe seeds, known
as Tu-si-zi, are commonly used in TCM to nourish and improve liver and kidney
conditions. Water extract of the whole plant is also used for nocturnal emissions
and prescribed for impotence in China. The plant contains flavonoids, saponins,
sterols/triterpenes and tannins; alkaloids, coumarins and quinones are reportedly
absent. Hot water extract of the whole plant produced CNS depressant activity in
mice, protected liver against CCl4-hepatotoxicity in rats, and produced
anti-inflammatory activity against carrageenan-induced paw edema in rats.
Water extract of the whole plant was also immunomodulatory, and markedly
delayed the appearance, and retarded growth of skin papillomas and carcinomas
in mice. Aqueous extract as a multicomponent prescription, administered to
AIDS patients to replenish the Ying and Yin of the heart, spleen and kidney,
resulted in improvement of the patients.

© Springer Nature Switzerland AG 2020 817

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_85
818 Cuscuta chinensis Lam. (or C. epithymum L.)

Keywords




Aftimun Amarbel vilayati Cabello de ángel Chinees warkruid Devil’s






hair Dodder Kasoos Linheiro-da-china Shajar-ul-Sabagh Tu-si-zi

Vernaculars: Urd.: Aftimun, Kasoos; Hin.: Akaasbel vilayati, Amarbel vilayati;

Ara.: Shajar-ul-sabagh; Chi.: Tu-si-zi, To-sa-za; Dut.: Chinees warkruid; Eng.:
Angelhair, Devil’s hair, Devil’s gut, Dodder, Hairweed, Goldthread, Strangleweed;
Fre.: Cuscute chinoise, Tu si zi; Jap.: Hama-ne-nashi-kazura; Por.: Linheiro-da-
china; Spa.: Cuscuta china, Cabello de ángel.
Description: A yellowish, rootless, apparently leafless, thread-like perennial par-
asitic vine, often found on many trees in temperate and tropical regions, especially
China and India, and is bitter in taste. Dodder uses airborne volatile organic
compounds as cues to locate its host plants. It flowers in the early summer, and the
flowers range in color from white to pink to yellow to cream. Seeds are minute and
produced in large quantities, have a hard coating, and typically can survive in the
soil for 5–10 years, sometimes longer (Figs. 1 and 2).LXXIX
Actions and Uses: Cuscuta species known as dodder, have been used in traditional
medicines of eastern and south Asian countries as liver and kidney tonic [6].
C. chinensis is used in the traditional medicines of China, Korea, Pakistan, Vietnam,
India, Thailand and other countries as an antiaging, anti-inflammatory and analgesic
agent, and aphrodisiac [3]. Ibn al-BaitarLXXIX described Aftimun as flowers of a hard
plant citing Dioscorides. He says the best is the one that is strongly aromatic and
reddish in color. Referencing to Avicenna, he mentioned it beneficial for epilepsy,
provided it is not boiled for long, and also for the treatment of abnormal uterine
bleeding [14]. Sharif calls it good for spasm and Reehi (due to air) inflammation,

Fig. 1 Cuscuta chinensis, Plant from India, Vinayaraj, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cuscuta_chinensis_01.JPG;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Cuscuta chinensis Lam. (or C. epithymum L.) 819

Fig. 2 Cuscuta chinensis, Plant from Cabo de Palos, Murcia, Spain, Retama, WikimediaCommons,
https://commons.wikimedia.org/wiki/File:Cuscuta_epithymum1.jpg

and Ibn Masawaiyh cautions that it should not be finely grounded as it loses its active
(johar) constituent. This author is not sure if the Aftimun described by Ibn
al-BaitarLXXIX is the same as what is known and sold in India as Aftimun. In
Unani medicine, it (temperament, hot 3° and dry 2°) is regarded anti-inflammatory,
carminative, anthelmintic, mulattif (emolient), and purgative of phlegm and black
bile; and is used in the treatment of insanity, melancholy, epilepsy, and less in
gastric, liver and spleen weakness, and jaundice; its paste is applied on boils and
pimples, and the decoction is used to kill and expel intestinal worms;LXXVII whereas
the seeds are regarded as tonic, diaphoretic and demulcent in Ayurveda.CXXVII It was
one of the most commonly used drugs in ancient times in China [5], and is classified
as a superior drug in Chinese medicine.LXVI Dried ripe seeds, known as Tu-si-zi, are
commonly used in TCM to nourish and improve liver and kidney conditions [20,
33], for treating the aching and weakness of loins and knees, tonifying the defects of
the liver and the kidney, ‘diarrhea due to hypofunction of the kidney and the spleen’
[11] and for nocturnal emissions, and enuresis.LXVI Water extract of the whole plant
is also used for nocturnal emissions and prescribed for impotence in China,LXXIX
and externally used to treat hyperpigmentation of the skin, such as melasma and
ephelides, in order to enhance the beauty of ladies [13].
Phytoconstituents: The plant contains flavonoids, saponins, sterols/triterpenes and
tannins; alkaloids, coumarins and quinones are reportedly absent [19]. b-sitosterol,
d-sesamin, 9(R)-hydroxy-d-sesamin, d-pinoresinol and daucosterol have been iso-
lated from the stem [30]. Flavonoids: hyperoside, isorhamnetin, d-sesamin, quer-
cetin, kaempferol, quercetin 3-O-b-D-galactoside-7-O-b-D-glucoside, quercetin
3-O-b-D-apiofuranosyl-(1 ! 2)-b-D-galactoside, 9(R)-hydroxy-d-sesamin, and rutin
[6, 9, 29, 31], polysaccharides [2, 24, 25], and lignan glycosides [7] have been
reported from the seeds.
820 Cuscuta chinensis Lam. (or C. epithymum L.)

Pharmacology: Hot water extract of the whole plant produced CNS depressant
activity in mice [1], protected liver against CCl4-hepatotoxicity in rats [16], and
produced anti-inflammatory activity against carrageenan-induced paw edema in rats
[15]. Water extract of the whole plant was also immunomodulatory [10], and
markedly delayed the appearance, and retarded growth of skin papillomas and
carcinomas in mice [17]. Chloroform and hydroalcoholic extracts of aerial parts
significantly reduced viability of human uterine cervical carcinoma (HeLa), human
colorectal adenocarcinoma (HT29) and human breast carcinoma (MDA-MB-468)
cells [8]. However, a novel resin glycoside, cuscutic resinoside A significantly
stimulated MCF-7 cells and T47D human breast cancer cells proliferation [23].
Polysaccharide from seeds decreased apoptosis of cardiomyocytes of D-galactose-
induced aging rats [22], and pretreatment with flavonoids fractions protected from
oxidative stress, inhibited apoptosis and increased survival of PC12 cells [35]. An
extract exerted a relaxing effect on rabbit penile corpus cavernous (PCC) tissue
ex vivo, and significantly enhanced sildenafil-induced PCC relaxation [21].
Aqueous seed extract ameliorated I/R-induced acute renal failure in rats [20],
and ethanol extract significantly prevented APAP-hepatotoxicity, and increased
levels of SOD, CAT, GPx, and reduced MDA levels [33]. A nanoparticle prepa-
ration produced the same hepatoprotective and antioxidant effects, but at a
five-times lower dose [32]. An extract is reported to prevent CP-induced nephro-
toxicity and bone marrow toxicity in mice [18]. Methanol seed extract exhibited
analgesic and anti-inflammatory activities [11]. Aqueous seed extract also produced
mild osteogenic activity in human osteoblast-like MG-63 cells [27].
A warming-Yang compound drug consisting of Cynomorium songoricum, Epi-
medium brevicornum and C. chinensis is reported to antagonize scopolamine-
induced dysmnesia in mice, and improved memory by inhibiting AChE activity and
invigorating Qi [12].
Clinical Studies: Aqueous extract as a multicomponent prescription, administered
to AIDS patients to replenish the Ying and Yin of the heart, spleen and kidney,
resulted in improvement of the patients [34]. Water extract was also effective when
used as a multicomponent prescription (including Schizandra chinensis, C. chi-
nensis, Plantago asiatica, Lycium barbarum, Curculigo orchioides, Epimedium
brevicornum and Rubus chungii) to induce ovulation in 95 female Chinese subjects
by replenishing the kidneys [4].
Mechanism of Action: Increase in antioxidant enzymes activities in the liver, and
decreased interleukins (IL-1b, IL-6), NF-jB, TNF-a, and COX-2 levels are sug-
gested mechanisms for analgesic and anti-inflammatory activities [11]. Kaempferol
and hyperoside are said to be responsible for osteogenic effect [28]. Its relaxing
effect on rabbit penile corpus cavernous tissue is mediated, in part by activation of
NO-cGMP pathway [21].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: LD50 (i. p.) of the defatted ethanol extract in mice was
1,000 mg/kg [26].
Cuscuta chinensis Lam. (or C. epithymum L.) 821

Commentary: This drug has only been clinically tested as part of polyherbal
formulations in Chinese medicine. Many of its traditional uses in regional
medicines are yet to be tested in formal clinical studies.

References
1. Akbar S, Nisa M, Tariq M. CNS depressant activity of Cuscuta chinensis
Lam. Int J Crude Drug Res. 1985;23:91–4.
2. Bao X, Wang Z, Fang J, Li X. Structural features of an immunostimulating
and antioxidant acidic polysaccharide from the seeds of Cuscuta chinensis.
Planta Med. 2002;68:237–43.
3. Donnapee S, Li J, Yang X, et al. Cuscuta chinensis Lam.: a systematic
review on ethnopharmacology, phytochemistry and pharmacology of an
important traditional herbal medicine. J Ethnopharmacol. 2014;157:292–
308.
4. Ge QS, Zhang YW, Shen LZ. Induction of ovulution with kidney-
replenishing herbal drugs: analysis of 95 cases. CTC. 1982;23:19–22.
5. Guo C, Zhang Z, Zheng H, Shu Z, Li C. Studies of the herbal and botanical
origins of seman Cuscutae. Zhongguo Zhong Yao Za Zhi. 1990;15:138–40,
189 (Chinese).
6. Hajimehdipoor H, Kondori BM, Amin GR, et al. Development of a
validated HPLC method for the simultaneous determination of flavonoids in
Cuscuta chinensis Lam. by ultraviolet detection. Daru. 2012;20:57.
7. He XH, Yang WZ, Meng AH, et al. Two new lignan glycosides from the
seeds of Cuscuta chinensis. J Asian Nat Prod Res. 2010;12:934–9.
8. Jafarian A, Ghannadi A, Mohebi B. Cytotoxic effects of chloroform and
hydroalcoholic extracts of aerial parts of Cuscuta chinensis and Cuscuta
epithymum on Hela, HT29 and MDA-MB-468 tumor cells. Res Pharm Sci.
2014;9:115–22.
9. Jin X, Li J, Yan M. Flavonoids in the seed of Cuscuta chinensis Lam.
Zhongguo Zhong Yao Za Zhi. 1992;17:292–4 (Chinese).
10. Kim MS, Lee NG, Lee JH, Byun SJ, Kim YC. Immunopotentiating activity
of water extract of some crude drugs. Korean J Pharmacog. 1988;19:
193–200.
11. Liao JC, Chang WT, Lee MS, et al. Antinociceptive and anti-inflammatory
activities of Cuscuta chinensis seeds in mice. Am J Chin Med. 2014;
42:223–42.
12. Liu ZY, Yang YG, Zheng B. Effect of improving memory and inhibiting
acetylcholinesterase activity by invigorating-qi and warming-yang recipe.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993;13:675–6, 646 (Chinese).
13. Masamoto Y, Iida S, Kuto M. Inhibitory effect of Chinese crude drugs on
tyrosinase. Planta Med. 1980;40:361–5.
822 Cuscuta chinensis Lam. (or C. epithymum L.)

14. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal

plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
15. Nisa M, Akbar S, Tariq M. Anti-inflammatory activity of Cuscuta chinensis.
Fitoterapia. 1985;56:315–7.
16. Nisa M, Tariq M, Akbar S. Effect of Cuscuta chinensis Lam. (Aftimun) on
carbon tetrachloride-induced liver damage. IRCS Med Sci. 1985;13:150.
17. Nisa M, Akbar S, Tariq M, Hussain Z. Effect of Cuscuta chinensis water
extract on 7,12-dimethylbenz[a]anthracene-induced skin papillomas and
carcinomas in mice. J Ethnopharmacol. 1986;18:21–31.
18. Raju N, Sakthivel KM, Kannan N, Vinod Prabhu V, Guruvayoorappan C.
Cuscuta chinensis ameliorates immunosuppression and urotoxic effect of
cyclophosphamide by regulating cytokines—GM-CSF and TNF-Alpha.
Appl Biochem Biotechnol. 2015;176:742–57.
19. Rizk AM, Heiba HI, Ma’Ayergi HA, Batanouny KH. Constituents of plants
growing in Qatar. Fitoterapia. 1986;57:3–9.
20. Shin S, Lee YJ, Kim EJ, et al. Effect of Cuscuta chinensis on renal function
in ischemia/reperfusion-induced acute renal failure rats. Am J Chin Med.
2011;39:889–902.
21. Sun K, Zhao C, Chen XF, et al. Ex vivo relaxation effect of Cuscuta
chinensis extract on rabbit corpus cavernosum. Asian J Androl. 2013;15:
134–7.
22. Sun SL, Guo L, Ren YC, et al. Antiapoptosis effect of polysaccharide
isolated from the seeds of Cuscuta chinensis Lam. on cardiomyocytes in
aging rats. Mol Biol Rep. 2014;41:6117–24.
23. Umehara K, Nemoto K, Ohkubo T, et al. Isolation of a new 15-membered
macrocyclic glycolipid lactone, Cuscutic Resinoside A from the seeds of
Cuscuta chinensis: a stimulator of breast cancer cell proliferation. Planta
Med. 2004;70:299–304.
24. Wang Z, Fang JN, Ge DL, Li XY. Chemical characterization and
immunological activities of an acidic polysaccharide isolated from the
seeds of Cuscuta chinensis Lam. Acta Pharmacol Sin. 2000;21:1136–40.
25. Wang Z, Fang JN. Studies on the polysaccharide H3 of Cuscuta chinensis
Lam. Yao Xue Xue Bao. 2001;36:192–5 (Article in Chinese).
26. Woo WS, Lee EB, Chang I. Biological evaluation of Korean medicinal
plants. II. Yakhak Hoe Chi. 1977;21:177–83.
27. Yang HM, Shin HK, Kang YH, Kim JK. Cuscuta chinensis extract
promotes osteoblast differentiation and mineralization in human osteoblast-
like MG-63 cells. J Med Food. 2009;12:85–92.
28. Yang L, Chen Q, Wang F, Zhang G. Antiosteoporotic compounds from
seeds of Cuscuta chinensis. J Ethnopharmacol. 2011;135:553–60.
29. Ye M, Li Y, Yan Y, Liu H, Ji X. Determination of flavonoids in Semen
Cuscutae by RP-HPLC. J Pharm Biomed Anal. 2002;28:621–8.
30. Ye M, Yan Y, Ni X, Qiao L. Studies on the chemical constituents of the
herba of Cuscuta chinensis. Zhong Yao Cai. 2001;24:339–41 (Chinese).
Cuscuta chinensis Lam. (or C. epithymum L.) 823

31. Ye M, Yan YN, Qiao L, Ni XM. Studies on chemical constituents of

Cuscuta chinensis. Zhongguo Zhong Yao Za Zhi. 2002;27:115–7 (Chinese).
32. Yen FL, Wu TH, Lin LT, et al. Nanoparticles formulation of Cuscuta
chinensis prevents acetaminophen-induced hepatotoxicity in rats. Food
Chem Toxicol. 2008;46:1771–7.
33. Yen FL, Wu TH, Lin LT, Lin CC. Hepatoprotective and antioxidant effects
of Cuscuta chinensis against acetaminophen-induced hepatotoxicity in rats.
J Ethnopharmacol. 2007;111:123–8.
34. Yu J, Chen KJ. Clinical observations of AIDS treated with herbal formulas.
Int J Orien Med. 1989;14:189–93.
35. Zhen GH, Jiang B, Bao YM, Li DX, An LJ. The protect effect of flavonoids
from Cuscuta chinensis in PC12 cells from damage induced by H2O2.
Zhong Yao Cai. 2006;29:1051–5 (Chinese).
Cuscuta reflexa Roxb.
(Convolvulaceae)

Abstract
A yellowish, parasitic, rootless, apparently leafless, thread-like vine, often found
on many trees in India and China, and is bitter in taste. Cuscuta reflexa has been
described as Kasoos in the translation of volume IV of Ibn al-Baitar’s Al-Jame-
al-Mufradat al-Advia wal Aghzia; the plant description in it corresponds to the
plant found in India, whereas Aftimun is mentioned as Cuscuta epithymum and
as flowers of a hard plant citing Dioscorides, as detailed under Cuscuta
chinensis. This author had a sample sold in India as Aftimun, identified by a
taxonomist as Cuscuta chinenesis. In Unani medicine, it is regarded very useful
in all black bile-caused diseases, including cancers, and is beneficial as blood
purifier and in splenic inflammation. For intestinal worms, the decoction is used,
and the crushed plant is applied to boils and inflammation. In Ayurveda, the
plant is used externally for itch and skin diseases, and internally in protracted
fevers, constipation, flatulence, liver complaints, bilious affections and piles.
Ethanol crude extract of the whole plant showed the presence of terpenoids,
phenols and alkaloids. Cuscutin, amarbelin, stigmasterol, b-sitosterol, kaemp-
ferol, dulcitol, myricetin, quercetin, coumarin and oleanolic acid have been
isolated from the plant. Methanol extract markedly protected against convulsion
in mice, with significant increase in GABA in mice brain after six-weeks
treatment, and exhibited broad-spectrum antimicrobial activity. Methanol extract
caused a remarkable delay in sexual maturation, reduction in weights of ovary,
uterus and pituitary of mice, with activities of delta5-3b-hydroxysteroid

Cuscuta chinensis and C. reflexa share the same Indian vernacular names and an identical
description.

© Springer Nature Switzerland AG 2020 825

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_86
826 Cuscuta reflexa Roxb.

dehydrogenase and G6PD significantly decreased after 17-days of treatment,

indicative of the inhibition of steroidogenesis. Methanol and chloroform extracts
also demonstrated significant hypoglycemic activity in glucose-loaded rats.

Keywords




Aftimun hindi Akaasbel Amarbel Amaravallari
Farhanj
Giant dodder




Grosse cuscute To-sa-za Zajmool

Vernaculars: Urd.: Aftimun hindi, Kasoos; Hin.: Aftimun, Akaasbel, Amarbel,

Amarabela, Kasus; San.: Ākãŝavalli, Amaravallari, Amaravela, Khavalli; Ben.:
Algusi, Haldi-algusilata, Haldi-algusi-lutta; Mal.: Akasagarudakkoti, Akasavalli,
Mutillattali; Mar.: Amarvela, Nirmuli, Nirmulia-kashavela; Tam.: Kodiyakundal,
Kodiyagundal, Sadadari; Tel.: Sitamma pogunalu, Sitama purgonalu; Chi.: 蛇系腰,
红无娘藤, To-sa-za, Tu-si-zi; Eng.: Angelhair, Devil’s gut, Devil’s hair, Giant
dodder, Goldthread, Hairweed, Strangleweed; Fre.: Grosse cuscute; Per.: Afti-
moon, Brush, Farhanj, Tukhme kasus (seeds), Zajmool.
Description: A yellowish, parasitic, rootless, apparently leafless, thread-like vine,
often found on many trees in India and China, and is bitter in taste. Dodder uses
airborne volatile organic compounds as cues to locate its host plants. It flowers in the
early summer and the flowers range in color from white to pink to yellow to cream.
Seeds are minute and produced in large quantities, have a hard coating, and typically
can survive in the soil for 5–10 years. It is called Amarbel in Hindi language,
because Amar means immortal, as it is an immortal twiner, growing during rainy
season, and the growth is afresh on the same plant (Figs. 1 and 2).LXXXI
Actions and Uses: C. reflexa has been described as Kasoos in the translation of
volume IV of Ibn al-Baitar’s Al-Jame-al-Mufradat al-Advia wal AghziaLXIX; the
plant description in it corresponds to the plant found in India, whereas Aftimun is
mentioned as Cuscuta epithymum and as flowers of a hard plant citing Dioscorides,
as detailed under Cuscuta chinensis. This author had a sample sold in India as
Aftimun, identified by a taxonomist as Cuscuta chinenesis. In Unani medicine, it
(temperament, hot 2° and dry 2°) is carminative, anti-inflammatory, anthelmintic,
deobstruent, excretes phlegm, yellow and black bile through feces, and is beneficial
in nervous diseases, such as epilepsy, melancholy, paralysis, palsy, mania, and
hallucinations. It is regarded very useful in all black bile-caused diseases, including
cancers, and is beneficial as blood purifier and in splenic inflammation.L For
intestinal worms, the decoction is used, and the crushed plant is applied to boils and
inflammation.LXXVII Tayyab1 described the seeds carminative, deobstruent, diuretic,
emmenagogue, anti-inflammatory and antipyretic for chronic fevers. It is also
regarded as alterative, and purgative, and the whole plant is used in constipation, liver
diseases and bilious affections;LXXXI the seeds are carminative and anodyne, and cold
infusion is used as a depurative and carminative in pains and stomachache.CV

1
Tayyab M: Personal Communication.
Cuscuta reflexa Roxb. 827

Fig. 1 Cuscuta reflexa, Plant, Dr. S. Soundarapandian, WikimediaCommons, https://commons.wiki

media.org/wiki/File:%E0%AE%85%E0%AE%AE%E0%AF%8D%E0%AE%AE%E0%AF%88%
E0%AE%AF%E0%AE%BE%E0%AE%B0%E0%AF%8D%E0%AE%95%E0%AF%82%E0%AE
%A8%E0%AF%8D%E0%AE%A4%E0%AE%B2%E0%AF%8D1.jpg

Fig. 2 Cuscuta reflexa, Flowers, Vijayanrajapuram, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Cuscuta_reflexa_moodill
athali_flowers.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

In Ayurveda, the plant is used externally for itch and skin diseases, and internally in
protracted fevers, constipation, flatulence, liver complaints, bilious affections and
piles.CXXVII It is also used as a folk remedy for the treatment of diabetes by tribals of
the Lohit district of the eastern Arunachal Himalayas in India [20], and by indigenous
communities of Bangladesh [15]. The Mehra Boxa tribe of Dehradun (India), exter-
nally uses a decoction to treat skin boils [18].
Phytoconstituents: Ethanol crude extract of the whole plant, partitioned with
different solvents showed the presence of terpenoids, phenols and alkaloids. All
828 Cuscuta reflexa Roxb.

extracts showed potential for protease and AChE inhibitory, and significant
antioxidant activity [16]. Cuscutin, amarbelin, stigmasterol, b-sitosterol, kaemp-
ferol, dulcitol, myricetin, quercetin, coumarin and oleanolic acid have been isolated
from the plant [12]. Two novel tetrahydrofuran derivatives, swarnalin and
cis-swarnalin with significant radical scavenging activity, and a coumarin,
5,6,7-trimethoxycoumarin [22], reflexin [21], and a-glucosidase inhibitory com-
pounds [1] have also been isolated. Nature of the host plant does not affect the
chemical composition of the plant [7]. Analysis of EO obtained from a plant sample
collected from Nepal showed the presence of 61 compounds, accounting for 99.6%
of the oil. cis-3-butyl-4-vinylcyclopentane (26.4%) was the major component of
the oil, other components included substantial amounts of limonene (5.1%) and
(E)-nerolidol (9.5%) [14].
Pharmacology: Petroleum ether extract of stems caused significant reduction in
spontaneous activity and exploratory behavior, analgesic activity and potentiation
of pentobarbitone sodium-, diazepam- and meprobamate-induced sleeping time in
mice [9]. Methanol extract markedly protected against convulsion in mice, with
significant increase in GABA in mice brain after six-weeks treatment [4], and
exhibited broad-spectrum antimicrobial activity [10]. Methanol and chloroform
extracts also demonstrated significant hypoglycemic activity in glucose-loaded rats
[15]. Water and ethanol extracts exhibit significant antipyretic activity in
yeast-induced pyrexia in rats [3], while a protein isolated from the aqueous extract
exhibited significant antiviral activity [2]. Water extract also produced in vitro
anti-inflammatory activity, downregulated LPS-induced overexpression of TNF-a
and COX-2 in RAW264.7 cells, and induced apoptosis in Hep3B cells [19].
Methanol extract caused a remarkable delay in sexual maturation, reduction in
weights of ovary, uterus and pituitary of mice [6], with activities of delta5-3b-
hydroxysteroid dehydrogenase and G6PD significantly decreased after 17-days of
treatment, indicative of the inhibition of steroidogenesis [5]. Petroleum ether extract
also inhibited 5a-reductase activity and exhibited promising hair growth-promoting
activity in testosterone-induced alopecia in mice [11], and CP-induced alopecia in
rats [13]. Topical application of a polyherbal formulation containing petroleum
ether extracts of Cuscuta reflexa, Citrullus colocynthis, and Eclipta alba, in varying
ratios, reduced hair growth initiation time to one third and the time required for
complete hair growth was reduced by 32% in shaved rats [17].
Human A/Es, Allergy and Toxicity: No known or reported human A/Es or
toxicity.
Animal Toxicity: Multiple weekly doses (i. p.) of methanol extract to mice did not
significantly affect RBC count or Hb levels in low dose (25 mg/kg), but clotting
time was increased in moderate and high doses (50 and 75 mg/kg), and high doses
caused hepatotoxicity and nephrotoxicity [8].
Cuscuta reflexa Roxb. 829

Commentary: There are no formal clinical studies reported on this plant, and it
remains to be explored clinically in RCTs.

References
1. Anis E, Anis I, Ahmed S, et al. Alpha-glucosidase inhibitory constituents
from Cuscuta reflexa. Chem Pharm Bull (Tokyo). 2002;50:112–4.
2. Awasthi LP. The purification and nature of an antiviral protein from
Cuscuta reflexa plants. Arch Virol. 1981;70:215–23.
3. Bhattacharya S, Roy B. Preliminary investigation on antipyretic activity of
Cuscuta reflexa in rats. J Adv Pharm Technol Res. 2010;1:83–7.
4. Gupta M, Mazumder UK, Pal D, et al. Studies on brain biogenic amines in
methanolic extract of Cuscuta reflexa Roxb. and Corchorus olitorius Linn.
seed treated mice. Acta Pol Pharm. 2003;60:207–10.
5. Gupta M, Mazumder UK, Pal DK, Bhattacharya S. Antisteroidogenic
activity of methanolic extract of Cuscuta reflexa Roxb. stem and Corchorus
olitorius Linn. seed in mouse ovary. Indian J Exp Biol. 2003;41:641–4.
6. Gupta M, Mazumder UK, Pal DK, Bhattacharya S. Onset of puberty and
ovarian steroidogenesis following adminstration of methanolic extract of
Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed in mice.
J Ethnopharmacol. 2003;89:55–9.
7. Khan SA, Chughtai AB, Bhatty MK. Effect of host plant on the chemical
composition of Cuscuta reflexa. Pak J Sci Ind Res. 1970;12:203–5.
8. Mazumder UK, Gupta M, Pal D, Bhattacharya S. Chemical and toxicolog-
ical evaluation of methanol extract of Cuscuta reflexa Roxb. stem and
Corchorus olitorius Linn. seed on hematological parameters and hepatore-
nal functions in mice. Acta Pol Pharm. 2003;60:317–23.
9. Pal D, Panda C, Sinhababu S, et al. Evaluation of psychopharmacological
effects of petroleum ether extract of Cuscuta reflexa Roxb. stem in mice.
Acta Pol Pharm. 2003;60:481–6.
10. Pal DK, Mandal M, Senthilkumar GP, Padhiari A. Antibacterial activity of
Cuscuta reflexa stem and Corchorus olitorius seed. Fitoterapia. 2006;77:
589–91.
11. Pandit S, Chauhan NS, Dixit VK. Effect of Cuscuta reflexa Roxb. on
androgen-induced alopecia. J Cosmet Dermatol. 2008;7:199–204.
12. Patel S, Sharma V, Chauhan NS, Dixit VK. An updated review on the
parasitic herb of Cuscuta reflexa Roxb. Zhong Xi Yi Jie He Xue Bao. 2012;
10:249–55.
13. Patel S, Sharma V, Chauhan NS, Dixit VK. A study on the extracts of
Cuscuta reflexa Roxb. in treatment of cyclophosphamide induced alopecia.
Daru. 2014;22:7.
14. Paudel P, Satyal P, Maharjan S, Shrestha N, Setzer WN. Volatile analysis
and antimicrobial screening of the parasitic plant Cuscuta reflexa Roxb.
from Nepal. Nat Prod Res. 2014;28:106–10.
830 Cuscuta reflexa Roxb.

15. Rahmatullah M, Sultan S, Toma TT, et al. Effect of Cuscuta reflexa stem
and Calotropis procera leaf extracts on glucose tolerance in glucose-
induced hyperglycemic rats and mice. Afr J Tradit Complement Altern Med.
2009;7:109–12.
16. Raza MA, Mukhtar F, Danish M. Cuscuta reflexa and Carthamus Oxyacan-
tha: potent sources of alternative and complimentary drug. Springerplus.
2015;4:76.
17. Roy RK, Thakur M, Dixit VK. Development and evaluation of polyherbal
formulation for hair growth-promoting activity. J Cosmet Dermatol. 2007;
6:108–12.
18. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
19. Suresh V, Sruthi V, Padmaja B, Asha VV. In vitro anti-inflammatory and
anticancer activities of Cuscuta reflexa Roxb. J Ethnopharmacol. 2011;134:
872–7.
20. Tag H, Kalita P, Dwivedi P, Das AK, Namsa ND. Herbal medicines used in
the treatment of diabetes mellitus in Arunachal Himalaya, Northeast, India.
J Ethnopharmacol. 2012;141:786–95.
21. Tripathi VJ, Yadav SB, Upadhyay AK. A new flavanone, reflexin, from
Cuscuta reflexa and its selective sensing of nitric oxide. Appl Biochem
Biotechnol. 2005;127:63–7.
22. Uddin SJ, Shilpi JA, Middleton M, et al. Swarnalin and cis-swarnalin, two
new tetrahydrofuran derivatives with free radical scavenging activity, from
the aerial parts of Cuscuta reflexa. Nat Prod Res. 2007;21:663–8.
Cydonia oblonga Mill.
(Rosaceae)

(Syns.: C. vulgaris Pers.; Pyrus cydonia L.)

Abstract
A fruit of the family of apples and pears. The fruit is regarded in Unani medicine
as refrigerant, astringent, diuretic, heart-, brain-, stomach and liver-tonic; its syrup
is used for heart weakness, hot palpitations, bilious diarrhea and to soothe heat of
stomach and liver. It has been mentioned by Avicenna in Canon of Medicine for
the treatment of abnormal uterine bleeding, and in Iran, various parts of quince are
used as traditional remedies for cough, bronchitis, nausea, fever, diarrhea,
cystitis, constipation, hemorrhoids, hypertension and diabetes, and dried quince
has been used as a tea for centuries. In traditional Uyghur medicine, quince is
used to treat or prevent cardiovascular diseases. The leaves are consumed as food
and used as a folk remedy for the treatment of diabetes in Turkey. Quince
varieties vary in their phenolic contents and some with higher contents may be
used to promote their positive effect on health. A study on fruits from seven
different locations in Portugal found the phenolic contents and total free amino
acids (most abundant amino acids were glycine, aspartic acid, and asparagines) to
be highest in the peel. Phenolics identified in peel were caffeoylquinic acids and
several flavonol glycosides: kaempferol glycoside, quercetin 3-galactoside, rutin,
kaempferol 3-glucoside, kaempferol 3-rutinoside and several unidentified com-
pounds; and the pulp contains mainly caffeoylquinic acids and a small amount of
rutin, a quercetin glycoside, and aspartic acid, asparagine, and hydroxyproline
as the major amino acids. Quince leaves have very high total phenolic contents
with 5-O-caffeoylquinic acid as the major phenolic compound, followed by
quercetin 3-O-rutinoside; they also have higher relative contents of kaempferol
derivatives than fruits. Aqueous fruit extract showed hypolipidemic, hepatopro-
tective, and renoprotective effects in diabetic rats as it significantly decreased
serum TGs, TC, and LDL-C levels and increased the HDL-C. Oral administration
of leaf ethanol extract to diabetic rats lowered blood glucose levels by 34%, and

© Springer Nature Switzerland AG 2020 831

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_87
832 Cydonia oblonga Mill.

significantly reduced TBARS levels only in heart tissue. In a double-blind, RCT,

quince syrup was effective in symptomatic relief of GERD in children and Iranian
adolescents.

Keywords



Ayva Behi Cognassier Cotogno

Gamboas
Marmeleiro
Marumero




Membrillero Quince Quittenbaum

Vernaculars: Urd.: Behi, Behidana; Hin.: Moghloi behedana, Bihidana; Tam.:

Shimai-ma-delaivirai; Tel.: Shima-dalima-vittulu; Ara.: Habbus-safarjal, Safarjal;
Dut.: Kwee, Kweeboom; Eng.: Quince fruit; Fre.: Cognassier, Coignier; Ger.:
Echte quitte, Quittenbaum; Ita.: Cotogno, Mela cotogna, Melocotogno; Jap.:
Marumero; Per.: Behi-dana, Tukhm-e-abi; Por.: Marmeleiro, Marmelo; Spa.:
Gamboas, Membrillero, Membrillo, Zamboero; Tur.: Ayva.
Description: A fruit of the family of apples and pears, similar in appearance to a
pear, and bright golden-yellow, when mature. Seeds are triangular in shape, brownish
in color, and mucilaginous. NadkarniCV described three kinds: sweet, sour and
subacid (Figs. 1 and 2).
Actions and Uses: Sweet and subacid quinces are cephalic, cardiac, demulcent,
astringent, restorative and tonic.CV The fruit (temperament, moderate and moist 1°)
is refrigerant, astringent, diuretic, heart-, brain-, stomach and liver-tonic; its syrup is
used for heart weakness, hot palpitations, bilious diarrhea and to soothe heat of
stomach and liver.LXXVII Seeds (temperament, cold 2° and moist 2°) are refrigerant,
tonic, and sedative; used in the treatment of cold and cough, throat irritation,
dry cough, pthisis, fevers, dysentery and hot headaches;1 are nutritive, astringent,
demulcent, and emollient; externally the mucilage is applied to burns and
scalds.LXXXI It has been mentioned by Avicenna in Canon of Medicine for the
treatment of abnormal uterine bleeding [16], and in Iran, various parts of quince are
used as traditional remedies for cough, bronchitis, nausea, fever, diarrhea, cystitis,
constipation, hemorrhoids, hypertension and diabetes [12], and dried quince has
been used as a tea for centuries [9]. In traditional Uyghur medicine, quince is used
to treat or prevent cardiovascular diseases [28]. The leaves are consumed as food
and used as a folk remedy for the treatment of diabetes in Turkey [4].
Phytoconstituents: Quince varieties vary in their phenolic contents and some with
higher contents may be used to promote their positive effect on health [27]. A study
on fruits from seven different locations in Portugal found the phenolic contents and
total free amino acids (most abundant amino acids were glycine, aspartic acid, and
asparagines) to be highest in the peel [21, 24]. Phenolics identified in peel were
caffeoylquinic acids and several flavonol glycosides: kaempferol glycoside, quercetin
3-galactoside, rutin, kaempferol 3-glucoside, kaempferol 3-rutinoside and several

1
Tayyab M: Personal Communication.
Cydonia oblonga Mill. 833

Fig. 1 Cydonia oblonga, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Cydonia_oblonga_-_K%C3%B6hler
%E2%80%93s_Medizinal-Pflanzen-049.jpg

Fig. 2 Cydonia oblonga, Quince Foliage and Ripening Fruits, Utilisateur: Spone, Wikimedia-
Commons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:
Cydonia.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
834 Cydonia oblonga Mill.

unidentified compounds; and the pulp contains mainly caffeoylquinic acids and a
small amount of rutin, a quercetin glycoside, and aspartic acid, asparagine, and
hydroxyproline as the major amino acids [21]. Phenolic compounds identified in
seeds include, 3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and 3,5-
dicaffeoylquinic acids, lucenin-2, vicenin-2, stellarin-2, schaftoside, isoschaftoside,
6-C-pentosyl-8-C-glucosyl chrysoeriol and 6-C-glucosyl-8-C-pentosyl chrysoeriol,
and the three most abundant free amino acids are glutamic and aspartic acids,
and asparagines [20, 22]. 5-O-caffeoylquinic acid is one of the two major phenolic
compounds present in methanol extracts of pulp, peel and leaves [5]. Phenolic
compounds analysis of quince fruit from China had considerable amounts
of hydroxycinnamic derivatives mainly composed of 3-caffeoylquinic acid and
5-caffeoylquinic acid and polymeric procyanidins [10]. Chlorogenic acid (5-O-
caffeoylquinic acid) was the most abundant phenolic compound in the pulp (37%),
and rutin (quercetin 3-O-rutinoside) in the peel (36%) of Tunisian quince [7].
Oven-dried than the sun-dried, and quince peel compared to the flesh contain higher
amounts of phenolics [9]. Quince leaves have very high total phenolic contents with
5-O-caffeoylquinic acid as the major phenolic compound (36.2%), followed by
quercetin 3-O-rutinoside (21.1%); they also have higher relative contents of
kaempferol derivatives than fruits (pulps, peels, and seeds) [18]. Ionone glucosides
were also reported from the leaves [13]. Organic acids profile of the leaves include
oxalic, citric, malic, quinic, shikimic and fumaric acids, with quinic acid (72.2%) as
the major compound, followed by citric acid (13.6%) [17]. A b-D-gentiobioside that
acts as a precursor of C13-norisoprenoid flavor compounds of quince EO was isolated
from quince fruit [26], and the seed oil also contains appreciable amounts of lipohilic
antioxidants [8].
Pharmacology: Aqueous fruit extract showed hypolipidemic, hepatoprotective,
and renoprotective effects in diabetic rats as it significantly decreased serum TGs,
TC, and LDL-C levels and increased the HDL-C [15]. Oral administration of leaf
ethanol extract for 5-days to diabetic rats lowered blood glucose levels by 34%, and
significantly reduced TBARS levels only in heart tissue [4]. Silva et al. [23, 24]
reported highest antioxidant capacity in methanol peel extract, but the phenolic
fraction of seed extract exhibited the strongest antioxidant activity. Leaf extract and
the flavonoid fraction produced antihyperlipidemic effects, and improved antioxi-
dant status of hyperlipidemic rats [1, 25], and leaf decoction protected from
hypercholesterolemia-induced damage to rabbits’ testes and spermatogenesis [2].
Hydroalcohol fruit extract exhibited aphrodisiac effect in rats [3], and protected rats
from TNBSA-induced ulcerative colitis [14]. Ethanol leaf extract decreased BP in
renal hypertensive rats and reduced whole blood viscosity, improved erythrocytes
deformability [29], decreased Ang.-II, PRA, apelin-12, endothelin and increased
NO, comparable to captopril [30]. Flavonoids fraction of the leaves also lowered BP
of SHRs and decreased contents of IL-1b, IL-6, TNF-a and CRP [31]. Aqueous
extract treatment of mice for 14-days prolonged bleeding time and clotting time, and
increased thrombolysis in vitro [28].
Cydonia oblonga Mill. 835

Methanol leaf extract shows antiproliferative activity against human colon

cancer cells, but no effect on renal adenocarcinoma cells, while fruit and seed
extracts exhibited no effect on colon cancer cells, but a strong antiproliferative
effect against renal cancer cells [5]. A crude hot-water extract of fruits significantly
decreased the development of atopic dermatitis-like skin lesions and lowered serum
IgE concentration in mice; and in vitro inhibited the release of b-hexosaminidase
from rat basophilic leukemia cell line, suggesting an inhibitory effect on type I
allergy by suppressing IgE production and IgE-mediated degranulation [19].
Clinical Studies: In a double-blind RCT, quince syrup was effective in symp-
tomatic relief of GERD in children and Iranian adolescents [32]. Nasal spray pre-
pared from lemon and quince is used in Germany to treat hay fever symptoms and
has been shown to inhibit histamine release from mast cells in vitro. However, a
three-way crossover study in healthy subjects did not show any significant effect on
intranasal mucociliar clearance [6], but a recent clinical study suggests the nasal
spray have an antiallergic effect in patients with grass pollen allergy [11].
Human A/Es, Allergy and Toxicity: No known or reported human A/Es or
toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Quince fruits are preserved in syrup and used in the Indian sub-
continent as nutritive, refrigerant and cardiotonic. Seeds are used in various tradi-
tional medicines, usually for pulmonary affections, and other ailments, but there are
no formal published clinical studies, other than the quince syrup being effective in
symptomatic relief of GERD in children and adolescents.

References
1. Abliz A, Aji Q, Abdusalam E, et al. Effect of Cydonia oblonga Mill. leaf
extract on serum lipids and liver function in a rat model of hyperlipidaemia.
J Ethnopharmacol. 2014;151:970–4.
2. Ashrafi H, Ghabili K, Alihemmati A, et al. The effect of quince leaf (Cydonia
oblonga Miller) decoction on testes in hypercholesterolemic rabbits: a pilot
study. Afr J Tradit Complement Altern Med. 2012;10:277–82.
3. Aslam M, Sial AA. Effect of hydroalcoholic extract of Cydonia oblonga
Miller (Quince) on sexual behaviour of Wistar rats. Adv Pharmacol Sci.
2014;2014:282698.
4. Aslan M, Orhan N, Orhan DD, Ergun F. Hypoglycemic activity and antioxi-
dant potential of some medicinal plants traditionally used in Turkey for
diabetes. J Ethnopharmacol. 2010;128:384–9.
5. Carvalho M, Silva BM, Silva R, et al. First report on Cydonia oblonga
Miller anticancer potential: differential antiproliferative effect against human
kidney and colon cancer cells. J Agric Food Chem. 2010;58:3366–70.
836 Cydonia oblonga Mill.

6. Degen J, Seiberling M, Meyer I, Thomann P, Schürholz T. The effect of a

nasal spray consisting of a standardized mixture of citrus limon (succus) and
an aqueous extract of Cydonia oblongata (fructus) on nasal mucociliary
clearance. Arzneimittel-forschung. 2000;50:39–42 (German).
7. Fattouch S, Caboni P, Coroneo V, et al. Antimicrobial activity of Tunisian
quince (Cydonia oblonga Miller) pulp and peel polyphenolic extracts.
J Agric Food Chem. 2007;55:963–9.
8. Fromm M, Bayha S, Kammerer DR, Carle R. Identification and quantitation
of carotenoids and tocopherols in seed oils recovered from different
Rosaceae species. J Agric Food Chem. 2012;60:10733–42.
9. Gheisari HR, Abhari KH. Drying method effects on the antioxidant activity
of quince (Cydonia oblonga Miller) tea. Acta Sci Pol Technol Aliment.
2014;13:129–34.
10. Hamauzu Y, Yasui H, Inno T, Kume C, Omanyuda M. Phenolic profile,
antioxidant property, and anti-influenza viral activity of Chinese quince
(Pseudocydonia sinensis Schneid.), quince (Cydonia oblonga Mill.), and
apple (Malus domestica Mill.) fruits. J Agric Food Chem. 2005;53:928–34.
11. Hoffmann A, Klein SD, Gründemann C, et al. Efficacy of a nasal spray from
Citrus limon and Cydonia oblonga for the treatment of hay fever symptoms—a
randomized, placebo controlled crossover study. Phytother Res. 2016;30:
1481–6.
12. Khoubnasabjafari M, Jouyban A. A review of phytochemistry and bioac-
tivity of quince (Cydonia oblonga Mill.). J Med Plant Res. 2011;5:3577–94.
13. Lutz-Röder A, Schneider M, Winterhalter P. Isolation of two new ionone
glucosides from quince (Cydonia oblonga Mill.) leaves. Nat Prod Lett.
2002;16:119–22.
14. Minaiyan M, Ghannadi A, Etemad M, Mahzouni P. A study of the effects of
Cydonia oblonga Miller (Quince) on TNBSA-induced ulcerative colitis in
rats. Res Pharm Sci. 2012;7:103–10.
15. Mirmohammadlu M, Hosseini SH, Kamalinejad M, et al. Hypolipidemic,
hepatoprotective and renoprotective effects of Cydonia Oblonga Mill. fruit
in streptozotocin-induced diabetic rats. Iran J Pharm Res. 2015;14:1207–14.
16. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal
plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
17. Oliveira AP, Pereira JA, Andrade PB, et al. Organic acids composition of
Cydonia oblonga Miller leaf. Food Chem. 2008;111:393–9.
18. Oliveira AP, Pereira JA, Andrade PB, et al. Phenolic profile of Cydonia
oblonga Miller leaves. J Agric Food Chem. 2007;55:7926–30.
19. Shinomiya F, Hamauzu Y, Kawahara T. Antiallergic effect of a hot-water
extract of quince (Cydonia oblonga). Biosci Biotechnol Biochem. 2009;73:
1773–8.
Cydonia oblonga Mill. 837

20. Silva BM, Andrade PB, Ferreres F, et al. Composition of quince (Cydonia
oblonga Miller) seeds: phenolics, organic acids and free amino acids. Nat
Prod Res. 2005;19:275–81.
21. Silva BM, Andrade PB, Ferreres F, et al. Phenolic profile of quince fruit
(Cydonia oblonga Miller) (pulp and peel). J Agric Food Chem. 2002;50:
4615–8.
22. Silva BM, Andrade PB, Martins RC, et al. Quince (Cydonia oblonga miller)
fruit characterization using principal component analysis. J Agric Food
Chem. 2005;53:111–22.
23. Silva BM, Andrade PB, Valentão P, et al. Quince (Cydonia oblonga Miller)
fruit (pulp, peel, and seed) and Jam: antioxidant activity. J Agric Food
Chem. 2004;52:4705–12.
24. Silva BM, Casal S, Andrade PB, et al. Free amino acid composition of
quince (Cydonia oblonga Miller) fruit (pulp and peel) and jam. J Agric Food
Chem. 2004;52:1201–6.
25. Umar A, Iskandar G, Aikemu A, et al. Effects of Cydonia oblonga Miller
leaf and fruit flavonoids on blood lipids and antioxydant potential in
hyperlipidemia rats. J Ethnopharmacol. 2015;169:239–43.
26. Winterhalter P, Harmsen S, Trani F. A C13-norisoprenoid gentiobioside
from quince fruit. Phytochemistry. 1991;30:3021–5.
27. Wojdyło A, Oszmiański J, Bielicki P. Polyphenolic composition, antioxi-
dant activity, and polyphenol oxidase (PPO) activity of quince (Cydonia
oblonga Miller) varieties. J Agric Food Chem. 2013;61:2762–72.
28. Zhou W, Abdurahman A, Umar A, et al. Effects of Cydonia oblonga Miller
extracts on blood hemostasis, coagulation and fibrinolysis in mice, and
experimental thrombosis in rats. J Ethnopharmacol. 2014;154:163–9.
29. Zhou W, Abdusalam E, Abliz P, et al. Effect of Cydonia oblonga Mill. fruit
and leaf extracts on blood pressure and blood rheology in renal hypertensive
rats. J Ethnopharmacol. 2014;152:464–9.
30. Zhou WT, Abdurahman A, Abdusalam E, et al. Effect of Cydonia oblonga
Mill. leaf extracts or captopril on blood pressure and related biomarkers in
renal hypertensive rats. J Ethnopharmacol. 2014;153:635–40.
31. Zhou WT, Yiming WL, Ma H, Mamat G, Umar A. Antihypertensive effect
of total flavonoids of Cydonia oblonga leaves and its mechanism based on
anti-inflammatory function. Zhong Yao Cai. 2015;38:2134–8 (Chinese).
32. Zohalinezhad ME, Imanieh MH, Samani SM, et al. Effects of Quince syrup
on clinical symptoms of children with symptomatic gastroesophageal reflux
disease: a double-blind randomized controlled clinical trial. Complement
Ther Clin Pract. 2015;21:268–76.
Cymbopogon schoenanthus (L.) Spreng.
(Poaceae/Graminae)

(Syns.: Andropogon schoenanthus L.; A. circinnatus Hochst. ex Steud.;

A. eriophorus Willd.)

Abstract
It is a typical desert species (grass), containing aromatic oil which persists in the
leaves for many years. The plant is found in South Asia and North Africa and
grows in hard lands and usually grows in the company of other plants. It is found
in all regions, including parts of Al-Rubb-al-Khali desert of Saudi Arabia, and is
locally known as Ethkher, Eskhabar or Hashma. Ethkher from Hijaz (a region in
west Saudi Arabia) is called Hurmi and is described as the 2nd best by Ishaq bin
Imran, and the one that grows in coastal Africa as the worst. Dymock et al.,
however, mentioned Andropogon laniger as the species called Izkhir or Ethkher.
Dioscorides described that the best kind grows in Arabia, that has an odor like
roses when rubbed between the hands, and a pungent taste. Arabian and Persian
authors identify Ethkher or Idkhir as Schoenus of the Greeks and Romans, as hot
and dry, lithotriptic, diuretic, carminative and emmenagogue. They recommend
it to be boiled in wine as a diuretic. Ground into a paste it is said to be a good
application for abdominal swellings. Added to purgatives, it is administered in
rheumatism; the flowers are used as hemostatic. Hippocrates mentioned the
emmenagogue property in the treatise on the diseases of women. Phytochemical
screening of the plant shows the presence of alkaloids and/or nitrogen bases,
flavonoids, sterols and/or triterpenes, tannins and volatile oils. Daily oral admini-
stration of C. schoenanthus extract produced significant diuretic activity and
prevented glycolic acid-induced nephrotoxicity, and kidney stone formation in
rats. Daily oral dose of ethanol extract to ICR mice for 2-weeks resulted in a
significant antistress effect, with a significant decrease in serum corticosterone
and increase in cerebral cortex levels of DA and NE.

Keywords




Aghin ghās Agiyā ghās Bhustrina Capim-cheiroso
Ethkher
Herbe à



chameau Kamelhewe Pasto de camellos Rusa grass

Zitronengras

© Springer Nature Switzerland AG 2020 839

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_88
840 Cymbopogon schoenanthus (L.) Spreng.

Vernaculars: Urd.: Aghin ghās, Agiyā ghās, Atigandha, Gandhel, Izkhar; Hin.:
Aghin ghas, Agiyā ghās, Atigandha, Bujina, Buraro, Gandhatrina, Gandhis,
Mirchiya gandh, Rajhans, Ruaghas, Rusa, Sugandha rosa; San.: Bhustrina, Bhu-
trina, Putimugdala, Rohisha, Rohishatrina, Sugandhatrinashita; Ben.: Agiya-ghas,
Gandha-bena, Ramakarpura, Roshel; Guj.: Roshdo, Roshghas Mal.: Sambarapul,
Shankanaru-pillu; Mar.: Gavati chaha, Hirva cha, Rohisha, Rohishe-gavat,
Rosegavath, Rushagavath, Sugandhirohisha; Tam.: Camparappul, Cukkunarippul,
Kamatcippul, Kantaketam, Karuppurappul, Kavattampu, Sakanaru-pillu; Ara.:
Askheer, Eskhabar, Ethkher, Hashmah, Idkhir, Khilal mamoon, Kur-al-eer, Taban
maka, Teeb al-ghareeb; Bur.: Sabalin-hmwe; Dut.: Kamelhewe; Eng.: Camel’s hay
or straw, Geranilum grass, Ginger grass, Rusa grass; Fre.: Citronnelle de Mada-
gascar, Herbe à chameau; Ger.: Kamelgras, Zitronengras; Gre.: Sajbuees; Per.:
Alaf-gorkhar, Gor giah, Kah makki, Kurta-e-dashti; Por.: Capim-cheiroso, Capim-
cidreira, Capim-cidrilho, Capim-ciri, Capim-de-cheiro, and Capim-limão (Br.);
Spa.: Pasto de camellos.
Description: It is a typical desert species (grass), containing aromatic oil which
persists in the leaves for many years. The plant is found in South Asia and North
Africa and grows in hard lands and usually grows in the company of other
plants.LXIX It is found in all regions, including parts of Al-Rubb-al-Khali desert of
Saudi Arabia, and is locally known as Ethkher, Eskhabar or Hashma [6]. Ethkher
from Hijaz (a region in west Saudi Arabia) is called Hurmi and is described as the
2nd best by Ishaq bin Imran, and the one that grows in coastal Africa as the
worst.LXIX Dymock et al.XL however, mentioned Andropogon laniger as the spe-
cies called Izkhir or Ethkher. Abu Hanifeh Ed-Dinawari, author of the Book of
Plants, described the plant as: “It has a root hidden in the ground, slender, pungent
in odor, and is like the straight stalks of the Kaulan (or papyrus plant), save that it is
wider, and smaller in the ku’oub (internodal spaces), and it has a fruit resembling
the blossom of reeds, but more slender and smaller; it is ground, and is an ingre-
dient in perfumes; it grows in rugged and in smooth grounds, but seldom does more
than one grow in the same spot; when it dries, becomes white” (Fig. 1).XL
Actions and Uses: Dioscorides described that the best kind grows in Arabia, that has
an odor like roses when rubbed between the hands, and a pungent taste. Arabian and
Persian authors identify Ethkher or Idkhir as Schoenus of the Greeks and Romans, as
hot and dry, lithotriptic, diuretic, carminative and emmenagogue. They recommend it
to be boiled in wine as a diuretic. Ground into a paste it is said to be a good application
for abdominal swellings. Added to purgatives, it is administered in rheumatism; the
flowers are used as hemostatic. Hippocrates mentioned the emmenagogue property in
the treatise on the diseases of women.XL In Unani medicine, the root (temperament,
hot 1° and dry 2°) is described as astringent, stomachic, digestive, appetizer, laxative,
deobstruent, antiflatulent, constipatory, and styptic,L diuretic and resolvent, and is
used in the treatment of paralysis, palsy, epilepsy, uterine, stomach and joint
inflammation.1 The oil is stimulant, carminative, antispasmodic and diaphoretic, and

1
Tayyab M: Personal Communication.
Cymbopogon schoenanthus (L.) Spreng. 841

Fig. 1 Cymbopogon schoenanthus, Plant, Daderot, WikimediaCommons, https://commons.wiki

media.org/wiki/File:Andropogon_schoenanthus_-_Val_Rahmeh_-_DSC04440.JPG

is also described as aromatic and stimulant, and useful in bilious and phlegmatic
affections. The plant is also reported to possess medicinal value as expectorant, and
anti-inflammatory.CXXVII
Phytoconstituents: Phytochemical screening of the plant shows the presence of
alkaloids and/or nitrogen bases, flavonoids, sterols and/or triterpenes, tannins and
volatile oils [2]. Khalil et al. [5] also reported the presence of coumarins in the
plant. Major component of the plant oil is geraniol (62.5%), which exhibits sig-
nificant anthelmintic activity against ovine trichostrongylids [4].
Pharmacology: Daily oral administration of C. schoenanthus extract produced
significant diuretic activity and prevented glycolic acid-induced nephrotoxicity, and
kidney stone formation in rats [1]. Daily oral dose of 100 and 200 mg/kg of ethanol
extract (CSEE) to ICR mice for 2-weeks resulted in a significant antistress effect,
with a significant decrease in serum corticosterone and increase in cerebral cortex
levels of DA and NE [3]. Ethanol extract produced mild sedation with slow and deep
respiration; and exhibited antibacterial activity against S. aureus, B. subtilis, and
P. vulgaris [2]. Pretreatment of human neuroblastoma SH-SY5Y cells with CSEE
significantly reversed H2O2-induced neurotoxicity and hsp expression in heat-
stressed HSP47-transformed cells [3].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
842 Cymbopogon schoenanthus (L.) Spreng.

Animal Toxicity: No animal toxicity studies are reported in the literature.

Commentary: This plant is widely used by common man in Saudi Arabia in their
daily lives. However, there are no clinical studies reported in published journals
listed on PubMed.

References
1. Al-Ghamdi SS, Al-Ghamdi AA, Shammah AA. Inhibition of calcium oxalate
nephrotoxicity with Cymbopogon schoenanthus (Al-Ethkher). Drug Metab
Lett. 2007;1:241–4.
2. Al-Yahya MA, Tariq M, Al-Meshal IA, Mossa JS. Chemical and biological
studies on Saudi medicinal plants. In: Proceedings of 43rd International
Congress on Pharmaceutical Sciences, Montreux; 1983. p. 18.
3. Ben Othman M, Han J, El Omri A, et al. Antistress effects of the ethanolic
extract from Cymbopogon schoenanthus growing wild in Tunisia. Evid
Based Complement Alternat Med. 2013;2013:737401.
4. Katiki LM, Chagas AC, Bizzo HR, et al. Anthelmintic activity of Cymbo-
pogon martinii, Cymbopogon schoenanthus and Mentha piperita essential oils
evaluated in four different in vitro tests. Vet Parasitol. 2011;183:103–8.
5. Khalil AM, El-Tawil BAH, et al. Constituents of lcal plants. Part 8. Distri-
bution of some coumarins in plants of different plant families grown in Saudi
Arabia. Pharmazie. 1981;36:569.
6. Migahid AM. Flora of Saudi Arabia, 2nd ed. Riyadh, Saudi Arabia: Riyadh
University Press; 1978. p. 695.
Cyperus rotundus L.
(Cyperaceae)

(Syns.: C. olivaris Targioni-Tozzetti; C. tuberosus Roxn.; Pycreus rotundus (L.)

Hayek)

Abstract
A species found throughout the plains of India especially south India, Asia,
Australia, southern Europe and North America. It is one of the world’s worst
invasive, most widespread, problematic, and economically damaging agronomic
weeds, growing wildly in various tropical and subtropical regions of the world.
Tuberous rhizomes are slightly fragrant and contain essential oil; the fragrance
resembles lemon and cardamom, and the tubers are used as perfume for clothing
and as a means to repel insects. Tubers are also aphrodisiac, and useful in infusion
or as soup in fevers, diarrhea, dysentery, dyspepsia, vomiting, and cholera. It is one
of the drugs mentioned by Dioscorides as cardiac, brain, nervine and gastric tonic,
carminative, mouth-freshener, diuretic, emmenagogue, astringent and stomachic.
It dilates blood vessels and causes diuresis in patients with kidney stones and
ascites, and is an antidote to scorpion poison. Topical application of decoction of
Indian variety completely removes hairs from the skin. In Ayurveda, its properties
are described as katu, tikta, and Kashaya taste; laghu and ruksha properties;
sita potency and katu taste after digestion; and its uses in agnimãndya, ajirna,
trsnã, jvara, sangrahani, ŝvãsa, kãsa, mutrakrcchra, stanyavikãra, vamana,
sutikãroga, atisãra, ãmavãta and krmiroga. In the Philippines, the rhizomes were
used in the treatment of dysentery, and roots for colic, indigestion, coughs and
heart troubles; and also worn by the Pokot as a protective charm against various
ailments in East Africa. In Chinese medicine, tubers are credited with vital-
energy-regulative, menstruation-corrective and analgesic properties; and are used
in the treatment of digestive disorders due to depressed vital energy of the liver,
retention of phlegm and fluid, chest and costal pain, irregular menstruation,
dysmenorrhea, and for various ailments during the perinatal period. From the
rhizomes/tubers sesquiterpenoids and sesquiterpene, iridoid glycosides, phenolic
compounds, b-selinene, sesquiterpene alkaloids, and a novel norsesquiterpene
have been isolated. Aqueous, ethanol, petroleum ether and other extracts of
rhizomes/tubers have exhibited significant anti-inflammatory effect in animal
models of inflammation. Rhizomes extract inhibits collagen-, thrombin-, and/or
© Springer Nature Switzerland AG 2020 843
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_89
844 Cyperus rotundus L.

AA-induced platelet aggregation; (+)-nootkatone, one of the components,

produces the most potent inhibitory effect on collagen-, thrombin-, and AA-
induced platelet aggregation.

Keywords





Castañuela Cipero orientale Herbe-à-oignon Hsiang-fu Junça Mustaka






Nagarmotha Nußgras Nut-grass Sa’ad kufi

Vernaculars: Urd.: Nagarmotha, Sa’ad kufi; Hin.: Korehi-jhar, Motha, Mutha,

Nagarmotha; San.: Abda, Ambuda, Gãñgeya, Ghana, Musta, Mustaka, Vãrida;
Ben.: Moothoo, Musta, Mutha, Nagarmothee, Sada-kufee; Mar.: Barik motha,
Bimbal, Moth, Nagarmoth; Tam.: Kora, Korai, Korai pul, Korai kizhangu,
Korakkarmooli, Tunga gaddai; Tel.: Bhadra-muste, Gandala, Kaivartakamuste,
Mustakamu, Shakhatungaveru, Tungamuste, Tungamustalu; Ara.: Suad kufi; Chi.:
Hsiang-fu, Suo cao, T’ien-t’ou ts’ao, Xiangfu, Xiangfuzi; Eng.: Coco grass,
Nut-grass, Nut sedge, Purple nut-grass, Purple nut sedge; Fre.: Herbe-à-oignon,
Souchet rond, Souchet à tubercules; Ger.: Nußgras, Rundes zypergras; Haw.: Kaa,
Mauu pukaa; Ita.: Cipero orientale, Cipero rotondo, Stancia rotunda, Zigolo
infestante; Jap.: Hamasuge; Nep.: Mothe; Per.: Mushk zer-e-zameen; Por.: Junça,
Junca-aromatica, Tiririca-comum; Spa.: Castañuela, Cebollín, Chufa silvestre,
Chunsa, Clavellet, Coquito, Juncia real, Totorilla; Tag.: Muthà; Tha.: Ya haeo mu,
Ya khon mu; Tur.: Topalak.
Description: A plentiful species found throughout the plains of India especially
south India, Asia, Australia, southern Europe and North America. It is one of the
world’s worst invasive, most widespread, problematic, and economically damaging
agronomic weeds, growing wildly in various tropical and subtropical regions of the
world. Its success in dominating natural habitats depends on its ability to prevent
herbivory, and to kill or suppress other plants growing in its vicinity [34, 41].
A perennial grass-like herb, 20–40 cm tall, glabrous, with an elaborate underground
system consisting of tubers, rhizomes and roots. The tubers are white and succulent
when young, and hard and black when mature. It thrives on all kinds of soils under
varying climatic conditions; once established, the plant spreads rapidly. Flowering
all the year; root stalk small, tuberous, stoloniferous; stolons elongate, slender,
bearing ovoid, hard tunicate, black, fragrant tubers 1–2.5 cm in diameter. Root
fibers wiry, covered with flexuous root hairs. Stem subsolitary 6–24 in number,
slender trigonous below and triquetrous above, base sometimes tuberous. Leaves
subradical, shorter or longer than the stem, narrowly linear 5–15 cm long and
2–6 mm broad, finely acuminate or narrowed from the middle to both ends, flat,
flaccid, and 1-veined.XL Dioscorides described solid, heavy and not easily break-
able root/rhizome as the best (Figs. 1, 2, 3 and 4).LXIX
Actions and Uses: Tuberous rhizomes are slightly fragrant and contain essential
oil;XXI the fragrance resembles lemon and cardamom,LXIV and the tubers are used
as perfume for clothing and as a means to repel insects.XXX It is one of the drugs
Cyperus rotundus L. 845

Fig. 1 Cyperus rotundus, Plants, Rickjpelleg, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Nutgrass_Cyperus_rotundus02.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Cyperus rotundus, Inflorescence, Jeevan Jose, © 2009 Jee & Rani Nature Photography,
WikimediaCommons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.
org/wiki/File:Cyperus_rotundus_by_kadavoor.JPG; https://creativecommons.org/licenses/by-sa/4.0/
deed.en
846 Cyperus rotundus L.

Fig. 3 Cyperus rotundus, Tuber, Rickjpelleg, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Cyperus_rotundus_tuber01.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 4 Cyperus rotundus, Flower Stem Cross Section, Rickjpelleg, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Nutgrass_
Cyperus_rotundus_stem_cross_section_and_flower_head.jpg; https://creativecommons.org/licenses/
by-sa/3.0/deed.en
Cyperus rotundus L. 847

mentioned by Dioscorides as cardiac, brain, nervine and gastric tonic, carminative,

mouth-freshener, diuretic, emmenagogue, astringent and stomachic.XXI,LXXVII It
dilates blood vessels and causes diuresis in patients with kidney stones and ascites,
and is an antidote to scorpion poison. Topical application of decoction of Indian
variety completely removes hairs from the skin.LXIX This author experimentally
verified, that application of its aqueous extract to the back of albino rats completely
removed hairs, leaving behind a shiny clean skin. Arab and Persian physicians
considered it diuretic, diaphoretic, astringent and stomachic, and prescribed it in
febrile affections and derangements of the bowel, and in one-ounce dose as an
anthelmintic; externally, it was applied to ulcers, and used as an ingredient in warm
plasters. It is the Suad of Abu Hanifeh Ed-Dinawari (author of the Book of Plants),
who described it as a certain kind of sweet-smelling root or rhizome, round, black,
hard like a knot, which is an ingredient in perfumes and medicines. Avicenna said
that the best kind of Suad is that which comes from Kufa in Chaldea, and that the
Indian drug (C. scariosus) makes the hair grow thin.XL Tubers are also aphrodisiac,
and useful in infusion or as soup in fevers, diarrhea, dysentery, dyspepsia, vomiting,
and cholera. Bulbous roots are scraped and pounded with green ginger, mixed with
honey and given in cases of dysentery, gastric and intestinal disorders. Romans
used it as emmenagogue in uterine complaints. Fresh tubers are applied to the breast
in the form of a paste or warm plaster to improve lactation. Paste is also applied to
scorpion stings and when dried to spreading ulcers.CV Tubers are used for edema,
urinary stones, leucorrhea, wound or mouth soreness in Indonesia, and the fruit is
used for kidney ailments in tropical America [12]. GhaniL describes it as lithotriptic,
deobstruent, digestive, improves intelligence and memory, and is beneficial for
jaundice, palpitation and halitosis due to indigestion. It also increases tone of the
external sphincter of the bladder. In Ayurveda, its properties are described as katu,
tikta, and Kashaya taste; laghu and ruksha properties; sita potency and katu taste
after digestion [31]; and its uses in agnimãndya, ajirna, trsnã, jvara, sangrahani,
ŝvãsa, kãsa, mutrakrcchra, stanyavikãra, vamana, sutikãroga, atisãra, ãmavãta
and krmiroga.CXXVII Decoction of the root (6–9 g) alone or in combination with the
root of Angelica sinensis and the leaves of Artemisia argyi are taken to regulate
menstruation and stop irregular bleeding [15, 16]. Khory and KatrakLXXXI descri-
bed the tubers as diaphoretic, diuretic, demulcent, stimulant and galactagogue, and
used in the treatment of fevers, dyspepsia, diarrhea, cholera, urinary calculi and
amenorrhea. Pirzada et al. [34] report its traditional uses in Pakistan as a home
remedy for diarrhea, diabetes, pyresis, inflammation, malaria, and stomach and
bowel disorders.
In the Philippines, the rhizomes were used in the treatment of dysentery,CXVII,
CXXXVIII
and roots for colic, indigestion, coughs and heart troubles; and also worn by
the Pokot as a protective charm against various ailments in East Africa.LXXXV The
root and tubers are used as aromatic stomachic in nervous gastralgia, dyspepsia,
diarrhea, and are also reported as sedative and analgesic, and used in dysmenorrhea,
amenorrhea and chronic metritis.LXXIX,CL In Tunisian traditional medicine, it is used
to treat stomach disorders and inflammatory diseases [47]. In Chinese medicine,
848 Cyperus rotundus L.

tubers are known as Xiangfu or Xiangfuzi, which are described as pungent, slightly
bitter and “mild.” They are credited with vital-energy-regulative (or carminative),
menstruation-corrective and analgesic properties; and are therefore, used in the
treatment of digestive disorders due to depressed vital energy of the liver, retention
of phlegm and fluid, chest and costal pain, irregular menstruation, dysmenorrhea,
and for various ailments during the perinatal period. It is the chief drug used in
various affections of the vital energy, and is an important remedy for gynecological
diseases.XVIII Dried tuber was originally named as Sha-Tsao recorded in Ming I Pieh
Lu (500 A.D.) and later called as Shiang-Fu-Tzu in Tang Pen Tsao (659 A.D.)LXVI
with emmenagogue, antispasmodic, antitussive, and analgesic properties, and used
for uterine disorders, distension and pain in the chest and abdomen, menstrual
irregularities and cramps; to relieve melancholia, and cardiac and stomachache.LXV
It is one of the indigenous Thai medicinal plants used in the treatment of dysuria
[49]. In the Hawaiian Islands, buds, leaves and roots along with whole plants of
Cassia occidentalis and Desmodium uncinatum are pounded together, put in salt
water, heated with red hot stones, cooled, strained and used for bath by patients with
whole body pain.LXXVI Menaut [30] mentions their use in Cambodia for liver
complaints with icterus, for malaria and headache; and in Java, used in urinary
disorders.LXII
Phytoconstituents: Rootstocks contain alkaloid, cardiac glycoside and flavonoids
[2, 51], tannins, phenolics, anthraquinones [51], fat, sugar, gum, carbohydrates,
essential oil, albuminous matter, starch, and fiber ash.CV From the rhizomes/tubers
sesquiterpenoids and sesquiterpene [19, 52, 59, 61], iridoid glycosides [64], phe-
nolic compounds [65], the antimalarial compound, b-selinene [57], sesquiterpene
alkaloids [18], and a novel norsesquiterpene, 8,11,11-trimethylbicyclo[5.3.1]
undecane-5a,8a-epoxy-3-one [60] have been reported. The sesquiterpenes possess
antiallergic activity [19]. From the aerial parts steroid glycoside and furochromones
(khellin, visnagin and ammiol) [38], adenosine, (-)-(E)-caffeoylmalic acid, vitexin,
isovitexin, orientin, epiorientin, myricetin 3-O-b-D-galactopyranoside, luteolin
7-O-b-D-glucuronopyranoside-6″-methyl ester, chlorogenic acid, luteolin 4′-O-b-D-
glucuronopyranoside, uridine, ellagic acid and luteolin 7-O-b-D-glucuronopyrano-
side [39] have been isolated.
Essential oil contains at least 27 components comprising sesquiterpene hydro-
carbons, sesquiterpene epoxides, sesquiterpene ketones, monoterpene and aliphatic
alcohols and some unidentified constituents [21]. Akbar et al. [1] reported presence
of tannins, proteins, glycosides, sterols, reducing and non-reducing sugars. The
volatile oil (0.3–1%) produced in China contained cyperene and patchoulenone,
whereas that produced in Japan contained cyperol, cyperene, a-cyperone, cypero-
tundone and cyperolone. Cyperene consists of cyperene I and cyperene II, both are
terpenes.XVIII Minor constituents of the EO are sesquiterpene hydrocarbons:
(−)-isorotundene, (−)-cypera-2,4(15)-diene and (−)-norrotundene, and the ketone,
(+)-cyperadione [46]. Essential oils of rhizomes collected from two different loca-
tions in the Kwa-Zulu Natal Province of South Africa, showed 41 and 43 compo-
nents, representing 89.9% and 92% of the samples, respectively. Alpha-cyperone
Cyperus rotundus L. 849

(11%), myrtenol (7.9%), caryophyllene oxide (5.4%) and b-pinene (5.3%) were
major compounds in one sample; whereas the main constituents of the other sample
were b-pinene (11.3%), a-pinene (10.8%), a-cyperone (7.9%), myrtenol (7.1%) and
a-selinene (6.6%) [25].
Pharmacology: Aqueous, ethanol, petroleum ether and other extracts of rhizomes/
tubers have exhibited significant anti-inflammatory effect in various animal models
of inflammation [1, 6, 43]. A triterpenoid isolated from petroleum ether extract
showed 8 greater anti-inflammatory activity than hydrocortisone; and also
showed antipyretic and analgesic effects [10, 11]. Yeast-induced pyrexia in rats was
alleviated by ethanol extract, and its efficacy was 6 that of sodium salicylate [43];
the active antipyretic principles are also triterpenes [10]. Extracts of aerial parts
and the EO of the rhizomes have shown anti-inflammatory activity [4, 47],
and methanol extract also significantly inhibited XO activity [48]. b-sitosterol,
isolated from the plant, produced antipyretic and potent anti-inflammatory activity
similar to both cortisone and oxyphenbutazone [11]. Anti-inflammatory activity of
b-sitosterol was independent of pituitary adrenal axis, with a wide margin of safety,
since the LD50 was more than 3 g/kg i. p. in mice and the minimum ulcerogenic
dose was 600 mg/kg i.p. in rats [9]. Ethanol extract markedly elevated pain
threshold in mice [33], and the analgesic effect of hydromethanol extract of whole
plant was suggested to be mediated through both peripheral and central mechanisms
[14]. Hydroalcohol [24, 62], methanol and aqueous extracts [48], and EO [23] of
tubers have shown in vitro antioxidant activity.
Daily administration of ethanol extract for 7-days significantly lowered blood
glucose of alloxan-diabetic rats; the antidiabetic activity was suggested to be due to
its antioxidant activity [36]. Methanol rhizome extract also inhibited activities of
a-glucosidase and a-amylase. Stilbene dimer, cassigarol E was identified as the
inhibitor of both a-glucosidase and a-amylase activities [54]. Hexane extract for
60-days to obese Zucker rats significantly reduced weight gain without affecting
food consumption or causing any toxicity; and stimulated lipolysis in 3T3-F442
adipocytes supposedly activating b-adrenoreceptors, known to induce thermo-
genesis [27].
Alcohol extract showed tranquillizing effect [33], enhanced anesthetic effect of
phenobarbital but no protection against MES- or PTZ-induced convulsions in mice;
protected guinea pigs from histamine-bronchospasm, and protected dogs against
apomorphine-induced emesis [42, 43], but did not modify scopolamine-induced
memory deficit in rats [13, 35]. Total oligomeric flavonoids also exhibit neuro-
protective effect in I/R and sodium nitrite-induced neurological deficits [17, 50].
Dabaghian et al. [5] reported no protection by ethanol extract against transient
global cerebral ischemia-induced cognitive impairments in rats. However, aqueous
extract in vitro protected against 6-OHDA-induced neuronal toxicity [26], and
hexane extract showed very potent inhibitory activity of Na+, K+-ATPase of rat
brain [32]. Aqueous extract also showed lactogenic activity in rats [3].
850 Cyperus rotundus L.

The rhizomes extract inhibits collagen-, thrombin-, and/or AA-induced platelet

aggregation; (+)-nootkatone, one of the components, produces the most potent
inhibitory effect on collagen-, thrombin-, and AA-induced platelet aggregation [40].
Intravenous ethanol extract produced a progressive fall in BP of dogs for up to one
hour, without affecting effects of epinephrine and ACh, but it partially blocked the
histamine effect [43]. Aqueous extract of the rhizome failed to show any diuretic
effects in rats [49], but methanol extract was significantly protective against CCl4-
hepatotoxicity in mice.XIX
Acetone and ethanol extracts showed modest antimicrobial activity against
E. coli, S. aureus, S. typhi, S. paratyphi, S. typhimurium, K. pneumoniae, and
S. flexineri [51], and the ethanol extract demonstrated potent anti-HBV activity in
HepG2 cell line [59]. The extract inhibited growth and acid production by
S. mutans, the causative bacteria for the formation of dental plaque and dental caries
[63]. The EO was significantly active against C. albicans [8], and Sini and Malathy
[44] reported moderate activity of hexane and aqueous extracts against B. pumilis
and E. coli; whereas a marked inhibitory effect of total oligomers flavonoids and
ethyl acetate extracts against S. enteritidis, S. aureus and E. faecalis was reported
by Kilani et al. [22] Hydroalcohol extract was also reported to have virucidal effect
against HSV-1 [45]. Alpha-cyperone showed significant antimalarial activity
against MDR strain of P. falciparum [57, 58]. Aqueous extract was active against
infectious diarrhea [7], while methanol extract showed significant activity against
castor oil-induced diarrhea in mice [56]. Methanol extract also significantly
inhibited ASA-induced gastric ulceration, comparable to ranitidine, and signifi-
cantly increased activity of SOD, cellular GSH and GPx and inhibited LPO in the
gastric mucosa of ulcerated rats [53].
Clinical Studies: A 2% sterilized methanol extract of the roots was nonirritant and
produced subjective as well as objective improvement within 24 h in 26 hospital-
ized cases of conjunctivitis [37]. Luda Health Bureau of China [29] reported that
Rhizoma cyperi (120 g) and Rhizoma Alpiniae officinarum (90 g) were ground to
fine powder and administered orally in a dose of 3 g once every morning to 30
patients of gastritis of the “cold” stasis and ‘vital-energy stagnation’ type, and
gastric spasm. An 80% effective rate was achieved.XVIII Liu et al. [28] reported a
compound preparation containing Cyperus rotundus to be effective in cases of
intestinal metaplasia (IM) and atypical hyperplasia (AH) of the gastric mucosa of
chronic gastritis. The 138 cases of IM and 104 cases of AH with diagnoses based on
pathological examination of gastric antrum biopsy specimens were randomly
divided into control and treated groups. The treated group was administered orally a
mixture of powdered Smilax glabrae, Hedyotis diffusae, Taraxacum mongolicum,
Caesalpinia sappan, Paeonia alba, Cyperus rotundus, Bletilla striata and Glyc-
errhiza uralensis, 5–7 g tid for 2–4 months. The effective rate in cases of IM was
91.3% and in cases of AH 92.16%, while the control groups had improvements in
21.3 and 14.46%, respectively. The compound powder revealed no toxic effects in
animal experiments.
Cyperus rotundus L. 851

Mechanism of Action: In vitro and in vivo studies have suggested heme oxyge-
nase (HO-1) induction as possible anti-inflammatory mechanism due, in part, to
sesquiterpenes, such as nootkatone and valencene [55]; whereas, anti-inflammatory
activity of a-cyperone was associated with downregulation of COX-2 and IL-6 via
the negative regulation of the NF-jB pathway [20].
Human A/Es, Allergy and Toxicity: Adverse effects are rare. However, in China,
caution is exercised when using this herb in patients with deficiency of “yin” and
weakness of vital energy.
Animal Toxicity: Acute LD50 (i.p.) of ethanol extract in mice was about
1,500 mg/kg [43]; whereas LD50 (i.p.) of the anti-inflammatory active triterpenoid
was 50 mg/kg, and the ED50 1.6 mg/kg [10, 11].
Commentary: While the pharmacological studies showed significant anti-inflamma-
tory, analgesic and sedative properties of the rhizomes, there are no formal clinical studies
reported except one methanol extract being effective in conjunctivitis, but no follow-up
studies to substantiate the effect. Chinese studies are on compound drugs, of which C.
rotundus was just one component. Based on these studies no informed impression of its
effectiveness in any clinical conditions can be generated.

References
1. Akbar S, Nisa M, Tariq M. Preliminary phytochemical studies on the tubers
of Cyperus rotundus Linn. Nagarjun. 1983;26:123–5.
2. Akperbekova BA. On the characteristic of chemical composition of rhizome
of Cyperus rotundus L. Farmatsiia. 1967;16:36–41 (Russian).
3. Badgujar SB, Bandivdekar AH. Evaluation of a lactogenic activity of an
aqueous extract of Cyperus rotundus Linn. J Ethnopharmacol. 2015;163:
39–42.
4. Chen Y, Zhao YY, Wang XY, et al. GC-MS analysis and analgesic activity
of essential oil from fresh rhizoma of Cyperus rotundus. Zhong Yao Cai.
2011;34:1225–9 (Chinese).
5. Dabaghian FH, Hashemi M, Entezari M, et al. Effect of Cyperus rotundus
on ischemia-induced brain damage and memory dysfunction in rats. Iran J
Basic Med Sci. 2015;18:199–204.
6. Dang GK, Parekar RR, Kamat SK, et al. Anti-inflammatory activity of
Phyllanthus emblica, Plumbago zeylanica and Cyperus rotundus in acute
models of inflammation. Phytother Res. 2011;25:904–8.
7. Daswani PG, Brijesh S, Tetali P, Birdi TJ. Studies on the activity of Cyperus
rotundus Linn. tubers against infectious diarrhea. Indian J Pharmacol.
2011;43:340–4.
8. Duarte MC, Figueira GM, Sartoratto A, et al. Anti-candida activity of
Brazilian medicinal plants. J Ethnopharmacol. 2005;97:305–11.
9. Gupta MB, Nath R, Srivastava N, et al. Anti-inflammatory and antipyretic
activities of b-sitosterol. Planta Med. 1980;39:157–63.
852 Cyperus rotundus L.

10. Gupta MB, Polit TK, Singh N, Bhargava KP. Pharmacological studies to isolate
the active constituents from Cyperus rotundus possessing anti-inflammatory,
antipyretic and analgesic activities. Indian J Med Res. 1971;59:76–82.
11. Gupta MB, Singh N, Palit TK, Bhargava KP. Anti-inflammatory activity of
an active constituent of Cyperus rotundus. Indian J Pharmacol. 1970;2:23.
12. Hirschhorn HH. Constructing a phytotherapeutic concordance based upon
tropical American and Indonesian examples. J Ethnopharmacol. 1983;7:
157–67.
13. Hsieh MT, Peng WH, Wu CR, Wang WH. The ameliorating effects of the
cognitive-enhancing Chinese herbs on scopolamine-induced amnesia in rats.
Phytother Res. 2000;14:375–7.
14. Imam MZ, Sumi CD. Evaluation of antinociceptive activity of hydro-
methanol extract of Cyperus rotundus in mice. BMC Complement Altern
Med. 2014;14:83.
15. Indira M, Murthy PSN, Sirsi M. Estrogenic activity, antibacterial action and
some pharmacodynamic properties of Cyperus rotundus (Linn.) (N.O.
Cyperaceae). J Mysore Med Assoc. 1956;21:1.
16. Indira M, Sirsi M, Radomir S, Sukhdev. The occurrence of some estrogenic
substances in plants. Part I. Estrogenic activity of Cyperus rotundus Linn.
J Sci Indust Res. 1956;15C:202.
17. Jebasingh D, Devavaram Jackson D, Venkataraman S, Adeghate E, Starling
Emerald B. The protective effects of Cyperus rotundus on behavior and
cognitive function in a rat model of hypoxia injury. Pharm Biol. 2014;52:
1558–69.
18. Jeong SJ, Miyamoto T, Inagaki M, et al. Rotundines A-C, three novel
sesquiterpene alkaloids from Cyperus rotundus. J Nat Prod. 2000;63:673–5.
19. Jin JH, Lee DU, Kim YS, Kim HP. Antiallergic activity of sesquiterpenes
from the rhizomes of Cyperus rotundus. Arch Pharm Res. 2011;34:223–8.
20. Jung SH, Kim SJ, Jun BG, et al. a-Cyperone, isolated from the rhizomes of
Cyperus rotundus, inhibits LPS-induced COX-2 expression and PGE2
production through the negative regulation of NFjB signalling in RAW
264.7 cells. J Ethnopharmacol. 2013;147:208–14.
21. Kapadia VH, Naik NG, Wadia MS, Sukhdev. Sesquiterpenoids from the
essential oil of Cyperus rotundus L. J Res Punj Agr Univ. 1969;6:383.
22. Kilani S, Ben Sghaier M, Limem I, et al. In vitro evaluation of antibacterial,
antioxidant, cytotoxic and apoptotic activities of the tubers infusion and
extracts of Cyperus rotundus. Bioresour Technol. 2008;99:9004–8.
23. Kilani S, Ledauphin J, Bouhlel I, et al. Comparative study of Cyperus
rotundus essential oil by a modified GC/MS analysis method. Evaluation of
its antioxidant, cytotoxic, and apoptotic effects. Chem Biodivers. 2008;5:
729–42.
Cyperus rotundus L. 853

24. Kumar KH, Khanum F. Hydroalcoholic extract of Cyperus rotundus

ameliorates H2O2-induced human neuronal cell damage via its anti-
oxidative and antiapoptotic machinery. Cell Mol Neurobiol. 2013;33:5–17.
25. Lawal OA, Oyedeji AO. Chemical composition of the essential oils of
Cyperu rotundus L. from South Africa. Molecules. 2009;14:2909–17.
26. Lee CH, Hwang DS, Kim HG, et al. Protective effect of Cyperi rhizoma
against 6-hydroxydopamine-induced neuronal damage. J Med Food. 2010;
13:564–71.
27. Lemaure B, Touché A, Zbinden I, et al. Administration of Cyperus rotundus
tubers extract prevents weight gain in obese Zucker rats. Phytother Res.
2007;21:724–30.
28. Liu XR, Han WQ, Sun DR. Treatment of intestinal metaplasia and atypical
hyperplasia of gastric mucosa with Xiao Wei Yan powder. Chung-Kuo
Chung Hsi i Chieh Ho Tsa Chih. 1992;12:602–3, 580 (Chinese).
29. Luda Health Bureau. Applications of Chinese Traditional Prescriptions.
1976. p. 101 (cited by Chang and But)XVIII.
30. Menaut H. Matiere medicale cambodgienne. (Les drogues uselles). Bull
Econ Indo-China. 1929;32:197–276.
31. Nagarajan M, Kuruvilla GR, Kumar KS, Venkatasubramanian P. Pharma-
cology of Ativisha, Musta and their substitutes. J Ayurveda Integr Med.
2015;6:121–33.
32. Ngamrojanavanich N, Manakit S, Pornpakakul S, Petsom A. Inhibitory
effects of selected Thai medicinal plants on Na+,K+-ATPase. Fitoterapia.
2006;77:481–3.
33. Pal D, Dutta S, Sarkar A. Evaluation of CNS activities of ethanol extract of
roots and rhizomes of Cyperus rotundus in mice. Acta Pol Pharm. 2009;66:
535–41.
34. Pirzada AM, Ali HH, Naeem M, et al. Cyperus rotundus L.: traditional uses,
phytochemistry, and pharmacological activities. J Ethnopharmacol. 2015;174:
540–60.
35. Rabbani M, Ghannadi A, Malekian N. Evaluation of the effect of Cyperus
rotundus L. in scopolamine-induced learning deficit in mice. Adv Biomed
Res. 2014;3:217.
36. Raut NA, Gaikwad NJ. Antidiabetic activity of hydroethanolic extract of
Cyperus rotundus in alloxan induced diabetes in rats. Fitoterapia. 2006;77:
585–8.
37. Saxena RC, Punhani KC, Palit TK, Singh N, Bhargava KP. Preliminary
report on the anti-inflammatory activity of Cyperus rotundus in conjunc-
tivitis. Indian J Pharmacol. 1971;3:9.
38. Sayed HM, Mohamed MH, Farag SF, et al. A new steroid glycoside and
furochromones from Cyperus rotundus L. Nat Prod Res. 2007;21:343–50.
39. Sayed HM, Mohamed MH, Farag SF, et al. Fructose-amino acid conjugate
and other constituents from Cyperus rotundus L. Nat Prod Res. 2008;22:
1487–97.
854 Cyperus rotundus L.

40. Seo EJ, Lee DU, Kwak JH, et al. Antiplatelet effects of Cyperus rotundus
and its component (+)-nootkatone. J Ethnopharmacol. 2011;135:48–54.
41. Sharma R, Gupta R. Cyperus rotundus extract inhibits acetylcholinesterase
activity from animal and plants as well as inhibits germination and seedling
growth in wheat and tomato. Life Sci. 2007;80:2389–92.
42. Singh N, Kulshreshtha VK, Gupta HB, Bhargava KP. Pharmacological
studies on Cyperus rotundus. Indian J Pharmacol. 1969;1:19.
43. Singh N, Kulshreshtha VK, Gupta MB, Bhargava KP. A pharmacological
study of Cyperus rotundus. Indian J Med Res. 1970;58:103–9.
44. Sini S, Malathy NS. Antimicrobial properties of roots of medicinal plants.
Anc Sci Life. 2005;25:62–5.
45. Soltan MM, Zaki AK. Antiviral screening of forty-two Egyptian medicinal
plants. J Ethnopharmacol. 2009;126:102–7.
46. Sonwa MM, König WA. Chemical study of the essential oil of Cyperus
rotundus. Phytochemistry. 2001;58:799–810.
47. Soumaya KJ, Dhekra M, Fadwa C, et al. Pharmacological, antioxidant,
genotoxic studies and modulation of rat splenocyte functions by Cyperus
rotundus extracts. BMC Complement Altern Med. 2013;13:28.
48. Soumaya KJ, Zied G, Nouha N, et al. Evaluation of in vitro antioxidant and
apoptotic activities of Cyperus rotundus. Asian Pac J Trop Med. 2014;7:
105–12.
49. Sripanidkulchai B, Wongpanich V, Laupattarakasem P, et al. Diuretic effects
of selected Thai indigenous medicinal plants in rats. J Ethnopharmacol.
2001;75:185–90.
50. Sunil AG, Kesavanarayanan KS, Kalaivani P, et al. Total oligomeric flavo-
noids of Cyperus rotundus ameliorates neurological deficits, excitotoxicity
and behavioral alterations induced by cerebral ischemic-reperfusion injury
in rats. Brain Res Bull. 2011;84:394–405.
51. Tambekar DH, Khante BS, Chandak BR, et al. Screening of antibacterial
potentials of some medicinal plants from Melghat forest in India. Afr J
Tradit Complement Altern Med. 2009;6:228–32.
52. Thebtaranonth C, Thebtaranonth Y, Wanauppathamkul S, Yuthavong Y.
Antimalarial sesquiterpenes from tubers of Cyperus rotundus: structure of
10,12-peroxycalamenene, a sesquiterpene endoperoxide. Phytochemistry.
1995;40:125–8.
53. Thomas D, Govindhan S, Baiju EC, et al. Cyperus rotundus L. prevents
nonsteroidal anti-inflammatory drug-induced gastric mucosal damage by
inhibiting oxidative stress. J Basic Clin Physiol Pharmacol. 2015;26:485–90.
54. Tran HH, Nguyen MC, Le HT, et al. Inhibitors of a-glucosidase and
a-amylase from Cyperus rotundus. Pharm Biol. 2014;52:74–7.
55. Tsoyi K, Jang HJ, Lee YS, et al. (+)-Nootkatone and (+)-valencene from
rhizomes of Cyperus rotundus increase survival rates in septic mice due to
heme oxygenase-1 induction. J Ethnopharmacol. 2011;137:1311–7.
56. Uddin SJ, Mondal K, Shilpi JA, Rahman MT. Antidiarrhoeal activity of
Cyperus rotundus. Fitoterapia. 2006;77:134–6.
Cyperus rotundus L. 855

57. Weenen H, Nkunya MH, Bray DH, et al. Antimalarial compounds containing
an alpha, beta-unsaturated carbonyl moiety from Tanzanian medicinal plants.
Planta Med. 1990;56:371–3.
58. Weenen H, Nkunya MH, Bray DH, et al. Antimalarial activity of Tanzanian
medicinal plants. Planta Med. 1990;56:368–70.
59. Xu HB, Ma YB, Huang XY, et al. Bioactivity-guided isolation of antihepatitis
B virus active sesquiterpenoids from the traditional Chinese medicine:
rhizomes of Cyperus rotundus. J Ethnopharmacol. 2015;171:131–40.
60. Xu Y, Zhang HW, Yu CY, et al. Norcyperone, a novel skeleton norsesquiter-
pene from Cyperus rotundus L. Molecules. 2008;13:2474–81.
61. Yang JL, Shi YP. Structurally diverse terpenoids from the rhizomes of
Cyperus rotundus L. Planta Med. 2012;78:59–64.
62. Yazdanparast R, Ardestani A. In vitro antioxidant and free radical
scavenging activity of Cyperus rotundus. J Med Food. 2007;10:667–74.
63. Yu HH, Lee DH, Seo SJ, You YO. Anticariogenic properties of the extract
of Cyperus rotundus. Am J Chin Med. 2007;35:497–505.
64. Zhou Z, Yin W, Zhang H, Feng Z, Xia J. A new iridoid glycoside and
potential MRB inhibitory activity of isolated compounds from the rhizomes
of Cyperus rotundus L. Nat Prod Res. 2013;27:1732–6.
65. Zhou Z, Yin W. Two novel phenolic compounds from the rhizomes of
Cyperus rotundus L. Molecules. 2012;17:12636–41.
Datura stramonium L.
(Solanaceae)

Abstract
A bushy annual herb found in India, Sri Lanka, northern Persia, Afghanistan,
Americas, Germany, France, and Hungary. It is an extremely poisonous plant that
may cause death upon ingestion. The name Jimsonweed is believed to have derived
from Jamestown weed, referring to an incident (about 1676 A.D.) when soldiers,
sent to quell a rebellion in the Jamestown Colony in North America, put some of
the herb into their cooking pot and spent the next 11-days in a state of incoherence.
Marc Antony’s troops also ate Datura when retreating from Parthia in 38 A.D. that
caused delirium, stupor, and ultimately death. Charles Millspaugh, a homeopathic
enthusiast mentioned in his book The American Plants Used As Homeopathic
Medicine that Baron Sttirck was the first to introduce the plant into medicine for
mania and epilepsy. Ibn-al-Baitar mentioned several authorities, such as Ghafiqi,
Razi, Ibn-e-Sina to describe this plant as CNS depressant in low doses and lethal in
more than 1.75 g dose, and most of its toxic effects are on the heart. According to
Razi, it produces nausea, vomiting and hallucinations, and is analgesic and
anesthetic on external application. Internally, it is a CNS depressant, antispas-
modic for respiratory tract, and is used in rheumatism, gout, headache, cough and
asthma; digestive, anthelmintic, hypnotic, relieves headache due to excessive
blood or yellow bile, and is useful in rabid dog bite. Hindu physicians describe it
useful in fever, skin diseases, boils, itch, worms, and insanity. Muslim physicians
of India preferred the purple-flowered variety and mentioned all parts of the plant
powerfully intoxicating and narcotic; and locally applied to relieve pain of tumors
and piles. It possesses properties analogous to that of belladonna, the leaves are
smoked to relieve asthmatic attacks and in the treatment of Parkinson’s disease.
It contains a variety of toxic tropane alkaloids; main alkaloids present in all
Datura species are the parasympatholytic alkaloids atropine (dl-hyoscyamine),
l-hyoscyamine (l-isomer of atropine) and hyoscine (scopolamine). Inhaling the

© Springer Nature Switzerland AG 2020 857

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_90
858 Datura stramonium L.

smoke of one Datura cigarette by asthmatic patients with mild airway obstruction
substantially decreased specific airway resistance, the mean maximal decrease
being 40% at 30th minute.

Keywords




Angel’s trumpet Boruçiçeği Burladora Dhatura Dhustura

Doornappel





Jimson weed Joz maasal Man tuo luo Mezzettoni

Vernaculars: Urd.: Dhatura, Joz maasal, Tatura; Hin.: Dhatura, Kanakbij; San.:
Dhattura, Dhustura, Henuka, Kanaka, Sveta, Unmatta, Unmeta; Ben.: Dhatura, Sada
dhutura; Mal.: Rotikubung, Ummatta; Mar.: Dhotara, Kante-dhotara, Pisola; Tam.:
Umattai; Tel.: Ummetta; Ara.: Bunj, Datura, Joz-almasal, Joz-dab, Joz-el-mathil,
Joz-mahabal, Joz-mahalik, Joz-maqatal, Joz-masa, Joz-mulsam, Shajratul murqad,
Tatura; Chi.: Man tuo luo; Dut.: Doornappel, Gewone doornappel; Eng.: Angel’s
trumpet, Jimson weed, Stink weed, Thorn-apple; Fre.: Datura officinale, Datura
stramoine, Datura tatula, Herbe à la taupe, Pomme épineuse, Stramoine commune;
Ger.: Gemeiner stechapfel, Gewöhnlicher stechapfel, Stechapfel, Weißer stechapfel;
Ita.: Mezzettoni, Noce spinosa, Stramonio comune; Jap.: Chôsen-asagao, Dachura,
Datsura, Shiro-bana-chôsen-asagao, Yôshu-chôsen-asagao; Per.: Gauz ma’sal,
Tatulah; Por.: Castanheiro-do-diabo, Erva-do-diabo, Erva-dos-bruxos, Erva-dos-
mágicos, Estramonio, Figueira-brava, Figueira-do-inferno, Mamoninho, Pomo-
espinhoso, Quinquilho (Br.); Spa.: Belladonna del pobre, Berenjena del diablo,
Burladora, Chamico azul, Chamico morado, Cornescopia espantarratones, Flor de la
trompeta, Hierba ratonera, Higuera del infierno, Trompetilla; Tur.: Boruçiçeği.
Description: A bushy annual herb found in India, Sri Lanka, northern Persia,
Afghanistan, Americas, Germany, France, and Hungary.CXXXXI It attains a height
of about 1.5 m, and has a large whitish root and numerous rootlets. The erect aerial
stem shows dischasial branchings to the stem, and branches are round, smooth and
green. Leaves of D. stramonium, D. fastuosa, and D. metel are very similar; have
long petioles, are unequal at the base, ovate, acuminate, sinuate-dentate, with large
irregular pointed lobes; when fresh they are firm and juicy, and have a disagreeable
fetid odor, which they lose when dry. All species have large trumpet-shaped,
night-scented flowers which in D. fastuosa vary much in color and are often double.
In D. stramonium they are white, and in D. metel purplish-white. Flowers are
solitary, axillary and short-stalked with a sweet scent; each has a tubular, fine
toothed calyx, a white funnel-shaped corolla, fine stamens and a bicarpellary ovary.
The plant flowers in summer and early autumn. Fruit is originally bilocular but as it
matures a false septum arises, except near the apex, so that the mature fruit is almost
completely four-celled. The ripe fruit is a thorny capsule about 3–4 cm long. Seeds
are dark-brown or blackish in color, reniform in outline and about 3 mm long; seeds
of both D. stramonium and D. fastuosa have a bitterish taste and disagreeable odor
when bruised. Fruits and seeds of D. metel are similar to those of D. fastuosa.
Sanskrit writers sometimes specify whether black or white Dhustura is to be used,
Datura stramonium L. 859

but do not draw any distinction between properties of different plants (species). In
India, the black or purple-flowered variety of D. fastuosa was preferred (Figs. 1, 2,
3 and 4).XL
Actions and Uses: It is an extremely poisonous plant that may cause death upon
ingestion. The name Jimsonweed is believed to have derived from Jamestown
weed, referring to an incident (about 1676 A.D.) when soldiers, sent to quell a
rebellion in the Jamestown Colony in North America, put some of the herb into
their cooking pot and spent the next 11-days in a state of incoherence. Marc
Antony’s troops also ate Datura when retreating from Parthia in 38 A.D. that caused
delirium, stupor, and ultimately death [26]. A number of ceramic forms found show
a distinctive spiny fruit characteristic of the North American species of this genus
with similarities in details of its medicinal and ceremonial use, over a wide area in
aboriginal North America, especially in the southwest United States to southern
Mexico and Guatemala [34]. Charles Millspaugh,XCVII a homeopathic enthusiast
mentioned in his book The American Plants Used As Homeopathic Medicine that
Baron Sttirck was the first to introduce the plant into medicine for mania and
epilepsy. Bergius states that he frequently saw maniacs restored to saneness of
mind, which they never afterward lost, by the continued use of the extract of
Stramonium; and that by the same means he effectually cured delirium so often
attendant upon childbirth. In general practice, Stramonium has been used as a
narcotic, soothing drug, in chorea, epilepsy, neuralgia, and tic douloureux, and as

Fig. 1 Datura stramonium, Leaves and Flower, Taka, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Datura_stramonium_2_
(2005_07_07).jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
860 Datura stramonium L.

Fig. 2 Datura stramonium, Flower (close-up), Júlio Reis, WikimediaCommons, https://comm

ons.wikimedia.org/wiki/File:Datura_stramonium_white_flower.jpg

Fig. 3 Datura stramonium, Seedpod, Nova, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Datura_stramonium_Bielu%C5%84_dzi%
C4%99dzierzawa_Seed_01.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

an ointment in recent burns and scalds, nymphomania and rheumatism. One of its
principal uses, however, has been that of the dried leaves, smoked as cigarettes,
during spasm of asthma. Dioscorides (40–90 A.D.) prescribed inhaled fumigation,
and pipes were also used to inhale hallucinogenic substances.
Datura stramonium L. 861

Fig. 4 Datura stramonium, Fruit and Seeds, Didier Descouens, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Datura_stramonium_
MHNT.BOT.2004.0.263a.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Ibn-al-BaitarLXIX mentioned several authorities, such as Ghafiqi, Razi, Ibn-e-

Sina to describe this plant as CNS depressant in low doses and lethal in more than
1.75 g dose, and most of its toxic effects are on the heart. According to Razi, it
produces nausea, vomiting and hallucinations, and is analgesic and anesthetic on
external application. Internally, it is a CNS depressant, antispasmodic for respira-
tory tract, and is used in rheumatism, gout, headache, cough and asthma;LXXVII
digestive, anthelmintic, hypnotic, relieves headache due to excessive blood or
yellow bile, and is useful in rabid dog bite.L It is used in hepatic colic, laryngeal
cough, chorea, stammering, dysmenorrhea, neuralgia, and sciatica, and also benefits
nymphomania and puerperal mania with a tendency to suicide.LXXXI Hindu
physicians describe it useful in fever, skin diseases, boils, itch, worms, and insanity.
Pounded leaves mixed with turmeric as a paste are topically applied to painful parts
as a household remedy. Muslim physicians of India preferred the purple-flowered
variety and mentioned all parts of the plant powerfully intoxicating and narcotic;
and locally applied to relieve pain of tumors and piles.XL It possesses properties
analogous to that of belladonna, the leaves are smoked to relieve asthmatic attacks
and in the treatment of Parkinson’s disease. The flower juice is used for earache,
and the juice expressed from fruit is applied to the scalp for curing dandruff and
falling hairs. Stramonium ointment is also applied for the treatment of hemor-
rhoids.XXI In Ayurveda, it has been used for the treatment of ulcers, wounds,
inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma
and bronchitis, and toothache [23].CXXXVII Indian physicians had been using datura
preparations to treat bronchial asthma for 4,000 years [4]. Cigarettes of datura
leaves were used by asthmatics until 1992 in Great Britain [16].
862 Datura stramonium L.

In East Africa, mature green fruit is buried in hot ashes until the inside gets very hot,
then removed and left to cool; when cooled, it is squeezed and the juice is put in a
seriously aching ear. The leaves are used as poultice for rheumatism and other swel-
lings; the seeds can be mixed with leaves, dried, ground, mixed with ghee and are used
for the treatment of ringworm.LXXXV The leaves are poulticed onto various types of
cancers, indurations and tumors, especially of breasts [29]. Seeds macerated in alcohol
are used as ointment for abscesses, fistula, hemorrhoids, neuralgia, and rheumatism.
Sexual functions are said to be excited, more especially in women, in whom it may
cause nymphomania (contrary to other reports where it is used to treat nymphoma-
nia).XCVII It is also used in China for flatulence, hyperacidity and night sweats of
tuberculosis. Chinese gather petals after the dew has evaporated in the morning, dry
them in sun, and use the decoction for skin problems, and the powder as a fumitory for
asthma, cough, and shortness of breath.XVIII Russians use the herb for asthma, bron-
chitis, epilepsy, pain, radiculitis and angina pectoris. They also administer seeds in
vodka to children “scared stiff” (paralyzed by fright).XXXVIII Flowers and seeds are
used to wash rectal prolapse and swollen feet. Mexican Indians use leaf decoction for
pains of parturition.C Costa Ricans apply crushed leaves to tumors and ulcers and
gargle the infusion for sore throat. Juice of the fruit is used to prevent baldness and juice
of the flowers for earache.XXXVIII Leaves are used as narcotic, for headache, wound
dressing for animals; seeds are used for rheumatism, head fungus, toothache, headache,
and for the treatment of wounds in Ethiopia [56]. Leaves are smoked with tobacco
against asthma and stomach troubles, and the juice of the leaves is used for toothache,
and seeds are also used by criminals for stupefying victims [49]. Grazing on the plant by
large animals is nephrotoxic [40].
Homeopaths prescribe the tincture for treatment of anasarca, aphasia, apoplexy,
burns, catalepsy, chorea, delirium tremens, diaphragmitis, ecstacy, enuresis, epi-
lepsy, erotomania, esophageal spasm, eye ailments, headache, hiccup, hydrophobia,
hysteria, lochia, locomotor ataxia, mania, meningitis, nymphomania, scarlatina,
stammering, strabismus, sunstroke, tetanus, thirst, tremors and typhus [23, 26, 51].
Phytoconstituents: It contains a variety of toxic tropane alkaloids; main alkaloids
present in all Datura species are the parasympatholytic alkaloids atropine (dl-hyos-
cyamine), l-hyoscyamine (l-isomer of atropine) and hyoscine (scopolamine). A total
of sixty-seven tropane alkaloids have been isolated from different organs [20].
Hyoscyamine and hyoscine are mainly found in the stems and leaves of young plants,
hyoscyamine being always the predominant component [36], and to a lesser extent in
the seeds. Secondary alkaloids include norscopolamine, metaloidine, hydroxy-6-
hyoscyamine and tiglic esters of dihydroxytropane [50]. Datura seeds crushed, and
then heated in water can provide atropine solution extract that can be used in severe
cases of organophosphate poisoning when medical help is not available. One hundred
seeds contain approximately 6 mg of atropine or 0.007 mg/seed [6]. A pseu-
dodipeptide was isolated and purified as gamma-L-glutamyl-L-aspartate that impairs
learning retention in mice and this deficit persisted even 7-days after the treatment [48,
59, 60]. D. metel is the species richest in hyoscine; the leaves contain approximately
0.5% of total alkaloids, of which 75% consists of hyoscine. In young leaves, hyos-
cyamine is the main alkaloid but as the leaves mature hyoscine dominates; whereas in
Datura stramonium L. 863

D. stramonium hyoscyamine predominates in adult leaves. Total alkaloidal content of

D. stramonium leaves is roughly the same as that of D. metel but of this over two-third
is hyoscyamine/atropine. In D. innoxia leaves, hyoscine predominates, whilst in the
seed it is the hyoscyamine/atropine fraction. Total alkaloids content in leaves are
0.25–0.45%,CXXXII and in seeds 0.47–0.65%. Hyoscine content in leaves are 0.1%, in
stems 0.05% and in roots 0.1%; and hyoscyamine content are 0.4% in leaves, 0.2% in
stems and 0.1% in roots.X Dry seeds contain 14%–19.4% protein, 18.4–28.5% fat and
2.7% ash. Seed fatty oil contains 87.7% fatty acids and 2.6% unsaponifiable matter
containing sitosterol.XXXVIII
Long and intense exposure of the plant to light produces an increase in hyoscine
content. The amount of alkaloids also varies with the origin of the plant and can be
increased by different methods such as deflowering, fertilizers, and mutations [31].
Alkaloid patterns of the roots, leaves and seeds of the varieties grown in identical
conditions in Bulgaria were very similar; whereas alkaloid pattern of D. stramo-
nium var. stramonium, grown in Egypt showed significant differences, indicating
the stronger influence of environmental factors than the genetic ones [7].
N-trans-feruloyl tryptamine, hyoscyamilactol, scopoletin, umckalin, daturaolone,
daturadiol, N-trans-ferulicacyltyramine, cleomiscosin A, fraxetin, scopolamine,
1-acetyl-7-hydrox-beta-carboline, and 7-hydroxy-b-carbolinel-propionic acid have
been isolated from the seeds [33].
Pharmacology: Male rats continuously administered the extract through water
supply for 30-days, after about 1-week of the induction of status epilepticus by a
single systemic injection of lithium and pilocarpine, remained seizures-free during
30-days observation period until the treatment was stopped [41]. Petroleum ether
extract shows significant antibacterial activity against S. epidermidis and E. coli
[61]. Methanol seed extract exhibited significant antileishmanial activity [39],
antibacterial activity against S. pyogens, but little or no activity against E. coli,
P. aeruginosa and P. vulgaris [19, 56].
Clinical Effects: Inhaling the smoke of one Datura cigarette by 12 asthmatic
patients with mild airway obstruction substantially decreased specific airway
resistance in 11 patients, the mean maximal decrease being 40% at 30th minute. In
seven patients, subsequent inhalation of 200 micrograms salbutamol caused no
further decrease in airway obstruction [13]. Significantly higher serum levels of
pancreatic polypeptide in patients with bronchial asthma and chronic bronchitis
during attacks are decreased after the use of D. stramonium [64].
Human A/Es, Allergy and Toxicity: Datura species and their alkaloids can pro-
duce delirium with vertigo, hallucinations and visions. The three main alkaloids
have both peripheral and a central action [31]. A small amount (about 5 g) of leaf or
seed can be fatal to a child. Raw plant material takes longer to act—up to several
hours. Sometimes food products, such as buckwheat products are contaminated
with D. stramonium seeds causing toxicity [12, 42, 45]. Teenagers and young
adolescents are more likely to use datura seeds voluntarily, that sometimes results in
death [5, 10, 15, 17, 21, 22, 25, 38, 52, 57, 58]. It affects only the parasympathetic
nervous system, and in full doses, the heart becomes irregular, causes mydriasis and
864 Datura stramonium L.

profound delirium.LXXXI Cases of datura poisoning are reported from around the
world [1, 2, 8, 11, 27, 28, 30, 32, 35, 44, 47, 53–55, 62, 63]. Patients with datura
poisoning, voluntary or involuntary or smoking cigarettes containing stramonium,
present with acute anticholinergic syndrome, hyperpyrexia and severe neurologic
derangement. Early symptoms are thirst and vision disturbances with fixed dilated
pupil (black objects appear green), gaiety, laughter, flushing and nervous twitching,
delirium, consciousness limitation, psychomotor agitation, mumbling speech, visual
hallucinations, plucking motion with the hands, aggression and a rapid weak
heartbeat are typical symptoms. These symptoms may be followed by convulsions,
coma and death. In nonfatal cases symptoms may continue for several days [10, 22,
24, 37, 58]. Author of Makhzan-al-Advia describes a patient with dhatura intoxi-
cation in these words: “Everything he (the patient) looks at appears dark; he fancies
that he really sees all the absurd impressions of his brain, his senses are deranged,
he talks in a wild, disconnected manner, tries to walk but is unable, cannot sit
straight, insects and reptiles float before his eyes, he tries to seize them, and laughs
inordinately at his failure. His eyes are bloodshot, he sees with difficulty, and
catches at his clothes, and furniture and walls of the room. In short, he has the
appearance of a mad man.”XL Typical atropine poisoning symptoms: “dry as bone,
red as beet, hot as pistol, blind as a bat and mad as a hatter.”
Serum CK concentrations may be elevated in many patients with datura toxicity
without any clinical evidence of rhabdomyolysis [9]. Exposure of the fetus to
dhatura inhalation by the mother for asthma may cause desensitizing of nicotinic
receptors due to continuous release of ACh that could result in permanent damage
to the fetus [43].
Tx of Human Toxicity: Gastric lavage or emesis is done immediately, and pilo-
carpine or physostigmine are administered. Patient is kept sedated and the tem-
perature is brought down by sponging with cold water. Licorice has been suggested
as the antidote [3, 46].
Animal Toxicity: Datura seed fed in diets to rats for 90-days decreased body-
weight gain, serum albumin and serum calcium; increased liver and testes weights,
serum ALP and BUN [14, 18].
Commentary: Datura leaves smoking has been an ancient therapy for bronchial
asthma, and the clinical trials proved that it caused the maximum bronchodilatation
because there was no further increase in bronchial dilatation by b2-agonist. Nev-
ertheless, this plant should be a subject for further explorations for clinical benefits.

References
1. Adegoke SA, Alo LA. Datura stramonium poisoning in children. Niger J
Clin Pract. 2013;16:116–8.
2. Al-Shaikh AM, Sablay ZM. Hallucinogenic plant poisoning in children.
Saudi Med J. 2005;26:118–21.
Datura stramonium L. 865

3. Amlo H, Haugeng KL, Wickstrøm E, et al. Poisoning with Jimson weed.

Five cases treated with physostigmine. Tidsskr Nor Laegeforen. 1997;117:
2610–2 (Norwegian).
4. Anderson PJ. History of aerosol therapy: liquid nebulization to MDIs to
DPIs. Respir Care. 2005;50:1139–50.
5. Arouko H, Matray MD, Bragança C, et al. Voluntary poisoning by ingestion
of Datura stramonium. Another cause of hospitalization in youth seeking
strong sensations. Ann Med Interne (Paris) 154 Spec No. 2003;1: S46–50
(French).
6. Bania TC, Chu J, Bailes D, O’Neill M. Jimson weed extract as a protective
agent in severe organophosphate toxicity. Acad Emerg Med. 2004;11:335–8.
7. Berkov S, Zayed R, Doncheva T. Alkaloid patterns in some varieties of
Datura stramonium. Fitoterapia. 2006;77:179–82.
8. Betz P, Janzen J, Roider G, Penning R. Psychopathologic manifestations of
oral administration of endemic nightshade plants. Arch Kriminol. 1991;188:
175–82 (German).
9. Blackford MG, Fitzgibbon JJ, Reed MD. Assessment of serum creatine
kinase among adolescent patients following jimsonweed (Datura stramo-
nium) and moonflower (Datura inoxia) ingestions: a review of 11 cases.
Clin Toxicol (Phila). 2010;48:431–4.
10. Boumba VA, Mitselou A, Vougiouklakis T. Fatal poisoning from ingestion
of Datura stramonium seeds. Vet Hum Toxicol. 2004;46:81–2.
11. Centers for Disease Control and Prevention (CDC). Jimson weed poisoning—
Texas, New York, and California, 1994. MMWR Morb Mortal Wkly Rep.
1995;44:41–4.
12. Centers for Disease Control and Prevention (CDC). Jimsonweed poisoning
associated with a homemade stew—Maryland, 2008. MMWR Morb Mortal
Wkly Rep. 2010;59:102–4.
13. Charpin D, Orehek J, Velardocchio JM. Bronchodilator effects of antiasth-
matic cigarette smoke (Datura stramonium). Thorax. 1979;34:259–61.
14. Crawford L, Friedman M. The effects of low levels of dietary toxic weed
seeds (jimson weed, Datura stramonium and sicklepod, Cassia obtusifolia)
on the relative size of rat liver and levels and function of cytochrome P-450.
Toxicol Lett. 1990;54:175–81.
15. de Germond-Burquier V, Narring F, Broers B. Intentional Datura stramo-
nium intoxication and circumstances of use in two adolescents. Presse Med.
2008;37 6 Pt 1:982–5.
16. Dessanges JF. A history of nebulization. J Aerosol Med. 2001;14:65–71.
17. Diker D, Markovitz D, Rothman M, Sendovski U. Coma as a presenting
sign of Datura stramonium seed tea poisoning. Eur J Intern Med. 2007;18:
336–8.
18. Dugan GM, Gumbmann MR, Friedman M. Toxicological evaluation of jimson
weed (Datura stramonium) seed. Food Chem Toxicol. 1989;27:501–10.
19. Eftekhar F, Yousefzadi M, Tafakori V. Antimicrobial activity of Datura
innoxia and Datura stramonium. Fitoterapia. 2005;76:118–20.
866 Datura stramonium L.

20. El Bazaoui A, Bellimam MA, Soulaymani A. Nine new tropane alkaloids from
Datura stramonium L. identified by GC/MS. Fitoterapia. 2011;82:193–7.
21. Forrester MB. Jimsonweed (Datura stramonium) exposures in Texas, 1998–
2004. J Toxicol Environ Health A. 2006;69:1757–62.
22. Francis PD, Clarke CF. Angel trumpet lily poisoning in five adolescents:
clinical findings and management. J Paediatr Child Health. 1999;35:93–5.
23. Gaire BP, Subedi L. A review on the pharmacological and toxicological
aspects of Datura stramonium L. J Integr Med. 2013;11:73–9.
24. Grandjean EM, de Moreloose P, Zwahlen A. Acute atropinic syndrome
caused by abuse of antiasthmatic cigarettes (Datura stramonium). Schweiz-
erische Medizinische Wochenschrift. 1980;110:1186–90 (French).
25. Greene GS, Patterson SG, Warner E. Ingestion of angel’s trumpet: an
increasingly common source of toxicity. South Med J. 1996;89:365–9.
26. Haas LF. Datura stramomium (Jimsonweed). J Neurol Neurosurg Psychi-
atry. 1995;58:654.
27. Hamouda C, Amamou M, Thabet H, et al. Plant poisonings from herbal
medication admitted to a Tunisian toxicologic intensive care unit, 1983–
1998. Vet Hum Toxicol. 2000;42:137–41.
28. Harrison EA, Morgan DH. Abuse of herbal cigarettes containing stramo-
nium. Br Med J. 1976;2:1195.
29. Hartwell JL. Plants used against cancer. A survey. Lloydia. 1969–1971;
32–4.
30. Jaspersen-Schib R, Theus L, Guirguis-Oeschger M, et al. Serious plant
poisonings in Switzerland 1966–1994. Case analysis from the Swiss Toxi-
cology Information Center. Schweiz Med Wochenschr. 1996;126:1085–98
(German).
31. Karnick CR, Saxena MD. On the variability of alkaloid production in
Datura species. Planta Med. 1970;18:266–9.
32. Khanra S, Khess CR, Srivastava N. Chronic nonfatal Datura abuse in a patient
of paranoid schizophrenia: a case report. Addict Behav. 2015;43:39–41.
33. Li J, Lin B, Wang G, Gao H, Qin M. Chemical constituents of Datura
stramonium seeds. Zhongguo Zhong Yao Za Zhi. 2012;37:319–22 (Chinese).
34. Litzinger WJ. Ceramic evidence for prehistoric Datura use in North
America. J Ethnopharmacol. 1981;4:57–74.
35. Mikolich JR, Paulson CW, Cross CJ. Acute anticholinergic syndrome due to
jimson seed ingestion; clinical and laboratory observations in 8 cases. Ann
Int Med. 1975;83:321–5.
36. Miraldi E, Masti A, Ferri S, Barni Comparini I. Distribution of hyoscyamine
and scopolamine in Datura stramonium. Fitoterapia. 2001;72:644–8.
37. Möbus U, Felscher D, Schulz K. Nightshade plants act almost like LSD.
Poisoning cases are on the rise. MMW Fortschr Med. 1999;141:46–8
(German).
Datura stramonium L. 867

38. Montcriol A, Kenane N, Delort G, et al. Intentional Datura stramonium

intoxication: an unknown etiology of mydriasis. Ann Fr Anesth Reanim.
2007;26:810–3 (French).
39. Nikmehr B, Ghaznavi H, Rahbar A, Sadr S, Mehrzadi S. In vitro anti-
leishmanial activity of methanolic extracts of Calendula officinalis flowers,
Datura stramonium seeds, and Salvia officinalis leaves. Chin J Nat Med.
2014;12:423–7.
40. Oladosu LA, Case AA. Large animal hepatotoxic and nephrotoxic plants.
Vet Hum Toxicol. 1979;21:363–5.
41. Peredery O, Persinger MA. Herbal treatment following postseizure
induction in rat by lithium pilocarpine: Scutellaria lateriflora (Skullcap),
Gelsemium sempervirens (Gelsemium) and Datura stramonium (Jimson
Weed) may prevent development of spontaneous seizures. Phytother Res.
2004;18:700–5.
42. Perharič L, Koželj G, Družina B, Stanovnik L. Risk assessment of buckwheat
flour contaminated by thornapple (Datura stramonium L.) alkaloids: a case
study from Slovenia. Food Addit Contam Part A Chem Anal Control Expo
Risk Assess. 2013;30:321–30.
43. Pretorius E, Marx J. Datura stramonium in asthma treatment and possible
effects on prenatal development. Environ Toxicol Pharmacol. 2006;21:331–7.
44. Roblot F, Montaz L, Delcoustal M, et al. Datura: an easily accessible
hallucinogen, a poisoning to be evoked. Apropos of 10 cases. Rev Med
Interne. 1993;14:956 (French).
45. Rwiza HT. Jimson weed food poisoning. An epidemic at Usangi rural
government hospital. Trop Geogr Med. 1991;43:85–90.
46. Salen P, Shih R, Sierzenski P, Reed J. Effect of physostigmine and gastric
lavage in a Datura stramonium-induced anticholinergic poisoning epidemic.
Am J Emerg Med. 2003;21:316–7.
47. Şanlıdağ B, Derinöz O, Yıldız N. A case of pediatric age anticholinergic
intoxication due to accidental Datura stramonium ingestion admitting with
visual hallucination. Turk J Pediatr. 2014;56:313–5.
48. Schmitz-Bourgeois M, Amiri I, Reinbolt J, Boulanger Y, Ungerer A.
Isolation and structure of a pseudopeptide gamma-L-glutamyl-L-aspartic
acid from Datura stramonium that impairs learning retention in mice.
Biochimie. 1988;70:1179–84.
49. Shah NC. Herbal folk medicines in Northern India. J Ethnopharmacol.
1982;6:293–301.
50. Shah CS, Khanna PN. A note on the alkaloidal content of Datura innoxia
Miller. J Pharm Pharmacol. 1965;17:115–7.
51. Soni P, Siddiqui AA, Dwivedi J, et al. Pharmacological properties of Datura
stramonium L. as a potential medicinal tree: an overview. Asian Pac J Trop
Biomed. 2012;2:1002–8.
52. Spina SP, Taddei A. Teenagers with Jimson weed (Datura stramonium)
poisoning. CJEM. 2007;9:467–8.
868 Datura stramonium L.

53. Stella L, Vitelli MR, Palazzo E, et al. Datura stramonium intake: a report on
three cases. J Psychoactive Drugs. 2010;42:507–12.
54. Suk SH, Kwak YT. Toxic encephalopathy after taking dried seeds of
Datura stramonium in two elderly subjects. Geriatr Gerontol Int. 2009;9:
326–8.
55. Taha SA, Mahdi AH. Datura intoxication in Riyadh. Trans R Soc Trop Med
Hyg. 1984;78:134–5.
56. Taye B, Giday M, Animut A, Seid J. Antibacterial activities of selected
medicinal plants in traditional treatment of human wounds in Ethiopia.
Asian Pac J Trop Biomed. 2011;1:370–5.
57. Tiongson J, Salen P. Mass ingestion of Jimson Weed by eleven teenagers.
Del Med J. 1998;70:471–6.
58. Torbus O, Jachimowicz M, Pikiewicz-Koch A, et al. Datura stramonium
poisoning—a new problem in children and young people’s toxicomania in
Poland. Wiad Lek. 2002;55 Suppl 1(Pt 2):950–7 (Polish).
59. Ungerer A, Schmitz-Bourgeois M, Melan C, et al. Gamma-L-glutamyl-
L-aspartate induces specific deficits in long-term memory and inhibits [3H]
glutamate binding on hippocampal membranes. Brain Res. 1988;446:205–11.
60. Ungerer A, Schuber F, Chauvin R. A factor isolated from Datura stramonium
that affects learning retention in mice. Behav Biol. 1978;24:349–63.
61. Uzun E, Sariyar G, Adsersen A, et al. Traditional medicine in Sakarya province
(Turkey) and antimicrobial activities of selected species. J Ethnopharmacol.
2004;95:287–96.
62. Vearrier D, Greenberg MI. Anticholinergic delirium following Datura
stramonium ingestion: implications for the Internet age. J Emerg Trauma
Shock. 2010;3:303.
63. Wiebe TH, Sigurdson ES, Katz LY. Angel’s Trumpet (Datura stramonium)
poisoning and delirium in adolescents in Winnipeg, Manitoba: Summer
2006. Paediatr Child Health. 2008;13:193–6.
64. Zhang JC. Preliminary report on the serum level of pancreatic polypeptide
in patients with chronic bronchitis and bronchial asthma during attacks.
Chung-Hua Chieh Ho Ho Hu Hsi Tsa Chih. 1989;12:141–2, 190 (Chinese).
Delphinium denudatum Wall. ex Hook.f. & Thomson
(Ranunculaceae)

Abstract
Hindus suppose that the only plant that can grow near aconite is the Jadwár, which is
an antidote to it, and they also affirm that there is a kind of rat called, Bish mush bisha,
which lives upon Jadwár. In Unani medicine, Jadwár is considered an antidote to
poisons, refrigerant, nerve tonic, cardiotonic, deobstruent, anti-inflammatory,
analgesic, demulcent, lithotriptic, diuretic, fattening, antipyretic for phlegmatic and
bilious fevers, and beneficial in the treatment of tremors, paralysis, epilepsy and
chronic sinusitis. Roots contain alkaloids, 8-acetylheterophyllisine, vilmorrianone,
panicutine, denudatine, isotalatizidine, and condelphine. Aqueous root extract
attenuated development of tolerance to the analgesic effect of morphine and
prevented opiates dependence, and inhibited naloxone-induced withdrawal in mice.
Pre-, post-morphine and simultaneous treatment with ethanol extract also prevented
development of opiate dependence in rats. Ethanol extract is also reported to
attenuate 6-OHDA-induced neuronal injury, prevented LPO and improved the
status of antioxidant enzymes in the striatum of rats.

Keywords






Baloot-el-ardh Bas’ha Jadwár Larkspur Nirbasi Sáturyús Vishalakarani


Zadwár

Vernaculars: Urd.: Jadwár; Hin.: Bas’ha, Nirbasi, Tarbasi; San.: Jadavâr, Nirvishi,
Vishalakarani; Mar.: Jadwár, Nirbishi; Ara.: Antila sauda, Baloot-el-ardh, Jadwar;
Eng.: Larkspur; Gre.: Sáturyús; Nep.: Nilobikh; Per.: Mafarfin, Mahparveen,
Zadwár.
Description: Dymock et al.XL mentioned: “Ibn Sina, Ibn Baitar, and Ibn Jazlah in
the Minhaj use almost the same words in speaking of these drugs: of Jadwar they
say: it is an antidote for all poisons, even those of aconite and viper.” He also says
“Ibn Sina of Bokhara describes Jadwár shortly in the following words: “it has the

© Springer Nature Switzerland AG 2020 869

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_91
870 Delphinium denudatum Wall. ex Hook.f. & Thomson

form of the root of Aristolochia, but smaller.” Haji Zein-el-attár, the well-known
Persian physician and apothecary, and the author of the Ikhtiarát (1368 A.D.)
described Jadwár as a root about the size and shape of Indian Cyprus root, but
harder and heavier, and the same as the Indian drug Nirbisi, the best of a purplish
tint internally. He stated that there are, as far as his experience goes, four drugs sold
as Jadwár, viz, a white kind, a purplish, a black and a yellowish; the people of
Cathay (historical name for China in English) call the yellow kind as Kurti and the
purplish Burbi; the other two kinds come from India. He also stated that there is a
mountain called Farájal between India and Cathay, where the plant grows along
with aconite, and that the latter whenever it grows near Jadwár, it loses its poi-
sonous properties and is eaten with impunity by the inhabitants. The author of
Makhzan-el-adwiya gives Antila as the Arabic name and Sáturyús as Greek. He
says that the Hindus suppose that the only plant that can grow near aconite is the
Jadwár, which is an antidote to it, and they also affirm that there is a kind of rat
called, Bish mush bisha, which lives upon Jadwár.XL Ibn Sina described five types
of Jadwár: first ‘Jadwár khatai’ is the best and is mostly used medicinally; it is
black outside and purplish-brown internally, ovoid in shape, knotted, tastes sweet
initially and very bitter afterward. The second is brown or yellowish-brown both
inside and outside, tastes bitter and is the 2nd best; it is imported from Nepal and
Tibet. The 3rd type is bitter in taste, black inside out and turns blue on grinding; the
4th kind is blackish and bitter, size of an olive, probably a tuber of Curcuma
species, comes from Deccan Hills; both 3rd and 4th types are also imported into
India from Nepal and Tibet. The 5th kind is called ‘Jadwar Andulusi’ (Spanish),
which is blackish, soft and very bitter.XL Ibn al-BaitarLXIX described it as one of the
best tonic and refrigerant, and an antidote of black snake bite and aconite (Bish).
Curcuma zedoaria is called Jadwár khatta in India (author) (Fig. 1).
Actions and Uses: In Unani medicine, Jadwár is considered an antidote to poisons,
refrigerant, nerve tonic, cardiotonic, deobstruent, anti-inflammatory, analgesic,
demulcent, lithotriptic, diuretic, fattening, and antipyretic for phlegmatic and bilious
fevers,LXXVII and beneficial in the treatment of tremors, paralysis, epilepsy and
chronic sinusitis. For scorpion bites it is applied to the bite site and the powdered root
with honey is licked every hour. In lymphadenitis, it is applied with Ushuq (Dorema
amoniacum) and Meda lakdi (Litsea sebifera).1 NadkarniCV described it as alter-
ative, stomachic, tonic and anodyne; decoction of the rootlets is used as a tonic. As
an alterative, it is used in the treatment of syphilis and rheumatism; and is chewed to
relieve toothache.LXXXI
Phytoconstituents: Roots contain alkaloids, 8-acetylheterophyllisine, vilmorrianone,
panicutine, denudatine, isotalatizidine, and condelphine [2]. Delphinine and staphis-
agrine are alkaloids found in Delphinium staphisagria seeds, not in D. denudatum root.
While delphinine is reportedly a neurotoxin similar to aconitine; staphisagrine acts like
curare and paralyses skeletal muscles.LXXXI

1
Tayyab M: Personal Communication.
Delphinium denudatum Wall. ex Hook.f. & Thomson 871

Fig. 1 Delphinium denudatum, Illustration, Kirtikar and Basu, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Indian_Medicinal_Plants_-_Plate_7_-_Delphinium_denudatum.
png

Pharmacology: Aqueous root extract attenuated development of tolerance to the

analgesic effect of morphine and prevented opiates dependence [8], and inhibited
naloxone-induced withdrawal in mice [7]. Pre-, post-morphine and simultaneous
treatment with ethanol extract also prevented development of opiate dependence in
rats [3]. Ethanol extract is also reported to attenuate 6-OHDA-induced neuronal
872 Delphinium denudatum Wall. ex Hook.f. & Thomson

injury, prevented LPO and improved the status of antioxidant enzymes in the
striatum of rats [1]. Ethanol extract, its aqueous fraction, and a subfraction of the
aqueous fraction exhibited significant anticonvulsant activity [4, 5]. The subfraction
is suggested to contain compounds that possibly interact with GABAA receptors to
produce anticonvulsant activity [6]. The alkaloids, 8-acetylheterophyllisine, vil-
morrianone, panicutine, are reported to exhibit antifungal activity against human
pathogenic fungi [2].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported on this plant; overall it is one
of the plants that has not been sufficiently investigated, both pharmacologically and
clinically.

References
1. Ahmad M, Yousuf S, Khan MB, et al. Protective effects of ethanolic extract
of Delphinium denudatum in a rat model of Parkinson’s disease. Hum Exp
Toxicol. 2006;25:361–8.
2. Atta-ur-Rahman, Nasreen A, Akhtar F, et al. Antifungal diterpenoid alkaloids
from Delphinium denudatum. J Nat Prod. 1997;60:472–4.
3. Rahman S, Ali Khan R, Kumar A. Experimental study of the morphine
de-addiction properties of Delphinium denudatum Wall. BMC Complement
Altern Med. 2002;2:6.
4. Raza M, Shaheen F, Choudhary MI, et al. Anticonvulsant activities of the
FS-1 subfraction isolated from roots of Delphinium denudatum. Phytother
Res. 2001;15:426–30.
5. Raza M, Shaheen F, Choudhary MI, et al. Anticonvulsant activities of
ethanolic extract and aqueous fraction isolated from Delphinium denudatum.
J Ethnopharmacol. 2001;78:73–8.
6. Raza M, Shaheen F, Choudhary MI, et al. In vitro inhibition of pentylenete-
trazole and bicuculline-induced epileptiform activity in rat hippocampal
pyramidal neurons by aqueous fraction isolated from Delphinium denudatum.
Neurosci Lett. 2002;333:103–6.
7. Zafar S, Ahmad MA, Siddiqui TA. Effect of roots aqueous extract of Delphinium
denudatum on morphine-induced tolerance in mice. Fitoterapia. 2002;73:553–6.
8. Zafar S, Ahmad MA, Siddiqui TA. Protective role of Delphinium denudatum
(Jadwar) against morphine induced tolerance and dependence in mice. J Ethnophar-
macol. 2001;78:95–8.
Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch.
(Parmeliaceae)

(Formerly Known as Usnea longissima)

Abstract
It is a lichen that normally grows on pine or spruce trees and is considered the
longest lichen in the world. It is found in Boreal forests and coastal woodland in
Europe, Asia, and North America. The plant was known to Greeks, and for
Romans as Muscus; Dioscorides and Pliny were aware of its medicinal properties,
as astringent, resolvent, and aperient, and used the decoction as tonic and
alterative. Dioscorides described that the best is that grows on oak or pine trees, is
whiter and aromatic, and the one that is darker is bad; he recommends sitz-bath in
its decoction as beneficial for uterine pain. Externally, the drug is emollient and
astringent, and the dry powder is applied to wounds and sores to promote
granulation. The First Nations people and Native American groups used to treat
animal wounds with it, which is still practiced in the ethnoveterinary medicine of
British Columbia, Canada. The lichen is used in the treatment of gastric ulcer in
folk medicine of Anatolia (Turkey). In Ayurveda, it is kapha and pitta suppressant,
astringent, bitter, acrid, cooling, anti-inflammatory, analgesic, expectorant,
aphrodisiac, and promotes wound healing, and is an important ingredient in
herbal formulations for the treatment of seminal weakness, male sexual debility,
and fungal infections in women, like vaginal candidiasis. In China, the herb is said
to be latent-heat-clearing, antipyretic, mucolytic, anti-inflammatory, channel-
deobstruent, detoxicant, analgesic, and to clear the liver of sthenic ‘heat,’ and is
used for the treatment of cough due to pathogenic ‘heat-phlegm,’ conjunctivitis,
headache, carbuncle and lymph node tuberculosis. (+)-Usnic acid is the major
constituent, found in all Usnea species. Its contents vary in Usnea species between
0.22 and 6.49% of dry weight; the increasing amount of usnic acid increases the
potential of antimicrobial activity. Aqueous extract, usic acid and diffractaic acid,
show gastroprotective effects against indomethacin-induced gastric damage in rats,
and cause a significant increase in the SOD, GPx and GSH levels, and a reduction
in CAT and LPO.

© Springer Nature Switzerland AG 2020 873

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_92
874 Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch.

Keywords




Black stone flower Charéla Dowálah Hazzáz-el-sakhar
Kalpasi
Lúmot




kahoi Ratipanché Silá-valká Songluo Ushnah

Vernaculars: Urd.: Chhadela, Ushnah; Hin.: Charéla, Charcharela, Dagar da Phool,

Patthar ka Phool, Silá-bák; San.: Shaileyam, Silá-valká; Mar.: Bárik-dagada-phúl,
Motha-dagada-phúl; Tam.: Kalapu, Kalpasi; Tel.: Raathi pootha, Ratipanché; Ara.:
Hazzáz-el-sakhar (Rock-scab), Hunna-i-korisha, Shibatul ajooz, Ushná; Chi.: Hai-
fengteng, Songluo; Eng.: Black stone flower, Methuselah’s beard or Old man’s beard;
Per.: Dowálah, Ushnáh; Tag.: Lúmot kahoi.
Description: It is a lichen that normally grows on pine or spruce (the coniferous
evergreen) trees, is sweet in odor and white, and is considered the longest lichen in
the world. It is found in Boreal forests and coastal woodlands in Europe, Asia, and
North America. This lichen has very long stems and short, side branches. Stems are
usually 15–30 cm in length, and the potential for its length is up to 3 m. Daniel
Mosquin [6] of the University of British Columbia’s Botanical Garden and Center
for Plant Research describes that the species is now threatened or extirpated due to

Fig. 1 Dolichousnea longissima in Washington, JonRichfield, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Lichen_Dolichousnea_longissima_IMG_4843R.JPG
Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch. 875

Fig. 2 Dolichousnea longissima, New York Botanic Garden Specimen, Ed Uebel, Wikimedia-
Commons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:
Usnea_longissima.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

habitat loss (clear-cutting) and air pollution, as it is very pollution-sensitive, and “its
presence can be used as an indication of pure air.” However, it remains strong in the
Pacific Northwest of North America. Another lichen named Parmotrema perlatum
(formerly known as Parmelia perlata), and commonly known as Black Stone
Flower or Patthar ka Phool in Hindi or Shaileyam in Sanskrit and used as a spice
and medicine in India, is listed as Ushnah by Wahid and Siddiqui,CXXXXVII and
also by Dymock et al.XL Two lichens, known as greater and lesser ‘stone-flowers’
were reportedly sold in the markets of undivided India; which were called Ushnah
by Arabs, a term derived from Persian, and ‘Hazzáz-el-sakhar’ (rock-scab) [8]. The
vernacular names mentioned here belong to Ushnah and not the botanical identity
(Figs. 1 and 2).
Actions and Uses: The plant was known to Greeks and for Romans as Muscus.
Dymock et al.XL mentioned that Dioscorides and Pliny were aware of its medicinal
properties, and quoted the author of Makhzan-el-Adwiya describing it as astringent,
resolvent, and aperient, and used the decoction as tonic and alterative. Externally, the
drug is emollient and astringent, and the dry powder is applied to wounds and sores to
promote granulation. Ibn al-BaitarLXIX quotes Ibn Samjoon that the host tree affects
the quality of the drug, and quoted Dioscorides who described that the best that grows
on oak or pine trees, is whiter and aromatic, and the one that is darker is bad; he
recommends sitz bath in its decoction as beneficial for uterine pain. It (temperament,
hot 1° and dry 1°) is also described by many ancient physicians as stomachic, antie-
metic, refrigerant, cardiotonic, analgesic, astringent and anti-inflammatory; normally
used in polyherbal formulations for cardiac diseases, liver pain and inflamma-
tions.LXXVII The First Nations people and Native American groups used to treat animal
wounds with it, which is still practiced in the ethnoveterinary medicine of British
Columbia, Canada [12]. The lichen is used in the treatment of gastric ulcer in folk
medicine of Anatolia (Turkey) [16]. Usnea philippina grows on coconut trees and is
regarded as cooling, astringent, prophylactic and anthelmintic, and its decoction is
876 Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch.

used as stomachic in the Philippines.CXVII Khory and KatrakLXXXI described Ushnah

under the botanical name of Paermelia perlata, as demulcent, tonic, febrifuge and
diuretic, and its uses in amenorrhea, chlorosis and leucorrhea, and as a soporific and
sedative to stop nocturnal emissions. Its powder as snuff relieves headache, and as a
poultice over the lumber and renal regions produces copious diuresis, such as in
dropsy.XL HonigbergerLXIII described its use at Lahore city, during undivided India, in
disorders of stomach, dyspepsia, vomiting, pain in the liver or womb, induration of the
uterus, amenorrhea, calculi, and nocturnal spermatic discharges.XL In Ayurveda, it is
kapha and pitta suppressant, astringent, bitter, acrid, cooling, anti-inflammatory,
analgesic, expectorant, promotes wound healing and aphrodisiac, and is an important
ingredient in herbal formulations for the treatment of seminal weakness, male sexual
debility, and fungal infections in women, like vaginal candidiasis. In China, the herb is
said to be latent-heat-clearing, antipyretic, mucolytic, anti-inflammatory, channel-
deobstruent, detoxicant, analgesic, and to clear the liver of sthenic ‘heat,’ and is used
for the treatment of cough due to pathogenic ‘heat-phlegm,’ conjunctivitis, headache,
carbuncle and lymph node tuberculosis.XVIII
Phytoconstituents: (+)-Usnic acid is the major constituent, found in all Usnea spe-
cies. Its contents vary in Usnea species between 0.22 and 6.49% of dry weight; the
increasing amount of usnic acid increases the potential of antimicrobial activity [4].
Other phytoconstituents include longissiminone A and B, and glutinol [5], longius-
nine and longissimausnone [8], ethyl hematommate, friedelin, b-amyrin, b-sitosterol,
methyl-2,4-dihydroxy-3,6-dimethylbenzoate, barbatinic acid, zeorin, ethyl orselli-
nate, b-hydroxy-glutin-5-ene, oleanolic acid, methylorsellinate, and 4-methyl-2,6-
dihydroxybenzaldehyde [7], (4aR,9bS)-2,6-diactyl-3,4a,7,9-tetrahydroxy-8,9b-di-
methyl-1-oxo-1,4, 4a,9b-tetrahydrodibenzo[b,d]furan, orcinol, 18R-hydroxydihydro-
alloprotolichensterinic acid, 5,8-epidioxy-5a,8a-ergosta-6, 22E-dien-3b-ol, ethyl
everninate, arabitol, apigenin 7-O-b-D-glucuronide, and 3-hydroxy-5-methoxy-
2-methylbenzoic acid [13], ethyl 2-(3,3-bis(7-acetyl-4,6- dihydroxy-3,5-dimethyl-
benzofuran-2-yl)acryloyl) [1], usnic acid derivatives: usenamines A–F, usone, and
isousone [18], and isoevernic acid, dibutyl phthalate and diisobutyl phthalate [11].
Usenamines A inhibits growth of human hepatoma HepG2 cells and induces apoptosis
[18], usnic acid exhibits highest inhibitory activity of tumor promoter-induced
Epstein-Barr virus activation [17], and logissiminone show potent in vitro
anti-inflammatory activity with no cytotoxicity [5]. Yamamoto et al. [17] identified
(+)-usnic acid, barbatic acid, diffractaic acid, 4-O-demethylbarbatic acid, and evernic
acid in the thallus. Lichens of Usnea genus grown in China contain higher amounts of
acids than lichens of other genera, and U. longissima contains 5.19% usnic acid.XVIII
Pharmacology: Aqueous extract, usic acid and diffractaic acid show gastropro-
tective effects against indomethacin-induced gastric damage in rats, and cause a
significant increase in the SOD, GPx and GSH levels, and a reduction in CAT and
LPO [2, 9, 16]. Methanol extract shows a concentration-dependent in vitro inhi-
bitory effect on ADP-induced platelet aggregation, and a significant inhibition of
thrombotic death or paralysis of mice challenged with an intravenous injection of a
mixture of collagen and epinephrine, suggesting an antithrombotic activity due to
Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch. 877

antiplatelet activity [14]. Methanol extract reduces melanin formation in human

melanoma cells by direct tyrosinase inhibition, and by affecting the activity of
tyrosinase via inhibition of tyrosinase glycosylation [10], shows potent antioxidant
activity despite having low phenolic contents [15], and a polysaccharide from the
lichen shows scavenging activity of free oxygen radicals [3]. Usic acid is the main
component responsible for antimicrobial activity, bacteriostatic at low concentra-
tions and bactericidal at higher concentrations; D. pneumoniae, S. hemolyticus, C.
diphtheriae, S. aureus, B. subtilis, P. vulgaris and M. tuberculosis are most sen-
sitive to it. It also strongly inhibits C. albicans and T. vaginalis.XVIII
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported in published English journals
listed on PubMed.

References
1. Bai L, Bao HY, Bau T. Isolation and identification of a new benzofuranone
derivative from Usnea longissima. Nat Prod Res. 2014;28:534–8.
2. Bayir Y, Odabasoglu F, Cakir A, et al. The inhibition of gastric mucosal
lesion, oxidative stress and neutrophil-infiltration in rats by the lichen
constituent diffractaic acid. Phytomedicine. 2006;13:584–90.
3. Bian X, Jin J, Ding D, Zhang H. Study on the scavenging action of
polysaccharide of Usnea longissima to oxygen radical and its antilipid
peroxidation effects. Zhong Yao Cai. 2002;25:188–9 (Chinese).
4. Cansaran D, Kahya D, Yurdakulola E, Atakol O. Identification and
quantitation of usnic acid from the lichen Usnea species of Anatolia and
antimicrobial activity. Z Naturforsch C. 2006;61:773–6.
5. Choudhary MI, Azizuddin, Jalil S, Atta-ur-Rahman. Bioactive phenolic com-
pounds from a medicinal lichen, Usnea longissima. Phytochemistry. 2005;
66:2346–50.
6. Daniel Mosquin. The Lichens of North America. UBC Botanical Garden
and Center for Plant Research, Vancouver, British Columbia, Canada.
7. Feng J, Yang X, Su S, He C. Studies on chemical constituents from herbs of
Usnea longissima. Zhongguo Zhong Yao Za Zhi. 2009;34:708–11 (Chinese).
8. Feng J, Yang X. New dibenzofuran and anthraquinone from Usnea longissima.
Zhongguo Zhong Yao Za Zhi. 2009;34:852–3 (Chinese).
9. Halici M, Odabasoglu F, Suleyman H, et al. Effects of water extract of
Usnea longissima on antioxidant enzyme activity and mucosal damage
caused by indomethacin in rats. Phytomedicine. 2005;12:656–62.
10. Kim MS, Cho HB. Melanogenesis inhibitory effects of methanolic extracts of
Umbilicaria esculenta and Usnea longissima. J Microbiol. 2007;45:578–82.
878 Dolichousnea longissima (Ach) Articus/Parmelia perlata Esch.

11. La XN, Liang H, Ba GN, Tai BD. Chemical constituents from Usnea
longgisima, a traditional Mongolian medicine (II). Zhong Yao Cai. 2015;38:
2541–2 (Article in Chinese).
12. Lans C. Possible similarities between the folk medicine historically used by
First Nations and American Indians in North America and the ethnovet-
erinary knowledge currently used in British Columbia, Canada. J Ethnophar-
macol. 2016;192:53–66.
13. Laxinamu J, Tang YX, Bao HY, Bau T. Chemical constituents from Usnea
longgisima, a traditional Mongolian medicine. Zhongguo Zhong Yao Za
Zhi. 2013;38:2125–8 (Chinese).
14. Lee KA, Kim MS. Antiplatelet and antithrombotic activities of methanol
extract of Usnea longissima. Phytother Res. 2005;19:1061–4.
15. Odabasoglu F, Aslan A, Cakir A, et al. Comparison of antioxidant activity and
phenolic content of three lichen species. Phytother Res. 2004;18:938–41.
16. Odabasoglu F, Cakir A, Suleyman H, et al. Gastroprotective and antioxidant
effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnophar-
macol. 2006;103:59–65.
17. Yamamoto Y, Miura Y, Kinoshita Y, et al. Screening of tissue cultures and
thalli of lichens and some of their active constituents for inhibition of tumor
promoter-induced Epstein-Barr virus activation. Chem Pharm Bull (Tokyo).
1995;43:1388–90.
18. Yu X, Guo Q, Su G, et al. Usnic acid derivatives with cytotoxic and antifungal
activities from the Lichen Usnea longissima. J Nat Prod. 2016;79:1373–80.
Doronicum pardalianches Roxb.
(Asteraceae/Compositae)

(Syns.: D. cordatum Lam.; D. matthiolii; Arnica scorpioides)

Abstract
An herbaceous perennial with rhizomes, that grows in Europe, Syria, and Turkey.
Some authors identified it as Doronicum hookeri, Roxb. The plant grows in
Andalusia and the mountainous parts of Syria, especially about Mount Yabrúrat,
where it goes by the name of Aqrabi (scorpion in Arabic). Dioscorides described
the root as like the tail of a scorpion and white as alabaster (gypsum); it was also
known to Theophrastus and Pliny. It is a resolvent of phlegm, adust bile, cardiacal
and tonic, useful in nervous depression, melancholy, and impaired digestion,
also in pain of the womb and flatulent dyspepsia. It is also a nerve tonic,
strong antidote, especially for scorpion bites, and carminative, and is used in the
treatment of nervous weakness, paralysis, melancholy, and to maintain pregnancy.
One gram powder is used with apple syrup or apple sauce. In palpitation patients
with hot temperament, it should be used with camphor; the powder is used with
milk in seminal debility.

Keywords
Akrabi

Darunaj aqrabi

Doronic panthère

Hartbladzonnebloem

Klostergemsrot

Kriechgamswurz

Leopard’s-bane

Omieg zachodni



Suvivuohenjuuri Zergevirág

Vernaculars: Urd.: Darunaj aqrabi; Hin.: Akrabi, Darunaj-i-akrabi; Ara.: Darunaj

aqrabi; Cze.: Kamzičník srdčitý; Dan.: Hjertebladet gemserod; Dut.: Hartblad-
zonnebloem; Eng.: Great false leopardbane, Great leopard’s bane, Leopard’s bane;
Fin.: Suvivuohenjuuri, Tarhavuohenjuuri; Fre.: Doronic à feuilles cordées, Doronic
à feuilles en cœur, Doronic panthère, Doronique romaine; Ger.: Kriechende
gemswurz, Kriechgamswurz, Schwindelwurz; Hun.: Zergevirág; Ita.: Doronico
medicinale; Pol.: Omieg zachodni; Spa.: Matalobos de flor compuesta; Swe.:
Klostergemsrot.

© Springer Nature Switzerland AG 2020 879

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_93
880 Doronicum pardalianches Roxb.

Description: An herbaceous perennial with rhizomes, upright stems growing up to

80 cm, with heart-shaped basal leaves and yellow flowers, generally 3–4 cm
across.CXXX It grows in Europe, Syria, and Turkey. Some authors identified it as
Doronicum hookeri, Roxb.CXXXXVII The plant grows in Andalusia and the moun-
tainous parts of Syria, especially about Mount Yabrúrat, where it goes by the name
of Aqrabi (scorpion in Arabic). There are two varieties of the drug, Persian and
Turkish; the latter is most esteemed. Author of Makhzan-al-Adwiya stated that
Darunaj is a scorpioid knotted root with a greyish exterior and white interior, hard,
faintly bitter and aromatic. He described the plant as having fleshy yellowish leaves
of the shape of those of almond, which lie flat upon the ground. Flower is yellow,
its stem hollow that rises from the midst of the leaves to a height of two spans,
and bears from 5 to 7 scattered leaves, thinner and longer than the lower leaves.
Rhizomes scorpioid, occasionally branched, flat, jointed, white in color, 7.5–10 cm
long, 1.2–1.8 cm broad and 0.2 cm thick. Upper surface scaly, under surface
marked by numerous scars of rootlets, brittle and horny, yellowish-white, central
portion somewhat spongy and odorless. Taste at first insipid and after a few minutes
a sensation of warmth and pricking is felt upon the tongue (Figs. 1 and 2).XL
Actions and Uses: Dioscorides described the root as like the tail of a scorpion and
white as alabaster (gypsum); it was also known to Theophrastus and Pliny. It is a
resolvent of phlegm, adust bile, cardiacal and tonic, useful in nervous depression,
melancholy, and impaired digestion, also in pain of the womb and flatulent dys-
pepsia.XL It (temperament, hot 3° and dry 3°) is one of the specific cardiac drugs
due to its cardiac refrigerant and cardiotonic property, and is especially useful in
heart weakness and cold palpitations. It is also phlegm and black bile resolvent,
nerve tonic, strong antidote, especially for scorpion bites, and carminative, and is
used in the treatment of nervous weakness, paralysis, melancholy, and to maintain

Fig. 1 Doronicum pardalianches, Plant, Rossier1954, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Great_Leopard%27s-Bane.JPG
Doronicum pardalianches Roxb. 881

Fig. 2 Doronicum pardalianches, Flowers, Isidre Blanc, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:DORONICUM_PARDAL
IANCHES_-_SANT_JUST_-_IB-223_(Dor%C3%B2nic_cordat).JPG; https://creativecommons.org/
licenses/by-sa/4.0/deed.en

pregnancy; 1 g powder is used with apple syrup or apple sauce. In palpitation

patients with hot temperament, it should be used with camphor;LXXVII the powder is
used with milk in seminal debility.LXXXI NadkarniCV mentioned it useful in nervous
depression, melancholy and scorpion bite. In Iran, the plant is used as a diuretic,
nerve tonic and for the treatment of snake and scorpion bites [1].
Pharmacology: There are no pharmacology studies reported in the literature.
Human A/Es, Allergy and Toxicity: Its use may cause headache.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This plant seems to have escaped the attention of scientists for
some reasons, as there are no published pharmacological or clinical studies listed on
PubMed.

Reference
1. Amiri MS, Joharchi MR. Ethnobotanical investigation of traditional medicinal
plants commercialized in the markets of Mashhad, Iran. Avicenna J Phytomed.
2013;3:254–71.
Embelia ribes Burm.f.
(Primulaceae)

Abstract
It is a climber, found in hilly parts of India, Sri Lanka, and Singapore. The fruit
is globular, smaller than a pepper-corn, dull-red, and grows in large bunches.
The fruit is carminative, anthelmintic, alterative and stimulant; in Sanskrit,
vrisha nusana means destroyer of the enemy (worms). Ancient Ayurveda
physicians, such as Sushruta described the fruit as anthelmintic, alterative and
tonic, and recommended its use along with liquorice root to strengthen body and
prevent effects of aging. In the Nighanthas, it is described as bitter, pungent, hot,
astringent, appetizing, and light; useful for abdominal pains, worms, flatulence,
and skin diseases. Methanol seed extract shows the presence of steroids, cardiac
glycosides, alkaloids, anthraquinones, tannins and phenolics. Ethanol, and
aqueous fruit extracts significantly decreased blood glucose, glycated Hb, HR
and SBP in diabetic rats, serum TC and TGs, and increased HDL-C, enhanced
antioxidant defense against ROS, and protected b-cells loss under hyper-
glycemic condition. Ethanol fruit extract also attenuated diabetic nephrotoxicity,
and improved antioxidant status. Aqueous fruit extract also protected against
myocardial injury due to isoproterenol-induced acute MI in rats.

Keywords
Amti
Baberang
Bao badang
Birang kabuli
Chitra-tandula
Embelia
fruits
False black pepper
Vayuvilangam
Vidanga
Viranga

Vernaculars: Urd.: Bao badang; Hin.: Baberang, Karkannie, Vayvarang, Viranga;

San.: Chitra-tandula, Janthunashana, Suchitra-vija, Vrishanusana, Vidanga; Ben.:
Babarang, Bhai-birrung, Biranga; Mal.: Vayuvilangam, Visha-al, Vizhal; Mar.:
Amti, Ambat, Vaivarang, Vavdinga; Tam.: Vaividangam, Vayu-vilamgam; Tel.:
Vaividungalu, Vayu velangam, Vellal; Ara.: Abranj, Barnaq, Biranj kabuli; Chi.:
水林果; Eng.: Baoberang, Embelia fruits, False black pepper, Vidanga; Nep.:
Himalcheri; Per.: Birang kabuli.
© Springer Nature Switzerland AG 2020 883
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_94
884 Embelia ribes Burm.f.

Description: It is a climber, found in hilly parts of India, Sri Lanka, and Singapore.
The fruit is globular, smaller than a pepper-corn, dull-red, and grows in large
bunches. Dried fruit is reddish-brown marked with dark spots, has five partite calyx
and stalk is often attached; the outer shell is striated from the base to the apex,
where there is a small beak. Inside the outer shell is the seed, enveloped in a delicate
membrane. Seed is horny of a reddish color, and its external surface appears to be
covered with spots of white mildew. If kept for any length of time the outer shell of
the fruit becomes much darker, but the quality of drug is not affected by it. The
berries are used to adulterate black pepper (Figs. 1 and 2).XL

Fig. 1 Embelia ribes, Plant, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Embelia_ribes_04.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Embelia ribes, Fruits (Berries), Earthshine, WikimediaCommons, https://commons.wiki

media.org/wiki/File:Vidanga_Seeds.JPG
Embelia ribes Burm.f. 885

Actions and Uses: Ancient Ayurveda physicians, such as Sushruta described the
fruit as anthelmintic, alterative and tonic, and recommended its use along with
liquorice root to strengthen body and prevent effects of aging. In the Nighanthas, it
is described as bitter, pungent, hot, astringent, appetizing, and light; useful for
abdominal pains, worms, flatulence, and skin diseases [10];XL other reported uses
include mental disorders, as brain tonic [29], tumors, ascites, bronchitis, jaundice,
diseases of the heart and brain [27]. The fruit is carminative, anthelmintic, alter-
ative and stimulant; in Sanskrit, vrisha nusana means destroyer of the enemy
(worms).LXXXI NadkarniCV mentioned fresh juice of berries as cooling, diuretic and
laxative. Ibn Sina described it as a strong anthelmintic, and Mir Muhammad
Hussain warns that it turns the urine red.XL Ibn al-BaitarLXIX quotes Hubaish and
Ibn-e-Masawaiyh that it very effectively kills roundworms, tapeworms and pin-
worms. Seeds (temperament, hot 2° and dry 2°) are described in Unani medicine as
anthelmintic, that also expel phlegm and black bile from the joints.LXXVII It is thus
useful in arthritis, and gargling with its decoction in tonsillitis is beneficial.1
Phytoconstituents: Methanol seed extract shows the presence of steroids, car-
diac glycosides, alkaloids, anthraquinones, tannins and phenolics [28]. Embelin,
embelinol, embeliol from the seeds [17], N-(3-carboxylpropyl)-5-amino-2-hydroxy-
3-tridecyl-1,4-benzoquinone, 5,6-dihydroxy-7tridecyl-3-[4-tridecyl-3-hydroxy-5-oxo-
2(5H)-furylidene]-2-oxo-3(2H)-benzofuran, daucosterol and sitosterol from the roots
[20], embeliphenol A from the stems [13], and embelamide from the leaves [14] with
significant a-glucosidase inhibitory activity have been isolated.
Pharmacology: Ethanol [10, 23], and aqueous fruit extracts significantly decreased
blood glucose [4], glycated Hb, HR and SBP in diabetic rats [6, 8], serum TC and
TGs, and increased HDL-C [10], enhanced antioxidant defense against ROS, and
protected b-cells loss under hyperglycemic condition [9]. Ethanol fruit extract also
attenuated diabetic nephrotoxicity, and improved antioxidant status [11]. Embelin
also lowers high-fat diet-induced hyperlipidemia and glucose in rats [12]. Pretreat-
ment of rats with aqueous and ethanol fruit extracts enhanced antioxidant defense
against methionine-induced hyperhomocysteinemia, hyperlipidemia and oxidative
stress in brain [1, 7]. Aqueous and ethanol fruit extracts pretreatment also exhibited
neuroprotective activity, enhanced antioxidant defense in MCA occlusion-induced
focal cerebral ischemia in rats [7, 22]. Methanol root extract is reported to show
potent in vitro AChE activity [31].
Embelin, a p-quinone, is considered the active constituent [3], protected against
LPS-induced airway inflammation [27], exhibited significant anticonvulsant activity
comparable to phenytoin and diazepam [21], protected against 3-nitropropionic
acid-neurotoxicity in rats [15], ICV STZ-induced sporadic dementia in rats [2],
apomorphine-induced behavioral changes in mice and rats [16], LPS-induced
sickness behavior in mice [26], and global I/R-induced brain injury in rats, and
significantly reducing cerebral infarction area and the LPO [30]. Aqueous fruit
extract also protected against myocardial injury due to isoproterenol-induced acute

1
Tayyab M: Personal Communication.
886 Embelia ribes Burm.f.

MI in rats [5]. Potassium embelate produced analgesia comparable to morphine, but

not antagonized by naloxone and no precipitation of abstinence syndrome [3].
Embelin pretreatment also significantly protected against intrarectal acetic acid-
induced colitis in rats, due to its antioxidant and anti-inflammatory activities [29].
Both ethanol leaves extract and embelin showed significant wound healing activity
in rats [19]. Ethanol extract shows very modest antibacterial activity against S.
aureus, E. aerogenes, and K. pneumoniae [28]. Methanol fruit extract was also
moderately active against MDR S. typhi [24], and showed modest antifungal
activity [25]. A mixture of the powders of E. ribes fruits and Veronia anthelmintica
seeds (Kali zeeri), and their methanol extracts are reportedly effective and safe in
treating natural gastrointestinal nematode infection of goats [18].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It is a fairly commonly used drug in Unani medicine in the Indian
subcontinent. However, most pharmacological studies were conducted on its
chemical constituents, and very minimal on aqueous or other extracts. There are
also no clinical studies conducted/reported on any of its traditional anecdotal uses.

References
1. Ansari MN, Bhandari U. Protective effect of Embelia ribes Burm on
methionine-induced hyperhomocysteinemia and oxidative stress in rat brain.
Indian J Exp Biol. 2008;46:521–7.
2. Arora R, Deshmukh R. Embelin attenuates intracerebroventricular strepto-
zotocin-induced behavioral, biochemical, and neurochemical abnormalities
in rats. Mol Neurobiol. 2017;54:6670–80.
3. Atal CK, Siddiqui MA, Zutshi U, et al. Nonnarcotic orally effective,
centrally acting analgesic from an Ayurvedic drug. J Ethnopharmacol. 1984;
11:309–17.
4. Bhandari U, Ansari MN, Islam F, Tripathi CD. The effect of aqueous extract
of Embelia ribes Burm on serum homocysteine, lipids and oxidative
enzymes in methionine induced hyperhomocysteinemia. Indian J Pharma-
col. 2008;40:152–7.
5. Bhandari U, Ansari MN, Islam F. Cardioprotective effect of aqueous extract
of Embelia ribes Burm fruits against isoproterenol-induced myocardial
infarction in albino rats. Indian J Exp Biol. 2008;46:35–40.
6. Bhandari U, Ansari MN. Antihyperglycaemic activity of aqueous extract of
Embelia ribes Burm in streptozotocin-induced diabetic rats. Indian J Exp
Biol. 2008;46:607–13.
7. Bhandari U, Ansari MN. Protective effect of aqueous extract of Embelia
ribes Burm fruits in middle cerebral artery occlusion-induced focal cerebral
ischemia in rats. Indian J Pharmacol. 2008;40:215–20.
Embelia ribes Burm.f. 887

8. Bhandari U, Jain N, Ansari MN, Pillai KK. Beneficial effect of Embelia

ribes ethanolic extract on blood pressure and glycosylated hemoglobin in
streptozotocin-induced diabetes in rats. Fitoterapia. 2008;79:351–5.
9. Bhandari U, Jain N, Pillai KK. Further studies on antioxidant potential and
protection of pancreatic beta-cells by Embelia ribes in experimental diabetes.
Exp Diabetes Res. 2007;2007:15803.
10. Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Embelia ribes
on dyslipidemia in diabetic rats. Int J Exp Diabetes Res. 2002;3:159–62.
11. Chaudhari HS, Bhandari U, Khanna G. Embelia ribes extract reduces high
fat diet and low dose streptozotocin-induced diabetic nephrotoxicity in rats.
EXCLI J. 2013;12:858–71.
12. Chaudhari HS, Bhandari U, Khanna G. Preventive effect of embelin from
Embelia ribes on lipid metabolism and oxidative stress in high-fat diet-
induced obesity in rats. Planta Med. 2012;78:651–7.
13. Dang PH, Nguyen HX, Nguyen NT, Le HN, Nguyen MT. a-Glucosidase
inhibitors from the stems of Embelia ribes. Phytother Res. 2014;28:1632–6.
14. Dang PH, Nguyen NT, Nguyen HX, et al. a-Glucosidase inhibitors from the
leaves of Embelia ribes. Fitoterapia. 2015;100:201–7.
15. Dhadde SB, Nagakannan P, Roopesh M, et al. Effect of embelin against
3-nitropropionic acid-induced Huntington’s disease in rats. Biomed Phar-
macother. 2016;77:52–8.
16. Durg S, Kumar N, Vandal R, et al. Antipsychotic activity of embelin isolated
from Embelia ribes: a preliminary study. Biomed Pharmacother. 2017;
90:328–31.
17. Hao K, Ali M, Siddiqui AW. New compounds from the seeds of Embelia
ribes Burm. Pharmazie. 2005;60:69–71.
18. Javed I, Akhtar MS. Screening of Veronica anthelmintica seed and Embella
ribes fruit mixed in equal parts against gastrointestinal nematodes. Pak J
Pharm Sci. 1990;3:69–74.
19. Kumara Swamy HM, Krishna V, Shankarmurthy K, et al. Wound healing
activity of embelin isolated from the ethanol extract of leaves of Embelia
ribes Burm. J Ethnopharmacol. 2007;109:529–34.
20. Lin P, Li S, Wang S, Yang Y, Shi J. A nitrogen-containing 3-alkyl-1,4-
benzoquinone and a gomphilactone derivative from Embelia ribes. J Nat Prod.
2006;69:1629–32.
21. Mahendran S, Thippeswamy BS, Veerapur VP, Badami S. Anticonvulsant
activity of embelin isolated from Embelia ribes. Phytomedicine. 2011;18:
186–8.
22. Nazam Ansari M, Bhandari U, Islam F, Tripathi CD. Evaluation of
antioxidant and neuroprotective effect of ethanolic extract of Embelia ribes
Burm in focal cerebral ischemia/reperfusion-induced oxidative stress in rats.
Fundam Clin Pharmacol. 2008;22:305–14.
23. Purohit A, Vyas KB, Vyas SK. Hypoglycaemic activity of Embelia ribes
berries (50% EtOH) extract in alloxan induced diabetic rats. Anc Sci Life.
2008;27:41–4.
888 Embelia ribes Burm.f.

24. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for

their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
25. Rani AS, Saritha K, Nagamani V, Sulakshana G. In vitro evaluation of
antifungal activity of the seed extract of Embelia ribes. Indian J Pharm Sci.
2011;73:247–9.
26. Shaikh A, Dhadde SB, Durg S, et al. Effect of embelin against lipopoly-
saccharide-induced sickness behaviour in mice. Phytother Res. 2016;30:
815–22.
27. Shirole RL, Shirole NL, Saraf MN. Embelia ribes ameliorates lipopoly-
saccharide-induced acute respiratory distress syndrome. J Ethnopharmacol.
2015;168:356–63.
28. Tambekar DH, Khante BS, Chandak BR, et al. Screening of antibacterial
potentials of some medicinal plants from Melghat forest in India. Afr J
Tradit Complement Altern Med. 2009;6:228–32.
29. Thippeswamy BS, Mahendran S, Biradar MI, et al. Protective effect of
embelin against acetic acid induced ulcerative colitis in rats. Eur J Pharmacol.
2011;654:100–5.
30. Thippeswamy BS, Nagakannan P, Shivasharan BD, et al. Protective effect of
embelin from Embelia ribes Burm. against transient global ischemia-induced
brain damage in rats. Neurotox Res. 2011;20:379–86.
31. Vinutha B, Prashanth D, Salma K, et al. Screening of selected Indian
medicinal plants for acetylcholinesterase inhibitory activity. J Ethnophar-
macol. 2007;109:359–63.
Euphorbia hirta L.; Chamaesyce hirta (L.) Mills.
(Euphorbiaceae)

(Syns.: E. bancana Miq.; E. capitata Lam.; E. gemella Lag.; E. globulifera Kunth)

Abstract
The plant is an annual, hairy herb, that is native to India but pantropic in
distribution, and grows in the Philippines in open grasslands, roadsides and
pathways. The plant supposedly possesses extraordinary qualities, such as a few
drops of it killing serpents, its efficacy in venereal complaints and bellyache, and
its being an antidote to poisons. Early experimental studies showed that it killed
small animals by paralyzing the respiration and heart, through its direct action on
respiratory and cardiac centers. The active principle is eliminated by the liver,
because in all animals which died during the experiments the gall bladder was
found distended with bile. It appears to act beneficially upon spasmodic dyspnea,
arising from whatever cause, and it unquestionably is a remedy of great power
and promise. In Ayurveda, whole plant is used in dadru, krmiroga, kãsa, kustha,
mūtrakrcchra, pūyameha, śūla, and tamakaśvãsa. In Unani medicine, ground
with water and strained, it is used as antidiarrheal, as anodyne in gonorrhea, and
to purify blood in cases of inflammation and boils. Powdered plant is used for
bleeding piles, leucorrhea, and premature ejaculation. The decoction was used in
Brazil to treat asthma, and gonorrhea, possibly due to its diuretic action. The
plant was also used in nursing mothers when there was deficient or no milk
production. In the Philippines, the entire plant is used as antidote, hemostatic,
sedative and soporific, and the decoction is very effective in relieving the
dyspnea of asthma. It is also claimed to cure dengue patients, and became one of
the most popular “folkloric medicine” for dengue in the Philippines. In East
Africa, juice from the leaves and stems is used for eye complaints, and for
certain swellings on the throat or under the arms, possibly boils; and as
antidiarrheal and antimalarial in Kinshasa, the Democratic Republic of Congo.
Nigerian traditional healers use it for male sexual dysfunction, whereas, Swahili
and Sukuma individuals use it to treat hypertension and edema. Triterpene,
taraxerol was isolated from the stems, while the leaves yielded phytol and phytyl
fatty acid esters, and the roots contained cycloartenyl fatty acid ester, lupeol fatty

© Springer Nature Switzerland AG 2020 889

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_95
890 Euphorbia hirta L.; Chamaesyce hirta (L.) Mills.

acid ester, a-amyrin fatty acid ester and b-amyrin fatty acid ester, linoleic acid,
b-sitosterol, and squalene.

Keywords




Amampatchaiarisi Budakiriya Doodhiklan Dudhi Euphorbe hérisée






Fēi yáng cǎo Garden spurge Hierba del asama Labneh Shimanishikiso

Vernaculars: Urd.: Doodhiklan, Dudhi, Sosfand, Sheerak, Sheergya; Hin.: Badi

dudhi, Dudheli; San.: Amampatchaiarisi, Ammāṉ pachchaṟisi, Cittirappaalaatai,
Dugdhikã, Ksirini, Nãgãrjuni, Rakta vinduchada; Ben.: Bara-dudhi, Bara-keru,
Barokhervi, Baro-kheruie, Bonokheruie; Guj.: Dudeli; Mal.: Nelapalai; Mar.:
Dudali, Dudhi, Goverdhan, Mothidudhi, Nayeti; Tam.: Ammanpacharisi, Amum-
patchai-arissi, Patchaiyarissi; Tel.: Bidarie, Nanabala, Reddinanabrolu, Reddivari
nanabalu; Ara.: Labneh; Chi.: 飞扬草, Fēi yáng cǎo, Fei yang ts’ao, Ju-chih ts’ao;
Eng.: Australian asthma weed, Cat’s hair, Common spurge, Garden spurge, Milk
herb, Snake weed; Fre.: Euphorbe hérisée, Euphorbe poilue, Malnommée; Ind.:
Patikan kerbau; Jap.: Shimanishikiso, Taiwannishikiso; Maly.: Gelang susu; Por.:
Erva-de-santa-luzia (Br.); Rus.: Molochai khirta; Sin.: Budakiriya, Dadakiriya,
Kepunkiriya; Spa.: Hierba golondrina, Hierba de la golondrina, Hierba de pelotitas,
Hierba del asama (Mexico), Tripa de pollo, Yerba de sapo; Tag.: Gatas-gatas,
Botobotonis, Saikan, Tawa-tawa.
Description: The plant is an annual, hairy herb, that is native to India but pantropic in
distribution, and grows in the Philippines in open grasslands, roadsides and pathways.
It is usually extensively branched from the base, the branches being simple or forked
and ascending or spreading, up to 40 cm long, and often reddish or purplish. Leaves
are opposite, distichous, elliptic-oblong or oblong-lanceolate, 1–2.5 cm long, dentate
and usually blotched with purple in the middle. Involucres are very numerous,
greenish or purplish, about 1 mm long, and borne on dense, axillary, stalkless or
short-stalked clusters or crowded cymes.CXVII KabeeruddinLXXVII described it as an
herb of three kinds; breaking its leaves or branches oozes milk, hence the name
Dudhiklan (dudh means milk). One of its kind is spread on hard grounds, with small
reddish-green leaves and thin branches. It is called ‘dudhi khurd’ and the kind used
mostly for medicinal purpose. The second type is an erect plant of 15–25 cm height,
with larger leaves and red branches; it is called ‘dudhi kalan,’ and the third type is a
vine ascending and spreading on trees (Figs. 1 and 2).
Actions and Uses: Dymock et al.XL quoting Ainslie mentioned that “the plant
supposedly possesses extraordinary qualities, such as a few drops of it killing ser-
pents, its efficacy in venereal complaints and bellyache, and its being an antidote to
poisons.” Early experimental studies showed that it killed small animals by para-
lyzing the respiration and heart, through its direct action on respiratory and cardiac
centers. The active principle is eliminated by the liver, because in all animals which
died during the experiments the gall bladder was found distended with bile. It appears
to act beneficially upon spasmodic dyspnea, arising from whatever cause, and it
Euphorbia hirta L.; Chamaesyce hirta (L.) Mills. 891

Fig. 1 Euphorbia hirta, Plant, Tauʻolunga, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Euphorbia_hirta.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Euphorbia hirta, Twig, Krish Dulal, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Euphorbia_hirta_NP.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en

unquestionably is a remedy of great power and promise, its action is not cumula-
tive.XL In Ayurveda, whole plant is used in dadru, krmiroga, kãsa, kustha,
mūtrakrcchra, pūyameha, śūla, and tamakaśvãsa.CXXXVI Caius [7] also mentioned
the fluid extract or tincture of the plant to be most suitable in asthmatic dyspnea, in
bronchitis of old people, in emphysema, and in angina pectoris. It is also a very useful
remedy for acute and chronic dysentery, is anthelmintic and the tincture is applied to
892 Euphorbia hirta L.; Chamaesyce hirta (L.) Mills.

cure ringworm.CV In Unani medicine, it (temperament, hot 2° and dry 2°; by some
cold and dry) is described as astringent, styptic, blood purifier, and antidote to snake
poison; ground with water and strained, it is used as antidiarrheal, as anodyne in
gonorrhea, and to purify blood in cases of inflammation and boils. Powdered plant is
used for bleeding piles, leucorrhea, and premature ejaculation.LXXVII GhaniL described
it diuretic, lithotriptic, cough suppressant, expectorant, anthelmintic, and beneficial for
gonorrhea, and he says that the use of 10 g powdered aerial parts every day for one year
would maintain hair color. Its paste is analgesic and anti-inflammatory. Its milk is sweet
and helps retain pregnancy and increases semen production. In Nepal, it is used for the
treatment of bronchial asthma by traditional healers [20]. Khory and KatrakLXXXI
described it as demulcent, antispasmodic, anthelmintic, and local parasiticide; used in
the treatment of cough, bronchial affections, worms, bowel complaints, acute and
chronic dysentery and gonorrhea. The decoction was used in Brazil to treat asthma, and
gonorrhea, possibly due to its diuretic action. The plant was also used in nursing
mothers when there was deficient or no milk production.CXVII In the Philippines, the
entire plant is used as antidote, hemostatic, sedative and soporific, and the decoction is
very effective in relieving the dyspnea of asthma. Leaves are also mixed with Datura
metel leaves and flowers to make a preparation called “asthma cigarettes” to treat
asthma symptoms.LVI It is also claimed to cure dengue patients, and became one of the
most popular ‘folkloric medicines’ for dengue in the Philippines [9]. In decoction, 30 g
of the fresh plant or 15 g of the dried plant may be used with 2 L of water, and be
reduced by simmering to 1 L; the addition of 45–60 ml of alcohol prevents it from
spoiling in cold climate, but in India, fresh decoction should be made every 2 days. The
decoction may be given in a dose of 70 ml three or four times a day after meals or
immediately before them; it should not be prescribed in pill form due to its irritant
action on the gastric mucous membrane.XL It is also the most preferred plant for the
treatment of dysentery and diarrhea by indigenous Bhoxa community in Uttarakhand
state of India [12]. An infusion of leaves is given to sheep, goats and cattle to increase
lactation. Leaves are chewed and the juice swallowed in case of heartburn. This
treatment is repeated as often as required. Any fresh wound is covered with the fresh
leaf, tied on with cloth which speeds up healing. In East Africa, juice from the leaves
and stems is used for eye complaints, and for certain swellings on the throat or under
the arms, possibly boils; and as antidiarrheal and antimalarial in Kinshasa, the
Democratic Republic of Congo [41–43]. Decoction of leaves is also used for the
treatment of asthma.LXXXV Nigerian traditional healers use it for male sexual dys-
function [47], while Swahili and Sukuma individuals use it to treat hypertension and
edema [18]. Aqueous extraction of fresh aerial parts at 100 °C allows efficient
extraction of active constituents, but drying the plant material before extraction con-
siderably reduces its cytotoxic activity [10].
Phytoconstituents: Triterpene, taraxerol was isolated from the stems, while the
leaves yielded phytol and phytyl fatty acid esters, and the roots contained cyclo-
artenyl fatty acid ester, lupeol fatty acid ester, a-amyrin fatty acid ester and b-amyrin
fatty acid ester, linoleic acid, b-sitosterol, and squalene [29]. Methanol extract of
Euphorbia hirta L.; Chamaesyce hirta (L.) Mills. 893

aerial parts is predominantly composed of terpenoid (60.5%) [28]. From aerial

parts, scopoletin, scoparone, isoscopoletin, quercetin, isorhamnetin, pinocembrin,
kaempferol, luteolin, and gallic acid have been isolated [46]. Other polyphenols
isolated from leaves are, myricitrin, 3,4-di-O-galloylquinic acid, 2,4,6-tri-O-galloyl-
D-glucose and 1,2,3,4,6-penta-O-galloyl-b-D-glucose [8]. Quercetin and rutin, a
glycosidic form of quercetin, are present in the acid-hydrolysed and nonhydrolysed
methanol extract, respectively [24]. Some skin irritating constituents have also been
isolated from the latex [32]. Hirtionosides A–C, gallates of megastigmane glucosides,
3-hydroxyoctanoic acid glucosides and a phenylpropanoid glucoside [27] and two
novel butanol rhamnosides: n-butyl-1-O-b-L-rhamnopyranoside and n-butyl-1-O-
a-L-rhamnopyranoside [25] were reported from the whole plant.
Pharmacology: Ethanol extract of aerial parts showed significant antihistaminic,
anti-inflammatory and immunosuppressive properties in various animal models [35],
and prominent antianaphylactic activity [48]. Lyophilized aqueous extract also
exerted antipyretic activity, significant anti-inflammatory effect, reduction in
inflammation-induced hyperalgesia, sedative, anxiolytic and central analgesic
effects, antagonized by naloxone [21, 22]. Low dosages of aqueous extract are
beneficial in reducing cartilage degeneration in cases of arthritis, by decreasing levels
of matrix metalloproteinases and increasing levels of tissue inhibitors of matrix
metalloproteinases; however, higher doses increased cartilage degeneration [23].
Ethanol extract of the whole plant produces bronchodilation in histamine-induced
bronchoconstriction of guinea pigs [39].
Aqueous and ethanol extracts produce time-dependent increase in urine output,
and significantly affect electrolyte excretion. Aqueous extract increases urinary
excretion of Na+, K+ and HCO3−; whereas the ethanol extract increases urinary
excretion of HCO3−, decreases loss of K+ and had little effect on Na+ [18]. Ethanol
extract protects against nitrobenzene-nephrotoxicity, primarily through its antioxi-
dant capacity [38]. Lyophilized aqueous decoction of the whole plant delays small
intestinal transit in experimental models of castor oil, AA-, and PGE2-induced
diarrhea, but not in normal conditions, and shows no effect on magnesium
sulfate-induced diarrhea [13, 16, 41]. Antiamebic and antidiarrheal activities are
concentrated in the polyphenolic fraction, inhibiting E. histolytica growth, and also
exhibit significant inhibition of ACh-, KCl solution-induced contractions of isolated
guinea-pig ileum [42].
Ethanol and petroleum ether flower extracts significantly reduced serum TC,
TGs, urea, creatinine, and ALP levels, and increased levels of HDL and total
proteins in diabetic mice [19]. Leaves extract lowered blood glucose and showed
significant antioxidant potentials in STZ-diabetic rats, comparable to gliclazide
[36]. Methanol leaf extract exhibited significant antioxidant activity, comparable to
ascorbic acid, followed by the flowers, roots and stems. Total flavonoid contents are
highest in leaves, followed by flowers, roots and stems extracts [6].
Ethanol extract exhibits a significant broad-spectrum antimicrobial activity,
against E. coli, P. vulgaris, P. aeruginosa and S. aureus [37], but weak activity
against H. pylori [26, 44]. Methanol leaf extract significantly inhibits growth of
894 Euphorbia hirta L.; Chamaesyce hirta (L.) Mills.

Gram-positive (S. aureus, Micrococcus sp., B. subtilis and B. thuringensis),

Gram-negative (E. coli, K. pneumonea, S. typhi and P. mirabilis) and one yeast
(C. albicans) [31]. Two flavonoids quercetin and kaempferol present in stem extract
were active against E. coli, P. aeruginosa, P. mirabilis, and S. aureus and four
fungi, A. flavus, A. niger, T. mentagrophytes, and C. albicans [34]. Taraxerone, a
triterpene isolated from the stems, was cytotoxic to a human colon carcinoma cell
line (HCT 116) and active against P. aeruginosa and S. aureus, but inactive against
E. coli and B. subtilis; while a mixture of 25-hydroperoxycycloart-23-en-3b-ol and
24-hydroperoxycycloart-25-en-3b-ol was active against P. aeruginosa, S. aureus
and E. coli, C. albicans and T. mentagrophytes. but inactive against B. subtilis and
A. niger [29]. Both aqueous and 50% methanol extracts show antiretroviral effect
against HIV-1 with 50% methanol extract exerting a higher antiretroviral effect than
the aqueous extract; the tannins are suggested to be responsible for this effect [14].
Ethyl acetate fraction of ethanol extract was also very effective in vitro against
Onchocerca volvulus microfilaria, which is the second major cause of blindness in
the world [5]. Ethanol and dichloromethane extracts also produce significant
chemosuppression of parasitemia in mice infected with P. berghei berghei, and
more than 60% inhibition of the P. falciparum growth in vitro [40, 43]. Ethanol
extract of whole plant also showed significant burn wound healing activity [17].
Mechanism of Action: The remarkable anti-inflammatory effect is mediated through
a dose-related inhibition of LPS-induced NO production by activated macrophages,
without affecting expression of iNOS gene that is much more potent and specific in NO
inhibition [33], and decrease in the production of IL-1b, TNF-a, IL-2 and IFN-c in
splenocytes and synovial fluid of adjuvant- and LPS-induced arthritic rats [1, 2, 11].
Reduced release of PGI2, PGE2, and PGD2 by the aqueous extract could also be
responsible for its analgesic, anti-inflammatory and inhibitory effect on platelet
aggregation [15]. Presence of b-amyrin in ethanol extract was suggested to be
responsible for anti-inflammatory effect [33]. Analgesic activity is mediated via a
central opioidergic mechanism, inhibited by naloxone [22]. Anxiolytic effect of the
ethanol extract was significantly reduced by flumazenil pretreatment, indicating
GABAA associated Cl− channels involvement [4]. Ethanol extract also restored
increased AChE activity in frontal cortex, hippocampus, and septum areas of the brain
due to anxiety, to normal levels [3].
Human A/Es, Allergy and Toxicity: The latex causes irritation on contact [32].
Animal Toxicity: A single oral high dose of 5,000 mg/kg of methanol leaf extract
produced mild behavioral changes, and caused mortality of one third of mice [30].
However, a single oral dose of 5,000 mg/kg of methanol extract to Sprague Dawley
rats did not produce any signs of toxicity or mortality during a 14-day observation
period, and no significant hematological and biochemical changes after 90-days
repeated oral doses [49]. Administration of sequential aqueous extract of the plant,
after extraction with n-hexane, chloroform and methanol, in increasing doses to
rats on alternate days for 50-days caused ultrastructural damage to basement
membrane of renal glomeruli and showed architectural damage to hepatocytes [45].
Euphorbia hirta L.; Chamaesyce hirta (L.) Mills. 895

Quercetin at low doses is strongly mutagenic in S. typhimurium TA98; however,

both aqueous and methanol extracts do not demonstrate any mutagenic properties at
concentrations up to 100 microg/mL in the absence and presence of S-9 metabolic
activation [24].
Commentary: Traditional uses and significant effects of the plant in pharmaco-
logical studies, have not resulted in any formal clinical investigations published in
journals listed on PubMed.

References
1. Ahmad SF, Attia SM, Bakheet SA, et al. Anti-inflammatory effect of
Euphorbia hirta in an adjuvant-induced arthritic murine model. Immunol
Invest. 2014;43:197–211.
2. Ahmad SF, Bani S, Sultan P, et al. TNF-a inhibitory effect of Euphorbia
hirta in rats. Pharm Biol. 2013;51:411–7.
3. Anuradha H, Srikumar BN, Deepti N, et al. Restoration of acetyl-
cholinesterase activity by Euphorbia hirta in discrete brain regions of
chronically stressed rats. Pharm Biol. 2010;48:499–503.
4. Anuradha H, Srikumar BN, Shankaranarayana Rao BS, Lakshmana M.
Euphorbia hirta reverses chronic stress-induced anxiety and mediates its
action through the GABA(A) receptor benzodiazepine receptor-Cl(-) channel
complex. J Neural Transm. 2008;115:35–42.
5. Attah SK, Ayeh-Kumi PF, Sittie AA, et al. Extracts of Euphorbia hirta Linn.
(Euphorbiaceae) and Rauvolfia vomitoria Afzel (Apocynaceae) demonstrate
activities against Onchocerca volvulus microfilariae in vitro. BMC Comple-
ment Altern Med. 2013;13:66.
6. Basma AA, Zakaria Z, Latha LY, Sasidharan S. Antioxidant activity and
phytochemical screening of the methanol extracts of Euphorbia hirta L.
Asian Pac J Trop Med. 2011;4:386–90.
7. Caius JF. The medicinal and poisonous spurges of India. J Bombay Nat Hist
Soc. 1938;40:274–313.
8. Chen L. Polyphenols from leaves of Euphorbia hirta L. China J Chinese
Mat Med. 1991;16:38–9, 64 (Chinese).
9. de Guzman GQ, Dacanay AT, Andaya BA, Alejandro GJ. Ethnopharmaco-
logical studies on the uses of Euphorbia hirta in the treatment of dengue in
selected indigenous communities in Pangasinan (Philippines). J Intercult
Ethnopharmacol. 2016;5:239–43.
10. Duez P, Livaditis A, Guissou PI, et al. Use of an Amoeba proteus model for
in vitro cytotoxicity testing in phytochemical research. Application to
Euphorbia hirta extracts. J Ethnopharmacol. 1991;34:235–46.
11. Fayaz Ahmad S, Sultan P, Ashour AE, et al. Modulation of Th1 cytokines
and inflammatory mediators by Euphorbia hirta in animal model of
adjuvant-induced arthritis. Inflammopharmacology. 2013;21:365–75.
896 Euphorbia hirta L.; Chamaesyce hirta (L.) Mills.

12. Gairola S, Sharma J, Gaur RD, Siddiqi TO, Painuli RM. Plants used for
treatment of dysentery and diarrhoea by the Bhoxa community of district
Dehradun, Uttarakhand, India. J Ethnopharmacol. 2013;150:989–1006.
13. Galvez J, Zarzuelo A, Crespo ME, et al. Antidiarrhoeic activity of Euphorbia
hirta extract and isolation of an active flavonoid constituent. Planta Med.
1993;59:333–6.
14. Gyuris A, Szlávik L, Minárovits J, et al. Antiviral activities of extracts of
Euphorbia hirta L. against HIV-1, HIV-2 and SIVmac251. In Vivo. 2009;23:
429–32.
15. Hiermann A, Bucar F. Influence of some traditional medicinal plants of
Senegal on prostaglandin biosynthesis. J Ethnopharmacol. 1994;42:111–6.
16. Hore SK, Ahuja V, Mehta G, et al. Effect of aqueous Euphorbia hirta leaf
extract on gastrointestinal motility. Fitoterapia. 2006;77:35–8.
17. Jaiprakash B, Chandramohan, Reddy DN. Burn wound healing activity of
Euphorbia hirta. Anc Sci Life. 2006;25:16–8.
18. Johnson PB, Abdurahman EM, Tiam EA, Abdu-Aguye I, Hussaini IM.
Euphorbia hirta leaf extracts increase urine output and electrolytes in rats.
J Ethnopharmacol. 1999;65:63–9.
19. Kumar S, Malhotra R, Kumar D. Antidiabetic and free radicals scavenging
potential of Euphorbia hirta flower extract. Indian J Pharm Sci. 2010;72:
533–7.
20. Kunwar RM, Shrestha KP, Bussmann RW. Traditional herbal medicine in
far-west Nepal: a pharmacological appraisal. J Ethnobiol Ethnomed. 2010;
6:35.
21. Lanhers MC, Fleurentin J, Cabalion P, et al. Behavioral effects of Euphorbia
hirta L.: sedative and anxiolytic properties. J Ethnopharmacol. 1990;29:
189–98.
22. Lanhers MC, Fleurentin J, Dorfman P, et al. Analgesic, antipyretic and anti-
inflammatory properties of Euphorbia hirta. Planta Med. 1991;57:225–31.
23. Lee KH, Chen YS, Judson JP, et al. The effect of water extracts of Euphorbia
hirta on cartilage degeneration in arthritic rats. Malays J Pathol. 2008;30:
95–102.
24. Loh DS, Er HM, Chen YS. Mutagenic and antimutagenic activities of aqueous
and methanol extracts of Euphorbia hirta. J Ethnopharmacol. 2009;126:
406–14.
25. Mallavadhani UV, Narasimhan K. Two novel butanol rhamnosides from an
Indian traditional herb, Euphorbia hirta. Nat Prod Res. 2009;23:644–51.
26. Ndip RN, Malange Tarkang AE, Mbullah SM, et al. In vitro anti-Helicobacter
pylori activity of extracts of selected medicinal plants from North West
Cameroon. J Ethnopharmacol. 2007;114:452–7.
27. Nomoto Y, Sugimoto S, Matsunami K, Otsuka H. Hirtionosides A-C,
gallates of mega-stigmane glucosides, 3-hydroxyoctanoic acid glucosides
and a phenylpropanoid glucoside from the whole plants of Euphorbia hirta.
J Nat Med. 2013;67:350–8.
Euphorbia hirta L.; Chamaesyce hirta (L.) Mills. 897

28. Perumal S, Mahmud R. Chemical analysis, inhibition of biofilm formation

and biofilm eradication potential of Euphorbia hirta L. against clinical
isolates and standard strains. BMC Complement Altern Med. 2013;13:346.
29. Ragasa CY, Cornelio KB. Triterpenes from Euphorbia hirta and their
cytotoxicity. Chin J Nat Med. 2013;11:528–33.
30. Rajeh MA, Kwan YP, Zakaria Z, et al. Acute toxicity impacts of Euphorbia
hirta L. extract on behavior, organs body weight index and histopathology
of organs of the mice and Artemia salina. Pharmacognosy Res. 2012;4:170–7.
31. Rajeh MA, Zuraini Z, Sasidharan S, et al. Assessment of Euphorbia hirta L.
leaf, flower, stem and root extracts for their antibacterial and antifungal
activity and brine shrimp lethality. Molecules. 2010;15:6008–18.
32. Saeed-ul-Hassan S, Khalil-ur-Rehman M, Niaz U. Isolation and character-
ization of irritant components of Euphorbia pilulifera L. Pak J Pharm Sci.
2013;26:31–7.
33. Shih MF, Cheng YD, Shen CR, Cherng JY. A molecular pharmacology
study into the anti-inflammatory actions of Euphorbia hirta L. on the
LPS-induced RAW 264.7 cells through selective iNOS protein inhibition.
J Nat Med. 2010;64:330–5.
34. Singh G, Kumar P. Phytochemical study and screening for antimicrobial
activity of flavonoids of Euphorbia hirta. Int J Appl Basic Med Res. 2013;
3:111–6.
35. Singh GD, Kaiser P, Youssouf MS, et al. Inhibition of early and late phase
allergic reactions by Euphorbia hirta L. Phytother Res. 2006;20:316–21.
36. Subramanian SP, Bhuvaneshwari S, Prasath GS. Antidiabetic and antioxidant
potentials of Euphorbia hirta leaves extract studied in streptozotocin-induced
experimental diabetes in rats. Gen Physiol Biophys. 2011;30:278–85.
37. Sudhakar M, Rao ChV, Rao PM, et al. Antimicrobial activity of Caesalpinia
pulcherrima, Euphorbia hirta and Asystasia gangeticum. Fitoterapia.
2006;77:378–80.
38. Suganya S, Sophia D, Raj CA, et al. Amelioration of nitrobenzene-induced
nephrotoxicity by the ethanol extract of the herb Euphorbia hirta. Pharma-
cognosy Res. 2011;3:201–7.
39. Sundari SK, Kumarappan CT, Jaswanth A, Valarmathy R. Bronchodilator
effect of alcoholic extract of Euphorbia hirta Linn. Anc Sci Life. 2004;23:1–5.
40. Tona L, Cimanga RK, Mesia K, et al. In vitro antiplasmodial activity of
extracts and fractions from seven medicinal plants used in the Democratic
Republic of Congo. J Ethnopharmacol. 2004;93:27–32.
41. Tona L, Kambu K, Mesia K, et al. Biological screening of traditional prepa-
rations from some medicinal plants used as antidiarrhoeal in Kinshasa, Congo.
Phytomedicine. 1999;6:59–66.
42. Tona L, Kambu K, Ngimbi N, et al. Antiamoebic and spasmolytic activities
of extracts from some antidiarrhoeal traditional preparations used in
Kinshasa, Congo. Phytomedicine. 2000;7:31–8.
898 Euphorbia hirta L.; Chamaesyce hirta (L.) Mills.

43. Tona L, Ngimbi NP, Tsakala M, et al. Antimalarial activity of 20 crude

extracts from nine African medicinal plants used in Kinshasa, Congo.
J Ethnopharmacol. 1999;68:193–203.
44. Wang YC, Huang TL. Screening of anti-Helicobacter pylori herbs deriving
from Taiwanese folk medicinal plants. FEMS Immunol Med Microbiol.
2005;43:295–300.
45. Wong JY, Chen YS, Chakravarthi S, et al. The effects of Euphorbia hirta on
the ultrastructure of the murine liver, kidney and aorta. Exp Ther Med.
2013;6:1247–50.
46. Wu Y, Qu W, Geng D, et al. Phenols and flavonoids from the aerial part of
Euphorbia hirta. Chin J Nat Med. 2012;10:40–2.
47. Yakubu MT, Akanji MA, Oladiji AT. Male sexual dysfunction and methods
used in assessing medicinal plants with aphrodisiac potentials. Pharmacog
Rev. 2007;1:49–56.
48. Youssouf MS, Kaiser P, Tahir M, et al. Antianaphylactic effect of Euphorbia
hirta. Fitoterapia. 2007;78:535–9.
49. Yuet Ping K, Darah I, Chen Y, Sreeramanan S, Sasidharan S. Acute and
subchronic toxicity study of Euphorbia hirta L. methanol extract in rats.
Biomed Res Int. 2013;182064.
Euphorbia resinifera O. Berg.
(Euphorbiaceae)

(Syn.: Tithymalus resiniferus (O. Berg) H. Karst.)

Abstract
The shrub is a native of Morocco; Dioscorides and Pliny described its collection on
Mount Atlas in Africa (Morocco), and noticed its extreme acridity. Its therapeutic
potentials were known during the reign of the Roman Emperor Augustus. Galen
said fresh Farfiyun is hotter than asafetida, and Razi mentioned its taste very hot
burning the tongue. Men who collect it have to cover their faces to prevent the dust
entering their mouths, as it would cause all their teeth to fall out. It tightens the
uterine cervix to such an extent that even abortifacients cannot expel the fetus; thus,
if used before conception it is useful in habitual abortions. Fresh, clean, yellow,
bitter and hotly aromatic, and one to three years old is the best. It is a useful
application in sciatica, palsy, colic, and lumbago, and removes phlegmatic humours
from the joints and limbs; internally administered it acts as a purgative of bile and
phlegm. It should always be diluted before use with such substances as oil of roses
(fatty extract), extract of liquorice, tragacanth or gum Arabic. When given to
women, it causes abortion; however, a pessary containing one grain of euphorbium
causes the mouth of the uterus to contract and prevent abortion. In modern
medicine, euphorbium is never used internally. The latex contains high concen-
tration of the toxin resiniferatoxin, an ultrapotent capsaicin analog that was isolated
in 1975. Also, present are phorbic acid, two major radioactive compounds, a
glycoside or oligosaccharide, and a lipid belonging to the group of triterpenoid
compounds. Vanilloid receptor 1 (TRPV1), a membrane-associated cation channel
is activated by the resiniferatoxin. Resiniferatoxin mediate apoptosis of prostate
cancer cells through a direct pathway interacting with caspases, particularly caspase
1 and 3 and through an indirect pathway.

Keywords



African spurge Euphorbe du maghreb Euforbia resinifera Farbiyun







Farfiyun Hartsityräkki Harz-wolfsmilch Maleiteira Prustkåda Takoot

© Springer Nature Switzerland AG 2020 899

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_96
900 Euphorbia resinifera O. Berg.

Vernaculars: Urd.: Afarbiyun, Akalbanafsha, Farbiyun, Farfiyun; Ara.: Farfiyun,

Hafizun-nakhal, Lubānā maghrabīyā, Takub, Tikjout (Morocco); Ber.: Takoot;
Dan.: Marokkansk euforbie; Eng.: African spurge, Gum euphorbia, Resin spurge,
Spurge wort; Fin.: Hartsityräkki; Fre.: Euphorbe cactiforme à quatre côtes,
Euphorbe du maghreb, Euphorbe du maroc, Euphorbe mellifère, Euphorbe résini-
fère; Ger.: Harz-wolfsmilch; Ita.: Euforbia resinifera; Por.: Maleiteira, Mama-leite;
Rus.: Molochai smolonosnyj; Swe.: Prustkåda.
Description: It is a native of Morocco; a shrub growing to 61 cm tall, forming
multistemmed cushion-shaped clumps up to 2 m wide. Stems are erect, succulent,
superficially like a cactus, four-angled, with short but sharp pairs of 6 mm spines on
the angles, spaced about 1 cm apart up the stem. Euphorbium was known to the
ancients, as both Dioscorides and Pliny described its collection on Mount Atlas in
Africa (Morocco), and noticed its extreme acridity. Avicenna described it under the
name, Farbiyun; Haji Zein states that, it is called Farbiyun, Afarbiyun, Farfiyun and
Takub, and that the men who collect it have to cover their faces to prevent the dust
entering their mouths, as it would cause all their teeth to fall out.XL As soon as
Farbiyun (the latex) is collected, it is mixed with husked beans to preserve its
strength, and when fresh it is of a yellow color, translucent, and easily soluble in
olive oil; when old it turns reddish-yellow; the odor is acrid (Figs. 1 and 2).
Actions and Uses: Its therapeutic potentials were known during the reign of the
Roman Emperor Augustus [1]. Galen said fresh Farfiyun is hotter than asafetida, and
Razi mentioned its taste very hot burning the tongue. It tightens the uterine cervix to
such an extent that even abortifacients cannot expel the fetus; thus, if used before

Fig. 1 Euphorbia resinifera, Tops of the Plants, BS Thurner Hof, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Euphorbia_resinifera_
050403.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Euphorbia resinifera O. Berg. 901

Fig. 2 Euphorbia resinifera, Bloom, Valérie & Agnès, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Euphorbia_resinifera.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

conception it is useful in habitual abortions. Fresh, clean, yellow, bitter and hotly
aromatic, and one to three years old is the best.LXIX Ibn Jazlah used it for paralysis,
kidney numbness, to prevent miscarriage, to stop lacrimation, for dog bites and
burning belly.LIII It is a useful application in sciatica, palsy, colic, and lumbago, and
removes phlegmatic humours from the joints and limbs; internally administered it acts
as a purgative of bile and phlegm. It should always be diluted before use with such
substances as oil of roses (fatty extract), extract of liquorice, tragacanth or gum Arabic;
the dose is from one carat (200 mg) to one dang (400 mg). When given to women, it
causes abortion; however, a pessary containing one grain of euphorbium causes the
mouth of the uterus to contract and prevent abortion. In modern medicine, euphorbium
is never used internally.XL,CV In proper doses, it is said to be emetic, nauseous,
purgative, diuretic and rubefacient.LXXXI In Unani medicine, topical application of the
dried latex (temperament, hot 4° and dry 4°) is considered rubefacient, irritant and
nervine tonic; and internally a phlegm purgative. It is used mainly in oils in the
treatment of palsy, paralysis, tremors, epilepsy, sciatica, ascites, colic, arthritis and
other phlegmatic and nervous conditions. It is also used as douche for abortion and as
emmenagogue in amenorrhea.L,LXXVII
902 Euphorbia resinifera O. Berg.

Phytoconstituents: The latex contains high concentration of the toxin resiniferatoxin,

an ultrapotent capsaicin analog that was isolated in 1975 [1]. Also, present are phorbic
acid, two major radioactive compounds, a glycoside or oligosaccharide, and a lipid
belonging to the group of triterpenoid compounds [4]. Resiniferatoxin is being used to
develop a novel class of analgesics, as it interacts with TRPV1, a known pain sensing
cation channel that also responds to capsaicin [5]. The irritant and tumor-promoting
principle was also isolated and identified as tigliane-type 12-deoxyphorbol ester that is
equipotent to the standard tumor promoter TPA. However, no promoting activity is
observed on internal administration [3]. Six euphane triterpenes, euphorol A–D, H and
I, and three tirucallane triterpenes, euphorol E–G, including four nortriterpenes, have
been isolated from the methanol extract [6]. Eighteen structurally diverse diterpenoids,
including 14 ingol-type diterpenoids, euphorblins A–N, and a rhamnofolane diter-
penoid, euphorblin O, have also been reported [7].
Pharmacology: Resiniferatoxin causes apoptosis of prostate cancer cells [8].
Mechanism of Action: Vanilloid receptor 1 (TRPV1), a membrane-associated
cation channel is activated by the resiniferatoxin [2]. Resiniferatoxin mediate
apoptosis through a direct pathway interacting with caspases, particularly caspase 1
and 3 and through an indirect pathway [8].
Human A/Es, Allergy and Toxicity: Extremely irritant to skin on touch, and
harmful to intestines, testes and uterus.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no formal clinical trials reported in published journals
listed on PubMed. It might prove rewarding to those who dare to investigate this
poisonous plant for its pharmacological and clinical effects.

References
1. Appendino G, Szallasi A. Euphorbium: modern research on its active principle,
resiniferatoxin, revives an ancient medicine. Life Sci. 1997;60:681–96.
2. Gavva NR, Klionsky L, Qu Y, et al. Molecular determinants of vanilloid
sensitivity in TRPV1. J Biol Chem. 2004;279:20283–95.
3. Hergenhahn M, Kusumoto S, Hecker E. On the active principles of the
spurge family (Euphorbiaceae). V. Extremely skin-irritant and moderately
tumor-promoting diterpene esters from Euphorbia resinifera Berg. J Cancer
Res Clin Oncol. 1984;108:98–109.
4. Nordal A, Benson AA. Phorbic acid biosynthesis in the latex vessel system of
euphorbia. Plant Physiol. 1969;44:78–84.
5. Szallasi A, Acs G, Cravotto G, et al. A novel agonist, phorbol 12-phenylacetate
13-acetate 20-homovanillate, abolishes positive cooperativity of binding by the
vanilloid receptor. Eur J Pharmacol. 1996;299:221–8.
6. Wang S, Liang H, Zhao Y, et al. New triterpenoids from the latex of Euphorbi
resinifera Berg. Fitoterapia. 2016;108:33–40.
Euphorbia resinifera O. Berg. 903

7. Zhao ND, Ding X, Song Y, et al. Identification of ingol and rhamnofolane

diterpenoids from Euphorbia resinifera and their abilities to induce lysosomal
biosynthesis. J Nat Prod. 2018;81:1209–18.
8. Ziglioli F, Frattini A, Maestroni U, et al. Vanilloid-mediated apoptosis in
prostate cancer cells through a TRPV-1 dependent and a TRPV-1-independent
mechanism. Acta Biomed. 2009;80:13–20.
Ferula assa-foetida L.
(Apiaceae/Umbelliferae)

Abstract
It is a perennial herb, a species native to the deserts of Iran, mountains of
Afghanistan and Turkistan, and is cultivated in India. In all stages of its growth,
every part of the plant exudes, upon abrasion, a milky juice which is collected and
the dried latex (oleogum resin) is marketed as asafetida that has a fetid smell. In
European medicine, hing was used as a stimulant and antispasmodic in chronic
bronchitis, hysteria and tympanites. It helps digestion of foods that are not easily
digestible, and does not produce flatulence or borborygmy. In Iranian traditional
medicine, asafoetida is used as antispasmodic, anthelminthic, carminative and
analgesic. In Unani medicine, it is also regarded as carminative, antispasmodic,
antiseptic, diuretic, nerve tonic, aphrodisiac, emmenagogue, rubefacient and
phlegm-expectorant, and beneficial in nerve diseases, such as epilepsy, palsy,
tremors, tetanus, and splenic diseases. In Ayurveda, it is used in nervous and
neurotic diseases, such as hysteria and hypochondriasis; in habitual cough, chronic
catarrh, bronchitis and asthma. In TCM, it is regarded as vermicide, sedative,
antispasmodic and digestive, and in Fiji, water extract of the dried gum is used for
the treatment of upset stomach. The oleo-gum-resin contains about 40–64% resin,
25% endogeneous gum, and 10–17% volatile oil; major constituents of the resin are
phenolic compounds, such as ferulic acid and its esters, sesquiterpene coumarins,
umbelliferone, coumarin derivatives, such as foetidin and kamolonol, farnesiferoles
A, B and C. Asafoetida exhibited significant analgesic effect on chronic and acute
pain in mice, and exhibited antioxidant and LOX inhibitory activities. Methanol
extract of asafoetida showed inhibitory activity against COX-1 enzyme. Oral
asafoetida significantly increased urine volume, excretion of Na+, K+ and
creatinine clearance in normal rats.

Keywords



Agi Agudagandhu Ah-wei Asafetida

Asa-fétide
Asant
Duivelsdrek




Dyvelsdræk Heeng Heltit Hingu

© Springer Nature Switzerland AG 2020 905
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_97
906 Ferula assa-foetida L.

Vernaculars: Urd.: Heeng, Hing; Hin.: Heeng, Hingiseh anguza, Hingu; San.:
Agudagandhu, Bahleeka, Bhuta nasana, Hinguhu, Romatham, Ramatta, Sahas-
rvedhi, Sulanasana; Ben.: Hing, Hingra; Guj.: Hing; Mal.: Kayam, Perungayam,
Perungkayam; Mar.: Moltani hing; Tam.: Kayam, Perungayam, Perunkayam; Tel.:
Hingu-patri, Ingumo, Inguva; Ara.: Hilteet, Samagh-ul-mahrus, Tyib; Bur.: Shinka;
Chi.: 阿魏, A wei, Ah-wei; Dan.: Dyvelsdræk; Dut.: Duivelsdrek; Eng.: Asafetida,
Asafoetida, Devil’s dung, Stinking gum; Fre.: Asa-fétide, Ase fètide, Férule per-
sique, Merde du diable; Ger.: Asafötida, Asant, Steckenkraut, Stinkasant, Stink-
endes, Teufelsdreck; Ita.: Assa fetida; Jap.: Agi; Maly.: Hingu; Per.: Angoyah,
Angustagooda, Angustha-gandha, Anguza, Anjadana, Aza, Heltit; Sin.: Perunk-
ayan; Spa.: Asafétida; Swe.: Dyvelsträck.
Description: It is a perennial herb that grows up to a height of 1.5 m. The species
is native to the deserts of Iran, mountains of Afghanistan and Turkistan, and is
cultivated in India. In all stages of its growth, every part of the plant exudes, upon
abrasion, a milky juice which is collected and the dried latex (oleogum resin) is
marketed as asafetida. Asafoetida or asafetida (hing) has a fetid smell. The best
hing occurs in tears or flat pieces; the external surface is yellowish, but the fresh
fracture is of pearly white, which on exposure to air becomes bright pink and finally
dirty-yellow (Figs. 1 and 2).XL
Actions and Uses: In European medicine, hing was used as a stimulant and
antispasmodic in chronic bronchitis, hysteria and tympanites. Dr. Paolo Negri suc-
cessfully treated two cases of habitual abortion with hing, administered to the extent of
1 g per day. In the first case, the woman had aborted twice and in the second case four
times; both were free from syphilitic affections and without any apparent cause.XL

Fig. 1 Ferula assa-foetida, Plant, National Arborium, Washington DC, David J. Stang, Wikimedia-
Commons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:
Ferula_assa-foetida_0zz.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
Ferula assa-foetida L. 907

Fig. 2 Ferula assa-foetida, Flowers, Uzbekistan, Valery Fassiaux, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Ferula_assa-foetida_(Uzbekistan)_3.jpg

Avicenna discussed the effects of asafoetida on digestion. Ibn al-BaitarLXIX described

some positive medicinal effects of it on the respiratory system. It helps digestion of
foods that are not easily digestible, and does not produce flatulence or borborygmy. In
Iranian traditional medicine, asafoetida is used as antispasmodic, anthelminthic,
carminative and analgesic [9]. In Unani medicine, it (temperament, hot 4° and dry 2°
but Al-Baitar put the temperament as hot 4° and dry 4°) is also regarded as carminative,
antispasmodic, antiseptic, diuretic, nerve tonic, aphrodisiac, emmenagogue, rubefa-
cient and phlegm-expectorant,LXXVII and beneficial in nerve diseases, such as epi-
lepsy, palsy, tremors, tetanus, and splenic diseases. With honey, its application to the
eyes improves eyesight, and benefits cataract.L It is a nervine and pulmonary stimulant,
acts on and stimulates the organs of circulation and secretion, and also increases sexual
appetite.CV In Ayurveda, it is used in nervous and neurotic diseases, such as hysteria
and hypochondriasis; in habitual cough, chronic catarrh, bronchitis and asthma; as a
carminative in dyspepsia, colic and other gastric affections, and to expel worms. An
enema is the best form in which it is effective in convulsions.LXXXI It has also been
prescribed in infantile convulsions, croup, flatulent colic and bronchitis; and as a dog
and cat repellant.XXIV,CXI,CXXXII,CXXXXI In TCM, it is regarded as vermicide, sedative,
antispasmodic and digestive,LXVI,LXXIX and in Fiji, water extract of the dried gum is
used for the treatment of upset stomach [22]. The resin with active principle of Embelia
ribes, Piper longum and borax taken daily in equally divided doses for 22-days and
abstaining from intercourse prevents conception for 1 year [16].
Phytoconstituents: The oleogum resin contains about 40–64% resin, 25% endo-
geneous gum, and 10–17% volatile oil; major constituents of the resin are phenolic
compounds, such as ferulic acid and its esters, sesquiterpene coumarins, umbellif-
erone, coumarin derivatives, such as foetidin and kamolonol, farnesiferoles A, B and
C [9]. Three sesquiterpene coumarins badrakemin acetate, kellerin and samarcandin
diastereomer were isolated from the resin [17]. Five sesquiterpene coumarins,
conferone, badrakemin, feslol, isosamarcandin and samarcandin were isolated from
the oleo-gum resin from Yasuj region in Iran [4]. The latex contains ferulic acid,
908 Ferula assa-foetida L.

farnesiferol A and C, and sesquiterpenoid coumarins, saradaferin [14] and asi-

mafoetida [18]. Ferula oil mainly contains b-pinene (47.1%), a-pinene (21.36%),
and 1,2-dithiolane (18.6%) [25]. However, EOs obtained from oleo-gum-resins from
Iran collected at different times on 15th June, 30th June and 15th July revealed
variations. Essential oil from 15th June sample had high levels of (E)-1-propenyl
sec-butyl disulfide (23.9%) and 10-epi-c-eudesmol (15.1%); whereas EO from 30th
June sample had high levels of (Z)-1-propenyl sec-butyl disulfide (27.7%) and
(E)-1-propenyl sec-butyl disulfide (20.3%); and b-pinene (47.1%) and a-pinene
(21.3%) were highest in oil samples of resin collected on 15th July, with more potent
antimicrobial activity [24]. Thiophene derivatives, foetithiophenes C-F, foetithio-
phenes A and B, coniferaldehyde, and sinapic aldehyde, have been isolated from the
roots [15].
Pharmacology: Asafoetida exhibited significant analgesic effect on chronic and
acute pain in mice [9], and exhibited antioxidant and LOX inhibitory activities [10].
Methanol extract of asafoetida showed inhibitory activity against COX-1 enzyme
[2], but did not show significant AChE activity [23]. The duration and intensity of
seizures of PTZ-kindled mice by the hydroalcohol extract [28], and of PTZ- and
amygdala kindled rats were significantly reduced by the resin [12]. Low doses of
asafetida were in vitro neuroprotective, and neurotoxic at higher doses [21], but
significantly attenuated glutamate-induced apoptotic/necrotic death of rat cerebellar
granule neurons [37], and exerted neuroprotective effects in neuropathic mice [20].
Pretreatment with methanol extract of aerial parts prevented naloxone-induced
withdrawal symptoms in morphine-dependent mice [27].
Asafetida extract significantly reduced blood glucose and increased serum
insulin levels in alloxan-diabetic rats [1]. Hydroalcohol extract of the stems sig-
nificantly lowered SBP of dexamethasone-induced hypertension in rats [36]. Oral
asafoetida significantly increased urine volume, excretion of Na+, K+ and creatinine
clearance in normal rats [11]. Diet of rats supplemented with seeds for 8-weeks,
caused an increase in pancreatic lipase, amylase and chymotrypsin activities [32],
and decrease in intestinal levels of phosphatases and sucrase [33]. Asafoetida
antagonized ACh induced contractions of isolated ileum of rat [6]. Ferula oil
exhibits significant antimicrobial activity against S. typhi, E. coli, S. aureus, B.
subtilis, A. niger, C. albicans [25], and T. vaginalis [35]. The resin also showed
significant antiparasitic activity against Leishmania major [5]. Powdered asafetida
markedly reduced worm burden and egg counts in experimentally infected mice
with S. mansoni [34]. Ethanol extract of assafoetida is devoid of estrogenic activity,
and still treatment of female rats with the extract from day 1–7 of pregnancy
resulted in pregnancy failure in about 65–85% of the animals. However, treatment
of male rats with asafoetida for six-weeks significantly increased the number and
viability of sperms [13].
Galbanic acid exerts anticancer activity with antiangiogenic and antiproliferative
effects [29]. Both asafoetida and its EO inhibited growth of breast cancer cells [8],
and treatment with asafoetida decreased tumor weight and volume, decreased
metastasis, and significantly increased body weight of female BALB/c mice with
Ferula assa-foetida L. 909

breast carcinoma [7]. Sodium ferulate partly prevented oxidative stress-induced

apoptosis in human lymphocytes [31].
Mechanism of Action: Its antimuscarinic activity may contribute to its antispas-
modic effect [6], and the mechanism for pregnancy interception is suggested to be
its ability to disrupt energy metabolism in rat uterus during implantation, especially
the oxidative pathway [26].
Human A/Es, Allergy and Toxicity: Topical application of oleogum resin EO in
gastrointestinal disorders like flatulence and colic in infants, a popular phytoremedy
in Thailand, has been associated with localized eczematous lesions after repeated
use [38].
Animal Toxicity: A single oral dose of up to 5,000 mg/kg was nontoxic to mice;
repeated dose of 250 mg/kg to Sprague Dawley rats for 28-days resulted in mild
nephrotoxicity [19].
CYP450 and Potential for Drug-Herb Interactions: Alcohol extract signifi-
cantly inhibited CYP3A4 in healthy human volunteers [3], and seven-days treat-
ment of rats with the herb strongly inhibited rat CYP2C11 gene expression [30].
Commentary: There are no clinical studies reported.

References
1. Abu-Zaiton AS. Antidiabetic activity of Ferula assafoetida extract in
normal and alloxan-induced diabetic rats. Pak J Biol Sci. 2010;13:97–100.
2. Ali SK, Hamed AR, Soltan MM, et al. In-vitro evaluation of selected
Egyptian traditional herbal medicines for treatment of Alzheimer disease.
BMC Complement Altern Med. 2013;13:121.
3. Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. Modulation of CYP2D6 and
CYP3A4 metabolic activities by Ferula asafetida resin. Saudi Pharm J.
2014;22:564–9.
4. Asghari J, Atabaki V, Baher E, Mazaheritehrani M. Identification of
sesquiterpene coumarins of oleogum resin of Ferula assa-foetida L. from
the Yasuj region. Nat Prod Res. 2016;30:350–3.
5. Bafghi AF, Bagheri SM, Hejazian SH. Antileishmanial activity of Ferula
assa-foetida oleo gum resin against Leishmania major: an in vitro study.
J Ayurveda Integr Med. 2014;5:223–6.
6. Bagheri S, Hejazian Sh, Dashti-R M. The relaxant effect of seed’s essential
oil and oleogum resin of Ferula assa-foetida on isolated rat’s ileum. Ann
Med Health Sci Res. 2014;4:238–41.
7. Bagheri SM, Abdian-Asl A, Moghadam MT, et al. Antitumor effect of Ferula
assa-foetida oleo gum resin against breast cancer induced by 4T1 cells in
BALB/c mice. J Ayurveda Integr Med. 2017;8:152–8.
910 Ferula assa-foetida L.

8. Bagheri SM, Asl AA, Shams A, Mirghanizadeh-Bafghi SA, Hafizibarjin Z.

Evaluation of cytotoxicity effects of oleogum resin and its essential oil
of Ferula assa-foetida and ferulic acid on 4t1 breast cancer cells. Indian J
Med Paediatr Oncol. 2017;38:116–20.
9. Bagheri SM, Dashti-R MH, Morshedi A. Antinociceptive effect of Ferula
assa-foetida oleogum resin in mice. Res Pharm Sci. 2014;9:207–12.
10. Bagheri SM, Hedesh ST, Mirjalili A, Dashti-R MH. Evaluation of anti-
inflammatory and some possible mechanisms of antinociceptive effect of
Ferula assa-foetida oleo gum resin. J Evid Based Complement Altern Med.
2016;21:271–6.
11. Bagheri SM, Mohammadsadeghi H, Dashti-R MH, Mousavian SM,
Aghaei ZA. Effect of Ferula assa-foetida oleogum resin on renal function
in normal Wistar rats. Indian J Nephrol. 2016;26:419–22.
12. Bagheri SM, Rezvani ME, Vahidi AR, Esmaili M. Anticonvulsant effect
of Ferula assa-foetida oleo gum resin on chemical and amygdala-kindled
rats. N Am J Med Sci. 2014;6:408–12.
13. Bagheri SM, Yadegari M, Porentezari M, et al. Effect of Ferula assa-
foetida oleo gum resin on spermatic parameters and testicular histopathology
in male Wistar rats. J Ayurveda Integr Med. 2015;6:175–80.
14. Bandyopadhyay D, Basak B, Chatterjee A, et al. Saradaferin, a new sesqui-
terpenoid coumarin from Ferula assafoetida. Nat Prod Res. 2006;20:961–5.
15. Chitsazian-Yazdi M, Agnolet S, Lorenz S, et al. Foetithiophenes C-F,
thiophene derivatives from the roots of Ferula foetida. Pharm Biol. 2015;
53:710–4.
16. Das PC. British Pat. 1,025,372 (Cl A 61K), Apr 6, 1956. Indian Appl. July
25, 1963; 2 pp: Through Chem Abstr 64, 19328h, 1966.
17. Ghannadi A, Fattahian K, Shokoohinia Y, Behbahani M, Shahnoush A.
Antiviral evaluation of sesquiterpene coumarins from Ferula assa-foetida
against HSV-1. Iran J Pharm Res. 2014;13:523–30.
18. Ghosh A, Banerji A, Mandal S, Banerji J. A new sesquiterpenoid coumarin
from Ferula assafoetida. Nat Prod Commun. 2009;4:1023–4.
19. Goudah A, Abdo-El-Sooud K, Yousef MA. Acute and subchronic toxicity
assessment model of Ferula assa-foetida gum in rodents. Vet World. 2015;
8:584–9.
20. Homayouni Moghadam F, Dehghan M, Zarepur E, et al. Oleo gum resin
of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice. J
Ethnopharmacol. 2014;154:183–9.
21. Homayouni Moghadam F, Vakili Zarch B, Shafiei M. Double edged effect
of gum-resin of Ferula assa-foetida on lifespan of neurons. Iran J Basic
Med Sci. 2013;16:660–3.
22. Iranshahi M. Traditional uses, phytochemistry and pharmacology of asa-
foetida (Ferula assa-foetida oleogum resin)—a review. J Ethnopharmacol.
2011;134:1–10.
Ferula assa-foetida L. 911

23. Jazayeri SB, Amanlou A, Ghanadian N, Pasalar P, Amanlou M. A prelim-

inary investigation of anticholinesterase activity of some Iranian medicinal
plants commonly used in traditional medicine. Daru. 2014;22:17.
24. Kavoosi G, Rowshan V. Chemical composition, antioxidant and antimicrobial
activities of essential oil obtained from Ferula assa-foetida oleogum resin:
effect of collection time. Food Chem. 2013;138:2180–7.
25. Kavoosi G, Tafsiry A, Ebdam AA, Rowshan V. Evaluation of antioxidant
and antimicrobial activities of essential oils from Carum copticum seed
and Ferula assafoetida latex. J Food Sci. 2013;78:T356–61.
26. Keshri G, Bajpai M, Lakshmi V, et al. Role of energy metabolism in the
pregnancy interceptive action of Ferula assafoetida and Melia azedarach
extracts in rat. Contraception. 2004;70:429–32.
27. Khanavi M, Maadani S, Farahanikia B, Eftekhari M, Sharifzadeh M. Effect
of the methanolic extracts of different parts of Ferula assa-foetida on
naloxone-induced withdrawal behavior in morphine-dependent mice. Avi-
cenna J Phytomed. 2017;7:426–35.
28. Kiasalari Z, Khalili M, Roghani M, Heidari H, Azizi Y. Antiepileptic and
antioxidant effect of hydroalcoholic extract of Ferula assa-foetida gum on
pentylentetrazole-induced kindling in male mice. Basic Clin Neurosci.
2013;4:299–306.
29. Kim KH, Lee HJ, Jeong SJ, et al. Galbanic acid isolated from Ferula
assafoetida exerts in vivo antitumor activity in association with anti-
angiogenesis and antiproliferation. Pharm Res. 2011;28:597–609.
30. Korashy HM, Al-Jenoobi FI, Raish M, et al. Impact of herbal medicines like
Nigella sativa, Trigonella foenum-graecum, and Ferula asafoetida, on
Cytochrome P450 2C11 gene expression in rat liver. Drug Res (Stuttg).
2015;65:366–72.
31. Lu Y, Xu C, Yang Y, Pan H. The effect of antioxidant sodium ferulate on
human lymphocytes apoptosis induced by H2O2. Zhongguo Yi Xue Ke Xue
Yuan Xue Bao. 1998;20:44–8 (Chinese)
32. Platel K, Srinivasan K. Influence of dietary spices and their active principles
on pancreatic digestive enzymes in albino rats. Nahrung. 2000;44:42–6.
33. Platel K, Srinivasan K. Influence of dietary spices or their active principles
on digestive enzymes of small intestinal mucosa in rats. Int J Food Sci Nutr.
1996;47:55–9.
34. Ramadan NI, Abdel-Aaty HE, Abdel-Hameed DM, et al. Effect of Ferula
assafoetida on experimental murine Schistosoma mansoni infection. J Egypt
Soc Parasitol. 2004;34(3 Suppl):1077–94.
35. Ramadan NI, Al Khadrawy FM. The in vitro effect of Assafoetida on
Trichomonas vaginalis. J Egypt Soc Parasitol. 2003;33:615–30.
36. Safaeian L, Ghannadi A, Javanmard SH, Vahidian MH. The effect of
hydroalcoholic extract of Ferula foetida stems on blood pressure and
oxidative stress in dexamethasone-induced hypertensive rats. Res Pharm
Sci. 2015;10:326–34.
912 Ferula assa-foetida L.

37. Tayeboon GS, Tavakoli F, Hassani S, et al. Effects of Cymbopogon citratus

and Ferula assa-foetida extracts on glutamate-induced neurotoxicity. In
Vitro Cell Dev Biol Anim. 2013;49:706–15.
38. Tempark T, Chatproedprai S, Wananukul S. Localized contact dermatitis
from Ferula assa-foetida oleogum resin essential oil, a traditional topical
preparation for stomach ache and flatulence. Net Letter. 2016;62:467.
Ficus carica L.
(Moraceae)

Abstract
Fig tree is a flowering, mulberry family deciduous tree growing in India, Asia
Minor, Iran, West Asia, and subtropics; also naturalized in North America. Fig has
been known to ancient Greeks, Romans, Arabs and Persians, and has been valued
from prehistoric times for its nutritious fruits. It is mentioned in the sacred books of
the Hebrews, early Greek and Latin writers, and has been mentioned in the Holy
Qur’an. Hippocrates described it as aperient, emollient and nutritious, and being
useful as an article of diet in phlegmatic affections. It carries off phlegm, and gravel
in the kidneys or bladder, and removes obstruction of the liver and spleen, and it
cures piles and gout. Both fresh and dried figs are important components of the
Mediterranean diet, are laxative, and pectoral, and are used in catarrh of respiratory
passages. Dried figs are carminative, laxative, nutritious, and beneficial for people
with cold temperament, backache and urinary incontinence. Fresh fruits are sweet,
wholesome and delicious; taken in moderate quantity they are digestive, laxative
and nutritious. Excessive use leads to flatulence, enteralgia and diarrhea. A poultice
of figs is used over gum boils and abscesses on the anus and vulva to hasten
suppuration. In some rural areas of Iran fig tree latex is traditionally used as topical
application for the treatment of warts. Latex is also traditionally used as a vermifuge
in Central and South America. Monomer sugars predominate in figs, and sugars as
well as organic acids contents are higher in dried figs; also, the total phenolic
content and antioxidant activity are higher after drying. Its crude extracts have
shown anticancer, hepatoprotective, hypoglycemic, hypolipidemic, and antimi-
crobial effects. Supplementation of diet with fig paste in Korean patients with
functional constipation for 8-weeks, significantly improved abdominal discomfort
and constipation. In a randomized study involving a small number of insulin-
dependent Spanish diabetic patients with HbA1c of 7.6, supplementation of fig leaf
decoction with breakfast to insulin treatment significantly lowered postprandial
blood sugar levels without affecting the preprandial level, and significantly reduced
the required insulin dose.

© Springer Nature Switzerland AG 2020 913

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_98
914 Ficus carica L.

Keywords
Aitoviikuna
Anjira
Feigenbaum
Fig
Figen
Injeer
Incir
Teen

Vijgenboom
Wú huā guǒ

Vernaculars: Urd.: Injeer; Hin.: Anjir; San.: Anjira, Udeunbara; Ben.: Anjir,
Doomoor; Guj.: Anjir; Mal.: Shima-atti; Mar.: Anjira; Tam.: Anjura, Shimai-atti,
Ten-atti; Tel.: Modipatu, Shima-atti, Tene-atti; Ara.: Teen, Teen barchomi; Bur.:
Saphansi, Thaphan, Thinbaw thapan; Chi.: 无花果, Wú huā guǒ; Cze.: Fíkovník
smokvoň, Smokvoň obecná; Dan.: Almindelig figen, Figen; Dut.: Gewone vijgeboom,
Vijgenboom; Eng.: Fig; Fin.: Aitoviikuna; Fre.: Arbre à carriques, Caprifiguier,
Figuier, Figuier commun, Figuier de carie; Ger.: Feigenbaum, Zahnfeigenbaum; Ita.:
Fico, Fico comune; Jap.: Ichijiku, Ichizhiku; Kor.: Mu hwa gwa; Nor.: Fiken; Per.:
Anjeer, Anjira, Jamir; Pol.: Figowiec właściwy; Por.: Bebereira, Caprifigos (Br.),
Figueira, Figueira-brava, Figueira-comum; Spa.: Cabrahigo, Higuera, Higuera común;
Swe.: Fikon, Vanlig fikonträd; Tur.: Incir; Vie.: Quả vả.
Description: Fig tree is a flowering, mulberry family deciduous tree growing in
India, Asia Minor, Iran, West Asia, and subtropics; also naturalized in North
America. The tree grows to a height of 7–10 m; leaves being wide and three or five
lobed. Its fruit (fig) is 3–5 cm in diameter with green skin, becoming purple or
brown on ripening. It consists of a thick, fleshy, hollow receptacle of a peer-shaped
form, on the inner face of which grow a multitude of minute fruits. Immature figs
are greenish or greenish-yellow, tough and leathery, exuding, when pricked, a
milky juice; mature figs are soft, juicy, fleshy, yellowish or brownish-red externally
and deep red within. Pulp is very mucilaginous, sweet, palatable with a fruity odor;
figs contain numerous whitish-yellow tiny seeds. Two varieties, the purple and the
green are cultivated in India (Figs. 1 and 2).XL

Fig. 1 Ficus carica, Tree with Ripe and Unripe Fruits, Fir0002, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Fig_tree.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Ficus carica L. 915

Fig. 2 Ficus carica, Fruits (Green and Purple Varieties), Prof. Akbar, Original

Actions and Uses: Fig has been known to ancient Greeks, Romans, Arabs and
Persians, and has been valued from prehistoric times for its nutritious fruits. It is
mentioned in the sacred books of the Hebrews, early Greek and Latin writers, and has
been mentioned in the Holy Qur’an. Hippocrates described it as aperient, emollient and
nutritious, and being useful as an article of diet in phlegmatic affections. It carries off
phlegm, and gravel in the kidneys or bladder, and removes obstruction of the liver and
spleen, and it cures piles and gout [11].XL Both fresh and dried figs are important
components of the Mediterranean diet [43], are laxative,LXIX and pectoral, and are used
in catarrh of respiratory passages. Dried figs are carminative, laxative, nutritious, and
beneficial for people with cold temperament, backache and urinary incontinence.LXIX
Fresh fruits are sweet, wholesome and delicious; taken in moderate quantity they are
digestive, laxative and nutritious. Excessive use leads to flatulence, enteralgia and
diarrhea. A poultice of figs is used over gum boils and abscesses on the anus and vulva
to hasten suppuration.LXXXI Figs were imported into Czech countries in the early
Middle Ages where they were integral part of the diet [18], and archaeobotanical
analysis of the early Roman incineration graves shows the existence of figs [48]. In
Unani medicine, fresh fruit (temperament, hot 1° and moist 2°) is regarded refrigerant,
fattening, hematinic, carminative, laxative, strengthens liver function, and beneficial in
phlegmatic diseases, such as epilepsy, paralysis, palpitation and asthma, and
strengthens urinary bladder.L Leaves are effective in various inflammatory conditions
like painful or swollen piles, insect sting and bites [4]. Figs remove gravel from
kidneys and bladder, and obstructions of the liver and spleen, and are also useful in the
treatment of piles and gout.CV In Iranian traditional medicine, it is used for the treat-
ment for digestive, endocrine, reproductive, and respiratory systems ailments, such as
anemia, cancer, diabetes, leprosy, liver diseases, paralysis, skin diseases, and ulcers [9].
In some rural areas of Iran fig tree latex is traditionally used as topical application for
the treatment of warts [14]. Latex is also traditionally used as a vermifuge in Central
and South America [19].
916 Ficus carica L.

Phytoconstituents: Monomer sugars predominate in figs, and sugars as well as

organic acids contents are higher in dried figs; also, the total phenolic content and
antioxidant activity are higher after drying [47]. Phenolic compounds identified in
figs, especially in fig peel, include chlorogenic acid, protocatechuic acid, vanillic acid,
rutin, luteolin-3,7-di-O-glucoside, luteolin 7-glucoside, apigenin-7-O-rutinoside,
quercetin-3-glucoside, and cyanidin-3-O-rutinoside; also found are amino acids
tyrosine and tryptophan. Turkish dried figs have the highest concentration of phe-
nolic compounds [43]. Tirucallane-type triterpenoids, ficutirucins A–I, were isolated
from the fruit [26], triterpenes [2], and 1-cyclohexyl-6,7-dimethoxy-1,4-di-
hydronaphthalene were isolated from the leaves [16]. Twenty-eight phenolic com-
pounds, including hydroxybenzoic acids, hydroxycinnamic acids, flavonoids and
hydroxycoumarins were identified in the ethanol extract of fruits from Tunisia [12].
Psoralen and bergapten are the only significant photoactive compounds present in
appreciable quantities in the leaf and shoot sap, but are not detected in the fruit or its
sap [53]. Proteolytic enzymes were reported from latex of green fig of Kadota variety
[28, 45]. In the leaves, furocoumarins psoralen, bergapten and the coumarins
umbelliferone, 4′,5′-dihydropsoralen and marmesin are present, that show seasonal
variations with total coumarinic content being maximum in early August, and lowest
in June. Quantity of psoralen being always greater than that of bergapten, umbellif-
erone, 4′,5′-dihydropsoralen and of marmesin [25, 53]. Quercetin and luteolin are the
major flavonoids in ethanol extract of leaves, with a total of 631 and 681 mg/kg
extract, respectively [50]. A common phenolic profile of leaves, pulp and peel,
consisting of 3-O- and 5-O-caffeoylquinic acids, ferulic acid, quercetin-3-O-
glucoside, quercetin-3-O-rutinoside, psoralen and bergapten, was reported in Por-
tuguese white varieties. Leaves [37] and latex [36] also contain organic acids:
oxalic, citric, malic, quinic, shikimic and fumaric acids. In methanol leaf extract
umbelliferone, caffeic acid, quercetin-3-O-b-d-glucopyranoside, quercetin-3-O-a-l-
rhamnopyranoside, and kaempferol-3-O-a-l-rhamnopyranoside have been identified
[46]. Volatile contents of the latex include phytosterols [35], aldehydes, alcohols,
ketone, monoterpenes, and sesquiterpenes; sesquiterpenes being the most abundant.
Pharmacology: Its crude extracts have shown anticancer, hepatoprotective, hypo-
glycemic, hypolipidemic, and antimicrobial effects [32]. Ethanol fruit extract signifi-
cantly lowered TC, TGs, and LDL-C and increased HDL-C of high-fat diet-induced
hyperlipidemic rats [12], whereas, methanol fruit extract significantly decreased BP in
both normotensive and glucose-treated hypertensive rats, and produced negative
inotropic and chronotropic effects on isolated heart [3]. Leaf extract significantly
lowers TG and IL-6 levels and elevates HDL-C better than pioglitazone, and signifi-
cantly lowers atherogenic index and the coronary risk index in high-fat diet-induced
dyslipidemic rats [27]. Even a single dose of leaf decoction to hypertriglyceridic rats
lowered TG levels [39]. Aqueous leaf extract decreased glucose in diabetic but not in
normal rats, significantly decreased plasma insulin levels in nondiabetic rats [41], and
normalized oxidative stress in STZ-diabetic rats [40]. Ethyl acetate leaf extract sig-
nificantly reduced blood glucose, TC, TGs, body weight and hepatic glycogen, and
normalized activities of key carbohydrate metabolizing enzymes of diabetic rats [49].
Ficus carica L. 917

Petroleum ether and methanol leaf extracts significantly reversed rifampicin-induced

biochemical, histological and functional hepatic changes [23], and CCl4-induced
hepatotoxicity and oxidative damage in rats [46]. Supplementation of fig paste in rat’s
diet reduces loperamide [31], and high protein diet-induced constipation in beagles
[34]. Contrarily, ethanol leaf extract reportedly significantly reduced castor oil-
induced diarrhea and significantly inhibited PGE2-induced enteropooling [38].
Hydroalcohol leaf extract treatment improved sperm count, nonprogressive motility of
spermatozoa, and other formaldehyde-induced cell injury and oxidative damage in
mice testes [33], and ameliorated gentamicin-nephrotoxicity in mice [22]. Leaves
possess the highest antiradical activity and inhibition of peroxidation, and exhibit
highest antiproliferative activity against C32 human melanoma cells [17]. Polysac-
charides isolated from fruits exhibited more notable scavenging activity than the
aqueous extract of fruits [52].
Aqueous-acetone leaf extract exhibited CNS depressant activity, significantly
prolonging ketamine-induced sleeping time, attenuating the anxiety-response,
delaying the onset of MES and PTZ-induced seizures and reducing duration of
seizures and mortality in mice [13]. Aqueous leaf extract exhibited distinct
anti-HSV-1 effect [51], and methanol extract inhibited growth of clinical isolates of
S. aureus, S. epidermidis, and S. pyogenes [5]. Hexane extract of the Tunisian
caprifig latex showed significant antibacterial activity against clinical isolate of S.
aureus and S. saprophyticus [30]. Methanol extract of latex significantly inhibited
growth of P. mirabilis and M. canis, and total inhibition of C. albicans; whereas,
ethyl acetate extract inhibited growth of E. fecalis, C. freundeii, P. aeruginosa,
E. coli and P. mirabilis [7]. Hexane and hexane-ethyl acetate extracts of fig fruit
latex inhibited multiplication of HSV-1, echovirus type 11 (ECV-11) and aden-
ovirus viruses [29]. Fig tree latex exhibits in vitro and in vivo anticancer activity
without affecting normal human cells [6, 24].
Clinical Studies: Supplementation of diet with fig paste in Korean patients with
functional constipation for 8-weeks, significantly improved abdominal discomfort
and constipation [10]. In a randomized study involving a small number of
insulin-dependent Spanish diabetic patients with HbA1c of 7.6 ± 0.9%, supple-
mentation of fig leaf decoction with breakfast to insulin treatment significantly
lowered postprandial blood sugar levels without affecting the preprandial level, and
significantly reduced the required insulin dose [44]. Topical application of an
aqueous fruit extract based cream was significantly effective in symptomatic relief
of atopic dermatitis in pediatric patients [1]. In a prospective, open, right/left trial,
application of fig tree latex on common warts caused resolution in 44% patients,
compared to 56% with cryotherapy [14].
Human A/Es, Allergy and Toxicity: Photodermatitis has occurred in workers
coming in physical contact with leaves or fruits, such as pruning fig tree branches,
resulting in blistering eruptions [21, 42]. A very rare occurrence, but anaphylactic
reaction has been reported in a French individual very shortly after ingestion of a
fresh fig [20]; cross-allergy with mulberries in certain individuals has also been
reported [15].
918 Ficus carica L.

Animal Toxicity: Oral LD50 of the dried aqueous leaf extract in mice is between
3,360 and 4,000 mg/kg body weight [8].
Commentary: Pharmacological studies showed that leaf extracts are as much
effective and valuable as the fig fruits. As a supplement to insulin, leaf decoction
was effective in improving postprandial blood glucose even in IDDM patients.
Other effects of fruits and latex were also corroborated in small clinical trials,
though further clinical studies are warranted to establish these effects. Leaves and
latex of this common tree and its delicious and nutritious fruits need further vali-
dation for clinical benefits.

References
1. Abbasi S, Kamalinejad M, Babaie D, et al. A new topical treatment of atopic
dermatitis in pediatric patients based on Ficus carica L. (Fig): a randomized,
placebo-controlled clinical trial. Complement Ther Med. 2017;35:85–91.
2. Ahmed W, Khan AQ, Malik A. Two triterpenes from the leaves of Ficus
carica. Planta Med. 1988;54:481.
3. Alamgeer, Iman S, Asif H, Saleem M. Evaluation of antihypertensive
potential of Ficus carica fruit. Pharm Biol. 2017;55:1047–53.
4. Ali B, Mujeeb M, Aeri V, et al. Anti-inflammatory and antioxidant activity
of Ficus carica Linn. leaves. Nat Prod Res. 2012;26:460–5.
5. Ali NH, Faizi S, Kazmi SU. Antibacterial activity in spices and local
medicinal plants against clinical isolates of Karachi. Pakistan. Pharm Biol.
2011;49:833–9.
6. Amara AA, El-Masry MH, Bogdady HH. Plant crude extracts could be the
solution: extracts showing in vivo antitumorigenic activity. Pak J Pharm Sci.
2008;21:159–71.
7. Aref HL, Salah KB, Chaumont JP, et al. In vitro antimicrobial activity of
four Ficus carica latex fractions against resistant human pathogens (antimi-
crobial activity of Ficus carica latex). Pak J Pharm Sci. 2010;23:53–8.
8. Awobajo FO, Omorodion-Osagie E, Olatunji-Bello II, et al. Acute oral
toxicity test and phytochemistry of some West African medicinal plants.
Nig Q J Hosp Med. 2009;19:53–8.
9. Badgujar SB, Patel VV, Bandivdekar AH, Mahajan RT. Traditional uses,
phytochemistry and pharmacology of Ficus carica: a review. Pharm Biol.
2014;52:1487–503.
10. Baek HI, Ha KC, Kim HM, et al. Randomized, double-blind, placebo-
controlled trial of Ficus carica paste for the management of functional
constipation. Asia Pac J Clin Nutr. 2016;25:487–96.
11. Barolo MI, Ruiz Mostacero N, López SN. Ficus carica L. (Moraceae): an
ancient source of food and health. Food Chem. 2014;164C:119–27.
12. Belguith-Hadriche O, Ammar S, Contreras Mdel M, et al. Antihyperlipi-
demic and antioxidant activities of edible Tunisian Ficus carica L. fruits in
Ficus carica L. 919

high fat diet-induced hyperlipidemic rats. Plant Foods Hum Nutr. 2016;71:
183–9.
13. Bhanushali MM, Makhija DT, Joshi YM. Central nervous system activity of
an aqueous acetonic extract of Ficus carica L. in mice. J Ayurveda Integr
Med. 2014;5:89–96.
14. Bohlooli S, Mohebipoor A, Mohammadi S, et al. Comparative study of fig
tree efficacy in the treatment of common warts (Verruca vulgaris) versus
cryotherapy. Int J Dermatol. 2007;46:524–6.
15. Caiaffa MF, Cataldo VM, Tursi A, Macchia L. Fig and mulberry cross- allergy.
Ann Allergy Asthma Immunol. 2003;91:493–5.
16. Chen SY, Zhang YP, Huang B, Yu JJ, Shi WY. 1-Cyclo-hexyl-6,7-dimeth-
oxy-1,4-di-hydronaphthalene. Acta Crystallogr Sect E Struct Rep [Online].
2014;70(Pt 6):o671.
17. Conforti F, Menichini G, Zanfini L, et al. Evaluation of phototoxic potential
of aerial components of the fig tree against human melanoma. Cell Prolif.
2012;45:279–85.
18. Culíková V. Assortment of the plants in the Medieval diet in Czech countries
(based on archaeobotanical finds). Acta Univ Carol [Med] (Praha). 2000;41:
105–18.
19. de Amorin A, Borba HR, Carauta JP, et al. Anthelmintic activity of the latex
of Ficus species. J Ethnopharmacol. 1999;64:255–8.
20. Dechamp C, Bessot JC, Pauli G, Deviller P. First report of anaphylactic
reaction after fig (Ficus carica) ingestion. Allergy. 1995;50:514–6.
21. Derraik JG, Rademaker M. Phytophotodermatitis caused by contact with a
fig tree (Ficus carica). N Z Med J. 2007;120:U2720.
22. Ghaffar A, Tahir M, Lone KP, Faisal B, Latif W. The effect of Ficus car-
ica l. (Anjir) leaf extract on gentamicin induced nephrotoxicity in adult male
albino mice. J Ayub Med Coll Abbottabad. 2015;27:398–401.
23. Gond NY, Khadabadi SS. Hepatoprotective activity of Ficus carica leaf
extract on rifampicin-induced hepatic damage in rats. Indian J Pharm Sci.
2008;70:364–6.
24. Hashemi SA, Abediankenari S, Ghasemi M, et al. The effect of fig tree latex
(Ficus carica) on stomach cancer line. Iran Red Crescent Med J. 2011;13:
272–5.
25. Innocenti G, Bettero A, Caporale G. Determination of the coumarinic con-
stituents of Ficus carica leaves by HPLC. Farmaco [Sci]. 1982;37:475–85
(Italian).
26. Jing L, Zhang YM, Luo JG, Kong LY. Tirucallane-type triterpenoids from
the fruit of Ficus carica and their cytotoxic activity. Chem Pharm Bull
(Tokyo). 2015;63:237–43.
27. Joerin L, Kauschka M, Bonnländer B, et al. Ficus carica leaf extract
modulates the lipid profile of rats fed with a high-fat diet through an
increase of HDL-C. Phytother Res. 2014;28:261–7.
920 Ficus carica L.

28. Kramer DE, Whitaker JR. Ficus enzymes. II. Properties of the proteolytic
enzymes from the latex of Ficus carica variety Kadota. J Biol Chem. 1964;
239:2178–83.
29. Lazreg Aref H, Gaaliche B, Fekih A, et al. In vitro cytotoxic and antiviral
activities of Ficus carica latex extracts. Nat Prod Res. 2011;25:310–9.
30. Lazreg-Aref H, Mars M, Fekih A, et al. Chemical composition and anti-
bacterial activity of a hexane extract of Tunisian caprifig latex from the
unripe fruit of Ficus carica. Pharm Biol. 2012;50:407–12.
31. Lee HY, Kim JH, Jeung HW, et al. Effects of Ficus carica paste on
loperamide-induced constipation in rats. Food Chem Toxicol. 2012;50:
895–902.
32. Mawa S, Husain K, Jantan I. Ficus carica L. (Moraceae): phytochemistry,
traditional uses and biological activities. Evid Based Complement Alternat
Med. 2013;2013:974256.
33. Naghdi M, Maghbool M, Seifalah-Zade M, et al. Effects of common fig
(Ficus carica) leaf extracts on sperm parameters and testis of mice intoxi-
cated with formaldehyde. Evid Based Complement Alternat Med. 2016;
2016:2539127.
34. Oh HG, Lee HY, Seo MY, et al. Effects of Ficus carica paste on
constipation induced by a high-protein feed and movement restriction in
beagles. Lab Anim Res. 2011;27:275–81.
35. Oliveira AP, Silva LR, Andrade PB, et al. Further insight into the latex
metabolite profile of Ficus carica. J Agric Food Chem. 2010;58:10855–63.
36. Oliveira AP, Silva LR, Ferreres F, et al. Chemical assessment and in vitro
antioxidant capacity of Ficus carica latex. J Agric Food Chem. 2010;58:
3393–8.
37. Oliveira AP, Valentão P, Pereira JA, et al. Ficus carica L.: metabolic and
biological screening. Food Chem Toxicol. 2009;47:2841–6.
38. Patil VV, Bhangale SC, Chaudhari KP, et al. Evaluation of the antidiarrheal
activity of the plant extracts of Ficus species. Zhong Xi Yi Jie He Xue Bao.
2012;10:347–52.
39. Pérez C, Canal JR, Campillo JE, et al. Hypotriglyceridaemic activity of
Ficus carica leaves in experimental hypertriglyceridaemic rats. Phytother
Res. 1999;13:188–91.
40. Pèrez C, Canal JR, Torres MD. Experimental diabetes treated with Ficus carica
extract: effect on oxidative stress parameters. Acta Diabetol. 2003;40:3–8.
41. Pérez C, Domínguez E, Canal JR, Campillo JE, Torres MD. Hypoglycaemic
activity of an aqueous extract from Ficus carica (fig tree) leaves in
streptozotocin diabetic rats. Pharm Biol. 2000;38:181–6.
42. Polat M, Oztas P, Dikilitas MC, Alli N. Phytophotodermatitis due to Ficus
carica. Dermatol Onlin J. 2008;14:9.
43. Russo F, Caporaso N, Paduano A, Sacchi R. Phenolic compounds in fresh and
dried figs from Cilento (Italy), by considering breba crop and full crop, in
comparison to Turkish and Greek dried figs. J Food Sci. 2014;79:C1278–84.
Ficus carica L. 921

44. Serraclara A, Hawkins F, Pérez C, et al. Hypoglycemic action of an oral

fig-leaf decoction in type-I diabetic patients. Diabetes Res Clin Pract.
1998;39:19–22.
45. Sgarbieri VC, Gupte SM, Kramer DE, Whitaker JR. Ficus enzymes.
I. Separation of the proteolytic enzymes of Ficus carica and Ficus glabrata
latices. J Biol Chem. 1964;239:2170–7.
46. Singab AN, Ayoub NA, Ali EN, Mostafa NM. Antioxidant and hepatopro-
tective activities of Egyptian moraceous plants against carbon tetrachloride-
induced oxidative stress and liver damage in rats. Pharm Biol. 2010;48:
1255–64.
47. Slatnar A, Klancar U, Stampar F, Veberic R. Effect of drying of figs (Ficus
carica L.) on the contents of sugars, organic acids, and phenolic compounds.
J Agric Food Chem. 2011;59:11696–702.
48. Sostarić R, Dizdar M, Kusan D, et al. Comparative analysis of plant finds
from Early Roman graves in Ilok (Cuccium) and Sćitarjevo (Andautonia),
Croatia—a contribution to understanding burial rites in southern Pannonia.
Coll Antropol. 2006;30:429–36.
49. Stephen Irudayaraj S, Christudas S, Antony S, et al. Protective effects of
Ficus carica leaves on glucose and lipids levels, carbohydrate metabolism
enzymes and b-cells in type 2 diabetic rats. Pharm Biol. 2017;55:1074–81.
50. Vaya J, Mahmood S. Flavonoid content in leaf extracts of the fig (Ficus
carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.).
Biofactors. 2006;28:169–75.
51. Wang G, Wang H, Song Y, et al. Studies on anti-HSV effect of Ficus carica
leaves. Zhong Yao Cai. 2004;27:754–6 (Chinese).
52. Yang XM, Yu W, Ou ZP, et al. Antioxidant and immunity activity of water
extract and crude polysaccharide from Ficus carica L. fruit. Plant Foods
Hum Nutr. 2009;64:167–73.
53. Zaynoun ST, Aftimos BG, Abi Ali L, et al. Ficus carica; isolation and
quantification of the photoactive components. Contact Dermatitis. 1984;11:
21–5.
Ficus racemosa L.
(Moraceae)

(Syns.: F. glomerata Roxb.; Covellia glomerata (Roxb.) Miq.)

Abstract
A large tree with crooked trunk, is found in Indian subcontinent, Australia, south-
east Asia, and Malaysia. Its fruits grow on or close to the trunk. Atharvaveda,
one of the oldest Hindu Scriptures, considers it a divine plant, recommends its use
in religious sacrifice, and considers it as a means for acquiring prosperity and
vanquishing foes. Bark, leaves and unripe fruits are astringent, carminative,
stomachic and vermicidal; the Ayurvedic Nighantus described the bark as
cooling, sweet and astringent. Rajniganthu mentioned that the bark protects fetus
of the pregnant and acts as galactagogue. In dysmenorrhea, leaves decoction is
used as a douche every morning. In Ayurvedic scriptures, it is mentioned as
Udumbara with great medicinal value; the bark, leaves and unripe fruits are used
externally and internally for the treatment of pravahika, pradara, raktapitta, and
diabetes, liver disorders, diarrhea, inflammatory conditions, hemorrhoids,
respiratory, and urinary diseases. Ripe fruit is refrigerant, nutritious, laxative,
and expectorant, and beneficial in dry cough, chest, spleen and kidney pain. Fruit
is a rich source of calcium, containing about 15 times the amount of calcium
present in wheat. b-sitosterol-D-glucoside (I), friedelin and lupeol were isolated
from the petroleum ether extract of stem bark; I is a known hypoglycemic agent.
Both aqueous and ethanol extracts of stem bark produced significant fall in blood
glucose, and HbA1c levels, and improved antioxidant enzymes activities,
reduced LPO level and CRP in diabetic rats. Chloroform and methanol leaf
extracts also exhibited significant hypoglycemic activity in normal and fasted
rabbits fed with glucose. Oral supplementation of the bark extract twice daily for
15-days, along with oral hypoglycemic drugs to 50 diabetic Pakistani patients of
either sex, markedly decreased fasting and post-breakfast blood sugar in both
males and females. Blood glucose lowering property is credited to the presence of
b-sitosterol, and is mediated via binding to PPARc and GLUT1 receptors.

© Springer Nature Switzerland AG 2020 923

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_99
924 Ficus racemosa L.

Keywords



Ayimit Duea kliang Elo Gullar

Indian fig
Jantuphala
Ju guo rong




Jummaiz Sung Teen-el-ahmaq

Vernaculars: Urd.: Gullar, Jummaiz; Hin.: Dimeri, Gullar, Lelka, Paroa, Umar,
Tue; San.: Hemadugdhaka, Jantuphala, Sadaphalah, Yajñodumbara, Udumbara,
Zajmiya; Ben.: Dumur, Jagnodumar, Jagya-domur, Jogdumur; Mal.: Aththi, Atti,
Atti-yalum, Gular; Mar.: Audumbar, Chapal, Umbara, Umber-gular; Tam.: Anai,
Athi, Aththi, Atti-payham; Tel.: Arri, Attimanu, Boda-mamidi, Bodda, Mari, Medi
pandu moyui, Paidi, Udumbaramu; Ara.: Jammaiz, Teen-el-ahmaq; Bur.: Hpak-lu,
Jagyadumbar, Mayen; Chi.: 聚果榕, Ju guo rong; Eng.: Cluster fig, Country fig,
Glorious fig, Gular fig, Indian fig; Ind.: Elo; Nep.: Dumrii; Per.: Adam, Injeer,
Samate-pashshah, Teen-el-ahmaq; Sin.: Attikka; Tag.: Ayimit, Ayúmit, Hagánit,
Hagimit; Tha.: Duea kliang, Duea nam; Vie.: Cây sung, Sung.
Description: A large tree with crooked trunk, thick rough bark of a rusty greenish
color; leaves alternate, petioled, oblong or broad lanceolate, tapering equally to each
end, entire, very slightly 3-nerved, smooth on both sides; racemes compound or
panicled, issuing immediately from the trunk or large branches; fruit pedicelled,
nearly as large as the common fig.XL The fruits grow on or close to the trunk. The tree
is found in Indian subcontinent, Australia, southeast Asia, and Malaysia (Figs. 1
and 2).
Actions and Uses: Atharvaveda, one of the oldest Hindu Scriptures, considers it a
divine plant, recommends its use in religious sacrifice, and considers it as a means
for acquiring prosperity and vanquishing foes.CXXIX Bark, leaves and unripe fruits
are astringent, carminative, stomachic and vermicidal; the Ayurvedic Nighantus

Fig. 1 Ficus racemosa, Tree with Fruits in different Stages of Ripening, A.J.T. Johnsingh, WWF-
India and NCF, WikimediaCommons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.
wikimedia.org/wiki/File:Ficus_racemosa_Panna_TR_IMG_3319.jpg; https://creativecommons.
org/licenses/by-sa/4.0/deed.en
Ficus racemosa L. 925

Fig. 2 Ficus racemosa, Unripe Fruits, Vengolis, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Ficus_racemosa_8756.jpg

described the bark as cooling, sweet and astringent. Seed powder mixed with honey
is regarded useful in reducing glycosuria, polydipsia and polyuria of diabetes; and
Rajniganthu mentioned that the bark protects fetus of the pregnant and acts as
galactagogue. In dysmenorrhea, leaves decoction is used as a douche every
morning.CV In Ayurvedic scriptures, it is mentioned as Udumbara with great
medicinal value [35]; the bark, leaves and unripe fruits are used externally and
internally for the treatment of pravahika, pradara, raktapitta [37], and diabetes,
liver disorders, diarrhea, inflammatory conditions, hemorrhoids, respiratory, and
urinary diseases [8]. The milky juice is used internally as an alterative and tonic,
and also applied as a poultice to the chest, abdomen, and to rheumatic joints,
mumps and other glandular enlargements.LXXXI Ripe fruit is refrigerant, nutritious,
laxative, and expectorant, and beneficial in dry cough, chest, spleen and kidney
pain; whereas, unripe fruit is astringent and styptic, and used as antidiarrheal and to
stop hemorrhoidal bleeding. The milky juice is inflammatory, and the root water is
cold and quenches thirst. Leaves decoction is used for cough, and asthma, and the
milk is applied to inflammations.L,LXXVII Traditional healers in Sri Lanka claim the
bark decoction to be antidiuretic [32]. The juice is also applied as a remedy for
toothache, and to cracked and inflamed soles of the feet.XL Ibn al-BaitarLXIX quoted
Sharif that eating 5 g grounded leaves first thing in the morning is curative for
chronic diarrhea unresponsive to all treatments. The Boxa tribe of Nainital district
(India), applies the latex to forehead and on the wrist to treat conjunctivitis [34]. In
the Philippines, the leaves are used topically as antirheumatic, and the sap is
employed as a beverage.CXVII
Phytoconstituents: Fruit is a rich source of calcium, containing about 15 times the
amount of calcium present in wheat [16]. b-sitosterol-D-glucoside (I), friedelin and
lupeol were isolated from the petroleum ether extract of stem bark; I is a known
hypoglycemic agent [12]. Bergenin was the major component in cold aqueous
extract of stem bark, while the hot aqueous extract showed the presence of ferulic
926 Ficus racemosa L.

acid, kaempferol, and coumarin, in addition to bergenin [2], and acetone bark
extract showed the presence of bergenin and bergapten [5]. Other compounds
reported from the plant include polyphenols, friedelane-type triterpenes, nor-
friedelane type triterpene, eudesmane-type sesquiterpene including glycosides [22].
An anti-inflammatory glucoside, racemosic acid, showed potent in vitro COX-1 and
5-LOX inhibitory activity, and a strong antioxidant activity to scavenge ABTS free
radical cations [23].
Pharmacology: Both aqueous and ethanol extracts of stem bark produced sig-
nificant fall in blood glucose, and HbA1c levels, and improved antioxidant enzymes
activities, reduced LPO level and CRP in diabetic rats [35]. Ethanol stem bark
extract significantly restored blood glucose and lipid levels in diabetic rats, and
improved antioxidant enzymes activities [21, 36]. Akhtar and Qureshi [9], however,
earlier reported that methanol fruit extract produced significant hypoglycemia in
diabetic rabbits, but the aqueous extract failed to produce this effect. Aqueous-
ethanol (80%) fruit extract and its water-soluble fraction did not lower serum
glucose in nondiabetic and type-2 diabetic rats in fasting condition, but the extract
significantly produced hypoglycemic effect in type-1 diabetic rats’ model. They
were ineffective when administered 30 min prior to glucose load, but when fed
simultaneously with glucose load, were consistently active in both nondiabetic and
types-1 and -2 diabetic model rats [20]. Chloroform and methanol leaf extracts
exhibited significant hypoglycemic activity in normal and fasted rabbits fed with
glucose [11]; methanol bark extract showed similar activity [14], and flavonoids
isolated from the stem bark also reduced blood glucose level and lipids, and
increased HDL-C [22]. The bark significantly inhibited in vitro porcine pancreatic
a-amylase, rat intestinal a-glucosidase, almond b-glucosidase, and sucrose [6].
Methanol bark extract showed potent in vitro antioxidant activity and significant
hepatoprotective effect against CCl4-hepatotoxicity in rats [7, 15], and demonstrated
significant antitussive activity against sulfur dioxide-induced cough reflex in mice
[13]. Pretreatment of rats with bark acetone extract ameliorated doxorubicin-induced
renal and testicular oxidative stress by inhibiting LPO and scavenging free radicals [3].
Methanol extract of fruits and bark significantly reversed CP-induced blood cell count
changes and showed significant phagocytic effect on human neutrophils [19]. Aqueous
root extract showed wound healing effect that was better than the ethanol extract [28].
Ethanol fruit extract exhibited significant gastroprotection against various noxious
challenges in rats and prevented oxidative damage of gastric mucosa [30]; whereas,
ethanol bark and leaf extracts significantly reduced gastrointestinal motility and
inhibited castor oil-induced diarrhea and PGE2-induced enteropooling in rats [27, 29].
Acetone stem bark extract scavenges free radicals and significantly protects against
doxorubicin-cardiotoxicity in rats [5]. Crude tannin fraction of acetone bark extract
significantly reversed increased blood glucose and dyslipidemia caused by high-fat
diet in rats, and restored insulin, HDL-C and activities of antioxidant enzymes to
almost normal levels [39]. Stem bark, green fruit and leaf gall extracts also showed
significant in vitro free radical scavenging activity [10, 17, 38, 40]. Methanol fruit
extract demonstrates significant in vitro thrombolytic activity [33].
Ficus racemosa L. 927

Both cold and hot aqueous extracts of the stem bark exhibited a dose dependent
rat brain AChE inhibitory activity, but none produced 50% inhibition [4], and
administration of aqueous bark extract to rats significantly increased ACh levels in
hippocampi [1]. Ethanol leaf extract significantly inhibited in vitro COX-1 with an
IC50 of 100 lg/ml [24], showed significant anti-inflammatory activity in different
experimental models [25], and the methanol stem bark extract significantly reduced
dose-dependently normal body temperature and yeast-induced elevated temperature
in rats [31]. Aqueous stem bark decoction significantly reduced total urine output in
rats, with rapid onset and for a period of 5 h [32]. Petroleum ether leaf extract
showed significant in vitro antibacterial activity, comparable to chloramphenicol,
against E. coli, B. pumilis, B. subtilis, P. aeruginosa and S. aureus [26].
Clinical Studies: Oral supplementation of the bark extract (5 mL; about 100 mg)
twice daily for 15-days, along with oral hypoglycemic drugs to 50 diabetic Pak-
istani patients of either sex, markedly decreased fasting and post-breakfast blood
sugar in both males and females, but the significant difference was only observed in
males after 1.5 h after breakfast [18].
Mechanism of Action: Blood glucose lowering property is credited to the pres-
ence of b-sitosterol [41], and is mediated via binding to PPARc and GLUT1
receptors [22].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Acetone stem bark extract was nontoxic and nonlethal to mice
up to a dose of 2,000 mg/kg [5].
Commentary: Various extracts of different parts of the plant have shown blood
glucose-lowering effect, that was also observed in clinical trial of diabetic patients.
The mechanism for hypoglycemic action of flavonoids has been suggested to be
mediated via binding to PPARc and GLUT1 receptors. There were also some
interesting observations regarding blood glucose lowering effect of aqueous-ethanol
fruit extract in animal models. However, more clinical studies are needed to explore
other beneficial effects observed in pharmacological studies, and their relationship
to broad-spectrum antioxidant activity exhibited by various extracts.

References
1. Ahmed F, Chandra JN, Manjunath S. Acetylcholine and memory-enhancing
activity of Ficus racemosa bark. Pharmacognosy Res. 2011;3:246–9.
2. Ahmed F, Siddesha JM, Urooj A, Vishwanath BS. Radical scavenging and
angiotensin converting enzyme inhibitory activities of standardized extracts
of Ficus racemosa stem bark. Phytother Res. 2010;24:1839–43.
3. Ahmed F, Urooj A, Karim AA. Protective effects of Ficus racemosa stem
bark against doxorubucin-induced renal and testicular toxicity. Pharmacogn
Mag. 2013;9:130–4.
928 Ficus racemosa L.

4. Ahmed F, Urooj A. Anticholinesterase activities of cold and hot aqueous

extracts of F. racemosa stem bark. Pharmacogn Mag. 2010;6:142–4.
5. Ahmed F, Urooj A. Cardioprotective activity of standardized extract of
Ficus racemosa stem bark against doxorubicin-induced toxicity. Pharm
Biol. 2012;50:468–73.
6. Ahmed F, Urooj A. Effect of Ficus racemosa stem bark on the activities of
carbohydrate hydrolyzing enzymes: an in vitro study. Pharm Biol. 2010;48:
518–23.
7. Ahmed F, Urooj A. Hepatoprotective effects of Ficus racemosa stem bark
against carbon tetrachloride-induced hepatic damage in albino rats. Pharm
Biol. 2010;48:210–6.
8. Ahmed F, Urooj A. Traditional uses, medicinal properties, and phytophar-
macology of Ficus racemosa: a review. Pharm Biol. 2010;48:672–81.
9. Akhtar MS, Qureshi AQ. Phytopharmacological evaluation of Ficus
glomerata, Roxb. fruit for hypoglycaemic activity in normal and diabetic
rabbits. Pak J Pharm Sci. 1988;1:87–96.
10. Anandjiwala S, Bagul MS, Parabia M, Rajani M. Evaluation of free radical
scavenging activity of an ayurvedic formulation, panchvalkala. Indian J
Pharm Sci. 2008;70:31–5.
11. Balaji K, Venkiteshwarlu V, Reddy VM. Hypoglycamic activity of extracts
of Ficus glomerata. Anc Sci Life. 1996;15:301–3.
12. Baslas RK, Agha R. Isolation of a hypoglycemic principle from the bark of
F. glomerata Roxb. Himalayan Chem Pharm Bull. 1985;2:13.
13. Bhaskara Rao R, Murugesan T, Pal M, et al. Antitussive potential of methanol
extract of stem bark of Ficus racemosa Linn. Phytother Res. 2003;17:
1117–8.
14. Bhaskara Rao R, Murugesan T, Sinha S, et al. Glucose lowering efficacy of
Ficus racemosa bark extract in normal and alloxan diabetic rats. Phytother
Res. 2002;16:590–2.
15. Channabasavaraj KP, Badami S, Bhojraj S. Hepatoprotective and antiox-
idant activity of methanol extract of Ficus glomerata. Nat Med (Tokyo).
2008;62:379–83.
16. Duhan A, Chauhan BM, Punia D. Nutritional value of some nonconventional
plant foods of India. Plant Foods Hum Nutr. 1992;42:193–200.
17. Eshwarappa RS, Iyer S, Subaramaihha SR, Richard SA, Dhananjaya BL.
Antioxidant activities of Ficus glomerata (Moraceae) leaf gall extracts.
Pharmacognosy Res. 2015;7:114–20.
18. Gul-e-Rana, Karim S, Khurhsid R et al. Hypoglycemic activity of Ficus
racemosa bark in combination with oral hypoglycemic drug in diabetic
human. Acta Pol Pharm. 2013;70:1045–9.
19. Heroor S, Beknal AK, Mahurkar N. Immunomodulatory activity of methano-
lic extracts of fruits and bark of Ficus glomerata Roxb. in mice and on human
neutrophils. Indian J Pharmacol. 2013;45:130–5.
20. Jahan IA, Nahar N, Mosihuzzaman M et al. Hypoglycaemic and antioxidant
activities of Ficus racemosa Linn. fruits. Nat Prod Res. 2009;23:399–408.
Ficus racemosa L. 929

21. Joshi H, Vaishnav D, Sanghvi G, et al. Ficus recemosa bark extract attenuates
diabetic complications and oxidative stress in STZ-induced diabetic rats.
Pharm Biol. 2016;54:1586–95.
22. Keshari AK, Kumar G, Kushwaha PS, et al. Isolated flavonoids from Ficus
racemosa stem bark possess antidiabetic, hypolipidemic and protective
effects in albino Wistar rats. J Ethnopharmacol. 2016;181:252–62.
23. Li RW, Leach DN, Myers SP, et al. A new anti-inflammatory glucoside
from Ficus racemosa L. Planta Med. 2004;70:421–6.
24. Li RW, Myers SP, Leach DN, et al. A crosscultural study: anti-inflammatory
activity of Australian and Chinese plants. J Ethnopharmacol. 2003;85:25–32.
25. Mandal SC, Maity TK, Das J, et al. Anti-inflammatory evaluation of Ficus
racemosa Linn. leaf extract. J Ethnopharmacol. 2000;72:87–92.
26. Mandal SC, Saha BP, Pal M. Studies on antibacterial activity of Ficus
racemosa Linn. leaf extract. Phytother Res. 2000;14:278–80.
27. Mukherjee PK, Saha K, Murugesan T, et al. Screening of antidiarrhoeal
profile of some plant extracts of a specific region of West Bengal. India.
J Ethnopharmacol. 1998;60:85–9.
28. Murti K, Kumar U. Enhancement of wound healing with roots of Ficus
racemosa L. in albino rats. Asian Pac J Trop Biomed. 2012;2:276–80.
29. Patil VV, Bhangale SC, Chaudhari KP, et al. Evaluation of the antidiarrheal
activity of the plant extracts of Ficus species. Zhong Xi Yi Jie He Xue Bao.
2012;10:347–52.
30. Rao ChV, Verma AR, Vijayakumar M, Rastogi S. Gastroprotective effect of
standardized extract of Ficus glomerata fruit on experimental gastric ulcers
in rats. J Ethnopharmacol. 2008;115:323–6.
31. Rao RB, Anupama K, Swaroop KR, et al. Evaluation of antipyretic potential
of Ficus racemosa bark. Phytomedicine. 2002;9:731–3.
32. Ratnasooriya WD, Jayakody JR, Nadarajah T. Antidiuretic activity of aqueous
bark extract of Sri Lankan Ficus racemosa in rats. Acta Biol Hung. 2003;54:
357–63.
33. Shivasharanappa K, Londonkar R. Clot lysis and antimitotic study of Ficus
glomerata Roxb. fruit extracts. SRN Pharmacol. 2014;2014:975303.
34. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
35. Solanki ND, Bhavsar SK. An evaluation of the protective role of Ficus
racemosa Linn. in streptozotocin-induced diabetic neuropathy with neu-
rodegeneration. Indian J Pharmacol. 2015;47:610–5.
36. Sophia D, Manoharan S. Hypolipidemic activities of Ficus racemosa Linn.
bark in alloxan induced diabetic rats. Afr J Tradit Complement Altern Med.
2007;4:279–88.
37. Subhaktha PK, Rajasekaran R, Narayana A. Udumbara (Ficus glomerata
Roxb.): a medicohistorical review. Bull Indian Inst Hist Med Hyderabad.
2007;37:29–44.
930 Ficus racemosa L.

38. Veerapur VP, Prabhakar KR, Parihar VK, et al. Ficus racemosa stem bark
extract: a potent antioxidant and a probable natural radioprotector. Evid
Based Complement Alternat Med. 2009;6:317–24.
39. Velayutham R, Sankaradoss N, Ahamed KF. Protective effect of tannins
from Ficus racemosa in hypercholesterolemia and diabetes induced vascu-
lar tissue damage in rats. Asian Pac J Trop Med. 2012;5:367–73.
40. Verma AR, Vijayakumar M, Rao CV, Mathela CS. In vitro and in vivo
antioxidant properties and DNA damage protective activity of green fruit
of Ficus glomerata. Food Chem Toxicol. 2010;48:704–9.
41. Yadav RK, Nandy BC, Maity S, Sarkar S, Saha S. Phytochemistry,
pharmacology, toxicology, and clinical trial of Ficus racemosa. Pharma-
cogn Rev. 2015;9:73–80.
Foeniculum vulgare Mill.
(Apiaceae/Umbelliferae)

(Syns.: F. officinale All.; F. commune Bubani; F. foeniculum (L.) H. Karst.; Anethum

foeniculum L.; Ligusticum foeniculum (L.) Crantz.; Meum foeniculum (L.) Spreng.)

Abstract
It is universally known as fennel and by more than 100 other names, and has been
used medicinally throughout the world since ancient times. Hippocrates and
Dioscorides mentioned fennel as diuretic and emmenagogue, and the juice was
supposed to sharpen the eyesight. As one of the ancient Saxon people’s nine
sacred herbs, fennel was credited with the power to cure, and was valued as a magic
herb. In the Middle Ages it was draped over doorways on Midsummer’s Eve to
protect the household from evil spirits. It is one of the most commonly consumed
herb by more than a quarter of Italian pregnant women every day for at least
3 months during pregnancy, and one of the most frequently quoted plants in
The Chilandar Medical Codex, the best preserved medieval Serbian manuscript
on European medical science from the 12th to 15th centuries. In Europe and
Mediterranean countries, fennel is traditionally used as antispasmodic, diuretic,
anti-inflammatory, analgesic, secretomotor, secretolytic, galactagogue, as eye
lotion, and antioxidant remedy and integrator; topically, fennel powder is used as a
poultice for snakebites. In Portugal, it is highly recommended for treatment of
diabetes, bronchitis and chronic coughs, and for kidney stones. In Unani medicine,
it is used to open liver and spleen obstructions, relieve flatulent colic, and to induce
diuresis and menstruation. In traditional Iranian medicine, it has been used for the
treatment of inflammatory bowel diseases. Boiled or roasted roots are used for the
treatment of gonorrhea in East Africa. In TCM, it is used to relieve chills, abdominal
distension, vomiting and diarrhea. Fennel infusion is approved for GI disorders use
in Europe since Nov. 2005 by the HMPC of the European Medicines Agency.
Fennel contains d-pinene, camphene, d-a-phellandrene, dipentine, anethole,
fenchone, methyl chavicol, aldehydes, and anisic acid. Bergapten, columbianetin,
osthenol, psoralen, scoparone seselin, vanillin, b-sistosterol and stigmasterol have
also been identified in fruits. In general, fennel oil extracted by either distillation-
extraction or supercritical fluid extraction shows similar compositions, with
trans-anethole, estragole, and fenchone as the main components.

© Springer Nature Switzerland AG 2020 931

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_100
932 Foeniculum vulgare Mill.

Keywords







Badyan Fenchel Fennel Fenouil Finokio Fiolho Huí xiāng Mudhurika




Razyanaj Rezene Saunf

Vernaculars: Urd.: Badyan, Saunf; Hin.: Bari saunf; San.: Methica, Mudhurika;
Ben.: Moori, Panmohuri; Mar.: Badishep, Bari sonpha, Shoap; Tam.: Perun,
Shombu, Sohikire, Sombu; Tel.: Peddajilakurra, Sopu; Ara.: Bisbas, Razyanaj,
Shua’r; Chi.: 茴香, Hsiao-hui, Hsiao-hui-hsiang, Hui-shiang, Huí xiāng, Xiao hui
xiang; Cze.: Fenykl; Dan.: Almindelig fennikel, Fennikel; Dut.: Tuinvenkel,
Venkel; Eng.: Fennel, Sweet fennel; Fre.: Aneth doux, Fenouil, Fenouil amer,
Fenouil commun; Ger.: Echter fenchel, Fenchel, Gartenfenchel, Gemeiner fenchel,
Gewöhnlicher fenchel; Gre.: Finokio, Maratho; Ita.: Finocchio, Finocchio comune,
Finocchio selvatico; Jap.: Fenneru, Uikyô; Nep.: Madesi sauf; Nor.: Fennikel;
Per.: Badian, Karafah, Razianeh; Pol.: Fenkuł; Por.: Fiolho, Fionho, Funcho,
Funcho-Amargo, Funcho-bravo, Funcho-comum; Rus.: Fenchel’ obyknovennyj;
Spa.: Acapate (Mexico), Cenojo, Fenojo, Fenol, Fonol común, Hierba santa,
Hinojo común, Mello, Perejil de gitano, Tenojo, Zenollo; Swe.: Fänkål; Tag.: Anis,
Haras; Tha.: Phak chi, Phak chi lom; Tur.: Rezene.
Description: An erect, aromatic, perennial herb 1–2 m high, similar in appearance
to dill; leaves alternate, 3 or 4 times pinnate, superior leaves with sheaths longer
than the blade. Flowers yellow (July–October), not involucrate. Fruits are greenish
or yellowish, glabrous, somewhat concave, ridged, aromatic, oblong or ellipsoid,
6 mm long and 2 mm in diameter, semicylindrical, with 5 prominent, nearly regular
ribs, sweet and pungent in taste, odor resembling anise (Figs. 1 and 2).LXXIX,CXVII
Actions and Uses: It is universally known as fennel and by more than 100 other
names, and has been used medicinally throughout the world since ancient times
[10, 30]. Hippocrates and Dioscorides mentioned fennel as diuretic and emmena-
gogue, and the juice was supposed to sharpen the eyesight.XL As one of the ancient
Saxon people’s nine sacred herbs, fennel was credited with the power to cure, and
was valued as a magic herb. In the Middle Ages it was draped over doorways on
Midsummer’s Eve to protect the household from evil spirits [37]. It is one of the most
commonly consumed herbs by more than a quarter of Italian pregnant women every
day for at least 3 months during pregnancy [31], and one of the most frequently quoted
plants in The Chilandar Medical Codex, the best preserved medieval Serbian manu-
script on European medical science from the 12th to 15th centuries [40]. In Europe and
Mediterranean countries, fennel is traditionally used as antispasmodic, diuretic,
anti-inflammatory, analgesic, secretomotor, secretolytic, galactagogue, as eye lotion,
and antioxidant remedy and integrator; topically, fennel powder is used as a poultice
for snakebites [37]. In Portugal, it is highly recommended for treatment of diabetes,
bronchitis and chronic coughs, and for kidney stones [14]. Fruits (seeds) are carmi-
native and stomachic,LXXIX emmenagogue [82],CL especially reputed to increase milk
secretion, promote menstruation, facilitate birth, alleviate symptoms of the male
climacteric, and increase libido [5]. In India, fennel fruit water is used to relieve colic
Foeniculum vulgare Mill. 933

Fig. 1 Foeniculum vulgare, Plant, Karelj, WikimediaCommons, https://commons.wikimedia.org/

wiki/File:Foeniculum_vulgare_prg_1.jpg

Fig. 2 Foeniculum vulgare, Fruits/Seeds, Prof. Akbar, Original

934 Foeniculum vulgare Mill.

and flatulence, and also as a diuretic and diaphoretic in children and infants. A hot
infusion is used to treat amenorrhea and to improve lactation.XL,LXXXI,CV In Unani
medicine, it (temperament, hot 1° and dry 1°) is used to open liver and spleen
obstructions, relieve flatulent colic, and to induce diuresis and menstruation.LXXVII
In traditional Iranian medicine, it has been used for the treatment of inflammatory
bowel diseases [78]. Fennel EO is widely used as carminative and flavoring agent in
food products such as liqueurs, bread, cheese, and as an ingredient of cosmetics and
pharmaceutical products [37].XXIV,CXXXII,CXXXXI In Mexican traditional medicine,
decoction is used as galactagogue,XCVI and to treat tuberculosis and other respiratory
diseases [19], and is traditionally used as digestive stimulant in northeast Lebanon
[43], and the infused fruits as carminative in the Philippines.CXVII Boiled or roasted
roots are used for the treatment of gonorrhea in East Africa.LXXXV In TCM, it is used to
relieve chills, abdominal distension, vomiting and diarrhea.LXV,LXVI Leaves infusion
is used to treat infant’s stomachache, and seeds are used by adults to dispel gases in
Guyana and Surinam.XXXIV Fennel infusion is traditionally used in Europe for nursing
babies to prevent flatulence and colicky spasm [37], and is approved for GI disorders
use in Europe since Nov. 2005 by the HMPC of the European Medicines Agency.
Phytoconstituents: It contains d-pinene, camphene, d-a-phellandrene, dipentine,
50–65% anethole, fenchone, methyl chavicol, aldehydes, anisic acid, and sometimes
1,3-dimethyl butadiene. Bergapten, columbianetin, osthenol, psoralen, scoparone
seselin, vanillin, b-sistosterol and stigmasterol have also been identified in fruits
[56]. Elements present in Ethiopean fennel fruits were reported as Ca, Mg, Fe, Mn, Cu,
Cr, Co, Zn, Ni, and Cd [30]. Fennel is also reported as one of the highest plant sources
of potassium, sodium, phosphorus, and calcium [10]. Methanol seed extract was
reported to contain flavonoids, terpenoids, alkaloids, phenols, and sterols; estragole
(71%) being the predominant alcohol, gallic acid the main phenolic compound
(18.9%), and l-limonene as the most prevalent monoterpene hydrocarbon (11.9%)
[61]. Methanolic seed extract was reported to have high amounts of total flavonoids
[38]. Extracts from air-dried aerial parts show highest antioxidant activity during the
early fruiting stage, which is characterized by lowest flavonoid content and high
phenolic acid content [73]. In general, fennel oil extracted by either distillation-
extraction or supercritical fluid extraction shows similar compositions, with trans-
anethole, estragole, and fenchone as the main components [12, 26]. Trans-anethole
(85.6%) is the predominant constituent of the oil [1, 22, 24, 27], while estragole is
found in small amounts (2.8%), and fenchone being <1% [22]. Miguel et al. [58],
however, reported methyl chavicol (estragole) as the dominant constituent in the fruit
EO, and trans-anethole, a-pinene and limonene being the main components of the
dried aerial parts EO of samples from Portugal; whereas, Cabral et al. [18] reported
E-anetol (47%), a-phellandrene (11%), a-pinene (10%) and fenchone (10.8%) as
the main constituents of fruit EO from Portugal. Essential oils obtained from various
wild Italian varieties contained five chemical groups characterized by a-phellandrene,
methyl chavicol and trans-anethole; a-pinene, limonene and trans-anethole; methyl
chavicol and a-phellandrene; methyl chavicol and a-pinene; and a-phellandrene [74].
The method of distillation significantly affects the yield and quantitative composition
Foeniculum vulgare Mill. 935

of essential oil [59]. Yield of Turkish EO (5 mL/kg) and content of trans-anethole

is very low (34.8%), whereas yield of EO in fennel from Norway and Austria (50.7
and 50.5 mL/kg, respectively) is maximum; these samples are richer in fenchone (21.2
and 22.8%), but contain less trans-anethole (64.6–63.7) than samples from Estonia
and Moldova (82.0 and 80.9%) [76]. Flavonoid constituents identified in fennel are
quercetin 3-glucuronide, isoquercitrin, rutin, and quercetin 3-arabinoside. Other con-
stitutents identified are kaempferol 3-glucuronide and kaempferol 3-arabinoside [48].
Two diglucoside stilbene trimers and a benzoisofuranone derivative have also been
isolated from the fruits [25]. In Chinese medicine various frying methods are used
before the fruits are incorporated in polyherbal preparations. After different frying
methods, contents of all twenty-four ingredients of the volatile oil are changed, and
eighteen new compounds, including linalylacetate, farnesene, p-allyiphenyl aromatic
oxide, menthone, and hexyl octanoate are created; trans-anethole remains the largest of
the effective ingredients in fried samples [99].
Pharmacology: Aqueous fruit extract increases gastric acid secretion by more than
three times of basal secretion in rats, not blocked by atropine; and significantly
reduces basal acid secretion in aspirin-induced gastric mucosal damage [93]. Pre-
treatment with aqueous extract significantly reduces ethanol-induced gastric dam-
age in rats [15], and oral administration of EO and anethole also significantly
protects against ethanol-induced gastric lesions in rats [90]. It has shown significant
diuretic activity in experimental studies [94]. Acetone fruit extract exhibits estro-
genic activity, increasing weight of mammary glands, vaginal cornification and
estrus cycle in female rats [54]. Aqueous extract was renoprotective in experimental
PCOS in rats [81], and prevented ovariectomy-induced bone loss, reducing both
osteoclast differentiation and function [47]. Fennel supplementation in diet also
protects rats against cyclosporine-nephrotoxicity [85]. Methanol fruit extract
exhibited inhibitory effects against acute and subacute inflammation and a cen-
tral analgesic effect. It also significantly increased plasma antioxidant enzymes
activities and the HDL-C level [21]. Ethanol extract is also reported to inhibit
carrageenin-induced inflammation by 36% [55]. Four coumarins isolated from
fruits show excellent in vitro antioxidant activities, and imperatorin had the greatest
anti-inflammatory activity [95]. Fennel EO is a potent hepatoprotective agent
against CCl4-hepatotoxicity [71]. Fruit extract also exhibits in vitro immunomod-
ulatory NFkappaB activities [45].
Oral administration of aqueous fruit extract lowered SBP of SHRs, and increased
water, Na+ and K+ excretion [28]. Intravenous boiled aqueous leaf extract also
significantly lowered arterial BP, whereas the nonboiled aqueous extract showed
insignificant hypotensive activity [2]. Oral administration of EO and anethole to
mice exhibited significant antithrombotic activity, and both, in vitro inhibited
platelet aggregation and prevented thrombin-induced clot retraction [90, 91].
Coadministration of fennel EO with emamectin benzoate (EB) to rats ameliorates
EB-induced coagulative necrosis and blood vessels congestion of the liver and
necrosis of white pulp of the spleen. EB is an avermectin insecticide used exten-
sively in pest control on vegetable and field crops [29]. Topical application of
936 Foeniculum vulgare Mill.

aqueous fruit extract significantly reduced intraocular pressure in both normoten-

sive and experimental glaucoma model in rabbits [3]. Methanol extract of the whole
plant administered for eight successive days ameliorated scopolamine-induced
amnesic effect, aging-induced memory deficits, and significantly inhibited AChE in
mice [44]. The EO exhibits potential anxiolytic activity in mice [57], and very
highly inhibits in vitro activities of AChE and BChE; however, the single com-
ponents of the oil were not as active as the oil [69]. Ethanol extract, and EO also
significantly produced in vitro relaxant effect on methacholine-induced contraction
of tracheal chain; calcium channels inhibition was not a contributing mechanism of
the relaxant effect [17].
Aqueous fruit extract demonstrates direct and significant in vitro NO scavenging
[13], and antioxidant activities [32, 83], and improved activities of antioxidant
enzymes in trichloroacetic acid-exposed rats [20]. n-Butanol and aqueous fruit
extracts also showed moderate radical scavenging properties in vitro [25]. Pre-
treatment of mice with methanol fruit extract exerted cytoprotective effect against
gamma irradiation [61]. Moderate antioxidant activity of ethanol fruit extract
showed no correlation with the total flavonoid content of the extract [67]. The EO
demonstrated in vitro antioxidant capacities, comparable to that of a-tocopherol and
butylated hydroxytoluene [80]. Shoots are reported to have the highest radical-
scavenging activity and LPO inhibition capacity, contain the highest content of
phenolics and ascorbic acid, and high concentration of tocopherols and are the only
part to contain flavonoids [14]. Fruit extract significantly inhibits generation of ROS
from H. pylori-infected gastric epithelial cells [97]. Infusion rather than decoction
of aerial parts shows better in vitro antioxidant activity [39].
The EO did not exhibit any significant antibacterial activity against standard
strains of E. coli, S. aureus, P. aeruginosa, B. megaterium, and B. cereus [9, 51, 63, 84,
86]; showed significant antifungal activity against C. albicans [8, 72], toxigenic
Aspergillus species [7], and potent activity against dermatophytes T. rubrum,
T. tonsurans, T. mentagrophytes and M. gypseum, better than the antifungal agents
fluconazole and amphotericin B [98]; and against isolates of MDR A. baumannii [42].
However, significant antibacterial activity of hot water and acetone extracts against
E. faecalis, S. aureus, E. coli, P. aeruginosa, S. typhi, S. typhimurium and Sh. flexneri
[46], and of EO against various strains of S. aureus, E. coli, S. enterica, B. cereus,
L. monocytogenes, C. albicans, A. niger, and Penicillium spp. have been reported [50].
Also, EO of Turkish fennel was effective against food-borne pathogens, E. coli,
L. monocytogenes, S. typhimurium, and S. aureus [24], and strains of K. pneumoniae
producing ESbetaL enzyme [70]. Essential oil from Portugal also exhibited activity
against E. faecalis, S. epidermidis and S. aureus; and against six Gram-negative
strains: E. coli, M. morganii, P. mirabilis, S. enteritidis, and P. aeruginosa [64], and
potent activity against C. neoformans and C. albicans [18]. Moderate activity of
methanol extract against 15 strains of H. pylori with an MIC of 50 mcg/ml [53],
significant activity of hydroethanol extract against C. jejuni [23], and against MDR
M. tuberculosis [19] have been observed. Fennel oil, used at subinhibitory concen-
trations, dose-dependently decreased expression of S. aureus exotoxins, including
a-toxin, Staphylococcal enterotoxins and toxic shock syndrome toxin 1 [75].
Foeniculum vulgare Mill. 937

Clinical Studies: In a randomized, placebo-controlled trial, use of fennel oil emul-

sion relieved colic in 65% of 2 to 12-weeks old infants [6]. In several clinical studies
in young high-school girls with moderate to severe dysmenorrhea, treatment with
fennel, fennel extract or essence of fennel’s fruit effectively reduced menstrual pain
and duration comparable to mefenamic acid [16, 36, 60, 66, 68]. Fennel (200 mg/d)
use for 8-weeks significantly relieved menopausal symptoms in triple-blind RCT of
Iranian women [79]. Fennel use with low-dose oral contraceptives also relieved depot
medroxyprogesterone acetate-induced amenorrhea in married women [62]. Once
daily intravaginal application of fennel 5% vaginal cream in postmenopausal women
for 8-weeks, in a double-blind RCT, significantly increased number of superficial
cells and significantly decreased vaginal pH [96]. However, oral administration of
fennel (300 mg/d) was not effective in relieving vaginal atrophy [35], did not affect
bone density after 12-weeks use [33], or significantly relieved anxiety and depression
symptoms in postmenopausal women [34]. In double-blind RCTs in women with
mild to moderate idiopathic hirsutism, topical application of 3% fennel gel [4], or
application of cream containing 2% ethanol fruit extract significantly reduced hair
thickness after 24-weeks of treatment [41]. In an RCT, Chinese women drinking
fennel tea after undergoing a laparotomy for gynecological malignancies, signifi-
cantly recovered bowel motility faster, with a shorter hospital stay and fewer com-
plications [52]. Drinking fennel tea before lunch led to decreased hunger, less
prospective food consumption, and increased feeling of fullness in overweight
Korean women [11].
Mechanism of Action: Pharmacologically active estrogenic agents are polymers
of anethole, such as dianethole and photoanethole [5].
Doses: European Medicine Agency recommended doses are:
Adults: 1.5–2.5 g of freshly comminuted fennel fruits with 0.25 L of boiling
water (brew for 15 min) three times daily as herbal tea.
Children: for symptomatic treatment of mild, spasmodic gastrointestinal com-
plaints including bloating and flatulence. Average daily dose:
3 months–1 year of age: 1–2 g of crushed fruits as an infusion
1–4 years of age: 1.5–3 g of crushed fruits as an infusion
4–12 years of age: 3–5 g of crushed fruits as an infusion.
Human A/Es, Allergy and Toxicity: Long-term use to relieve gas and regulate
intestinal function in children may also cause premature thelarche [92]. Intoxication
in infants resulting in methemoglobinemia after eating homemade fennel purée has
also been reported [65]. An epileptic patient with well-controlled epilepsy devel-
oped a typical generalized tonic-clonic seizure after consuming a number of cakes
containing an unknown quantity of fennel EO. Therefore, one should be aware of
the risk of seizures in patients with epilepsy on fennel EO ingestion [87]. Risk of
observed estragole carcinogenicity in rodent is suggested to be overestimated, and
cannot be extrapolated to humans, as metabolism of estragole differs in humans and
rodents. Furthermore, pure estragole is inactivated by other substances present in
the fruit decoction [37].
938 Foeniculum vulgare Mill.

Animal Toxicity: No animal toxicity studies are reported in the literature.

CYP450 and Potential for Drug-Herb Interactions: Aqueous fennel extract is
reported to potently inhibit CYP2D6 and CYP3A4, potentially cause a clinically
relevant inhibition of intestinal CYP3A4, and may influence the pharmacokinetics
of drugs metabolized by these isozymes [49, 77]. Methanol fruit extract also time-
dependently inhibited CYP3A4 in human liver microsomes [88]; 5-methoxypsoralen
was identified responsible for the CYP3A4 inhibitory activity [89]. Concomitant
administration of aqueous extract with ciproflxacin to rats affected absorption, dis-
tribution and elimination, significantly lowering maximum plasma concentration,
AUC and urinary recovery of ciprofloxacin [100].
Commentary: Variations in antibacterial activity of various extracts and EO of
fruits from different geographical locations and time of harvest, demonstrate and
emphasize the influence of phytoconstituents. Many of the expected clinical effects,
including esterogenic effects, were observed in clinical trials, substantiating the
traditional uses and results from pharmacological studies. Nevertheless, extensive
RCTs are needed to establish some of these clinical benefits, and more of this
simple and inexpensive herbal. Because of its CYP2D6 and CYP3A4 inhibitory
activity, more drug-interaction studies would be required to avoid any inadvertent
negative effects of its use with conventional drugs.

References
1. Abdollahi A, Hassani A, Ghosta Y, et al. Evaluation of essential oils for
maintaining postharvest quality of Thompson seedless table grape. Nat Prod
Res. 2012;26:77–83.
2. Abdul-Ghani AS, Amin R. The vascular action of aqueous extracts of
Foeniculum vulgare leaves. J Ethnopharmacol. 1988;24:213–8.
3. Agarwal R, Gupta SK, Agrawal SS, Srivastava S, Saxena R. Oculohy-
potensive effects of Foeniculum vulgare in experimental models of
glaucoma. Indian J Physiol Pharmacol. 2008;52:77–83.
4. Akha O, Rabiei K, Kashi Z, et al. The effect of fennel (Foeniculum vulgare)
gel 3% in decreasing hair thickness in idiopathic mild to moderate
hirsutism, A randomized placebo controlled clinical trial. Caspian J Intern
Med. 2014;5:26–9.
5. Albert-Puleo M. Fennel and anise as estrogenic agents. J Ethnopharmacol.
1980;2:337–44.
6. Alexandrovich I, Rakovitskaya O, Kolmo E, et al. The effect of fennel
(Foeniculum vulgare) seed oil emulsion in infantile colic: a randomized,
placebo-controlled study. Altern Ther Health Med. 2003;9:58–61.
Foeniculum vulgare Mill. 939

7. Alizadeh A, Zamani E, Sharaifi R, et al. Antifungal activity of some essential

oils against toxigenic Aspergillus species. Commun Agric Appl Biol Sci.
2010;75:761–7.
8. Aprotosoaie AC, Hăncianu M, Poiată A, et al. In vitro antimicrobial
activity and chemical composition of the essential oil of Foeniculum
vulgare Mill. Rev Med Chir Soc Med Nat Iasi. 2008;112:832–6.
9. Aridoğan BC, Baydar H, Kaya S, et al. Antimicrobial activity and chemical
composition of some essential oils. Arch Pharm Res. 2002;25:860–4.
10. Badgujar SB, Patel VV, Bandivdekar AH. Foeniculum vulgare Mill.: a
review of its botany, phytochemistry, pharmacology, contemporary appli-
cation, and toxicology. Biomed Res Int. 2014;2014:842674.
11. Bae J, Kim J, Choue R, Lim H. Fennel (Foeniculum vulgare) and
fenugreek (Trigonella foenum-graecum) tea drinking suppresses subjective
short-term appetite in overweight women. Clin Nutr Res. 2015;4:168–74.
12. Băjan M, Aprotosoaie AC, Spac A, Stănescu U. Chemical composition of
essential oil obtained from Romanian fennel fruits. Rev Med Chir Soc Med
Nat Iasi. 2011;115:590–4 (Article in Romanian).
13. Baliga MS, Jagetia GC, Rao SK, Babu K. Evaluation of nitric oxide
scavenging activity of certain spices in vitro: a preliminary study. Nahrung.
2003;47:261–4.
14. Barros L, Heleno SA, Carvalho AM, Ferreira IC. Systematic evaluation of
the antioxidant potential of different parts of Foeniculum vulgare Mill.
from Portugal. Food Chem Toxicol. 2009;47:2458–64.
15. Birdane FM, Cemek M, Birdane YO, et al. Beneficial effects of
Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in
rats. World J Gastroenterol. 2007;13:607–11.
16. Bokaie M, Farajkhoda T, Enjezab B, Khoshbin A, Karimi-Zarchi M. Oral
fennel (Foeniculum vulgare) drop effect on primary dysmenorrhea:
Effectiveness of herbal drug. Iran J Nurs Midwifery Res. 2013;18:128–32.
17. Boskabady MH, Khatami A, Nazari A. Possible mechanism(s) for relaxant
effects of Foeniculum vulgare on guinea pig tracheal chains. Pharmazie.
2004;59:561–4.
18. Cabral C, Miranda M, Gonçalves MJ, et al. Assessment of safe bioactive
doses of Foeniculum vulgare Mill. essential oil from Portugal. Nat Prod
Res. 2017;31:2654–9.
19. Camacho-Corona Mdel R, Ramírez-Cabrera MA, Santiago OG, et al.
Activity against drug resistant-tuberculosis strains of plants used in
Mexican traditional medicine to treat tuberculosis and other respiratory
diseases. Phytother Res. 2008;22:82–5.
20. Celik I, Isik I. Determination of chemopreventive role of Foeniculum vul-
gare and Salvia officinalis infusion on trichloroacetic acid-induced increased
serum marker enzymes lipid peroxidation and antioxidative defense systems
in rats. Nat Prod Res. 2008;22:66–75.
21. Choi EM, Hwang JK. Anti-inflammatory, analgesic and antioxidant
activities of the fruit of Foeniculum vulgare. Fitoterapia. 2004;75:557–65.
940 Foeniculum vulgare Mill.

22. Coşge B, Kiralan M, Gürbüz B. Characteristics of fatty acids and essential

oil from sweet fennel (Foeniculum vulgare Mill. var. dulce) and bitter
fennel fruits (F. vulgare Mill. var. vulgare) growing in Turkey. Nat Prod
Res. 2008;22:1011–6.
23. Cwikla C, Schmidt K, Matthias A, et al. Investigations into the antibacterial
activities of phytotherapeutics against Helicobacter pylori and Campy-
lobacter jejuni. Phytother Res. 2010;24:649–56.
24. Dadalioglu I, Evrendilek GA. Chemical compositions and antibacterial
effects of essential oils of Turkish oregano (Origanum minutiflorum), bay
laurel (Laurus nobilis), Spanish lavender (Lavandula stoechas L.), and
fennel (Foeniculum vulgare) on common foodborne pathogens. J Agric
Food Chem. 2004;52:8255–60.
25. De Marino S, Gala F, Borbone N, et al. Phenolic glycosides from Foenicu-
lum vulgare fruit and evaluation of antioxidative activity. Phytochemistry.
2007;68:1805–12.
26. Díaz-Maroto MC, Díaz-Maroto Hidalgo IJ, Sánchez-Palomo E, Pérez-Coello
MS. Volatile components and key odorants of fennel (Foeniculum vulgare
Mill.) and thyme (Thymus vulgaris L.) oil extracts obtained by simultaneous
distillation-extraction and supercritical fluid extraction. J Agric Food Chem.
2005;53:5385–9.
27. Díaz-Maroto MC, Pérez-Coello MS, Esteban J, Sanz J. Comparison of the
volatile composition of wild fennel samples (Foeniculum vulgare Mill.)
from central Spain. J Agric Food Chem. 2006;54:6814–8.
28. El Bardai S, Lyoussi B, Wibo M, Morel N. Pharmacological evidence of
hypotensive activity of Marrubium vulgare and Foeniculum vulgare in
spontaneously hypertensive rat. Clin Exp Hypertens. 2001;23:329–43.
29. El-Sheikh el-SA, Galal AA. Toxic effects of subchronic exposure of
male albino rats to emamectin benzoate and possible ameliorative role of
Foeniculum vulgare essential oil. Environ Toxicol Pharmacol. 2015;39:
1177–88.
30. Endalamaw FD, Chandravanshi BS. Levels of major and trace elements in
fennel (Foeniculum vulgari Mill.) fruits cultivated in Ethiopia. Spring-
erPlus. 2015;4:5.
31. Facchinetti F, Pedrielli G, Benoni G, et al. Herbal supplements in pregnancy:
unexpected results from a multicentre study. Hum Reprod. 2012;27:3161–7.
32. Faudale M, Viladomat F, Bastida J, et al. Antioxidant activity and phenolic
composition of wild, edible, and medicinal fennel from different Mediter-
ranean countries. J Agric Food Chem. 2008;56:1912–20.
33. Ghazanfarpour M, Amini E, Khadivzadeh T, et al. The effect of short-term
treatment with fennel on bone density in postmenopausal women: a
randomized controlled trial. J Menopausal Med. 2017;23:124–30.
34. Ghazanfarpour M, Mohammadzadeh F, Shokrollahi P, et al. Effect of
Foeniculum vulgare (fennel) on symptoms of depression and anxiety in
postmenopausal women: a double-blind randomised controlled trial.
J Obstet Gynaecol. 2018;38:121–6.
Foeniculum vulgare Mill. 941

35. Ghazanfarpour M, Shokrollahi P, Khadivzadeh T, et al. Effect of Foeniculum

vulgare (fennel) on vaginal atrophy in postmenopausal women: a double-
blind, randomized, placebo-controlled trial. Post Reprod Health. 2017;23:
171–6.
36. Ghodsi Z, Asltoghiri M. The effect of fennel on pain quality, symptoms, and
menstrual duration in primary dysmenorrhea. J Pediatr Adolesc Gynecol.
2014;27:283–6.
37. Gori L, Gallo E, Mascherini V, et al. Can estragole in fennel seed deco-
ctions really be considered a danger for human health? A fennel safety
update. Evid Based Complement Alternat Med. 2012;2012:860542.
38. Goswami N, Chatterjee S. Assessment of free radical scavenging potential
and oxidative DNA damage preventive activity of Trachyspermum ammi
L. (carom) and Foeniculum vulgare Mill. (fennel) seed extracts. Biomed
Res Int. 2014;2014:582767.
39. Guimarães R, Barreira JC, Barros L, et al. Effects of oral dosage form and
storage period on the antioxidant properties of four species used in
traditional herbal medicine. Phytother Res. 2011;25:484–92.
40. Jarić S, Mitrović M, Djurdjević L, et al. Phytotherapy in medieval Serbian
medicine according to the pharmacological manuscripts of the Chilandar
Medical Codex (15-16th centuries). J Ethnopharmacol. 2011;137:601–19.
41. Javidnia K, Dastgheib L, Mohammadi Samani S, Nasiri A. Antihirsutism
activity of fennel (fruits of Foeniculum vulgare) extract. A double-blind
placebo-controlled study. Phytomedicine. 2003;10:455–8.
42. Jazani NH, Zartoshti M, Babazadeh H, et al. Antibacterial effects of Iranian
fennel essential oil on isolates of Acinetobacter baumannii. Pak J Biol Sci.
2009;12:738–41.
43. Jeambey Z, Johns T, Talhouk S, Batal M. Perceived health and medicinal
properties of six species of wild edible plants in northeast Lebanon. Public
Health Nutr. 2009;12:1902–11.
44. Joshi H, Parle M. Cholinergic basis of memory-strengthening effect of
Foeniculum vulgare Linn. J Med Food. 2006;9:413–7.
45. Kaileh M, Berghe WV, Boone E, et al. Screening of indigenous Palestinian
medicinal plants for potential anti-inflammatory and cytotoxic activity.
J Ethnopharmacol. 2007;113:510–6.
46. Kaur GJ, Arora DS. Antibacterial and phytochemical screening of Anethum
graveolens, Foeniculum vulgare and Trachyspermum ammi. BMC Com-
plement Altern Med. 2009;9:30.
47. Kim TH, Kim HJ, Lee SH, Kim SY. Potent inhibitory effect of Foeniculum
vulgare Miller extract on osteoclast differentiation and ovariectomy-
induced bone loss. Int J Mol Med. 2012;29:1053–9.
48. Kunzemann J, Herrmann K: Isolation and identification of flavon(ol)-
O-glycosides in caraway (Carum carvi L.), fennel (Foeniculum vulgare
Mill.), anise (Pimpinella anisum L.), and coriander (Coriandrum sativum L.),
and of flavon-C-glycosides in anise. I. Phenolics of spices (author’s transl).
Z Lebensm Unters Forsch. 1977;164:194–200 (German).
942 Foeniculum vulgare Mill.

49. Langhammer AJ, Nilsen OG. In vitro inhibition of human CYP1A2,

CYP2D6, and CYP3A4 by six herbs commonly used in pregnancy.
Phytother Res. 2014;28:603–10.
50. Lixandru BE, Drăcea NO, Dragomirescu CC, et al. Antimicrobial activity
of plant essential oils against bacterial and fungal species involved in food
poisoning and/or food decay. Roum Arch Microbiol Immunol. 2010;69:
224–30.
51. Lo Cantore P, Iacobellis NS, De Marco A, et al. Antibacterial activity of
Coriandrum sativum L. and Foeniculum vulgare Miller var. vulgare
(Miller) essential oils. J Agric Food Chem. 2004;52:7862–6.
52. Ma HW, Zhao JT, Zhao X. The effect of fennel tea drinking on
postoperative gut recovery after gynecological malignancies operation.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2015;46:940–3 (Chinese).
53. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helico-
bacter pylori to botanical extracts used traditionally for the treatment of
gastrointestinal disorders. Phytother Res. 2005;19:988–91.
54. Malini T, Vanithakumari G, Megala N, et al. Effect of Foeniculum vulgare
Mill. seed extract on the genital organs of male and female rats. Indian J
Physiol Pharmacol. 1985;29:21–6.
55. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal
plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
56. Menez J, Castro-Poceiro J. Coumarins in Foeniculum vulgare fruits. Rev
Latinoam Quim. 1981;12:91–2.
57. Mesfin M, Asres K, Shibeshi W. Evaluation of anxiolytic activity of the
essential oil of the aerial part of Foeniculum vulgare Miller in mice. BMC
Complement Altern Med. 2014;14:310.
58. Miguel MG, Cruz C, Faleiro L, et al. Foeniculum vulgare essential oils:
chemical composition, antioxidant and antimicrobial activities. Nat Prod
Commun. 2010;5:319–28.
59. Mimica-Dukić N, Kujundzić S, Soković M, Couladis M. Essential oil
composition and antifungal activity of Foeniculum vulgare Mill. obtained
by different distillation conditions. Phytother Res. 2003;17:368–71.
60. Modaress Nejad V, Asadipour M. Comparison of the effectiveness of
fennel and mefenamic acid on pain intensity in dysmenorrhoea. East
Mediterr Health J. 2006;12:423–7.
61. Mohamad RH, El-Bastawesy AM, Abdel-Monem MG, et al. Antioxidant
and anticarcinogenic effects of methanolic extract and volatile oil of fennel
seeds (Foeniculum vulgare). J Med Food. 2011;14:986–1001.
62. Mohebbi-Kian E. Mohammad-Alizadeh-Charandabi S, Bekhradi R: Effi-
cacy of fennel and combined oral contraceptive on depot medroxyproges-
terone acetate-induced amenorrhea: a randomized placebo-controlled trial.
Contraception. 2014;90:440–6.
63. Mohsenzadeh M. Evaluation of antibacterial activity of selected Iranian
essential oils against Staphylococcus aureus and Escherichia coli in
nutrient broth medium. Pak J Biol Sci. 2007;10:3693–7.
Foeniculum vulgare Mill. 943

64. Mota AS, Martins MR, Arantes S, et al. Antimicrobial activity and
chemical composition of the essential oils of Portuguese Foeniculum
vulgare fruits. Nat Prod Commun. 2015;10:673–6.
65. Murone AJ, Stucki P, Roback MG, Gehri M. Severe methemoglobinemia
due to food intoxication in infants. Pediatr Emerg Care. 2005;21:536–8.
66. Namavar Jahromi B, Tartifizadeh A, Khabnadideh S. Comparison of fennel
and mefenamic acid for the treatment of primary dysmenorrhea. Int J
Gynaecol Obstet. 2003;80:153–7.
67. Nickavar B, Abolhasani FA. Screening of antioxidant properties of seven
Umbelliferae fruits from Iran. Pak J Pharm Sci. 2009;22:30–5.
68. Omidvar S, Esmailzadeh S, Baradaran M, Basirat Z. Effect of fennel on pain
intensity in dysmenorrhoea: a placebo-controlled trial. Ayu. 2012;33:311–3.
69. Orhan I, Kartal M, Kan Y, Sener B. Activity of essential oils and individual
components against acetyl- and butyrylcholinesterase. Z Naturforsch C.
2008;63:547–53.
70. Orhan IE, Ozcelik B, Kan Y, Kartal M. Inhibitory effects of various
essential oils and individual components against extended-spectrum beta-
lactamase (ESBL) produced by Klebsiella pneumoniae and their chemical
compositions. J Food Sci. 2011;76:M538–46.
71. Ozbek H, Uğraş S, Dülger H, et al. Hepatoprotective effect of Foeniculum
vulgare essential oil. Fitoterapia. 2003;74:317–9.
72. Pai MB, Prashant GM, Murlikrishna KS, et al. Antifungal efficacy of Punica
granatum, Acacia nilotica, Cuminum cyminum and Foeniculum vulgare on
Candida albicans: an in vitro study. Indian J Dent Res. 2010;21:334–6.
73. Papageorgiou V, Mallouchos A, Komaitis M. Investigation of the antiox-
idant behavior of air- and freeze-dried aromatic plant materials in relation
to their phenolic content and vegetative cycle. J Agric Food Chem. 2008;
56:5743–52.
74. Piccaglia R, Marotti M. Characterization of some Italian types of wild
fennel (Foeniculum vulgare Mill.). J Agric Food Chem. 2001;49:239–44.
75. Qiu J, Li H, Su H, et al. Chemical composition of fennel essential oil and its
impact on Staphylococcus aureus exotoxin production. World J Microbiol
Biotechnol. 2012;28:1399–405.
76. Raal A, Orav A, Arak E. Essential oil composition of Foeniculum vulgare
Mill. fruits from pharmacies in different countries. Nat Prod Res. 2012;26:
1173–8.
77. Rahimi R, Ardekani MR. Medicinal properties of Foeniculum vulgare
Mill. in traditional Iranian medicine and modern phytotherapy. Chin J
Integr Med. 2013;19:73–9.
78. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J
Gastroenterol. 2010;16:4504–14.
944 Foeniculum vulgare Mill.

79. Rahimikian F, Rahimi R, Golzareh P, Bekhradi R, Mehran A. Effect of

Foeniculum vulgare Mill. (fennel) on menopausal symptoms in post-
menopausal women: a randomized, triple-blind, placebo-controlled trial.
Menopause. 2017;24:1017–21.
80. Ruberto G, Baratta MT, Deans SG, Dorman HJ. Antioxidant and antimi-
crobial activity of Foeniculum vulgare and Crithmum maritimum essential
oils. Planta Med. 2000;66:687–93.
81. Sadrefozalayi S, Farokhi F. Effect of the aqueous extract of Foeniculum
vulgare (fennel) on the kidney in experimental PCOS female rats.
Avicenna J Phytomed. 2014;4:110–7.
82. Saha JC, Kasinathan S. Ecbolic properties of Indian medicinal plants. II.
Indian J Med Res. 1961;49:1094–8.
83. Satyanarayana S, Sushruta K, Sarma GS, et al. Antioxidant activity of the
aqueous extracts of spicy food additives—evaluation and comparison with
ascorbic acid in in-vitro systems. J Herb Pharmacother. 2004;4:1–10.
84. Shahat AA, Ibrahim AY, Hendawy SF, et al. Chemical composition,
antimicrobial and antioxidant activities of essential oils from organically
cultivated fennel cultivars. Molecules. 2011;16:1366–77.
85. Shalby AB, Hamza AH, Ahmed HH. New insights on the anti-inflammatory
effect of some Egyptian plants against renal dysfunction induced by
cyclosporine. Eur Rev Med Pharmacol Sci. 2012;16:455–61.
86. Singh G, Kapoor IP, Pandey SK, et al. Studies on essential oils: part 10;
antibacterial activity of volatile oils of some spices. Phytother Res. 2002;
16:680–2.
87. Skalli S, Soulaymani Bencheikh R. Epileptic seizure induced by fennel
essential oil. Epileptic Disord. 2011;13:345–7.
88. Subehan, Usia T, Iwata H, Kadota S, Tezuka Y. Mechanism-based inhibition
of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharma-
col. 2006;105:449–55.
89. Subehan, Zaidi SF, Kadota S, Tezuka Y. Inhibition on human liver
cytochrome P450 3A4 by constituents of fennel (Foeniculum vulgare): iden-
tification and characterization of a mechanism-based inactivator. J Agric
Food Chem. 55:10162–7.
90. Tognolini M, Ballabeni V, Bertoni S, et al. Protective effect of Foeniculum
vulgare essential oil and anethole in an experimental model of thrombosis.
Pharmacol Res. 2007;56:254–60.
91. Tognolini M, Barocelli E, Ballabeni V, et al. Comparative screening of
plant essential oils: phenylpropanoid moiety as basic core for antiplatelet
activity. Life Sci. 2006;78:1419–32.
92. Türkyilmaz Z, Karabulut R, Sönmez K, Can Başaklar A. A striking and
frequent cause of premature thelarche in children: Foeniculum vulgare.
J Pediatr Surg. 2008;43:2109–11.
93. Vasudevan K, Vembar S, Veeraraghavan K, Haranath PS. Influence of
intragastric perfusion of aqueous spice extracts on acid secretion in anes-
thetized albino rats. Indian J Gastroenterol. 2000;19:53–6.
Foeniculum vulgare Mill. 945

94. Wright CI, Van-Buren L, Kroner CI, Koning MM. Herbal medicines as
diuretics: a review of the scientific evidence. J Ethnopharmacol. 2007;114:
1–31 (Review).
95. Yang IJ, Lee DU, Shin HM. Anti-inflammatory and antioxidant effects of
coumarins isolated from Foeniculum vulgare in lipopolysaccharide-stimulated
macrophages and 12-O-tetradecanoylphorbol-13-acetate-stimulated mice.
Immunopharmacol Immunotoxicol. 2015;37:308–17.
96. Yaralizadeh M, Abedi P, Najar S, Namjoyan F, Saki A. Effect of Foeniculum
vulgare (fennel) vaginal cream on vaginal atrophy in postmenopausal
women: A double-blind randomized placebo-controlled trial. Maturitas.
2016;84:75–80.
97. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and cytopro-
tective effects of selected Pakistani medicinal plants in Helicobacter pylori-
infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
98. Zeng H, Chen X, Liang J. In vitro antifungal activity and mechanism of
essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species.
J Med Microbiol. 2015;64:93–103.
99. Zhang F, Li Z, Tian S, Ma L. Analysis on changes of chemical compounds
in different samples of fried Foeniculum vulgare. Zhongguo Zhong Yao Za
Zhi. 2009;34:829–32 (Article in Chinese).
100. Zhu M, Wong PY, Li RC. Effect of oral administration offennel (Foeniculum
vulgare) on ciprofloxacin absorption and disposition in the rat. J Pharm
Pharmacol. 1999;51:1391–6.
Fumaria officinalis L. (F. parviflora Lam.)
(Papaveraceae)

Abstract
It is a dainty, fern-like, annual herb, found in Persia, Nepal, and as a weed in many
other countries. Both F. officinalis and F. parviflora are known as Shahatra in India
and used interchangeably. Greeks and Romans were aware of this plant for its
diuretic and alterative properties. Dioscorides called it Kapnos and Pliny named it
Fumaria from Fumus (smoke), because the plant irritates the eyes like smoke. Ibn
al-Baitar mentioned its Greek names as Fasaniyus and Faqeez with reference to
Dioscorides. Highly esteemed by generations of herbalists, fumitory is a superb
liver tonic—as befits a plant ruled by Jupiter. A good digestive herb, highly
recommended for all hepatic ailments, from simple biliousness to chronic
malfunctioning of the liver; it cures nausea, vomiting and painful cramps and
also dispels lassitude and improves concentration. In the Ayurvedic classic texts of
Charaka and Sushruta, Fumaria parviflora is recommended for the treatment of
fevers, blood disorders, chronic skin diseases, urinary diseases and cough. Indian
fumitory (Fumaria indica) is known as Parpat in Ayurveda and traditionally used to
calm brain. In Germany, F. officinalis is approved for “colicky pain affecting the
gallbladder and biliary system, together with the gastrointestinal tract.” It contains
isoquinoline alkaloids, potassium salts, and tannins, and is a major source of
fumaric acid. Aqueous and ethanol extracts of leaves of F. parviflora exhibited
significant anti-inflammatory activity and reduced levels of TNF-a, IL-6 and IL-1.
Pretreatment of rats with aqueous-methanol extract significantly prevented
APAP-hepatotoxicity, but failed to prevent CCI4-induced liver damage. Coadmini-
stration of ethanol extract prevented lead-induced testicular toxicity in male rats. In
a double-blind, RCT, fumitory was devoid of any significant therapeutic benefit
over placebo in German patients with IBS.

Keywords



Baqlat-el-malik Conejitos Fumária Fumitory

Jordrøyk
Kshetera




parapati Pitpapra Şahtere Shahatra Yān jǐn

© Springer Nature Switzerland AG 2020 947
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_101
948 Fumaria officinalis L. (F. parviflora Lam.)

Vernaculars: Urd.: Shahatra, Shahtaraj; Hin.: Pitpapra, Shahtera; San.: Kshetera

parapati, Yavana paipata; Ben.: Ban-sulpha, Pitpapra, Shahtera, Shotara; Mar.:
Papara, Pitpapra, Shatra; Tam.: Tura, Turu; Tel.: Chata-rashi; Ara.: Baqlat-el-malik,
Baglatulmulk, Shahteraj; Chi.: 烟堇, Tsze-hwa-ti-ting, Yān jǐn; Cze.: Zemědým
lékařský; Dan.: Læge-jordrøg; Dut.: Gewone duivekervel, Gewone duivenkervel;
Eng.: Earth smoke, Fumitory; Fin.: Peltoemäkki; Fre.: Fiel de terre, Fleur de terre,
Fumeterre officinale, Herbe à la veuve, Pied de céline; Ger.: Echter erdrauch,
Erdrauch, Gewöhnlicher erdrauch, Gebräuchlicher gemeiner erdrauch; Ita.: Feccia,
Fumaria comune, Fumosterno, Fumoterra; Jap.: Karakusakeman, Murasakikeman;
Nor.: Jordrøyk; Per.: Shahtereh; Pol.: Dymnica pospolita; Por.: Erva-molarinha,
Erva-moleirinha, Fumária; Spa.: Capa de reina, Conejitos, Fumaria, Fumaria oficinal,
Fumaria palomilla, Fumaterris, Gitanillas, Hierba del conejo, Hierba de la culebra,
Herba dels innocents, Pendientitos; Swe.: Jordrök; Tur.: Şahtere.
Description: It is a dainty, fern-like annual herb, found in Persia, Nepal, and as a
weed in many other countries. It is smoky-green in color and growing in a dense tuft
some 10–50 cm high. A long thin stem, crowned in summer with clusters of white,
mauve or yellow 7–9 mm irregular, asymmetrical flowers, two lipped and spurred,
with sepals running a quarter the length of the petals; the fruit is an achene.XXVI
Available drug in Indian market consists of broken leaves, stems, capsules, flowers and
seeds. Leaves are greenish, thick and narrow, stems greyish-yellow, 2.5–5 cm long,
furrowed and rather quadrangular; capsules very small, greyish-green, tubercled,
slightly compressed and with a transverse ridge scar to the apex; seeds very small and
consist of fleshy albumen, taste bitter, acrid, astringent; odor acrid and disagreeable
(Figs. 1, 2 and 3).LXXXI
Actions and Uses: Both F. officinalis and F. parviflora are known as Shahatra in
India and used interchangeably. Greeks and Romans were aware of this plant for its
diuretic and alterative properties. Dioscorides called it Kapnos and Pliny named it
Fumaria from Fumus (smoke), because the plant irritates the eyes like smoke. Ibn
al-BaitarLXIX mentioned its Greek names as Fasaniyus and Faqeez with reference to
Dioscorides. Arabian writers, such as in Makhzan-el-Adwiya, described two varieties,
one with violet-colored flowers, and a large kind with white flowers. It is described as
diuretic and alterative, removing hepatic obstructions, aperient and purges humours,
especially atrabilis.LXIX Highly esteemed by generations of herbalists, fumitory is a
superb liver tonic—as befits a plant ruled by Jupiter. A good digestive herb, highly
recommended for all hepatic ailments, from simple biliousness to chronic malfunc-
tioning of the liver; it cures nausea, vomiting and painful cramps and also dispels
lassitude and improves concentration. The infusion is made in wine or water from
finely chopped whole herb above the ground.XXVI It is imported from Iran and used in
the folk medicine of Turkey against hepatobiliary dysfunction [8]. In Unani medicine,
it (temperament, moderate in heat and dry 2°) is considered blood-purifier, diuretic,
antipyretic, stomachic and appetizer, and mainly used for diseases deemed to be due to
blood sepsis, such as syphilis, eczema, boils, etc.LXXVII GhaniL says that it opens
Fumaria officinalis L. (F. parviflora Lam.) 949

Fig. 1 Fumaria officinalis, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://commons.
wikimedia.org/wiki/File:Illustration_Fumaria_officinalis0.jpg

obstructions of liver and spleen, strengthens functions of liver and stomach, and
excretes yellow bile through feces; dry plant is diuretic, appetizer, and is useful in
chronic fevers, jaundice, and diseases caused by black bile. Khory and KatrakLXXXI
described it as diuretic, diaphoretic, tonic, alterative, anthelmintic and aperient, and
useful in syphilis, scrofula, constipation, and dyspepsia due to torpor of the liver or
intestines; also used to purify blood in skin diseases.CV In the Ayurvedic classic texts of
Charaka and Sushruta, Fumaria parviflora is recommended for the treatment of
fevers, blood disorders, chronic skin diseases, urinary diseases and cough [8]. Indian
fumitory (Fumaria indica) is known as Parpat in Ayurveda and traditionally used to
calm brain [15]. In Germany, F. officinalis is approved for “colicky pain affecting the
gallbladder and biliary system, together with the gastrointestinal tract” [6].
Phytoconstituents: It contains isoquinoline alkaloids (fumaranine, fumarostrejdine,
protopine, allocryptopine, parfumidine, sinactine), potassium salts, and tannins, and is
a major source of fumaric acid [2, 7, 16]. Aqueous-methanol extract of F. parviflora
from India tested positive for the presence of alkaloids, saponins, tannins and anthra-
quinones [10]. Protopine and adlumidiceine were reported as the major alkaloids, and
950 Fumaria officinalis L. (F. parviflora Lam.)

Fig. 2 Fumaria officinalis, Plant, Anneli Salo, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Fumaria_officinalis_Peltoem%C3%A4kki_C_H6057.jpg

Fig. 3 Fumaria officinalis, Flowers, Isidre blanc, WikimediaCommons; ShareAlike 4.0 Interna-
tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:FUMARIA_OFFICINALIS_-_
AGUDA_-_IB-074_(Fum%C3%A0ria).JPG; https://creativecommons.org/licenses/by-sa/4.0/deed.en

parfumine, fumariline, dihydrofumariline, cryptopine, (-)-stylopine, 8-oxocoptisine,

sanguinarine, and oxysanguinarine as the minor ones in F. parviflora from Bulgaria
[12]; whereas, Válka et al. [17], isolated (-)-stylopine, (-)-canadine, coptisine, berberine,
Fumaria officinalis L. (F. parviflora Lam.) 951

protopine, cryptopine, chelidonine, papaverine, bulbocapnine, and parfumine. From

aerial parts of F. parviflora, (5aH,11aH)-8-oxo-homoiridolide, n-docosanyl-2-O-b-
D-glucopyranosyl salicylate, 2-methyl-6-hydroxymethylenedodecan-10-oyl-12,15-
olide14-O-b-D-xylopyrano-side, 4-oxo-stigmast-5-en-3b-ol-D-glucopyranoside, sali-
cylic acid-O-b-D-xylopyranoside, a-D-gluco-pyranosyl hexadecanoate and a-D-glu-
copyranosyl-(2!1′)-a-D-glucopyranoside have also been isolated [8].
Pharmacology: Methanol extract did not show any significant antioxidant and
antimicrobial activity [14]. Isolated alkaloids were also devoid of any notable
antibacterial effect, but had significant antifungal activity against C. albicans,
selective inhibition of PI-3 virus and completely inactive against HSV [11], and
trematodes [4].
Aqueous and ethanol extracts of leaves of F. parviflora exhibited significant
anti-inflammatory activity and reduced levels of TNF-a, IL-6 and IL-1 [13]. Pre-
treatment of rats with aqueous-methanol extract significantly prevented APAP-
hepatotoxicity, but failed to prevent CCI4-induced liver damage [5]. Coadministration
of ethanol extract prevented lead-induced testicular toxicity in male rats [3]. A novel
compound, n-octacosan-7b-ol, isolated from methanol extract of whole plant of
F. parviflora, exhibited significant activity against L. donovani promastigotes,
S. epidermidis, E. coli, C. albicans and A. niger [9].
Clinical Studies: In a double-blind RCT, fumitory was devoid of any significant
therapeutic benefit over placebo in German patients with IBS [1].
Human A/Es, Allergy and Toxicity: KabeeruddinLXXVII described it harmful for
lungs, while GhaniL said it weakens the heart.
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interactions: Both protopine and allocryp-
topine dose-dependently increase CYP1A1 and CYP1A2 mRNA levels in human
hepatocytes, and significantly increase CYP1A1 mRNA levels in human hepatoma
HepG2 cells, without any elevated CYP1A protein or activity levels [18].
Commentary: Fumitory is mostly used and recommended as a blood purifier in
skin diseases and for the treatment of all hepatobiliary dysfunctions. However, there
are no RCTs reported for these uses. The negative results of RCT in German
patients with IBS would be expected, as there is no documented recommendation
for this condition in indigenous traditional medicines.

References
1. Brinkhaus B, Hentschel C, Von Keudell C, et al. Herbal medicine with
curcuma and fumitory in the treatment of irritable bowel syndrome: a ran-
domized, placebo-controlled, double-blind clinical trial. Scand J Gastroen-
terol. 2005;40:936–43.
952 Fumaria officinalis L. (F. parviflora Lam.)

2. Chlebek J, Novák Z, Kassemová D et al. Isoquinoline alkaloids from

Fumaria officinalis L. and their biological activities related to Alzheimer’s
disease. Chem Biodivers. 2016;13:91–9.
3. Dorostghoal M, Seyyednejad SM, Jabari A. Protective effects of Fumaria
parviflora L. on lead-induced testicular toxicity in male rats. Andrologia.
2014;46:437–46.
4. Ferreira JF, Peaden P, Keiser J. In vitro trematocidal effects of crude alcoholic
extracts of Artemisia annua, A. absinthium, Asimina triloba, and Fumaria
officinalis: trematocidal plant alcoholic extracts. Parasitol Res. 2011;109:
1585–92.
5. Gilani AH, Janbaz KH, Akhtar MS. Selective protective effect of an extract
from Fumaria parviflora on paracetamol-induced hepatotoxicity. Gen
Pharmacol. 1996;27:979–83.
6. Hentschel C, Dressler S, Hahn EG. Fumaria officinalis (fumitory)—clinical
applications. Fortschr Med. 1995;113:291–2 (Review, German).
7. Hermansson J, Sandberg F. Alkaloids of Fumaria officinalis. Acta Pharma-
ceut Suecica. 1973;10:520–2.
8. Jameel M, Ali A, Ali M. New phytoconstituents from the aerial parts of
Fumaria parviflora Lam. J Adv Pharm Technol Res. 2014;5:64–9.
9. Jameel M, Islamuddin M, Ali A, Afrin F, Ali M. Isolation, characterization
and antimicrobial evaluation of a novel compound N-octacosan 7b ol, from
Fumaria parviflora Lam. BMC Complement Altern Med. 2014;14:98.
10. Najeeb-ur-Rehman, Mehmood MH, Al-Rehaily AJ, Mothana RA, Gilani AH.
Species and tissue-specificity of prokinetic, laxative and spasmodic effects of
Fumaria parviflora. BMC Complement Altern Med. 2012;12:16.
11. Orhana I, Ozçelik B, Karaoğlu T, Sener B. Antiviral and antimicrobial
profiles of selected isoquinoline alkaloids from Fumaria and Corydalis
species. Z Naturforsch. 2007;62:19–26.
12. Popova ME, Simánek V, Dolejs L, Smysl B, Preininger V. Alkaloids from
Fumaria parviflora and F. kralikii. Planta Med. 1982;45:120–2.
13. Rizvi W, Fayazuddin M, Singh O, et al. Anti-inflammatory effect of
Fumaria parviflora leaves based on TNF-a, IL-1, IL-6 and antioxidant
potential. Avicenna J Phytomed. 2017;7:37–45.
14. Sengul M, Yildiz H, Gungor N, et al. Total phenolic content, antioxidant
and antimicrobial activities of some medicinal plants. Pak J Pharm Sci.
2009;22:102–6.
15. Singh GK, Rai G, Chatterjee SS, Kumar V. Effects of ethanolic extract of
Fumaria indica L. on rat cognitive dysfunctions. Ayu. 2013;34:421–9.
16. Sturm S, Strasser EM, Stuppner H. Quantification of Fumaria officinalis
isoquinoline alkaloids by nonaqueous capillary electrophoresis-electrospray
ion trap mass spectrometry. J Chromatogr A. 2006;1112:331–8.
Fumaria officinalis L. (F. parviflora Lam.) 953

17. Válka I, Walterová D, Popova ME, Preininger V, Simánek V. Separation

and quantification of some alkaloids from Fumaria parviflora by capillary
isotachophoresis1. Planta Med. 1985;51:319–22.
18. Vrba J, Vrublova E, Modriansky M, Ulrichova J. Protopine and allocryptopine
increase mRNA levels of cytochromes P450 1A in human hepatocytes and
HepG2 cells independently of AhR. Toxicol Lett. 2011;203:135–41.
Gentiana lutea L.
(Gentianaceae)

Abstract
It is a perennial plant that grows naturally in the central and southern areas of
Europe. Dioscorides described two types: one called Roman that grows in damp,
cold and snowy mountains; the second type also grows in damp places, but
its roots are less bitter and weaker in properties than the first one. Gentian is
anthelmintic, antiseptic, emmenagogue, febrifuge, stimulant, stomachic, and
tonic, and is used to stimulate gastric secretion, improve appetite and digestion
and alleviate debility; also, for blood disorders, cancer, cold, convulsions, diar-
rhea, dog-bite, dysmenorrhea, dyspepsia, gastritis, gout, jaundice, malaria, olig-
uria, snakebite, splenitis, stomachache, syncope and wounds. In the central and
southern Europe, gentian extract is used in nonalcoholic beverages, frozen dairy
desserts, candy, baked goods, gelatins and puddings; and in some antismok-
ing compounds and cosmetics. In Montenegro, leaves are traditionally utilized
as hepatoprotective, hypoglycemic and anti-inflammatory agents. G. lutea is
approved for GI disorders use in Europe since Sep. 2007 by the HMPC of the
European Medicines Agency. The roots contain glucosides: gentiopicrine;
also, gentiamarine, amarogentine, the glycoside gentiin; the tannin like principle
gentiamarin, gentisin, gentisic acid and the trisaccharide gentianose, triter-
pinoids, iridoids, secoiridoids, xanthones, xanthone glycosides, and MAO-B inhi-
bitors. Amarogentin is one of the most bitter natural compounds and is used to
measure comparative bitterness. In a crossover randomized study, a microencap-
sulated bitter ingredient of the root extract consumed by twenty healthy subjects
at breakfast on two different occasions, significantly reduced energy intake over
the postlunch period, and showed a trend for a higher response of glucagon-like
peptide-1, but no significant difference from placebo on appetite. Administration
of gentian flavored water to healthy individuals increased peripheral vascular
resistance and decreased cardiac output, primarily by reducing stroke volume.

© Springer Nature Switzerland AG 2020 955

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_102
956 Gentiana lutea L.

Keywords




Argençana Bitter root Bitterwurz Chansana Gullgentiana

Juntiana




Kaff-ul-darnab LongDan Pakhânbhêd Sarı afat

Vernaculars: Urd.: Juntiana; Hin.: Pakhânbhêd; Ara.: Dawa-ul-haaiya, Juntiana

rumi, Kaff-ul-Darnab, Kaff-ul-dayyab; Chi.: LongDan or Dancao; Cze.: Hořec žlutý;
Dan.: Gul ensian; Dut.: Gele gentiaan; Eng.: Bitter root, Great yellow gentian; Fin.:
Keltakatkero; Fre.: Gentiane jaune, Grande gentian, Jansonna, Quinquina indigène;
Ger.: Bitterwurz, Gelber enzian; Gre.: Shambali; Hun.: Sárga tárnics; Ita.: Genziana
gialla, Genziana maggiore; Per.: Gintiyana, Kaushad, Koshaad; Pol.: Goryczka żółta;
Por.: Argençana, Argençana-dos-pastores, Genciana-amarela, Genciana-das-boticas,
Genciana-das-farmácias; Rom.: Saliqaan; Rus.: Gorečavka želtaja; Spa.: Chansana,
Chonzana, Genciana amarilla, Junciana; Swe.: Gullgentiana; Syr.: Feesa nardeen;
Tur.: Sarı afat.
Description: It is a perennial 1–2 m tall plant that grows naturally in the central
and southern areas of Europe. Ibn-BaitarLXIX quotes Ishaq-bin-Imran and Diosco-
rides in describing its two types: one called Roman that grows in damp, cold and
snowy mountains; the second type also grows in damp places, but its roots are less
bitter and weaker in properties than the first one. These are knotty fibrous roots; the
taste is sweeter initially which turns bitter afterward.1 Leaves are widely sepa-
rated, resemble walnut leaves but reddish (leaves in the photograph do not appear
reddish); broad lanceolate to elliptic 10–30 cm long and 4–12 cm broad. Stem is
hollow, smooth, knotty and about one m tall; flowers are yellow and the roots are
darker and bitter. Dymock et al.XL have described Saxifraga lingulata, Wall. as
Pakhânbhêd (Figs. 1 and 2).
Actions and Uses: Gentian is anthelmintic, antiseptic, emmenagogue, febrifuge,
stimulant, stomachic, and tonic, and is used to stimulate gastric secretion, improve
appetite and digestion and alleviate debility; also, for blood disorders, cancer, cold,
convulsions, diarrhea, dog-bite, dysmenorrhea, dyspepsia, gastritis, gout, jaundice,
malaria, oliguria, snakebite, splenitis, stomachache, syncope and wounds.XXXVIII,LV,
LXXXVII
Ibn-BaitarLXIX quoted Galen that it opens obstructions. Unani physicians
regard it (temperament, hot 3° and dry 3°) stomachic, digestive, carminative, appetizer,
tonic and stimulatory of nerves1 and use it as antidote to snake and scorpion poisons
and as a component of a special antidote to poisons. As powder, it is used for weakness
of the stomach and bladder, as a diuretic, emmenagogue, abortifacient and for stom-
achache.LXXVII Khory and KatrakLXXXI described it a simple bitter without astrin-
gency or aroma, and valuable as stomachic tonic, used to improve appetite and
strengthen digestion, gout, hysteria, and jaundice. Herpes is alleviated by application
of gentian violet flowers. Gentiopicrine, a glucoside present in the root, was used as an
antimalarial.XXIV,XXXXI In the central and southern Europe, gentian extract is used in
nonalcoholic beverages, frozen dairy desserts, candy, baked goods, gelatins and

1
Tayyab M: Personal Communication.
Gentiana lutea L. 957

Fig. 1 Gentiana lutea, Plant, Javier Martin, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Gentiana_lutea_fr.jpg

puddings; and in some antismoking compounds and cosmetics [2].LXXXVII In Mon-

tenegro, leaves are traditionally utilized as hepatoprotective, hypoglycemic and
anti-inflammatory agents [5]. In China, the root and rhizomes derived from G. man-
shurica, G. scabra and other species of Gentiana are known as LongDan, Dancao or
Lung-Tan and described as a general drug.LXVI The herb has a bitter taste and cold
property, and clears up pathogenic “damp-heat” from the liver and gall bladder, and is
stomachic. It is used in the treatment of jaundice, pain in the hypochondrium, hepatitis,
cholecystitis, anorexia, acute conjunctivitis, otitis media, UTIs, herpes zoster, acute
eczema, pruritus vulvae,XVIII chills, fever, agitated epilepsy, intercostal neuralgia, sore
throat, bitter taste in the mouth and swelling carbuncles.LXVI It is also used in tradi-
tional Serbian medicine for its beneficial gastrointestinal and anti-inflammatory
properties [12]. G. lutea is approved for GI disorders use in Europe since Sep. 2007 by
the HMPC of the European Medicines Agency.
Phytoconstituents: Phytoconstituents of the roots include glucosides: 2% gen-
tiopicrine; also, gentiamarine, amarogentine,CXXIV the glycoside gentiin; the tannin
like principle gentiamarin, gentisin (gentianin or gentianic acid), gentisic acid
and the trisaccharide gentianose,XXIV triterpinoids [11, 29], iridoids (loganic acid),
secoiridoids (swertiamarin, gentiopicroside, sweroside, amarogentin), xanthones
958 Gentiana lutea L.

Fig. 2 Gentiana lutea, Flower, Heinz Staudacher, WikimediaCommons; ShareAlike 4.0 Inter-
national CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Gelber_Enzian_(Gentiana_
lutea),_Bl%C3%BCtenstand.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

(gentisin, isogentisin), xanthone glycosides (gentiosides) [1, 9], and MAO-B inhi-
bitors [10]. Amarogentin is one of the most bitter natural compounds and is used to
measure comparative bitterness. It is free from aromatic oils or tannins, and hence
without astringency.LXXIX Methanol extracts of the leaves and flowers show xan-
thones as one of the dominant class of compounds, in addition to secoiridoids and
flavonoids [19]. Secondary metabolites vary depending on different developmental
stages; before flowering, compounds with O-glycoside structures accumulate, and
during flowering, leaves are rich with compounds possessing C-glycoside structures
[19]. Secoiridoids, C-glucoflavones, xanthones, swertiamarin derivatives (eusto-
moside, eustomorusside and septemfidoside), gentiopicrin, mangiferin, isogentisin,
and isovitexin, were isolated from leaves collected from northern regions of Mon-
tenegro [5]. Gentiopicrin, mangiferin and isogentisin exerted strong cytotoxicity
against HeLa cells [5]. Seeds from Italy were reported to contain sweroside,
getiopicroside, loganic acid and trifloroside as main glycosidic components [6].
Pharamacology: Methanol root extract was moderately active against 15 strains
of H. pylori with an MIC of 100 mcg/ml [17]. Methanol extracts of flowers and
leaves and the isolated compounds, mangiferin, isogentisin and gentiopicrin,
showed significant antimicrobial activity against a variety of Gram-positive and
Gram-negative bacteria and the yeast C. albicans [27]. Methanol extracts of leaves
Gentiana lutea L. 959

and root exhibit significant antioxidant activity [14]; ethyl acetate and chloroform
fractions also show hydroxyl scavenging activity [7]. However, among methanol
(100%), water and ethanol aqueous extracts, the 50% ethanol aqueous extract
showed the highest antioxidant capacity; it was also the best inhibitor of myelo-
peroxidase activity [22]. Ethanol root extract increased in vitro and in vivo lipid
synthesis in isolated human keratinocytes and in forearms of volunteers [31].
Methanol extract significantly increased swimming endurance of mice and exhib-
ited slight analgesic activity [24]. Gentiopicroside, one of the secoiridoids, exhibits
analgesic activity and inhibits expression of GluN2B-containing NMDA receptors
in the anterior cingulate cortex in mice [16].
Ether and methanol root extracts show greater inhibitory activities against both rat
lens and human aldose reductase, whereas the water and ethanol extracts showed
moderate inhibitory activities; also, significantly inhibited sorbitol accumulation
in human erythrocytes under high glucose conditions, indicating possible beneficial
effects in diabetes mellitus [2]. G. lutea extract protected human vascular endothelial
cells from cigarette smoke-induced damage. Addition of isogentisin, one of the
constituents, to the endothelial cells as long as 4.5 h after exposure to cigarette smoke
chemicals protected cells from death, by activating cellular repair functions [28].
Aqueous root extract, containing bellidifolin-8-O-glucoside, demethylbellidifolin-
8-O-glucoside, gentisin, gentiopicroside, isovitexin, swertiamarin and amarogentin
prevented platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of
aortic smooth muscle cells [12]. Aqueous root extract, root powder and isovitexin
exhibited antiatherosclerotic activity [13]. Gentisin has been identified as the inhi-
bitor of proliferation of vascular smooth muscle cells, that could be utilized to prevent
restenosis [30]. The extract also protected against ketoconazole-induced testicular
damage due to its antioxidant properties [3]. Multiple intraduodenally administered
doses of lyophilized ethanol extract to rats normalized CCl4-induced decrease in bile
flow; whereas single dose therapy was ineffective [26]. Amarogentin possesses
antitumor, antidiabetic, antioxidative properties, and inhibits platelet aggregation
induced by collagen, but not thrombin, AA-, and U46619-induced, probably through
inhibition of PLC c2-PKC cascade and MAPK pathway [32]. Aerial parts extract is
also reported to increase blood coagulation [4]. Oral administration of aqueous-
ethanol extract reduced cytotoxic effect of X-ray irradiation on normal human
immunocompetent peripheral blood mononuclear cells (PBMC) of some healthy
human volunteers, without altering susceptibility of malignant cells to irradiation.
Mangiferin inhibited in vitro cytotoxic action of ionizing irradiation only on normal
resting human PBMC, not on stimulated for proliferation [20].
Clinical Studies: In a crossover randomized study, a microencapsulated bitter
ingredient of the root extract consumed by twenty healthy subjects at breakfast on two
different occasions, significantly (30%) reduced energy intake over the postlunch
period, and showed a trend for a higher response of glucagon-like peptide-1, but no
significant difference from placebo on appetite [21]. Administration of gentian
960 Gentiana lutea L.

flavored water to healthy individuals increased peripheral vascular resistance and

decreased cardiac output, primarily by reducing stroke volume rather than heart
rate [18].
Mechanism of Action: The alleged value in improving digestion and appetite is
partly ascribed to the bitter tonic (amarum) effect, i.e., the stimulation of gastric
juices via the vagus nerve [23]. Analgesic effect of gentiopicroside to persistent
inflammatory pain involves downregulation of glutamate NMDA NR2B receptors
in the anterior cingulate cortex [8], and reserpine-induced pain/depression dyad by
downregulating GluN2B receptors in the amygdala [15]. Gentiopicroside inhibited
morphine dependence through downregulation of GluN2B-containing NMDA
receptors in the nucleus accumbens [16]. Wound healing activity of Gentian
(ssp. Symphyandra) is mainly due to increase in stimulation of collagen production,
and mitotic activity by sweroside and swertiamarine, respectively [25].
Human A/Es, Allergy and Toxicity: The drug may not be tolerated well by those
having very high BP or by expectant mothers.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This drug is mainly used in traditional medicines as a stomachic tonic
to improve appetite and strengthen digestion. One crossover study in healthy volun-
teers did not show any significant increase in appetite by the root extract. These clinical
studies would serve a better purpose if conducted in patients with digestive problems,
mimicking the actual usage conditions, because effects of a drug usually differ in health
and disease states. Other studies have mainly been conducted on its constituents.

References
1. Aberham A, Schwaiger S, Stuppner H, Ganzera M. Quantitative analysis of
iridoids, secoiridoids, xanthones and xanthone glycosides in Gentiana lutea
L. roots by RP-HPLC and LC-MS. J Pharm Biomed Anal. 2007;45:437–42.
2. Akileshwari C, Muthenna P, Nastasijević B, et al. Inhibition of aldose
reductase by Gentiana lutea extracts. Exp Diabetes Res. 2012;2012:147965.
3. Amin A. Ketoconazole-induced testicular damage in rats reduced by
Gentiana extract. Exp Toxicol Pathol. 2008;59:377–84.
4. Bakuridze AD, Nikolaev SM, Tsagarenshvili NT, et al. Influence of Gentiana
lutea L. extract on blood coagulation. Georgian Med News. 2009;172–173:
89–91 (Article in Russian).
5. Balijagić J, Janković T, Zdunić G, et al. Chemical profile, radical scavenging
and cytotoxic activity of yellow gentian leaves (Genitaneae luteaefolium)
grown in northern regions of Montenegro. Nat Prod Commun. 2012;7:
1487–90.
6. Bianco A, Ramunno A, Melchioni C. Iridoids from seeds of Gentiana lutea.
Nat Prod Res. 2003;17:221–4.
Gentiana lutea L. 961

7. Calliste CA, Trouillas P, Allais DP, et al. Free radical scavenging activities
measured by electron spin resonance spectroscopy and B16 cell antipro-
liferative behaviors of seven plants. J Agric Food Chem. 2001;49:3321–7.
8. Chen L, Liu JC, Zhang XN, et al. Downregulation of NR2B receptors
partially contributes to analgesic effects of Gentiopicroside in persistent
inflammatory pain. Neuropharmacology. 2008;54:1175–81.
9. Citová I, Ganzera M, Stuppner H, Solich P. Determination of gentisin,
isogentisin, and amarogentin in Gentiana lutea L. by capillary electrophore-
sis. J Sep Sci. 2008;31:195–200.
10. Haraguchi H, Tanaka Y, Kabbash A, et al. Monoamine oxidase inhibitors
from Gentiana lutea. Phytochemistry. 2004;65:2255–60.
11. Kakuda R, Machida K, Yaoita Y, et al. Studies on the constituents of Gentiana
species. II. A new triterpenoid, and (S)-(+)- and (R)-(−)-gentiolactones from
Gentiana lutea. Chem Pharm Bull (Tokyo). 2003;51:885–7.
12. Kesavan R, Potunuru UR, Nastasijević B, et al. Inhibition of vascular
smooth muscle cell proliferation by Gentiana lutea root extracts. PLoS One.
2013;8:e61393.
13. Kesavan R, Chandel S, Upadhyay S, et al. Gentiana lutea exerts anti-
atherosclerotic effects by preventing endothelial inflammation and smooth
muscle cell migration. Nutr Metab Cardiovasc Dis. 2016;26:293–301.
14. Kusar A, Zupancic A, Sentjurc M, Baricevic D. Free radical scavenging
activities of yellow gentian (Gentiana lutea L.) measured by electron spin
resonance. Hum Exp Toxicol. 2006;25:599–604.
15. Liu SB, Zhao R, Li XS, et al. Attenuation of reserpine-induced pain/depression
dyad by gentiopicroside through downregulation of GluN2B receptors in the
amygdala of mice. Neuromolecular Med. 2014;16:350–9.
16. Liu SB, Ma L, Guo HJ, et al. Gentiopicroside attenuates morphine rewarding
effect through downregulation of GluN2B receptors in nucleus accumbens.
CNS Neurosci Ther. 2012;18:652–8.
17. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of
Helicobacter pylori to botanical extracts used traditionally for the treatment
of gastrointestinal disorders. Phytother Res. 2005;19:988–91.
18. McMullen MK, Whitehouse JM, Whitton PA, Towell A. Bitter tastants alter
gastric-phase postprandial haemodynamics. J Ethnopharmacol. 2014;154:
719–27.
19. Menković N, Savikin-Fodulović K, Savin K. Chemical composition and
seasonal variations in the amount of secondary compounds in Gentiana
lutea leaves and flowers. Planta Med. 2000;66:178–80.
20. Menkovic N, Juranic Z, Stanojkovic T, et al. Radioprotective activity
of Gentiana lutea extract and mangiferin. Phytother Res. 2010;24:1693–6.
21. Mennella I, Fogliano V, Ferracane R, et al. Microencapsulated bitter com-
pounds (from Gentiana lutea) reduce daily energy intakes in humans. Br J
Nutr. 2016;1–10.
962 Gentiana lutea L.

22. Nastasijević B, Lazarević-Pašti T, Dimitrijević-Branković S, et al. Inhibition

of myeloperoxidase and antioxidative activity of Gentiana lutea extracts.
J Pharm Biomed Anal. 2012;66:191–6.
23. Olivier DK, van Wyk BE. Bitterness values for traditional tonic plants of
southern Africa. J Ethnopharmacol. 2013;147:676–9.
24. Oztürk N, Başer KH, Aydin S, et al. Effects of Gentiana lutea ssp. sym-
phyandra on the central nervous system in mice. Phytother Res. 2002;16:
627–31.
25. Oztürk N, Korkmaz S, Oztürk Y, Başer KH. Effects of gentiopicroside,
sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea
ssp. symphyandra), on cultured chicken embryonic fibroblasts. Planta Med.
2006;72:289–94.
26. Oztürk N, Herekman-Demir T, Oztürk Y, et al. Choleretic activity of
Gentiana lutea ssp. symphyandra in rats. Phytomedicine. 1998;5:283–8.
27. Savikin K, Menković N, Zdunić G et al. Antimicrobial activity of Gentiana
lutea L. extracts. Z Naturforsch C. 2009;64:339–42.
28. Schmieder A, Schwaiger S, Csordas A, et al. Isogentisin—a novel compound
for the prevention of smoking-caused endothelial injury. Atherosclerosis.
2007;194:317–25.
29. Toriumi Y, Kakuda R, Kikuchi M, et al. New triterpenoids from Gentiana
lutea. Chem Pharm Bull (Tokyo). 2003;51:89–91.
30. Waltenberger B, Liu R, Atanasov AG, et al. Nonprenylated xanthones
from Gentiana lutea, Frasera caroliniensis, and Centaurium erythraea as
novel inhibitors of vascular smooth muscle cell proliferation. Molecules.
2015;20:20381–90.
31. Wölfle U, Haarhaus B, Seiwerth J, et al. The herbal bitter drug Gentiana
lutea modulates lipid synthesis in human keratinocytes in vitro and in vivo.
Int J Mol Sci. 2017;18, pii: E1814.
32. Yen TL, Lu WJ, Lien LM, et al. Amarogentin, a secoiridoid glycoside,
abrogates platelet activation through PLC c 2-PKC and MAPK pathways.
Biomed Res Int. 2014;2014:728019.
Glycyrrhiza glabra L.
(Fabaceae/Leguminosae)

(Syns.: G. glandulifera Waldst. & Kit.; G. hirsuta Pall.; G. pallida Boiss. & Noe;
G. violacea Boiss. & Noe)

Abstract
Liquorice is a perennial, temperate-zone herb or subshrub, native of India,
Pakistan and southern Europe; also cultivated in England, Belgium, France,
Germany, Spain, Italy, Greece, Turkey, Russia, South Africa, Egypt, Syria
and Iraq. It has also been grown experimentally in the United States. Ancient
historical manuscripts from China, India and Greece mention its use for
symptoms of viral respiratory tract infections and hepatitis. The plant has also
been described by Theophrastus. Licorice from Egypt has been described to be
the best, followed by from Iraq and Syria; the root should be decorticated before
use. It concocts viscid humours in diseases of liver, bladder and lungs, and
expectorates them. It has been used in Iranian herbal medicine for skin eruptions,
including dermatitis, eczema, pruritus and cysts, and for treatment of stomach
disorders including peptic ulcers. The herb extract inhibits gastric motility in vivo,
which is regarded to be an important aspect for its antiulcer activity. Licorice
possesses both anti-inflammatory and antiulcer activities; whereas most anti-
inflammatory agents are ulcerogenic. Former German Commission E believed it
to be effective in the treatment of atopic dermatitis. Licorice root has been used
for years to regulate gastrointestinal function in TCM, has been used for
generations as an antidote, demulcent, and elixir in folk medicine of China, and is
the most commonly used crude drug in Kampo Medicines, the Japanese form of
modified TCM, for the treatment of peptic ulcer. Roots contain glycyrrhizin, the
main water-soluble constituent that is 50 sweeter than sugar, 2-b-glucuronosyl
glucuronic acid, and isoliquiritigenin-4-glucoside. Glycyrrhizin is a nonhemolytic
saponin with foaming property, and one of the most potent hydroxyl radical
scavengers. No significant effect of deglycyrrhizinised liquorice was observed on
gastric ulcer in an RCT of British patients. Treatment of healthy men with licorice
for one-week decreased salivary testosterone values by 26% but no significant
decrease in free testosterone, and nine healthy women treated with licorice daily

© Springer Nature Switzerland AG 2020 963

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_103
964 Glycyrrhiza glabra L.

for two cycles, had their mean total serum testosterone decreased by 37% at the
end of 2nd month. This property could be useful as an adjunct therapy of
hirsutism and PCOS.

Keywords






Alcarzuz Aslussoos Gancao Liquorice Meyan kökü Muletthi Regaliz





Soos Süßholz Yashtimadhu

Vernaculars: Urd.: Aslussoos; Hin.: Jethi-madh, Muletthi, Mithi-lakri; San.: Mad-

huka, Yashtimadhu; Ben.: Jaishto-modhu; Mal.: Irattimadhuram; Mar.: Jeshti-madh;
Tam.: Adhimadhuram, Athimathuram, Athimathurappal (extract), Atimad-uram
(root); Tel.: Athimathuram, Yashti-madhukam; Ara.: Oudussoos (root), Irk-es-sus,
Rubbus-soos (extract), Soos; Chi.: Gām chóu, Gancao, Yáng gān cǎo; Dut.: Zoethout;
Eng.: Licorice, Liquorice, Sweetwood; Fre.: Bois doux, Réglisse, Réglisse glabre;
Ger.: Gewöhnliches süßholz, Kahles süßholz, Lakritze, Lakritzpflanze, Süßholz;
Gre.: Glikoriza, Glykoriza; Ita.: Legno dolce, Liquirizia, Liquirizia comune, Regolizia;
Jap.: Gurukiruriza gurabura; Kor.: Mingamtscho; Per.: Ausareha mahaka, Beekh-
e-mehak; Por.: Alcaçuz, Pau-cachucho, Raiz-doce, Regaliz; Rus.: Koren solodki; Sin.:
Atimaduram; Spa.: Agarradera, Alcarzuz, Alfendol, Chocolate del moro, Erregaliz,
Fendoces, Palo dulce, Palo-luz, Regaliz; Tha.: Cha em thet; Tur.: Meyan kökü; Vie.:
Cam thảo.
Description: Liquorice is a perennial, temperate-zone herb or subshrub, native of
India, Pakistan and southern Europe; also cultivated in England, Belgium, France,
Germany, Spain, Italy, Greece, Turkey, Russia, South Africa, Egypt, Syria and Iraq.
It has also been grown experimentally in the United States [6]. It grows up to 2 m
high, with a long, cylindrical, branched, flexible, burrowing rootstock and hori-
zontal, creeping, underground stems (stolons) of up to 1.8 m long, having buds
which send up stems in the 2nd year.LV Leaves are alternate, pinnate, yellow-green
leaflets, viscid on the underside. G. glabra var. typica is the most commonly used
variety of glycyrrhiza. Its rootstalk and stolons are 6 to 18 mm thick, longitudinally
wrinkled and sweeter than other types. It is one of the pharmaceutically important
plants of India that is designated as on the verge of being endangered due to
overexploitation and collection from the wild [115] (Figs. 1, 2 and 3).
Actions and Uses: Ancient historical manuscripts from China, India and Greece
mention its use for symptoms of viral respiratory tract infections and hepatitis [48].
The plant has also been described by Theophrastus.XXI Author of Makhzan-el-
Adwiya described licorice from Egypt to be the best, followed by from Iraq and
Syria, and directs the root to be decorticated before use. The root is considered hot,
dry and suppurative, demulcent and lenitive, relieving thirst and cough, and
removing unhealthy humours from the body. It is also emmenagogue and diuretic,
useful in asthma and irritable conditions of the bronchial passages. Avicenna rec-
ommended decoction in chronic fevers, tracheal pain, cold colic, and to clear voice;
also dropped into eyes to strengthen sight.XL,LXIX,LXXVII Ibn Jazlah used it in
Glycyrrhiza glabra L. 965

Fig. 1 Glycyrrhiza glabra, Inflorescence, Pharaoh han, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Glycyrrhiza_glabra_infloresc
ence.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Glycyrrhiza glabra, Roots from India, Prof. Akbar, Original

leprosy, spleen ailments and scorpion sting, and in the Middle East it is used to
relieve acute indigestion.LIII It concocts viscid humours in diseases of liver, bladder
and lungs, and expectorates them.CV It has been used in Iranian herbal medicine for
966 Glycyrrhiza glabra L.

Fig. 3 Glycyrrhiza glabra, Roots from South Africa, Prof. Akbar, Original

skin diseases, including dermatitis, eczema, pruritus and cysts [95], and for treatment
of stomach disorders including peptic ulcers [58]. The herb extract inhibits gastric
motility in vivo, which is regarded to be an important aspect for its antiulcer activity.
GaborXLVIII reported paradoxical profile of licorice as possessing both anti-
inflammatory and antiulcer activities; whereas most anti-inflammatory agents are
ulcerogenic. It is a common ingredient of cough syrups, throat lozenges and pastilles
for its flavor as well as its demulcent, mildly expectorant, and anti-inflammatory
effects,XXI and is also used in irritable conditions of mucous membranes of urinary
organs, gastric ulcers, Addison’s disease and inflammatory conditions [6]. Former
German Commission E believed it to be effective in the treatment of atopic
dermatitis [92]. Decoctions of peeled dried root were formerly used to allay coughs,
catarrh, bronchitis, sore throat, laryngitis, urinary irritation and pain associated with
diarrhea. Liquorice provides two derivatives which reduce or cure gastric ulcers [37].
Licorice root has been used for years to regulate gastrointestinal function in TCM
[28], has been used for generations as an antidote, demulcent, and elixir in folk
medicine of China [2], and is the most commonly used crude drug in Kampo
Medicines, the Japanese form of modified TCM, for the treatment of peptic ulcer
[46]. In old Chinese pharmacy the drug was regarded rejuvenating for those who
consumed it for long periods. In Chinese medicine, it is known as Gancao and is also
derived from G. uralensis Fisch., and described to regulate functions of the stomach,
is “Qi” (vital energy)-tonifying, lung demulcent, expectorant, latent heat-clearing,
antipyretic, detoxicant, anti-inflammatory, “spleen-invigorative,” and is a corrective
adjuvant and harmonizing ingredient in many preparations. It is thus used in
pharyngolaryngitis, cough, palpitation, stomachache due to asthenia, peptic ulcer,
pyogenic infection and ulceration of the skin.XVIII Hsu described its uses in Chinese
medicine for toxic states, excessive sputum, muscular pain due to tension, peptic
ulcer, duodenal ulcer, and sore throat.LXVI Glycyrrhizin (GR) has been used for the
treatment of chronic liver diseases in Japan, with distinct improvement in liver
Glycyrrhiza glabra L. 967

function tests [45]. Glabridin is commonly used in China for the treatment of CVS
and CNS diseases [23]. Stronger Neo-Minophagen C® is a glycyrrhizin-containing
preparation approved in Japan for the treatment of chronic hepatic diseases, and is
marketed in Japan, China, Korea, Taiwan, and India [61, 66].
Licorice pieces are popular chew sticks in Italy, Spain, the Netherlands (where
they are called Palu dushi) and West Indies. It is also employed in chewing gum,
confectionery, soft drinks, liqueurs, ice creams, puddings, bakery products, soy sauce
and soybean-protein meat substitutes [34], added to beer to enhance the “head”XXIV
and aroma [6], and to porter and stout to provide more body and a darker hue.LV
Mouthwashes, breath ‘purifiers’ and toothpastes [34], and tobacco industry also used
it to enhance flavor, which was banned by the U.S. FDA [81]. In pharmaceutical
industry it is customarily added to bitter laxative preparations of senna, aloe, cascara
and other drugs to improve their flavor and because it sensitizes intestines and thus
potentiates their action.CXVIII In Egypt, it was studied and promoted under the aus-
pices of various governmental research and academic institutions [96].
Phytoconstituents: Roots contain glycyrrhizin (glycyrrhizic acid or glycyrrhizinic
acid), the main water-soluble constituent that is 50 sweeter than sugar, 2-b-
glucuronosyl glucuronic acid, and isoliquiritigenin-4-glucoside. Glycyrrhizin (GR)
is a nonhemolytic saponin with foaming property [98], and one of the most potent
hydroxyl radical scavengers [79]. Glycyrrhizin content in roots vary with season and
age, rapidly increasing from October to November in 1-year-old roots, but did not
show any significant increase from May to August in 3-years-old plants, whereas the
isoliquiritigenin glycoside content increased up to October [52]. Glycyrrhizin con-
tent is higher in thick roots and rhizomes than in thin ones, and the highest content of
GR is found in rhizomes 1.1–2 cm in diameter; there is little difference in the GR
content of vertical and horizontal rhizomes [51, 78]. Hayashi et al. reported variation
in GR contents from 3.3 to 6.1% of the dry weight, and that of glabridin, from 0.08 to
0.35% of dry weight in samples of rhizomes and roots collected from Uzbekistan
[53]. Samples collected from various sites in Italy also showed remarkable differ-
ences in active constituents and biological activity [106]. Roots also contain phe-
nolic compounds, formononetin, hemileiocarpin, hispaglabridin B, isoliquiritigenin,
glabrene, glabridin, 4′-O-methylglabridin, paratocarpin B, phaseollinisoflavone
(phytoalexin), glabrol, salicylic acid, and O-acetyl salicylic acid (0.15%) [73]; his-
paglabridin B, isoliquiritigenin, and paratocarpin B are reported as the most potent
antioxidant agents [29]. Kitagawa et al. isolated flavonoids, glucoliquiritin apioside,
prenyllicoflavone A, shinflavone, shinpterocarpin and 1-methoxyphaseollin from
samples collected from Xinjiang province of China [62]. Phenolic constituents,
licopyranocoumarin, glycycoumarin and/or licocoumarone, are found in G. uralen-
sis but not in G. glabra; whereas glabridin and glabrene are found in G. glabra but
not in G. uralensis [50]. Glabridin is a species-specific flavonoid of G. glabra, and
not found in other species of glycyrrhiza [53]. Other phenolic compounds, 5′-for-
mylglabridin, (2R,3R)-3,4′,7-trihydroxy-3′-prenylflavane, (3R)-2′,3′,7-trihydroxy-4′-
methoxyisoflavan, kanzonol X, kanzonol W, glabrol, echinatin, shinpterocarpin,
licoflavanone A, shinflavanone, gancaonin L, and glabrone exhibit significant PPAR-c
968 Glycyrrhiza glabra L.

ligand-binding activity [65]. Two flavonosides, glychionide A and B, were isolated

from the roots by Li et al. [68]. Two caffeic acid derivative esters, viz. eicosanyl
caffeate and docosyl caffeate possess potent elastase inhibitory activity, and moderate
antioxidant activity [36]. Two saponins, glabranin-A and B, are glycosides of gly-
cyrrhetic acid [113]. Oleanane-type triterpene saponins, licorice-saponin M3, licorice-
saponin N4, and licorice-saponin O4, were isolated by Wei et al. [119]. Seven
constituents, with antioxidant capacity were identified as the isoflavans (hispaglabridin
A and B, glabridin, and 4′-O-methylglabridin), the two chalcones (isoprenylchalcone
derivative and isoliquiritigenin), and the isoflavone, formononetin; glabridin being the
most abundant and potent LDL antioxidant [114]. Coumarin derivatives present are
herniarin and umbelliferone;XXIV also, the flavones liquiritin, liquiritigenin [55],
isoliquiritin and isoliquiritigenin (responsible for yellow color) and the glycosides
liquiritoside and isoliquiritoside, which, together are credited with licorice’s antiulcer
activity, and two flavonoids, rhamnoliquiritin and rhamnoisoliquiritin have been
reported [112].
Pharmacology: The extract, powder, GR and glycyrrhetic acid possess gluco-
corticoid and mineralocorticoid-like activities. Licorice has been shown to inhibit
tyrosinase activity in vitro, a rate-limiting oxidase enzyme involved in the forma-
tion of melanin [67]. Glyderinine, a derivative of GR produced pronounced anti-
inflammatory effects [12], exceeding activities of hydrocortisone and amidopyrine;
also showed analgesic and antipyretic effects, but unlike most NSAID, did not
suppress hemopoiesis or cause gastrointestinal ulceration. Hydroalcohol extract
showed antiulcer activity against various ulcerogenic stimuli, comparable to cime-
tidine and even better than omeprazole [58]. GutGard®, the standardized extract
reduced ulcer index and increased gastric pH, due to its cytoprotective and anti-
oxidant properties [76], also protected against indomethacin-induced gastric ulcers
in rats, with reduced acid output and increased mucin secretion, increase in PGE2
release and decrease in leukotrienes [60]. Combination of cimetidine and degly-
cyrrhizinated liquorice provided greater protection against aspirin-induced gastric
ulcers in rats than low doses of either drug alone [17]. Aqueous extract is a strong
inhibitor of adhesion of H. pylori to human stomach tissue [120]. The flavonoids,
glabridin and glabrene inhibit in vitro growth of sensitive, and clarithromycin- and
amoxicillin-resistant strains of H. pylori [46]. Isoliquiritigenin produces dual
dose-dependent effect on the intestine, inhibitory at low doses and prokinetic at the
high doses; the former effect is predominantly due to calcium channels blockade,
while the latter may involve muscarinic receptors activation [28]. Aqueous extract
was protective against APAP-induced hepatorenal damage in mice [102]. Oral or i.
v. administration of licorice extract caused choleretic effect in rats, and umbellif-
eron, a minor component, was identified responsible for it [90].
Both aqueous and ethanol licorice extracts are effective against S. mutans and
L. acidophilus, comparable to chlorhexidine [3], and methanol extract was espe-
cially bactericidal to S. mutans within 2 min at 50 lg/ml [56] and also selectively
active against P. falciparum and P. berghei [40]. Fresh aqueous extract inhibited
growth of standard strain and two clinical isolates of C. albicans; however, the
Glycyrrhiza glabra L. 969

activity was lost after storage for 24 h, even at 4 °C [75]. Ethanol extract is remark-
ably active against P. acnes, with negligible induction of resistance [80]. The
flavonoid rich standardized commercial extract (GutGard®) and one of its con-
stituents, glabridin were significantly active against H. pylori, but even at higher
concentration, GR showed no activity [10]. Glabridin was also active against
M. tuberculosis and many Gram-positive and Gram-negative bacteria [48], and
against drug resistant mutants of C. albicans [41]. Aqueous extract was active
against HSV-1, [94] and GR inhibited plaque formation in three strains of Japanese
encephalitis virus [13]. Hispaglabridin A and B, 4′-O-methylglabridin, glabridin,
glabrol and 3-hydroxyglabrol, all exhibit significant antimicrobial activity [73].
Glycyrrhizin inhibits growth and cytopathology of several unrelated DNA and
RNA viruses, without affecting cell activity and ability to replicate [87]. Animal
studies showed reduction of mortality and viral activity in HSV encephalitis and
influenza A virus pneumonia. In vitro studies revealed antiviral activity against
HIV-1, SARS related coronavirus, RSV, arboviruses, vaccinia virus and vesicular
stomatitis virus [43]. 18-b glycyrrhetinic acid was also active in a pH-dependent
manner against C. albicans strains, isolated from patients with recurrent vulvo-
vaginal candidiasis [86], and strong antiviral activity against rotavirus [63].
Pretreatment of mice with aqueous extract for 7-days significantly improved
learning and memory [85], reversed scopolamine-induced amnesia [38], decreased
brain AChE activity [37], and produced antidepressant-like effect [39]. Aqueous
extract pretreatment of rats also significantly enhanced spatial memory retention
[101] and learning [26]. Pretreatment of rats with glabridin [122], and isoliquirit-
igenin [125] significantly protected against cerebral ischemia-induced neurological
deficit; glabridin also significantly antagonized scopolamine-induced amnesia and
remarkably reduced brain AChE activity in mice [35], improved learning and
memory in normal rats and reversed diabetes-induced cognition deficit in rats [49].
Ethanol extract acting on GABAA-benzodiazepine receptors produced hypnotic
effect in mice [30], and ameliorated PTZ-induced convulsions in rats [31]. Licorice
extract is protective against myocardial I/R injury [82], and isoproterenol-induced
MI [83]. Aqueous extract exhibits modest in vitro thrombolytic activity [88], and
GR was identified as a selective in vitro thrombin inhibitor [44], reduced thrombus
size in venous thrombosis model, and in high doses caused significant hemorrhagic
effect. Glycyrrhetinic acid also directly inhibited Factor Xa in vitro, increased
plasma clotting time and prothrombin time, and caused moderate hemorrhagic
effect [59].
Chinese researchers reported that intragastric administration of the herb powder to
rabbits at a dose of 1 and 3 g/day was ineffective in preventing experimental
atherosclerosis.XVIII However, plasma lipid profile was significantly positively
affected in normal and dyslipidemic rats by root powder administration, while the
HDL-C was significantly increased [116]. It was reported to be the most potent out of
a number of Indian medicinal plants for its hypolipidemic/hypocholesterolemic and
antioxidant effects [116]. Ethanol extract significantly reduced LDL-C and increased
HDL-C of dyslipidemic Syrian golden hamsters [72]. Methanol and aqueous
methanol extracts [121] and aqueous and ethanol extracts [117] demonstrated high
970 Glycyrrhiza glabra L.

in vitro radical-scavenging activity. Licorice extract, due to its antioxidant proper-

ties, protected rats against toxic effects of ochratoxin A, one of the most common
food-contaminating mycotoxins [71]. Freeze-dried aqueous extract is a strong sup-
pressor of adrenal-pituitary axis in rats, significantly decreases concentrations of
cortisol, ACTH, aldosterone and K+, and increases concentrations of Na+, and
stimulates renin production by the kidneys [4]. Ethanol extract has shown antian-
drogenic property in castrated rats [123]. Fractions of ethyl acetate extract have
displayed estrogenic activity; several of them showing higher responses than
the natural hormone 17b-estradiol, but glabridin not exerting any estrogenic
activity [105].
Aqueous extract demonstrates potent antiangiogenic and antitumor activity
inhibiting in vivo and in vitro proliferation of Ehrlich ascites tumor cells [103].
Petroleum ether extract showed significant in vitro cytotoxic effect against Yoshida
ascites sarcoma cells [111]. Glycyrrhizin feeding in drinking water to Sencar mice
substantially protected against DMBA-induced skin tumorigenesis. Binding of
topically applied [3H]B(a)P and [3H]DMBA to epidermal DNA was also signifi-
cantly inhibited. Intraperitoneal pretreatment of animals with GR or addition of GR
to the culture medium antagonized E. coli endotoxin (LPS) and hydrocortisone-
induced myelosuppression of mouse bone marrow cells in culture [57]. Antimuta-
genic activity of extracts or their components has also been reported [99, 100, 124].
Clinical Studies: In a double-blind RCT, 30-days treatment with GutGuard®
significantly decreased symptoms of Indian patients with functional dyspepsia [91],
and was also significantly effective in patients with H. pylori infection [89].
Bardhan and colleagues reported no significant effect of deglycyrrhizinised
liquorice on gastric ulcer in an RCT of British patients [15]; whereas, Brogden and
associates had earlier reported it effective in peptic ulcers [20]. Treatment of healthy
men with licorice for one-week decreased salivary testosterone values by 26% but
no significant decrease in free testosterone [7], and nine healthy women treated with
3.5 g of licorice containing 7.6% of GR daily for two cycles, had their mean total
serum testosterone decreased by 37% at the end of 2nd month. This property could
be useful as an adjunct therapy of hirsutism and PCOS [8]. In a double-blind RCT,
topical application of a gel preparation (2%, containing 19.6% GR) was effective in
significantly reducing scores of erythema, edema and itching after two-weeks
treatment of 30 Iranian patients with atopic dermatitis [95]. An emollient cream
containing milk proteins and licorice extract used as adjuvant to topical corticos-
teroid treatment of palmoplantar psoriasis in Italian patients for four-weeks also
produced significantly greater improvement than the cortiocosteroid therapy alone
[24]. Licorice tincture stimulates immune cells in humans within 24 h of ingestion
that continues for at least 7 days [21, 126].
Acharya and associates [1] reported a highly significant favorable response in 18
patients of subacute hepatic failure due to viral hepatitis, treated with a substance
isolated from G. glabra. The substance, named Stronger Neo Minophagen-C
(SNMC), is an interferon stimulator. Survival rate amongst the patients treated with
SNMC was 72.2% compared to the survival rate of 31.1% in 98 patients who received
Glycyrrhiza glabra L. 971

only supportive therapy. RCTs confirmed that glycyrrhizin and its derivatives
reduced hepatocellular damage in chronic hepatitis B and C, and the risk of hepa-
tocellular carcinoma was reduced in hepatitis C virus-induced cirrhosis [43].
Mechanism of Action: Various mechanisms have been suggested for its antiulcer
activity. cAMP and cGMP have been implicated in the regulation of gastric acid
secretion. One of licorice constituents, glycyrrhetinic acid inhibits PDE activity,
thus increasing levels of cAMP of gastric mucosa of the pylorus and cardia, and
suppressing gastric acid secretion. It did not, however, affect adenylate cyclase [5].
Antiulcer effect of GR is due to increased local concentration of PGs that promotes
mucous secretion, and the hepatoprotective effect is mediated through inhibition of
PLA2, and increasing hepatocytes survival [72]. Isoliquiritigenin relaxes isolated
guinea-pig trachea through various intracellular actions, including inhibition of
PDEs [69]. Hydroalcohol extract also inhibited 5-LOX and COX-2 enzymes,
inhibiting formation of both eicosanoids and LTs [54]. GR, due to the steroid-like
structure of its aglycone, b-glycyrrhetinic acid is credited for its anti-inflammatory
and antiallergic activities, which also possesses immunomodulatory properties [64];
and liquiritigenin is credited for the antiallergic activity [104]. However, the in vitro
inhibitory effect on formation of both eicosanoids and LTs has been ascribed to
glabridin and isoliquiritigenin and not GR [27, 107]. Antidepressant activity of
aqueous extract is suggested to be mediated by increase of brain NE and DA, and
MAO inhibiting effect [39]. Inhibition of carcinogen metabolism to active metabo-
lite and DNA adduct formation could be the possible mechanism(s) of antitumor
activity [2].
Human A/Es, Allergy and Toxicity: Revers first reported reduction in abdominal
symptoms as well as radiographic evidence of healing of gastric ulcer, after
administration of a paste prepared from dried watery extract of the roots [93].
However, later clinical studies observed that approximately 20% of treated patients
developed facial and dependent edema, often accompanied by headache, shortness
of breath, stiffness, and pain in the upper abdomen, which subsided after reduction
of the dose [97]. Various reports of licorice toxicity emerged from Western
countries in the 1950s, 60s and 70s about hypokalemia, hypertension and paralysis
[11, 109]. Licorice was even declared to damage health [108]. Chopra et al. warned
that licorice should be avoided by persons with cardiac problems, hypertension,
kidney ailments, and those who are overweight or having difficult pregnancies.XXI
Excessive licorice ingestion led to cardiac dysfunction and severe hypertension [16,
18, 32, 33, 47, 118];XXVIII most cases were resolved after cessation of licorice and
potassium replacement without any sequelae. However, some cases of serious
poisoning were reported, including death due to cardiac arrest [14]. A Californian
woman developed pain in arms and legs, aggravated by muscular activity, after
consuming large quantities of licorice to lose weight [110]; women also developed
acute quadriparesis and paralysis due to severe hypokalemia, after consuming for
long period a product containing licorice [9, 77]. Borst et al. [19] first reported that
the GR moiety of liquorice was responsible for fluid retention and electrolyte
imbalance. Glycyrrhizin in licorice has mineralocorticoid-like effect, and chronic
972 Glycyrrhiza glabra L.

intake induces a primary hyperaldosteronism-like syndrome resulting in sodium

and water retention and loss of potassium, increasing extracellular fluid and plasma
volume, leading to hypertension, hypokalemia, and metabolic alkalosis [25].CXI
The hypermineralocorticoidism and pseudoaldosteronism are due to the inhibitory
activity of GR on 11-hydroxysteroid dehydrogenase [42]. Kabeeruddin mentions it
harmful for kidneys and spleen.LXXVII
Animal Toxicity: Oral LD50 of hydroalcohol extract in mice was reported as
2,950 mg/kg [58]. LD100 of the herb extract in mice by subcutaneous injection was
calculated as 3,600 mg/kg; the animals died of respiratory paralysis. Mean lethal
dose (MLD) of glycyrrhizin by this route was found to be 1,000 mg/kg.
CYP450 and Potential for Drug-Herb Interactions: Ethanol extract in vitro
inhibits CYP3A4 [22], and CYP2D6 [84]. Inhibition of CYP450 enzymes could
result in reduced metabolism of drugs metabolized by these enzymes, such as
warfarin, synergistically increasing its activity and prolonging clotting times. An
80-year-old woman with atrial fibrillation, being treated with warfarin, developed
black tarry stools and an elevated INR, after eating a pound of black licorice [70].
Pretreatment of rats with methanol extract for 6-days significantly increased
cumulative biliary and urinary excretions of APAP-glucuronide conjugate [74].
In Chinese medicine, four drugs collectively known as “Zao Jie She Yuan”
(Sargassum fusiforme, root of Euphorbia pekinensis, root of Euphorbia kansui, and
flower buds of Daphne genkwa) are considered incompatible with Gancao.
Administration of G. glabra with any of these drugs either enhances the combined
effect (toxic) or inhibits activity of each other.XVIII
Commentary: Since the first scientific report in 1950s of healed gastric ulcers after
treatment with licorice that could be proven by radiology, licorice has been a
subject of controversy due to its glucocorticoid and mineralocorticoid-like activities
as adverse effects. Nevertheless, it continues to be used in traditional medicines, and
continues to be a subject of scientific curiosity, and investigated for various
activities.

References
1. Acharya SK, Dasarathy S, Tandon A, et al. A preliminary open trial on
interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the
treatment of subacute hepatic failure. Indian J Med Res Sect A—Infect Dis.
1993;98:69–74.
2. Agarwal R, Wang ZY, Mukhtar H. Inhibition of mouse skin tumor-
initiating activity of DMBA by chronic oral feeding of glycyrrhizin in
drinking water. Nutr Cancer. 1991;15:187–93.
3. Ajagannanavar SL, Battur H, Shamarao S, et al. Effect of aqueous and
alcoholic licorice (Glycyrrhiza glabra) root extract against Streptococcus
mutans and Lactobacillus acidophilus in comparison to chlorhexidine: an
in vitro study. J Int Oral Health. 2014;6:29–34.
Glycyrrhiza glabra L. 973

4. Al-Qarawi AA, Abdel-Rahman HA, Ali BH, El Mougy SA. Liquorice

(Glycyrrhiza glabra) and the adrenal-kidney-pituitary axis in rats. Food
Chem Toxicol. 2002;40:1525–7.
5. Amer MS, McKinney GR, Akcasu A. Effect of glycyrrhetinic acid on the
cyclic nucleotide system of the rat stomach. Biochem Pharmacol. 1974;23:
3085–92.
6. Anonymous (1948–1972). The wealth of India (Raw Material), vol. 4. New
Delhi: CSIR;1956. p. 151–4.
7. Armanini D, Bonanni G, Mattarello MJ, et al. Licorice consumption and
serum testosterone in healthy man. Exp Clin Endocrinol Diabetes. 2003;
111:341–3.
8. Armanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testos-
terone in healthy women. Steroids. 2004;69:763–6.
9. Arne L, Julien J, Ponzetto C et al. Paralysis with hypokalemia following
prolonged ingestion of licorice extract. J Med Bordeaux. 1965;142:1383–
91 (French)
10. Asha MK, Debraj D, Prashanth D, et al. In vitro anti-Helicobacter pylori
activity of a flavonoid rich extract of Glycyrrhiza glabra and its probable
mechanisms of action. J Ethnopharmacol. 2013;145:581–6.
11. Aumaitre J. Severe hypokalemia by a drug flavored with liquorice. J Nouv
Presse Med. 1978;7:3942 (French)
12. Azimov MM, Zakirov UB, Radzhapova ShD. Pharmacological study of
the anti-inflammatory agent glyderinine. Farmakologiia i Toksikologiia.
1988;51:90–3 (Russian).
13. Badam L. In vitro antiviral activity of indigenous glycyrrhizin, licorice and
glycyrrhizic acid (Sigma) on Japanese encephalitis virus. J Commun Dis.
1997;29:91–9.
14. Bannister B, Ginsburg R, Shneerson J. Cardiac arrest due to liquorice-
induced hypokalemia. Br Med J. 1977;2:738–9.
15. Bardhan KD, Cumberland DC, Dixon RA, Holdsworth CD. Clinical trial
of deglycyrrhizinised liquorice in gastric ulcer. Gut. 1978;19:779–82.
16. Bel A, Rousset H, Fournier G. Quadriplegia, severe hypokalemic alkalosis,
tetany, arterial hypertension in relation to excessive licorice extract con-
sumption in a chronic alcoholic. Lyon Med. 1972;228:55–62 (French).
17. Bennett A, Clark-Wibberley T, Stamford IF, Wright JE. Aspirin-induced
gastric mucosal damage in rats: cimetidine and deglycyrrhizinated liquorice
together give greater protection than low doses of either drug alone. J Pharm
Pharmacol. 1980;32:151.
18. Beretta-Piccoli C, Salvadé G, Crivelli PL, Weidmann P. Body-sodium and
blood volume in a patient with licorice-induced hypertension. J Hypertens.
1985;3:19–23.
19. Borst JGG, Blomhert G, Molhuysen JA, et al. De uitscheiding van water en
electrolyten gedurende het etmaal en ouder invloed van succur liquiritiae.
Acta Clin Belg. 1950;5:405–9 (German).
974 Glycyrrhiza glabra L.

20. Brogden RN, Speight TM, Avery GS. Deglycyrrhizinised liquorice: a

report of its pharmacologic properties and therapeutic efficacy in peptic
ulcer. Drugs. 1974;8:330–9.
21. Brush J, Mendenhall E, Guggenheim A, et al. The effect of Echinacea
purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69
expression and immune cell activation in humans. Phytother Res. 2006;20:
687–95.
22. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro
evaluation of human cytochrome P450 3A4 inhibition by selected
commercial herbal extracts and tinctures. Phytomedicine. 2000;7:273–82.
23. Cao J, Chen X, Liang J, et al. Role of P-glycoprotein in the intestinal
absorption of glabridin, an active flavonoid from the root of Glycyrrhiza
glabra. Drug Metab Dispos. 2007;35:539–53.
24. Cassano N, Mantegazza R, Battaglini S, et al. Adjuvant role of a new
emollient cream in patients with palmar and/or plantar psoriasis: a pilot
randomized open-label study. G Ital Dermatol Venereol. 2010;145:789–92.
25. Celik MM, Karakus A, Zeren C, et al. Licorice induced hypokalemia,
edema, and thrombocytopenia. Hum Exp Toxicol. 2012;31:1295–8.
26. Chakravarthi KK, Avadhani R. Beneficial effect of aqueous root extract of
Glycyrrhiza glabra on learning and memory using different behavioral
models: an experimental study. J Nat Sci Biol Med. 2013;4:420–5.
27. Chandrasekaran CV, Deepak HB, Thiyagarajan P, et al. Dual inhibitory
effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products.
Phytomedicine. 2011;18:278–84.
28. Chen G, Zhu L, Liu Y, et al. Isoliquiritigenin, a flavonoid from licorice,
plays a dual role in regulating gastrointestinal motility in vitro and in vivo.
Phytother Res. 2009;23:498–506.
29. Chin YW, Jung HA, Liu Y, et al. Antioxidant constituents of the roots and
stolons of licorice (Glycyrrhiza glabra). J Agric Food Chem. 2007;55:
4691–7.
30. Cho S, Park JH, Pae AN, et al. Hypnotic effects and GABAergic
mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major
flavonoid constituent glabrol. Bioorg Med Chem. 2012;20:3493–501.
31. Chowdhury B, Bhattamisra SK, Das MC. Anticonvulsant action and
amelioration of oxidative stress by Glycyrrhiza glabra root extract in
pentylenetetrazole-induced seizure in albino rats. Indian J Pharmacol. 2013;
45:40–3.
32. Cibelli G, De Mari M, Pozio G, Lamberti P. Hypokalemic myopathy associ-
ated with liquorice ingestion. Ital J Neurol Sci. 1984;5:463–6.
33. Conn JW, Rovner DR, Cohen EL. Licorice-induced pseudoaldosteronism.
Hypertension, hypokalemia, aldosteronopenia and suppressed plasma renin
activity. JAMA. 1968;205:492–6.
34. Cook MK, Gominger BH. Glycyrrhizin. Chap. 19 (p. 211–15). In: Inglett
GE, editor. Symposium: Sweetners. Westport, Connecticut: The AVI Pub-
lishing Co., Inc.; 1974. p. 240.
Glycyrrhiza glabra L. 975

35. Cui YM, Ao MZ, Li W, Yu LJ. Effect of glabridin from Glycyrrhiza

glabra on learning and memory in mice. Planta Med. 2008;74:377–80.
36. Dey S, Deepak M, Setty M, et al. Bioactive caffeic acid esters
from Glycyrrhiza glabra. Nat Prod Res. 2009;23:1657–63.
37. Dhingra D, Parle M, Kulkarni SK. Comparative brain cholinesterase-
inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic
acid, and metrifonate in mice. J Med Food. 2006;9:281–3.
38. Dhingra D, Parle M, Kulkarni SK. Memory enhancing activity of
Glycyrrhiza glabra in mice. J Ethnopharmacol. 2004;91:361–5.
39. Dhingra D, Sharma A. Antidepressant-like activity of Glycyrrhiza glabra L.
in mouse models of immobility tests. Prog Neuropsychopharmacol Biol
Psychiatry. 2006;30:449–54.
40. Esmaeili S, Naghibi F, Mosaddegh M, et al. Screening of antiplasmodial
properties among some traditionally used Iranian plants. J Ethnopharmacol.
2009;121:400–4.
41. Fatima A, Gupta VK, Luqman S, et al. Antifungal activity of Glycyrrhiza
glabra extracts and its active constituent glabridin. Phytother Res. 2009;
23:1190–3.
42. Ferrari P, Sansonnens A, Dick B, Frey FJ. In vivo 11b-HSD-2 activity:
variability, self-sensitivity, and effect of licorice. Hypertension. 2001;38:
1330–6.
43. Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza
species. Phytother Res. 2008;22:141–8.
44. Francischetti IM, Monteiro RQ, Guimarães JA. Identification of gly-
cyrrhizin as a thrombin inhibitor. Biochem Biophys Res Commun. 1997;
235:259–63.
45. Fujisawa K, Watanabe Y, Kimura K. Therapeutic approach to chronic active
hepatitis with glycyrrhizin. Asian Med J. 1980;23:745–56.
46. Fukai T, Marumo A, Kaitou K, et al. Anti-Helicobacter pylori flavonoids
from licorice extract. Life Sci. 2002;71:1449–63.
47. Garcin R, Goulon M, Tournilhac M, Amor B. New case of paralysis with
hypokalemia and metabolic alkalosis secondary to excessive and pro-
longed ingestion of licorice extract after treatment of alcoholic intoxica-
tion. Rev Neurol (Par). 1961;104:461–8 (French)
48. Gupta VK, Fatima A, Faridi U, et al. Antimicrobial potential of Glycyrrhiza
glabra roots. J Ethnopharmacol. 2008;116:377–80.
49. Hasanein P. Glabridin as a major active isoflavan from Glycyrrhiza
glabra (licorice) reverses learning and memory deficits in diabetic rats.
Acta Physiol Hung. 2011;98:221–30.
50. Hatano T, Fukuda T, Liu YZ, et al. Phenolic constituents of licorice. IV.
Correlation of phenolic constituents and licorice specimens from various
sources, and inhibitory effects of licorice extracts on xanthine oxidase and
monoamine oxidase. Yakugaku Zasshi. 1991;111:311–21 (Japanese).
51. Hayashi H, Fukui H, Tabata M. Distribution pattern of saponins in
different organs of Glycyrrhiza glabra. Planta Med. 1993;59:351–3.
976 Glycyrrhiza glabra L.

52. Hayashi H, Hiraoka N, Ikeshiro Y, et al. Seasonal variation of glycyrrhizin

and isoliquiritigenin glycosides in the root of Glycyrrhiza glabra L. Biol
Pharm Bull. 1998;21:987–9.
53. Hayashi H, Hattori S, Inoue K, et al. Field survey of Glycyrrhiza plants in
Central Asia (3). Chemical characterization of G. glabra collected in
Uzbekistan. Chem Pharm Bull (Tokyo). 2003;51:1338–40.
54. Herold A, Cremer L, Călugaru A, et al. Hydroalcoholic plant extracts with
anti-inflammatory activity. Roum Arch Microbiol Immunol. 2003;62:117–29.
55. Homma M, Oka K, Yamada T, et al. A strategy for discovering
biologically active compounds with high probability in traditional Chinese
herb remedies: an application of saiboku-to in bronchial asthma. Analyt.
Biochem. 1992;202:179–87.
56. Hwang JK, Shim JS, Chung JY. Anticariogenic activity of some tropical
medicinal plants against Streptococcus mutans. Fitoterapia. 2004;75:596–8.
57. Inada K, Mohri H, Suzuki M, et al. Prevention of the in vitro myelosup-
pressive effect of liopopolysaccharide and hydrocortisone by glycyrrhizin.
Igaku no Ayumi. 1983;125:554–6.
58. Jalilzadeh-Amin G, Najarnezhad V, Anassori E, Mostafavi M, Keshipour H.
Antiulcer properties of Glycyrrhiza glabra L. extract on experimental
models of gastric ulcer in mice. Iran J Pharm Res. 2015;14:1163–70.
59. Jiang L, Wang Q, Shen S, Xiao T, Li Y. Discovery of glycyrrhetinic acid
as an orally active, direct inhibitor of blood coagulation factor Xa. Thromb
Res. 2014;133:501–6.
60. Khayyal MT, el-Ghazaly MA, Kenawy SA, et al. Antiulcerogenic effect of
some gastrointestinally acting plant extracts and their combination. Arzneimit-
telforschung. 2001;51:545–53.
61. Kim SW, Lim CM, Lee HK, Lee JK. The use of Stronger Neo-Minophagen C,
a glycyrrhizin-containing preparation, in robust neuroprotection in the post-
ischemic brain. Anat Cell Biol. 2011;44:304–13.
62. Kitagawa I, Chen WZ, Hori K, et al. Chemical studies of Chinese
licorice-roots. I. Elucidation of five new flavonoid constituents from the
roots of Glycyrrhiza glabra L. collected in Xinjiang. Chem Pharm Bull
(Tokyo). 1994;42:1056–62.
63. Knipping K, Garssen J, van’t Land B. An evaluation of the inhibitory effects
against rotavirus infection of edible plant extracts. Virol J. 2012;9:137.
64. Kroes BH, Beukelman CJ, van den Berg AJ, et al. Inhibition of human
complement by beta-glycyrrhetinic acid. Immunology. 1997;90:115–20.
65. Kuroda M, Mimaki Y, Honda S, et al. Phenolics from Glycyrrhiza
glabra roots and their PPAR-gamma ligand-binding activity. Bioorg Med
Chem. 2010;18:962–70.
66. Lee CH, Park SW, Kim YS, et al. Protective mechanism of glycyrrhizin on
acute liver injury induced by carbon tetrachloride in mice. Biol Pharm
Bull. 2007;30:1898–904.
Glycyrrhiza glabra L. 977

67. Lee KT, Kim BJ, Kim JH, et al. Biological screening of 100 plant extracts
for cosmetic use (I): inhibitory activities of tyrosinase and DOPA auto-
oxidation. Int J Cosmet Sci. 1997;19:291–8.
68. Li JR, Wang YQ, Deng ZZ. Two new compounds from Glycyrrhiza
glabra. J Asian Nat Prod Res. 2005;7:677–80.
69. Liu B, Yang J, Wen Q, Li Y. Isoliquiritigenin, a flavonoid from licorice,
relaxes guinea-pig tracheal smooth muscle in vitro and in vivo: role of
cGMP/PKG pathway. Eur J Pharmacol. 2008;587:257–66.
70. Liu JF, Srivatsa A, Kaul V. Black licorice ingestion: yet another
confounding agent in patients with melena. World J Gastrointest Surg.
2010;2:30–1.
71. Malekinejad H, Mirzakhani N, Razi M, et al. Protective effects of melatonin
and Glycyrrhiza glabra extract on ochratoxin A-induced damages on testes
in mature rats. Hum Exp Toxicol. 2011;30:110–23.
72. Maurya SK, Raj K, Srivastava AK. Antidyslipidaemic activity of
Glycyrrhiza glabra in high fructose diet induced dsyslipidaemic Syrian
golden hamsters. Indian J Clin Biochem. 2009;24:404–9.
73. Mitscher LA, Park YH, Clark D, Beal JL. Antimicrobial agents from
higher plants. Antimicrobial isoflavanoids and related substances from
Glycyrrhiza glabra L. var. typica. J Nat Prod. 1980;43:259–69.
74. Moon A, Kim SH. Effect of Glycyrrhiza glabra roots and glycyrrhizin on
the glucuronidation in rats. Planta Med. 1997;63:115–9.
75. Motsei ML, Lindsey KL, van Staden J, Jäger AK. Screening of tradi-
tionally used South African plants for antifungal activity against Candida
albicans. J Ethnopharmacol. 2003;86:235–41.
76. Mukherjee M, Bhaskaran N, Srinath R, et al. Antiulcer and antioxidant
activity of GutGard. Indian J Exp Biol. 2010;48:269–74.
77. Mukherjee T, Bhatt K, Sirsat R. A young female with quadriparesis.
J Assoc Physicians India. 2006;54:400–2.
78. Nadezhina TP. The glycyrrhizin content of licorice roots and rhizomes.
Bot Zhur. 1963;48:1332–7.
79. Nagai T, Egashira T, Yamanaka Y, Kohno M. The protective effect of
glycyrrhizin against injury of the liver caused by ischemia-reperfusion.
Arch. Environ. Contam. Toxicol. 1991;20:432–6.
80. Nam C, Kim S, Sim Y, Chang I. Antiacne effects of Oriental herb extracts:
a novel screening method to select antiacne agents. Skin Pharmacol Appl
Skin Physiol. 2003;16:84–90.
81. Nishi H, Morishita J. Components of licorice root used for tobacco
flavouring. I. Fractionation of the substances in licorice root effective in
improving the tobacco smoking quality. Nippon Nogei Kagaku Kaishi.
1971;45:507–12.
82. Ojha S, Golechha M, Kumari S, et al. Glycyrrhiza glabra protects from
myocardial ischemia-reperfusion injury by improving hemodynamic, bio-
chemical, histopathological and ventricular function. Exp Toxicol Pathol.
2013;65:219–27.
978 Glycyrrhiza glabra L.

83. Ojha SK, Sharma C, Golechha MJ, et al. Licorice treatment prevents
oxidative stress, restores cardiac function, and salvages myocardium in rat
model of myocardial injury. Toxicol Ind Health. 2015;31:140–52.
84. Pandit S, Ponnusankar S, Bandyopadhyay A, et al. Exploring the possi-
ble metabolism mediated interaction of Glycyrrhiza glabra extract with
CYP3A4 and CYP2D6. Phytother Res. 2011;25:1429–34.
85. Parle M, Dhingra D, Kulkarni SK. Memory-strengthening activity of
Glycyrrhiza glabra in exteroceptive and interoceptive behavioral models.
J Med Food. 2004;7:462–6.
86. Pellati D, Fiore C, Armanini D, Rassu M, Bertoloni G. In vitro effects of
glycyrrhetinic acid on the growth of clinical isolates of Candida albicans.
Phytother Res. 2009;23:572–4.
87. Pompei R, Flore O, Marccialis MA, et al. Glycyrrhizic acid inhibits virus
growth and inactivates virus particles. Nature. 1979;281:689–90.
88. Prasad S, Kashyap RS, Deopujari JY, et al. Effect of Fagonia arabica
(Dhamasa) on in vitro thrombolysis. BMC Complement Altern Med. 2007;
7:36.
89. Puram S, Suh HC, Kim SU, et al. Effect of GutGard in the management of
Helicobacter pylori: a randomized double-blind placebo-controlled study.
Evid Based Complement Alternat Med. 2013;2013:263805.
90. Raggi MA, Bugamelli F, Nobile L, et al. The choleretic effects of licorice:
identification and determination of the pharmacologically active compo-
nents of Glycyrrhiza glabra. Boll Chim Farm. 1995;134:634–8 (Italian).
91. Raveendra KR, Jayachandra, Srinivasa V, et al. An extract of Glycyrrhiza
glabra (GutGard) alleviates symptoms of functional dyspepsia: a random-
ized, double-blind, placebo-controlled study. Evid Based Complement
Alternat Med. 2012;2012:216970.
92. Reuter J, Wölfle U, Weckesser S, Schempp C. Which plant for which skin
disease? Part 1: Atopic dermatitis, psoriasis, acne, condyloma and herpes
simplex. J Dtsch Dermatol Ges. 2010;8:788–96 (Article in English, German).
93. Revers FE. Clinical and pharmacological investigations on extract of
licorice. Acta Med Scand Suppl. 1956;312:749–51.
94. Sabouri Ghannad M, Mohammadi A, Safiallahy S, et al. The effect of
aqueous extract of Glycyrrhiza glabra on Herpes Simplex Virus 1. Jundisha-
pur J Microbiol. 2014;7:e11616.
95. Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic
dermatitis with licorice gel. J Dermatolog Treat. 2003;14:153–7.
96. Sayed MD. Traditional medicine in health care. J Ethnopharmacol. 1980;2:
19–22.
97. Schambelan M. Licorice ingestion and blood pressure regulating hor-
mones. Steroids. 1994;59:127–30 (Review).
98. Segal R, Milo-Goldzweig I, Kaplan G, Weisenberg E. The protective
action of glycyrrhizin against saponin toxicity. Biochem Pharmacol. 1977;
26:643–5.
Glycyrrhiza glabra L. 979

99. Shankel DM, Clarke CH. Specificity of antimutagens against chemical

mutagens in microbial systems. Basic Life Sci. 1990;52:457–60.
100. Shankel DM, Kuo S, Haines C, Mitscher LA. Extracellular interception of
mutagens. Basic Life Sci. 1993;6:65–74 (Review).
101. Sharifzadeh M, Shamsa F, Shiran S, et al. A time course analysis of
systemic administration of aqueous licorice extract on spatial memory
retention in rats. Planta Med. 2008;74:485–90.
102. Sharma A, Rathore HS. Prevention of acetaminophen induced hepatorenal
damage in mice with rhizomes of Glycyrrhiza glabra A histophysiological
study. Anc Sci Life. 2011;30:72–7.
103. Sheela ML, Ramakrishna MK, Salimath BP. Angiogenic and proliferative
effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by
Glycyrrhiza glabra. Int Immunopharmacol. 2006;6:494–8.
104. Shin YW, Bae EA, Lee B, et al. In vitro and in vivo antiallergic effects of
Glycyrrhiza glabra and its components. Planta Med. 2007;73:257–61.
105. Simons R, Vincken JP, Mol LA, et al. Agonistic and antagonistic estrogens
in licorice root (Glycyrrhiza glabra). Anal Bioanal Chem. 2011;401:305–13.
106. Statti GA, Tundis R, Sacchetti G, et al. Variability in the content of active
constituents and biological activity of Glycyrrhiza glabra. Fitoterapia.
2004;75:371–4.
107. Thiyagarajan P, Chandrasekaran CV, Deepak HB, Agarwal A. Modulation
of lipopolysaccharide-induced proinflammatory mediators by an extract
of Glycyrrhiza glabra and its phytoconstituents. Inflammopharmacology.
2011;19:235–41.
108. Toner JM, Ramsey LE. Liquorice can damage your health. Practitioner.
1985;229:858, 860.
109. Tourniaire J, Pousset G, Bizollon C, Toulouse P, Desirat C. Licorice poison-
ing with hyperaldosteronuria. Lyon Med. 1968;219:1321–33 (French).
110. Tourtellotte CR, Hirst AE. Hypokalemia, muscle weakness and myo-
globinuria due to licorice ingestion. Calif Med. 1970;113:51–3.
111. Trovato A, Monforte MT, Rossitto A, Forestieri AM. In vitro cytotoxic
effect of some medicinal plants containing flavonoids. Boll Chim Farm.
1996;135:263–6.
112. Van Hulle C, Braeckman P, Vandewalle M. Isolation of two new
flavonoids from the root of Glycyrrhiza glabra var. typica. Planta Med.
1971;20:278–82.
113. Varshney IP, Jain DC. Study of saponins from Glycyrrhiza glabra root.
Int J Crude Drug Res. 1983;21:169–72.
114. Vaya J, Belinky PA, Aviram M. Antioxidant constituents from licorice
roots: isolation, structure elucidation and antioxidative capacity toward
LDL oxidation. Free Radic Biol Med. 1997;23:302–13.
115. Verma P, Mathur AK, Jain SP, Mathur A. In vitro conservation of twenty-
three overexploited medicinal plants belonging to the Indian subcontinent.
ScientificWorldJournal. 2012;2012:929650.
980 Glycyrrhiza glabra L.

116. Visavadiya NP, Narasimhacharya AV. Hypocholesterolaemic and antiox-

idant effects of Glycyrrhiza glabra (Linn.) in rats. Mol Nutr Food Res.
2006;50:1080–6.
117. Visavadiya NP, Soni B, Dalwadi N. Evaluation of antioxidant and
antiatherogenic properties of Glycyrrhiza glabra root using in vitro mod-
els. Int J Food Sci Nutr. 2009;60 Suppl 2:135–49.
118. Wash LK, Bernard JD. Licorice-induced pseudoaldosteronism. Am J Hosp
Pharm. 1975;32:73–4.
119. Wei JH, Zheng YF, Li CY, Tang YP, Peng GP. Bioactive constituents of
oleanane-type triterpene saponins from the roots of Glycyrrhiza glabra.
J Asian Nat Prod Res. 2014;16:1044–53.
120. Wittschier N, Faller G, Hensel A. Aqueous extracts and polysaccharides
from liquorice roots (Glycyrrhiza glabra L.) inhibit adhesion of Helicobacter
pylori to human gastric mucosa. J Ethnopharmacol. 2009;125:218–23.
121. Wojcikowski K, Stevenson L, Leach D, et al. Antioxidant capacity of 55
medicinal herbs traditionally used to treat the urinary system: a comparison
using a sequential three-solvent extraction process. J Altern Complement
Med. 2007;13:103–9.
122. Yu XQ, Xue CC, Zhou ZW, et al. In vitro and in vivo neuroprotective
effect and mechanisms of glabridin, a major active isoflavan from
Glycyrrhiza glabra (licorice). Life Sci. 2008;82:68–78.
123. Zamansoltani F, Nassiri-Asl M, Sarookhani MR, et al. Antiandrogenic
activities of Glycyrrhiza glabra in male rats. Int J Androl. 2009;32:417–22.
124. Zani F, Cuzzoni MT, Daglia M, et al. Inhibition of mutagenicity in
Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid,
18 alpha- and 18 beta-glycyrrhetinic acids. Planta Med. 1993;59:502–7.
125. Zhan C, Yang J. Protective effects of isoliquiritigenin in transient middle
cerebral artery occlusion-induced focal cerebral ischemia in rats. Pharma-
col Res. 2006;53:303–9.
126. Zwickey H, Brush J, Iacullo CM, et al. The effect of Echinacea purpurea,
Astragalus membranaceus and Glycyrrhiza glabra on CD25 expression in
humans: a pilot study. Phytother Res. 2007;21:1109–12.
Gymnema sylvestre R. Br.
(Apocynaceae)

(Syns.: Asclepias germinata Roxb.; Periploca sylvestris Retz.)

Abstract
It is a stout large woody climber growing abundantly in the western Ghats of
India and in tropical Africa. Sushruta (6th century B.C.) described the plant as
destroyer of madhumeha (glycosuria) and other urinary disorders. The herb has
been used in Ayurveda of India for 2000 years for the treatment of diabetes, arthritis,
anemia, osteoporosis, hypercholesterolemia, cardiopathy, asthma, constipation,
microbial infections, indigestion, inflammation, ulcer, dyspepsia, eyes pain, in
snakebite, for family planning, and as diuretic, hepatoprotective, and in the form of
Gymnema tea to control obesity. Chewing one or two leaves destroys the taste for
sugar immediately, which lasts for one to two hours. However, it does not affect the
taste of pungent saline things, astringents and acids. This property is limited to only
sweets and bitters. In Japan, it is widely used as health food and sold in the forms of
tea bags, tablets, beverages and confectioneries. The leaves lower blood sugar,
stimulate heart, uterus, circulatory system and increase urinary output. Aqueous
leaf extract exhibited the presence of alkaloids, triterpenes, flavonoids, steroids,
and saponins. Leucine, isoleucine, valine, alanine and c-amino-n-butyric acid are
the amino acids present in the leaves. In certain animal experiments and clinical
trials there was no reduction of blood sugar and no effect on urinary sugar. Feeding
of dried leaf powder to normal rats for 25-days did not significantly alter blood
glucose, but significantly attenuated serum glucose response to oral administration
of glucose; the aqueous extract, however, significantly reduced blood glucose of
normal and diabetic rats. A water-soluble leaf extract administered to 27 Indian
patients with insulin-dependent diabetes on insulin therapy, brought down required
dose of insulin and lowered FBG, HbA1c and glycosylated plasma protein levels,
and returned serum lipids to near normal levels; the same extract supplemented
with oral antidiabetic drugs in 22 type-2 diabetic patients produced similar results

© Springer Nature Switzerland AG 2020 981

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_104
982 Gymnema sylvestre R. Br.

and about a quarter of patients completely stopped their conventional drugs after
18–20 months. The hypoglycemic effect has been attributed to reduced intestinal
glucose uptake and increased insulin release from b-cells.

Keywords





Ajaballi Ayagam Chi geng teng Cowplant Gurmar Kaoli Masbaedda






Medhasingi Oinaansarviliaani Vishanika

Vernaculars: Urd.: Gurmar-booti, Gurmar-patta; Hin.: Gurmar, Gurmar-booti,

Medhasingi, Mera-singi; San.: Ajaballi, Anyada, Kshinavartta, Madhunashini
Meshashringi (Ram’s horn), Meshavalli, Mesha vishánika, Sarpa darushtrika,
Vrik-shikali, Vishanika; Ben.: Mera-singi; Guj.: Gudmar; Mal.: Chakkarakolli,
Madhunaasini, Sarkarakolli, Shiru kuranja; Mar.: Bedakuli, kalikardori, Kaoli,
Kavali, Vakundi; Tam.: Adigam, Amudupushpam, Ayagam, Kannu minnayam,
Kodi pasaani, Kogilam, Shirukuriy, Sirukurinjann, Siru-kurinja; Tel.: Bodaparta,
Podapatri, Vodapatte; Chi.: 狗屎藤, Chi geng teng; Eng.: Australian cowplant,
Cowplant, Miracle-fruit; Fin.: Oinaansarviliaani; Sin.: Masbaedda.
Description: It is a stout large woody climber growing abundantly in the western
Ghats (central and southern regions of Goa) of IndiaCXXIII and in tropical Africa.XXI
It also grows in Pakistan, Bangladesh, Myanmar, Nepal, Bhutan, Sri Lanka, the
Maldives, Japan, Malaysia, Indonesia, Thailand, Cambodia, Laos, Vietnam, Brunei,
Singapore, the Philippines, East Timor, and Malaysia. Leaves are 10–12 cm long,
from ovate-lanceolate to obovate; upper surface dark green, shining, under surface
pale-green, shortly pubescent; venation transverse and reticulate with a marginal vein;
taste saltish and acrid. The root is about the size of little finger or less, it has a tough

Fig. 1 Gymnema sylvestre, Plant, Lalithamba, WikimediaCommons; 2.0 Generic CC BY 2.0,

https://commons.wikimedia.org/wiki/File:Gymnema_sylvestre_R.Br_-_Flickr_-_lalithamba.jpg;
https://creativecommons.org/licenses/by/2.0/deed.en
Gymnema sylvestre R. Br. 983

wood, and when fresh a soft spongy bark, which is reddish-brown and fissured
longitudinally; but loses much bulk in drying and becomes loose and transversely
fissured. The root taste is acrid and saltish; the whole plant abounds in milky juice
(Fig. 1).XL
Actions and Uses: Sushruta (6th century B.C.) described the plant as destroyer of
madhumeha (glycosuria) and other urinary disorders [44]. The herb has been used in
Ayurveda of India for 2000 years for the treatment of diabetes, arthritis, anemia,
osteoporosis, asthma, hypercholesterolemia, cardiopathy, constipation, microbial
infections, indigestion, inflammation, and as diuretic [13, 28, 56], ulcer, hepatopathy,
dyspepsia, eyes pain and in snakebite [13, 28], for family planning, and in the form of
Gymnema tea to control obesity [13]. Dymock et al.XL mentioned its repute amongst
Hindu physicians as a remedy for snakebite, the powdered root being applied to the
bitten part and a decoction administered internally. It is described as pungent in taste,
having properties of an astringent and a bitter stomachic, and used in cough, bil-
iousness, boils, and sore eyes. Hooper tested the observation of Edgeworth that
chewing one or two leaves destroys the taste for sugar immediately, which lasts for
one to two hours. However, it does not affect the taste of pungent saline things,
astringents and acids. This property is limited to only sweets and bitters. It is used as
antiperiodic, stomachic, diuretic, antidiabetic and in urinary disorders.XXI,CV In
Japan, it is widely used as health food and sold in the forms of tea bags, tablets,
beverages and confectioneries [46]. A tea prepared from loose leaves reversibly
impairs the ability to taste sugar by blocking sweet receptors on the tongue, without
altering the perception of other primary tastes. The tea itself tastes slightly bitter, like a
“spinach tea” [40]. The leaves lower blood sugar, stimulate heart [57], uterus, cir-
culatory system [8] and increase urinary output.CIII The roots,CXXIII and leavesLXXXI
are astringent, stomachic tonic and refrigerant, and are used in fever and cough;
externally, the leaves are applied to enlarged liver and spleen, and the powdered root
mixed with castor oil is applied to snake and insect bites.LXXXI
Phytoconstituents: Aqueous leaf extract exhibited the presence of alkaloids, triter-
penes, flavonoids, steroids, and saponins [4]; other bases present are choline, betaine
and adenine (a combined yield of 0.04%). Leucine, isoleucine, valine, alanine and
c-amino-n-butyric acid are the amino acids present in the leaves [51]. Leaves contain
tritepenoid saponins: gymnemic acids (a mixture of triterpene glycosides), gymne-
masaponins, gymnemasides, gymnemosides A–F [24, 65], gymnemoside-W1 and
W2 [68], gymnemasins A–D [37], and others [64, 66], oleanane-type triterpene
glycosides [63], and flavonol glycosides [22]; gymnemic acids and gymnemas-
aponins are oleanane saponins, and gymnemasides are dammarene saponins. Other
compounds isolated from stems include conduritol A, 1-heptadecanol, stigmasterol-
3-O-b-D-glucoside, stigmasterol, 1-quercitol, 1-octadecanol, potassium nitrate,
lupeol, lupeol cinnamate [23, 67], and pregnane glycosides: gymsylvestrosides A–D
[60]. Gymnemic acid content were reported as 2.40% (w/w) in methanol leaf extract
[50]. Leaves also contain flavones, anthraquinones, hentriacontane, pentatriacontane,
a and b-chlorophylls, phytin, quercitol, resins, tartaric acid, formic acid, butyric acid,
lupeol, and b-amyrin related glycosides [9]. Gymnemic acids, gymnemasaponins,
984 Gymnema sylvestre R. Br.

and a polypeptide, gurmarin are credited for its sweet suppression activity [56].
Gymnemic acid also possesses antiobesity property, decreases body weight and
inhibits glucose absorption [30]. Gymnemagenin and gymnestrogenin in the leaves
are the aglycones of gymnemic acids (glycosides) A & B and C & D, respectively [52].
Fifty-five volatile components were isolated from flowers; the principal constituents
were identified as phytol, pentacosane, 10-heneicosene, 3-Eicosene, (E)- and 2-methyl-
Z-2-docosane [33].
Pharmacology: In certain animal experiments and clinical trials there was no reduc-
tion of blood sugar and no effect on urinary sugar [8]. Feeding of dried leaf powder to
normal rats for 25-days did not significantly alter blood glucose [31], but significantly
attenuated serum glucose response to oral administration of glucose [27]; the aqueous
extract, however, significantly reduced blood glucose of normal and diabetic rats [39].
Dried leaf powder, though, reduced blood sugar in diabetic rabbits, and increased
uptake and incorporation of glucose into glycogen and protein in the liver, kidney and
muscle [45]. In mildly diabetic rats a diet supplemented with the leaves showed a
tendency to reduce serum glucose in the fed state and to improve glucose tolerance after
4-weeks of treatment [27]. Aqueous extracts are reported to return FBG to normal in
diabetic rats after 60-days of treatment, with an increase in serum insulin closer to
normal levels, and double the numbers of islet and pancreatic b-cell [42]. Leaf alcohol
extract significantly reduced blood sugar in normal and STZ-diabetic rats [6], and an
aqueous fraction of the alcohol extract failed to alter hepatic glycogen content in nor-
mal rats, but significantly lowered glycogen content in glucose fed rats [7]. The extracts
exhibited hypoglycemic activity without altering serum cortisol concentration [11].
Ethanol leaf extract exhibited the highest hypoglycemic and antihyperglycemic activity
in rats [61], returning blood glucose levels of diabetic rats to normal levels, and
strong in vitro antioxidant [14], and moderate free radical scavenging activities [34].
Six-hours after i.v. administration, gymnemic acid reduced blood glucose levels by
13.5–60%, but did not change blood glucose levels of normal mice; and increased
plasma insulin in STZ-diabetic mice, but did not inhibit a-glycosidase activity in the
brush border membrane of normal rat small intestines [54].
Shigematsu and colleagues [46] reported that daily administration of leaves
hydroalcohol extract to high-fat diet-fed rats for 3-weeks, significantly decreased
serum TC and TGs; however, a following publication reported that 10-weeks
administration of the extract decreased food intake, suppressed body weight gain and
accumulation of liver lipids, without lowering plasma TC [47]. Water soluble fraction
of ethanol extract for 21-days to obese rats and to diabetic obese rats significantly
reduced serum lipids, leptin, insulin, glucose, apolipoprotein B and LDH levels, and
significantly increased HDL-C, apolipoprotein A1 and antioxidant enzymes [18, 20].
The saponin-rich fraction of the aqueous leaf extract orally administered daily to
normal and high-fat diet-induced obese rats for eight-weeks significantly decreased
food consumption, body weight, and levels of TGs, TC, LDL, VLDL, glucose,
and increased the levels of HDL-C [19, 36]; similar result were reported for
methanol extract [15]. Addition of G. sylvestre to sucrose-containing diet of SHRs
also decreased circulating cholesterol concentrations [32]. Pretreatment of rats with
Gymnema sylvestre R. Br. 985

ethanol leaf extract protected against gastric mucosal damage [3], and acetic acid-
induced ulcerative colitis [2]; the aqueous extract also showed antigastric ulcer
effect [4].
Ethanol leaf extract was active against S. aureus, B. pumilis, B. subtilis, and
P. aeruginosa, and inactive against P. vulgaris and E. coli [38], while Selvi et al. [41],
reported both aqueous and ethanol extracts moderately active against S. aureus,
B. subtilis, S. typhi, K. pneumoniae, E. coli, P. vulgaris, and Pseudomonas. Ethanol
extract also exhibited significant antitumor-promoting activity in two-stage skin
carcinogenesis [62].
Clinical Studies: A water-soluble leaf extract administered to 27 Indian patients
with insulin-dependent diabetes on insulin therapy, brought down required dose of
insulin and lowered FBG, HbA1c and glycosylated plasma protein levels, and
returned serum lipids to near normal levels [43]; the same extract supplemented
with oral antidiabetic drugs in 22 type-2 diabetic patients produced similar results
and about a quarter of patients completely stopped their conventional drugs after
18–20 months [5]. In another open label study, Indian patients with type-2 diabetes
were supplemented with 500 mg of the herb daily for 3-months; it reduced
polyphagia, fatigue, FBG, HbA1c and favorably shifted the lipid profile [17].
A study conducted by Beijing University in Pakistani patients with type-2 diabetes
reported a reduction of 37% in blood glucose, 13% in TC, 19% in LDL-C and 5%
in TGs, after 30-days treatment with the powdered herb 1 g/day [21]. The tea also
exhibited antioxidant activity in healthy human volunteers [26].
Mechanism of Action: The hypoglycemic effect has been attributed to reduced
intestinal glucose uptake [48] and increased insulin release from b-cells [5]. Anti-
sweet properties of Gymnema have been attributed to a variety of compounds
including the triterpene glycoside, gymnemic acid and a 35-amino acid polypeptide
(reviewed by Suttisri et al. [55]). Gymnemoside B and gymnemic acids III, V, and
VII slightly inhibit glucose absorption, but gymnemic acid I and gymnemasaponin
V, completely lack this activity [65]. Gymnemic acid inhibits intestinal absorption of
glucose in humans and rats, and also potently inhibits absorption of oleic acid in
intestine of rats [58]. Alcohol extract stimulates in vitro insulin release from pan-
creatic b-cell lines and from rat islets of Langerhans in the absence of any other
stimulus [29]. Pretreatment with the extract restores the area occupied by
b-endocrinocytes in the pancreatic islets of diabetic rats [53]. The extract also
possesses potent dipeptidyl peptidase-4 (DPP-4) inhibitory action, and the hypo-
glycemic action is attributed through an increase in plasma active glucagon-like
peptide-1 (GLP-1) levels [16]. Gymnemic acids show by far the strongest
sodium-dependent glucose transporter 1 (SGLT1) inhibitory effect; SGLT1 is found
in high levels in brush-border membranes of intestinal epithelial cells [59].
Glucose-induced increase in the portal gastric inhibitory peptide (GIP) is also sig-
nificantly depressed by concomitantly infused leaf extract and purified gymnemic
acid [10]. Methanol leaf extract also produced antidiabetic activity through regen-
erating b-cells [1].
986 Gymnema sylvestre R. Br.

Human A/Es, Allergy and Toxicity: Only one rare case of drug-induced liver
injury in an Israeli patient treated with G. sylvestre for diabetes mellitus has been
reported [49].
Animal Toxicity: A mean daily intake of >500 mg of leaf extract to rats for
52-weeks was nontoxic [25].
CYP450 and Potential for Drug-Herb Interactions: Concomitant oral admin-
istration of the herb extract with glimepiride in diabetic rats for 28-days did not
show any alterations in the pharmacokinetics of glimepiride except a synergistic
hypoglycemic effect [12]. Ethyl acetate and chloroform extracts moderately inhibit
CYP1A2 and CYP3A4, while the aqueous extract has negligible inhibitory activity
toward CYP450s [35].
Commentary: This drug has been used in Ayurveda for thousands of years as an
antidiabetic drug, usually in powdered or water extract form. However, all formal
clinical trials have been conducted in Indian or Pakistani patients, which necessitates
that more widespread studies in patients of various ethnicity and cultural back-
grounds be conducted to establish its antidiabetic effects across ethnicities. Clinical
studies could be expanded to include other effects observed in animal studies.

References
1. Ahmed AB, Rao AS, Rao MV. In vitro callus and in vivo leaf extract of
Gymnema sylvestre stimulate b-cells regeneration and antidiabetic activity
in Wistar rats. Phytomedicine. 2010;17:1033–9.
2. Aleisa AM, Al-Rejaie SS, Abuohashish HM, et al. Pretreatment of Gymnema
sylvestre revealed the protection against acetic acid-induced ulcerative colitis
in rats. BMC Complement Altern Med. 2014;14:49.
3. Al-Rejaie SS, Abuohashish HM, Ahmed MM, et al. Possible biochemical
effects following inhibition of ethanol-induced gastric mucosa damage
by Gymnema sylvestre in male Wistar albino rats. Pharm Biol. 2012;50:
1542–50.
4. Arun LB, Arunachalam AM, Arunachalam KD, Annamalai SK, Kumar KA.
In vivo antiulcer, antistress, antiallergic, and functional properties of gymne-
mic acid isolated from Gymnema sylvestre R Br. BMC Complement Altern
Med. 2014;14:70.
5. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmuga-
sundaram ER. Antidiabetic effect of a leaf extract from Gymnema sylvestre in
noninsulin-dependent diabetes mellitus patients. J Ethnopharmacol. 1990;30:
295–300.
6. Chattopadhyay RR. A comparative evaluation of some blood sugar
lowering agents of plant origin. J Ethnopharmacol. 1999;67:367–72.
7. Chattopadhyay RR. Possible mechanism of antihyperglycemic effect of
Gymnema sylvestre leaf extract, part I. Gen Pharmacol. 1998;31:495–6.
Gymnema sylvestre R. Br. 987

8. Chopra RN, Bose JP, Chatterjee NR. Gymnema sylvestre in diabetes

mellitus. Indian J Med Res. 1928;16:115–20.
9. Dateo GP, Long L. Gymnemic acid, the antisaccharine principle of
Gymnema sylvestre. Studies on isolation and heterogenesity of gymnemic
acid A1. J Agric Food Chem. 1973;21:899–903.
10. Fushiki T, Kojima A, Imoto T, et al. An extract of Gymnema sylvestre
leaves and purified gymnemic acid inhibits glucose-stimulated gastric
inhibitory peptide secretion in rats. J Nutr. 1992;122:2367–73.
11. Gholap S, Kar A. Hypoglycaemic effects of some plant extracts are possibly
mediated through inhibition in corticosteroid concentration. Pharmazie.
2004;59:876–8.
12. Kamble B, Gupta A, Moothedath I, et al. Effects of Gymnema sylvestre ex-
tract on the pharmacokinetics and pharmacodynamics of glimepiride in
streptozotocin induced diabetic rats. Chem Biol Interact. 2016;245:30–8.
13. Kanetkar P, Singhal R, Kamat M. Gymnema sylvestre: a memoir. J Clin
Biochem Nutr. 2007;41:77–81.
14. Kang MH, Lee MS, Choi MK, et al. Hypoglycemic activity of Gymnema
sylvestre extracts on oxidative stress and antioxidant status in diabetic rats.
J Agric Food Chem. 2012;60:2517–24.
15. Kim HJ, Hong SH, Chang SH, et al. Effects of feeding a diet containing
Gymnema sylvestre extract: attenuating progression of obesity in C57BL/6J
mice. Asian Pac J Trop Med. 2016;9:437–44.
16. Kosaraju J, Dubala A, Chinni S, et al. A molecular connection of
Pterocarpus marsupium, Eugenia jambolana and Gymnema sylvestre with
dipeptidyl peptidase-4 in the treatment of diabetes. Pharm Biol. 2014;52:
268–71.
17. Kumar SN, Mani UV, Mani I. An open label study on the supplementation
of Gymnema sylvestre in type 2 diabetics. J Diet Suppl. 2010;7:273–82.
18. Kumar V, Bhandari U, Tripathi CD, Khanna G. Antiobesity effect of
Gymnema sylvestre extract on high fat diet-induced obesity in Wistar rats.
Drug Res (Stuttg). 2013;63:625–32.
19. Kumar V, Bhandari U, Tripathi CD, Khanna G. Evaluation of antiobesity
and cardioprotective effect of Gymnema sylvestre extract in murine model.
Indian J Pharmacol. 2012;44:607–13.
20. Kumar V, Bhandari U, Tripathi CD, Khanna G. Protective effect of Gym-
nema sylvestre ethanol extract on high fat diet-induced obese diabetic Wistar
rats. Indian J Pharm Sci. 2014;76:315–22.
21. Li Y, Zheng M, Zhai X, et al. Effect of Gymnema sylvestre, Citrullus
colocynthis and Artemisia absinthium on blood glucose and lipid profile in
diabetic human. Acta Pol Pharm. 2015;72:981–5.
22. Liu X, Ye W, Yu B, et al. Two new flavonol glycosides from Gymnema
sylvestre and Euphorbia ebracteolata. Carbohydr Res. 2004;339:891–5.
23. Liu Y, Xu TH, Zhang MQ, et al. Chemical constituents from the stems of
Gymnema sylvestre. Chin J Nat Med. 2014;12:300–4.
988 Gymnema sylvestre R. Br.

24. Murakami N, Murakami T, Kadoya M, et al. New hypoglycemic constituents

in “gymnemic acid” from Gymnema sylvestre. Chem Pharm Bull (Tokyo).
1996;44:469–71.
25. Ogawa Y, Sekita K, Umemura T, et al. Gymnema sylvestre leaf extract: a
52-week dietary toxicity study in Wistar rats. Shokuhin Eiseigaku Zasshi.
2004;45:8–18 (Japanese).
26. Ohmori R, Iwamoto T, Tago M, et al. Antioxidant activity of various teas
against free radicals and LDL oxidation. Lipids. 2005;40:849–53.
27. Okabayashi Y, Tani S, Fujisawa T, et al. Effect of Gymnema sylvestre, R.Br.
on glucose homeostasis in rats. Diabetes Res Clin Pract. 1990;9:143–8.
28. Pandey AK, Yadav S. Variation in gymnemic acid content and nondestructive
harvesting of Gymnema sylvestre (Gudmar). Pharmacognosy Res. 2010;2:
309–12.
29. Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates
insulin release in vitro by increased membrane permeability. J Endocrinol.
1999;163:207–12.
30. Pothuraju R, Sharma RK, Chagalamarri J, Jangra S, Kumar Kavadi P. A sys-
tematic review of Gymnema sylvestre in obesity and diabetes management.
J Sci Food Agric. 2014;94:834–40.
31. Prakash AO, Mathur S, Mathur R. Effect of feeding Gymnema sylvestre
leaves on blood glucose in beryllium nitrate treated rats. J Ethnopharmacol.
1986;18:143–6.
32. Preuss HG, Jarrell ST, Scheckenbach R, et al. Comparative effects of
chromium, vanadium and Gymnema sylvestre on sugar-induced blood
pressure elevations in SHR. J Am Coll Nutr. 1998;17:116–23.
33. Qiu Q, Zhen HS, Huang PQ. Study on volatile components from flowers of
Gymnema sylvestre (Article in Chinese). Zhong Yao Cai. 2013;36:575–7.
34. Rahman MM, Habib MR, Hasan MA, et al. Comparative assessment on in vitro
antioxidant activities of ethanol extracts of Averrhoa bilimbi, Gymnema
sylvestre and Capsicum frutescens. Pharmacognosy Res. 2014;6:36–41.
35. Rammohan B, Samit K, Chinmoy D, et al. Human Cytochrome P450
enzyme modulation by Gymnema sylvestre: a predictive safety evaluation
by LC-MS/MS. Pharmacogn Mag. 2016;12 Suppl 4:S389–94.
36. Reddy RM, Latha PB, Vijaya T, Rao DS. The saponin-rich fraction of a
Gymnema sylvestre R. Br. aqueous leaf extract reduces cafeteria and
high-fat diet-induced obesity. Z Naturforsch C. 2012;67:39–46.
37. Sahu NP, Mahato SB, Sarkar SK, Poddar G. Triterpenoid saponins from
Gymnema sylvestre. Phytochemistry. 1996;41:1181–5.
38. Satdive RK, Abhilash P, Fulzele DP. Antimicrobial activity of Gymnema
sylvestre leaf extract. Fitoterapia. 2003;74:699–701.
39. Sathya S, Kokilavani R, Gurusamy K. Hypoglycemic effect of Gymnema
sylvestre (Retz.) R. Br. leaf in normal and alloxan induced diabetic rats. Anc
Sci Life. 2008;28:12–4.
Gymnema sylvestre R. Br. 989

40. Schroeder JA, Flannery-Schroeder E. Use of the herb Gymnema sylvestre to

illustrate the principles of gustatory sensation: an undergraduate neuro-
science laboratory exercise. J Undergrad Neurosci Educ. 2005;3:A59–62.
41. Selvi S, Devi PU, Chinnaswamy P, et al. Antibacterial efficacy and
phytochemical observation of some Indian medicinal plants. Anc Sci Life.
2007;26:16–22.
42. Shanmugasundaram ER, Gopinath KL, Radha SK, Rajendran VM. Possible
regeneration of the islets of Langerhans in streptozotocin-diabetic rats given
Gymnema sylvestre leaf extracts. J Ethnopharmacol. 1990;30:265–79.
43. Shanmugasundaram ER, Rajeswari G, Baskaran K, et al. Use of Gymnema
sylvestre leaf extract in the control of blood glucose in insulin-dependent
diabetes mellitus. J Ethnopharmacol. 1990;30:281–94.
44. Shanmugasundaram ERB, Venkatasubramanyam M, Vijendran N, Radha SK.
Effect of an isolate from Gymnema sylvestre, R. Br. in the control of diabetes
mellitus and the associated pathological changes. Ancient Sci Life. 1988;6:
183–94.
45. Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasun-
daram ER. Enzyme changes and glucose utilisation in diabetic rabbits: the
effect of Gymnema sylvestre, R.Br. J Ethnopharmacol. 1983;7:205–34.
46. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Effect of administration
with the extract of Gymnema sylvestre R. Br leaves on lipid metabolism in
rats. Biol Pharm Bull. 2001;24:713–7.
47. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Effect of long-term-
administration with Gymnema sylvestre R. BR on plasma and liver lipid in
rats. Biol Pharm Bull. 2001;24:643–9.
48. Shimizu K, Iino A, Nakajima J, et al. Suppression of glucose absorption by
some fractions extracted from Gymnema sylvestre leaves. J Vet Med Sci.
1997;59:245–51.
49. Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema
sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci.
2010;340:514–7.
50. Singh VK, Dwivedi P, Chaudhary BR, Singh R. Immunomodulatory effect
of Gymnema sylvestre (R.Br.) leaf extract: an in vitro study in rat model.
PLoS One. 2015;10: e0139631.
51. Sinsheimer JE, McIlhenny HM. Constituents from Gymnema sylvestre
leaves II. J Pharm Sci. 1967;56:732–6.
52. Sinsheimer JE, Rao GS. Constituents from Gymnema sylvestre leaves. VI.
Acylated genins of the gymnemic acids—isolated and preliminary charac-
terization. J Pharm Sci. 1970;59:629–32.
53. Snigur GL, Samokhina MP, Pisarev VB, Spasov AA, Bulanov AE. Structural
alterations in pancreatic islets in streptozotocin-induced diabetic rats treated
with of bioactive additive on the basis of Gymnema sylvestre. Morfologiia.
2008;133:60–4 (Russian).
990 Gymnema sylvestre R. Br.

54. Sugihara Y, Nojima H, Matsuda H, et al. Antihyperglycemic effects of

gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in
streptozotocin-diabetic mice. J Asian Nat Prod Res. 2000;2:321–7.
55. Suttisri R, Lee IS, Kinghorn AD. Plant-derived triterpenoid sweetness
inhibitors. J Ethnopharmacol. 1995;47:9–26.
56. Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological
properties of Gymnema sylvestre: an important medicinal plant. Biomed Res
Int. 2014;2014:830285.
57. Wahi SP, Chunekar KC. Pharmacological studies of Gymnema sylvestre R.
Br. J Sci Res. 1964;15:205–10.
58. Wang LF, Luo H, Miyoshi M, et al. Inhibitory effect of gymnemic acid on
intestinal absorption of oleic acid in rats. Can J Physiol Pharmacol. 1998;76:
1017–23.
59. Wang Y, Dawid C, Kottra G, Daniel H, Hofmann T. Gymnemic acids
inhibit sodium-dependent glucose transporter 1. J Agric Food Chem. 2014;
62:5925–31.
60. Xu R, Yang Y, Zhang Y, et al. New pregnane glycosides from Gymnema
sylvestre. Molecules. 2015;20:3050–66.
61. Yadav M, Lavania A, Tomar R, et al. Complementary and comparative study
on hypoglycemic and antihyperglycemic activity of various extracts of
Eugenia jambolana seed, Momordica charantia fruits, Gymnema sylvestre,
and Trigonella foenum graecum seeds in rats. Appl Biochem Biotechnol.
2010;160:2388–400.
62. Yasukawa K, Okuda S, Nobushi Y. Inhibitory effects of Gymnema
(Gymnema sylvestre) leaves on tumour promotion in two-stage mouse skin
carcinogenesis. Evid Based Complement Alternat Med. 2014;2014:328684.
63. Ye W, Liu X, Zhang Q, et al. Antisweet saponins from Gymnema sylvestre.
J Nat Prod. 2001;64:232–5.
64. Ye WC, Zhang QW, Liu X, Che CT, Zhao SX. Oleanane saponins from
Gymnema sylvestre. Phytochemistry. 2000;53:893–9.
65. Yoshikawa M, Murakami T, Kadoya M, et al.. Medicinal foodstuffs. IX.
The inhibitors of glucose absorption from the leaves of Gymnema sylvestre
R. BR. (Asclepiadaceae): structures of gymnemosides a and b. Chem Pharm
Bull (Tokyo). 1997;45:1671–6.
66. Zhang MQ, Liu Y, Xie SX, et al. A new triterpenoid saponin from Gym-
nema sylvestre. J Asian Nat Prod Res. 2012;14:1186–90.
67. Zhen HS, Zhu XY, Lu RM et al. Research on chemical constituents from
stem of Gymnema sylvestre. Zhong Yao Cai. 2008;31:1154–6 (Chinese).
68. Zhu XM, Xie P, Di YT, et al. Two new triterpenoid saponins from
Gymnema sylvestre. J Integr Plant Biol. 2008;50:589–92.
Helleborus niger L.
(Ranunculaceae)

Abstract
It is an evergreen plant, found in Europe and hilly ghats of India. It excretes
phlegm and yellow bile, and is beneficial in epilepsy, melancholy, insanity,
arthritis, and paralysis, and as a douche is emmenagogue and kills the fetus
(abortifacient). It is a drastic hydragogue cathartic, cardiotonic, diuretic,
mydriatic, narcotic, nervine, poison, rodenticide and vermifuge; in large toxic
doses, it causes gradual paralysis of the heart, convulsions and death. It has been
used as a purgative in mania (1400 B.C.), and root, root-bark or seeds have been
used for cancer or indurations, especially of the spleen, ulcers and warts. In
combination with Holarrhena antidysenterica seeds, it is used for the treatment
of amenorrhea, melancholia, mania, insanity, worms, dropsies and skin diseases.
Externally, with vinegar or alone, it cures eczema, wet itching and Bahaq. It
contains two poisonous glucosides, helleborin and helleborein, resin, fat,
saponin, starch, and hellebrin. Main constituent, helleborein acts like digitalis,
increasing cardiac contractility and slowing heart rate; and was used as a
substitute for digitalis. Aqueous whole plant extract strongly inhibits prolifer-
ation of different cancer and leukemia cell lines by inducing apoptosis. Other
extracts also induced apoptosis and inhibited proliferation of lymphoblastic
leukemia cells, myosarcoma and melanoma cells.

Keywords




Black hellebore Čemeřice černá Christrose Elabro nero
Hereborusu






Julros Kali kutki Katurohini Kerstroos Kharbaq aswad

Vernaculars: Urd.: Kali kutki, Kharbaq siah; Hin.: Khorasani-kutki, Kutki, Kudu;
San.: Kataka-rohani, Katurohini, Katuruni, Krishnabhedi, Vakragra; Ben.: Kala kutki;
Mal.: Katukarohini; Mar.: Bala-kadu, Kutki; Tam.: Kadagaruganie, Kataka-rohani;
Tel.: Katukarohini; Ara.: Kharbaq aswad, Khartik, Kuerbeek; Cze.: Čemeřice
černá; Dan.: Almindelig julerose, Hvid julerose; Dut.: Kerstroos, Zwarte nieswortel;
© Springer Nature Switzerland AG 2020 991
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_105
992 Helleborus niger L.

Eng.: Black hellebore, Christmas rose; Fin.: Vaaleajouluruusu; Fre.: Ellébore noir,
Hellébore noir, Rose de noël; Ger.: Christblume, Christrose, Schneerose, Schwarze
nieswurz; Hun.: Fekete hunyor; Ita.: Elabro nero, Elleboro bianco, Elleboro nero, Rosa
di natale; Jap.: Hereborusu, Kurisumasu-rôzu, Renten-rôzu; Nor.: Julerose; Per.:
Kharbaq-e-hindi; Pol.: Ciemiernik biały, Ciemiernik czarny; Swe.: Julros, Svart
prustrot.
Description: It is an evergreen plant, 25–30 cm tall, with dark leathery leaves, and
found in Europe and hilly ghats of India. Roots are black, knotty, resembling a
goose quill, smooth, very fragile, slightly shriveled and marked with scars of fallen
rootlets; taste somewhat acrid and very bitter.LXXXI In Unani medicine, both
Picrorhiza kurroa and Helliborus niger were described as Kali Kutki (black Kutki)
and Gentiana kurroo as Kutki or Safed Kutki (white Kutki). However, Dymock
et al.XL have disputed the description of black Hellebore as Kutki and they quoted
Ainslie who said that the drug available in Indian bazaars was very different in
appearance from the black Hellebore available in European markets. Later, Muslim
writers and others confirmed kutki as being the rhizome of P. kurroa. Therefore,
description of kutki in some Unani books as Helliborus niger seems to be incorrect.
However, all description and studies presented here are for H. niger (Figs. 1 and 2).

Fig. 1 Helleborus niger, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von Deutschland,
Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://commons.
wikimedia.org/wiki/File:Illustration_Helleborus_niger0.jpg
Helleborus niger L. 993

Fig. 2 Helleborus niger, Leaves and Flowers, 3268zauber, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Christrose_im_Februar.JPG

Actions and Uses: It excretes phlegm and yellow bile, and is beneficial in epilepsy,
melancholy, insanity, arthritis, and paralysis, and as a douche is emmenagogue and
kills the fetus (abortifacient) [7]. It is a drastic hydragogue cathartic, cardiotonic,
diuretic, mydriatic, narcotic, nervine, poison, rodenticide and vermifuge; in large
toxic doses, it causes gradual paralysis of the heart, convulsions and death.XXXVIII,CV
In Unani medicine, rhizomes (temperament, hot 3° and dry 3°) are considered
stomachic, carminative, anthelmintic, and laxative; purgative in high doses; used to
strengthen stomach function in cases of indigestion, in ascites due to hepatic
involvement, to kill and expel intestinal worms, and especially useful for brain
ailments.L,LXXVII Externally, with vinegar or alone, it cures eczema, wet itching and
Bahaq.LXIX In combination with Holarrhena antidysenterica seeds, it is used for the
treatment of amenorrhea, melancholia, mania, insanity, worms, dropsies and skin
diseases.LXXXI It has been used as a purgative in mania (1400 B.C.), and root,
root-bark or seeds have been used for cancer or indurations, especially of the spleen,
ulcers and warts [3]. Extracts of Helleborus species are used with immunostimulatory
properties in the treatment of rheumatoid arthritis or viral infections in Romanian
traditional medicine [1, 8]. In homeopathy, it is used for meningitis, encephalitis,
nephritis, epilepsy, hydrocephaly, psychosis, melancholy, collapse, cardiac insuffi-
ciency, dementia praecox (schizophrenia),LV,XC and as an adjuvant therapy in the
treatment of various types of brain tumors in children, as well as prostate cancer,
leukemia and lymphoma in anthroposophical medicine [1, 4].
Phytoconstituents: It contains two poisonous glucosides, helleborin and hellebor-
ein,LV resin, fat, saponin, starch, and hellebrin.XC Ranuncoside [5, 6], phenolic
glucoside derivative and two flavonoid glycosides [9], quercetin and kaempferol
oligoglycosides, protoanemonin and its precursor ranunculin, b-ecdysone, the
sapogenins, sarsasapogenyl, diosgenyl, and macranthogenyl have been reported from
994 Helleborus niger L.

the leaves and stems [2]. Main constituent, helleborein acts like digitalis, increasing
cardiac contractility and slowing heart rate; and was used as a substitute for
digitalis.LXXXI
Pharmacology: Aqueous whole plant extract strongly inhibits proliferation of dif-
ferent cancer and leukemia cell lines by inducing apoptosis [4]. Other extracts
also induced apoptosis and inhibited proliferation of lymphoblastic leukemia cells,
myosarcoma and melanoma cells [8].
Human A/Es, Allergy and Toxicity: Leaves are photosensitizers;CXXXV inter-
nally, it is violently narcotic, and applied locally the fresh root is severely irritant.LV
The plant has been considered poisonous by all major authors from Dioscorides to
the 20th century physicians. The purgative glycoside principles, upon ingestion
may produce gastric distress and other effects; secondary nervous effects may also
be observed.LXXXIII In toxic doses, it is a violent gastrointestinal irritant, causing
vomiting, purging, vertigo, cramps and convulsions, often ending in death.LXXXI
Others have described the main symptoms of toxicity as dry or scratchy throat
and mouth, salivation, nausea, stomachache, vomiting, colic, diarrhea, irregular slow
pulse, dyspnea, vertigo, ringing ears, mydriasis, disturbed vision, excitement in fatal
doses, coronary arrest and collapse.XXXVIII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This plant has not been studied pharmacologically and clinically in
a formal way, probably due to its toxicity. However, it is commonly used in Indian
traditional medicines.

References
1. Büssing A, Schweizer K. Effects of a phytopreparation from Helleborus niger
on immunocompetent cells in vitro. J Ethnopharmacol. 1998;59:139–46.
2. Duckstein SM, Stintzing FC. Comprehensive study of the phenolics and
saponins from Helleborus niger L. leaves and stems by liquid chromatography/
tandem mass spectrometry. Chem Biodivers. 2014;11:276–98.
3. Hartwell JL. Plants used against cancer. A survey. Lloydia. 1969–71;32–34.
4. Jesse P, Mottke G, Eberle J, et al. Apoptosis-inducing activity of Helleborus
niger in ALL and AML. Pediatr Blood Cancer. 2009;52:464–9.
5. Martinek A. Quantitative determination of a new glycoside from Helleborus
niger. Planta Med. 1974;25:376–84.
Helleborus niger L. 995

6. Martinek A. Ranuncoside in dried stems, leaves and flowers of Helleborus

niger. Planta Med. 1974;26:218–24 (Eng. Abstr.).
7. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
8. Schink M, Garcia-Käufer M, Bertrams J, et al. Differential cytotoxic prop-
erties of Helleborus niger L. on tumour and immunocompetent cells.
J Ethnopharmacol. 2015;159:129–36.
9. Vitalini S, Braca A, Fico G. Study on secondary metabolite content of
Helleborus niger L. leaves. Fitoterapia. 2011;82:152–4.
Hemidesmus indicus (L.) R. Br.
(Apocynaceae)

(Syn.: Periploca indica L.)

Abstract
It is a slender, twining, sometimes prostrate or semi-erect shrub. Root is used to
treat a wide variety of illnesses, including rheumatism, leprosy, impotence,
urinary tract and skin infections, and is traditionally used by herbal practitioners
for the treatment of snakebite in Tamil Nadu state of India. Muslim physicians
of India called the Andalusian as the best Ushbah. It was found to have
remarkable diuretic action; it also acts as a diaphoretic and tonic, and increases
appetite. In Ayurveda, it is considered demulcent, alterative, and tonic, and is
prescribed in dyspepsia, skin diseases, syphilis, fever and dysentery, generally
in combination with bitters and aromatics. It contains tannins, saponins, flavo-
noids, glycosides, phenolic compounds, carbohydrates, proteins, and fragrant
phenolic compounds, 2-hydroxy-4-methoxybenzaldehyde (HMBA) and 4-
hydroxy-3-methoxybenzaldehyde (vanillin). Vanillin is an efficient in vitro
inhibitor of AChE, and HMBA is the major compound (>90%) of the root
volatile oil. Aqueous root extract significantly decreased blood glucose in fed,
fasted and glucose-loaded diabetic rats, and normalized electrolytes, glucose
metabolizing enzymes, and corrected related metabolic alterations. b-amyrin
palmitate was identified as the active antidiabetic constituent. Ethanol root
extract also significantly decreased blood glucose, serum TC, TGs, FFAs and
phospholipid of diabetic rats after four-weeks treatment. Root powder was
protective against gentamicin-nephrotoxicity, and the aqueous extract pro-
tected against cisplatin- and bromobenzene-nephrotoxicity in rats. HMBA was
suggested to be the active principle for hypolipidemic effect.

Keywords




Anantamul Anslabatunnar Indian sarsaparilla Periploea des Indes
Salsa





Sarsaparillwurzel Sugandhi Upercao Ushbah Yasmine barri

© Springer Nature Switzerland AG 2020 997

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_106
998 Hemidesmus indicus (L.) R. Br.

Vernaculars: Urd.: Salsa, Ushbah; Hin.: Anantamul, Kalisar, Kapuri, Magrabu,

Salsa; San.: Ananta, Ananthamoola, Gopa-kanga, Gopasuta, Gopimulam, Kshirini,
Nagajihva, Sariva, Shariva, Sugandhi, Utpala-sariva; Ben.: Anantamul; Guj.: Anan-
tamul, Upalsaari; Mal.: Nannari-kizhanna, Narsoninti; Mar.: Anantavel, Dudha-sali,
Gopa-kanga, Upalsari, Upersara; Tam.: Kizhanna, Nannari, Naru-ninti, Sugan-
thipaalaa; Tel.: Gadi sugandhi, Pala sugandhi, Sugandhipala; Ara.: Anslabatunnar,
Ausaba lunnara, Zaiyana; Eng.: Country sarsaparilla, Indian sarsaparilla; Fre.: Peri-
ploea des Indes, Recine de salsepareille; Ger.: Hemidesmus wurzel, Sarsaparillwurzel;
Per.: Aushbahe-hindi, Ushbah-e-hindi, Yasmine barri; Por.: Upercao.
Description: It is a slender, twining, sometimes prostrate or semi-erect shrub. Root
is cylindrical, tortuous, woody and aromatic, 5–18 mm in diameter, seldom bran-
ched. Bark is transversely cracked and fissured longitudinally, of a reddish-brown
or dark brown color, sometimes with a slight violet hue when viewed in a strong
light; the wood is yellow and porous. Fresh or freshly-dried roots have a fine odor
of tonka bean or melilot, and a sweet but slightly acrid taste (Figs. 1 and 2).XL
Actions and Uses: In Ayurveda, it is considered demulcent, alterative, and tonic,
and is prescribed in dyspepsia, skin diseases, syphilis, fever and dysentery, gen-
erally in combination with bitters and aromatics. Its milky juice is dropped into
inflamed eyes; it causes copious lacrimation and afterward a cooling sensation.
Roots wrapped in plantain leaves and roasted in hot ashes are pounded into a mass
with cumin and sugar, and administered with ghee (purified butter) as a remedy for
heat or inflammation of urinary passages. Muslim physicians of India called the
Andalusian as the best Ushbah. It was found to have remarkable diuretic action;
two ounces (*60 g) infused in a pint (*500 ml) of hot water was the quantity
employed daily in divided doses, which would increase micturition three to
four-fold. It also acts as a diaphoretic and tonic, and increases appetite.XL As an
alterative, it is used in chronic rheumatism, skin diseases, scrofula, syphilis,
cachexia, and constitutional debility. Infusion with onion and coconut oil is used in

Fig. 1 Hemidesmus indicus, Plant, Shyamal, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Hemidesmus_scandens.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Hemidesmus indicus (L.) R. Br. 999

Fig. 2 Hemidesmus indicus, Inflorescence, Vinayaraj, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Hemidesmus_indicus_at_
Peravoor.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

piles;LXXXI other uses include dyspepsia, anorexia, nutritional disorders, fever, and
ulceration, especially those of syphilitic origin, constitutional syphilis and leucor-
rhea.CV In Unani medicine, it (temperament, hot 3° and dry 3°) is regarded as
anti-inflammatory, diaphoretic, diuretic, and blood purifier, and is used in cold and
moist diseases, such as paralysis, facial palsy, sciatica, dyspnea, liver obstruction,
ascitis, and arthritis. It is considered especially useful for syphilis and leprosy [22].
Root is used to treat a wide variety of illnesses, including rheumatism, leprosy,
impotence, urinary tract and skin infections [13], and is traditionally used by herbal
practitioners for the treatment of snakebite in Tamil Nadu state of India [36].
Phytoconstituents: Yield of aqueous root extract is reported to be 3.7% [18], and
it contains tannins, saponins, flavonoids, glycosides, phenolic compounds, carbo-
hydrates, proteins [17], and fragrant phenolic compounds, 2-hydroxy-4-methoxy-
benzaldehyde (HMBA) and 4-hydroxy-3-methoxybenzaldehyde (vanillin); vanillin
is an efficient in vitro inhibitor of AChE [24]. HMBA is the major compound
(>90%) of the root volatile oil [27]. Pregnane oligoglycosides (medidesmine,
hemisine and desmisine) [14], pregnane glycosides (denicunine, heminine) [46],
hindicusine [45] from dried stems, and six pentacyclic triterpenes [34], one con-
densed phenylpropanoid glucoside and three pregnenolone glycosides, named
hemidesmosides A–C, and plocoside A [54] have been isolated from the roots.
Pharmacology: Ethanol root extract exhibited antinociceptive effect, and blocked
both the neurogenic and inflammatory pain [52]. Ethanol extract also suppressed
both cell-mediated and humoral components of immune system [8]. Hydroalcoholic
extract demonstrated anti-inflammatory activity in rats [53], comparable to anti-
arthritic activity of methotrexate [26]. Anti-inflammatory activity was also evident
from the suppression of P. acnes-induced ROS and proinflammatory cytokines
formation, the two important inflammatory mediators [20].
1000 Hemidesmus indicus (L.) R. Br.

Aqueous root extract significantly decreased blood glucose in fed, fasted and
glucose-loaded diabetic rats, and normalized electrolytes, glucose metabolizing
enzymes, and corrected related metabolic alterations [18]. b-amyrin palmitate was
identified as the active antidiabetic constituent that lowers blood glucose in both
alloxan- and STZ-induced diabetes [28]. Oral ethanol root extract to diabetic rats for
four-weeks significantly decreased blood glucose, serum TC, TGs, FFAs and phos-
pholipid [47]. Root powder was protective against gentamicin-nephrotoxicity [23],
and the aqueous extract protected against cisplatin- [37] and bromobenzene-
nephrotoxicity in rats [32]. Ethanol root extract also protected against ethanol-
induced oxidative damage to rat kidneys [41] and significantly prevented rifampicin
and isoniazid-hepatotoxicity [30], while methanol extract protected against CCl4-
hepatotoxicity [9], and both ethanol extract and HMBA afforded protection against
ethanol-induced liver injury in rats [38, 40, 42, 43]. HMBA also significantly
decreased lipids and lipoprotein concentrations in ethanol-induced hyperlipidemia in
rats [39]. Ethanol root extract was cardioprotective and significantly restricted the
infarct size in I/R injury of isolated rats’ heart [21, 22]. Aqueous extract also showed
modest in vitro thrombolytic activity [31]. Both aqueous and ethanol extracts sig-
nificantly increased urine output, and markedly increased urinary excretion of Na+ and
K+ [16]; moderate diuretic activity of aqueous extract in rats was first reported by
Gujral et al. [19].
Aqueous extract shows significant antibacterial activity against S. aureus,
K. pneumonia and P. aeruginosa, and exhibits synergism with ampicillin, tetracy-
cline and chloramphenicol [17]. Ethanol extract was active against MRSA, MDR
bacteria, and against ESbetaL-producing MDR enteric bacteria, E. coli and Shigella
[1, 5, 6, 44]. Methanol root extract was potently active against Sh. flexneri [11]. Both
aqueous and methanol leaf extracts were equally active against B. cereus, E. coli, and
Sh. dysenteriae, and methanol extract was also active against S. aureus [29]. Aqueous-
ethanol root extract protected rats against experimental gastric ulcers [4], and
methanol root extract inhibited castor oil-induced diarrhea in rats, probably by inhi-
bition of intestinal motility and bactericidal activity [12]. Methanol root extract
inhibited in vitro LPO and scavenged hydroxyl and superoxide radicals, and inhibited
ADP-induced platelet aggregation [25], and methanol root bark extract potently
scavenged DPPH and superoxide radicals, but moderately scavenged NO radical, and
inhibited LPO of liver homogenate [33]. Ethanol extract is an effective skin chemo-
preventive agent and ameliorates hydroperoxide-induced cutaneous oxidative stress
and tumor promotion [50]. Topical application of the extract significantly inhibited
oxidative stress, reduced LPO and significantly protected against DMBA-induced
cutaneous tumorigenesis in mice [49]. A root decoction demonstrated cytotoxicity
against human hepatoma HepG2 cells [35, 48, 51]. Methanol root extract [2], HMBA
[3], and lupeol acetate [10] possess antiviper venom activity. A purified fraction
provided significant protection to mice against rattlesnake venom, and reversed
changes in serum SOD and lipid peroxidase levels [36]. Aqueous decoction also
showed potent in vitro antiosteoclastic activity without toxic effect on osteogenic
precursors [15].
Hemidesmus indicus (L.) R. Br. 1001

Mechanism of Action: Active principle for hypolipidemic effect was suggested to

be HMBA [39]. One of its mechanisms of action of hypoglycemic effect was also
suggested to be the blockade of glucose absorption from intestine, and b-amyrin
palmitate was identified as the active antidiabetic constituent [28].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Root powder was relatively safe up to 7,000 mg/kg bodyweight
in Swiss albino mice [23]. It does not contain pyrrolizidine alkaloids, but feeding
the plant to rats is reported to have produced hepatic lesions which included central
vein abnormalities [7].
Commentary: There are no formal clinical studies on this widely used plant in Unani
and Ayurveda. In addition to antidiabetic and diuretic activities, various extracts of the
plant have exhibited significant hepato-reno-cardioprotective activities, that could be
further explored, both pharmacologically and clinically.

References
1. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal
plants against ESbetaL-producing multidrug-resistant enteric bacteria.
Microbiol Res. 2007;162:264–75.
2. Alam MI, Auddy B, Gomes A. Isolation, purification and partial charac-
terization of viper venom inhibiting factor from the root extract of the Indian
medicinal plant sarsaparilla (Hemidesmus indicus R. Br.). Toxicon. 1994;
32:1551–7.
3. Alam MI, Gomes A. Viper venom-induced inflammation and inhibition of
free radical formation by pure compound (2-hydroxy-4-methoxy benzoic
acid) isolated and purified from anantamul (Hemidesmus indicus R. Br.)
root extract. Toxicon. 1998;36:207–15.
4. Anoop A, Jegadeesan M. Biochemical studies on the antiulcerogenic potential
of Hemidesmus indicus R.Br. var. indicus. J Ethnopharmacol. 2003;84:
149–56.
5. Aqil F, Ahmad I, Owais M. Evaluation of antimethicillin-resistant Staphy-
lococcus aureus (MRSA) activity and synergy of some bioactive plant
extracts. Biotechnol J. 2006;1:1093–102.
6. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian
medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
7. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies of medicinal
plants of Sri Lanka. Part 14: toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–35.
8. Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of
plant origin. I: preliminary screening. J Ethnopharmacol. 1986;18:133–41.
9. Baheti JR, Goyal RK, Shah GB. Hepatoprotective activity of Hemidesmus
indicus R. Br. in rats. Indian J Exp Biol. 2006;44:399–402.
1002 Hemidesmus indicus (L.) R. Br.

10. Chatterjee I, Chakravarty AK, Gomes A. Daboia russellii and Naja kaouthia
venom neutralization by lupeol acetate isolated from the root extract of Indian
sarsaparilla Hemidesmus indicus R.Br. J Ethnopharmacol. 2006;106:38–43.
11. Das S, Devaraj SN. Antienterobacterial activity of Hemidesmus indicus R.
Br. root extract. Phytother Res. 2006;20:416–21.
12. Das S, Prakash R, Devaraj SN. Antidiarrhoeal effects of methanolic root
extract of Hemidesmus indicus (Indian sarsaparilla)—an in vitro and in vivo
study. Indian J Exp Biol. 2003;41:363–6.
13. Das S, Bisht SS. The bioactive and therapeutic potential of Hemidesmus
indicus R. Br. (Indian Sarsaparilla) root. Phytother Res. 2013;27:791–801.
14. Deepak D, Srivastava S, Khare A. Pregnane glycosides from Hemidesmus
indicus. Phytochemistry. 1997;44:145–51.
15. Di Pompo G, Poli F, Mandrone M et al. Comparative in vitro evaluation of
the antiresorptive activity residing in four Ayurvedic medicinal plants.
Hemidesmus indicus emerges for its potential in the treatment of bone loss
diseases. J Ethnopharmacol. 2014;154:462–70.
16. Gadge NB, Jalalpure SS. Natriuretic and saluretic effects of Hemidesmus
indicus R. Br. root extracts in rats. Indian J Pharmacol. 2011;43:714–7.
17. Gayathri M, Kannabiran K. Antimicrobial activity of Hemidesmus indicus,
Ficus bengalensis and Pterocarpus marsupium Roxb. Indian J Pharm Sci.
2009;71:578–81.
18. Gayathri M, Kannabiran K. Hypoglycemic activity of Hemidesmus indicus
R. Br. on streptozotocin-induced diabetic rats. Int J Diabetes Dev Ctries.
2008;28:6–10.
19. Gujral ML, Saxena PN, Mishra SS. An experimental study of the comparative
activity of indigenous diuretics. J Indian Med Assoc. 1955;25:49.
20. Jain A, Basal E. Inhibition of Propionibacterium acnes-induced mediators
of inflammation by Indian herbs. Phytomedicine. 2003;10:34–8.
21. Khandelwal VK, Balaraman R, Ondrejcáková M, et al. Effect of Hemi-
desmus indicus on ischemia-reperfusion injury in the isolated rat heart.
Pharm Biol. 2010;48:611–4.
22. Khandelwal VK, Balaraman R, Pancza D, Ravingerová T. Hemidesmus
indicus and Hibiscus rosa-sinensis affect ischemia reperfusion injury in isolated
rat hearts. Evid Based Complement Alternat Med. 2011;2011. pii: 802937.
23. Kotnis MS, Patel P, Menon SN, Sane RT. Renoprotective effect of Hemidesmus
indicus, a herbal drug used in gentamicin-induced renal toxicity. Nephrology
(Carlton). 2004;9:142–52.
24. Kundu A, Mitra A. Flavoring extracts of Hemidesmus indicus roots and
Vanilla planifolia pods exhibit in vitro acetylcholinesterase inhibitory
activities. Plant Foods Hum Nutr. 2013;68:247–53.
25. Mary NK, Achuthan CR, Babu BH, Padikkala J. In vitro antioxidant and
antithrombotic activity of Hemidesmus indicus (L.) R.Br. J Ethnopharmacol.
2003;87:187–91.
Hemidesmus indicus (L.) R. Br. 1003

26. Mehta A, Sethiya NK, Mehta C, Shah GB. Antiarthritis activity of roots of
Hemidesmus indicus R.Br. (Anantmul) in rats. Asian Pac J Trop Med.
2012;5:130–5.
27. Nagarajan S, Rao LJ. Determination of 2-hydroxy-4-methoxybenzaldehyde
in roots of Decalepis hamiltonii (Wight & Arn.) and Hemidesmus indicus
R.Br. J AOAC Int. 2003;86:564–7.
28. Nair SA, Sabulal B, Radhika J, Arunkumar R, Subramoniam A. Promising
antidiabetes mellitus activity in rats of b-amyrin palmitate isolated from
Hemidesmus indicus roots. Eur J Pharmacol. 2014;734:77–82.
29. Panda SK, Mohanta YK, Padhi L, et al. Large scale screening of ethnomedicinal
plants for identification of potential antibacterial compounds. Molecules. 2016;
21:293.
30. Prabakan M, Anandan R, Devaki T. Protective effect of Hemidesmus
indicus against rifampicin and isoniazid-induced hepatotoxicity in rats.
Fitoterapia. 2000;71:55–9.
31. Prasad S, Kashyap RS, Deopujari JY, et al. Effect of Fagonia arabica (Dhamasa)
on in vitro thrombolysis. BMC Complement Altern Med. 2007;7:36.
32. Ramakrishna V, Gopi S, Setty OH. Protective effect of Hemidesmus indicus
L. R. Br. against bromobenzene-induced mitochondrial dysfunction in rat
kidney. Am J Chin Med. 2012;40:567–80.
33. Ravishankara MN, Shrivastava N, Padh H, Rajani M. Evaluation of
antioxidant properties of root bark of Hemidesmus indicus R. Br. (Anantmul).
Phytomedicine. 2002;9:153–60.
34. Roy SK, Ali M, Sharma MP, Ramachandram R. New pentacyclic triterpenes
from the roots of Hemidesmus indicus. Pharmazie. 2001;56:244–6.
35. Samarakoon SR, Thabrew I, Galhena PB, Tennekoon KH. Modulation of
apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standard-
ized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots
and Smilax glabra rhizomes with antihepatocarcinogenic effects. BMC
Complement Altern Med. 2012;12:25.
36. Samy RP, Thwin MM, Gopalakrishnakone P, Ignacimuthu S. Ethnobotan-
ical survey of folk plants for the treatment of snakebites in Southern part of
Tamilnadu. India. J Ethnopharmacol. 2008;115:302–12.
37. Sandeep D, Krishnan Nair CK. Amelioration of cisplatin-induced nephro-
toxicity by extracts of Hemidesmus indicus and Acorus calamus. Pharm
Biol. 2010;48:290–5.
38. Saravanan N, Nalini N. Antioxidant effect of Hemidesmus indicus on
ethanol-induced hepatotoxicity in rats. J Med Food. 2007;10:675–82.
39. Saravanan N, Nalini N. Effect of 2-hydroxy 4-methoxy benzoic acid on an
experimental model of hyperlipidaemia, induced by chronic ethanol
treatment. J Pharm Pharmacol. 2007;59:1537–42.
1004 Hemidesmus indicus (L.) R. Br.

40. Saravanan N, Nalini N. Hemidesmus indicus protects against ethanol-induced

liver toxicity. Cell Mol Biol Lett. 2008;13:20–37.
41. Saravanan N, Nalini N. Impact of Hemidesmus indicus R.Br. extract on
ethanol-mediated oxidative damage in rat kidney. Redox Rep. 2007;12:229–35.
42. Saravanan N, Nalini N. Inhibitory effect of Hemidesmus indicus and its
active principle 2-hydroxy 4-methoxy benzoic acid on ethanol-induced liver
injury. Fundam Clin Pharmacol. 2007;21: 507–14. Erratum in: Fundam Clin
Pharmacol. 2008;22:105.
43. Saravanan N, Rajasankar S, Nalini N. Antioxidant effect of 2-hydroxy-4-
methoxy benzoic acid on ethanol-induced hepatotoxicity in rats. J Pharm
Pharmacol. 2007;59:445–53.
44. Saritha K, Rajesh A, Manjulatha K, Setty OH, Yenugu S. Mechanism of
antibacterial action of the alcoholic extracts of Hemidesmus indicus (L.) R.
Br. ex Schult, Leucas aspera (Wild.), Plumbago zeylanica L., and Tridax
procumbens (L.) R. Br. ex Schult. Front Microbiol. 2015;6:577.
45. Sethi A, Bhatia A, Srivastava S, et al. Pregnane glycoside from Hemi-
desmus indicus as a potential antioxidant and antidyslipidemic agent. Nat
Prod Res. 2010;24:1371–8.
46. Sigler P, Saksena R, Deepak D, Khare A. C21 steroidal glycosides from
Hemidesmus indicus. Phytochemistry. 2000;54:983–7.
47. Sowmia C, Kokilavani R. Antidiabetic and antihypercholesterolemic effect
of Hemidesmus indicus Linn.R. root in alloxan induced diabetic rats. Anc
Sci Life. 2007;26:4–10.
48. Statti G, Marrelli M, Conforti F, et al. Inhibition of cancer cell proliferation
and antiradical effects of decoction, hydroalcoholic extract, and principal
constituents of Hemidesmus indicus R. Br. Phytother Res. 2015;29:857–63.
49. Sultana S, Alam A, Khan N, Sharma S. Inhibition of cutaneous oxidative
stress and two-stage skin carcinogenesis by Hemidesmus indicus (L.) in
Swiss albino mice. Indian J Exp Biol. 2003;41:1416–23.
50. Sultana S, Khan N, Sharma S, Alam A. Modulation of biochemical parameters
by Hemidesmus indicus in cumene hydroperoxide-induced murine skin:
possible role in protection against free radicals-induced cutaneous oxidative
stress and tumor promotion. J Ethnopharmacol. 2003;85:33–41.
51. Thabrew MI, Mitry RR, Morsy MA, Hughes RD. Cytotoxic effects of a
decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on
human hepatoma HepG2 cells. Life Sci. 2005;77:1319–30.
52. Verma PR, Joharapurkar AA, Chatpalliwar VA, Asnani AJ. Antinociceptive
activity of alcoholic extract of Hemidesmus indicus R.Br. in mice.
J Ethnopharmacol. 2005;102:298–301.
Hemidesmus indicus (L.) R. Br. 1005

53. Vijayalakshmi K, Shyamala R, Thirumurugan V, et al. Physicophytochem-

ical investigation and anti-inflammatory screening of Capsicum annum L.
and Hemidesmus indicus (Linn.) R. Br. Anc Sci Life. 2010;29:35–40.
54. Zhao Z, Matsunami K, Otsuka H, et al. A condensed phenylpropanoid
glucoside and pregnane saponins from the roots of Hemidesmus indicus.
J Nat Med. 2013;67:137–42.
Hibiscus rosa-sinensis L.
(Malvaceae)

(Syns.: H. arnottii Griff. ex Mast.; H. boryanus DC.; H. cooperi auct.; H. festalis

Salisb.; H. rosiflorus Stokes; H. liliiflorus Griff. ex Mast.; H. storckii Seem.)

Abstract
A commonly cultivated bushy, evergreen garden shrub or small tree. Flowers are
demulcent and emollient, fried in ghee are used in the treatment of menorrhagia,
and infusion of dark red petals is used in dysuria, cystitis, and other irritable
conditions of the genitourinary tract, and as refrigerant drink in fevers and
demulcent in cough, and combined with milk, sugar and cumin in gonorrhea.
Syrup of flowers is recommended for palpitation, heart weakness and insanity.
Avicenna recommended a dose of 18 g to stop hiccups and vomiting. The plant is
attributed with antifertility activity in Ayurvedic medicine. It is used to treat child
sleeplessness by the Ati Negrito indigenous people of the Philippines, and it has
the highest use value for exogenous diseases, certain infectious and parasitic
diseases, injuries, and poisonings for the indigenous people of Batan Island of the
Philippines; pounded flowerbuds into paste are applied as a poultice to boils,
cancerous swellings, and mumps, and the decoction of roots, bark, leaves and
flowers is used as emollient. Methanol flower extract showed the presence of
flavonoids, saponins, cardiac glycosides and phenols, the ethanol flower extract
contained alkaloids, phytosterol, phenolic compounds and tannins, flavonoids
and saponins. Ethanol flower extract significantly lowered blood glucose, TC and
TGs, and increased serum insulin and HDL-C in diabetic rats. Ethanol leaf extract
caused 84% of the average hypoglycemic activity of 100 mg/kg of tolbutamide,
and 41% average hypoglycemic activity of glybenclamide in glucose-loaded rats;
whereas the aqueous leaf extract shows 51.5% activity of tolbutamide in
glucose-loaded rats but no activity in STZ-diabetic rats. Benzene flower extract
disrupts estrous cycle, causing significant reduction in the weight of ovaries,

© Springer Nature Switzerland AG 2020 1007

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_107
1008 Hibiscus rosa-sinensis L.

uterus, and pituitary gland, and ovarian follicular atresia and uterine atrophy, and
100% pregnancy was prevented, especially by the extract of flowers collected
during winter.

Keywords



Anghar-e-hindi Bussôge China rose Gudhal

Hibisco
Ibisco cinese




Japapushpam Jasund Shaknicha Zhu jin

Vernaculars: Urd.: Gudhal, Siyuti; Hin.: Jasund, Juva, Taran; San.: Arkapriya,
Japa, Japapushpam, Rudhrapushpa; Ben.: Joba, Juva, Orphul, Uru; Mal.: Kam-
bangsaptu, Shempariti; Mar.: Jasa-vanda; Tam.: Sapatta-cherri, Sembaruthi; Tel.:
Dasana-japa-pushpam, Mamdaram; Ara.: Anghar-e-hindi, Ward seeni; Chi.: 朱槿,
Da hong hua, Fo sang, Zhu jin; Dut.: Chinese heemstroos; Eng.: China rose,
Chinese hibiscus, Shoe flower, Hawaiian hibiscus; Fre.: Hibiscus de Chine à
feuilles panachées, Ketmie, Rose de Chine; Ger.: Chinesischer roseneibisch,
Rosenstundenblume; Ita.: Ibisco cinese, Rosa della Cina; Jap.: Bussôge, Fûrin-
bussôge, Haibisukasu, Ryûkiyûmukuge; Per.: Anghar-e-hind, Gul-e-mushkin,
Shaknicha; Por.: Hibisco, Rosa-da-China, Mimo de vênus variegato (Br.); Spa.:
Cucarda, Hibisco pacific, Rosa de China; Tag.: Antoláñgan, Gomaméla, Guma-
méla, Tapoláñga.
Description: A commonly cultivated bushy, evergreen garden shrub or small tree
growing 2.5–5 m tall and 1.5–3 m wide, with ovate, cordate, closely serrate,
acuminate, green or darkish green glossy leaves; flowers large, 5-petaled, 10 cm in
diameter, solitary, and brilliant red in color, with prominent orange-tipped red
anthers, flowers during summer and autumn (Figs. 1, 2 and 3).LXXXI

Fig. 1 Hibiscus rosa-sinensis, Brilliant Red Hibiscus, Andrew Fogg, WikimediaCommons; 2.0
Generic CC BY 2.0, https://commons.wikimedia.org/wiki/File:Hibiscus_Brilliant.jpg; https://
creativecommons.org/licenses/by/2.0/deed.en
Hibiscus rosa-sinensis L. 1009

Fig. 2 Hibiscus rosa-sinensis, Pink Hibiscus from Dehradun, Debasish Dey, Wikimedia-
Commons, https://upload.wikimedia.org/wikipedia/en/f/f4/Shoe_Flower_Dehradun_2009.jpg

Fig. 3 Hibiscus rosa-sinensis, Dried Flowers as sold in the U.S., Prof. Akbar, Original

Actions and Uses: In Unani medicine, flowers (temperament, hot 2° and dry 2°) are
regarded cardiorefrigerant and cardiotonic, strengthen and blacken hair, sedative,
emollient, aphrodisiac, and cough suppressant. In hoarseness of voice and throat
irritation, cough and dysuria, the decoction offresh flower petals is very beneficial. For
palpitation and anxiety, leaves are cleaned and covered in a bowl with sugar and
1010 Hibiscus rosa-sinensis L.

sprinkled with lemon, are kept in sunlight for 2–3 days before use.1 Flowers are
demulcent and emollient, fried in ghee are used in the treatment of menorrhagia, and
infusion of dark red petals is used in dysuria, cystitis, and other irritable conditions of
the genitourinary tract, and as refrigerant drink in fevers and demulcent in cough,CV
and combined with milk, sugar and cumin in gonorrhea.LXXXI Kabeeruddin recom-
mends the syrup of flowers for palpitation, heart weakness and insanity.LXXVII Avi-
cenna recommended a dose of 18 g to stop hiccups and vomiting.LXIX The plant
is attributed with antifertility activity in Ayurvedic medicine [38]. It is used to treat
child sleeplessness by the Ati Negrito indigenous people of the Philippines [20], and it
has the highest use value for exogenous diseases, certain infectious and parasitic
diseases, injuries, and poisonings for the indigenous people of Batan Island of the
Philippines [1]; pounded flowerbuds into paste are applied as a poultice to boils,
cancerous swellings, and mumps,CXVII and the decoction of roots, bark, leaves and
flowers is used as emollient.LVI It is also used for menstrual pain, unspecified female
complaints, and reproductive issues by women in Trinidad and Tobago [13]. The root,
in combination with Cissampelos pareira, is reportedly used by women of Assam
state in India for temporary and permanent sterilization [37]. The petals are also used
by the Chinese to blacken their eyebrows and to blacken shoe leather.LXXXI In tra-
ditional Malaysian medicine, it is used to induce abortion, ease menstrual cramps,
assist in childbirth and relieve headache, fever and inflammation [3]. Leaves are used
for the treatment of dysentery and diarrhea, and externally to promote draining of
abscesses and as analgesic agent in the traditional medicines of Cook Islands, Haiti,
Japan and Mexico [19].
Phytoconstituents: Phytochemical screening of methanol flower extract showed the
presence of flavonoids, saponins, cardiac glycosides and phenols [33], the ethanol
flower extract contained alkaloids, phytosterol, phenolic compounds, tannins, fla-
vonoids and saponins [4], and the hydroalcohol leaf extract was positive for the
presence of alkaloids, steroids, flavonoids and polyphenols [7]. Ethyl acetate fraction
of methanol root extract showed the presence of glycosides, flavonoids, tannins and
saponins [16]. Dried root ethanol extract contained saponins and tannins [8].
Pharmacology: Repeated oral administration of ethanol leaf extract (250 mg/kg)
in glucose-loaded rats, caused 84% of the average hypoglycemic activity of
100 mg/kg of tolbutamide [26], and 41% average hypoglycemic activity of gly-
benclamide [29]; whereas the aqueous leaf extract showed 51.5% activity of
tolbutamide in glucose-loaded rats but no activity in STZ-diabetic rats [28]. Ethanol
flower extract significantly lowered blood glucose, TC and TGs, and increased
serum insulin and HDL-C in diabetic rats [27]. Ethyl acetate flower petals extract is
also reported to significantly reduce serum glucose and HbA1c in diabetic rats,
comparable to metformin [23].
Benzene flower extract disrupts estrous cycle, causing significant reduction in the
weight of ovaries, uterus, and pituitary gland, and ovarian follicular atresia and uterine
atrophy [9], significantly reduced glycogen contents in the uterus [24], and 100%

1
Tayyab M: Personal Communication.
Hibiscus rosa-sinensis L. 1011

pregnancy was prevented, especially by the extract of flowers collected during winter
[10, 35]. At a dose of 1 g/kg body weight, the benzene extract inhibited implantation
in 93% of mice, with decrease in uterine weight, its protein content and alkaline and
acid phosphatase activity [6, 22]. Benzene extract administration from day 5 to 8 of
gestation also led to termination of pregnancy in about 92% of animals, associated
with a significant fall in peripheral level of progesterone and increase in uterine acid
phosphatase activity [21]. Benzene flower extract is also reported to show estrogenic
activity in immature mice [14]. Ethanol root extract produced 100% anti-implantation
and uterotropic activity at a dose of 400 mg/kg body weight in rats [38]. Aqueous and
alcohol flower extracts, however, did not significantly affect weights of the testis,
epididymis, ventral prostate, and seminal vesicle of male rats treated for 30-days [36].
Pretreatment of rats with oral methanol root extract for 6-days attenuated the
oxidative stress, anxiety and improved learning and memory deficit, caused by
bilateral common carotid artery occlusion-induced global cerebral ischemia and
reperfusion [17]; coadministration of the extract also protected rats against reserpine-
induced orofacial dyskinesia and oxidative stress [15]. Ethyl acetate soluble fraction
of methanol root extract protected mice against scopolamine-induced amnesia [16].
Methanol flower extract, containing anthocyanins and anthocyanidins, produced
antidepressant-like effects in mice [33]. Oral administration of dried pulverized
flowers in 2% CMC to rats, 6-days a week for 4-weeks, protected rats from death and
myocardial damage due to isoproterenol-induced MI [5]. Total phenolic content and
the total anthocyanin content in flower petals correlated with their antioxidant
activity [31]. Local application of ethanol root extract also significantly protected
isolated ischemic rat heart from damage, reducing the numbers of ectopic beats,
duration of ventricular tachycardia and the size of infarction [8]. Root extract treat-
ment of hyperlipidemic and diabetic rats lowered plasma levels of glucose, TC, TGs,
and phospholipids [11, 12]. Pretreatment of rats with hydroalcohol leaf extract for
7-days significantly lowered oxidative stress, proinflammatory mediators and
improved levels of SOD and GSH in acetic acid-induced colitis [7]. Sahu reported
hepatoprotective effect of ethanol leaf extract against piroxicam hepatotoxicity in
mice [30].
Ethanol flower extract significantly promoted healing and increased wound
epithelialization in rats [4, 34]. Topical application of petroleum ether extract of leaves
and flower in liquid paraffin to shaved skin of rats improved hair growth [2]. Petroleum
ether flower extract significantly inhibits growth of MRSA, comparable to vancomycin
[3], and methanol flower extract inhibited growth of B. subtillis and E. coli, while the
ethanol extract inhibited growth of Salmonella spp [25]. Hot ethanol leaf extract showed
significant antimicrobial activity against S. mutans and L. acidophilus [18]. Topical
application of hibiscus extract 30-min prior to application of croton oil twice weekly for
20-weeks in two-stage skin carcinogenesis, significantly delayed appearance, reduced
number of tumors per mouse and the percentage of tumor-bearing mice [32].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Methanol leaf extract was nontoxic to mice up to a single oral
dose of 2,000 mg/kg, but repeated dosing of 800 mg/kg daily for 14-days caused
1012 Hibiscus rosa-sinensis L.

hepatourinary damage [19]. Hydroalcohol leaf extract was nontoxic in mice up to

an oral dose of 5,000 mg/kg [7], and the ethanol root extract was nontoxic to mice
up to an oral dose of 4,000 mg/kg [38].
Commentary: Pharmacology screenings have verified some of the traditional uses
of the plant. However, no formal clinical studies are reported in published journals
listed on PubMed.

References
1. Abe R, Ohtani K. An ethnobotanical study of medicinal plants and traditional
therapies on Batan Island, the Philippines. J Ethnopharmacol. 2013;145:
554–65.
2. Adhirajan N, Ravi Kumar T, Shanmugasundaram N, Babu M. In vivo and
in vitro evaluation of hair growth potential of Hibiscus rosa-sinensis Linn.
J Ethnopharmacol. 2003;88:235–9.
3. Arullappan S, Zakaria Z, Basri DF. Preliminary screening of antibacterial
activity using crude extracts of Hibiscus rosa sinensis. Trop Life Sci Res.
2009;20:109–18.
4. Bhaskar A, Nithya V. Evaluation of the wound-healing activity of Hibiscus
rosa sinensis L. (Malvaceae) in Wistar albino rats. Indian J Pharmacol. 2012;
44:694–8.
5. Gauthaman KK, Saleem MT, Thanislas PT, et al. Cardioprotective effect of
the Hibiscus rosa sinensis flowers in an oxidative stress model of myocardial
ischemic reperfusion injury in rat. BMC Complement Altern Med. 2006;6:32.
6. Kabir SN, Bhattacharya K, Pal AK, Pakrashi A. Flowers of Hibiscus rosa-
sinensis, a potential source of contragestative agent: I. Effect of benzene
extract on implantation of mouse. Contraception. 1984;29:385–97.
7. Kandhare AD, Raygude KS, Ghosh P, et al. Effect of hydroalcoholic extract
of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats. Asian
Pac J Trop Biomed. 2012;2:337–44.
8. Khandelwal VK, Balaraman R, Pancza D, Ravingerová T. Hemidesmus
indicus and Hibiscus rosa-sinensis affect ischemia reperfusion injury in
isolated rat hearts. Evid Based Complement Alternat Med. 2011;2011. pii:
802937.
9. Kholkute SD, Chatterjee S, Udupa KN. Effect of Hibiscus rosa sinensis
Linn. on oestrous cycle and reproductive organs in rats. Indian J Exp Biol.
1976;14:703–4.
10. Kholkute SD, Mudgal V, Udupa KN. Studies on the antifertility potentiality
of Hibiscus rosa sinensis. Parts of medicinal value; selection of species and
seasonal variations. Planta Med. 1977;31:35–9.
11. Kumar V, Mahdi F, Khanna AK, et al. Antidyslipidemic and antioxidant
activities of Hibiscus rosa sinensis root extract in alloxan induced diabetic
rats. Indian J Clin Biochem. 2013;28:46–50.
Hibiscus rosa-sinensis L. 1013

12. Kumar V, Singh P, Chander R, et al. Hypolipidemic activity of Hibiscus

rosa sinensis root in rats. Indian J Biochem Biophys. 2009;46:507–10.
13. Lans C. Ethnomedicines used in Trinidad and Tobago for reproductive
problems. J Ethnobiol Ethnomed. 2007;3:13.
14. Murthy DR, Reddy CM, Patil SB. Effect of benzene extract of Hibiscus rosa
sinensis on the estrous cycle and ovarian activity in albino mice. Biol Pharm
Bull. 1997;20:756–8.
15. Nade VS, Dwivedi S, Kawale LA, Upasani CD, Yadav AV. Effect of
Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochem-
ical alterations in rats. Indian J Exp Biol. 2009;47:559–63.
16. Nade VS, Kanhere SV, Kawale LA, Yadav AV. Cognitive enhancing and
antioxidant activity of ethyl acetate soluble fraction of the methanol extract
of Hibiscus rosa sinensis in scopolamine-induced amnesia. Indian J
Pharmacol. 2011;43:137–42.
17. Nade VS, Kawale LA, Dwivedi S, Yadav AV. Neuroprotective effect of
Hibiscus rosa sinensis in an oxidative stress model of cerebral post-ischemic
reperfusion injury in rats. Pharm Biol. 2010;48:822–7.
18. Nagarajappa R, Batra M, Sharda AJ, et al. Antimicrobial effect of Jasminum
grandiflorum L. and Hibiscus rosa-sinensis L. extracts against pathogenic
oral microorganisms—an in vitro comparative study. Oral Health Prev Dent.
2015;13:341–8.
19. Nath P, Yadav AK. Acute and subacute oral toxicity assessment of the
methanolic extract from leaves of Hibiscus rosa-sinensis L. in mice.
J Intercult Ethnopharmacol. 2015;4:70–3.
20. Ong HG, Kim YD. Quantitative ethnobotanical study of the medicinal
plants used by the Ati Negrito indigenous group in Guimaras island.
Philippines. J Ethnopharmacol. 2014;157:228–42.
21. Pakrashi A, Bhattacharya K, Kabir SN, Pal AK. Flowers of Hibiscus
rosa-sinensis, a potential source of contragestative agent. III: interceptive
effect of benzene extract in mouse. Contraception. 1986;34:523–36.
22. Pal AK, Bhattacharya K, Kabir SN, Pakrashi A. Flowers of Hibiscus
rosa-sinensis, a potential source of contragestative agent: II. Possible mode
of action with reference to anti-implantation effect of the benzene extract.
Contraception. 1985;32:517–29.
23. Pillai SS, Mini S. Hibiscus rosa sinensis Linn. petals modulate glycogen
metabolism and glucose homeostasis signaling pathway in streptozotocin-
induced experimental diabetes. Plant Foods Hum Nutr. 2016;71:42–8.
24. Prakash AO. Glycogen contents in the rat uterus: response to Hibiscus
rosa-sinensis Linn. extracts. Experientia. 1979;35:1122–3.
25. Ruban P, Gajalakshmi K. In vitro antibacterial activity of Hibiscus rosa-
sinensis flower extract against human pathogens. Asian Pac J Trop Biomed.
2012;2:399–403.
26. Sachdewa A, Khemani LD. A preliminary investigation of the possible
hypoglycemic activity of Hibiscus rosa-sinensis. Biomed Environ Sci.
1999;12:222–6.
1014 Hibiscus rosa-sinensis L.

27. Sachdewa A, Khemani LD. Effect of Hibiscus rosa sinensis Linn. ethanol
flower extract on blood glucose and lipid profile in streptozotocin induced
diabetes in rats. J Ethnopharmacol. 2003;89:61–6.
28. Sachdewa A, Nigam R, Khemani LD. Hypoglycemic effect of Hibiscus rosa
sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic
rats. Indian J Exp Biol. 2001;39:284–6.
29. Sachdewa A, Raina D, Srivastava AK, Khemani LD. Effect of Aegle
marmelos and Hibiscus rosa sinensis leaf extract on glucose tolerance in
glucose induced hyperglycemic rats (Charles Foster). J Environ Biol. 2001;
22:53–7.
30. Sahu CR. Mechanisms involved in toxicity of liver caused by piroxicam in
mice and protective effects of leaf extract of Hibiscus rosa-sinensis L. Clin
Med Insights Arthritis Musculoskelet Disord. 2016;9:9–13.
31. Sarkar B, Kumar D, Sasmal D, Mukhopadhyay K. Antioxidant and DNA
damage protective properties of anthocyanin-rich extracts from Hibiscus
and Ocimum: a comparative study. Nat Prod Res. 2014;28:1393–8.
32. Sharma S, Khan N, Sultana S. Study on prevention of two-stage skin
carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical
constituent, gentisic acid, in the inhibition of tumour promotion response
and oxidative stress in mice. Eur J Cancer Prev. 2004;13:53–63.
33. Shewale PB, Patil RA, Hiray YA. Antidepressant-like activity of antho-
cyanidins from Hibiscus rosa-sinensis flowers in tail suspension test and
forced swim test. Indian J Pharmacol. 2012;44:454–7.
34. Shivananda Nayak B, Sivachandra Raju S, Orette FA, Chalapathi Rao AV.
Effects of Hibiscus rosa sinensis L. (Malvaceae) on wound healing activity: a
preclinical study in a Sprague Dawley rat. Int J Low Extrem Wounds. 2007;
6:76–81.
35. Singh MP, Singh RH, Udupa KN. Antifertility activity of a benzene extract
of Hibiscus rosa-sinensis flowers on female albino rats. Planta Med.
1982;44:171–4.
36. Tan CH. Is Hibiscus rosa sinensis Linn. a potential source of antifertility
agents for males? Int J Fertil. 1983;28:247–8.
37. Tiwari KC, Majumder R, Bhattacharjee S. Folklore information from Assam
for family planning and birth control. Int J Crude Drug Res. 1982;20:133–7.
38. Vasudeva N, Sharma SK. Postcoital antifertility activity of Hibiscus rosa-
sinensis Linn. roots. Evid Based Complement Alternat Med. 2008;5:91–4.
Holarrhena pubescens Wall. ex G. Don.
(Apocynaceae)

(Syn.: H. antidysenterica (Roth) Wall. ex A.DC.)

Abstract
It is native to central and southern Africa, the Indian subcontinent, Indochina, and
parts of China. Bark is bitter, stomachic, astringent, powerful antidysenteric,
febrifuge and anthelmintic, and constitutes the principal medicine for dysentery in
all systems of traditional Indian medicine. The bark is one of the most important
drugs in Hindu Materia Medica, and is described as astringent, cold and digestive,
and is a remedy for piles, dysentery, leprosy and phlegmatic humours. Sushruta
said it is expectorant, an antidote to poisons, cures dysuria, urinary and skin
diseases, checks nausea and vomiting, allays pruritus, improves the condition of
bad ulcers, relieves stomach pain and checks the derangement of three humours,
i.e. phlegm, air and bile. According to Charaka and Sushruta, every part of the
plant except the flower is used as a snakebite remedy; certain authors have
disputed this property. Seeds are cooling, appetizer, astringent, anthelmintic,
analgesic and used for leprosy, burning sensations, dysentery, skin diseases,
biliousness, bleeding piles, fatigue and hallucinations. In Portugese traditional
medicine, the bark is used as plaster in rheumatism, hot decoction is used against
toothache and bowel affections and the root-bark is used in chronic fevers. Kurchi
contains numerous steroidal alkaloids, including norconessine, isoconessine, and
kurchine. Conessine hydrobromide is obtained from seeds. Alkaloidal contents
seasonally vary in different parts, and in the bark during different stages. Steroidal
alkaloids, conessine, conessimine, conarrhimin and conimine show strong AChE
inhibitory activity, conessimine being the strongest. In a clinical trial of 40 Indian
patients with 15 patients stool positive for E. histolytica cysts, 20 for G. lamblia
and five for both, the bark powder for 15-days significantly improved symptoms
and stools negative for E. histolytica cyst in 70% cases.

© Springer Nature Switzerland AG 2020 1015

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_108
1016 Holarrhena pubescens Wall. ex G. Don.

Keywords
Bhadrayava

Bitter oleander

Ecoree-decodagapala
Inderjau talkh






Kirimllikai Kuda Kurchi Kutaja Tellicherry bark

Zaban-e-kunjashk-e-talkh

Vernaculars: Urd.: Inderjau talkh; Hin.: Indrajab, Karwa inderjau, Kauriya, Kuda,
Kura, Kurchi, Tita-indrajao (seeds); San.: Bhadrayava, Girimallika, Indrayava
(seeds), Kutaj, Kutaja, Kalinga (tree), Sakra sakhin, Sakravija (seeds), Vatsakavija,
Vatsika; Ben.: Kurchi, Kureya, Kutaja, Tita-indrajau; Guj.: Kadavo indrajav; Mal.:
Kadalapala, Kadavelapparintholi, Kotakappala; Mar.: Kadu-indrajau, Kuda,
Pandhara-kuda; Tam.: Kashappu-vetpalarishi, Kirimllikai, Kudasappalai,
Kuluppalai-virai (seeds), Kutaca-p-palai, Mlaimllikai, Veppalai; Tel.: Amkuda,
Amkuda-vittulu, Girimallika, Indravrakshamu, Kakakodise, Kodisepala, Kon-
damalle, Kutajamu; Ara.: Lisan-ul-asafir-almurr; Chi.: 止泻木; Eng.: Bitter ole-
ander, Conessi, Easter tree, Jasmine tree, Ivory tree, Kurchi, Tellicherry bark; Fre.:
Ecoree-decodagapala; Per.: Indarjavi-talkh, Zaban-e-kunjashk-e-talkh.
Description: It is native to central and southern Africa, the Indian subcontinent,
Indochina, and parts of China. It is reported to occur throughout India in tropical
wet deciduous forests. The commercial zone of bark extraction falls in the states of
Utter Pradesh, Madhya Pradesh, Punjab, Orissa and Bihar. Small quantities of bark
come from Assam and south India, and in Maharashtra, it is found in Ratnagiri
district [19]. Wrightia antidysenterica (L.) R.Br. is also known as Kutaja in
Ayurveda, but is a separate species and is known in Unani as Inderjau Shireen or

Fig. 1 Holarrhena pubescens, Leaves and Flowers, J.M. Garg, WikimediaCommons; 3.0 Unported
CC BY 3.0, https://commons.wikimedia.org/wiki/File:Holarrhena_pubescens_flowers_%26_leaves_
W_IMG_0293.jpg; https://creativecommons.org/licenses/by/3.0/deed.en
Holarrhena pubescens Wall. ex G. Don. 1017

Fig. 2 Wrightia antidysenterica, Flower, KayEss, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Flower-01-KayEss-1.jpeg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

sweet Inderjau. Stem bark is thick, brittle, often twisted or quilled, color dirty-white
or snuff-like; surface rugous and soft internally, taste slightly bitter at first, which
soon increases in intensity. Root bark reddish-brown, less thick than the stem bark,
and studded with prominent small warty growths, tastes very bitter. Seeds whitish,
resembling oats, or of cinnamon-brown color, narrow, elongated about 1.2–1.9 cm
long, compressed and chanelled on one side, have a tuft of hairs on the end most
remote from the foot-stalk, convex on one side, concave and marked by a pale line
on the other, easily broken between fingers; taste bitter, odor unpleasant, resembling
that of Inderjau shireen (Wrightia tinctoria) (Figs. 1 and 2).XL,LXXXI
Actions and Uses: Bark is bitter, stomachic, astringent, powerful antidysenteric,
febrifuge and anthelmintic, and constitutes the principal medicine for dysentery in all
systems of traditional Indian medicine.XXI,CV Nadkarni, quoting a drug committee
report, stated that some chronic cases of dysentery which could not be cured by
emetine in European medical treatment were cured by the preparations from this
bark.CIV The bark is one of the most important drugs in Hindu Materia Medica, and is
described as astringent, cold and digestive, and is a remedy for piles, dysentery,
leprosy and phlegmatic humours. Sushruta said it is expectorant, an antidote to
poisons, cures dysuria, urinary and skin diseases, checks nausea and vomiting, allays
pruritus, improves the condition of bad ulcers, relieves stomach pain and checks the
derangement of three humours, i.e. phlegm, air and bile. The seeds are considered
astringent, febrifuge and anthelmintic; both bark and seeds are usually combined
with other drugs which are principally astringents, bitters and aromatics.XL In
Ayurveda, the stem-bark is also used as anthelmintic, antidiarrhetic, antipyretic, for
diseases of spleen and biliousness. Seeds are cooling, appetizer, astringent, anthel-
mintic, analgesic and used for leprosy, burning sensations, dysentery, skin diseases,
1018 Holarrhena pubescens Wall. ex G. Don.

biliousness, bleeding piles, fatigue and hallucinations. In Portugese traditional

medicine, the bark is used as plaster in rheumatism, hot decoction is used against
toothache and bowel affections and the root-bark is used in chronic fevers [19]. In
Unani medicine, seeds (temperament, hot 2° and moist 1°) are described as carmi-
native, aphrodisiac, diuretic, lithotriptic, increase semen production,LXXVII anthel-
mintic, antispasmodic, and beneficial in chronic diarrhea, cough, asthma and
palpitation.L According to Charaka and Sushruta, every part of the plant except the
flower is used as a snakebite remedy; certain authors have disputed this prop-
erty.LXXXIV Muslim Arab and Persian physicians regard seeds astringent, carmina-
tive, lithotriptic, tonic and aphrodisiac, and prescribe them in chronic chest affections
such as asthma, in colic and as diuretic. A pessary made up of the seeds with honey
and saffron is supposed to favor conception.XL Bark and seeds are antiperiodic
similar to cinchona alkaloids, but do not produce nausea, vomiting or headache.
They are used in fever, chronic diarrhea, dysentery, worms, internal hemorrhages,
renal colic, chronic chest diseases, such as asthma, and to control vomiting in cho-
lera. They are used after the delivery to tone up vagina.LXXXI The Boxa tribe of
Nainital district (India), applies seed paste on penis or vagina, and the lower part of
the stomach to treat urinary complaints [31].
Phytoconstituents: Kurchi contains numerous steroidal alkaloids, amounting to
about 1.8–4.5%, including norconessine, isoconessine, and kurchine. The bark was
required to contain not less than 2% of alkaloids and kurchine bismuth iodide, a
preparation much used for amoebic dysentery. Conessine hydrobromide is obtained
from seeds.CXXXXI Alkaloidal contents seasonally vary in different parts, and in the
bark during different stages [16]. From stem bark, steroidal alkaloids, holacine and
holacimine [30], pubadysone [11a-hydroxy-18,20-oxido-3-oxo-pregna-1,4, 17(20)-
triene], puboestrene [3-acetoxy-17-oxo-1,3,5(10)-estratriene], and pubamide
[3,18-dioxo-11a-hydroxycona-1,4-diene] [29], holadysenterine [23], mokluangins
A–C, antidysentericine, holaphyllamine, and methylholaphyllamine [11], and
antidysentericine from seeds have been reported [22]. Two alkaloids, conessine and
conimine were isolated from tissue culture [14]. Aminoglycosteroids, holantosines
A and B [18], and naringenin glycoside, together with naringin, naringenin
7-O-b-D-glucoside, lupeol b-hydroxyhexadecanoate, lupeol, and ursolic acid have
been isolated from leaves [33]. Other alkaloids include concuressine, conessimine,
isoconessimine, holarrhimine, holonamine, kurchessine, kurcholessine, kurchicine,
and a protoplasmic poison like emetin. Methanol leaf extract contains high level of
total phenolic content and possesses significant antioxidant activity [17].
Pharmacology: Steroidal alkaloids, conessine, conessimine, conarrhimin and
conimine show strong AChE inhibitory activity, conessimine being the strongest
[36]. Conessine also show in vitro antiplasmodial activity and significantly reduces
parasitemia in P. berghei-infected mice [15, 34]. Alcohol bark extract demonstrated
broad-spectrum antibacterial activity [2], against clinical isolates of b-lactamase
producing MRSA [4], and methicillin-sensitive S. aureus [6], relatively high activity
against ESbetaL-producing MDR enteric bacteria, E. coli and Shigella [1, 5], and a
remarkable resistant modifying ability against A. baumannii in combination with
Holarrhena pubescens Wall. ex G. Don. 1019

novobiocin [12, 13, 24]. Methanol bark extract showed strong activity against MDR
S. typhi [26], and was active against S. aureus, S. epidermidis, S. faecalis, B. subtilis,
E. coli and P. aeruginosa, due to its alkaloidal contents [10, 28]. Alkaloids from
ethanol seed extract showed strong activity against enteropathogenic E. coli strains
[20, 21, 35], and reduced castor oil-induced diarrhea in rats [20]. Conessine showed
highest activity against M. luteus with an MIC of 15.6 µg [28]. Mokluangins B
showed moderate antibacterial activity against B. subtilis and E. coli [11].
Chloroform-soluble fraction of ethanol leaf extract produced cytotoxicity higher
than 5-FU, adriamycin, mitomycin-C and paclitaxel, against a number of human
cancer cell lines [27]. Methanol and aqueous bark extracts exhibited strong
antioxidant activity, and methanol extract showed significant hypoglycemic activity
in glucose overloaded hyperglycemic mice [9]. Hydromethanol seed extract and
ethanol bark extract also exhibited a-glucosidase inhibitory activity [3, 25]. Ethanol
seed extract stimulates phagocytic function while inhibiting the humoral component
of immune system [8].
Clinical Studies: In a clinical trial of 40 Indian patients with 15 patients stool
positive for E. histolytica cysts, 20 for G. lamblia and five for both, the bark powder
in doses of 4 g/day in three divided doses for 15-days, significantly improved
symptoms and rendered stools negative for E. histolytica cyst in 70% cases. No
adverse effects were listed in patients during the trial [32].
Human A/Es, Allergy and Toxicity: Oral conessine used in amoebic dysentery
and vaginitis, caused psychological issues in some patients.CXI,CXXXII,CXXXXI
Animal Toxicity: Pyrrolizidine alkaloids have been reported from H. antidysen-
terica (L.) Br., that produced hepatotoxicity in rats [7]. Oral LD50 of the ethanol
seed extract (yield 12%) was reported to be 1,250 mg/kg (864–1,635 mg/kg) [8].
Commentary: In addition to the treatment of amoebiasis in traditional medicines,
Ayurveda and Unani, it used to be the virtually officially sanctioned treatment of
amoebiasis in India. However, other than one old clinical study in patients with
E. histolytica and G. lamblia infections, there are no formal reports of clinical trials.
Nevertheless, the broad-spectrum antimicrobial activity of its bark and seed extracts
and alkaloids requires further formal exploration of its clinical effects.

References
1. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal
plants against ESbetaL-producing multidrug-resistant enteric bacteria.
Microbiol Res. 2007;162:264–75.
2. Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal
plants for their antimicrobial properties. J Ethnopharmacol. 1998;62:183–93.
3. Ali KM, Chatterjee K, De D, et al. Inhibitory effect of hydromethanolic
extract of seed of Holarrhena antidysenterica on alpha-glucosidase activity
1020 Holarrhena pubescens Wall. ex G. Don.

and postprandial blood glucose level in normoglycemic rat. J Ethnophar-

macol. 2011;135:194–6.
4. Aqil F, Ahmad I, Owais M. Evaluation of antimethicillin-resistant
Staphylococcus aureus (MRSA) activity and synergy of some bioactive
plant extracts. Biotechnol J. 2006;1:1093–102.
5. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian
medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
6. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant
extracts on clinical isolates of beta-lactamase producing methicillin resistant
Staphylococcus aureus. J Basic Microbiol. 2005;45:106–14.
7. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies on medicinal
plants of Sri Lanka: occurrence of pyrrolizidine alkaloids and hepatotoxic
properties in some traditional medicinal herbs. J Ethnopharmacol. 1981;4:
159–77.
8. Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of
plant origin. I: preliminary screening. J. Ethnopharmacol. 1986;18:133–41.
9. Bhusal A, Jamarkattel N, Shrestha A, et al. Evaluation of antioxidative and
antidiabetic activity of bark of Holarrhena pubescens Wall. J Clin Diagn
Res. 2014;8:HC05–8.
10. Chakraborty A, Brantner AH. Antibacterial steroid alkaloids from the stem
bark of Holarrhena pubescens. J Ethnopharmacol. 1999;68:339–44.
11. Cheenpracha S, Jitonnom J, Komek M, Ritthiwigrom T, Laphookhieo S.
Acetylcholinesterase inhibitory activity and molecular docking study of
steroidal alkaloids from Holarrhena pubescens barks. Steroids. 2016;108:
92–8.
12. Chusri S, Na-Phatthalung P, Siriyong T, Paosen S, Voravuthikunchai SP. Holar-
rhena antidysenterica as a resistance modifying agent against Acinetobacter
baumannii: its effects on bacterial outer membrane permeability and efflux
pumps. Microbiol Res. 2014;169:417–24.
13. Chusri S, Siriyong T, Na-Phatthalung P, Voravuthikunchai SP. Synergistic
effects of ethnomedicinal plants of Apocynaceae family and antibiotics
against clinical isolates of Acinetobacter baumannii. Asian Pac J Trop Med.
2014;7:456–61.
14. Dohnal B, Miedzobrodzki J, Włodarczyk B. Alkaloids in the tissue culture
of Holarrhena antidysenterica. Acta Pol Pharm. 1990;47:71–3.
15. Dua VK, Verma G, Singh B, et al. Antimalarial property of steroidal
alkaloid conessine isolated from the bark of Holarrhena antidysenterica.
Malar J. 2013;12:194.
16. Dutta AT, Ghosh BK, Gupta JC. The seasonal variation of alkaloids in
different parts of Holarrhena antidysenterica Wall. and the alkaloid content
in the bark at different ages. Part 1. Indian J Med Res. 1950;38:467–72.
17. Ganapathy PS, Ramachandra YL, Rai SP. In vitro antioxidant activity of
Holarrhena antidysenterica Wall. methanolic leaf extract. J Basic Clin
Pharm. 2011;2:175–8.
Holarrhena pubescens Wall. ex G. Don. 1021

18. Janot MM, Khuong-Huu Q, Monneret C et al. Alkaloidal steroids-C.

Holantosines A and B, new aminoglycosteroids isolated from leaves of
Holarrhena antidysenterica (Roxb.). Wall. (Apocynacees). (French) Tetra-
hedron. 1970;26:1695–709.
19. Kaul MK, Atal CK. Studies on Holarrhena antidysenterica Wall. 1. Botany,
medicoethnobotany and distribution. J Ethnopharmacol. 1983;8:349-56.
20. Kavitha D, Shilpa PN, Devaraj SN. Antibacterial and antidiarrhoeal effects
of alkaloids of Holarrhena antidysenterica Wall. Indian J Exp Biol. 2004;
42:589–94.
21. Kavitha D, Niranjali S. Inhibition of enteropathogenic Escherichia coli
adhesion on host epithelial cells by Holarrhena antidysenterica (L.) Wall.
Phytother Res. 2009;23:1229–36.
22. Kumar A, Ali M. A new steroidal alkaloid from the seeds of Holarrhena
antidysenterica. Fitoterapia. 2000;71:101–4.
23. Kumar N, Singh B, Bhandari P, Gupta AP, Kaul VK. Steroidal alkaloids
from Holarrhena antidysenterica (L.) Wall. Chem Pharm Bull (Tokyo).
2007;55:912–14.
24. Phatthalung PN, Chusri S, Voravuthikunchai SP. Thai ethnomedicinal
plants as resistant modifying agents for combating Acinetobacter baumannii
infections. BMC Complement Altern Med. 2012;12:56.
25. Prashanth D, Amit A, Samiulla DS, et al. alpha-Glucosidase inhibitory
activity of Mangifera indica bark. Fitoterapia. 2001;72:686–8.
26. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
27. Sharma V, Hussain S, Bakshi M, Bhat N, Saxena AK. In vitro cytotoxic
activity of leaves extracts of Holarrhena antidysenterica against some
human cancer cell lines. Indian J Biochem Biophys. 2014;51:46–51.
28. Siddiqui BS, Ali ST, Rizwani GH et al. Antimicrobial activity of the
methanolic bark extract of Holarrhena pubescens (Buch. Ham), its fractions
and the pure compound conessine. Nat Prod Res. 2012;26:987–92.
29. Siddiqui BS, Usmani SB, Ali ST, Begum S, Rizwani GH. Further constituents
from the bark of Holarrhena pubescens. Phytochemistry. 2001;58:1199–204.
30. Siddiqui S, Siddiqui BS. Isolation and structure of holacine, a new alkaloid
from the bark of Holarrhena antidysenterica Linn. Pak J Sci Ind Res.
1982;25:201–3.
31. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
32. Singh KP. Clinical studies on amoebiasis and giardiasis evaluating the
efficacy of kutaja (Holarrhena antidysenterica) in Entamoeba histolytica
cyst passers. Anc Sci Life. 1986;5:228–31.
33. Tuntiwachwuttikul P, Pootaeng-on Y, Phansa P, et al. Constituents of the
leaves of Holarrhena pubescens. Fitoterapia. 2007;78:271–3.
1022 Holarrhena pubescens Wall. ex G. Don.

34. Verma G, Dua VK, Agarwal DD, Atul PK. Antimalarial activity of
Holarrhena antidysenterica and Viola canescens, plants traditionally used
against malaria in the Garhwal region of northwest Himalaya. Malar J.
2011;10:20.
35. Voravuthikunchai S, Lortheeranuwat A, Jeeju W, et al. Effective medicinal
plants against enterohaemorrhagic Escherichia coli O157:H7. J Ethnophar-
macol. 2004;94:49–54.
36. Yang ZD, Duan DZ, Xue WW, et al. Steroidal alkaloids from Holarrhena
antidysenterica as acetylcholinesterase inhibitors and the investigation for
structure-activity relationships. Life Sci. 2012;90:929–33.
Hyoscyamus niger L.
(Solanaceae)

(Syn.: H. bohemicus F.W. Schmidt)

Abstract
A biennial or annual herb found in Asia, northwest China, Europe, and North
Africa. Its name is derived from the Anglo-Saxon Hen (chicken) and Bana
(murderer), because when fowls eat the seeds of this plant, they become paralyzed
and die. All parts of the plant are poisonous, even small amounts cause from
dizziness to delirium along with other anticholinergic effects. Seeds are also
poisonous to children, rodents, pigs, and fish. Three kinds were known to the
Greeks: black, white and yellow. Pliny mentioned four kinds, first with black seeds
(H. reticulatus), the second with brownish-gray seeds (H. niger), the third with
reddish seeds (H. aureus), and the fourth with white seeds (H. albus), which is
medicinally preferred. The white variety was also the only one recommended by
Dioscorides and Galen. Henbane is described as intoxicating, narcotic and
anodyne. Its uses include a poultice made of leaf juice with barley flour to relieve
pain of inflammatory swellings. Seeds increase blood clotting, and are used in a
dose of 15 mg in bleeding conditions. Ibn Jazlah did not recommend its use due to
its toxicity, and Razi called it Saykarān al-Dūr, which indicates in Arabic a person
who is drunk. It is one of the four plants that are used in Ayurveda for the treatment
of Parkinson’s disease. It has peculiarly sedative effect beneficial in irritable
affections of the lungs, bowels, and genitourinary tract, such as cystitis. Leaves
contain about 0.04% alkaloids (mainly hyoscyamine and scopolamine), the
glycoside hyoscypicrin, and choline. Withanolide class steroids, lignanamides,
rutin, hyoscyamide, b-sitosterol, daucosterol, coumarinolignans, tetrahydrofura-
nolignan, and steroidal glycosides, have been isolated from seeds. Methanol seed
extract produced significant analgesic, anti-inflammatory and antipyretic activ-
ities; cleomiscosin A is suggested to play a role in anti-inflammatory effect.
Methanol seed extract also exhibited anticonvulsant activity against picrotoxin-
induced seizures in mice.

© Springer Nature Switzerland AG 2020 1023

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_109
1024 Hyoscyamus niger L.

Keywords



Ajowain khorasani Banotu Bazar-al-banj-abiad Bilzekruid

Dormidera





Henbane Kohi-bang Parasikava Sickran Ulmeurt

Vernaculars: Urd.: Ajowain khorasani, Bazar-al-banj-abiad, Khurasani ajmo;

Hin.: Khorasani ajowain, Kohi-bang; San.: Khorasani yamani, Parasikava, Yavani;
Ben.: Khorasani ajowain; Mal.: Puka-yila; Mar.: Khorasani-ova; Tam.: Huyamani,
Kurosani omam, Kurashani-yomam (seeds), Pugai Ilai; Tel.: Kurasani-vamam,
Kurasaniyamani, Pogaku dhumra pattramu; Ara.: Bazrul-banj; Chi.: 天仙子; Cze.:
Blín černý; Dan.: Ulmeurt; Dut.: Bilzekruid; Eng.: Black henbane, Fetid night-
shade, Henbane, Hog bean, Indian henbane, Poison tobacco; Fin.: Hullukaali,
Pihahullukaali, Villikaali; Fre.: Hannebane, Herbe aux dents, Jusquiame noire,
Porcelet; Ger.: Schwarzes bilsenkraut; Hun.: Beléndek; Ita.: Alterco, Dente cav-
allino, Disturbo, Fava parcina, Guisquiamo nero; Nor.: Bulmeurt, Villrot; Per.:
Bang, Sickran; Pol.: Bielun, Lulek; Por.: Meimendro-negro; Rus.: Belena ernaja;
Spa.: Beleno negro, Dormidera, Herba queixalera, Jurcuano, Torna locos; Swe.:
Bolmört; Tur.: Banotu.
Description: A biennial or annual herb found in Asia, northwestern China, Eur-
ope, and North Africa; 30–80 cm tall, with 15–20 cm long alternate leaves, the
basal leaves petiolate, cauline sessile, clasping, oval-oblong, sinuate, pinnatifid;
lobes irregular, triangular and lanceolate. Flowers (June) in terminal, scorpioid
cymes, or axillary, nearly entirely sessile. Fruit a capsule, enclosed in the persistent
and enlarged calyx; seeds small, compressed, nearly ovoid, slightly reniform, 1 mm
in diameter, brownish-gray, surface reticulate (Figs. 1 and 2).LXXIX
Actions and Uses: Its name is derived from the Anglo-Saxon Hen (chicken) and
Bana (murderer), because when fowls eat the seeds of this plant, they become
paralyzed and die. All parts of the plant are poisonous, even small amounts cause
from dizziness to delirium along with other anticholinergic effects. Seeds are also
poisonous to children, rodents, pigs, and fish [5]. Effects of the drug are similar to
those of belladonna but are less intense due to lower alkaloid content. Presence of
scopolamine imparts a central narcotic effect. In Ladakh, Amchis use the whole
plant as a vermifuge. In the southern part of Kashmir Himalayas, leaves are smoked
with tobacco as hallucinogen [15]. Three kinds were known to the Greeks: black,
white and yellow. Pliny mentioned four kinds, first with black seeds (H. reticula-
tus), the second with brownish-gray seeds (H. niger), the third with reddish seeds
(H. aureus), and the fourth with white seeds (H. albus), which is medicinally
preferred. Mir Mohammad Hussain of Makhzan-al-Adwiya, also described three
kinds, i.e. black, white and red, and instructs to prefer the white variety. The white
variety was also the only one recommended by Dioscorides and Galen.LXIX Hen-
bane is described as intoxicating, narcotic and anodyne. Its uses include a poultice
made of leaf juice with barley flour to relieve pain of inflammatory swellings. Seeds
(temperament, cold 3° and dry 3°) in wine are also applied to gouty enlargements,
inflamed breasts, and swelled testicles. Equal parts of seeds and opium are powerful
Hyoscyamus niger L. 1025

Fig. 1 Hyoscyamus niger, Flowering Plant, Mikenorton, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Henbane2.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Hyoscyamus niger, Henbane with Flowers, Лoбaчeв Bлaдимиp, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:%D0%91%
D0%B5%D0%BB%D0%B5%D0%BD%D0%B0_%D1%87%D1%91%D1%80%D0%BD%D0%
B0%D1%8F_KR_01.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
1026 Hyoscyamus niger L.

narcotic. About 1.5 g seeds with 3 g poppy seeds is made into a mixture with honey
and water, and given as an anodyne in cough, and gout.XL,L Seeds increase blood
clotting, and are used in a dose of 15 mg in bleeding conditions.LXIX Ibn Jazlah did
not recommend its use due to its toxicity, and Razi called it Saykarān al-Dūr, which
indicates in Arabic a person who is drunk.LIII It is one of the four plants that are
used in Ayurveda for the treatment of Parkinson’s disease [21]; the seeds are
described as intoxicating, narcotic, anodyne, digestive, astringent and anthelmintic,
and the leaves as sedative, anodyne, antispasmodic, stimulant, and mydriatic; and
used in maniacal excitement, insanity, delirium tremens, chronic dementia with
insomnia, dry tickling night cough, asthma and hiccup. It has peculiarly sedative
effect beneficial in irritable affections of the lungs, bowels, and genitourinary tract,
such as cystitis.CV The delirium caused by it is never furious and is generally
accompanied by insomnia. As a laxative, its action is confined to intestines, and it is
a marked sedative of urinary passages.LXXXI Leaves and flowering tops taste bitter
and are poisonous, and used as antispasmodic, analgesic, narcotic in asthma, gas-
tralgia, gastrospasm, sciatica, pertussis, and neuralgia.LXXIX
Phytoconstituents: Alkaloids present are mainly hyoscyamine with some hyoscine
and atropine. Leaves contain about 0.04% alkaloids (mainly hyoscyamine and
scopolamine), the glycoside hyoscypicrin, and choline (The Merck Index, 1952). Three
withanolide class steroids [8]; four lignanamides, rutin, hyoscyamide, grossamide,
cannabisin D, cannabisin G, vanillic acid, b-sitosterol and daucosterol daturalactone-4,
hyoscyamilactol and 16a-acetoxyhyoscyamilactol [7]; coumarinolignans, hyosgerin,
venkatasin, cleomiscosin A and B [12]; a tetrahydrofuranolignan, hyoscyamal, bal-
anophonin, pongamoside C and pongamoside D [1]; lignanamides [21], and steroidal
glycosides, hyoscyamoside G, hyoscyamoside E and hyoscyamoside F1 [20], have
been isolated from seeds.
Pharmacology: Methanol seed extract produced significant analgesic, anti-inflam-
matory and antipyretic activities; cleomiscosin A is suggested to play a role in anti-
inflammatory effect [2]. Methanol seed extract exhibited anticonvulsant activity against
picrotoxin-induced seizures in mice [11]. Administration of aqueous-methanol seed
extract significantly attenuates motor disabilities (akinesia, catalepsy and reduced swim
score) and striatal dopamine loss in MPTP-induced Parkinson’s disease in mice, and
caused significant inhibition of MAO activity [14].
Human A/Es, Allergy and Toxicity: Deliberate ingestion to produce euphoria
[3, 9, 13, 16] or accidental exposure [6, 10, 17] may result in poisoning. Patients
may present with uni- or bilateral dilatation of pupils, not reactive to light and lack
of miosis in response to 1% pilocarpine [19]. Although many cases of poisoning
have occurred, especially in children, its comparative rarity makes such cases
infrequent. Symptoms include delirium, visual disturbances, rapid weak pulse,
convulsions, coma and may end in death. Its poisoning can be distinguished by its
excessive salivation, from that caused by atropa or datura [18].CXXXV Intoxication
in children is self-terminating and responds well to supportive therapy [4].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Hyoscyamus niger L. 1027

Commentary: There are no clinical studies on this potentially toxic plant, though,
it holds some promise for certain diseases, such as Parkinson’s disease, for which it
is used in Ayurveda.

References
1. Begum AS, Verma S, Sahai M, et al. Hyoscyamal, a new tetrahydrofurano
lignan from Hyoscyamus niger Linn. Nat Prod Res. 2009;23:595–600.
2. Begum S, Saxena B, Goyal M, et al. Study of anti-inflammatory, analgesic
and antipyretic activities of seeds of Hyoscyamus niger and isolation of a
new coumarinolignan. Fitoterapia. 2010;81:178–84.
3. Betz P, Janzen J, Roider G, Penning R. Psychopathologic manifestations of oral
administration of endemic nightshade plants. Arch Kriminol. 1991;188:175–82.
4. Doneray H, Orbak Z, Karakelleoglu C. Clinical outcomes in children with
Hyoscyamus niger intoxication not receiving physostigmine therapy. Eur J
Emerg Med. 2007;14:348–50.
5. Haas LF. Hyoscyamus niger (henbane). J Neurol Neurosurg Psychiatry.
1995;59:114.
6. Jaspersen-Schib R, Theus L, Guirguis-Oeschger M, et al. Serious plant
poisonings in Switzerland 1966–1994. Case analysis from the Swiss Toxicol-
ogy Information Center. Schweiz Med Wochenschr. 1996;126:1085–98
(German).
7. Ma CY, Liu WK, Che CT. Lignanamides and nonalkaloidal components of
Hyoscyamus niger seeds. J Nat Prod. 2002;65:206–9.
8. Ma CY, Williams ID, Che CT. Withanolides from Hyoscyamus niger seeds.
J Nat Prod. 1999;62:1445–7.
9. Manríquez O, Varas J, Ríos JC, Concha F, Paris E. Analysis of 156 cases of
plant intoxication received in the Toxicologic Information Center at
Catholic University of Chile. Vet Hum Toxicol. 2002;44:31–2.
10. Oztekin-Mat A. Plant poisoning cases in Turkey. Ann Pharm Fr. 1994;52:260–
5 (Review, French).
11. Reza HM, Mohammad H, Golnaz E, Gholamreza S. Effect of methanolic
extract of Hyoscymus niger L. on the seizure induced by picritoxin in mice.
Pak J Pharm Sci. 2009;22:308–12.
12. Sajeli B, Sahai M, Suessmuth R, et al. Hyosgerin, a new optically active
coumarinolignan, from the seeds of Hyoscyamus niger. Chem Pharm Bull
(Tokyo). 2006;54:538–41.
13. Sands JM, Sands R. Henbane chewing. Med J Aust. 1976;2:55, 58.
14. Sengupta T, Vinayagam J, Nagashayana N, et al. Antiparkinsonian effects
of aqueous methanolic extract of Hyoscyamus niger seeds result from its
monoamine oxidase inhibitory and hydroxyl radical scavenging potency.
Neurochem Res. 2011;36:177–86.
15. Shah NC. Herbal folk medicines in North India. J. Ethnopharmacol. 1982;6:
293–301.
1028 Hyoscyamus niger L.

16. Spoerke DG, Hall AH, Dodson CD, et al. Mystery root ingestion. J Emerg
Med. 1987;5:385–8.
17. Stefánek J, Dufincová J, Vychytil P, Holmes S. Mystery of mydriatic pupils.
Vnitr Lek. 2000;46:808–10 (Czech).
18. Vidović D, Brecić P, Haid A, Jukić V. Intoxication with henbane. Lijec
Vjesn. 2005;127:22–3 (Article in Croatian).
19. Wilhelm H, Wilhelm B, Schiefer U. Mydriasis caused by plant contact.
Fortschr Ophthalmol. 1991;88:588–91 (Article in German).
20. Zhang W, Zhang W, Luo J, Kong L. A new steroidal glycoside from the
seeds of Hyoscyamus niger. Nat Prod Res. 2013;27:1971–4.
21. Zhang WN, Luo JG, Kong LY. Phytotoxicity of lignanamides isolated from
the seeds of Hyoscyamus niger. J Agric Food Chem. 2012;60:1682–7.
Hyssopus officinalis L.
(Lamiaceae)

(Syns.: H. altissimus Mill.; H. angustifolius M.Bieb.; H. hirsutus Hill; H. torresii

Sennen; H. vulgaris Bubani)

Abstract
The plant grows in central Europe and the Middle East, and is cultivated as an
aromatic herb and medicinal plant in the Mediterranean countries (except
southeast), Russia, Black Sea, and Caucasus. In Central Europe, the herb is used
as a spice. Hyssop, a cleansing herb, relieves catarrh and reduces mucus secretion,
regulates BP (high or low), clears the chest and calms the nerves. As it promotes
sweating, this herb is useful when coping with fevered patients. It also improves
digestion and protects body from infection. Muslim physicians in India considered it
stimulant, anthelmintic and deobstruent. Dioscorides described dry hyssop as useful
for swelling, exterminating worms and for chest troubles, and used moist hyssop for
swelling in the womb and in the liver. In central Europe, including Hungary, the
essential oil is used as a folk remedy against certain respiratory diseases. In
Romania, it is used to flavor food, and in traditional medicine as stomachic,
antispasmodic, antifungal, and for cough treatment. In Uygur medicine also, it is
used to relieve cough and asthma, and in Lebanon, as an antidiabetic herb. Major
flavone, diosmin, is mainly located in sepals and leaves; flavonoid glycosides were
reported from samples cultivated in Xinjiang Uygur Autonomous Region of China.
b-pinene, limonene, pinocamphone, isopinocamphone are the main components of
the essential oil. Treatment with water extract normalized eosinophil ratio in the
bronchoalveolar lavage fluid and levels of serum IgE and IgG in ovalbumin
sensitized and challenged model of chronic asthma in mice, ameliorated patholog-
ical changes, including collagen deposition, mucus secretion, and smooth muscle
proliferation, and prevented lung remodeling. Oral preadministration of hyssop
extract significantly suppressed sucrose- and maltose-loaded-hyperglycemia in
mice, and in vitro inhibited intestinal a-glucosidase activity.

Keywords



Erva-sagrada Gul-e-zufah Hisopo Hyssop

Isop
Iisoppi
Jupha
Shén


xiāng cǎo Ushnaz-daoud Zufa otu

© Springer Nature Switzerland AG 2020 1029
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_110
1030 Hyssopus officinalis L.

Vernaculars: Urd.: Gul-e-zufah, Zufah-yabis; Hin.: Jupha, Zupha; Ara.: Zufa;

Chi.: 神香草, Ngau sat chou, Shén xiāng cǎo; Cze.: Yzop lékařský; Dan.: Isop;
Dut.: Hysop; Eng.: Herbe de Joseph, Herbe sacrée, Herbe sainte, Hiope, Hisopo,
Hissopo, Hysope, Hyssop, Jufa, Rabo de gato, Ysop.; Fin.: Iisoppi; Fre.: Herbe
sacrée, Hysope, Hysope officinal; Ger.: Echter ysop, Kirchenseppl, Ysop; Hun.:
Izsóp, Kerti izsóp; Ita.: Issopo; Jap.: Hisoppu, Yanagihakka; Kor.: Hiseopu; Nor.:
Isop; Per.: Ushnaz-daoud; Pol.: Hyzop lekarski; Por.: Erva-sagrada, Hissopo,
Hissopo-das-farmácias; Rus.: Issop; Spa.: Hisopillo de los órdenes, Hisopillo
húmedo, Hisopo, Hisopo común, Hisopo hortelano, Rabillo, Rabillo de gato; Swe.:
Isop; Tag.: Hyssop; Tur.: Çördük out, Zufa otu.
Description: There is disagreement about the identity of the plant called Zufah-
i-yabis that was imported into India from Persia, and the plant described here is
Hyssopus officinalis. The plant grows in central Europe and the Middle East, and is
cultivated as an aromatic herb and medicinal plant in the Mediterranean countries
(except southeast), Russia, Black Sea, and Caucasus. In central Europe, the herb is
used as a spice [13], and under optimal weather conditions it is harvested twice a year,
once at the end of spring and again at the beginning of the fall, during flowering stage.
It is one of the most important pharmaceutical herbs cultivated in Romania [14]. It is a
small, 15–25 cm high plant, stem not thicker than a crow-quill, quadrangled, reddish
or brownish purplish, branched from the base, which is woody. This aromatic plant has
long lanceolate leaves and clusters of purplish flowers.XXVI Flower-heads numerous,
oblong, calyx striated, hairy, purple, with five sharp teeth; four seeds naked, oblong,
triangular, of a pale-brown color, studded with rows of small round tubercles very
closely set, and on the other two elongated white prominences; the root woody, seldom
branched. The plant sold in Indian bazaars is very broken and has a pleasant odor like
sweet hay and bitter taste (Figs. 1, 2 and 3).XL,XXXI
Actions and Uses: Hyssop, a cleansing herb, relieves catarrh and reduces mucus
secretion, regulates BP (high or low), clears the chest and calms the nerves. As it
promotes sweating, this herb is useful when coping with fevered patients. It also
improves digestion and protects body from infection.XXVI Muslim physicians in India
considered it stimulant, anthelmintic and deobstruent.XL Ibn Jazlah used it in the
treatment of cough, hard swellings, for spleen ailments, and to exterminate worms.
Moist hyssop is employed for spleen and swellings, and Razi quotes Dioscorides that
dry hyssop is useful for swelling, exterminating worms and for chest troubles, and
used moist hyssop for swelling in the womb and in the liver.LIII In Unani medicine, it
is described as diaphoretic, anti-inflammatory, concoctive, mucolytic (munaffis-
e-balgham),1 expectorant, deobstruent, carminative and anthelmintic, and used
as decoction for the treatment of asthma, phlegmatic cough, pleurisy, cough and
cold,L,LXXVII ascites and liver obstruction.1 Leaves are also stimulant, stomachic, and
emmenagogue.LXXXI Infusion or syrup of leaves is prescribed for the treatment of
hysteria, colic, dyspepsia, flatulence, chronic cough, asthma, chronic bronchitis in

1
Tayyab M: Personal Communication.
Hyssopus officinalis L. 1031

Fig. 1 Hyssopus officinalis, Blooming Plants, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0. https://commons.wikimedia.org/wiki/File:Hyssopus_officinalis_001.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Hyssopus officinalis, Flowers, H. Zell, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Hyssopus_officinalis_005.JPG
1032 Hyssopus officinalis L.

Fig. 3 Hyssopus officinalis, Dried Hyssop as sold in the U.S., Prof. Akbar, Original

older people, fever complicated with cough, and uterine affections, such as amen-
orrhea, and indurations of the liver and spleen.CV In central Europe, including
Hungary, the essential oil is used as a folk remedy against certain respiratory diseases
[13]. In Romania, it is used to flavor food, and in traditional medicine as stomachic,
antispasmodic, antifungal, and for cough treatment [14]. In Uygur medicine also, it is
used to relieve cough and asthma [5], and in Lebanon, as an antidiabetic herb [3]. It is
also a source of natural antioxidants [10].
Phytoconstituents: Major flavone, diosmin, is mainly located in sepals and leaves
[7]; flavonoid glycosides, quercetin 7-O-b-D-apiofuranosyl-(1!2)-b-D-xylopyr-
anoside and quercetin 7-O-b-D-apiofuranosyl-(1!2)-b-D-xylopyranoside 3′-O-b-
D-glucopyranoside were reported from samples cultivated in Xinjiang Uygur
Autonomous Region of China [15]. b-pinene, limonene, pinocamphone, isopinocam-
phone are the main components of the essential oil; the non-volatile components are
rosmarinic, and caffeic acids [13]. In Romanian samples, ferulic, caftaric, gentisic,
caffeic, chlorogenic and p-coumaric acids; three flavonoid glycosides, isoquercitrin,
rutin and quercitrin; and two flavonoid aglycone, quercetin and luteolin were iden-
tified in the ethanolic extract [14]. From the hydromethanol extract of aerial parts of
Iranian origin, apigenin 7-O-b-D-glucuronide was the major flavonoid; and myrtenyl
acetate, camphor, germacrene, spathulenol were the main compounds of the oil, in
which 20 compounds representing 99.97% of the oil were identified [2]. Major
components of the oil of plant from Western Himalaya are pinocarvone, cis-
pinocamphone, and b-pinene [12]. b-sitosterol and stigmasterol, and pentacyclic
triterpenes: oleanolic acid, ursolic acid, 2a,3b-dihydroxyolean-12-en-28-oic acid,
2a,3b-dihydroxyurs-12-en-28-oic acid, 2a,3b,24-trihydroxyolean-12-en-28-oic acid,
Hyssopus officinalis L. 1033

and 2a,3b,24-trihydroxyurs-12-en-28-oic acid from cell suspension cultures [11],

and a-glucosidase inhibitors from aqueous methanol extract of dried hyssop leaves
[8], and isoferulyl D-glucose ester from whole plant [7] have been isolated.
Pharmacology: Treatment with water extract normalized eosinophil ratio in the
bronchoalveolar lavage fluid and levels of serum IgE and IgG in ovalbumin sensi-
tized and challenged model of chronic asthma in mice [5], ameliorated pathological
changes, including collagen deposition, mucus secretion, and smooth muscle pro-
liferation, and prevented lung remodeling [6]. Ethanol extract of aerial parts showed
significant antimicrobial activity against S. aureus, L. monocytogenes, E. coli,
S. typhimurium and C. albicans [14]. Hydroalcohol (50%) extract inhibited HIV-1
induced infections in MT-2 cells [1]. Oral preadministration of hyssop extract sig-
nificantly suppressed sucrose- and maltose-loaded-hyperglycemia in mice within
30–60 min, and in vitro inhibited intestinal a-glucosidase activity [3, 10]. N-butanol
extract of aerial parts, due to its highest total phenolic content shows the best
antioxidant activity, while the purified flavonoid had weak radical scavenging
activity [2, 14]. Using EO as an additive to vacuum-packed ground beef prevented
development of undesirable sensory changes and growth of enterobacteriaceae, and
increased its shelf life [9]. Essential oil and its component, isopinocamphone, inhibit
ACh- and barium chloride-induced contractions of isolated guinea-pig ileum [4].
Mechanism of Action: Antimuscarinic effect on ileum may contribute to its
antispasmodic effect and a-glucosidase activity may be responsible for antidiabetic
activity.
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: The plant has been widely used for respiratory diseases, both in the
East and the West, for a long time. However, very little pharmacological studies
have been conducted, and there are no formal clinical studies reported on this plant.

References
1. Bedoya LM, Palomino SS, Abad MJ, et al. Screening of selected plant
extracts for in vitro inhibitory activity on human immunodeficiency virus.
Phytother Res. 2002;16:550–4.
2. Fathiazad F, Mazandarani M, Hamedeyazdan S. Phytochemical analysis and
antioxidant activity of Hyssopus officinalis L. from Iran. Adv Pharm Bull.
2011;1:63–7.
3. Loizzo MR, Saab AM, Tundis R, et al. In vitro inhibitory activities of plants
used in Lebanon traditional medicine against angiotensin converting
enzyme (ACE) and digestive enzymes related to diabetes. J Ethnopharmacol.
2008;119:109–16.
1034 Hyssopus officinalis L.

4. Lu M, Battinelli L, Daniele C, et al. Muscle relaxing activity of Hyssopus

officinalis essential oil on isolated intestinal preparations. Planta Med.
2002;68:213–6.
5. Ma X, Ma X, Ma Z, et al. Effect of Hyssopus officinalis L. on inhibiting
airway inflammation and immune regulation in a chronic asthmatic mouse
model. Exp Ther Med. 2014;8:1371–4.
6. Ma X, Ma X, Ma Z, et al. The effects of Uygur herb Hyssopus officinalis L.
on the process of airway remodeling in asthmatic mice. Evid Based
Complement Alternat Med. 2014;2014:710870.
7. Marin FR, Ortuño A, Benavente-Garcia O, Del Rio JA. Distribution of
flavone glycoside diosmin in Hyssopus officinalis plants: changes during
growth. Planta Med. 1998;64:181–2.
8. Matsuura H, Miyazaki H, Asakawa C, et al. Isolation of alpha-glusosidase
inhibitors from hyssop (Hyssopus officinalis). Phytochemistry. 2004;65:91–7.
9. Michalczyk M, Macura R, Tesarowicz I, Banaś J. Effect of adding essential
oils of coriander (Coriandrum sativum L.) and hyssop (Hyssopus officinalis
L.) on the shelf life of ground beef. Meat Sci. 2012;90:842–50.
10. Miyazaki H, Matsuura H, Yanagiya C, et al. Inhibitory effects of hyssop
(Hyssopus officinalis) extracts on intestinal alpha-glucosidase activity and
postprandial hyperglycemia. J Nutr Sci Vitaminol (Tokyo). 2003;49:346–9.
11. Skrzypek Z, Wysokińska H. Sterols and triterpenes in cell culture of Hyssopus
officinalis L. Z Naturforsch. 2003;58:308–12.
12. Stappen I, Wanner J, Tabanca N, et al. Chemical composition and biological
activity of essential oils of Dracocephalum heterophyllum and Hyssopus
officinalis from Western Himalaya. Nat Prod Commun. 2015;10:133–8.
13. Varga E, Hajdú Z, Veres K, et al. Investigation of variation of the production
of biological and chemical compounds of Hyssopus officinalis L. Acta Pharm
Hung. 1998;68:183–8.
14. Vlase L, Benedec D, Hanganu D, et al. Evaluation of antioxidant and
antimicrobial activities and phenolic profile for Hyssopus officinalis, Ocimum
basilicum and Teucrium chamaedrys. Molecules. 2014;19:5490–507.
15. Wang N, Yang XW. Two new flavonoid glycosides from the whole herbs of
Hyssopus officinalis. J Asian Nat Prod Res. 2010;12:1044–50.
Illicium verum Hook.f.
(Schisandraceae)

(Syns.: I. anisatum Lour.; Badianifera officinarum Kuntze.)

Abstract
This evergreen aromatic tree is indigenous to southwest China, and Vietnam. It
had been used in China and Japan for a long time, but was not known to Indians
and Persians, and was introduced to Europe in the sixteenth century. In TCM it
is described as stomachic and stimulant, and used to dispel cold, regulate the
flow of Qi and to relieve pain. In European medicine also, it is described as
aromatic, stimulant and carminative. It is best used in the form of infusion. An
herbal tea or infusion is used to treat colic pain in infants in many cultures. Anise
oil is also applied to the abdomen of children to relieve colicky pains, to joints in
rheumatism, and around the ear in cases of earache. Three neurotropic
sesquiterpenoids, veranisatins A–C, were isolated from star anise. Volatiles,
secoprezizaane-type sesquiterpenes, phenylpropanoids, phenylpropanoid glu-
coside, phytoquinoids, lignans, flavonoids, and illiciumflavane acid have been
reported from the fruits. Substantial antibacterial activity of supercritical CO2
and ethanol extracts of fruits against clinical drug-resistant isolates, including A.
baumannii, P. aeruginosa, and MRSA strains was reported. Anise oil exhibited
in vitro virucidal activity against HSV-2, aciclovir-sensitive HSV-1 and an
aciclovir-resistant clinical HSV-1 isolate as well as an aciclovir-resistant strain.
Methanol fruit extract prolonged phenobarbitone-induced sleeping time, reduced
locomotor activity, and produced alteration in general behavior pattern, and
anxiolytic effects without significantly altering motor coordination.

Keywords





Anason tchini Anasphal Anice stellato Anís estrellado Badian khatai Ba






jiao Daiuikyô Star anise Steranijs Stjerneanis

Vernaculars: Urd.: Badian khatai; Hin.: Anasphal, Badayan, Phoolchakri; Mal.:

Thakkolam; Tam.: Anasuppan, Annashuppu; Tel.: Anasapurvem, Anása-puvvu,
Marati-mogga; Ara.: Badian khatai, Raziyanje-khatai; Chi.: Baat gok, Ba jiao,
© Springer Nature Switzerland AG 2020 1035
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_111
1036 Illicium verum Hook.f.

Pa-chiao-hui-shiang; Cze.: Badyán, Badyáník; Dan.: Sterneanis, Stjerneanis; Dut.:

Steranijs; Eng.: Aniseed, Badian star anise, Star anise, Chinese star anise; Fin.:
Taehtianis, Tähtianis; Fre.: Anis de la Chine, Anis étoilé, Badiane, Badianier de Chine,
Badianier vrai; Ger.: Badian, Chinesischer sternanis, Echter sternanis, Echter ster-
nanisbaum, Sternanis, Sternanisbaum; Hun.: Csillagánizs, Kínai ánizs; Ind.: Bunga
lawang; Ita.: Anice stellato, Badiana, Finocchio della cina; Jap.: Daiuikyô, Sutaa
anisu, Tou shikimi; Nor.: Stjerneanis; Per.: Badian-e-khatai; Pol.: Anyz gwiazd-
kowaty, Gwiazdkowy; Por.: Anis-estrelado; Rus.: Bad’ian nastoiashchii, Zvezdchatyi
anis; Spa.: Anís de China, Anis da Sibéria, Anís estrellado, Badiana; Swe.: Stjärnanis,
Stjaernanis; Tag.: Sanque; Tha.: Chan paetklip, Dok chan, Poikak, Poy kak bua; Tur.:
Anason tchini; Vie.: Bát giác hương, Cái hồi, Đại hồi, Hồi, Hồi hương.
Description: This evergreen aromatic tree is indigenous to southwest China, and
Vietnam. Fruits are pedunculate of an iron-brown color, formed of 8 carpels
arranged like a star. Each carpel is oval with a broad base, compressed on both
walls, and having a boat-like prominence at the top, woody, wrinkled and hard to
touch. Each carpel contains one seed, smooth, shining, ovato-oval, ribbed only on
one side and glossy, of brown or chestnut color and oily; taste is sweet, aromatic,
acrid at first, then astringent and finally bitter (Figs. 1 and 2).LXXXI
Actions and Uses: It had been used in China and Japan for a long time, but was
not known to Indians and Persians, and was introduced to Europe in the sixteenth
century.XL In TCM it is described as stomachic and stimulant,LXVI and used to
dispel cold, regulate the flow of Qi and to relieve pain [26]. In European medicine

Fig. 1 Illicium anisatum, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Illicium_anisatum_-_K%C3%B6hler
%E2%80%93s_Medizinal-Pflanzen-075.jpg
Illicium verum Hook.f. 1037

Fig. 2 Illicium verum, Fruits and Seeds, Prof. Akbar, Original

also, it is described as aromatic, stimulant and carminative.XL In Unani medicine,

the fruits (temperament, hot 2° and dry 2°) are described as digestive, carminative,
deobstruent, stomachic and diuretic,XL,L,LXXVII and are considered stimulant,
anodyne, and expectorant; an infusion of fruits is useful in flatulent colic, spasmodic
affections of intestines, and in infantile retention of urine.LXXXI It is best used in the
form of infusion. Anise oil is applied to the abdomen of children to relieve colicky
pains, to joints in rheumatism, and around the ear in cases of earache.CV An herbal
tea or infusion is used to treat colic pain in infants in many cultures [6, 9, 11]. The
fruits (essential oil 2.5–5%) are also used as a flavor and carminative.CXXXXI
Phytoconstituents: Three neurotropic sesquiterpenoids, veranisatins A, B and C,
were isolated from star anise [20]. Volatiles, secoprezizaane-type sesquiterpenes,
phenylpropanoids [25], phenylpropanoid glucoside [15], phytoquinoids, lignans and
flavonoids [26], and illiciumflavane acid [27] have been reported from the fruits.
Anethole content of the fruits are more than 4.5% [31]. The EO contains 80–90%
anethole; also, chavicol, methyl ether, p-methoxyphenylacetone and safrole.CXXXXI
Recent fruit EO analysis identified trans-anethole (89.5%), 2-(1-cyclopentenyl)-furan
(0.9%) and cis-anethole (0.7%) as the main components among 22-compounds, which
accounted for 94.6% of the total oil [7]. From roots, illiverin A, tashironin, tashironin A,
illicinole, (−)-illicinone-A, 4-allyl-2-(3-methylbut-2-enyl)-1,6-methylenedioxybenzene-
3-ol, 3-hydroxy-4,5-methylenedioxyallylbenzene, 4-allyl-4-(3-methylbut-2-enyl)-1,2-
methylenedioxycyclohexa-2,6-dien-5-one, 3,4-seco-(24 Z)-cycloart-4(28),24-diene-
3,26-dioic acid, and 26-methyl ester have been isolated [23].
Pharmacology: Methanol fruit extract prolonged phenobarbitone-induced sleep-
ing time, reduced locomotor activity, and produced alteration in general behavior
pattern, and anxiolytic effects without significantly altering motor coordination [3];
trans-anethole produced anxiolytic effects in mice [19]. Veranisatin A and anisatin
at 0.1 and 0.03 mg/kg doses, respectively, demonstrated analgesic effect, decreased
1038 Illicium verum Hook.f.

methamphetamine-enhanced locomotion, and caused hypothermia [20]. Twelve-

weeks treatment with ethanol fruit extract of high-fat diet-fed apolipoprotein
E-knockout mice, counteracted the characteristic changes in body weight, BP, and
lipid levels, reduced aortic atherosclerotic plaque lesions, and expression of
inflammatory adhesion molecules and cytokines, better than treatment with ator-
vastatin [22]. The spice also possesses antioxidant activity [29]. Treatment with star
anise reduced tumor burden, lowered oxidative stress and increased levels of phase
II enzymes in NDEA-initiated and phenobarbital promoted hepatocarcinogenesis in
rats [28]. Phenylpropanoids and phytoquinoids from fruits significantly inhibited
histamine release from rat’s A23187-stimulated basophilic leukemia cells, and
reduced TNFa levels [17]. Ethanol extract inhibited secretion of histamine, IL-4,
IL-6, and TNF-a from mast cells, and its topical application significantly reduced
ear thickness, dermatitis scores, and serum levels of IgE, histamine, IL-6, and
intercellular adhesion molecule in a mouse model of atopic dermatitis [24].
The fruits possess potent antimicrobial efficacy against bacteria, yeast and fungi,
mainly due to the presence of anethole [4]. Substantial antibacterial activity of
supercritical CO2 and ethanol extracts of fruits against 67 clinical drug-resistant
isolates, including A. baumannii, P. aeruginosa, and MRSA strains was reported
[30]. Anise oil exhibited dose-dependent in vitro virucidal activity against HSV-2,
aciclovir-sensitive HSV-1 and an aciclovir-resistant clinical HSV-1 isolate as well
as an aciclovir-resistant strain [13, 14].
Mechanism of Action: Reduction of inflammation-associated gene expression is
suggested for its beneficial effect in hyperlipidemia-associated atherosclerosis [28],
and anethole is responsible for its anti-AChE activity [1], and may contribute to its
digestive, carminative, stomachic and diuretic effects.
Human A/Es, Allergy and Toxicity: Anisatin is a neurotoxic sesquiterpene, a
noncompetitive GABA-antagonist that can cause CNS hyperactivity and tonic-
clonic seizures [10, 12, 21]. A Dutch man suffered epileptic seizures after drinking a
cup of Japanese star anise herbal tea [2], and a number of persons reported symptoms
of general malaise, nausea and vomiting 2–4 h following consumption of herbal tea.
Out of which 22 persons required hospitalization, of whom 16 were due to gener-
alized tonic-clonic seizures. The suspected herbal tea possibly contained Japanese
star anise [10]. A number of cases of infants with serious gastrointestinal and neu-
rological symptoms, such as irritability, abnormal movements, vomiting and nys-
tagmus due to use of star anise infusion were reported in Spain [5]. An one-month
old girl developed convulsion after given a considerable amount of star anis infusion
possibly to relieve infantile colic [6]. More cases of infantile poisoning were reported
from France [18], and the U.S. [8, 9, 16], possibly due to contamination or adul-
teration of Chinese star anise (Illicium verum) with Japanese star anise (Illicium
anisatum or Illicium religiosum). Japanese star anise has been documented to cause
both neurologic and gastrointestinal toxicities [8].
Animal Toxicity: Intraperitoneal toxic doses of methanol, hexane and ethyl
acetate extracts of fruits in rats were 2,000 mg/kg; methanol extract being the most
Illicium verum Hook.f. 1039

potent [3]. Veranisatins produced convulsions and lethal toxicity in mice at a very
low oral dose of 3 mg/kg, and at lower doses caused hypothermia, and decreased
methamphetamine-enhanced locomotion [20].
Commentary: Despite Chinese star anise being used as an herbal tea for its
supposedly beneficial effects, its use in cooking and wide-spread traditional use to
relieve flatulent colic, there are no formal clinical studies reported.

References
1. Bhadra S, Mukherjee PK, Kumar NS, Bandyopadhyay A. Anticholinesterase
activity of standardized extract of Illicium verum Hook. f. fruits. Fitoterapia.
2011;82:342–6.
2. Biessels GJ, Vermeij FH, Leijten FS. Epileptic seizure after a cup of tea:
intoxication with Japanese star anise. Ned Tijdschr Geneeskd. 2002;146:
808–11 (Dutch).
3. Chouksey D, Upmanyu N, Pawar RS. Central nervous system activity of
Illicium verum fruit extracts. Asian Pac J Trop Med. 2013;6:869–75.
4. De M, De AK, Sen P, Banerjee AB. Antimicrobial properties of star anise
(Illicium verum Hook. f.). Phytother Res. 2002;16:94–5.
5. Garzo Fernández C, Gómez Pintado P, Barrasa Blanco A, et al. Cases of
neurological symptoms associated with star anise consumption used as a
carminative. An Esp Pediatr. 2002;57:290–4 (Spanish).
6. Gil Campos M, Pérez Navero JL, Ibarra De La Rosa I. Convulsive status
secondary to star anise poisoning in a neonate. An Esp Pediatr. 2002;57:
366–8 (Spanish).
7. Huang Y, Zhao J, Zhou L, et al. Antifungal activity of the essential oil of
Illicium verum fruit and its main component trans-anethole. Molecules.
2010;15:7558–69.
8. Ize-Ludlow D, Ragone S, Bernstein JN, et al. Chemical composition of
Chinese star anise (Illicium verum) and neurotoxicity in infants. JAMA.
2004;291:562–3.
9. Ize-Ludlow D, Ragone S, Bruck IS, et al. Neurotoxicities in infants seen
with the consumption of star anise tea. Pediatrics. 2004;114:e653–6.
10. Johanns ES, van der Kolk LE, van Gemert HM, et al. An epidemic of
epileptic seizures after consumption of herbal tea. Ned Tijdschr Geneeskd.
2002;146:813–6 (Dutch).
11. Joshi VC, Srinivas PV, Khan IA. Rapid and easy identification of Illicium
verum Hook. f. and its adulterant Illicium anisatum Linn. by fluorescent
microscopy and gas chromatography. J AOAC Int. 2005;88:703–6.
12. Kakemoto E, Okuyama E, Nagata K, Ozoe Y. Interaction of anisatin with
rat brain gamma-aminobutyric acid A receptors: allosteric modulation by
competitive antagonists. Biochem Pharmacol. 1999;58:617–21.
1040 Illicium verum Hook.f.

13. Koch C, Reichling J, Kehm R, et al. Efficacy of anise oil, dwarf-pine oil and
chamomile oil against thymidine-kinase-positive and thymidine-kinase-
negative herpesviruses. J Pharm Pharmacol. 2008;60:1545–50.
14. Koch C, Reichling J, Schneele J, Schnitzler P. Inhibitory effect of essential
oils against herpes simplex virus type 2. Phytomedicine. 2008;15:71–8.
15. Lee SW, Li G, Lee KS, et al. A new phenylpropanoid glucoside from the
fruits of Illicium verum. Arch Pharm Res. 2003;26:591–3.
16. Madden GR, Schmitz KH, Fullerton K. A case of infantile star anise
toxicity. Pediatr Emerg Care. 2012;28:284–5.
17. Matsui T, Ito C, Itoigawa M, et al. Anti-inflammatory activity of phenyl-
propanoids and phytoquinoids from Illicium species in RBL-2H3 cells. Planta
Med. 2007;73:662–5.
18. Minodier P, Pommier P, Moulène E, et al. Star anise poisoning in infants.
Arch Pediatr. 2003;10:619–21 (French).
19. Miyagawa M, Satou T, Yukimune C, et al. Anxiolytic-like effect of Illicium
verum fruit oil, trans-anethole and related compounds in mice. Phytother
Res. 2014;28:1710–2.
20. Nakamura T, Okuyama E, Yamazaki M. Neurotropic components from star
anise (Illicium verum Hook. fil.). Chem Pharm Bull (Tokyo). 1996;44:
1908–14.
21. Okuyama E, Nakamura T, Yamazaki M. Convulsants from star anise
(Illicium verum Hook. f.). Chem Pharm Bull (Tokyo). 1993;41:1670–1.
22. Park SH, Sung YY, Nho KJ, Kim HK. Protective activity ethanol extract of
the fruits of Illicium verum against atherogenesis in apolipoprotein E
knockout mice. BMC Complement Altern Med. 2015;15:232.
23. Song WY, Ma YB, Bai X, et al. Two new compounds and anti-HIV active
constituents from Illicium verum. Planta Med. 2007;73:372–5.
24. Sung YY, Yang WK, Lee AY, et al. Topical application of an ethanol extract
prepared from Illicium verum suppresses atopic dermatitis in NC/Nga mice.
J Ethnopharmacol. 2012;144:151–9.
25. Sy LK, Brown GD. Novel phenylpropanoids and lignans from Illicium
verum. J Nat Prod. 1998;61:987–92.
26. Wang GW, Hu WT, Huang BK, Qin LP. Illicium verum: a review on its
botany, traditional use, chemistry and pharmacology. J Ethnopharmacol.
2011;136:10–20.
27. Wu LD, Xiong CL, Chen ZZ, et al. A new flavane acid from the fruits of
Illicium verum. Nat Prod Res. 2016;30:1585–90.
28. Yadav AS, Bhatnagar D. Chemopreventive effect of star anise in N-nitrosodi-
ethylamine initiated and phenobarbital promoted hepato-carcinogenesis.
Chem Biol Interact. 2007;169:207–14.
29. Yadav AS, Bhatnagar D. Inhibition of iron induced lipid peroxidation and
antioxidant activity of Indian spices and Acacia in vitro. Plant Foods Hum
Nutr. 2010;65:18–24.
Illicium verum Hook.f. 1041

30. Yang JF, Yang CH, Chang HW, et al. Chemical composition and anti-
bacterial activities of Illicium verum against antibiotic-resistant pathogens.
J Med Food. 2010;13:1254–62.
31. Zhou J, Lü G, Zhong X, Wen H. Quantitative determination of anethole in
the fruit of Illicium verum from various places of Guangxi province. Zhong
Yao Cai. 2005;28:106–7 (Chinese).
Iris germanica L.
(Iridaceae)

Abstract
The plant grows in India, Iran, central and northern Europe, China, Korea and
Russia. Iris was mentioned by Theophrastus, Dioscorides and other Greek
medical writers; it is the Illyrian Iris of the ancients. The Greek name Iris is of
Persian origin, and cognate with Aersa, and probably with Arastan “to adorn to
obey.” Orris root is the Pushkaramula of Sanskrit writers, though not recognized
as such by modern Hindus. The root is considered to be deobstruent, aperient,
diuretic, especially useful in removing bilious obstructions, and is used in a large
number of diseases; externally, it is applied to small sores and pimples.
Avicenna said rinsing mouth or gargling with its decoction relieves uvulitis and
toothache. It is considered in Unani medicine especially useful to remove
sputum from lungs and is used in the treatment of asthma, pneumonia, pleurisy,
paralysis, palsy, arthritis, inflammation of liver and spleen, and ascites. It is a
rich source of secondary metabolites such as flavonoids, triterpenes, benzene and
benzoquinones derivatives. Ethanol extract significantly lowered TC and TGs of
hyperlipidemic rats, and methanol root extract showed potent gastric antiulcer
activity in rats. Some triterpenes are reported to be more effective than
doxorubicine on some drug-sensitive and drug-resistant cultured human tumor
cell lines.

Keywords
Aasman joni
Bearded iris
Bifelfürz
Carrizas
Göksüsen
Inderdhanushi


pushpi Irsa
Lírio-cárdeno
Padma-pushkara
Trädgårdsiris

Vernaculars: Urd.: Irsa; Hin.: Inderdhanushi pushpi; San.: Padma-pushkara,

Pushkaráhva, Pushkaramula, Pushkaránghrija; Ara.: Irsa, Kusht-el-bahri, Kusht-el-
hali; Cze.: Kosatec německý; Dut.: Duitse lis; Eng.: Bearded iris, Fleur-de-lis,
German Iris, Orris root; Fin.: Saksankurjenmiekka; Fre.: Flambé, Iris d’Allemagne,
Iris de Germanie; Ger.: Bachblume, Bifelfürz, Blauer Spieß, Deutsche schwertlilie,

© Springer Nature Switzerland AG 2020 1043

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_112
1044 Iris germanica L.

Gartenkrötenblume, Lilie; Gre.: Iris; Hun.: Kék liliom, Kerti nőszirom, Német
kardliliom; Ita.: Fior de San Marco, Giaggiolo, Giglio azurro, Gladiolo celestre,
Siaggiolo; Jap.: Jamana-irisu; Per.: Aasman joni, Bekh banafshah (root), Bekh-e-
sausan (root), Susan-i-asmanguni; Pol.: Irys bródkowy, Kosaciec niemiecki; Por.:
Iris-de-florença, Lírio-cárdeno, Lírio-da-alemanha; Spa.: Cárdeno, Carrizas, Car-
rucia, Cebollas de lirios, Cuchillos, Espadañas, Fresilla de monte, Lírio cárdeno;
Swe.: Trädgårdsiris; Tur.: Göksüsen.
Description: The plant grows in India, Iran, central and northern Europe, China,
Korea and Russia. It grows in the wetlands and is the most extensively cultivated
variety in Japanese gardens. Ibn al-Baitar,LXIX quoting Dioscorides, said it is
Sausan that is called Irsa, but its leaves are larger and wider than the leaves of
desert Sausan; its flowers are opposite to each other, of different colors, white,
yellow, violet and blue; hence its name that means rainbow. The root is hard,
knotted and aromatic; the best quality is described as small, thick, reddish in color,
very aromatic and hard to break. Its fragrance is relatively more when old,
worm-eaten and with holes in it. Dymock et al.XL differentiated the Eastern Orris
root from the European one saying it is smaller and of a darker color, and the bark
of the rhizome is not removed (Figs. 1 and 2).
Actions and Uses: Iris was mentioned by Theophrastus, Dioscorides and other
Greek medical writers; it is the Illyrian Iris of the ancients. The root is considered to
be deobstruent, aperient, diuretic, especially useful in removing bilious obstructions,
and is used in a large number of diseases; externally, it is applied to small sores and
pimples. Dymock et al.XL said that Orris root is the Pushkaramula of Sanskrit writers,
though not recognized as such by modern Hindus. The Greek name Iris is of Persian
origin, and cognate with Aersa, and probably with Arastan “to adorn to obey.” Root

Fig. 1 Iris germanica, Flower, GinoMM, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Iris_Germanica_2012-2.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Iris germanica L. 1045

Fig. 2 Iris ensata, Flower, Laitche, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA
3.0, https://commons.wikimedia.org/wiki/File:Iris_ensata_Thunb.jpg; https://creativecommons.org/
licenses/by-sa/3.0/deed.en

is described as having properties similar to costus. Ibn al-BaitarLXIX said it relieves

cough, thins thick sputum, purges bile, is spasmolytic, and dusting with its powder
accelerates wound healing; and quotes Avicenna that rinsing mouth or gargling with
its decoction relieves uvulitis and toothache. KabeeruddinLXXVII described it as
resolvent, anesthetic, emollient, mucolytic, detergent, diuretic, expels yellow bile,
increases thirst and local antidote to snake, scorpion and stings’ poisons. It is espe-
cially useful to remove sputum from lungs and is used in the treatment of asthma,
pneumonia, pleurisy, paralysis, palsy, arthritis, inflammation of liver and spleen,
and ascites; externally, it is used in inflammations, acne, impetigo, rosacea, and
sebhorrheic dermatitis. Root decoction has been used as antispasmodic, anti-inflam-
matory, emmenagogue, stimulant, diuretic, aperient, violent cathartic [1, 16], and to
treat liver and spleen ailments in traditional systems of medicine [7]. NadkarniCV
described the root as alterative, aperient, diuretic and cathartic, and its uses in the
treatment of liver and gall bladder diseases.
Phytoconstituents: Iris germanica is a rich source of secondary metabolites such as
flavonoids [14], triterpenes [4, 5, 8, 9, 11, 12, 15], and benzene and benzoquinones
derivatives [1, 2]. Compounds identified as isoflavones: 2′-methyl-6′-hydroxy
cyclohexenyl-3-methyl-1-acetophenone ether, isopenol, irisolone and irisolidone,
isoflavone glycosides: iriskashmirianin 4′-O-b-D-glucoside, nigricin 4′-O-b-D-
glucoside, irilone 4′-O-b-D-glucoside and iridin, and acetovanillone have been
isolated from rhizomes [2, 3, 18]. Other compounds isolated include isopeonol,
5,7-dihydroxy-3-(3′-hydroxy-4′,5′dimethoxy)-8-methoxy-4H-1-benzopyran-4-one,
5,7-dihydroxy-3-(3′-hydroxyl-4′, 5′-dimethoxy)-6-methoxy-4H-1-benzopyran-4-one,
5,7-dihydroxy-3-(4′-hydroxy)-6-methoxy-4H-1-benzopyrane-4-one, 5-hydroxy-3-(4′-
hydroxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one, 5-hydroxy-3-(4′-methoxy)-6,7-
methylenedioxy-4H-1-benzopyran-4-one, 5-methoxy-3-(4′-hydroxy)-6,7-methyenedi-
oxy-4H-1-benzopyran-4-one, 5,7-dihydroxy-3-(3′-hydroxy-4′-methoxy)-6-methoxy-
1046 Iris germanica L.

4H-1-benzopyran-4-one, 5,7-dihydroxy-3-(3′-methoxy-4′-hydroxy)-6-methoxy-4H-
1-benzopyran-4-one [16], irisolidone 7-O-a-D-glucoside, irigenin, irilone, iriskash-
mirianin and iriflogenin [19]; iriflogenin-4′-O-gentiobioside [18], tectorigenin, tectori-
din, irisxanthone, pyroglutamic acid, mangiferin, ombuin, genistein, irilin D, munin-
gin, apocynin, androsin, b-sitosterol, naringenin, daucosterol, 5,3,3′-trihydroxy-7,4′-
dimethoxyflavanone, cirsiliol-4′-glucoside, 3b,4′-dihydroxy-7,3′-dimethoxyflavonone-
5-O-b-D-glucopyranoside, 5,7,4′-trihydroxy-6,3′,5′-trimethoxy-isoflavone, 2,4′,6-tri-
hydroxy-4-methoxybenzophenone-2-O-b-D-glucoside [20], germanaism H and iris-
kashmirianin A [21], irigenin S, iriside A, stigmasterol, a-irone, c-irone, 3-hydroxy-
5-methoxyacetophenone, irilone, irisolidone, irigenin, stigmasterol-3-O-b-D-glucopyr-
anoside, irilone 4′-O-b-D-glucopyranoside and iridin [10], triterpenes: irigermanal and
iridogermanal [12], and a monocyclic triterpene ester, iristectorone K [15]. Isoflavones
from I. germanica grown in Morocco were reported as irigenin, iristectorigenin A,
nigricin, nigricanin, irisflorentin, iriskumaonin methyl ether, irilone, iriflogenin, and
irisolidone [17].
Pharmacology: Ethanol extract administration to hyperlipidemic rats for 10-weeks
significantly lowered TC and TGs [7], and methanol root extract showed potent
gastric antiulcer activity in rats [13]. Some triterpenes are reported to be more
effective than doxorubicine on some drug-sensitive and drug-resistant cultured
human tumor cell lines [6]. Chloroform and ethyl acetate extracts of rhizomes
exhibited bactericidal activity [14]. The triterpene, iridal showed significant activity
against chloroquine-sensitive and -resistant strains of P. falciparum [4].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interactions: Some isoflavones have been
reported to potently inhibit CYP1A activity [19].
Commentary: This is one of those plants included here that has been sufficiently
characterized chemically, but not investigated enough for pharmacological activities
and none for clinical effects, at least not reported in mainstream English publications.

References
1. Asghar SF, Aziz S, Rehman HU, et al. Secondary metabolites isolated from
Iris germanica. Rec Nat Prod. 2009;3:139–52.
2. Asghar SF, Habib-ur-Rehman, Atta-ur-Rahman, Choudhary MI. Phyto-
chemical investigations on Iris germanica. Nat Prod Res. 2010;24:131–9.
3. Atta-Ur-Rahman, Nasim S, Baig I, et al. Isoflavonoid glycosides from the
rhizomes of Iris germanica. Chem Pharm Bull (Tokyo). 2002;50:1100–2.
4. Benoit-Vical F, Imbert C, Bonfils JP, Sauvaire Y. Antiplasmodial and
antifungal activities of iridal, a plant triterpenoid. Phytochemistry. 2003;62:
747–51.
Iris germanica L. 1047

5. Bonfils J, Sauvaire Y. Localization of iridals in Iris germanica rhizomes.

Phytochemistry. 1996;41:1281–5.
6. Bonfils JP, Pinguet F, Culine S, Sauvaire Y. Cytotoxicity of iridals,
triterpenoids from Iris, on human tumor cell lines A2780 and K562. Planta
Med. 2001;67:79–81.
7. Choudhary MI, Naheed S, Jalil S, Alam JM, Atta-ur-Rahman. Effects of
ethanolic extract of Iris germanica on lipid profile of rats fed on a high-fat
diet. J Ethnopharmacol. 2005;98:217–20.
8. Crawford MMR, Lindsay DA, Walton JC, Wollenweber-Ratzer B. Towards
the characterization of radicals formed in rhizomes of Iris germanica.
Phytochemistry. 1994;37:979–85.
9. Hideyuki I, Yoko M, Takashi Y. New piscicidal triterpenes from Iris
germanica. Chem Pharm Bull. 1995;43:1260–2.
10. Ibrahim SR, Mohamed GA, Al-Musayeib NM. New constituents from the
rhizomes of Egyptian Iris germanica L. Molecules. 2012;17:2587–98.
11. Ito H, Miyake Y, Yoshida T. New piscicidal triterpenes from Iris
germanica. Chem Pharm Bull. 1995;43:1260–2.
12. Marner FJ, Krick W, Gellrich B, Jaenicke L, Winter W. Irigermanal and
iridogermanal: two new triterpenoids from rhizomes of Iris germanica L.
J Org Chem. 1982;47:2531–6.
13. Muto Y, Ichikawa H, Kitagawa O, et al. Studies on antiulcer agents. I. The
effects of various methanol and aqueous extracts of crude drugs on antiulcer
activity. Yakugaku Zasshi. 1994;114:980–94 (Japanese).
14. Orhan I, Nasim S, Sener B, et al. Two isoflavones and bioactivity spectrum
of the crude extracts of Iris germanica rhizomes. Phytother Res. 2003;17:
575–7.
15. Orhan I, Sener B, Hashimoto T, et al. Iristectorone K, a novel monocyclic
triterpene ester from Iris germanica rhizomes growing in Turkey. Fitoter-
apia. 2002;73:316–9.
16. Rahman AU, Nasim S, Baig I, et al. Anti-inflammatory isoflavonoids from
the rhizomes of Iris germanica. J Ethnopharmacol. 2003;86:177–80.
17. Roger B, Jeannot V, Fernandez X, Cerantola S, Chahboun J. Characterisation
and quantification of flavonoids in Iris germanica L. and Iris pallida Lam.
resinoids from Morocco. Phytochem Anal. 2012;23:450–5.
18. Schütz C, Quitschau M, Hamburger M, Potterat O. Profiling of isoflavonoids
in Iris germanica rhizome extracts by microprobe NMR and HPLC-PDA-
MS analysis. Fitoterapia. 2011;82:1021–6.
19. Wollenweber E, Stevens JF, Klimo K, et al. Cancer chemopreventive
in vitro activities of isoflavones isolated from Iris germanica. Planta Med.
2003;69:15–20.
20. Xie GY, Chen YJ, Wen R, et al. Chemical constituents from rhizomes of
Iris germanica. Zhongguo Zhong Yao Za Zhi. 2014;39:846–50 (Chinese).
21. Xie GY, Qin XY, Liu R, et al. New isoflavones with cytotoxic activity from
the rhizomes of Iris germanica L. Nat Prod Res. 2013;27:2173–7.
Juniperus communis L.
(Cupressaceae)

Abstract
It is a native of Greece, but has widespread distribution in both hemispheres,
primarily in lower elevations, and found in Europe, Africa, Northern Asia,
temperate Eurasia, India, Iran, and North America. Dioscorides described its
diuretic and digestive properties, and use in cough and pectoral affections.
Avicenna said that abhal fruit boiled in rose oil in an iron vessel until the fruit
becomes darker, and using this oil as ear drops is very beneficial for hearing loss.
Berries ground with vinegar and applied topically cures ringworm of the scalp.
In Unani medicine, fruit is regarded astringent, strong resolvent, carminative,
stomachic, anthelmintic, deobstruent, strong diuretic, and emmenagogue. Pow-
dered fruits are used in cases of amenorrhea, but it is contraindicated in women
with hot temperament. It is such a powerful diuretic that its continuous use may
cause hematuria and abortion in pregnant women. Navajo tribe of the native
Americans used berries for the treatment of diabetes, and as a traditional cure for
tuberculosis and other respiratory diseases. The First Nations of the Canadian
Maritimes use infusions of juniper primarily as a tonic and for the treatment of
tuberculosis. Fruits (berries) contain oil, tannins, carbohydrate, diterpenes,
hypolaetin glycosides, and biflavonoids. Constituents of fruit volatile oil may
vary with region and may contain 1-terpinen-4-ol, a-pinene, camphene and the
sesquiterpene candinene, d-limonene, cymene, borneol and myrcene. Dried
berries supplied in diet reduced STZ-induced hyperglycemia with reduction in
polydipsia, and a reduced rate of body weight loss in mice. Berries decoction also
decreased glycemic levels in normoglycemic rats and significantly reduced blood
glucose, mortality index, and loss of body weight of STZ-diabetic rats. The oil is
bactericidal against both Gram-positive and Gram-negative bacterial species,
strong fungicidal against yeasts, yeast-like fungi and dermatophytes.

© Springer Nature Switzerland AG 2020 1049

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_113
1050 Juniperus communis L.

Keywords





Aaraar Abhal Ardıç Azotacristos Common juniper
Feuerbaum





Genièvre Hapusha Kataja Ou zhou ci bai

Vernaculars: Urd.: Abhal, Hub-el-a’ra’r; Hin.: Aaraar, Hobair; San.: Hapusha,

Havusa, Matsyagandha; Ben.: Hayusha; Mar.: Hosh; Tel.: Hapusha; Ara.: Abhal,
Arar, Hub-el-a’ra’r, Shajrat-allah; Chi.: 欧洲刺柏, Ou zhou ci bai; Cze.: Jalovec
obecný; Dan.: Almindelig ene, Ene; Dut.: Jeneverbes, Jeneverboom; Eng.:
Common juniper, Ground juniper, Juniper berry, Mountain juniper; Fin.: Kataja,
Kotikataja; Fre.: Baies de genièvre (fruit), Genévrier, Genièvre, Genibre, Peteron,
Petrot, Piket; Ger.: Feuerbaum, Gemeiner wacholder, Heidewacholder, Kram-
metsbeerbaum, Kranawitt, Kraunbaum, Machandel, Wacholderbeeren, Wacholderol
and WacholderbeerÖl (oil); Gre.: Baraasi; Hun.: Boróka, Közönséges boróka; Ita.:
Coccola di ginepro, Ginepro comune; Jap.: Junipa, Seiyo-suzu, Seiyo-toshyo; Kor.:
Chyunipo, Jyunipeo; Nor.: Einer; Pol.: Jałowiec pospolity; Per.: Tukhm-e-rahl;
Pol.: Jałowiec pospolity; Por.: Junípero, Zimbro-comum; Rus.: Bepec,
Mozhzhevelnik; Spa.: Azotacristos, Enebro común, Enebro real, Xinebro; Swe.: En,
Vanlig en; Tur.: Ardıç, Ardıç yemişi; Vie.: Cây bách xù.
Description: J. communis is a native of Greece,XL but has widespread distribution
in both hemispheres, primarily in lower elevations [13], and found in Europe,
Africa, northern Asia, temperate Eurasia, India, Iran, and North America. Juniper
fruits are berry-like cones, nearly globular, about 5–7 mm in diameter, green while
unripe, dark purplish, and covered with a bluish-gray bloom when ripe; the short
stalk at the base contains one or two whorls of the small scales, and the apex is
marked by three radiating furrows, which are surrounded by ridges enclosing a
triangular space. Berries have an aromatic somewhat balsamic odor, and a sweet,
terebinthinate, bitter, and slightly acrid taste. Three bony seeds, ovate, triangular
above, have six to ten large oil sacs on their surface, are imbedded in a brownish
pulp which also contains oil cells. Oil of juniper berries is colorless or pale
greenish-yellow, limpid, but on exposure to air rapidly thickens and turns yellow,
and ultimately reddish-brown and acquiring an acid reaction; the fresh distilled oil
from old juniper-berries is thick and yellow. Old oil of juniper contains formic acid.
It is said that juniper is the enemy of Date tree, and that the two will not grow
together in the same place (Figs. 1, 2 and 3).XL
Actions and Uses: Dioscorides described its diuretic and digestive properties, and
use in cough and pectoral affections.XL Avicenna said that abhal fruit boiled in rose
oil (Roghan gul) in an iron vessel until the fruit becomes darker, and using this oil
as ear drops is very beneficial for hearing loss,CXXXXVII and 5 drops of oil may
cause abortion.1 Ibn al-BaitarLXIX quoted Dioscorides in describing two plant
varieties of it; one with big thorn and unpleasant smell that grows more in width
than in height; and is astringent, diuretic, emmenagogue, abortifacient, purgative,

1
Tayyab M: Personal Communication.
Juniperus communis L. 1051

Fig. 1 Juniperus communis, Young Shoots in Slovakia, Cruiser, WikimediaCommons; 3.0

Unported CC BY 3.0, https://commons.wikimedia.org/wiki/File:Juniperus_communis_MF.JPG;
https://creativecommons.org/licenses/by/3.0/deed.en

Fig. 2 Juniperus communis, Ripe and Unripe Cones in Estonia, Pt, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Juniperus_
communis_at_Valjala_on_2005-08-11.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
1052 Juniperus communis L.

Fig. 3 Juniperus communis, Berries as sold in the U.S., Prof. Akbar, Original

anthelmintic, and can cause hematuria. Razi (Rhazes) said application of powdered
abhal relieves gum sores and foul smell. Sharief says that powdered abhal (35 g)
mixed with ghee (purified butter 20 g) and honey (35 g) is beneficial for bronchial
asthma. Abhal ground with vinegar and applied topically cures ringworm of the
scalp. In Unani medicine, fruit (temperament, hot 2° and dry 2°) is regarded
astringent, strong resolvent, carminative, stomachic, anthelmintic, deobstruent,
strong diuretic, and emmenagogue. Powdered fruits (7–10 g) are used in cases of
amenorrhea, but it is contraindicated in women with hot temperament. It is such a
powerful diuretic that its continuous use may cause hematuria and abortion in
pregnant women.LXXVII Ripe fruit is extracted in alcohol to produce Juniperus
Communis Extract. Oil produced using steam distillation is solely used as fragrance
ingredient [2]. The oil is stomachic, diuretic and carminative in small doses, and a
powerful renal stimulant and diuretic in normal doses; externally, the oil is skin
irritant.XXI,CV
Navajo tribe of the native Americans used berries for the treatment of diabetes
[26], and as a traditional cure for tuberculosis and other respiratory diseases [15].
The First Nations of the Canadian Maritimes use infusions of juniper primarily as a
tonic and for the treatment of tuberculosis. Isocupressic acid, communic acid and
deoxypodophyllotoxin have been identified as the principal constituents responsible
for the antimycobacterial activity of aerial parts [5]. In Turkish folk medicine,
Juniperus genera are used as diuretic, stimulant, and antiseptic, for common cold
and wound healing [41]. Juniperus leaves are also described as urinary antiseptic
and antiadhesion [43]. A drug composition containing tobacco leaves tincture acts
on tumors of stomach, pylorus, esophagus and duodenum. The tincture may be
combined with an adjuvant made up of a mineral-vegetable medicament or it
may be in the form of pills, pellets or liquids to be taken at the same time as
the mineral-vegetable medicament. The adjuvant is composed of 6 parts Juniper
Juniperus communis L. 1053

berries, 3 parts gum Arabic and optionally 2 parts St. John’s wort and 1-part bitter
orange peel extract with reference to 1-part Fe2O3. Tobacco leaf tincture is obtained
by coarsely cutting washed fresh leaves, adding 1.5–2 parts ethyl alcohol/leaf,
macerating (up to 15 days), filtering and pressing. Thus, a composition contained
40 drops tobacco leaf tincture and 200 g adjuvant [39]. It is also reportedly used as
diuretic and diaphoretic and for treatment of chronic skin diseases by folk medicine
practitioners of Saudi Arabia, and also used in lotions for facial skin only [23], and
in hair lotion [3]. In South Korea, fruits are used in the treatment of skin diseases
[20]. The carbonic (CO2) extract of juniper berries is reported to improve
treatment-prophylaxis effect of tooth paste [11]. J. communis is approved for GI
disorders use in Europe since Oct. 2007 by the HMPC of the European Medicines
Agency.
Phytoconstituents: Fruits (berries) contain 1.2% oil and 21.6% tannins, and the
carbohydrate content range 30.6–32.3% (on dry matter basis) with glucose and
fructose being the main fruit carbohydrates [36], diterpenes [28], flavonoids, such
as hypolaetin-7-pentoside and quercetin-hexoside, gossypetin-hexoside-pentoside
and gossypetin-hexoside [31], isoscutellarein and 8-hydroxyluteolin or hypolaetin
glycosides, and biflavonoids, amentoflavone, hynokiflavone, cupressoflavone, and
methyl-biflavones [19], imbricatolic acid and juniperoside A [10]. Constituents of
fruit volatile oil may vary with region and may contain 1-terpinen-4-ol, a-pinene,
camphene and the sesquiterpene candinene, d-limonene, cymene, borneol and
myrcene.XXIV,CXXXXI Essential oil (yield 2.95%) from berries of J. communis
growing wild in Greece consisted of high content of a-pinene (ca 27%), sabinene
(13%), germacrene-D (10%), and myrcene (9%), which showed mainly seasonal
quantitative variations [6]. Yield of EO from berries collected from various loca-
tions in Kosovo varied and ranged from 0.4 to 3.8% (v/w, based on the dry weight).
In total, 42 compounds were identified in the EO; the principal components being
a-pinene, followed by b-myrcene, sabinene, and D-limonene [17]. Yield of EO of
dried berries of Estonian origin ranged between 0.2 and 0.6%, rich in a-pinene
(53.6–62.3%), b-myrcene (6.5–6.9%) and germacrene D (4.5–6.1%) [32]; a-pinene
and myrcene also constituted the bulk (67.56%) of EO of J. communis growing
wild in Sardinia. Amongst fifteen species of conifers, the highest content of
ascorbic acid is found in J. communis during winter, regardless of the age of the tree
[37]. Juniper berry oil from Bulgaria comprised of monoterpene hydrocarbons, such
as a-pinene (51.4%), myrcene (8.3%), sabinene (5.8%), limonene (5.1%) and
b-pinene (5.0%) [18]. Quantity of oil in fruits increased with altitude from 300 to
700 m; from there to 1,300 m the subminimal values decreased [9]. Concentration
of soluble phenolic and terpenoids in juniper needles, collected in Finland,
increased with latitude and altitude with higher content of monoterpenoids,
proanthocyanidins and flavonols in northern latitudes [29]. Chemical composition
of J. communis oil and Juniperus Communis Extract is reported to be similar, each
containing terpenoids and aromatic compounds, with occasional aliphatic alcohols
and aldehydes, and rarely alkanes [2].
1054 Juniperus communis L.

Pharmacology: Juniper berries decoction decreased glycemic levels in normo-

glycemic rats and significantly reduced blood glucose, mortality index, and loss of
body weight of STZ-diabetic rats [38]. Dried berries supplied in diet (6.25% by
weight) reduced STZ-induced hyperglycemia with reduction in polydipsia, and a
reduced rate of body weight loss in mice [40]. Methanol berries extract showed
significant antioxidant activity [31]. Juniper oil from Bulgaria exhibited antioxidant
activity both in vitro and in vivo [18], and from trees growing in Mediterranean and
Isparta (Greece) regions decreased oxidative stress and increased antioxidant
enzymes activity in hearts of hypercholesterolemic rats [16]. Aqueous-ethanol
extract of bark exhibited strong pancreatic lipase inhibitory activity [24].
The oil was bactericidal against both Gram-positive and Gram-negative bacterial
species, strong fungicidal against yeasts, yeast-like fungi and dermatophytes [34, 42].
Strong antibacterial and antifungal activity of juniper berry oil is probably due to high
concentrations of (-)-a-pinene, p-cymene and b-pinene, but none of the single oil
components showed better activity than the oil itself [12]. Leaf oil is the most
effective sporicidal against B. subtilis spores, reducing the number of viable spores by
3 logs at concentrations above 1%. However, none of the major oil components
exhibited equivalent activity compared to the oil [25]. The fact that oil components,
either alone or in combination did not show the same level of sporicidal activity
indicates a synergistic activity of all constituents. The oil, however, failed to inhibit
any of the foodborne pathogens and spoilage microorganisms at the highest con-
centrations tested [8]. Methanol extract of needles was active against both
antibiotic-sensitive and -resistant S. aureus strains [29], also inhibited growth of
M. tuberculosis [21], and methanol extract of berries inhibited growth of 15 strains of
H. pylori with an MIC of 100 mcg/ml [27].
Ethanol extract of berry-like cones produced 60% inhibition of carrageenan-
induced inflammation in rats [30]. Agrawal et al. [1] reported anti-implantation
activity of seeds; this anti-implantation activity of the acetone and ethanol seed
extracts has been corroborated [7, 35]. Ethanol extract exhibited antiprogestrone
activity [33]. Juniper needles are also reported abortifacient in cows [14]. Berries
extracts showed significant in vitro cytotoxicity against liver and colon carcinomas,
and myosarcoma cells in G2, M and G0 phases [4].
Mechanism of Action: Juniper berry EO reduces reperfusion liver injury by
inhibiting activation of Kupffer cells, reducing vasoactive eicosanoid release and
improving hepatic microcirculation under oxidative stress [22]. Antiprogestrone
activity might be responsible for its anti-implantation activity [33].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: The oil is neither skin irritant, nor phototoxic in animal tests.
Rats tolerated an oral dose of up to 2,500 mg/kg without any adverse effects [30].
However, Juniperus Communis Extract affects fertility and was abortifacient in
albino rats [2].
Juniperus communis L. 1055

Commentary: A plant with long historical background and potentials for signi-
ficant clinical uses, has not been sufficiently investigated pharmacologically, and no
formal clinical studies have been conducted.

References
1. Agrawal OP, Bhardwaj S, Mathur R. Antifertility effects of fruits of
Juniperus communis. Planta Med Suppl. 1980;98–101.
2. Anonymous. Final report on the safety assessment of Juniperus communis
Extract, Juniperus oxycedrus Extract, Juniperus oxycedrus Tar, Juniperus
phoenicea extract, and Juniperus virginiana Extract. Int J Toxicol. 2001;20
Suppl 2:41–56.
3. Banfi A, Leibinger J, Molnar L, et al. Lotion for hair treatment. Belg.
1981;884:621 (Cl.A61K).
4. Bayazit V. Cytotoxic effects of some animal and vegetable extracts and
some chemicals on liver and colon carcinoma and myosarcoma. Saudi
Med J. 2004;25:156–63.
5. Carpenter CD, O’Neill T, Picot N, et al. Antimycobacterial natural products
from the Canadian medicinal plant Juniperus communis. J Ethnopharmacol.
2012;143:695–700.
6. Chatzopoulou PS, Katsiotis ST. Study of the essential oil from Juniperus
communis “Berries” (Cones) growing wild in Greece. Planta Med. 1993;
59:554–6.
7. Chaudhury RR. The quest for a herbal contraceptive. Natl Med J India. 1993;
6:199–201.
8. Cosentino S, Barra A, Pisano B, et al. Composition and antimicrobial
properties of Sardinian Juniperus essential oils against foodborne pathogens
and spoilage microorganisms. J Food Prot. 2003;66:1288–91.
9. Del Rio Ibanez J. Quantity and characteristics of the essential oil of
J. communis harvested at various altitudes. Farm Sci Tec (Pavia). 1952;7:
319–23.
10. De Marino S, Cattaneo F, Festa C, et al. Imbricatolic acid from Juniperus
communis L. prevents cell cycle progression in CaLu-6 cells. Planta Med.
2011;77:1822–8.
11. Fedorov YA, Kaliberdina NV, Todorashko VP. Effect of (tooth) pastes
containing biologically active ingredients on the oral cavity tissues.
Maslo-Zhir Prom St. 1977;12:22.
12. Filipowicz N, Kamiński M, Kurlenda J, et al. Antibacterial and antifungal
activity of juniper berry oil and its selected components. Phytother Res.
2003;17:227–31.
13. Filipowicz N, Piotrowski A, Ochocka JR, Asztemborska M. The phyto-
chemical and genetic survey of common and dwarf juniper (Juniperus
communis and Juniperus nana) identifies chemical races and close
taxonomic identity of the species. Planta Med. 2006;72:850–3.
1056 Juniperus communis L.

14. Gardner DR, Panter KE, James LF, Stegelmeier BL. Abortifacient effects of
lodgepole pine (Pinus contorta) and common juniper (Juniperus communis)
on cattle. Vet Hum Toxicol. 1998;40:260–3.
15. Gordien AY, Gray AI, Franzblau SG, Seidel V. Antimycobacterial terpenoids
from Juniperus communis L. (Cuppressaceae). J Ethnopharmacol. 2009;126:
500–5.
16. Gümral N, Doguc Kumbul D, Aylak F, et al. Juniperus communis Linn oil
decreases oxidative stress and increases antioxidant enzymes in the heart of
rats administered a diet rich in cholesterol. Toxicol Ind Health. 2015;31:
85–91.
17. Hajdari A, Mustafa B, Nebija D, et al. Chemical composition of Juniperu
communis L. cone essential oil and its variability among wild populations in
Kosovo. Chem Biodivers. 2015;12:1706–17.
18. Höferl M, Stoilova I, Schmidt E, et al. Chemical composition and
antioxidant properties of juniper berry (Juniperus communis L.) essential
oil action of the essential oil on the antioxidant protection of Saccharomyces
cerevisiae model organism. Antioxidants (Basel). 2014;3:81–98.
19. Innocenti M, Michelozzi M, Giaccherini C, et al. Flavonoids and biflavonoids
in Tuscan berries of Juniperus communis L.: detection and quantitation by
HPLC/DAD/ESI/MS. J Agric Food Chem. 2007;55:6596–602.
20. Jegal J, Park SA, Chung K, et al. Tyrosinase inhibitory flavonoid from
Juniperus communis fruits. Biosci Biotechnol Biochem. 2016;80:2311–7.
21. Jimenez-Arellanes A, Meckes M, Ramirez R, et al. Activity against
multidrug-resistant Mycobacterium tuberculosis in Mexican plants used to
treat respiratory diseases. Phytother Res. 2003;17:903–8.
22. Jones SM, Zhong Z, Enomoto N, et al. Dietary juniper berry oil minimizes
hepatic reperfusion injury in the rat. Hepatology. 1998;28:1042–50.
23. Karapet’yan SY, Kokoshvili EM, Tarasenko YA. Lotion for oily facial skin.
USSR. 1972;333:947 (Cl. A61K).
24. Kim HY, Kang MH. Screening of Korean medicinal plants for lipase
inhibitory activity. Phytother Res. 2005;19:359–61.
25. Lawrence HA, Palombo EA. Activity of essential oils against Bacillus
subtilis spores. J Microbiol Biotechnol. 2009;19:1590–5.
26. McCabe M, Gohdes D, Morgan F, et al. Herbal therapies and diabetes
among Navajo Indians. Diabetes Care. 2005;28:1534–5.
27. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helico-
bacter pylori to botanical extracts used traditionally for the treatment of
gastrointestinal disorders. Phytother Res. 2005;19:988–91.
28. Martin AM, Queiroz EF, Marston A, Hostettmann K. Labdane diterpenes
from Juniperus communis L. berries. Phytochem Anal. 2006;17:32–5.
29. Martz F, Peltola R, Fontanay S, et al. Effect of latitude and altitude on the
terpenoid and soluble phenolic composition of juniper (Juniperus commu-
nis) needles and evaluation of their antibacterial activity in the boreal zone.
J Agric Food Chem. 2009;57:9575–84.
Juniperus communis L. 1057

30. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal

plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
31. Miceli N, Trovato A, Dugo P, et al. Comparative analysis of flavonoid
profile, antioxidant and antimicrobial activity of the berries of Juniperus
communis L. var. communis and Juniperus communis L. var. saxatilis Pall
from Turkey. J Agric Food Chem. 2009;57:6570–7.
32. Orav A, Kailas T, Muurisepp M. Chemical investigation of the essential oil
from berries and needles of common juniper (Juniperus communis L.)
growing wild in Estonia. Nat Prod Res. 2010;24:1789–99.
33. Pathak S, Tewari RK, Prakash AO. Hormonal properties of ethanolic extract
of Juniperus communis Linn. Anc Sci Life. 1990;10:106–13.
34. Pepeljnjak S, Kosalec I, Kalodera Z, Blazević N. Antimicrobial activity of
juniper berry essential oil (Juniperus communis L., Cupressaceae). Acta
Pharm. 2005;55:417–22.
35. Prakash AO, Saxena V, Shukla S, et al. Anti-implantation activity of some
indigenous plants in rats. Acta Europ Fert. 1985;16:441–8.
36. Ramić S, Murko D. Chemical composition of fruit of Juniperus species.
Arch Farm. 1983;33:15–20.
37. Retezeanu M, Bojor O, Mihailescu S, Albinescu R. Variability of ascorbic
acid content in various species of conifers in Romania. Farmacia (Rom).
1965;13:109–16.
38. Sánchez de Medina F, Gámez MJ, Jiménez I, et al. Hypoglycemic activity
of juniper “Berries”. Planta Med. 1994;60:197–200.
39. Soliman H. Antitumoral drug from tobacco leaves. Fr Demande. 1972;2:129
(Cl.A61K) 8 Dec 1972.
40. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatments
for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetolo-
gia. 1990;33:462–4.
41. Tumen I, Süntar I, Keleş H, Küpeli Akkol E. A therapeutic approach for
wound healing by using essential oils of Cupressus and Juniperus species
growing in Turkey. Evid Based Complement Alternat Med. 2012;2012:
728281.
42. Wanner J, Schmidt E, Bail S, et al. Chemical composition and antibacterial
activity of selected essential oils and some of their main compounds. Nat
Prod Commun. 2010;5:1359–64.
43. Yarnell E. Botanical medicines for the urinary tract. World J Urol. 2002;20:
285–93.
Justicia adhatoda L.
(Acanthaceae)

(Syns.: Adhatoda vasica Nees.; A. pubescens Moench.; A. zeylanica Medik.;

Dianthera latifolia Salisb)

Abstract
It is a small tree or a large bushy shrub, found in India and Sri Lanka. The shrub
has considerable reputation all over India as an expectorant, antispasmodic and
alterative, and is largely prescribed in chest affections associated with cough,
asthma, dyspnea, emphysema, and hectic fever. Leaves possess aromatic,
antiseptic, insecticidal, expectorant and hemostatic properties, and are recom-
mended to lessen throat inflammation, to reduce cough, to lessen gingival
inflammation, and to arrest bleeding from the mouth, nose, rectum and urinary
tract. In the Nighanthas it is described to remove phlegm, bile and impurities of
the blood; a remedy for asthma, cough, fever, vomiting, gonorrhea, leprosy and
phthisis. Sanskrit writers call it Vasaka, Vansa, Sinha-mukhi (lion-mouthed),
Sinha-parni (lion-leaved), and Atarŭsha. In Hindu Materia Medica, there was a
saying ‘that no man suffering from phthisis need despair as long as the Vasaka
plant exists.’ In Unani medicine, four varieties based on the color of the flowers
have been described. Black variety is bitter and tangy; used for the treatment of
phlegmatic inflammations, colic, leprosy and wounds. White variety is glossy,
bitter and sweetish-tangy; used for the treatment of teeth and hair, leprosy, blood
and phlegm impurity. Red variety is bitter and hot; used for bilious colic, cough
and asthma. Yellow variety is hot, bitter and astringent; used for digestive
weakness and blood impurity. Six different quinazoline alkaloids, vasicoline,
vasicolinone, vasicinone, vasicine, adhatodine and anisotine have been isolated
from the leaves. Oral administration of the extract shows antitussive activity,
similar to codeine, against irritant aerosol-induced cough in guinea pigs.
Antitubercular activity of the plant extracts and vasicine derivatives was
observed by various authors. Aqueous leaf extract and alkaloids, vasicine acetate
and 2-acetyl benzylamine, were active against sensitive and MDR strains of
M. tuberculosis. Application of leaf extract and massage of inflammed gums by
patients suffering from pyorrhea produced a significant and consistent improve-
ment in inflammation and bleeding.

© Springer Nature Switzerland AG 2020 1059

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_114
1060 Justicia adhatoda L.

Keywords





Arusa Bansa Basak Carmantine en arbre Hashishatul-sua’l Malabar nut





Malabarnußbaum Valkopantterinkita Vasaka Ya zui hua

Vernaculars: Urd.: Arusa, Bansa, Bisonta; Hin.: Adalsa, Adosa, Adulasa, Arusa,
Arusha, Asganda, Bansa, Rus; San.: Adarushah, Arusak, Sinhaparni, Utarosha,
Vaidyamatru, Vansa, Varisha sinhamukhi, Vasaka, Vrikshaha; Ben.: Adulsa,
Bakash, Bāsaka pātā, Vasaka; Guj.: Adulso, Aduraspee, Aradusī, Bansa; Mal.:
Adalodakam, Ataloetakam; Mar.: Adalsa, Adulsa, Arusa; Tam.: Adadoda,
Adadodai, Adatodai, Eidhadad, Pavettai; Tel.: Adampaka, Addasaram, Addasar-
amu, Lion-mouthed, Senha parni, Sinha-makki; Ara.: Hashishatul-Sua’l; Chi.:
大还魂, 鸭嘴花, Ya zui hua; Dan.: Malabarnød; Eng.: Coral-wood tree, Malabar
nut; Fin.: Valkopantterinkita; Fre.: Carmantine en arbre, Carmantine de Ceylan,
Noix de Malabar, Noyer des Indes; Ger.: Malabarnußbaum; Ind.: Adotodai, Basak,
Vasaka; Maly.: Kacang malabar; Nep.: Asuro, Kalo vasak; Per.: Bansa; Sin.:
Adathoda, Agaladara, Pawatta; Swe.: Malabarnöt.
Description: It is a small tree or a large bushy shrub, found in India (from Punjab
to Assam) and Sri Lanka; trunk straight; bark pretty smooth, ash-colored; branches
suberect, with bark like that of trunk but smoother; leaves opposite, short petioled,
broad lanceolar, long, taper-pointed, smooth on both sides, about 12–15 cm long
and 3–4 cm broad; spikes from the exterior axills, solitary, long peduncled, the
whole end of the branchlet forming a leafy panicle, flower bearing portion short and
covered with large bracts; flowers in the cold season, flowers opposite, large,
white with small ferruginous dots, the lower part of both lips streak with purple
(Figs. 1 and 2).XL

Fig. 1 Justicia adhatoda, Plants, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Justicia_adhatoda_001.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Justicia adhatoda L. 1061

Fig. 2 Justicia adhatoda, Flower, ShineB, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Justicia_adhatoda_1.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Actions and Uses: The shrub has considerable reputation all over India as an
expectorant, antispasmodic and alterative, and is largely prescribed in chest affec-
tions associated with cough, asthma, dyspnea, emphysema, and hectic fever.LXXXI,CV
Leaves possess aromatic, antiseptic, insecticidal, expectorant and hemostatic prop-
erties, and are recommended to lessen throat inflammation, to reduce cough, to lessen
gingival inflammation, and to arrest bleeding from the mouth, nose, rectum and
urinary tract.XXI,LXXXIV,CV In the Nighanthas it is described to remove phlegm, bile
and impurities of the blood; a remedy for asthma, cough, fever, vomiting, gonorrhea,
leprosy and phthisis. Sanskrit writers call it Vasaka, Vansa, Sinha-mukhi
(lion-mouthed), Sinha-parni (lion-leaved), and Atarŭsha. In Hindu Materia Medica,
there was a saying ‘that no man suffering from phthisis need despair as long as the
Vasaka plant exists.’XL In Ayurveda, dried mature leaves are used in kāsa, śwāsa,
ksaya, raktapitta, prameha, kāmalā, and kustha.LIX Leaves, either dried or fresh, are
used as mucolytic agents; also active against Tubercle bacilli.LXXXVIII Naga tribes of
India use the plant to treat intestinal worm infestation [42]. The author of Makhzan-
ul-Advia described that the wood is used to make tooth picks and gun powder.
Medicinally, flowers are useful in hectic fever, heat of blood and gonorrhea; the root
in cough, asthma, febrile disturbance and gonorrhea. In Unani medicine, four vari-
eties based on the color of the flowers have been described. Black variety is bitter and
tangy (charpara); used for the treatment of phlegmatic inflammations, colic, leprosy
and wounds. White variety is glossy, bitter and sweetish-tangy; used for the treatment
1062 Justicia adhatoda L.

of teeth and hair, leprosy, blood and phlegm impurity. Red variety is bitter and hot;
used for bilious colic, cough and asthma. Yellow variety is hot, bitter and astringent;
used for digestive weakness and blood impurity.L KabeeruddinLXXVII described it
(temperament, hot 1° and dry 1°) expectorant, removes phlegm from the bronchioles,
anticonvulsant, vermifuge, blood purifier, febrifuge and coagulant. It is used for the
treatment of asthma, cough and hoarseness of voice; and its root decoction is used in
whooping cough, and as a remedy for tuberculosis. Due to its blood purifying activity
it is used in leprosy and scabies; also used in epistaxis and hemoptysis.
Ainslie states. ‘in Ceylon the tree is said to grow to the height of fourteen or
fifteen feet and are prescribed in certain cases of asthma and to prevent the return of
rigor in intermittent fever.’ Strong testimony in favor of the remedial properties of
the drug was furnished to the authors of the Pharmacopoeia of India by Drs.
Jackson and Dutt, who employed it with marked success in chronic bronchitis,
asthma and other pulmonary and catarrhal affections. In Bengal, leaves are smoked
in asthma. Most of the evidence shows that the drug has a definite expectorant
action. In acute bronchitis it always afforded relief, specially where the sputum was
thick and tenacious. The depression of the vagal terminations further relieves irri-
tation and spasm of the bronchioles.XXI Flowers and roots with ginger are used in
ague, rheumatism, asthma, chronic bronchitis and other chest afflictions; and the
leaves are often smoked in asthma.LXXXI
Phytoconstituents: Constituents of leaves include adhatodic acid and the alkaloid,
vasicine (peganine); the alkaloid is found in leaves to the extent of 0.25%.CXXXXI
Six different quinazoline alkaloids, vasicoline, vasicolinone, vasicinone, vasicine,
adhatodine and anisotine have been isolated from the leaves [25]. Anisotinine,
betaine, vasakin, vasicinine, vasicinol have also been reported in the plant [21, 27].
Dymock et al.XL mentioned the following analysis of the leaves: volatile odorous
principle 0.2%, chlorophyll, fat, and alkaloid 3.2%, adhatodale of vasicine, resin
and sugar 12.5%, gum 3.87%, coloring matter 4.83%, other organic matters and
salts 10.38%, organic residue 40.71%, inorganic residue 9.59%. Ash contains water
soluble portion 23.38%, acid soluble portion 75.12% and insoluble residue 1.5%.
Pharmacology: Oral administration of the extract shows antitussive activity,
similar to codeine, against irritant aerosol-induced cough in guinea pigs. However,
antitussive activity of intravenous injection against mechanically and electrically-
induced coughing in rabbits and guinea pigs was only 1/20–1/40 to that of codeine.
Administration (i.v.) of alkaloids produces slight but persistent bronchodilatation,
which is potentiated by pretreatment with atropine, and antagonized with small
doses of pilocarpine [10]. Antitubercular activity of the plant extracts and vasicine
derivatives was observed by various authors [3, 13, 14, 35]. Aqueous leaf extract
and alkaloids, vasicine acetate and 2-acetyl benzylamine, were active against sen-
sitive and MDR strains of M. tuberculosis [18, 20]. However, vasicine and its salts
showed no inhibitory effect on the cultures and growth of Streptococci, Staphylo-
cocci, Balanitides coli, B. diphtheria or B. tuberculosis, but was effective against
E. coli and C. albicans [38]. Antiseptic properties of leaves reported by previous
observers are suggested to be due to volatile principle. Methanol leaf extract in
Justicia adhatoda L. 1063

800 mg/kg dose showed anticestodal activity better than praziquantal (5 mg/kg) in a
Hymenolepis diminuta-rat model [42].
Leaf powder showed considerable gastric antiulcer activity in rats, especially
against ethanol-induced ulceration [37]. However, methanol, acetone and water
extracts did not show significant activity against H. pylori [2]. A significant hep-
atoprotective effect of leaf water extract in rats was also reported [5]. Petroleum
ether, ether and water extracts of leaves, administered 7-days before and 14-days
during cohabitation in mice and 5-days after mating in rats produced no antifertility
activity [4]. However, the ethanol extract showed 60–70% anti-implantation
activity in rats [33], and leaf aqueous or 90% ethanol extracts administered orally to
rats for 10-days after insemination caused abortion in 100% rats at doses equivalent
to 175 mg/kg of starting dry material [31]. Ethanol leaf extract had no in vitro
insulinotropic effect [19].
Chloroform soluble portion of ethanol extract showed activity against P 388
lymphocytic leukemia and epidermoid carcinoma of the nasopharynx [22]. Pre-
treatment of mice with ethanol leaf extract reduced radiation-induced percent
mortality, increased survival time, prevented chromosomal damage, and signifi-
cantly lessened testicular damage [28, 29]. Leaf extract also significantly reduced
cadmium chloride-induced mutagenic effects, LPO and XO activity [23] and was
protective against oxidative stress and renal carcinogenesis [24]. Methanol leaf
extract exhibited radical scavenging activity, that was correlated to its phenolic
contents [26]; whereas, petroleum ether extract with high phenolic contents was
reported with significant antioxidant activity due to an acyclic triterpenoid [9].
Pretreatment of rats with a spray-dried formulation of leaf extract protected against
aflatoxin B1 toxicity [6]; the antiaflatoxin B1 activity of water extract was also
observed in in vitro tests [40].
Clinical Studies: Application of leaf extract and massage of inflamed gums twice
daily for 3-weeks by patients suffering from pyorrhea produced a significant and
consistent improvement in inflammation and bleeding on a daily and weekly basis
[12, 32].
Mechanism of Action: Essential oil contents may be responsible for its well-
marked expectorant action, while the alkaloid vasicinone has been credited for
bronchodilating activity [1, 30, 34]. Mechanism of action for its antiallergic activity
is unknown [41]; and the protective effect against allergen-induced bronchial
obstruction in guinea pigs was ascribed to unknown alkaloids [11]. Chakraborty
and Brantner [7] reported potent anti-inflammatory activity of alkaloid fraction
comparable to hydrocortisone; vasicinone and vasicine are the alkaloids responsible
for this effect [38]. Vasicine was also suggested to be responsible for its antioxidant
activity [36].
Human A/Es, Allergy and Toxicity: Abortifacient activity of both aqueous and
ethanol extracts, especially the commonly used aqueous extract, has raised concern
about its safe use during pregnancy [8]. Vasicine has been identified as the
1064 Justicia adhatoda L.

uterotonic abortifacient [15–17]. It is also described not suitable for people with
cold temperament.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interactions: It acts as a bifunctional
inducer of both phase I and phase II liver enzymes. Other organs viz., lung, kidney
and forestomach are also stimulated to increase detoxification of xenobiotics; but
liver and lung show a more consistent induction [39].
Commentary: It is inconceievable that no formal clinical studies on this exten-
sively used drug in Indian traditional medicines for cough and bronchial asthma for
hundreds of years, have been conducted. Also, the observations in the only clinical
trials in patients suffering from pyorrhea have not been reproduced.

References
1. Amin AH, Mehta DR. A bronchodilator alkaloid (vasicinone) from Adhatoda
vasica. Nature. 1959;184 Suppl 17:1317.
2. Amin M, Anwar F, Naz F, et al. Anti-Helicobacter pylori and urease
inhibition activities of some traditional medicinal plants. Molecules. 2013;
18:2135–49.
3. Barry VC, Conalty ML, Rylance HJ, Smith FR. Antitubercular effect of an
extract of Adhatoda vasica. Nature. 1955;176:119–20.
4. Bhaduri B, Ghose CR, Bose AN, et al. Antifertility activity of some
medicinal plants. Indian J Exp Biol. 1968;6:252–3.
5. Bhattacharyya D, Pandit S, Jana U, et al. Hepatoprotective activity of
Adhatoda vasica aqueous leaf extract on D-galactosamine-induced liver
damage in rats. Fitoterapia. 2005;76:223–5.
6. Brinda R, Vijayanandraj S, Uma D, et al. Role of Adhatoda vasica (L.) Nees
leaf extract in the prevention of aflatoxin-induced toxicity in Wistar rats.
J Sci Food Agric. 2013;93:2743–8.
7. Chakraborty A, Brantner AH. Study of alkaloids from Adhatoda vasica
Nees on their anti-inflammatory activity. Phytother Res. 2001;15:532–4.
8. Claeson UP, Malmfors T, Wikman G, Bruhn JG. Adhatoda vasica: a critical
review of ethnopharmacological and toxicological data. J Ethnopharmacol.
2000;72:1–20.
9. Dhankhar S, Dhankhar S, Ruhil S, et al. Isolation and biological evaluation
of novel tetracosahexaene hexamethyl, an acyclic triterpenoids derivatives
and antioxidant from Justicia adhatoda. Comb Chem High Throughput
Screen. 2014;17:723–32.
10. Dhuley JN. Antitussive effect of Adhatoda vasica extract on mechanical or
chemical stimulation-induced coughing in animals. J Ethnopharmacol. 1999;
67:361–5.
11. Dorsch W, Wagner H. New antiasthmatic drugs from traditional medicine?
Int Arch Allergy Appl Immunol. 1991;94:262–5.
Justicia adhatoda L. 1065

12. Doshi JJ, Patel VK, VenkataKrishna-Bhatt H. Effect of Adhatoda vasica

massage in pyarroea. Int J Crude Drug Res. 1983;21:173–6.
13. Grange JM, Snell NJ. Activity of bromhexine and ambroxol, semisynthetic
derivatives of vasicine from the Indian shrub Adhatoda vasica, against
Mycobacterium tuberculosis in vitro. J Ethnopharmacol. 1996;50:49–53.
14. Gupta KC, Chopra IC. Antitubercular action of Adhatoda vasica (N.O.
acanthacea). Indian J Med Res. 1954;42:355–8.
15. Gupta OP, Anand KK, Ghatak BJ, Atal CK. Vasicine, alkaloid of Adhatoda
vasica, a promising uterotonic abortifacient. Indian J Exp Biol. 1978;16:
1075–7.
16. Gupta OP, Sharma ML, Ghatak BJ, Atal CK. Pharmacological investiga-
tions of vasicine and vasicinone—the alkaloids of Adhatoda vasica. Indian J
Med Res. 1977;66:680–91.
17. Gupta OP, Sharma ML, Ghatak M, et al. Potent uterine activity of alkaloid
vasicine. Indian J Med Res. 1977;66:865.
18. Gupta R, Thakur B, Singh P, et al. Antituberculosis activity of selected
medicinal plants against multidrug resistant Mycobacterium tuberculosis
isolates. Indian J Med Res. 2010;131:809–13.
19. Hussain Z, Waheed A, Qureshi RA, et al. The effect of medicinal plants of
Islamabad and Murree region of Pakistan on insulin secretion from INS-1
cells. Phytother Res. 2004;18:73–7.
20. Ignacimuthu S, Shanmugam N. Antimycobacterial activity of two natural
alkaloids, vasicine acetate and 2-acetyl benzylamine, isolated from Indian
shrub Adhatoda vasica Ness. leaves. J Biosci. 2010;35:565–70.
21. Ikram M, Ehsanul Haq M. Estimation of vasicine from the flowering tops of
Adhatoda vasica. Pakistan J Sci Res. 1966;18:109–10.
22. Ikram M. Screening of medicinal plants of Pakistan for anticancer activity.
Fitoterapia. 1983;LIV:123.
23. Jahangir T, Khan TH, Prasad L, Sultana S. Reversal of cadmium chloride-
induced oxidative stress and genotoxicity by Adhatoda vasica extract in
Swiss albino mice. Biol Trace Elem Res. 2006;111:217–28.
24. Jahangir T, Sultana S. Tumor promotion and oxidative stress in ferric
nitrilotriacetate-mediated renal carcinogenesis: protection by Adhatoda vasica.
Toxicol Mech Methods. 2007;17:421–30.
25. Jha DK, Panda L, Lavanya P, et al. Detection and confirmation of alkaloids
in leaves of Justicia adhatoda and bioinformatics approach to elicit its
antituberculosis activity. Appl Biochem Biotechnol. 2012;168:980–90.
26. Jha DK, Panda L, Ramaiah S, Anbarasu A. Evaluation and comparison of
radical scavenging properties of solvent extracts from Justicia adhatoda leaf
using DPPH assay. Appl Biochem Biotechnol. 2014;174:2413–25.
27. Johne S, Groeger D, Hesse M. Alkaloids. 142. New alkaloids from Adhatoda
vasica. Helv Chim Acta. 1971;54:826–34.
28. Kumar A, Ram J, Samarth RM, Kumar M. Modulatory influence of Adhatoda
vasica Nees leaf extract against gamma irradiation in Swiss albino mice.
Phytomed. 2005;12:285–93.
1066 Justicia adhatoda L.

29. Kumar M, Samarth R, Kumar M, et al. Protective effect of Adhatoda vascia

Nees against radiation-induced damage at cellular, biochemical and chro-
mosomal levels in Swiss albino mice. Evid Based Complement Alternat
Med. 2007;4:343–50.
30. Mithal BM, Arora RB, Agarwal SL. Vasicinone—an indigenous respiratory
stimulant. Ind Pract. 1956;9:81.
31. Nath D, Sethi N, Singh RK, Jain AK. Commonly used Indian abortifacient
plants with special reference to their teratologic effects in rats. J Ethnophar-
macol. 1992;36:147.
32. Patel VK, Venkatakrishna-Bhatt H. In vitro study of antimicrobial activity
of Adhatoda vasica Linn. (leaf extract) on gingival inflammation—a
preliminary report. Indian J Med Sci. 1984;38:70–2.
33. Prakash AO, Saxena V, Shukla S, et al. Anti-implantation activity of some
indigenous plants in rats. Acta Eur Fertil. 1985;16:441–8.
34. Rajaramarao MR. Studies on vegetable expectorants. Indian J Pharmacy.
1961;23:115.
35. Roy SK. Trial of ‘Tantrapuspi Vasaka’ (Adhatoda vasica) in the treatment
of pulmonary tuberculosis. Nagarjun. 1968;11:274.
36. Shahwar D, Raza MA, Tariq S, et al. Enzyme inhibition, antioxidant and
antibacterial potential of vasicine isolated from Adhatoda vasica Nees. Pak J
Pharm Sci. 2012;25:651–6.
37. Shrivastava N, Srivastava A, Banerjee A, Nivsarkar M. Antiulcer activity of
Adhatoda vasica Nees. J Herb Pharmacother. 2006;6:43–9.
38. Singh B, Sharma RA. Anti-inflammatory and antimicrobial properties of
pyrroloquinazoline alkaloids from Adhatoda vasica Nees. Phytomedicine.
2013;20:441–5.
39. Singh RP, Padmavathi B, Rao AR. Modulatory influence of Adhatoda
vasica (Justicia adhatoda) leaf extract on the enzymes of xenobiotic
metabolism, antioxidant status and lipid peroxidation in mice. Mol Cell
Biochem. 2000;213:99–109.
40. Vijayanandraj S, Brinda R, Kannan K, et al. Detoxification of aflatoxin B1
by an aqueous extract from leaves of Adhatoda vasica Nees. Microbiol Res.
2014;169:294–300.
41. Wagner H. Search for new plant constituents with potential antiphlogistic
and antiallergic activity. Planta Med. 1989;55:235–41.
42. Yadav AK, Tangpu V. Anticestodal activity of Adhatoda vasica extract
against Hymenolepis diminuta infections in rats. J Ethnopharmacol. 2008;
119:322–4.
Lactuca sativa L.
(Asteraceae/Compositae)

(Syns.: L. capitata (L.) DC; L. crispa (L.) Roth; L. laciniata Roth; L. palmata Willd.)

Abstract
Lettuce was introduced to the Greeks and Romans by the Egyptians, who first
cultivated it as early as 2680 B.C. for its oil seeds and edible leaves. Lettuce also
became the first vegetable to be grown in space on International Space Station.
In the 19th century Poland, desiccated lactucarium was considered intoxicant
and used as a sedative and analgesic. Seeds are considered cooling, demulcent,
and refrigerant, while leaves are slightly hypnotic and sedative; decoction or
tincture of seeds is useful in insomnia and wakefulness due to mental overwork,
in rheumatism, insanity and nocturnal emissions. Powdered seeds are used in
fevers, active inflammations, cough, bronchitis, asthma and pertussis. In Unani
medicine, seeds are considered analgesic, sedative, hypnotic, quenching thirst,
and dowsing the blood and yellow bile heat. Paste of the seeds is topically
applied to forehead to relieve headache due to heat and to induce sleep in cases
of insomnia. Internally seeds are used to treat melancholia, insanity and bilious
fevers, and also used to reduce semen production, sexual urge and desire, and
nocturnal emissions. Romaine lettuce has one of the highest concentrations of
total phytosterol among vegetables. (S)-malic acid 1′-O-b-gentiobioside, isolated
from lettuce is an ACE inhibitor, which is stable against salivary glycosidases
and stomach acid. Crude methanol/petroleum ether extract of seeds showed
presence of triterpenoids, saponins and simple phenols. Hydroalcohol leaf
extract exhibited anxiolytic activity, and potentiated pentobarbital-induced
sleeping time in mice. An agent isolated from the extract of lettuce stem
produced CNS depressant effect on motor activity and flaccid paralysis in high
doses. Aqueous extract exhibited moderate diuretic activity in rats. Feeding
lettuce in diet to rats for 3-weeks significantly decreased dietary cholesterol

© Springer Nature Switzerland AG 2020 1067

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_115
1068 Lactuca sativa L.

absorption, liver cholesterol and LDL/HDL ratio, and increased cholesterol fecal
excretion. Consumption of fresh lettuce produced better antioxidant effects than
the stored lettuce in healthy Italian volunteers.

Keywords




Alface Baş salata Bazrul-al-khas Bindsalade
Kahu
Kahu-khaskabija




Lechuga de mesa Lettuce Salat Wo ju

Vernaculars: Urd.: Kahu; Hin.: Kahu-khaskabija; Ben.: Kahu; Tam.: Shallatul-

virai; Tel.: Kavu-vittulu, Shallattu; Ara.: Al-Khas nabat, Bazrul-al-khas; Chi.:
莴苣, Sheng cai, Wo ju; Cze.: Částech salátu, Dārza salāti, Hlávkový salát, Locika
salát; Dan.: Havesalat, Salat; Dut.: Bindsalade, Gewone sla; Eng.: Lettuce;
Fin.: Ruokasalaatti, Salaattii; Fre.: Laitue, Laitue cultivée; Ger.: Batavia salat,
Eisbergsalat, Gartenlattich, Grüner salat; Gre.: Marouli; Hun.: Fejessaláta, Kerti
saláta; Ita.: Insalata, Lattuga; Jap.: Abirako, Chisha, Retasu; Nor.: Hagesalat; Per.:
Khas, Tukhm-e-kahu; Pol.: Sałata, Sałata siewna; Por.: Alface; Rus.: Laktuk, Salat
latuk; Spa.: Lechuga de mesa, Lattuga coltivata; Swe.: Huvudsallat, Laktuk, Sallad,
Sallat, Trädgårdssallat; Tag.: Legas, Letsugas; Tur.: Baş salata, Marul; Vie.: Salàt.
Description: This vegetable is an erect, simple, annual, smooth and very leafy herb
reaching a height of 30 cm or more. Leaves are stalkless, obovate to oblong-obovate,
6–20 cm long, entire or lobed, thin and numerous at the base. Flowers are yellow;
the involucral bracts are ovate, the inner ones linear.CXVII Lettuce was introduced
to the Greeks and Romans by the Egyptians, who first cultivated it as early as
2680 B.C. for its oil seeds and edible leaves.LXXVIII Lettuce also became the first
vegetable to be grown in space on International Space Station. Five varieties of
lettuce, called butterhead, crisphead, green leaf, red leaf, and romaine are commonly
available in the U.S. markets. Botanical name “Lactuca” is derived from the milky
juice that lettuce contains; the dried juice or extract of lettuce is known as lactu-
carium, which possesses narcotic components, and has been used as sedative and
soporific from the time of the Roman Empire. In France, the lactucarium has been
used in cough mixtures as a substitute for opium (Figs. 1, 2 and 3).LXXXVIII
Actions and Uses: In the 19th century Poland, desiccated lactucarium was con-
sidered intoxicant and used as a sedative and analgesic [39]. Seeds are considered
cooling, demulcent, and refrigerant, while leaves are slightly hypnotic and sedative;
decoction or tincture of seeds is useful in insomnia and wakefulness due to mental
overwork, in rheumatism, insanity and nocturnal emissions. Powdered seeds are used
in fevers, active inflammations, cough, bronchitis, asthma and pertussis.LXXXI,CV
In Unani medicine, seeds (temperament, cold 2° and dry 2°) are considered analgesic,
sedative, hypnotic, quenching thirst, and dowsing the blood and yellow bile heat.
Paste of the seeds is topically applied to forehead to relieve headache due to heat and
to induce sleep in cases of insomnia. Internally, seeds are used to treat melancholia,
Lactuca sativa L. 1069

Fig. 1 Lactuca sativa in a field, Geographer, WikimediaCommons; 1.0 Generic CC BY 1.0,

https://commons.wikimedia.org/wiki/File:Iceberg_lettuce_in_SB.jpg; https://creativecommons.org/
licenses/by/1.0/deed.en

Fig. 2 Lactuca sativa, Flowers, Rasbak, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Lactuca_sativa,_botersla.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

insanity and bilious fevers, and also used to reduce semen production, sexual urge
and desire, and nocturnal emissions.L,LXXVII Leaves produce good blood, purifiy and
thin blood, and unwashed leaves cause diuresis.L In Iranian folk medicine, seeds are
used to relieve inflammation and osteodynia [32], and to reduce semen production,
sperm count and sexuality [1]. The extract from fresh plant is a mild sedative and
anodyne, purgative, diuretic, diaphoretic and antispasmodic; and useful in the
treatment of coughs, phthisis, bronchitis, asthma and pertussis. Lettuce poultice is a
soothing application to painful and irritable ulcers.LXXXIV A seed decoction is used as
1070 Lactuca sativa L.

Fig. 3 Lactuca sativa, Seeds, Tracey Slotta @ USDA-NRCS PLANTS Database; Wikimedia-
Commons, http://plants.usda.gov/java/largeImage?imageID=lasa3_001_ahp.tif; https://commons.
wikimedia.org/wiki/File:Lactuca_sativa_seeds.jpg

demulcent in cases of bronchitis, especially of the chronic type,CXXXXIX to quench

excessive thirst, and sensation of heat in the stomach, and to reduce spermatic
secretion by relaxing genital organs.CXVII
Phytoconstituents: Romaine lettuce has one of the highest concentrations of total
phytosterol among vegetables [15]. (S)-malic acid 1′-O-b-gentiobioside, isolated
from lettuce is an ACE inhibitor, which is stable against salivary glycosidases and
stomach acid [22]. Crude methanol/petroleum ether (70/30, v/v) extract of seeds
showed presence of triterpenoids, saponins and simple phenols [32]. Dominant
compounds isolated from EO of seeds were n-hexanol (36.31%), n-hexanal
(13.71%), trans-2-octen-l-ol (8.09%) and 2-n-pentylfuran (4.41%) [42]; whereas
major constituents of EOs from fresh and dried leaves were identified as a-pinene,
c-cymene, thymol, durenol, a-terpinene, thymol acetate, caryophyllene, spathu-
lenol, camphene, and limonene, the contents being slightly lower in dried leaves
[3]. Seed oil, marketed in Egypt as a sleep aid, mainly contains oleic acid (61.5%),
stearic acid (20.4%), palmitic acid (9.7%), myristic acid (2.8%), cis-palmitoleic
(1.2%), behenic acid (0.5%), lignoseric acid (0.3%), b-sitosterol and b-amryn [43].
Pharmacology: A crude methanol/petroleum ether extract of seeds exhibited a
time- and dose-dependent analgesic effect and a dose-dependent anti-inflammatory
activity in a carrageenan model of inflammation, but no analgesic effect in tail-flick
test up to the highest dose of 6 g/kg [32]. Hydroalcohol leaf extract exhibited
anxiolytic activity [16], and potentiated pentobarbital-induced sleeping time in mice
[10]. An agent isolated from the extract of lettuce stem produced CNS depressant
effect on motor activity and flaccid paralysis in high doses [12]. Aqueous extract
exhibited moderate diuretic activity in rats [8, 14, 34]. Seed oil demonstrated sig-
nificant sedative, analgesic, anti-inflammatory and anticonvulsant activity against
PTZ-induced convulsions, and potentiated hypnotic effect of barbiturates [31].
Lactuca sativa L. 1071

Hydroalcoholic and aqueous extracts of seeds significantly decreased sperm count

and viability in mice [1].
Feeding lettuce in diet (20%) to rats for 3-weeks significantly decreased dietary
cholesterol absorption, liver cholesterol and LDL/HDL ratio, and increased
cholesterol fecal excretion [25]. Water-soluble fraction of the hydroalcohol extract
and ethyl acetate extract of leaves protected against DNA damage and LPO in
neuron-like N2a and PC12 cells [4, 11]. Lettuce contains relatively low levels of
antioxidative phytochemicals than most commonly used vegetables, but lettuce leaf
extracts contain compounds with high specific peroxyl radical scavenging activities
[6, 7]. Methanol leaf extract of Indian origin showed significant antioxidant
potential both in vitro and in vivo [9], whereas aqueous/methanol extract of lettuce
from U.K. did reportedly have least antioxidant activity, compared to other regu-
larly used vegetables, such as onions, leek, spinach and green cabbage [29], and
antioxidant activity of methanol extract of lettuce from Iran was reported compa-
rable to dl-alpha-tocopherol and quercetin [35]. Juice of lettuce from Yemen even
showed initial prooxidant activity [2]. Neutral and acidic flavonoids of red lettuce
showed significant antioxidant activity that was not corelated with total phenolics
content [17]. Water extract inhibited growth of HL-60 leukemia cells and MCF-7
breast cancer cells [13]. The latex saps inhibited growth of C. albicans [24].
Clinical Studies: In a double-blind RCT of 60 Egyptian patients suffering from
insomnia or sleeping difficulty with or without anxiety, administration of 1,000 mg
seed oil for a week significantly improved sleep scores [43]. Consumption of fresh
lettuce produced better antioxidant effects than the stored lettuce in eleven healthy
Italian volunteers [33].
Mechanism of Action: It is postulated that a phytol from the plant elevates GABA
levels in CNS through its inhibitory action on one of the GABA degradative
enzymes, succinic semialdehyde dehydrogenase [5]. The in vitro anti-inflammatory
and antioxidant potential of polyphenols extracted from lettuce demonstrated sig-
nificant decreases in ROS, NO release, iNO synthase and COX-2 expression [27].
Polyphenols, such as quercetin, kaempferol, luteolin, apigenin, and crysoeriol
derivatives, and hydroxycinnamic acids present in leaves are credited for its
antioxidant activity [2, 6, 7, 9, 17–20, 29, 35, 38]. Polyphenols in dietary products
also reduce nitrite to *NO that may exert a biological impact as a local intestinal
relaxant [30]. Anticancer activity is mediated through induction of tumor sup-
pressor p21, and severe downregulation of the proto-oncogene cyclin D1 [13].
Human A/Es, Allergy and Toxicity: It reduces sexual drive, and lettuce use is
also reported to increase risk of gallstones, which are a major risk factor for biliary
tract cancer [21, 26]. However, no adverse effects of seed oil were reported by
patients in clinical trial. Due to its one of the highest nitrate (NO3 ) contents among
vegetables [36, 37], which are highest during winter and lowest in summer [28],
and are absorbed very effectively from the gut [40], ingestion of lettuce increases
nitrous oxide (N2O) in exhaled air due to denitrification of nitrates by intestinal
microflora [23].
1072 Lactuca sativa L.

Animal Toxicity: Oral LD50 of seed oil in mice was 19.75 mL/kg [31], whereas
the LD50 (i.p.) for hydroalcoholic leaf extract in mice was 4,800 mg/kg [10], and
the methanol/petroleum ether extract produced no abnormal behavior and lethality
up to the dose of 6,000 mg/kg [32].
Drug Interactions: Butterhead lettuce contains sufficient vitamin K to antagonize
effects of warfarin, that may result in serious consequences [41].
Commentary: The safe and effective sedative/hypnotic effect of seed oil observed
in a pilot study of insomniac Egyptian patients has not been duplicated in other
patient populations. Another interesting use of lettuce seeds to be tested in clinical
trials would be in patients with excessive sexual urge, for which it is successfully
used in Unani medicine, and is a widely accepted clinical use in other traditional
medicines.

References
1. Ahangarpour A, Oroojan AA, Radan M. Effect of aqueous and hydroal-
coholic extracts of lettuce (Lactuca sativa) seed on testosterone level and
spermatogenesis in NMRI mice. Iran J Reprod Med. 2014;12:65–72.
2. Al-Mamary MA Jr. Antioxidant activity of commonly consumed vegetables
in Yemen. Malays J Nutr. 2002;8:179–89.
3. Al Nomaani RS, Hossain MA, Weli AM, et al. Chemical composition of
essential oils and in vitro antioxidant activity of fresh and dry leaves crude
extracts of medicinal plant of Lactuca sativa L. native to Sultanate of Oman.
Asian Pac J Trop Biomed. 2013;3:353–7.
4. Asadpour E, Ghorbani A, Sadeghnia HR. Water-soluble compounds of
lettuce inhibit DNA damage and lipid peroxidation induced by glucose/
serum deprivation in N2a cells. Acta Pol Pharm. 2014;71:409–13.
5. Bang MH, Choi SY, Jang TO, et al. Phytol, SSADH inhibitory diterpenoid
of Lactuca sativa. Arch Pharm Res. 2002;25:643–6.
6. Caldwell CR. Alkylperoxyl radical scavenging activity of red leaf lettuce
(Lactuca sativa L.) phenolics. J Agric Food Chem. 2003;51:4589–95.
7. Chu YF, Sun J, Wu X, Liu RH. Antioxidant and antiproliferative activities
of common vegetables. J Agric Food Chem. 2002;50:6910–6.
8. Dhawan BN, Patnaik GK, Rastogi RP, Singh KK, Tandon JS. Screening of
Indian plants for biological activity: part VI. Indian J Exp Biol. 1977;15:
208–19.
9. Garg M, Garg C, Mukherjee PK, Suresh B. Antioxidant potential of Lactuca
sativa. Anc Sci Life. 2004;24:6–10.
10. Ghorbani A, Rakhshandeh H, Sadeghnia HR. Potentiating effects of Lactuca
sativa on pentobarbital-induced sleep. Iran J Pharm Res. 2013;12:401–6.
Lactuca sativa L. 1073

11. Ghorbani A, Sadeghnia HR, Asadpour E. Mechanism of protective effect of

lettuce against glucose/serum deprivation-induced neurotoxicity. Nutr Neu-
rosci. 2015;18:103–9.
12. Gonzalex-Lima F, Valedon A, Stiehil WL. Depressant pharmacological
effects of a component isolated from lettuce, Lactuca sativa. Int J Crude
Drug Res. 1986;24:154–66.
13. Gridling M, Popescu R, Kopp B, et al. Antileukaemic effects of two extract
types of Lactuca sativa correlate with the activation of Chk2, induction of
p21, downregulation of cyclin D1 and acetylation of alpha-tubulin. Oncol
Rep. 2010;23:1145–51.
14. Gujral ML, Saxena PN, Mishra SS. An experimental study of the compar-
ative activity of indigenous diuretics. J Indian Med Assoc. 1955;25:49–51.
15. Han JH, Yang YX, Feng MY. Contents of phytosterols in vegetables and
fruits commonly consumed in China. Biomed Environ Sci. 2008;21:449–
53.
16. Harsha SN, Anilakumar KR. Anxiolytic property of hydroalcohol extract of
Lactuca sativa and its effect on behavioral activities of mice. J Biomed Res.
2013;27:37–42.
17. Hassimotto NM, Genovese MI, Lajolo FM. Antioxidant activity of dietary
fruits, vegetables, and commercial frozen fruit pulps. J Agric Food Chem.
2005;53:2928–35.
18. Heimler D, Isolani L, Vignolini P, et al. Polyphenol content and anti-
oxidative activity in some species of freshly consumed salads. J Agric Food
Chem. 2007;55:1724–9.
19. Im SE, Yoon H, Nam TG, et al. Antineurodegenerative effect of phenolic
extracts and caffeic acid derivatives in romaine lettuce on neuron-like PC-12
cells. J Med Food. 2010;13:779–84.
20. Kang HM, Saltveit ME. Antioxidant capacity of lettuce leaf tissue increases
after wounding. J Agric Food Chem. 2002;50:7536–41.
21. Kato I, Kato K, Akai S, Tominaga S. A case-control study of gallstones: a
major risk factor for biliary tract cancer. Jpn J Cancer Res. 1990;81:578–83.
22. Lagemann A, Dunkel A, Hofmann T. Activity-guided discovery of (S)-
malic acid 1′-O-b-gentiobioside as an angiotensin I-converting enzyme
inhibitor in lettuce (Lactuca sativa). J Agric Food Chem. 2012;60:7211–7.
23. Mitsui T, Kondo T. Vegetables, high nitrate foods, increased breath nitrous
oxide. Dig Dis Sci. 1999;44:1216–9.
24. Moulin-Traffort J, Giordani R, Régli P. Antifungal action of latex saps from
Lactuca sativa L. and Asclepias curassavica L. Mycoses. 1990;33:383–92.
25. Nicolle C, Cardinault N, Gueux E, et al. Health effect of vegetable-based
diet: lettuce consumption improves cholesterol metabolism and antioxidant
status in the rat. Clin Nutr. 2004;23:605–14.
26. Ozaras R, Mert A, Akman C, et al. Hepatopulmonary masses after eating
Romaine lettuce. Scand J Infect Dis. 2003;35:914–5.
1074 Lactuca sativa L.

27. Pepe G, Sommella E, Manfra M, et al. Evaluation of anti-inflammatory

activity and fast UHPLC-DAD-IT-TOF profiling of polyphenolic com-
pounds extracted from green lettuce (Lactuca sativa L.; var. Maravilla de
Verano). Food Chem. 2015;167:153–61.
28. Petersen A, Stoltze S. Nitrate and nitrite in vegetables on the Danish market:
content and intake. Food Addit Contam. 1999;16:291–9.
29. Proteggente AR, Pannala AS, Paganga G, et al. The antioxidant activity of
regularly consumed fruit and vegetables reflects their phenolic and vitamin
C composition. Free Radic Res. 2002;36:217–33.
30. Rocha BS, Gago B, Barbosa RM, Laranjinha J. Dietary polyphenols
generate nitric oxide from nitrite in the stomach and induce smooth muscle
relaxation. Toxicology. 2009;265:41–8.
31. Said SA, Kashef HE, Mazar ME, Salama O. Phytochemical and pharma-
cological studies on Lactuca sativa seed oil. Fitoterapia. 1996;67:215–9.
32. Sayyah M, Hadidi N, Kamalinejad M. Analgesic and anti-inflammatory
activity of Lactuca sativa seed extract in rats. J Ethnopharmacol. 2004;92:
325–9.
33. Serafini M, Bugianesi R, Salucci M, et al. Effect of acute ingestion of fresh
and stored lettuce (Lactuca sativa) on plasma total antioxidant capacity and
antioxidant levels in human subjects. Br J Nutr. 2002;88:615–23.
34. Seth UK, Sethy VH. Indigenous diuretics. In: Udupa KN, Sheth UK, Vaz A,
Delliwala CV, Bellare RA, editors. Advances in research in Indian medicine.
Arch Int Pharmacodyn. 1963;114:34.
35. Souri E, Amin G, Farsam H, Andaji S. The antioxidant activity of some
commonly used vegetables in Iranian diet. Fitoterapia. 2004;75:585–8.
36. Susin J, Kmecl V, Gregorcic A. A survey of nitrate and nitrite content of
fruit and vegetables grown in Slovenia during 1996–2002. Food Addit
Contam. 2006;23:385–90.
37. Tamme T, Reinik M, Roasto M, et al. Nitrates and nitrites in vegetables and
vegetable-based products and their intakes by the Estonian population. Food
Addit Contam. 2006;23:355–61.
38. Tarwadi K, Agte V. Potential of commonly consumed green leafy vegetables
for their antioxidant capacity and its linkage with the micronutrient profile.
Int J Food Sci Nutr. 2003;54:417–25.
39. Trojanowska A. Lettuce, Lactuca sp., as a medicinal plant in Polish
publications of the 19th century. Kwart Hist Nauki Tech. 2005;50:123–34
(Article in Polish).
40. van Velzen AG, Sips AJ, Schothorst RC, et al. The oral bioavailability of
nitrate from nitrate-rich vegetables in humans. Toxicol Lett. 2008;181:
177–81.
41. Walker FB 4th. Myocardial infarction after diet-induced warfarin resistance.
Arch Intern Med. 1984;144:2089–90.
Lactuca sativa L. 1075

42. Xu F, Wang Q, Haji AA. Analysis of essential oil extracted from Lactuca
sativa seeds growing in Xinjiang by GC-MS. Zhong Yao Cai. 2011;34:
1887–91 (Chinese).
43. Yakoot M, Helmy S, Fawal K. Pilot study of the efficacy and safety of
lettuce seed oil in patients with sleep disorders. Int J Gen Med. 2011;4:
451–6.
Lavandula stoechas L.
(Lamiaceae)

Abstract
It is an ornamental plant, native to southern Europe (Spain) and various species
are called Lavender. Dioscorides stated that this plant is called Stoechus from its
growing on the Stoechades, a group of islands on the south coast of Gaul
(a region in Western Europe) near Massilia (modern Marseilles). Three species,
L. stoechas, L. pedunculata and L. dentata were known to Romans, and in Spain
L. stoechas was known as ‘Romero Santo’ (sacred rosemary), and its oil was
used as hemostatic and for cleansing wounds. Avicenna called it Astaadus or
Astiqoos, mentioned in his book of cardiotonic drugs as the most effective in
expelling black bile from brain, and is especially useful as brain tonic and for
diseases like epilepsy, melancholy, mania and amnesia. It has been called the
‘broom of the brain’ that it sweeps away all phlegmatic impurities, and removes
obstructions, strengthening its powers, expelling vain crudities and rarifying the
intellect, and is also used as a carminative, resolvent, antispasmodic and
stimulant. In Murcia (southeastern Spain), it is used as an herbal remedy for
stomachache, and is one of the most commonly used plant in the traditional
medicine of Marmaris district of southwest Anatolia of Turkey, and in Sakarya
province of northwest Turkey to treat infections. Ibn al-Baitar said that if it is
used continuously until one develops diarrhea, then the diseases of melancholy
and epilepsy are cured. Aerial parts show the presence of novel acetylated
glucosides, apigenin 7-O-glucoside and luteolin 7-O-glucoside. Essential oils
extracted by supercritical carbon dioxide (SCCD) extraction and steam
distillation show different compositions. Essential oils obtained by SCCD
extraction showed higher antioxidant activity than steam distilled oil. Fifty-one
constituents were identified in the EO of L. stoechas growing wild in Greece,
and the oil was rich in fenchone and camphor; whereas in the majority of
lavender species, the main component is linalool. Hydromethanol extract of

© Springer Nature Switzerland AG 2020 1077

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_116
1078 Lavandula stoechas L.

flowers significantly reduced the severity, increased the latency of PTZ-induced

convulsions, and reduced mortality of mice. It was devoid of hypnotic effect
per se but prolonged pentobarbital sleeping time in mice.

Keywords






Arçã Cantahueso Dharu French lavender Karabaş Mumsik al-arwah





Schopflavendel Stechas Tupsulaventeli Ustokhuddoos

Vernaculars: Urd.: Ustokhuddoos; Hin.: Alaphajana, Dharu; Ara.: Aanas-al-

arwah, Azhar al-khazann, Khuzzama, Mumsik al-arwah, Ustokhuddoos; Dut.: Ste-
chas; Eng.: Arabic lavender, Butterfly lavender, French lavender, Spanish lavender;
Fin.: Ranskanlaventeli, Tupsulaventeli, Tupsupäälaventeli; Fre.: Lavande à fleurs
alignées, Lavande à toupet, Lavande des maures, Lavande des stoechades, Lavande
maritime, Lavande papillon, Lavande stéchade, Lavande stéchas, Tomillo cantueso
caballar, Tomillo de flor morada lavande des Îles d’Hyères, Stoechas arabique: Ger.:
Ahrenförmiger lavendel, Schopflavendel; Ita.: Lavanda selvatica, Lavanda stecade,
Steca, Stecaole, Stigadosso; Por.: Alfazema-brava, Arçã, Cabeçuda, Rasmonino,
Rasmono, Rosmaninho, Rosmano, Tomelo; Spa.: Almoraduz de cuello corto,
Cantahueso, Cantuerca, Cantueso, Espliego, Estecados, Flor del Corpus, Flor del
Señor, Hierba de San Juan, Lavanda romana, Romero de señor, Rosmano, Tomillo
borriquero, Tomillo cantimpalo, Tomillo cantueso; Tur.: Karabaş.
Description: It is an ornamental plant, native to southern Europe (Spain) and
various species are called Lavender. Dioscorides stated that this plant is called
Stoechus from its growing on the Stoechades, a group of islands on the south coast
of Gaul (a region in Western Europe) near Massilia (modern Marseilles). Three
species, L. stoechas, L. pedunculata and L. dentata were known to Romans, and in
Spain L. stoechas was known as ‘Romero Santo’ (sacred rosemary), and its oil was
used as hemostatic and for cleansing wounds. Avicenna called it Astaadus or
Astiqoos.XL An evergreen shrub, grows to 30–100 cm tall and wide; pink to purple
flowers appear in late spring and early summer, occur on spikes 2 cm long at the
top of slender, leafless stems 10–30 cm long, and are situated in the axils of downy,
heart-shaped bracts. The drug has a camphoraceous odor and a hot bitter taste.
Unani medicine practitioners in India identify Ustokhuddoos as Lavandula stoe-
chas; however, a sample sold in India as Ustokhuddoos, collected by the author was
identified by a taxonomist as Lavandula dentata (Figs. 1, 2 and 3).
Actions and Uses: The author of Makhzan-al-Adwiya labeled it as the ‘broom of
the brain’ that it sweeps away all phlegmatic impurities, and removes obstructions,
strengthening its powers, expelling vain crudities and rarifying the intellect,LXIX
and used it as a carminative, resolvent, antispasmodic and stimulant.LIII In Murcia
(southeastern Spain), it is used as an herbal remedy for stomachache,LI and is one of
the most commonly used plants in the traditional medicine of Marmaris district of
southwest Anatolia [12], and Sakarya province of northwest Turkey to treat
infections [25]. Ibn al-BaitarLXIX said that if it is used continuously until one
Lavandula stoechas L. 1079

Fig. 1 Lavandula stoechas, Spanish Lavender, Xemenendura, WikimediaCommons; ShareAlike

2.1 Unported CC BY-SA 2.1, https://commons.wikimedia.org/wiki/File:Lavandula_stoechas_1.
JPG; https://creativecommons.org/licenses/by-sa/2.1/es/deed.en

Fig. 2 Lavandula stoechas, Italian Lavender, Gabriella C. Marino, WikimediaCommons;

ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Lavanda_
papillon.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

develops diarrhea, then the diseases of melancholy and epilepsy are cured. In Unani
medicine, flowers and leaves (spikes) (temperament, hot 1° and dry 1°) are used,
and considered as cephalic, resolvent, deobstruent and carminative, and prescribed
in chest affections, and to expel bilious and phlegmatic humours.CV It is mainly
used for brain and nervous diseases, such as epilepsy, amnesia, nerve pain, and for
arthritis, inflammations and ascites;LXXVII palsy and paralysis.1 GhaniL says it
strengthens the heart, brain, liver, spleen, GIT and the body as a whole, and

1
Tayyab M: Personal Communication.
1080 Lavandula stoechas L.

Fig. 3 Lavandula stoechas, Flowerheads as sold in the U.S., Prof. Akbar, Original

mentioned that Avicenna in his book of cardiotonic drugs described this drug as the
most effective in expelling black bile from brain, and is especially useful as brain
tonic and for diseases like epilepsy, melancholy, mania and amnesia. Lavender oil
is claimed to be antibacterial, antifungal, carminative (smooth muscle relaxant),
sedative, antidepressant and effective for burns and insect bites, and its traditional
uses are supported by both scientific and clinical data [6].
Phytoconstituents: Aerial parts show the presence of novel acetylated glucosides,
apigenin 7-O-glucoside and luteolin 7-O-glucoside [8]. Essential oils extracted by
supercritical carbon dioxide (SCCD) extraction and steam distillation show different
compositions. Essential oils obtained by SCCD extraction showed higher antioxi-
dant activity than steam distilled oil [22]. Fifty-one constituents were identified in
the EO of L. stoechas growing wild in Greece [14], and the oil was rich in fenchone
(34.3%) and camphor (27.4%) [4, 16, 24]; whereas in the majority of lavender
species, the main component is linalool [26]. Essential oil from plants growing wild
in Turkey showed a-fenchone, 1,8-cineole, camphor, and viridiflorol as the main
components in leaves; and a-fenchone, myrtenyl acetate, a-pinene, camphor and
1,8-cineole in the flowers [13]. All EO samples hydrodistilled from flowers of wild
L. stoechas, collected from three locations in Sicily (Italy) were identified as fen-
chone chemotype, with percentage content ranging between 52.8 and 71.1% [15].
d-Fenchone (29.28%), a-pinene (23.18%), camphor (15.97%), camphene (7.83%),
eucapur (3.29%), limonene, (2.71%), linalool, (2.01%) and endobornyl acetate
(1.03%) were reported as the main constituent of hydrodistilled EO of aerial parts
from Tunisia [19]. One hundred twenty-one compounds were identified in various
samples growing wild in Algeria, but only 66 compounds were common to all oils;
major components were fenchone, camphor, 1,8-cineole, and viridiflorol [5], similar
Lavandula stoechas L. 1081

to those wild samples from Turkey. An earlier finding reported pulegone (40.4%),
menthol (18.1%), and menthone (12.6%) as the main components of leaves oil from
Turkey [11]. The roots contain triterpenes, steroids and aromatics [23].
Pharmacology: Hydromethanol extract of flowers significantly reduced the
severity, increased the latency of PTZ-induced convulsions, and reduced mortality of
mice. It was devoid of hypnotic effect per se but prolonged pentobarbital sleeping
time in mice [10]. The sedative effect of the extract was confirmed as similar to that
of diazepam. Lavender extract exhibits moderate anti-inflammatory activity in paw
edema, which is speculated to be due to neutrophil apoptosis and antioxidant activity
[3], and also showed anti-inflammatory effects in the TNBSA-induced colitis [2].
Gámez et al. [9] reported hypoglycemic activity; EO (i.p.) for 15-days significantly
protected against alloxan hyperglycemia and decrease in antioxidant enzymes
activities [19]. The oil was also protective against hyperglycemic oxidative stress
and reproductive function damage in male rats [20], and against malathion-induced
oxidative stress, and showed potential hepato- and nephroprotective effects in mice
[21]. Essential oil was very effective against C. albicans, and both Gram-positive
and Gram-negative bacteria, including multiple-antibiotic resistant strains, except
P. aeruginosa and P. fluorescens [18]. Both MSSA and MRSA were inhibited by the
EO [17]; however, MRSA were relatively more susceptible to inhibition by the
flower oil than the leaf oil [13]. The oil also effectively inactivated Rhizoctonia
solani and Fusarium oxysporum (plant pathogenic fungi), and was less effective
against A. flavus [4], but active against E. coli, L. monocytogenes, and S. typhi-
murium [7].
Human A/Es, Allergy and Toxicity: A Turkish patient was admitted to emer-
gency department with supraventricular tachycardia due to anticholinergic syn-
drome triggered by drinking lavender tea. The patient’s sinus rhythm was restored
after carotid sinus massage [1]. It is emetic, causes thirst, and unsuitable for indi-
viduals with bilious temperament.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: While lavender use in modern times is mostly confined to the
commercial use of its oil in perfumes, and cosmetics, etc., it is a drug to reckon with
for its medicinal properties. There are no formal clinical studies on its effects on the
CNS, as envisaged by ancient physicians. However, the wide variations in the
phytoconstituents of its oil must be kept in mind when subjecting the plant or its oil
for clinical studies.

References
1. Acikalin A, Gulen M, Kara B, et al. Anticholinergic syndrome and supraven-
tricular tachycardia caused by lavender tea toxicity. Keio J Med. 2012;61:
66–8.
1082 Lavandula stoechas L.

2. Algieri F, Rodriguez-Nogales A, Vezza T, et al. Anti-inflammatory activity

of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas
L. J Ethnopharmacol. 2016;190:142–58.
3. Amira S, Dade M, Schinella G, Ríos JL. Anti-inflammatory, antioxidant,
and apoptotic activities of four plant species used in folk medicine in the
Mediterranean basin. Pak J Pharm Sci. 2012;25:65–72.
4. Angioni A, Barra A, Coroneo V, et al. Chemical composition, seasonal
variability, and antifungal activity of Lavandula stoechas L. ssp. stoechas
essential oils from stem/leaves and flowers. J Agric Food Chem. 2006;54:
4364–70.
5. Benabdelkader T, Zitouni A, Guitton Y, et al. Essential oils from wild popu-
lations of Algerian Lavandula stoechas L.: composition, chemical variabil-
ity, and in vitro biological properties. Chem Biodivers. 2011;8:937–53.
6. Cavanagh HM, Wilkinson JM. Biological activities of lavender essential oil.
Phytother Res. 2002;16:301–8 (Review).
7. Dadalioglu I, Evrendilek GA. Chemical compositions and antibacterial
effects of essential oils of Turkish oregano (Origanum minutiflorum), bay
laurel (Laurus nobilis), Spanish lavender (Lavandula stoechas L.), and
fennel (Foeniculum vulgare) on common foodborne pathogens. J Agric
Food Chem. 2004;52:8255–60.
8. Gabrieli C, Kokkalou E. A new acetylated glucoside of luteolin and two
flavone glucosides from Lavandula stoechas ssp. stoechas. Pharmazie.
2003;58:426–7.
9. Gámez MJ, Jiménez J, Risco S, Zarzuelo A. Hypoglycemic activity in
various species of the genus Lavandula. Part 1: Lavandula stoechas L. and
Lavandula multifida L. Pharmazie. 1987;42:706–7.
10. Gilani AH, Aziz N, Khan MA, et al. Ethnopharmacological evaluation of
the anticonvulsant, sedative and antispasmodic activities of Lavandula
stoechas L. J Ethnopharmacol. 2000;71:161–7.
11. Gören A, Topçu G, Bilsel G, et al. The chemical constituents and biological
activity of essential oil of Lavandula stoechas ssp. stoechas. Z Naturforsch.
2002;57:797–800.
12. Gürdal B, Kültür S. An ethnobotanical study of medicinal plants in Marmaris
(Muğla, Turkey). J Ethnopharmacol. 2013;146:113–26.
13. Kirmizibekmez H, Demirci B, Yeşilada E, et al. Chemical composition and
antimicrobial activity of the essential oils of Lavandula stoechas L.
ssp. stoechas growing wild in Turkey. Nat Prod Commun. 2009;4:1001–6.
14. Kokkalou E. The constituents of the essential oil from Lavandula stoechas
growing wild in Greece. Planta Med. 1988;54:58–9.
15. La Bella S, Tuttolomondo T, Dugo G, et al. Composition and variability of
the essential oil of the flowers of Lavandula stoechas from various
geographical sources. Nat Prod Commun. 2015;10:2001–4.
16. Messaoud C, Chograni H, Boussaid M. Chemical composition and antiox-
idant activities of essential oils and methanol extracts of three wild
Lavandula L. species. Nat Prod Res. 2012;26:1976–84.
Lavandula stoechas L. 1083

17. Roller S, Ernest N, Buckle J. The antimicrobial activity of high-necrodane

and other lavender oils on methicillin-sensitive and -resistant Staphylococcus
aureus (MSSA and MRSA). J Altern Complement Med. 2009;15:275–9.
18. Sarac N, Ugur A. The in vitro antimicrobial activities of the essential oils of
some Lamiaceae species from Turkey. J Med Food. 2009;12:902–7.
19. Sebai H, Selmi S, Rtibi K, et al. Lavender (Lavandula stoechas L.) essential
oils attenuate hyperglycemia and protect against oxidative stress in alloxan-
induced diabetic rats. Lipids Health Dis. 2013;12:189.
20. Sebai H, Selmi S, Rtibi K, Gharbi N, Sakly M. Protective Effect of Lavandula
stoechas and Rosmarinus officinalis essential oils against reproductive
damage and oxidative stress in alloxan-induced diabetic rats. J Med Food.
2015;18:241–9.
21. Selmi S, Jallouli M, Gharbi N, Marzouki L. Hepatoprotective and renopro-
tective effects of lavender (Lavandula stoechas L.) essential oils against
malathion-induced oxidative stress in young male mice. J Med Food. 2015;
18:1103–11.
22. Topal U, Sasaki M, Goto M, Otles S. Chemical compositions and
antioxidant properties of essential oils from nine species of Turkish plants
obtained by supercritical carbon dioxide extraction and steam distillation.
Int J Food Sci Nutr. 2008;59:619–34.
23. Topçu G, Ayral MN, Aydin A, et al. Triterpenoids of the roots of Lavandula
stoechas ssp. stoechas. Pharmazie. 2001;56:892–5.
24. Tzakou O, Bazos I, Yannitsaros A. Essential oil composition and enantiomeric
distribution of fenchone and camphor of Lavandula cariensis and L. stoechas
subsp. stoechas grown in Greece. Nat Prod Commun. 2009;4:1103–6.
25. Uzun E, Sariyar G, Adsersen A, et al. Traditional medicine in Sakarya
province (Turkey) and antimicrobial activities of selected species. J Ethno-
pharmacol. 2004;95:287–96.
26. Végh A, Bencsik T, Molnár P, et al. Composition and antipseudomonal
effect of essential oils isolated from different lavender species. Nat Prod
Commun. 2012;7:1393–6.
Lawsonia inermis L.
(Lythraceae)

(Syn.: L. speciosa L.)

Abstract
The plant is native to India, North Africa, Arabian Peninsula and East Africa, but
has pantropical distribution. Use of henna for medicinal and cosmetic purposes
is linked to ancient and modern cultures of North Africa and Asia. Historically it
was applied to hands and feet to protect against fungal pathogens, and to hair to
combat lice and dandruff, but also traditionally used for the treatment of liver
and digestive disorders, to reduce tissue loss in leprosy, diabetic foot disorders
and ulcers. Henna is best known as a dye for dyeing nails, palm of the hands and
the sole of the feet in Asia, Africa, Arab and many other countries. Siddha
physicians prepare a specific thailam (oil) for grey hair. Leaves are described as
analgesic, anti-inflammatory, diuretic and blood purifier in Unani system of
medicine. Application of its oil with olive oil and coal-tar to a bald person’s head
is claimed to grow hair; also applied to feet to allay the sensation of burning of
feet. It is also reported as one of the most widely used hepatoprotective plant
species for traditional treatment of jaundice in India. It contains quinones,
phenylpropanoids, flavonoids, terpenoids, phenolic compounds and fatty acids.
Henna extracts and constituents exhibit numerous biological activities, including
antioxidant, anti-inflammatory, antibacterial and anticancer activities. Applica-
tion of henna in patients with hand-foot syndrome (HFS) due to capecitabine
chemotherapy produced complete response in four out of six of Grade 3 HFS
and all of Grade 2, eliminating the need to reduce capecitabine dose.

Keywords


Alcana Alcanna vera
Alfeneiro
Arkan
Henna
Hennastrauch
Henné



Mehndi Raktagarbha
Zhi jia hua

© Springer Nature Switzerland AG 2020 1085

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_117
1086 Lawsonia inermis L.

Vernaculars: Urd.: Henna, Mehndi; Hin.: Hena, Mehndi; San.: Kuravaka, Men-
dika, Raktagarbha; Ben.: Mehedi, Mendi, Shudi; Mal.: Mailanchi, Mailanji,
Mail-linshi, Pontaletshi; Mar.: Mendi; Ori.: Momjaathi; Tam.: Aivanam, Mar-
ithondi, Marudhani, Maruthondri; Tel.: Goeranta, Iveni, Kuravamu; Ara.: al Henna,
Hinna; Chi.: 指甲叶, Zhi jia hua, Zhi jia ye, Zhou jia mu; Eng.: Egyptian privet,
Henna, Mignonette tree, Samphire; Fin.: Hennapensas; Fre.: Henné, Reseda; Ger.:
Hennastrauch; Gre.: Arkan, Fakuliyun; Ita.: Alcanna vera, Arbusto della henna;
Maly.: Hinie, Pontaletsche; Per.: Henna; Por.: Alfeneiro; Spa.: Alcana, Alheña;
Tag.: Shinamomo.
Description: The plant is native to India, North Africa, Arabian Peninsula and East
Africa, but has pantropical distribution. It is an erect, much branched shrub or small
tree, 3–6 m high, that is semi-cultivated. Leaves are oblong-elliptic, 1.5–4 cm long,
and pointed at both ends. Flowers are fragrant, straw-yellow colored, and borne on
panicles 7–30 cm long. The capsules are nearly spherical, depressed, 5–7 mm in
diameter, and the seeds are angular. Its leaves are commonly used for cosmetic
staining of hands and feet, and as an ingredient in medicinal preparations in the
Middle East and Asia [62] (Figs. 1 and 2).CXVII
Actions and Uses: Use of henna for medicinal and cosmetic purposes is linked to
ancient and modern cultures of North Africa and Asia [48]. Historically it was
applied to hands and feet to protect against fungal pathogens, and to hair to combat
lice and dandruff, but also traditionally used for the treatment of liver and digestive
disorders, to reduce tissue loss in leprosy, diabetic foot disorders and ulcers [13].
Henna is best known as a dye for dyeing nails, palm of the hands and the sole of the
feet in Asia, Africa, Arab and many other countries [39]. Siddha physicians prepare
a specific thailam (oil) for grey hair.CV Leaves (temperament, cold 2° and dry 2°)

Fig. 1 Lawsonia inermis, Plants, Atamari, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Lawsonia_inermis_0002.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Lawsonia inermis L. 1087

Fig. 2 Lawsonia inermis, Flowers, Dinesh Valke, Thane, WikimediaCommons; Share Alike
2.0 Generic CC BY-SA 2.0, https://commons.wikimedia.org/wiki/File:Lawsonia_inermis_
(3709419835).jpg; https://creativecommons.org/licenses/by-sa/2.0/deed.en

are described as analgesic, anti-inflammatory, diuretic and blood purifier in Unani

system of medicine. They are deobstruent, and cure leprosy if the leaves covered in
water, soaked, crushed and filtered, and 10 g of the filtrate is consumed with twice
as much brown sugar daily in initial stages of leprosy for one-month; if not cured
then the disease is incurable. Another claim is that application of its oil with olive
oil and coal-tar to a bald person’s head will grow hair;L also applied to feet to allay
the sensation of burning of feet.LXXVII It is also reported as one of the most widely
used hepatoprotective plant species for traditional treatment of jaundice in India
[54]. The tribals of Phulbani district of Orissa (India) ground 5 g of the root with 3–
4 peppers, mix it with 50 ml of rice wash and use it on empty stomach in the
morning for 3–7-days to treat jaundice [25]. Powdered leaves are used as sup-
pository in prolapse of rectum and vagina, and fresh leaves are applied with vinegar
and catechu to burning soles of the feet.LXXXI Leaves are used in shampoos, and
rinses to give hair a rich, sunburn tint and brilliance; and being astringent, are used
as decoction by Malaysians for hoarseness of voice, and for stomachache after
childbirth, and for venereal diseases. In Java, it is also used for leucorrhea.XVII
Henna decoction is ingested as a traditional drug to induce abortion in several
countries [44].
Bark is alterative, sedative and astringent,LXXXI and bark decoction is applied to
burns and scalds to soothe burning sensation, also used internally for jaundice,
spleen enlargement and calculi, and as an alterative in leprosy and obstinate skin
afflictions.XL,LXXXIV,CV Roots are reported to be powerful abortifacient [52],XXX
emmenagogue [52], and regarded to be useful in hysteria and nervous disorders.XXX
Leaves are believed to have both emmenagogue and anthelmintic properties [52],
and are also traditionally used to treat anemia in Tanzania [45]. In Jeddah region of
Saudi Arabia, a small percentage of diabetic patients with foot disorders such as
open wounds, ulcers, and skin cracks, are reported to traditionally use henna [14].
1088 Lawsonia inermis L.

Phytoconstituents: It contains quinones, phenylpropanoids, flavonoids, terpenoids,

phenolic compounds and fatty acids [2, 35]. A number of phenolic compounds have
been isolated from various parts of the plant; 2-hydroxy-1,4-naphthoquinone (HNQ;
lawsone) is one of the naphthaquinones and the principal natural dye ingredient of
henna leaves that possesses many pharmacological activities [13, 31, 47, 53].
Phenolic glucosides, lawsoniaside and lalioside [61], lawsoniasides A and B [17],
and p-coumaric acid, 2-methoxy-3-methyl-1,4-naphthoquinone and apiin, lawsone,
apigenin, luteolin, and cosmosiin have been isolated from leaves [40]. It also contains
b-sitosterol glucoside [38], coumarins [19], quinoids and gallic acid, naphthalene
derivatives [3] and xanthones [16]. The pungent odor of EO isolated from flowers is
due to a terpene, b-ionone [13]. Three compounds, a bicoumarin A, a biflavonoid A,
and a biquinone A, were isolated from flowers; biquinone A was cytotoxic against
MCF-7, HeLa, HCT-116, and HT-29 cell lines [34]. A sterol, lawsaritol, was isolated
from the root [5].
Pharmacology: Henna extracts and constituents exhibit numerous biological
activities, including antioxidant, anti-inflammatory, antibacterial and anticancer
activities [15, 21, 26, 36, 47]. Ethanol leaf extract produced inhibition of inflam-
mation in hind paw edema test, granuloma pouch test and lint pellet test, compa-
rable to hydrocortisone on w/w basis [59], analgesic, and antipyretic effects in rats,
and significantly increased pentobarbitone-induced sleeping time; lawsone was
identified as the active constituent [6]; significantly improved wound healing in rats
[43], and exhibited protective potential against AAF-hepatotoxicity in rats [1].
Lawsochylin A and lawsonaphthoate A also show potent in vitro anti-inflammatory
activity by inhibition of superoxide anion generation [37]. Both henna leaf powder
and lawsone, either administered orally or applied topically in two stage skin
carcinogenesis exhibited cancer chemopreventive activity [30]. Ethanol leaf extract
also significantly reduced tumor incidence and tumor burden in B(a)P-induced
forestomach and DMBA-skin papillomagenesis [18]. It was also reported active
against Yoshida sarcoma [42].
Aqueous and petroleum ether extracts of leaves have shown reproducible in vitro
activity against B. cereus, B. anthracis and S. aureus [39, 58], ethanol leaf extract
against P. aeruginosa [7, 23, 24], Sh. dysenteriae [4], ß-hemolytic streptococci and
coagulase negative staphylococci, S. aureus and P. aeruginosa [9], clinical isolates
of b-lactamase producing MRSA and MSSA [11], synergistic interaction with
tetracycline, chloramphenicol and ciprofloxacin against S. aureus and/or E. coli
[10], and as tuberculostatic [55]. Ethyl acetate extract of flower showed highest
inhibitory effect against S. aureus and P. aeruginosa, and ethyl acetate fruit extract
on E. coli and B. subtilis [27]. Hot aqueous extract also showed retroviral reverse
transcriptase inhibitory activity [60]. Various extracts and lawsone exhibited strong
antifungal activity [50, 62]. Bark extract also exhibited broad fungitoxic spectrum
against 13 ringworm fungi, and fungistatic activity against M. gypseum and
T. mentagrophytes [56]. Both ethanol leaf extract and lawsone also showed sig-
nificant trypsin inhibitory activity [65].
Lawsonia inermis L. 1089

Clinical Studies: Application of henna in patients with hand-foot syndrome

(HFS) due to capecitabine chemotherapy produced complete response in four out of
six of Grade 3 HFS and all of Grade 2, and two Grade 3 HFS improved to Grade 1,
eliminating the need to reduce capecitabine dose [66].
Human A/Es, Allergy and Toxicity: Allergic reactions resulting in urticaria,
contact dermatitis or eczema and angioneurotic edema may sometimes occur as a
result of henna application, which is usually due to addition of p-phenylenediamine
to the commercial henna mixture to darken the color [12, 20, 22, 28, 33, 41, 46, 57,
63, 64]. Nevertheless, henna is dangerous to people with G-6-PD deficiency,
causing hemolytic anemia, which is more common in males than females. Infants
and children of particular ethnic groups are especially vulnerable, and may result in
death [13, 29, 32, 44, 51]. Most of the A/Es and toxicities are either in individuals
with G-6-PD deficiency or due to adulteration with p-phenylenediamine [13]. Acute
renal failure and intravascular hemolysis developed in a Saudi patient who con-
sumed henna decoction as a remedy for his chronic bloating and constipation, due
to long history of irritable bowel syndrome [49]. It is described harmful in patients
with respiratory diseases.LXXVII
Animal Toxicity: LD50 (i.p.) of glycoside extract of leaves was 2,116.6 mg/kg in
mice [8].
Metabolizing Enzymes and Potential for Drug-Herb Interaction: Ethanol leaf
extract induces phase II enzymes activity associated with carcinogen detoxification
in liver of mice and inhibited phase I enzyme activities; and significantly increases
activities of antioxidant enzymes, SOD, CAT and the hepatic GR [18].
Commentary: The only clinical trial reported verified its cooling effect in sensa-
tion of burning feet, in this case due to hand-foot syndrome caused by capecitabine
therapy. Nonetheless, there are other traditional uses, examined in pharmacological
studies, that could be the subject of formal clinical investigations of this simple,
easily available and inexpensive plant.

References
1. Adetutu A, Olorunnisola OS. Hepatoprotective potential of some local medi-
cinal plants against 2-acetylaminoflourene-induced damage in rat. J Toxicol.
2013;2013:272097.
2. Afzal M, A-Oriquat G, Al-Hassan JM, Muhammed N. Heterocycles. 1980;14:
1973.
3. Afzal M, A-Oriquat G, Al-Hassan JM, Muhammed N. Heterocycles. 1984;22:
813.
4. Akter A, Neela FA, Khan MS, et al. Screening of ethanol, petroleum ether and
chloroform extracts of medicinal plants, Lawsonia inermis L. and Mimosa
pudica L. for antibacterial activity. Indian J Pharm Sci. 2010;72: 388–92.
1090 Lawsonia inermis L.

5. Alam MS, Niwa M, Sakai T, Gupta S, Ali M. 24b-Ethylcholest-4-en-3b-ol

from the roots of Lawsonia inermis. Phytochemistry. 1992;31:2558–60.
6. Ali BH, Bashir AK, Tanira MO. Anti-inflammatory, antipyretic, and
analgesic effects of Lawsonia inermis L. (henna) in rats. Pharmacology.
1995;51:356–63.
7. Ali NA, Jülich WD, Kusnick C, Lindequist U. Screening of Yemeni medicinal
plants for antibacterial and cytotoxic activities. J Ethnopharmacol. 2001;74:
173–9.
8. Al-Jubory SY. Lethal dose (LD50) and acute toxicity, histopathological
effects of glycosides extract of Lawsonia inermis (henna) leaves in mice.
J Babylon Univ/Pure and Appl Sci. 2013;21:1093–101.
9. Al-Rubiay KK, Jaber NN, Al-Mhaawe BH, Alrubaiy LK. Antimicrobial
efficacy of henna extracts. Oman Med J. 2008;23:253–6.
10. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian
medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
11. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant
extracts on clinical isolates of beta-lactamase producing methicillin resistant
Staphylococcus aureus. J Basic Microbiol. 2005;45:106–14.
12. Arranz Sánchez DM, Corral de la Calle M, Vidaurrázaga Díaz de Arcaya C,
de Lucas Laguna R, Díaz Díaz R. Risks of black henna tattoos. An Pediatr
(Barc). 2005;63:448–52 (Spanish).
13. Badoni Semwal R, Semwal DK, Combrinck S, Cartwright-Jones C,
Viljoen A. Lawsonia inermis L. (henna): ethnobotanical, phytochemical
and pharmacological aspects. J Ethnopharmacol. 2014;155:80–103.
14. Bakhotmah BA, Alzahrani HA. Self-reported use of complementary and
alternative medicine (CAM) products in topical treatment of diabetic foot
disorders by diabetic patients in Jeddah, Western Saudi Arabia. BMC Res
Notes. 2010;3:254.
15. Ben Hsouna A, Mongi S, Culioli G, et al. Protective effects of ethyl acetate
fraction of Lawsonia inermis fruits extract against carbon tetrachloride-
induced oxidative damage in rat liver. Toxicol Ind Health. 2016;32:694–706.
16. Bhardwaj DK, Jain RK, Jain BC, Mehta CK. 1-Hydroxy-3,7-dimethoxy-6-
acetoxyxanthone, a new xanthone from Lawsonia inermis. Phytochem.
1978;17:1440.
17. Cuong NX, Nhiem NX, Thao NP, et al. Inhibitors of osteoclastogenesis
from Lawsonia inermis leaves. Bioorg Med Chem Lett. 2010;20:4782–4.
18. Dasgupta T, Rao AR, Yadava PK. Modulatory effect of henna leaf
(Lawsonia inermis) on drug metabolizing phase I and phase II enzymes,
antioxidant enzymes, lipid peroxidation and chemically induced skin and
forestomach papillomagenesis in mice. Mol Cell Biochem. 2003;245:11–22.
19. Dzhuraev KS, Nuraliev YN, Kurabanov M, Akhmedova LF, Abyshev AZ.
Rastit Resur. 1982;18:377 (Chem Abstr 1982;97:107108w).
20. Eager RP. Atopy to henna tattoos in children. Eur J Emerg Med. 2005;12:
189–90.
Lawsonia inermis L. 1091

21. Guha G, Rajkumar V, Kumar RA, Mathew L. Antioxidant activity of

Lawsonia inermis extracts inhibits chromium (VI)-induced cellular and
DNA toxicity. Evid Based Complement Alternat Med. 2011;2011:576456.
22. Gulen F, Zeyrek D, Altinoz S, et al. Urticaria and angioneurotic edema due
to the temporary henna tattoo. Minerva Pediatr. 2006;58:583–5.
23. Habbal O, Hasson S, El-Hag A, et al. Antibacterial activity of Lawsonia
inermis Linn. (henna) against Pseudomonas aeruginosa. Asian Pac J Trop
Biomed. 2011;1:173–6.
24. Habbal OA, Al-Jabri AA, El-Hag AH, et al. In-vitro antimicrobial activity
of Lawsonia inermis Linn. (henna). A pilot study on the Omani henna.
Saudi Med J. 2005;26:69–72.
25. Hemadri K, Rao SS. Jaundice: tribal medicine. Ancient Sci Life. 1984;3:
209–12.
26. Imam H, Mahbub NU, Khan MF, Hana HK, Sarker MM. Alpha amylase
enzyme inhibitory and anti-inflammatory effect of Lawsonia inermis. Pak J
Biol Sci. 2013;16:1796–800.
27. Jeyaseelan EC, Jenothiny S, Pathmanathan M, Jeyadevan J. Antibacterial
activity of sequentially extracted organic solvent extracts of fruits, flowers
and leaves of Lawsonia inermis L. from Jaffna. Asian Pac J Trop Biomed.
2012;2:798–802.
28. Jovanovic DL, Slavkovic-Jovanovic MR. Allergic contact dermatitis from
temporary henna tattoo. J Dermatol. 2009;36:63–5.
29. Kandil HH, Al-Ghanem MM, Sarwat MA, Al-Thallab FS. Henna (Lawsonia
inermis Linn,) inducing haemolysis among G6PD-deficient newborns.
A new clinical observation. Ann Trop Paediatr. 1996;16:287–91.
30. Kapadia GJ, Rao GS, Sridhar R, et al. Chemoprevention of skin cancer:
effect of Lawsonia inermis L. (henna) leaf powder and its pigment artifact,
lawsone in the Epstein-Barr virus early antigen activation assay and in two-
stage mouse skin carcinogenesis models. Anticancer Agents Med Chem.
2013;13:1500–7.
31. Kirkland D, Marzin D. An assessment of the genotoxicity of 2-hydroxy-
1,4-naphthoquinone, the natural dye ingredient of henna. Mutat Res. 2003;
537:183–99.
32. Kök AN, Ertekin MV, Ertekin V, Avci B. Henna (Lawsonia inermis Linn.)
induced haemolytic anaemia in siblings. Int J Clin Pract. 2004;58:530–2.
33. Lamchahab FZ, Guerrouj B, Benomar S, et al. Henna symbolic tattoo and
real dermatitis. Arch Pediatr. 2011;18:653–6.
34. Li Q, Gao W, Cao J, et al. New cytotoxic compounds from flowers of
Lawsonia inermis L. Fitoterapia. 2014;94:148–54.
35. Li Q, Gao WQ, Zhao YQ. Advances in studies on chemical constituents and
biological activities of Lawsonia inermis. Zhongguo Zhong Yao Za Zhi.
2013;38:795–9 (Chinese).
36. Ling LT, Radhakrishnan AK, Subramaniam T, et al. Assessment of antioxi-
dant capacity and cytotoxicity of selected Malaysian plants. Molecules.
2010;15:2139–51.
1092 Lawsonia inermis L.

37. Liou JR, El-Shazly M, Du YC, et al. 1,5-Diphenylpent-3-en-1-ynes and

methyl naphthalene carboxylates from Lawsonia inermis and their anti-
inflammatory activity. Phytochemistry. 2013;88:67–73.
38. Mahmoud ZF, Abdel Salam NA, Khafagy SM. Constituents of henna leaves
(Lawsonia inermis L.) growing in Egypt. Fitoterapia. 1980;51:153–5.
39. Malekzadeh F. Antimicrobial activity of Lawsonia inermis L. Appl Micro-
biol. 1968;16:663–4.
40. Mikhaeil BR, Badria FA, Maatooq GT, Amer MM. Antioxidant and
immunomodulatory constituents of henna leaves. Z Naturforsch. 2004;59:
468–76.
41. Mikkelsen CS, Liljefred F, Mikkelsen DB. Erythema multiforme-like
reaction to para-phenylenediamine. Ugeskr Laeger. 2011;173:51–2 (Danish).
42. Nakanishi K, Sasaki S, Kiang AK, et al. Phytochemical survey of Malaysian
plants preliminary chemical and pharmacological screening. Chem Pharm
Bull (Tokyo). 1965;13:882–90.
43. Nayak BS, Isitor G, Davis EM, Pillai GK. The evidence based wound
healing activity of Lawsonia inermis Linn. Phytother Res. 2007;21:827–31.
44. Perinet I, Lioson E, Tichadou L, Glaizal M, de Haro L. Hemolytic anemia
after voluntary ingestion of henna (Lawsonia inermis) decoction by a young
girl with G6PD deficiency. Med Trop (Mars). 2011;71:292–4 (French).
45. Peter EL, Rumisha SF, Mashoto KO, Malebo HM. Ethnomedicinal
knowledge and plants traditionally used to treat anemia in Tanzania: a
cross-sectional survey. J Ethnopharmacol. 2014;154:767–73.
46. Polat M, Dikilitaş M, Oztaş P, Alli N. Allergic contact dermatitis to pure
henna. Dermatol Online J. 2009;15:15.
47. Pradhan R, Dandawate P, Vyas A, et al. From body art to anticancer
activities: perspectives on medicinal properties of henna. Curr Drug Targets.
2012;13:1777–98.
48. Prosen H, Antonić J, Klobcar A. Determination of some organochlorine
compounds in herbal colouring agent henna (Lawsonia inermis) and in tea
(Thea sinensis). Arh Hig Rada Toksikol. 2005;56:1–7.
49. Qurashi HE, Qumqumji AA, Zacharia Y. Acute renal failure and
intravascular hemolysis following henna ingestion. Saudi J Kidney Dis
Transpl. 2013;24:553–6.
50. Rahmoun N, Boucherit-Otmani Z, Boucherit K, et al. Antifungal activity of
the Algerian Lawsonia inermis (henna). Pharm Biol. 2013;51:131–5.
51. Raupp P, Hassan JA, Varughese M, Kristiansson B. Henna causes life
threatening haemolysis in glucose-6-phosphate dehydrogenase deficiency.
Arch Dis Child. 2001;85:411–2.
52. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
53. Sauriasari R, Wang DH, Takemura Y, et al. Cytotoxicity of lawsone and
cytoprotective activity of antioxidants in catalase mutant Escherichia coli.
Toxicology. 2007;235:103–11.
Lawsonia inermis L. 1093

54. Sharma J, Gairola S, Gaur RD, Painuli RM. The treatment of jaundice with
medicinal plants in indigenous communities of the Sub-Himalayan region of
Uttarakhand, India. J Ethnopharmacol. 2012;143:262–91.
55. Sharma VK. Tuberculostatic activity of henna (Lawsonia inermis Linn.).
Tubercle. 1990;71:293–5.
56. Singh VK, Pandey DK. Fungitoxic studies on bark extract of Lawsonia
inermis against ringworm fungi. Hindustan Antibiot Bull. 1989;31:32–5.
57. Suárez Fernández R, García P, Chavarría E, Lázaro P. Allergic contact
eczema caused by henna tattoo. Allergol Immunopathol (Madr). 2002;30:
292–4 (Spanish).
58. Sudharameshwari K, Radhika J. Antibacterial screening of Aegle marmelos,
Lawsonia inermis and Albizzia libbeck. Afr J Tradit Complement Altern
Med. 2006;4:199–204.
59. Singh Sujata. Shrivastava NM, Modi NT, Saifi AQ. Anti-inflammatory
activity of Lawsonia inermis (Ethnobotany). Current Sci. 1982;51:470–1.
60. Suthienkul O, Miyazaki O, Chulasiri M, Kositanont U, Oishi K. Retroviral
reverse transcriptase inhibitory activity in Thai herbs and spices: screening
with Moloney murine leukemia viral enzyme. Southeast Asian J Trop Med
Public Health. 1993;24:751–5.
61. Takeda Y, Fatope MO. New phenolic glucosides from Lawsonia inermis.
J Nat Prod. 1988;51:725–9.
62. Tripathi RD, Srivastava HS, Dixit SN. A fungitoxic principle from the
leaves of lawsonia inermis Lam. Experientia. 1978;34:51–2.
63. Turan H, Okur M, Kaya E, et al. Allergic contact dermatitis to para-
phenylenediamine in a tattoo: a case report. Cutan Ocul Toxicol. 2013;32:
185–7.
64. Uzuner N, Olmez D, Babayigit A, Vayvada O. Contact dermatitis with
henna tattoo. Indian Pediatr. 2009;46:423–4.
65. Yogisha S, Samiulla DS, Prashanth D, et al. Trypsin inhibitory activity of
Lawsonia inermis. Fitoterapia. 2002;73:690–1.
66. Yucel I, Guzin G. Topical henna for capecitabine induced hand-foot
syndrome. Invest New Drugs. 2008;26:189–92.
Lepidium sativum L.
(Brassicaceae)

(Syns.: L. hortense Forssk.; L. spinescens DC.; Cardamon sativum (L.) Fourr.;

Arabis chinensis Rottler ex Wight)

Abstract
The shrub is a cultivated vegetable all over Asia, and is the Garden Cress of
Europe. Seeds are considered functional food, containing significant amounts of
protein, fat, dietary fiber and potassium, and amino acids, glutamic acid, leucine
and methionine, with linolenic acid being the major fatty acid. Seeds are
regarded in Unani medicine as expectorant, appetizer, diuretic, emmenagogue,
resolvent, detergent, aphrodisiac and oxytocic. Seed infusion or decoction,
chiefly due to their mucilaginous property, are useful in diarrhea, dysentery, and
skin diseases caused by impurity of the blood. A cold infusion of seeds is used to
relieve hiccough. Seeds contain sinapic acid ethyl ester, N,N′-dibenzylthiourea,
N,N′-dibenzyl-urea, dimeric imidazole alkaloids lepidine, lepidine B–F, and
monomeric alkaloids, semilepidinoside A and B. Aqueous extract significantly
lowered BP of SHRs without affecting BP of normotensive rats, and significantly
increased urinary excretion of Na+, K+ and chloride in both normotensive and
SHRs. Repeated oral administration of aqueous extract normalized glucose
levels in STZ diabetic rats, and significantly reduced blood glucose of normal
rats without altering basal plasma insulin levels. Aqueous suspension of seed
powder produced significant analgesic effect against various noxious stimuli,
and seed oil significantly decreased production of inflammatory mediators by
peritoneal macrophages in response to different stimuli, and modulated
inflammatory mediators such as NO and LTB4 in rats.

Keywords







Agrião Aselio Bahçe teresi Chandrasura Cress Haleem Kuan ye jia du



xing cai Lepido Rashad Shahi

Vernaculars: Urd.: Haleem; Hin.: Akalam, Aselio, Chandrika, Chansaur, Halim,

Hurf, Tara-tezak; San.: Ahaleeva, Chandrasura; Ben.: Aliveri, Halim, Halim-shak;
Guj.: Asaliya; Mal.: Aasali, Asali; Mar.: Ahaliva, Alhiv; Tam.: Alivirai;
© Springer Nature Switzerland AG 2020 1095
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_118
1096 Lepidium sativum L.

Tel.: Adala vitala, Adityalu; Ara.: Hab-er-rashad, Haraf, Rashad; Bur.: Mongnyin;
Chi.: 台尔台孜, Kuan ye jia du xing cai; Cze.: Řeřicha setá, Řeřicha zahradní;
Dan.: Havekarse; Dut.: Tuinkers; Eng.: Broad-leaved garden cress, Cress, Water-
cress; Fin.: Vihanneskrassi; Fre.: Cresson alénois, Passerage cultivée; Ger.: Bre-
itblättrige gartenkresse, Gartenkresse; Hun.: Amerikai zsázsa, Kerti zsázsa; Ita.:
Agretto, Cerconcello, Crescione inglese, Lepidio; Jap.: Koshôsô; Kor.: Kundadag-
naengi; Lat.: Nasturtium; Nor.: Matkarse; Per.: Shahi, Tokhm taretizak, Turrah-
tezak; Pol.: Pieprzyca siewna; Por.: Agrião, Erva-do-esforzo, Mastruco; Rus.: Kress-
salat; Spa.: Berro hortense, Lepido, Mastuerzo de huerta; Swe.: Kryddkrassing,
Smörgåskrasse, Trädgårdskrasse; Tha.: Thian-dan; Tur.: Bahçe teresi, Tere, Tere out;
Vie.: Xa lach son.
Description: The shrub is a cultivated vegetable all over Asia, and is the Garden
Cress of Europe. Seeds are of a reddish color, odorless, of a pungent and
mucilaginous taste, oblong, somewhat angular and curved slightly on one side and
surface wrinkled. Near the point of attachment there is a white scar, from which a
small channel extends to one third of the length of the seed.LXXXI Pharmacognostical
features of seeds have been described by Raval and Pandya [21] (Figs. 1, 2 and 3).
Actions and Uses: Seeds are considered functional food, containing significant
amounts of protein, fat, dietary fiber and potassium, and amino acids, glutamic
acid, leucine and methionine, with linolenic acid being the major fatty acid [15].
In Unani medicine, seeds (temperament, hot 3° and dry 3°) are regarded expec-
torant, appetizer, diuretic, emmenagogue, resolvent, detergent, aphrodisiac and
oxytocic.L,LXXVII Seeds are also aperient, alterative, demulcent, carminative, tonic,
and galactagogue; whereas the leaves are gentle stimulant and diuretic. Seed
infusion or decoction, chiefly due to their mucilaginous property, are useful in
diarrhea, dysentery, and skin diseases caused by impurity of the blood.CV A cold
infusion of seeds is used to relieve hiccough. As alterative, they are used in chronic
enlargement of liver and spleen, and as a restorative tonic in seminal debility and

Fig. 1 Lepidium sativum in a field, Till Westermayer, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Img_0717_garden_cress.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Lepidium sativum L. 1097

Fig. 2 Lepidium sativum, Blooming, Corinna John, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Gartenkresse_bl%C3%BChend.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Lepidium sativum, Seeds, Frank Vincentz, WikimediaCommons; https://commons.

wikimedia.org/wiki/File:Lepidium_sativum_01_ies.jpg

leucorrhea. Bruised seeds mixed with lime-juice are used as application to relieve
inflammatory and rheumatic pains.LXXXI Seeds are used in traditional Iranian
medicine for the treatment of IBD [20], and are also widely used in folk medicines
for the treatment of hyperactive airways disorders, such as asthma, bronchitis and
cough [23], as effective diuretic [28], abortifacient, ecbolic and oxytocic,CL and as
photosensitizers.CXXXV They are also one of the most frequently used plant-derived
drugs to treat diabetes in the Errachidia province in southeastern Morocco [26]. In
some Arab countries, seeds are used by traditional healers to enhance healing of
fractures [16], and as contraceptives [25].
1098 Lepidium sativum L.

Phytoconstituents: Seeds contain sinapic acid ethyl ester, N,N′-dibenzylthiourea,

N,N′-dibenzyl-urea [7], dimeric imidazole alkaloids lepidine, lepidine B, C, D, E
and F, and monomeric alkaloids, semilepidinoside A and B [18]. Garden cress seed
oil is one of the richest sources of omega-3 fatty acid and contains 29–34.5% of
a-linolenic acid [10]. Oleic acid and linoleic acid are the other major fatty acids, and
d-tocopherol is the most abundant in seed oil [29].
Pharmacology: Aqueous suspension of seed powder produced significant anal-
gesic effect against various noxious stimuli [22], and seed oil significantly decreased
production of inflammatory mediators by peritoneal macrophages in response to
different stimuli, and modulated inflammatory mediators such as NO and LTB4 in
rats [11]. Aqueous extract significantly lowered BP of SHRs without affecting BP of
normotensive rats, and increased urinary excretion of Na+, K+ and chloride in both
normotensive and SHRs [17]. Repeated oral administration of aqueous extract for
2-weeks normalized glucose levels in STZ diabetic rats, and significantly reduced
blood glucose of normal rats without altering basal plasma insulin levels [13].
While it normalized glycemia, it enhanced glycosuria by inhibiting renal glucose
reabsorption and decreased the amount of urinary transforming growth factor (TGF)-
beta1 in diabetic rats [12]. The oil has significant antioxidant potential [29], and the
aqueous-methanol extract was described as prokinetic and laxative in mice, and
partially sensitive to atropine [19]. However, the same group of researchers
described it as antidiarrheal and spasmolytic [14, 24]; they have also reported
bronchodilatory effect of the extract in guinea pig tracheal rings that is mediated
through a combination of anticholinergic, Ca++ antagonist and PDE inhibitory
pathways [23]. Administration of seeds to rabbits significantly enhanced healing of
experimental fractures in rabbits [16]. Methanol extract reduced activity of amoxi-
cillin against standard strain, but enhanced its activity against resistant strains of
E. coli [8]. Combination of methanol extract with chloramphenicol, gentamicin and
cephalosporin inhibited growth of resistant strain of P. aeruginosa, and significantly
improved activity of nalidixic acid on standard strain [1]. Feeding of seeds in diet to
female mice prevented contraception in 100% mice, that was reversible after short
interruption [25]. Pharmacological studies suggested the presence of a cardioactive
substance, which was unstable in solution, showed tachyphylaxis and probably
exerted its actions through adrenergic mechanisms [27]. Protein extract of seeds
demonstrated significant immunostimulatory activity [9].
Human A/Es, Allergy and Toxicity: There are no known A/Es or toxicity of
Garden Cress.
Animal Toxicity: Seeds fed in diet to Wistar albino rats at 2% (w/w) were non-
toxic, while 10% were toxic but not fatal and 50% of the diet for 6-weeks were
lethal and slowed growth rate and caused entero-hepato-nephrotoxicity, accompa-
nied with anemia and leukopenia [2]. A lectin from seeds agglutinates human
erythrocytes, without specificity for the A, B and O blood groups; the hemagglu-
tinating activity is abolished by heating the lectin solution at 70 °C [30].
Potential for Drug-Herb Interactions: Oral coadministration of aqueous extract
increased Cmax, absorption rate, and half-life of carbamazepine [4], and signifi-
cantly delayed absorption of cyclosporine in rabbits [3], modestly increased Cmax
Lepidium sativum L. 1099

and half-life of phenytoin and reduced its clearance by 33% [5], and significantly
reduced Cmax and AUC of sildenafil in beagle dogs [6].
Commentary: The anti-inflammatory, antibacterial, antidiabetic, antihypertensive
and diuretic activities should be of interest for further pharmacological investiga-
tions, and potential clinical studies.

References
1. Aburjai T, Darwish RM, Al-Khalil S, et al. Screening of antibiotic resistant
inhibitors from local plant materials against two different strains of
Pseudomonas aeruginosa. J Ethnopharmacol. 2001;76:39–44.
2. Adam SE. Effects of various levels of dietary Lepidium sativum L. seeds in
rats. Am J Chin Med. 1999;27:397–405.
3. Al-Jenoobi FI, Al-Suwayeh SA, Muzaffar I, et al. Effects of Nigella sativa
and Lepidium sativum on cyclosporine pharmacokinetics. Biomed Res Int.
2013;2013:953520.
4. Alkharfy KM, Al-Jenoobi FI, Alam MA, et al. Lepidium sativum but not
Nigella sativa affects carbamazepine disposition in an animal model. Drug
Metab Lett. 2013;7:47–51.
5. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium
sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin
pharmacokinetics in beagle dogs. Phytother Res. 2013;27:1800–4.
6. Al-Mohizea AM, Ahad A, El-Maghraby GM, et al. Effects of Nigella sativa,
Lepidium sativum and Trigonella foenum-graecum on sildenafil disposition
in beagle dogs. Eur J Drug Metab Pharmacokinet. 2015;40:219–24.
7. Bahroum A, Damak M. Contribution to the study of Lepidium sativum
(Cruciferae). Structure of a new compound isolated from the seed: Lepidine.
J Soc Chim Tunis. 1985;2:15–24.
8. Darwish RM, Aburjai TA. Effect of ethnomedicinal plants used in folklore
medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli.
BMC Complement Altern Med. 2010;10:9.
9. Daoudi A, Aarab L, Abdel-Sattar E. Screening of immunomodulatory activity
of total and protein extracts of some Moroccan medicinal plants. Toxicol Ind
Health. 2013;29:245–53.
10. Diwakar BT, Dutta PK, Lokesh BR, Naidu KA. Bioavailability and
metabolism of n-3 fatty acid rich garden cress (Lepidium sativum) seed oil in
albino rats. Prostaglandins Leukot Essent Fatty Acids. 2008;78:123–30.
11. Diwakar BT, Lokesh BR, Naidu KA. Modulatory effect of a-linolenic
acid-rich garden cress (Lepidium sativum L.) seed oil on inflammatory
mediators in adult albino rats. Br J Nutr. 2011;106:530–9.
12. Eddouks M, Maghrani M. Effect of Lepidium sativum L. on renal glucose
reabsorption and urinary TGF-beta 1 levels in diabetic rats. Phytother Res.
2008;22:1–5.
13. Eddouks M, Maghrani M, Zeggwagh NA, Michel JB. Study of the
hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal
and diabetic rats. J Ethnopharmacol. 2005;97:391–5.
1100 Lepidium sativum L.

14. Gilani AH, Rehman NU, Mehmood MH, Alkharfy KM. Species differences
in the antidiarrheal and antispasmodic activities of Lepidium sativum and
insight into underlying mechanisms. Phytother Res. 2013;27:1086–94.
15. Gokavi SS, Malleshi NG, Guo M. Chemical composition of garden cress
(Lepidium sativum) seeds and its fractions and use of bran as a functional
ingredient. Plant Foods Hum Nutr. 2004;59:105–11.
16. Juma AH. The effects of Lepidium sativum seeds on fracture-induced
healing in rabbits. MedGenMed. 2007;9:23.
17. Maghrani M, Zeggwagh NA, Michel JB, Eddouks M. Antihypertensive
effect of Lepidium sativum L. in spontaneously hypertensive rats. J Ethnophar-
macol. 2005;100:193–197.
18. Maier UH, Gundlach H, Zenk MH. Seven imidazole alkaloids from
Lepidium sativum. Phytochemistry. 1998;49:1791–5.
19. Najeeb-Ur-Rehman, Mehmood MH, Alkharfy KM, Gilani AH. Prokinetic
and laxative activities of Lepidium sativum seed extract with species and
tissue selective gut stimulatory actions. J Ethnopharmacol. 2011;134:878–83.
20. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J
Gastroenterol. 2010;16:4504–14.
21. Raval ND, Pandya TN. Pharmacognostic study of Lepidium sativum Linn.
(Chandrashura). Ayu. 2011;32:116–9.
22. Raval ND, Ravishankar B. Analgesic effect of Lepidium sativum Linn.
(Chandrashura) in experimental animals. Ayu. 2010;31:371–3.
23. Rehman NU, Khan AU, Alkharfy KM, Gilani AH. Pharmacological basis
for the medicinal use of Lepidium sativum in airways disorders. Evid Based
Complement Alternat Med. 2012;2012:596524.
24. Rehman NU, Mehmood MH, Alkharfy KM, Gilani AH. Studies on
antidiarrheal and antispasmodic activities of Lepidium sativum crude extract
in rats. Phytother Res. 2012;26:136–41.
25. Sharief M, Gani ZH. Garden cress Lepidium sativum seeds as oral contraceptive
plant in mice. Saudi Med J. 2004;25:965–6.
26. Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B. Ethnopharmacological survey
of plants used in the traditional treatment of hypertension and diabetes in
southeastern Morocco (Errachidia province). J Ethnopharmacol. 2007;110:
105–17.
27. Vohra SB, Khan MS. Pharmacological studies on Lepidium sativum Linn.
Indian J Physiol Pharmacol. 1977;21:118–20.
28. Wright CI, Van-Buren L, Kroner CI, Koning MM. Herbal medicines as
diuretics: a review of the scientific evidence. J Ethnopharmacol. 2007;114:
1–31.
29. Zia-Ul-Haq M, Ahmad S, Calani L, et al. Compositional study and antioxi-
dant potential of Ipomoea hederacea Jacq. and Lepidium sativum L. seeds.
Molecules. 2012;17:10306–21.
30. Ziska P, Kindt A, Franz H. Isolation and characterization of a lectin from
garden cress (Lepidium sativuum). Acta Histochem. 1982;71:29–33.
Linum usitatissimum L.
(Linaceae)

(Syns.: L. crepitans (Boenn.) Dumort.; L. humile Mill.)

Abstract
This annual plant, as a food and fiber crop, is mainly cultivated in Central Asia,
Egypt, Mediterranean countries, and southern Europe. Flaxseeds (linseeds) are
regarded as functional food. Both Dioscorides and Pliny described and used this
plant. Ibn al-Baitar described it as a good abortifacient, and quoted Dioscorides
that using it mixed with black pepper and honey stimulates sexual desire.
Linseed poultice is recommended for gouty and rheumatic swellings, and with
honey they are prescribed for coughs and colds. The oil is applied in both
external and internal inflammations, such as pleurisy, pneumonia, and arthritis.
Application of the oil with lime-water to burns is very beneficial; and taking oil
internally helps atherosclerosis and nephritis. Linseed oil was used in painter’s
colic and other spasmodic affections of the bowel. In traditional Iranian
medicine, seeds have been used for the treatment of IBD. Smaller seeds in whole
and powdered form have higher swelling factors than the larger seeds; however,
the amount of fatty oil is higher in the larger seeds than in the smaller one. In
addition to being one of the richest dietary sources of a-linolenic acid, they are
also a good source of soluble fiber mucilage. Flaxseeds are also one of the
richest sources of lignans, that are metabolized after ingestion by colonic
bacteria into enterolignans, enterodiol and enterolactone, are not degraded by
heat, even after heating at 250 °C. Crushing and milling seeds substantially
improves the bioavailability of enterolignans. Secoisolariciresinol diglucoside is
the characteristic lignan present in seeds. The oil contains unsaturated fatty acids
like oleic acid, linoleic acid, and linolenic acid, and other phenolic compounds,
such as phenolic acids. Raw ground flaxseed intake for 4-weeks by healthy
Canadian female volunteers lowered serum TC by 9% and LDL-C by 18%, and
significantly decreased postprandial blood glucose. Even partially defatted
flaxseed in muffins for 3-weeks significantly reduced TC, LDL-C, apo B and apo
A-I in a controlled crossover trial of Canadian hyperlipidemic subjects.

© Springer Nature Switzerland AG 2020 1101

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_119
1102 Linum usitatissimum L.

Keywords


Alsi Atasi
Bazen
Flaxseed
Katan
Keten
Len setý
Lijnzaad
Lino

Yà má

Vernaculars: Urd.: Alsi, Katan; Hin.: Alsi, Tisi; San.: Atasi; Ben.: Mosina, Tesi;
Mal.: Cheru-chana, Vittiute-eima; Mar.: Alashi, Javas; Tam.: Alishi-virai, Alivi-
raaii; Tel.: Allivi-tullu, Atasi, Madana-gingelu; Ara.: Bazar-el-Katan, Bazen, Kattân;
Chi.: 亚麻, Hu-ma-tsze, Yà má; Cze.: Len setý; Dan.: Almindelig hør; Dut.: Lijn-
zaad, Vlas; Eng.: Flaxseed, Linseed; Fin.: Peltopellava; Fre.: Lin, Lin commun, Lin
cultivé, Lin usuel; Ger.: Echter lein, Lein, Flachs, Flachslein, Saatlein; Ita.: Lino,
Lino coltivato, Lino comune; Nep.: Tisii; Per.: Tukhm-e-katan, Tukhm-e-zaghira;
Por.: Linho, Linho-comum; Spa.: Lino, Lino común; Swe.: Lin; Tur.: Keten.
Description: This annual plant, as a food and fiber crop, is mainly cultivated in
Central Asia, Egypt, Mediterranean countries, and southern Europe. The capsule,
which is globose, splits into 5 carpels, each containing two seeds separated by a
partition. Seeds, 6–9 mm long, are of a flattened elongated ovoid form, with an
acute edge, and a slightly oblique point blunt at one end. They have a brown glossy
polished surface, which under a lens is seen to be marked with extremely fine pits.
The hilum occupies a slight hollow in the edge just below the apex. When
immersed in water, the seeds become surrounded by a thin, slippery, colorless
mucous envelope, which quickly dissolves as a neutral jelly, while the seeds
slightly swell and lose their polish (Figs. 1, 2, 3, 4 and 5).XL
Actions and Uses: Flaxseeds (linseeds) are regarded as functional food [59]. Both
Dioscorides and Pliny described and used this plant. Ibn al-BaitarLXIX described it
as a good abortifacient, and quoted Dioscorides that using it mixed with black
pepper and honey stimulates sexual desire. Manual flax processing originated in
Egypt in 2000 B.C. [93]. In Allopathic medicine, Linseed tea was used as a
demulcent drink in cough due to irritated and inflamed pharynx and URT. It was
also useful in irritation of the intestines and urinary passages. Unani physicians
regard seeds (temperament, hot 1° and dry 1°) as resolvent, anti-inflammatory,
mucolytic, laxative, concoctive, analgesic, wound healing, and aphrodisiac; and, the
flowers are considered cardiac tonic. Linseed poultice is recommended for gouty
and rheumatic swellings, and with honey they are prescribed for coughs and colds.
The oil is applied in both external and internal inflammations, such as pleurisy,
pneumonia, and arthritis.LXXVII Application of the oil with lime-water to burns is
very beneficial; and taking oil internally helps atherosclerosis and nephritis.1 Lin-
seed oil was used in painter’s colic and other spasmodic affections of the bowel.XL
The oil with an equal part of lime-water forms ‘carron oil’ (so called because it was
first extensively used in the Carron iron foundry) that was used for burns and scalds,
and given internally (60 ml bid) as an aperient for piles.XL In traditional Iranian

1
Tayyab M: Personal Communication.
Linum usitatissimum L. 1103

Fig. 1 Linum usitatissimum, Blooming, H. Zell, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Linum_usitatissimum_001.JPG

Fig. 2 Linum usitatissimum, Flowers, D. Gordon Robertson, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Flax_flowers.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

medicine, seeds have been used for the treatment of IBD [117]. Smaller seeds in
whole and powdered form have higher swelling factors than the larger seeds;
however, the amount of fatty oil is higher in the larger seeds than in the smaller ones
[43]. Flaxseeds are now being increasingly used in food, as laxatives and as dietary
health supplements for menopausal symptoms [42], due to their high content of
omega-3 fatty acid and a-linolenic acid (ALA). ALA is suggested to positively
impact cardiovascular diseases [123], and in doses of 14 g/day or greater reduces
1104 Linum usitatissimum L.

Fig. 3 Linum usitatissimum, Capsules, Rasbak, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Linum_usitatissimum_capsules,_vlas_
zaadbollen.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 4 Linum usitatissimum, Brown Flaxseeds, Sanjay Acharaya, WikimediaCommons; Share-

Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Brown_Flax_Seeds.
jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Linum usitatissimum L. 1105

Fig. 5 Linum usitatissimum, Golden Flaxseeds, Bdevel, WikimediaCommons; ShareAlike 2.5

Generic CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Flax_seeds.jpg; https://creative
commons.org/licenses/by-sa/2.5/deed.en

inflammatory mediators/markers [111]. In addition to being one of the richest

dietary sources of ALA, they are also a good source of soluble fiber mucilage [26,
123]. Flaxseeds are also one of the richest sources of lignans [141], that are
metabolized after ingestion by colonic bacteria into enterolignans, enterodiol and
enterolactone [75], and are not degraded by heat, even after heating at 250 °C [49].
Crushing and milling seeds substantially improves the bioavailability of
enterolignans [74]. Lignans are phytoestrogens [152] and their dietary intake lowers
plasma TC and LDL-C, and are suggested to reduce the risk of cardiovascular
disease [8, 103] by preventing atherosclerosis [110], and retard the development
and progression of chronic renal disease [147]. Flaxseed lignans also demonstrate
antioxidant and anti-inflammatory activity [3]. Flaxseed was one of the most
commonly used herbs (18%) by U.S. healthcare professionals (HCPs) surveyed,
where 51% of the 1,249 HCPs enrolled in an online course about herbs and dietary
supplements reported using an herb in the previous week [48]. Ingestion of flaxseed
oil and milled flaxseed delivers significant levels of ALA to plasma, but not the
whole flaxseeds [6]. Secoisolariciresinol diglucoside (SDG), a lignan complex, is
hypothesized to be cardioprotective due to its estrogen-like effects [56], and may
reduce breast cancer risk [139]. Flaxseed is approved for GI disorders use in Europe
by the HMPC of the European Medicines Agency. However, scientific data is still
lacking for its use in constipation, despite being added to the inventory since Jan.
2005. Up to 50 g high-ALA flaxseeds per day has been determined as palatable,
safe and may be nutritionally beneficial in humans [26].
Phytoconstituents: SDG is the characteristic lignan present in seeds [130]. The oil
contains unsaturated fatty acids like oleic acid (12–30%), linoleic acid (8–29%),
and linolenic acid (35–67%) [5], and other phenolic compounds, such as phenolic
acids [62]. Levels of caffeic acid, p-coumaric acid and ferulic acid, and SDG are not
1106 Linum usitatissimum L.

significantly different between fiber and flaxseed oil, suggesting equal value of fiber
as a functional food [149]. Presence of omega-3, omega-6 rich oil, SDG, protein
and minerals justifies their utilization for health benefits [2]. Cyclic peptides,
cyclolinopeptides F-I, have also been isolated from the seeds [88]. Phytosterols
present include cholesterol, campesterol, brassicasterol, stigmasterol, b-sitosterol,
ô5-avenasterol, cycloartenol, 24-methylene cycloartanol, obtusifoliol, and citro-
stadienol. During linseed development, b-sitosterol is the major 4-desmethylsterol,
followed by campesterol and stigmasterol [61]. The viscous seed mucilage is a
mixture of rhamnogalacturonan I and arabinoxylan [90]. Flax oil of Turkish origin
contains ALA as the major fatty acid, and is also rich in c-tocopherol [18].
Pharmacology: Linseed oil inhibited PGE2-, leukotriene-, histamine- and
bradykinin-induced inflammation [70], and carrageenan and AA-induced paw
edema in rats [133]. The oil (i.p.) significantly inhibited castor oil-induced diarrhea
and turpentine oil-induced exudative joint edema, formaldehyde-induced prolifer-
ative global edematous arthritis, and Complete Freund’s Adjuvant-induced arthritis
in rats [69, 134]. It inhibits local vasodilatation, capillary permeability, exudation,
and leucocytes migration during inflammation [67]. Pretreatment with linseed oil
ameliorates CP-induced oxidative stress in mice [12], and feeding rats with flaxseed
supplemented diet restores levels of antioxidant enzymes, such as CAT, SOD, and
peroxidase that are decreased by CCl4 challenge [118]. Topical application of
linseed oil significantly shortened healing period of burn wounds in rabbits [10],
and application of a semisolid formulation of linseed oil on skin wounds of rats
reepithelialized 100% of wounds, compared to 33% of those treated with petroleum
jelly [28].
Flaxseed or SDG-supplemented diet in rats reduced plasma insulin-like growth
factor I (IGF-I), which is implicated with the increased risk of breast cancer [122].
Flaxseed reduced metastasis and inhibited growth of metastatic secondary tumors in
animals [153]. Supplementation of diet with 10% flaxseed to nude mice with
established breast tumors reduced tumor growth and metastasis [22, 27], and
decreased extracellular levels of VEGF [27]. Flaxseed and SDG treatment delayed
the progression of N-methyl-N-nitrosourea-induced mammary tumors [121], and
significantly reduced plasma IGF-I concentrations in rats [122]. Maternal dietary
intake of flaxseed during pregnancy or lactation, however, shortened DMBA-
induced tumor latency, and 10% flaxseed exposure also increased tumor multi-
plicity in rat offsprings [72]. Flaxseed significantly decreased tumor multiplicity and
size in the small intestine and colon of Apc(Min) mice [17], and significantly
decreased expression of COX-1 and COX-2 [16]. However, intake of flaxseed in a
Western-style diet did not protect against intestinal tumor development in mice
[145]. Diet supplemented with 5% flaxseed also inhibited development and growth
of prostate cancer in transgenic mice [79]. Combining flaxseed oil enhanced
tumor-reducing effects of trastuzumab in mice, the primary drug for HER2 positive
breast cancer [86], and enhanced effect of tamoxifen in reducing growth of
Linum usitatissimum L. 1107

established estrogen receptor positive breast tumors [126], possibly due to its
antiestrogenic effects on estrogen receptor-positive breast cancer [9].
Flaxseed-supplemented diet also significantly reduced body weight and fat
accumulation, improved lipid profile, and BP in high-fat diet-treated rats [99],
markedly reduced cholesterol-induced plaque formation in rabbits [44], and
reduced by 67% the number of animals with aortic arch atherosclerotic lesions in
ovariectomized female Golden Syrian hamsters [20, 81]. Flax lignan complex and
isolated SDG also significantly reduced acceleration of cholesterol-induced aortic
atherosclerotic lesions and reduced oxidative stress in rabbits [108, 113], that was
independent of ALA contents [107]. Flaxseed flour supplementation in diet to
mothers during postnatal lactation period, and continuing it in male offsprings of
rats for 250-days significantly lowered body weight, visceral fat mass, TC, TGs,
HDL, VLDL, glucose and thickness of the aortas [21]. Tunisian flaxseed oil in vitro
inhibited ACE, and treatment with it [32] and flaxseed supplementation noticeably
protected against isoproterenol-induced MI in rats [92]. Flaxseed oil administration
to Holtzman rats for sixty-days lowered TC and TGs, and increased HDL-C [51].
Flaxseed supplemented diet significantly decreased body mass, LDL-C, glucose
and uric acid, and increased HDL-C in 47% of normal rats [142]. Flaxseed meal
also significantly lowered fat deposition in livers, significantly lowered LDL-C,
HDL-C, and TGs in obese phenotype rats [11], and modest dietary flaxseed intake
effectively reduced hypercholesterolemic atherosclerosis, without significantly
lowering TC in rats [109]. A four-weeks flaxseed consumption by rabbits reduced
LDL-C and TC levels due to hypercholesterolemic diet, but did not reduce
atherosclerotic lesions induced by it [115]. Supplementation of cholesterol-enriched
diet with 10% (w/w) ground flaxseed lowered plasma cholesterol and saturated
fatty acids, and inhibited plaque formation in aorta and aortic sinus of LDL-
receptor-deficient mice [37, 102], and the same treatment in hypercholesterolemic
rabbits had significantly reduced atherosclerotic lesions in aorta and carotid arteries
for up to 8-weeks, but the effect completely disappeared by 16th week [38]. Flax
lignan complex suppressed the development of hypercholesterolemic atheroscle-
rosis with reductions in oxidative stress [110, 112], and protected rats against lead
acetate-induced oxidative damage and hyperlipidemia [91]. SDG reduced rate of
body-weight gain, hepatic lipid accumulation, and serum TC and LDL-C [41],
significantly reduced high-fat diet-induced visceral and liver fat accumulation,
hyperlipemia, hypercholesterolemia, hyperinsulinemia and hyperleptinemia in mice
[47]. SDG also retarded development of diabetes, and prevented diabetes associated
increase in oxidative stress, TC, TGs, and HbA1c [114]. Flaxseed supplemented
diet to diabetic hamsters significantly reduced serum TC, TC/HDL-C ratio, and
increased serum HDL-C without affecting serum TGs [52]. Feeding flaxseed-meal
supplemented diet to obese SHRs/NIH-corpulent rats significantly reduced plasma
insulin, proteinurea, and nephropathy [146].
Pretreatment of rats with flaxseed oil substantially protected against various
experimental gastric ulcers [36, 68]. The oil also significantly inhibited pylorus and
forestomach ligation-induced esophagitis, gastric secretion, and total acidity [119].
Moderate to high doses of partially defatted flaxseed meal markedly increased stool
1108 Linum usitatissimum L.

frequency and weight in both normal and constipated mice [152]. Flaxseed and flax
oil in diet are renoprotective in rat model of polycystic kidney disease and ame-
liorated the associated chronic interstitial nephritis [7, 94, 95, 127, 128], and pre-
vented rise in BP and significantly attenuated increase in plasma TGs and TC of rats
after 5/6 nephrectomy [64]. Dietary flaxseed and its extracts also reduced oxidative
stress in diabetic nephropathy [53, 71], and protected against CCl4-hepatotoxicity
[39, 60].
Flaxseed and SDG produced antiestrogenic effect in rats [96, 144]. Flaxseed
supplemented diet to rats throughout gestation and to offspring until they were
weaned, resulted in significant increases in serum LH, cauda epididymal weight,
cauda epididymal sperm numbers and a decrease in prostate weight in male off-
springs [136]. Exposure of rats to high doses of flaxseed during gestation did not
affect fetal development [24], and exposure of male or female offspring to flaxseed
(10%) or SDG during lactation also had no significant effects on reproductive
indices [150]. Lifetime exposure of male rats to higher dose of flaxseed raised
serum testosterone and estradiol levels and produced higher relative sex organ
weights and prostate cell proliferation, while lower dose exposure reduced adult
relative prostate weight and cell proliferation [143]. Flaxseeds with low-dose
estrogen preserve vertebral bone mass and strength in ovariectomized rats at the
lumbar vertebrae [124], but do not enhance the estrogenic effect on uterine health
[125].
Clinical Studies: Raw ground flaxseed intake (50 g/day) for 4-weeks by healthy
Canadian female volunteers lowered serum TC by 9% and LDL-C by 18%, and
significantly decreased postprandial blood glucose [26], and flaxseed supplement
consisting of three slices of flaxseed-containing bread and 15 g of ground flaxseed
for 12-weeks significantly reduced serum TC and LDL-C in 15 hyperlipemic sub-
jects [13]. Even partially defatted flaxseed in muffins for 3-weeks significantly
reduced TC, LDL-C, apo B and apo A-I in a controlled crossover trial of Canadian
hyperlipidemic subjects [65]. However, healthy Canadian men, aged 22 to 47 years,
after consuming 32.7 g of flaxseed in muffins daily for 4-weeks had no significant
changes in BP, HR, Hb, RBC and WBC counts, and serum TC, HDL-C, LDL-C, and
VLDL-C [137]. Ground flaxseed (30 g) or flaxseed oil intake by younger (18–
29 years) and older (45–69 years) Canadian subjects for 4-weeks also had no
significant effect on platelet aggregation, plasma TC, LDL-C or HDL-C [101].
Average plasma glucose, SBP, and DBP were within normal clinical range in
healthy 49–87 years old Canadian participants, who consumed a commercial lignan
enriched product (BeneFlax®) or placebo in an RCT for six-months [14]. Canadian
patients with PAD and 75% hypertensive, after consuming 30 g of milled flaxseed/d
for 6-months had their SBP and DBP significantly reduced, suggestively due to
inhibition of soluble epoxide hydrolase [19]. A flaxseed fiber drink (3 times a day)
by young Danish men and women lowered fasting TC and LDL-C by 12 and 15%,
respectively, and increased fecal fat excretion [73]. Six-weeks consumption of
600 mg/day of SDG from flaxseed extract by hypercholesterolemic Chinese subjects
significantly decreased serum TC, LDL-C and glucose [154], and addition of
Linum usitatissimum L. 1109

flaxseed (30 g/day) to lifestyle counseling to Chinese patients with metabolic syn-
drome had significant additional reduction in body weight, waist circumference,
serum glucose, TC, LDL-C, Apo B, ApoE, and BP [151]. Administration of SDG
(20 or 100 mg) to moderately hypercholesterolemic Japanese men for 12-weeks also
exhibited significant reduction in the ratio of LDL-C/HDL-C [46]. Roasted flaxseed
powder (30 g/day) in diets of dyslipidemic Indian patients for 3-months significantly
reduced body weight, BMI, SBP, DBP, TC, LDL-C, VLDL-C and TGs, with a
simultaneous increase in HDL-C levels [129]. Flaxseed (20 g daily) for two-months
was as effective as statin treatment in significantly lowering TC, LDL-C, TG, and
TC/HDL-C ratio in mildly hyperlipidemic Romanian patients [84]. Consumption of
40 g of ground flaxseed daily for 3-months by U.S. postmenopausal women had
significantly lowered serum TC, LDL-C, HDL-C and TGs [82]. Crushed flaxseed
(40 g daily) and oral estrogen-progesterone equally improved mild menopausal
symptoms and lowered glucose and insulin levels in hypercholesterolemic meno-
pausal Canadian women [76]. In a double-blind RCT, flaxseed (40 g/day)-
containing baked products consumption for 10-weeks caused a modest but short
lived LDL-C lowering effect, but significantly reduced Lp(a) and improved insulin
sensitivity in hyperlipidemic U.S. men and postmenopausal women [15]. Dietary
flaxseed for three-months lowered TC and LDL-C by approximately 7% and 10%,
respectively in moderately hypercholesterolemic Native American postmenopausal
women [100]. Use of 40 g flaxseed daily by healthy menopausal Canadian women
for 12-months increased Apo A-1 and B, Lp(a) and decreased LDL peak particle
size [34].
Consumption of Linola 989, a strain of flaxseed highest in lignan and lowest in
a-linolenic acid, caused the least increase in peripheral resistance, greatest reduction
in plasma cortisol, and the smallest increase in plasma fibrinogen during mental stress
test in postmenopausal Canadian women with vascular disease [135]. Intake of a
lignan complex isolated from flaxseed, providing 500 mg/day of SDG, by healthy
postmenopausal Danish women for 6-weeks lowered CRP [54], without affecting
TC, LDL-C, HDL-C, and TGs [55], or endothelial function [56]. Flaxseed flour
(30 g/day) for 2-weeks also lowered CRP in morbidly obese, mainly female
Brazilian individuals [40]. Blood glucose AUC over 120 min in a small number of 15
healthy adults was significantly reduced when an oral glucose challenge was sup-
plemented with flaxseeds [148]. Indian Type-2 diabetics consuming 10 g of flaxseed
powder daily for a month had significantly reduced FBG and HbA1c, as well as a
significant decrease in TC, TGs, LDL-C, and apo B, and an increase in HDL-C [85];
and 40 g flaxseed powder daily for 12-weeks improved insulin resistance in obese
glucose intolerant people [120]. Flax gum (5 g daily for 3-months) significantly
lowered FBG, TC, and LDL-C in Indian type-2 diabetics [140], and flaxseed-lignan
for 12-weeks also modestly but significantly improved glycemic control of type-2
diabetic Chinese patients with mild hypercholesterolemia [98].
Current observational studies suggest that flaxseed intake is associated with
decreased risk of breast cancer and all-cause mortality, especially in postmenopausal
women [42, 80, 87]. Dietary flaxseed intake did not favorably alter breast cancer risk
through shifts in estrogen metabolism pathways in postmenopausal women [139],
1110 Linum usitatissimum L.

though significant reduction in serum concentrations of 17b-estradiol and estrone

and increased prolactin in postmenopausal women [63], and nonsignificant declines
in estradiol, estrone, and testosterone levels, especially in overweight/obese women
had been noted [138]. Dietary flaxseed in Swedish women significantly increased
endostatin levels in normal breast tissue with no alteration in VEGF or angiogenin
levels [1]. A six-months intake of flaxseed extract or flaxseed meal by menopausal
Brazilian women exerted no clinically discernible estrogenic effects on vaginal
epithelium or endometrium [23], or a significant difference in menopausal symptoms
after consuming flaxseed [35, 116, 132]; though significantly less severe hot flashes
in Canadian women after consuming muffins with 25 g of flaxseed daily for
16-weeks have been reported [78]. Flaxseed powder ingestion was consistently
associated with longer luteal phase lengths in three consecutive cycle and signifi-
cantly higher progesterone/estradiol ratios during this phase in women with normal
menstrual cycle [104]. Systematic reviews and meta-analyses of RCTs found that
flaxseed may have estrogenic effects and beneficial for hot flashes frequency and
intensity, but the evidence is inconclusive [33, 50]. In a pilot study and a multisite
RCT conducted by M. D. Anderson Cancer Center, Houston (USA), prostate cancer
patients maintained on flaxseed-supplemented diet presurgery and not fat-restricted
diet, had significantly lower proliferation rates [30, 31].
Flax oil (*14 g/day) in diet of older Canadian adults (>65 years) for 12-weeks
lowered IL-6 in men but not in women, with minimal effect on muscle mass and
strength during resistance training [25]. Oral flaxseed oil capsules 1 or 2 g/day
significantly improved ocular surface inflammation and symptoms of keratocon-
junctivitis sicca in Sjögren’s syndrome patients [105]. Topical application of flax-
seed oil for 4-weeks significantly improved symptoms and function in Iranian
patients with mild to moderate idiopathic carpal tunnel syndrome [58, 131]. Flax oil
significantly improved symptoms of ADHD in Indian children [66], and ingestion
of flax oil by German women for twelve-weeks significantly increased skin
hydration, and decreased transepidermal water loss [29].
Mechanism of Action: Both seeds and SDG [57], and isopropanol seed extract
show strong pancreatic a-amylase inhibitory activity [97], and ethanol extract has
shown strong pancreatic lipase inhibitory activity [89]. Increased bile acid synthesis
has been proposed as one of the major cholesterol-lowering mechanisms of flaxseed
[83].
Human A/Es, Allergy and Toxicity: Whole flaxseeds and flaxseed oil prepara-
tions cause most of the gastrointestinal effects, compared to milled flaxseed [6].
Seeds and linseed oil are photosensitizers,CXXXV and may cause allergic reactions,
sometimes severe enough, including anaphylaxis and rhabdomyolysis [4, 77, 106].
In a sample of 1,317 French patients attending an allergy department, 5.8% were
sensitive to flaxseeds and cross-reactive to peanut, soybean, rapeseed, lupine and
wheat [45]. Administration of 600 mg daily of SDG for 24-weeks was completely
safe to healthy community-dwelling adults aged 60–80 years [3].
Linum usitatissimum L. 1111

Animal Toxicity: Oral LD50 of linseed oil in rats is above the dose of 37 g/kg
[51].
Commentary: There are enough clinical observations in healthy, and dyslipidemic
and diabetic men and women of various ethnicity and nationalities, to draw the
conclusion that flaxseeds have a positive influence on both blood glucose and lipid
profiles, despite some negative results. Even, effects on postmenopausal hot flashes,
though inconclusive, show a positive trend. Severe allergic reactions in some
patients is a cause for concern, and the reasons behind them should be investigated.
Overall, flaxseeds intake seems to be beneficial for health, though more RCTs
would be helpful to further validate these results.

References
1. Åberg UW, Saarinen N, Abrahamsson A, et al. Tamoxifen and flaxseed
alter angiogenesis regulators in normal human breast tissue in vivo.
PLoS ONE. 2011;6:e25720.
2. Akhtar S, Ismail T, Riaz M. Flaxseed—a miraculous defense against some
critical maladies. Pak J Pharm Sci. 2013;26:199–208.
3. Alcorn J, Whiting S, Viveky N, et al. Protocol for a 24-week randomized
controlled study of once-daily oral dose of flax lignan to healthy older
adults. JMIR Res Protoc. 2017;6:e14.
4. Alvarez-Perea A, Alzate-Pérez D, Doleo Maldonado A, Baeza ML.
Anaphylaxis caused by flaxseed. J Investig Allergol Clin Immunol. 2013;
23:446–7.
5. Anonymous. The wealth of India, Industrial Products, Part IX, Publica-
tions and Information Directorate. CSIR; 1976.
6. Austria JA, Richard MN, Chahine MN, et al. Bioavailability of
alpha-linolenic acid in subjects after ingestion of three different forms of
flaxseed. J Am Coll Nutr. 2008;27:214–21.
7. Banković-Calić N, Ogbori MR, Nicman E. Effect of a modified low
protein and low fat diet on histologic changes and metabolism in kidneys
in an experimental model of polycystic kidney disease. Srp Arh Celok Lek.
2002;130:251–7 (Serbian).
8. Bassett CM, Rodriguez-Leyva D, Pierce GN. Experimental and clinical
research findings on the cardiovascular benefits of consuming flaxseed.
Appl Physiol Nutr Metab. 2009;34:965–74.
9. Bergman Jungeström M, Thompson LU, Dabrosin C. Flaxseed and its
lignans inhibit estradiol-induced growth, angiogenesis, and secretion of
vascular endothelial growth factor in human breast cancer xenografts
in vivo. Clin Cancer Res. 2007;13:1061–7.
10. Beroual K, Agabou A, Abdeldjelil MC, et al. Evaluation of crude flaxseed
(Linum usitatissimum L) oil in burn wound healing in New Zealand
rabbits. Afr J Tradit Complement Altern Med. 2017;14:280–6.
1112 Linum usitatissimum L.

11. Bhathena SJ, Ali AA, Haudenschild C, et al. Dietary flaxseed meal is more
protective than soy protein concentrate against hypertriglyceridemia and
steatosis of the liver in an animal model of obesity. J Am Coll Nutr.
2003;22:157–64.
12. Bhatia AL, Manda K, Patni S, Sharma AL. Prophylactic action of linseed
(Linum usitatissimum) oil against cyclophosphamide-induced oxidative
stress in mouse brain. J Med Food. 2006;9:261–4.
13. Bierenbaum ML, Reichstein R, Watkins TR. Reducing atherogenic risk in
hyperlipemic humans with flax seed supplementation: a preliminary report.
J Am Coll Nutr. 1993;12:501–4.
14. Billinsky J, Glew RA, Cornish SM, et al. No evidence of hypoglycemia or
hypotension in older adults during 6 months of flax lignan supplementa-
tion in a randomized controlled trial: a safety evaluation. Pharm Biol.
2013;51:778–82.
15. Bloedon LT, Balikai S, Chittams J, et al. Flaxseed and cardiovascular risk
factors: results from a double blind, randomized, controlled clinical trial.
J Am Coll Nutr. 2008;27:65–74.
16. Bommareddy A, Arasada BL, Mathees DP, Dwivedi C. Chemopreventive
effects of dietary flaxseed on colon tumor development. Nutr Cancer.
2006;54:216–22.
17. Bommareddy A, Zhang X, Schrader D, et al. Effects of dietary flaxseed on
intestinal tumorigenesis in Apc(Min) mouse. Nutr Cancer. 2009;61:276–83.
18. Bozan B, Temelli F. Chemical composition and oxidative stability of flax,
safflower and poppy seed and seed oils. Bioresour Technol. 2008;99:6354–9.
19. Caligiuri SP, Aukema HM, Ravandi A, et al. Flaxseed consumption
reduces blood pressure in patients with hypertension by altering circulating
oxylipins via an a-linolenic acid-induced inhibition of soluble epoxide
hydrolase. Hypertension. 2014;64:53–9.
20. Campbell SC, Bakhshalian N, Sadaat RL, et al. Flaxseed reverses
atherosclerotic lesion formation and lowers lipoprotein(a) in ovarian
hormone deficiency. Menopause. 2013;20:1176–83.
21. Cardozo LF, Vicente GC, Brant LH, et al. Prolonged flaxseed flour intake
decreased the thickness of the aorta and modulates some modifiable risk
factors related to cardiovascular disease in rats. Nutr Hosp. 2014;29:376–81.
22. Chen J, Stavro PM, Thompson LU. Dietary flaxseed inhibits human breast
cancer growth and metastasis and downregulates expression of insulin-like
growth factor and epidermal growth factor receptor. Nutr Cancer. 2002;43:
187–92.
23. Colli MC, Bracht A, Soares AA, et al. Evaluation of the efficacy of
flaxseed meal and flaxseed extract in reducing menopausal symptoms.
J Med Food. 2012;15:840–5.
24. Collins TF, Sprando RL, Black TN, et al. Effects of flaxseed and defatted
flaxseed meal on reproduction and development in rats. Food Chem
Toxicol. 2003;41:819–34.
Linum usitatissimum L. 1113

25. Cornish SM, Chilibeck PD. Alpha-linolenic acid supplementation and

resistance training in older adults. Appl Physiol Nutr Metab. 2009;34:49–59.
26. Cunnane SC, Ganguli S, Menard C, et al. High alpha-linolenic acid
flaxseed (Linum usitatissimum): some nutritional properties in humans.
Br J Nutr. 1993;69:443–53.
27. Dabrosin C, Chen J, Wang L, Thompson LU. Flaxseed inhibits metastasis
and decreases extracellular vascular endothelial growth factor in human
breast cancer xenografts. Cancer Lett. 2002;185:31–7.
28. de Souza Franco E, de Aquino CM, de Medeiros PL, et al. Effect of a
semisolid formulation of Linum usitatissimum L. (Linseed) oil on the repair
of skin wounds. Evid Based Complement Alternat Med. 2012;2012:270752.
29. De Spirt S, Stahl W, Tronnier H, et al. Intervention with flaxseed and
borage oil supplements modulates skin condition in women. Br J Nutr.
2009;101:440–5.
30. Demark-Wahnefried W, Polascik TJ, George SL, et al. Flaxseed supple-
mentation (not dietary fat restriction) reduces prostate cancer proliferation
rates in men presurgery. Cancer Epidemiol Biomarkers Prev. 2008;17:
3577–87.
31. Demark-Wahnefried W, Price DT, Polascik TJ, et al. Pilot study of dietary
fat restriction and flaxseed supplementation in men with prostate cancer
before surgery: exploring the effects on hormonal levels, prostate-specific
antigen, and histopathologic features. Urology. 2001;58:47–52.
32. Derbali A, Mnafgui K, Affes M, et al. Cardioprotective effect of linseed oil
against isoproterenol-induced myocardial infarction in Wistar rats: a
biochemical and electrocardiographic study. J Physiol Biochem. 2015;71:
281–8.
33. Dew TP, Williamson G. Controlled flax interventions for the improvement
of menopausal symptoms and postmenopausal bone health: a systematic
review. Menopause. 2013;20:1207–15.
34. Dodin S, Cunnane SC, Mâsse B, et al. Flaxseed on cardiovascular disease
markers in healthy menopausal women: a randomized, double-blind,
placebo-controlled trial. Nutrition. 2008;24:23–30.
35. Dodin S, Lemay A, Jacques H, et al. The effects of flaxseed dietary
supplement on lipid profile, bone mineral density, and symptoms in
menopausal women: a randomized, double-blind, wheat germ placebo-
controlled clinical trial. J Clin Endocrinol Metab. 2005;90:1390–7.
36. Dugani A, Auzzi A, Naas F, Megwez S. Effects of the oil and mucilage
from flaxseed (Linum usitatissimum) on gastric lesions induced by ethanol
in rats. Libyan J Med. 2008;3:166–9.
37. Dupasquier CM, Dibrov E, Kneesh AL, et al. Dietary flaxseed inhibits
atherosclerosis in the LDL receptor-deficient mouse in part through
antiproliferative and anti-inflammatory actions. Am J Physiol Heart Circ
Physiol. 2007;293:H2394–402.
1114 Linum usitatissimum L.

38. Dupasquier CM, Weber AM, Ander BP, et al. Effects of dietary flaxseed on
vascular contractile function and atherosclerosis during prolonged hyper-
cholesterolemia in rabbits. Am J Physiol Heart Circ Physiol. 2006;291:
H2987–96.
39. Endoh D, Okui T, Ozawa S, et al. Protective effect of a lignan-containing
flaxseed extract against CCl(4)-induced hepatic injury. J Vet Med Sci.
2002;64:761–5.
40. Faintuch J, Horie LM, Barbeiro HV, et al. Systemic inflammation in
morbidly obese subjects: response to oral supplementation with alpha-
linolenic acid. Obes Surg. 2007;17:341–7.
41. Felmlee MA, Woo G, Simko E, et al. Effects of the flaxseed lignans
secoisolariciresinol diglucoside and its aglycone on serum and hepatic
lipids in hyperlipidaemic rats. Br J Nutr. 2009;102:361–9.
42. Flower G, Fritz H, Balneaves LG, et al. Flax and breast cancer: a
systematic review. Integr Cancer Ther. 2014;13:181–92.
43. Fluck H, Kunz-Anderegg G. On the relationship between organ size and
active constituent content of drugs, studied on Stramonium leaves and
Linum seeds. Pharm Acta Helv. 1963;38:293–305 (German).
44. Francis AA, Deniset JF, Austria JA, et al. The effects of dietary flaxseed on
atherosclerotic plaque regression. Am J Physiol Heart Circ Physiol. 2013;
304:H1743–51.
45. Fremont S, Moneret-Vautrin DA, Franck P, et al. Prospective study of
sensitization and food allergy to flaxseed in 1,317 subjects. Eur Ann
Allergy Clin Immunol. 2010;42:103–11.
46. Fukumitsu S, Aida K, Shimizu H, Toyoda K. Flaxseed lignan lowers blood
cholesterol and decreases liver disease risk factors in moderately
hypercholesterolemic men. Nutr Res. 2010;30:441–6.
47. Fukumitsu S, Aida K, Ueno N, et al. Flaxseed lignan attenuates high-fat
diet-induced fat accumulation and induces adiponectin expression in mice.
Br J Nutr. 2008;100:669–76.
48. Gardiner P, Legedza A, Woods C, et al. Herb use among health care
professionals enrolled in an online curriculum on herbs and dietary
supplements. J Herb Pharmacother. 2006;6:51–64.
49. Gerstenmeyer E, Reimer S, Berghofer E, et al. Effect of thermal heating on
some lignans in flax seeds, sesame seeds and rye. Food Chem. 2013;138:
1847–55.
50. Ghazanfarpour M, Sadeghi R, Latifnejad Roudsari R, et al. Effects of
flaxseed and Hypericum perforatum on hot flash, vaginal atrophy and
estrogen-dependent cancers in menopausal women: a systematic review
and meta-analysis. Avicenna J Phytomed. 2016;6:273–83.
51. Gorriti A, Arroyo J, Quispe F, et al. Oral toxicity at 60-days of sacha inchi
oil (Plukenetia volubilis L.) and linseed (Linum usitatissimum L.), and
determination of lethal dose 50 in rodents. Rev Peru Med Exp Salud
Publica. 2010;27:352–60 (Article in Spanish).
Linum usitatissimum L. 1115

52. Haliga R, Mocanu V, Oboroceanu T, et al. The effects of dietary flaxseed

supplementation on lipid metabolism in streptozotocin-induced diabetic
hamsters. Rev Med Chir Soc Med Nat Iasi. 2007;111:472–6.
53. Haliga R, Mocanu V, Păduraru I, et al. Effects of dietary flaxseed
supplementation on renal oxidative stress in experimental diabetes. Rev
Med Chir Soc Med Nat Iasi. 2009;113:1200–4.
54. Hallund J, Tetens I, Bügel S, et al. The effect of a lignan complex isolated
from flaxseed on inflammation markers in healthy postmenopausal women.
Nutr Metab Cardiovasc Dis. 2008;18:497–502.
55. Hallund J, Ravn-Haren G, Bügel S, Tholstrup T, Tetens I. A lignan
complex isolated from flaxseed does not affect plasma lipid concentrations
or antioxidant capacity in healthy postmenopausal women. J Nutr. 2006;
136:112–6.
56. Hallund J, Tetens I, Bügel S, et al. Daily consumption for six weeks of a
lignan complex isolated from flaxseed does not affect endothelial function
in healthy postmenopausal women. J Nutr. 2006;136:2314–8.
57. Hano C, Renouard S, Molinié R, et al. Flaxseed (Linum usitatissimum L.)
extract as well as (+)-secoisolariciresinol diglucoside and its mammalian
derivatives are potent inhibitors of a-amylase activity. Bioorg Med Chem
Lett. 2013;23:3007–12.
58. Hashempur MH, Homayouni K, Ashraf A, et al. Effect of Linum
usitatissimum L. (linseed) oil on mild and moderate carpal tunnel syn-
drome: a randomized, double-blind, placebo-controlled clinical trial. Daru.
2014;22:43.
59. Hasler CM, Kundrat S, Wool D. Functional foods and cardiovascular
disease. Curr Atheroscler Rep. 2000;2:467–75.
60. Hemmings SJ, Song X. The effects of dietary flaxseed on the Fischer 344
rat. III. Protection against CCl(4)-induced liver injury. Cell Biochem
Funct. 2005;23:389–98.
61. Herchi W, Harrabi S, Sebei K, et al. Phytosterols accumulation in the seeds
of Linum usitatissimum L. Plant Physiol Biochem. 2009;47:880–5.
62. Herchi W, Arráez-Román D, Trabelsi H, et al. Phenolic compounds in
flaxseed: a review of their properties and analytical methods. An overview
of the last decade. J Oleo Sci. 2014;63:7–14.
63. Hutchins AM, Martini MC, Olson BA, et al. Flaxseed consumption
influences endogenous hormone concentrations in postmenopausal women.
Nutr Cancer. 2001;39:58–65.
64. Ingram AJ, Parbtani A, Clark WF, et al. Effects of flaxseed and flax oil
diets in a rat-5/6 renal ablation model. Am J Kidney Dis. 1995;25:320–9.
65. Jenkins DJ, Kendall CW, Vidgen E, et al. Health aspects of partially
defatted flaxseed, including effects on serum lipids, oxidative measures,
and ex vivo androgen and progestin activity: a controlled crossover trial.
Am J Clin Nutr. 1999;69:395–402.
66. Joshi K, Lad S, Kale M, et al. Supplementation with flax oil and vitamin C
improves the outcome of Attention Deficit Hyperactivity Disorder
(ADHD). Prostaglandins Leukot Essent Fatty Acids. 2006;74:17–21.
1116 Linum usitatissimum L.

67. Kaithwas G, Majumdar DK. Effect of L. usitatissimum (flaxseed/linseed)

fixed oil against distinct phases of inflammation. ISRN Inflamm.
2013;2013:735158.
68. Kaithwas G, Majumdar DK. Evaluation of antiulcer and antisecretory
potential of Linum usitatissimum fixed oil and possible mechanism of
action. Inflammopharmacology. 2010;18:137–45.
69. Kaithwas G, Majumdar DK. Therapeutic effect of Linum usitatissimum
(flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino
rats. Inflammopharmacology. 2010;18:127–36.
70. Kaithwas G, Mukherjee A, Chaurasia AK, Majumdar DK. Anti-inflam-
matory, analgesic and antipyretic activities of Linum usitatissimum L.
(flaxseed/linseed) fixed oil. Indian J Exp Biol. 2011;49:932–8.
71. Kaur N, Kishore L, Singh R. Therapeutic effect of Linum usitatissimum L.
in STZ-nicotinamide induced diabetic nephropathy via inhibition of AGE’s
and oxidative stress. J Food Sci Technol. 2017;54:408–21.
72. Khan G, Penttinen P, Cabanes A, et al. Maternal flaxseed diet during
pregnancy or lactation increases female rat offspring’s susceptibility to
carcinogen-induced mammary tumorigenesis. Reprod Toxicol. 2007;23:
397–406.
73. Kristensen M, Jensen MG, Aarestrup J, et al. Flaxseed dietary fibers lower
cholesterol and increase fecal fat excretion, but magnitude of effect
depends on food type. Nutr Metab (Lond). 2012;9:8.
74. Kuijsten A, Arts IC. van’t Veer P, Hollman PC. The relative bioavailability
of enterolignans in humans is enhanced by milling and crushing of
flaxseed. J Nutr. 2005;135:2812–6.
75. Lamblin F, Hano C, Fliniaux O, et al. Interest of lignans in prevention and
treatment of cancers. Med Sci (Paris). 2008;24:511–9 (Review, French).
76. Lemay A, Dodin S, Kadri N, et al. Flaxseed dietary supplement versus
hormone replacement therapy in hypercholesterolemic menopausal women.
Obstet Gynecol. 2002;100:495–504.
77. León F, Rodríguez M, Cuevas M. Anaphylaxis to Linum. Allergol
Immunopathol (Madr). 2003;31:47–9.
78. Lewis JE, Nickell LA, Thompson LU, et al. A randomized controlled trial
of the effect of dietary soy and flaxseed muffins on quality of life and hot
flashes during menopause. Menopause. 2006;13:631–42.
79. Lin X, Gingrich JR, Bao W, et al. Effect of flaxseed supplementation on
prostatic carcinoma in transgenic mice. Urology. 2002;60:919–24.
80. Lowcock EC, Cotterchio M, Boucher BA. Consumption of flaxseed, a rich
source of lignans, is associated with reduced breast cancer risk. Cancer
Causes Control. 2013;24:813–6.
81. Lucas EA, Lightfoot SA, Hammond LJ, et al. Flaxseed reduces plasma
cholesterol and atherosclerotic lesion formation in ovariectomized Golden
Syrian hamsters. Atherosclerosis. 2004;173:223–9.
Linum usitatissimum L. 1117

82. Lucas EA, Wild RD, Hammond LJ, et al. Flaxseed improves lipid profile
without altering biomarkers of bone metabolism in postmenopausal
women. J Clin Endocrinol Metab. 2002;87:1527–32.
83. Lucas EA, Mahajan SS, Soung do Y, et al. Flaxseed but not flaxseed oil
prevented the rise in serum cholesterol due to ovariectomy in the Golden
Syrian hamsters. J Med Food. 2011;14:261–7.
84. Mandaşescu S, Mocanu V, Dăscaliţa AM, et al. Flaxseed supplementation
in hyperlipidemic patients. Rev Med Chir Soc Med Nat Iasi. 2005;109:
502–6.
85. Mani UV, Mani I, Biswas M, Kumar SN. An open-label study on the effect
of flaxseed powder (Linum usitatissimum) supplementation in the manage-
ment of diabetes mellitus. J Diet Suppl. 2011;8:257–65.
86. Mason JK, Chen J, Thompson LU. Flaxseed oil-trastuzumab interaction in
breast cancer. Food Chem Toxicol. 2010;48:2223–6.
87. Mason JK, Thompson LU. Flaxseed and its lignan and oil components: can
they play a role in reducing the risk of and improving the treatment of
breast cancer? Appl Physiol Nutr Metab. 2014;39:663–78.
88. Matsumoto T, Shishido A, Morita H, et al. Cyclolinopeptides F-I, cyclic
peptides from linseed. Phytochemistry. 2001;57:251–60.
89. Möller NP, Roos N, Schrezenmeir J. Lipase inhibitory activity in alcohol
extracts of worldwide occurring plants and propolis. Phytother Res.
2009;23:585–6.
90. Naran R, Chen G, Carpita NC. Novel rhamnogalacturonan I and arabinoxy-
lan polysaccharides of flaxseed mucilage. Plant Physiol. 2008;148:132–41.
91. Newairy AS, Abdou HM. Protective role of flax lignans against lead
acetate induced oxidative damage and hyperlipidemia in rats. Food Chem
Toxicol. 2009;47:813–8.
92. Nounou HA, Deif MM, Shalaby MA. Effect of flaxseed supplementation
and exercise training on lipid profile, oxidative stress and inflammation in
rats with myocardial ischemia. Lipids Health Dis. 2012;11:129.
93. Noweir MH, El-Sadik YM, El-Dakhakhny AA, Osman HA. Dust exposure
in manual flax processing in Egypt. Br J Ind Med. 1975;32:147–54.
94. Ogborn MR, Nitschmann E, Bankovic-Calic N, et al. Effects of flaxseed
derivatives in experimental polycystic kidney disease vary with animal
gender. Lipids. 2006;41:1141–9.
95. Ogborn MR, Nitschmann E, Weiler H, et al. Flaxseed ameliorates
interstitial nephritis in rat polycystic kidney disease. Kidney Int. 1999;55:
417–23.
96. Orcheson LJ, Rickard SE, Seidl MM, Thompson LU. Flaxseed and its
mammalian lignan precursor cause a lengthening or cessation of estrous
cycling in rats. Cancer Lett. 1998;125:69–76.
97. P S, Zinjarde SS, Bhargava SY, Kumar AR. Potent a-amylase inhibitory
activity of Indian Ayurvedic medicinal plants. BMC Complement Altern
Med. 2011;11:5.
1118 Linum usitatissimum L.

98. Pan A, Sun J, Chen Y, et al. Effects of a flaxseed-derived lignan supplement

in type 2 diabetic patients: a randomized, double-blind, crossover trial.
PLoS ONE. 2007;2:e1148.
99. Park JB, Velasquez MT. Potential effects of lignan-enriched flaxseed
powder on body weight, visceral fat, lipid profile, and blood pressure in
rats. Fitoterapia. 2012;83:941–6.
100. Patade A, Devareddy L, Lucas EA, et al. Flaxseed reduces total and LDL
cholesterol concentrations in Native American postmenopausal women.
J Womens Health (Larchmt). 2008;17:355–66.
101. Patenaude A, Rodriguez-Leyva D, Edel AL, et al. Bioavailability of
alpha-linolenic acid from flaxseed diets as a function of the age of the
subject. Eur J Clin Nutr. 2009;63:1123–9.
102. Pellizzon MA, Billheimer JT, Bloedon LT, et al. Flaxseed reduces plasma
cholesterol levels in hypercholesterolemic mouse models. J Am Coll Nutr.
2007;26:66–75.
103. Peterson J, Dwyer J, Adlercreutz H, et al. Dietary lignans: physiology and
potential for cardiovascular disease risk reduction. Nutr Rev. 2010;68:
571–603.
104. Phipps WR, Martini MC, Lampe JW, et al. Effect of flaxseed ingestion on
the menstrual cycle. J Clin Endocrinol Metab. 1993;77:1215–9.
105. Pinheiro MN Jr, dos Santos PM, dos Santos RC, et al. Oral flaxseed oil
(Linum usitatissimum) in the treatment for dry-eye Sjögren’s syndrome
patients. Arq Bras Oftalmol. 2007;70:649–55 (Portuguese).
106. Prasad A, Kumar R, Ramanan H, et al. A case of flaxseed induced
rhabdomyolysis. J Clin Diagn Res. 2012;6:1770–1.
107. Prasad K, Mantha SV, Muir AD, Westcott ND. Reduction of hypercholes-
terolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic
acid. Atherosclerosis. 1998;136:367–75.
108. Prasad K. A study on regression of hypercholesterolemic atherosclerosis in
rabbits by flax lignan complex. J Cardiovasc Pharmacol Ther. 2007;12:
304–13.
109. Prasad K. Dietary flaxseed in prevention of hypercholesterolemic atheroscle-
rosis. Atherosclerosis. 1997;132:69–76.
110. Prasad K. Flax lignan complex slows down the progression of atherosclerosis
in hyperlipidemic rabbits. J Cardiovasc Pharmacol Ther. 2009;14:38–48.
111. Prasad K. Flaxseed and cardiovascular health. J Cardiovasc Pharmacol.
2009;54:369–77.
112. Prasad K. Hypocholesterolemic and antiatherosclerotic effect of flax lignan
complex isolated from flaxseed. Atherosclerosis. 2005;179:269–75.
113. Prasad K. Regression of hypercholesterolemic atherosclerosis in rabbits by
secoisolariciresinol diglucoside isolated from flaxseed. Atherosclerosis.
2008;197:34–42.
114. Prasad K. Secoisolariciresinol diglucoside from flaxseed delays the devel-
opment of type 2 diabetes in Zucker rat. J Lab Clin Med. 2001;138:32–9.
Linum usitatissimum L. 1119

115. Prim CR, Baroncini LA, Précoma LB, et al. Effects of linseed consumption
for a short period of time on lipid profile and atherosclerotic lesions in
rabbits fed a hypercholesterolaemic diet. Br J Nutr. 2012;107:660–4.
116. Pruthi S, Qin R, Terstreip SA, et al. A phase III, randomized, placebo-
controlled, double-blind trial of flaxseed for the treatment of hot flashes:
North Central Cancer Treatment Group N08C7. Menopause. 2012;19:
48–53.
117. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J
Gastroenterol. 2010;16:4504–14.
118. Rajesha J, Murthy KN, Kumar MK, et al. Antioxidant potentials of
flaxseed by in vivo model. J Agric Food Chem. 2006;54:3794–9.
119. Renu N, Kaithwas G, Ramteke PW, Saraf SA. Effect of Linum usitatis-
simum (linseed/flaxseed) fixed oil on experimental esophagitis in albino
rats. Acta Gastroenterol Belg. 2012;75:331–5.
120. Rhee Y, Brunt A. Flaxseed supplementation improved insulin resistance in
obese glucose intolerant people: a randomized crossover design. Nutr J.
2011;10:44.
121. Rickard SE, Yuan YV, Chen J, Thompson LU. Dose effects of flaxseed
and its lignan on N-methyl-N-nitrosourea-induced mammary tumorigen-
esis in rats. Nutr Cancer. 1999;35:50–7.
122. Rickard SE, Yuan YV, Thompson LU. Plasma insulin-like growth factor I
levels in rats are reduced by dietary supplementation of flaxseed or its
lignan secoisolariciresinol diglycoside. Cancer Lett. 2000;161:47–55.
123. Rodriguez-Leyva D, Dupasquier CM, McCullough R, Pierce GN. The
cardiovascular effects of flaxseed and its omega-3 fatty acid, alpha-
linolenic acid. Can J Cardiol. 2010;26:489–96.
124. Sacco SM, Jiang JM, Reza-López S, et al. Flaxseed combined with
low-dose estrogen therapy preserves bone tissue in ovariectomized rats.
Menopause. 2009;16:545–54.
125. Sacco SM, Jiang JM, Thompson LU, Ward WE. Flaxseed does not
enhance the estrogenic effect of low-dose estrogen therapy on markers of
uterine health in ovariectomized rats. J Med Food. 2012;15:846–50.
126. Saggar JK, Chen J, Corey P, Thompson LU. Dietary flaxseed lignan or oil
combined with tamoxifen treatment affects MCF-7 tumor growth through
estrogen receptor- and growth factor-signaling pathways. Mol Nutr Food
Res. 2010;54:415–25.
127. Sankaran D, Bankovic-Calic N, Peng CY, et al. Dietary flax oil during
pregnancy and lactation retards disease progression in rat offspring with
inherited kidney disease. Pediatr Res. 2006;60:729–33.
128. Sankaran D, Bankovic-Calic N, Cahill L, et al. Late dietary intervention
limits benefits of soy protein or flax oil in experimental polycystic kidney
disease. Nephron Exp Nephrol. 2007;106:e122–8.
129. Saxena S, Katare C. Evaluation of flaxseed formulation as a potential
therapeutic agent in mitigation of dyslipidemia. Biomed J. 2014;37:386–90.
1120 Linum usitatissimum L.

130. Schmidt TJ, Klaes M, Sendker J. Lignans in seeds of Linum species.

Phytochemistry. 2012;82:89–99.
131. Setayesh M, Sadeghifar AR, Nakhaee N, Kamalinejad M, Rezaeizadeh H.
A topical gel from flax seed oil compared with hand splint in carpal tunnel
syndrome: a randomized clinical trial. J Evid Based Complementary Altern
Med. 2017;3:462–7.
132. Simbalista RL, Sauerbronn AV, Aldrighi JM, Arêas JA. Consumption of a
flaxseed-rich food is not more effective than a placebo in alleviating the
climacteric symptoms of postmenopausal women. J Nutr. 2010;140:293–7.
133. Singh S, Nair V, Jain S, Gupta YK. Evaluation of anti-inflammatory
activity of plant lipids containing alpha-linolenic acid. Indian J Exp Biol.
2008;46:453–6.
134. Singh S, Nair V, Gupta YK. Linseed oil: an investigation of its antiarthritic
activity in experimental models. Phytother Res. 2012;26:246–52.
135. Spence JD, Thornton T, Muir AD, Westcott ND. The effect of flaxseed
cultivars with differing content of alpha-linolenic acid and lignans on
responses to mental stress. J Am Coll Nutr. 2003;22:494–501.
136. Sprando RL, Collins TF, Black TN, et al. The effect of maternal exposure
to flaxseed on spermatogenesis in F(1) generation rats. Food Chem
Toxicol. 2000;38:325–34.
137. Stuglin C, Prasad K. Effect of flaxseed consumption on blood pressure,
serum lipids, hemopoietic system and liver and kidney enzymes in healthy
humans. J Cardiovasc Pharmacol Ther. 2005;10:23–7.
138. Sturgeon SR, Heersink JL, Volpe SL, et al. Effect of dietary flaxseed on
serum levels of estrogens and androgens in postmenopausal women. Nutr
Cancer. 2008;60:612–8.
139. Sturgeon SR, Volpe SL, Puleo E, et al. Effect of flaxseed consumption on
urinary levels of estrogen metabolites in postmenopausal women. Nutr
Cancer. 2010;62:175–80.
140. Thakur G, Mitra A, Pal K, Rousseau D. Effect of flaxseed gum on
reduction of blood glucose and cholesterol in type 2 diabetic patients. Int J
Food Sci Nutr. 2009;60 Suppl 6:126–36.
141. Tham DM, Gardner CD, Haskell WL. Clinical review 97: potential health
benefits of dietary phytoestrogens: a review of the clinical, epidemiological,
and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223–35.
142. Tomaz Pacheco J, Beltrame Daleprame J, Teles Boaventura G. Impact of
dietary flaxseed (Linum usitatissimum) supplementation on biochemical
profile in healthy rats. Nutr Hosp. 2011;26:798–802.
143. Tou JC, Chen J, Thompson LU. Dose, timing, and duration of flaxseed
exposure affect reproductive indices and sex hormone levels in rats.
J Toxicol Environ Health A. 1999;56:555–70.
144. Tou JC, Chen J, Thompson LU. Flaxseed and its lignan precursor,
secoisolariciresinol diglycoside, affect pregnancy outcome and reproduc-
tive development in rats. J Nutr. 1998;128:1861–8.
Linum usitatissimum L. 1121

145. van Kranen HJ, Mortensen A, Sørensen IK, et al. Lignan precursors from
flaxseed or rye bran do not protect against the development of intestinal
neoplasia in ApcMin mice. Nutr Cancer. 2003;45:203–10.
146. Velasquez MT, Bhathena SJ, Ranich T, et al. Dietary flaxseed meal
reduces proteinuria and ameliorates nephropathy in an animal model of
type II diabetes mellitus. Kidney Int. 2003;64:2100–7.
147. Velasquez MT, Bhathena SJ. Dietary phytoestrogens: a possible role in
renal disease protection. Am J Kidney Dis. 2001;37:1056–68.
148. Vuksan V, Choleva L, Jovanovski E, et al. Comparison of flax (Linum
usitatissimum) and Salba-chia (Salvia hispanica L.) seeds on postprandial
glycemia and satiety in healthy individuals: a randomized, controlled,
crossover study. Eur J Clin Nutr. 2017;71:234–8.
149. Wang H, Wang J, Qiu C, et al. Comparison of phytochemical profiles and
health benefits in fiber and oil flaxseeds (Linum usitatissimum L.). Food
Chem. 2017;214:227–33.
150. Ward WE, Chen J, Thompson LU. Exposure to flaxseed or its purified
lignan during suckling only or continuously does not alter reproductive
indices in male and female offspring. J Toxicol Environ Health A. 2001;
64:567–77.
151. Wu H, Pan A, Yu Z, et al. Lifestyle counseling and supplementation with
flaxseed or walnuts influence the management of metabolic syndrome.
J Nutr. 2010;140:1937–42.
152. Xu J, Zhou X, Chen C, et al. Laxative effects of partially defatted flaxseed
meal on normal and experimental constipated mice. BMC Complement
Altern Med. 2012;12:14.
153. Yan L, Yee JA, Li D, et al. Dietary flaxseed supplementation and
experimental metastasis of melanoma cells in mice. Cancer Lett. 1998;
124:181–6.
154. Zhang W, Wang X, Liu Y, et al. Dietary flaxseed lignan extract lowers
plasma cholesterol and glucose concentrations in hypercholesterolaemic
subjects. Br J Nutr. 2008;99:1301–9.
Lupinus albus L.
(Fabaceae/Leguminosae)

(Syn.: L. termis Forssk.)

Abstract
An annual crop which is widely cultivated in the countries of the Mediterranean
region, Balkans and Turkey, and Europe for its edible seeds, and has been
consumed in western Europe for many years. In central Italy’s regions of
Abruzzo, Latium and Marche, older people use the plant as antiparasitic, repellent
and to treat calluses. In Jordan, a significant number of diabetic patients use seeds
as adjunctive therapy with the knowledge of their physicians. In Unani medicine,
seeds are regarded detergent, anti-inflammatory, diuretic, emmenagogue, and
anthelmintic; externally applied to resolve inflammations. Application of a paste of
seeds thins hairs, and washing hair with the decoction for five days makes hair
golden in color. Presence of quinolizidine alkaloids in seeds varies with regions
where it is grown. Some regions tend to have a high (Azores) or low (Egypt, Near
East, Maghreb) total alkaloid content. Lupine alkaloids include (+)-lupanine, (−)-
multiflorine, (+)-angustifoline, (+)-13-hydroxylupanine, (+)-lupanine N-oxide
and (−)-Δ5-dehydromultiflorine. Whole seeds extract increased tolerance to an oral
glucose bolus challenge but not to intraperitoneally injected glucose. Aqueous
suspension of the herb to diabetic rats for 4-weeks also significantly reduced levels
of glucose, urea, creatinine and bilirubin. Liver CYP450s and their associated
enzymes, involved in the activation of polycyclic aromatic hydrocarbons and
nitrosamines, were reduced by the herb, that would offer protection against the
deleterious effects of these carcinogens in the liver. A 2-weeks treatment with
lupine protein significantly reduced TC, VLDL and LDL-C in hypercholes-
terolemic rats, and increased LDL-uptake in human hepatoma cell line (HepG2)
by 53%.

Keywords


Aci bakla Altramuz


Bai yu shan dou Baqla-e-misri Hvid lupin






Tremoceiro Turmus Valkolupiini White lupine Wolfsbohne

© Springer Nature Switzerland AG 2020 1123

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_120
1124 Lupinus albus L.

Vernaculars: Urd.: Baqla-e-misri, Turmus; Hin.: Turmus; Ben.: Turmuz; Ara.:

Baqla-e-misri, Bâqilâ shâmî, Turmus; Chi.: 白羽扇豆, Bai yu shan dou; Cze.:
Lupina bílá, Vlčí bob bílý; Dan.: Hvid bitterlupin, Hvid lupin; Dut.: Bittere lupine,
Witte lupine; Eng.: Broadleaf lupin, Egyptian lupine, White lupine; Fin.:
Valkolupiini; Fre.: Lupin blanc, Lupin d’Egypte, Lupin termis; Ger.: Ägyptische
lupine, Weiße bitterlupine, Weiße lupine, Weiße wolfsbohne, Wolfsbohne; Hun.:
Fehérvirágú csillagfürt; Ita.: Lupino bianco, Lupino egiziano; Jap.: Shiro bana
ruupin; Kor.: Paek saek ru p’in; Nor.: Hvitlupid; Per.: Tira misha; Pol.: Lubin
bialy; Por.: Tremoceiro, Tremoceiro-branco, Tremoço, Tremoço-branco; Rus.:
Ljupin belyj; Spa.: Altramuz, Altramuz blanco, Chochos, Lupino blanco; Swe.:
Vitlupin; Tur.: Aci bakla, Ak aci bakla, Misir baklasi, Termiye.
Description: An annual crop which is widely cultivated in the countries of the
Mediterranean region, Balkans and Turkey, and Europe for its edible seeds, and has
been consumed in western Europe for many years [22, 25]. Seeds are thick, white
outside and yellow internally, globular and hard, with a depression at the center of
both surfaces, taste bitter. It is known as sweet lupin and has a high potential for
protein nutrition as lupin protein is highly bioavailable [7, 15] (Figs. 1 and 2).
Actions and Uses: In central Italy’s regions of Abruzzo, Latium and Marche, older
people use the plant as antiparasitic, repellent and to treat calluses [8, 9]. In Jordan,

Fig. 1 Lupinus albus, Plant, Ghislain, WikimediaCommons; Share Alike 3.0 Unported CC BY-
SA 3.0, https://commons.wikimedia.org/wiki/File:Lupinus_albus_1.jpg; https://creativecommons.
org/licenses/by-sa/3.0/deed.en
Lupinus albus L. 1125

Fig. 2 Lupinus albus, Beans, Cooked and Pickled in Brine, Calapito, WikimediaCommons,
https://commons.wikimedia.org/wiki/File:Lupinus_albus.JPG

a significant number of diabetic patients use seeds as adjunctive therapy with the
knowledge of their physicians [20]. In Unani medicine, seeds (temperament, hot 1°
and dry 2°) are regarded detergent, anti-inflammatory, diuretic, emmenagogue, and
anthelmintic; externally applied to resolve inflammations.LXXVII Soaking seeds in
water and washing the body of a person with itching relieves it. Decoction with rue
and pepper is given in fever, loss of appetite, nausea and in leprosy. Boiled in
vinegar, seeds are applied to disperse swollen, scrofulous or parotid glands.LXXXI
Application of a paste of seeds thins hairs, and washing hair with the decoction for
five days makes hair golden in color.L NadkarniCV also described seeds as
anti-inflammatory, anthelmintic, diuretic, emmenagogue, pectoral, and tonic; the
decoction relieves inflammation of spleen and is externally applied as poultice for
inflammation.
Phytoconstituents: Presence of quinolizidine alkaloids in seeds varies with
regions where it is grown. Some regions tend to have a high (Azores) or low
(Egypt, Near East, Maghreb) total alkaloid content. Lupine alkaloids include (+)-
lupanine, (−)-multiflorine, (+)-angustifoline, (+)-13-hydroxylupanine, (+)-lupanine
N-oxide and (−)-Δ5-dehydromultiflorine [17]. Lupanine is the most abundant
quinolizidine alkaloid, followed by albine and 13a-hydroxylupanine [3]. Some of
these alkaloids possess significant activity against C. albicans, A. flavus and
B. subtilis [6]. Isoflavone contents are higher in leaves than in stems, and highest
before flowering which decline during maturity [4].
Pharmacology: Whole seeds extract increased tolerance to an oral glucose bolus
challenge but not to intraperitoneally injected glucose [12]. Aqueous suspension of
the herb to alloxan-diabetic rats for 4-weeks also significantly reduced levels of
glucose, urea, creatinine and bilirubin [13]. Liver CYP450s and their associated
enzymes (NADPH-cytochrome C reductase, aryl hydrocarbon (B(a)P) hydroxylase,
1126 Lupinus albus L.

N-nitroso-dimethylamine N-demethylase I), involved in the activation of polycyclic

aromatic hydrocarbons and nitrosamines, were reduced by the herb, that would
offer protection against the deleterious effects of these carcinogens in the liver [21].
Lupine seed extract and its fractions produced immunotropic activity and sup-
pressed graft versus host reaction when recipients were treated with the extract [2].
A 2-weeks treatment with lupine protein significantly reduced TC, VLDL and
LDL-C in hypercholesterolemic rats and a minor protein component, conglutin
gamma increased LDL-uptake in human hepatoma cell line (HepG2) by 53% [22].
Lupin protein also lowered TGs in liver and plasma of rats [23]. It also showed
hypolipidemic effect in hypercholesterolemic rabbits and significantly reduced
progression of experimental focal carotids lesion [14]. Cows fed with whole lupins
produce milk with higher fat content [16], and seed-flour fed to rats increased their
growth rate without any adverse effects on fertility or lactation [1]. However,
addition of lupin protein into chicken diet caused growth depression and lowered
serum cholesterol and glucose [26].
Mechanism of Action: Triglyceride-lowering effect of lupin protein is partly
mediated through downregulation of hepatic gene expression of sterol regulatory
element-binding protein-1c [23].
Human A/Es, Allergy and Toxicity: Patients allergic to peanuts show cross
allergy to lupine, and several cases of allergic reactions in such patients have been
reported [5, 10, 11, 18]. An 8-year-old asthmatic child, allergic to peanuts, suffered an
asthma attack simply after inhaling lupine seeds which his brother was eating as
snack [19]. Another healthy 8-year-old boy, with no peanut allergy, developed
anaphylactic reaction after eating an industrially prepared waffle containing lupine
flour [27]. It is not easily digested and may produce gastrointestinal symptoms.LXXVII
Animal Toxicity: Ethanol seed extract that contained about 10% alkaloids was
nontoxic, and the LD50 in mice was more than 4,000 mg/kg, an indication that
despite the presence of alkaloids, presence of other constituents may modify the
toxicity of lupin extract [24].
Commentary: There are no formal clinical studies reported on this plant, except
informal use by diabetic patients.

References
1. Ballester DR, Brunser O, Saitúa MT, et al. Safety evaluation of sweet lupine
(Lupinus albus cv. Multolupa). II. Nine-month feeding and multigeneration
study in rats. Food Chem Toxicol. 1984;22:45–8.
2. Błaszczyk B, Stobiecki M, Kowalczyk-Bronisz SH, et al. Immunotropic
activity of lupin seeds extracts and fractions from Lupinus angustifolius and
Lupinus albus. Arch Immunol Ther Exp (Warsz). 1994;42:147–53.
Lupinus albus L. 1127

3. Boschin G, Annicchiarico P, Resta D, et al. Quinolizidine alkaloids in seeds of

lupin genotypes of different origins. J Agric Food Chem. 2008;56:3657–63.
4. D’Agostina A, Boschin G, Resta D, et al. Changes of isoflavones during the
growth cycle of Lupinus albus. J Agric Food Chem. 2008;56:4450–6.
5. Dooper MM, Holden L, Faeste CK, et al. Monoclonal antibodies against the
candidate lupin allergens alpha-conglutin and beta-conglutin. Int Arch
Allergy Immunol. 2007;143:49–58.
6. El-Shazly A, Ateya AM, Wink M. Quinolizidine alkaloid profiles of
Lupinus varius orientalis, L. albus albus, L. hartwegii, and L. densiflorus.
Z Naturforsch C. 2001;56:21–30.
7. Gross R, Morales E, Gross U, von Baer E. Lupine, a contribution to the
human food supply. 3. Nutritional physiological study with lupine (Lupinus
albus) flour. Z Ernahrungswiss. 1976;15:391–5 (German).
8. Guarrera PM. Traditional antihelmintic, antiparasitic and repellent uses of
plants in Central Italy. J Ethnopharmacol. 1999;68:183–92.
9. Guarrera PM. Traditional phytotherapy in Central Italy (Marche, Abruzzo,
and Latium). Fitoterapia. 2005;76:1–25.
10. Guillamón E, Rodríguez J, Burbano C, et al. Characterization of lupin major
allergens (Lupinus albus L.). Mol Nutr Food Res. 2010;54:1668–76.
11. Kanny G, Guérin L, Moneret-Vautrin DA. Risk of serious acute asthma due
to lupine flour associated with peanut allergy. Rev Med Interne. 2000;21:
191–4 (French).
12. Knecht KT, Nguyen H, Auker AD, Kinder DH. Effects of extracts of lupine
seed on blood glucose levels in glucose resistant mice: antihyperglycemic
effects of Lupinus albus (white lupine, Egypt) and Lupinus caudatus
(tailcup lupine, Mesa Verde National Park). J Herb Pharmacother. 2006;6:
89–104.
13. Mansour HA, Newairy AS, Yousef MI, Sheweita SA. Biochemical study on
the effects of some Egyptian herbs in alloxan-induced diabetic rats.
Toxicology. 2002;170:221–8.
14. Marchesi M, Parolini C, Diani E, et al. Hypolipidaemic and anti-
atherosclerotic effects of lupin proteins in a rabbit model. Br J Nutr.
2008;100:707–10.
15. Mariotti F, Pueyo ME, Tomé D, Mahé S. The bioavailability and
postprandial utilisation of sweet lupin (Lupinus albus)-flour protein is
similar to that of purified soyabean protein in human subjects: a study using
intrinsically 15N-labelled proteins. Br J Nutr. 2002;87:315–23.
16. May MG, Otterby DE, Linn JG, et al. Lupins (Lupinus albus) as a protein
supplement for lactating Holstein dairy cows. J Dairy Sci. 1993;76:2682–91.
17. Mohamed MH, Saito K, Murakhoshi I. A new lupine alkaloid (−)-Δ5-
dehydromultiflorine, from the seeds of Lupinus termis. J Nat Prod. 1990;53:
1578–80.
18. Moneret-Vautrin DA, Guérin L, Kanny G, et al. Cross-allergenicity of
peanut and lupine: the risk of lupine allergy in patients allergic to peanuts.
J Allergy Clin Immunol. 1999;104:883–8.
1128 Lupinus albus L.

19. Moreno-Ancillo A, Gil-Adrados AC, Domínguez-Noche C, Cosmes PM.

Lupine inhalation induced asthma in a child. Pediatr Allergy Immunol.
2005;16:542–4.
20. Otoom SA, Al-Safi SA, Kerem ZK, Alkofahi A. The use of medicinal herbs
by diabetic Jordanian patients. J Herb Pharmacother. 2006;6:31–41.
21. Sheweita SA, Newairy AA, Mansour HA, Yousef MI. Effect of some
hypoglycemic herbs on the activity of phase I and II drug-metabolizing
enzymes in alloxan-induced diabetic rats. Toxicology. 2002;174:131–9.
22. Sirtori CR, Lovati MR, Manzoni C, et al. Proteins of white lupin seed, a
naturally isoflavone-poor legume, reduce cholesterolemia in rats and
increase LDL receptor activity in HepG2 cells. J Nutr. 2004;134:18–23.
23. Spielmann J, Shukla A, Brandsch C, et al. Dietary lupin protein lowers
triglyceride concentrations in liver and plasma in rats by reducing hepatic
gene expression of sterol regulatory element-binding protein-1c. Ann Nutr
Metab. 2007;51:387–92.
24. Stobiecki M, Blaszczyk B, Kowalczyk-Bronisz SH, Gulewicz K. The
toxicity of seed extracts and their fractions from Lupinus angustifolius L.
and Lupinus albus L. J Appl Toxicol. 1993;13:347–52.
25. Tackholm V. Students flora of Egypt. 2nd ed. Cairo: Cairo University Press,
Academic Press; 1974. p. 224.
26. Viveros A, Centeno C, Arija I, Brenes A. Cholesterol-lowering effects of
dietary lupin (Lupinus albus var. multolupa) in chicken diets. Poult Sci.
2007;86:2631–8.
27. Wassenberg J, Hofer M. Lupine-induced anaphylaxis in a child without
known food allergy. Ann Allergy Asthma Immunol. 2007;98:589–90.
Malva sylvestris L.
(Malvaceae)

(Syns.: M. glabra Des.; M. mauritiana L.; M. sylvestris subsp. mauritiana (L.)

Thellung; M. sylvestris var. mauritiana (L.) Boiss)

Abstract
The plant is a native of Europe, North Africa and Asia, and wildly grows in the
Mediterranean region. It is called khubbazi because its fruits resemble the Arabic
bread (khubz). Greeks and Romans used it due to its mucilaginous and cooling
properties. It is also described as the Khitmi-i-kuchak or small Khitmi of
Persians. Pliny mentioned the seeds aphrodisiac. Due to its mucilaginous,
demulcent and cooling properties it is used in the treatment of coughs, and other
irritable conditions of the mucous membrane of pulmonary tract, the inflam-
mation of urinary bladder, and in hemorrhoids. It is still one of the two most
important plants used for medicinal purposes in northeastern Sicily, Italy, and
was cited with largest relative frequency and cultural importance as medicinal
plant in Sirjan of Kerman Province of Iran, in Kirklareli Province of Turkey, and
is one of the most commonly used plant to treat jaundice in Mashhad, and
topically as a remedy for dermal infected wounds by traditional healers of Iran. It
was also reported as one of the most frequently prescribed and self-medicated
plants in the Buenos Aires province in Argentina, used in popular Brazilian
cuisines, in salads, soups and teas, and in traditional medicine for the treatment
of gastrointestinal disorders, and inflammatory conditions. It is one of the wild
edible plants used in Spain, Portugal, and in the traditional Mediterranean diet
that contains high levels of K+ and zinc. Its various parts contain flavonoids,
phenol derivatives, terpenoids, fatty acids and sterols, particularly omega-3 and
omega-6, polysaccharides, mucilage and coumarins. Leaves are a rich source of
nutraceuticals such as antioxidants, unsaturated fatty acids, and minerals. Leaves
are reported to possess anti-inflammatory, anticomplementary, antioxidant,
anticancer and potent gastric antiulcer activities. Oral administration of ground
plant was cardioprotective against I/R oxidative stress and damage in rats.
Aqueous flower extract syrup was effective in adult functional constipation in a
four-weeks placebo-controlled study of Iranian patients.

© Springer Nature Switzerland AG 2020 1129

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_121
1130 Malva sylvestris L.

Keywords





Alboeza Algier-malve Blue mallow Crow’s bread Ebegümeci Gurchanti






Jin kui Khubbazi Rödmalva Vilayatiikangai

Vernaculars: Urd.: Gul-e-khair and Gul-e-khubbazi (flowers), Khubbazi,

Tukhm-e-khubbazi and Toodri (seeds); Hin.: Gurchanti, Socholi; San.: Vilayati-
ikangai; Mar.: Kubaajee; Ara.: Khubbazi; Chi.: 锦葵, Jin kui; Cze.: Sléz lesní;
Dan.: Almindelig katost; Dut.: Groot kaasjeskruid; Eng.: Blue mallow, Cheeses,
Common mallow, Crow’s bread, High cheeseweed, High mallow, Mallards, Tall
mallow; Fin.: Kiiltomalva, Metsämalva, Pikkukiiltomalva; Fre.: Grande mauve,
Mauve des bois, Mauve sauvage; Ger.: Algier-malve, Große käsepappel,
Roßpappel, Wilde malve; Hun.: Erdei mályva; Ita.: Malva selvatica, Nalba,
Riandell; Jap.: Usu-beni-aoi, Zeni-aoi; Nor.: Apotekerkattost; Per.: Nan-i-kulagh,
Panirak; Pol.: Ślaz dziki; Por.: Malva, Malva-das-boticas, Malva-mourisca,
Malva-selvagem; Rus.: Mal’va lesnaja, Prosvirnik lesnoj; Spa.: Alboeza, Malva
alta, Malva común, Malva hiedra; Swe.: Rödmalva; Tur.: Ebegümeci.
Description: The plant is a native of Europe, North Africa and Asia, and wildly
grows in the Mediterranean region [14]. It is called khubbazi because its fruits
resemble the Arabic bread (khubz).LIII The plant is described as “leaves roundish,
tasteless, a little hairy on the under surface; flowers small, reddish-purple; fruit
round and flat, depressed in the center, color white or brown. The plant is much
smaller than Khitmi.”XL Some authors have described Malva rotundifolia as
Khubbazi and M. sylvestris as Resha Khatmi in Unani medicine,CXXXXVII whereas
Khory and KatrakLXXXI grouped M. rotundifolia, M. sylvestris and M. vulgaris as
Khubbazi or common mallow (Figs. 1, 2, and 3).

Fig. 1 Malva sylvestris, Plant with Flowers, Alvesgaspar, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Mallow_January_2008-1.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Malva sylvestris L. 1131

Fig. 2 Malva sylvestris, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen in

naturgetreuen Abbildungen mit kurz erläuterndem Texte: Atlas zur Pharmacopoea germanica,
Volume 1 of 3 WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.
wikimedia.org/wiki/File:Malva_sylvestris_-_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-
222.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Malva sylvestris, Ripe Nutlets, Qniemiec, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Malva_sylvestris_seeds.jpg; https://creative-
commons.org/licenses/by-sa/3.0/deed.en
1132 Malva sylvestris L.

Actions and Uses: Greeks and Romans used it due to its mucilaginous and cooling
properties. It is also described as the Khitmi-i-kuchak or small Khitmi of Persians.
Pliny mentioned the seeds aphrodisiac.XL Due to its mucilaginous, demulcent and
cooling properties it is used in the treatment of coughs, and other irritable condi-
tions of the mucous membrane of pulmonary tract, the inflammation of urinary
bladder, and in hemorrhoids.LXXXI It is still one of the two most important plants
used for medicinal purposes in northeastern Sicily, Italy [35], and was cited with
largest relative frequency and cultural importance as medicinal plant in Sirjan of
Kerman Province of Iran [20], in Kirklareli Province of Turkey [22], and is one of
the most commonly used plants to treat jaundice in Mashhad [3], and topically as a
remedy for dermal infected wounds by traditional healers of Iran [27]. It was also
reported as one of the most frequently prescribed and self-medicated plants in the
Buenos Aires province in Argentina [9], used in popular Brazilian cuisines, in
salads, soups and teas [29], and in traditional medicine for the treatment of gas-
trointestinal disorders [8], and inflammatory conditions [21]. It is one of the wild
edible plants used in Spain, Portugal, and in the traditional Mediterranean diet
[4, 12, 19, 32] that contains high levels of K+ and zinc [32]. It is also traditionally
used in Tunisian cuisine, and as an antiulcer, laxative and antihemorrhoid drug [18].
Leaves of Malva sylvestris var. mauritiana collected from Muradiye region of
Manisa-Turkey, also contained high concentrations of Ca2+ and Mg2+ [17].
Phytoconstituents: Its various parts contain flavonoids [7], phenol derivatives,
terpenoids [10], fatty acids and sterols, particularly omega-3 and omega-6 [15],
polysaccharides [34], mucilage and coumarins [14]. Leaves are a rich source of
nutraceuticals such as antioxidants (phenols, flavonoids, carotenoids, and toco-
pherols), unsaturated fatty acids (e.g. a-linolenic acid), and minerals [4].
4-Hydroxybenzoic acid, 4-methoxybenzoic acid, 4-hydroxy-3-methoxybenzoic
acid, 4-hydroxycinnamic acid, ferulic acid, methyl 2-hydroxydihydrocinnamate,
scopoletin, N-trans-feruloyl tyramine, a sesquiterpene, (3R,7E)-3-hydroxy-5,7-
megastigmadien-9-one, and (10E,15Z)-9,12,13-trihydroxyoctadeca-10,15-dienoic
acid were isolated from aqueous extract [11]. Presence of scopoletin, quercetin and
malvidin 3-glucoside was confirmed in hydroalcohol leaf extract [29]. Six steroidal
lactones, a homomonoterpenic glucoside, and b-sitosterol-3-b-D-glucopyranoside
were isolated from ethanol extract of defatted fruits [25]. Kaempferol-3-O-
rutinoside was the main flavonol present in the flowers collected from Iberian
Peninsula of northeastern Portugal [5]. A phytoalexin, malvone A, was also isolated
from the plant [37]. A light-yellow oil (yield 0.039%) with a sweet odor was
obtained from dried flowers with 143 volatile constituents (89.86%) identified;
main compounds being hexadecanoic acid (10.1%), pentacosane (4.8%) and
6,10,14-trimethyl-2-pentadecanone (4.1%) [36].
Pharmacology: Leaves are reported to possess anti-inflammatory [14, 19], anti-
complementary, antioxidant, anticancer and potent gastric antiulcer activities [14].
Topical application of the hydroalcoholic extract reduced keratinocyte hyperpro-
liferation due to repeated TPA applications [30], and TPA-induced ear edema,
PMNL influx, myeloperoxydase activity and IL-1b levels; malvidin 3-glucoside
Malva sylvestris L. 1133

was identified as the major anti-inflammatory constituent of the extract [29].

Topical application of the aqueous [1], ethanol [27], and diethyl ether flower
extracts significantly enhanced wound healing [28], while the ethanol leaf extract in
an orabase failed to affect wound healing in the palatal mucosa of rats [21]. Oral
administration of ground plant was cardioprotective against I/R oxidative stress and
damage in rats [38]. Aqueous extract exhibited significant in vitro antioxidant and
radical scavenging activity [11], and aqueous decoction of dried leaves and flowers
protected against vanadium nephrotoxicity [23], and aqueous-ethanol leaf extract
protected against I/R nephrotic injury [26], and lithium carbonate-nephrotoxicity
[6], and damage to testes and heart, and reduced oxidative stress in rats [33].
Pretreatment of rats with hydroalcohol extract ameliorated cisplatin-induced tissue
damage and leukocytes infiltration in kidneys and liver, and reduced levels of
plasma creatinine, urea-nitrogen, AST, and ALT [24]. Aqueous extract was also
effective against experimental ulcerative colitis in rats [16], and reduced
loperamide-induced constipation by increasing gastrointestinal motility, and stim-
ulation of intestinal water secretion in rats [18]. Ethanol extract of inflorescence and
leaves moderately inhibited growth of H. pylori [8]. Methanol macerate of the
whole plant significantly prevented cognitive dysfunction due to repetitive mild
traumatic brain injury in rats [31].
Clinical Studies: Aqueous flower extract syrup was effective in adult functional
constipation in a four-weeks placebo-controlled study of Iranian patients [13].
Human A/Es, Allergy and Toxicity: A 36-year-old Turkish woman developed
nausea and headache after eating Ebegümeci (M. sylvestris) at dinner. Next day she
developed lethargy and was admitted to hospital in a coma, with fulminant hepatic
failure and renal failure that resulted in her death [2].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This important and commonly used plant lacks organized clinical
trials, especially the protective effects against various nephrotoxic challenges
observed in pharmacological studies.

References
1. Afshar M, Ravarian B, Zardast M, et al. Evaluation of cutaneous wound
healing activity of Malva sylvestris aqueous extract in BALB/c mice. Iran J
Basic Med Sci. 2015;18:616–22.
2. Aktaş B, Coban S, Başar O, et al. Fulminant liver failure and renal failure
related with Malva sylvestris. Turk J Gastroenterol. 2014;25:437.
3. Amiri MS, Joharchi MR, Taghavizadehyazdi ME. Ethnomedicinal plants
used to cure jaundice by traditional healers of Mashhad. Iran. Iran J Pharm
Res. 2014;13:157–62.
1134 Malva sylvestris L.

4. Barros L, Carvalho AM, Ferreira IC. Leaves, flowers, immature fruits and
leafy flowered stems of Malva sylvestris: a comparative study of the
nutraceutical potential and composition. Food Chem Toxicol. 2010;48:
1466–72.
5. Barros L, Dueñas M, Carvalho AM, Ferreira IC, Santos-Buelga C.
Characterization of phenolic compounds in flowers of wild medicinal
plants from Northeastern Portugal. Food Chem Toxicol. 2012;50:1576–82.
6. Ben Saad A, Rjeibi I, Brahmi D, et al. Malva sylvestris extract protects upon
lithium carbonate-induced kidney damages in male rat. Biomed Pharma-
cother. 2016;84:1099–107.
7. Billeter M, Meier B, Sticher O. 8-Hydroxyflavonoid glucuronides from
Malva sylvestris. Phytochemistry. 1991;30:987–90.
8. Cogo LL, Monteiro CL, Miguel MD, et al. Anti-Helicobacter pylori activity
of plant extracts traditionally used for the treatment of gastrointestinal
disorders. Braz J Microbiol. 2010;41:304–9.
9. Consolini AE, Ragone MI. Patterns of self-medication with medicinal plants
and related adverse events—a South American survey. Curr Drug Saf.
2010;5:333–41.
10. Cutillo F, D’Abrosca B, Dellagreca M, Fiorentino A, Zarrelli A. Terpenoids
and phenol derivatives from Malva sylvestris. Phytochemistry. 2006;67:
481–5.
11. DellaGreca M, Cutillo F, D’Abrosca B, et al. Antioxidant and radical
scavenging properties of Malva sylvestris. Nat Prod Commun. 2009;4:893–6.
12. El SN, Karakaya S. Radical scavenging and iron-chelating activities of some
greens used as traditional dishes in Mediterranean diet. Int J Food Sci Nutr.
2004;55:67–74.
13. Elsagh M, Fartookzadeh MR, Kamalinejad M, et al. Efficacy of the Malva
sylvestris L. flowers aqueous extract for functional constipation: a placebo-
controlled trial. Complement Ther Clin Pract. 2015;21:105–11.
14. Gasparetto JC, Martins CA, Hayashi SS, Otuky MF, Pontarolo R. Ethnob-
otanical and scientific aspects of Malva sylvestris L.: a millennial herbal
medicine. J Pharm Pharmacol. 2012;64:172–89.
15. Guil JL, Torija ME. Gime´nez JJ, Rodrı´guez I. Identification of fatty acids in
edible wild plants by gas chromatography. J Chromatogr A. 1996;719:229–35.
16. Hamedi A, Rezaei H, Azarpira N, Jafarpour M, Ahmadi F. Effects of Malva
sylvestris and its isolated polysaccharide on experimental ulcerative colitis
in rats. J Evid Based Complementary Altern Med. 2016;21:14–22.
17. Hiçsönmez U, Ereeş FS, Ozdemir C, Ozdemir A, Cam S. Determination of
major and minor elements in the Malva sylvestris L. from Turkey using
ICP-OES techniques. Biol Trace Elem Res. 2009;128:248–57.
18. Jabri MA, Wannes D, Hajji N, et al. Role of laxative and antioxidant
properties of Malva sylvestris leaves in constipation treatment. Biomed
Pharmacother. 2017;89:29–35.
Malva sylvestris L. 1135

19. Jeambey Z, Johns T, Talhouk S, Batal M. Perceived health and medicinal

properties of six species of wild edible plants in northeast Lebanon. Public
Health Nutr. 2009;12:1902–11.
20. Khajoei Nasab F, Khosravi AR. Ethnobotanical study of medicinal plants of
Sirjan in Kerman Province, Iran. J Ethnopharmacol. 2014;154:190–7.
21. Kovalik AC, Bisetto P, Pochapski MT, et al. Effects of an orabase
formulation with ethanolic extract of Malva sylvestris L. in oral wound
healing in rats. J Med Food. 2014;17:618–24.
22. Kültür S. Medicinal plants used in Kirklareli Province (Turkey).
J Ethnopharmacol. 2007;111:341–64.
23. Marouane W, Soussi A, Murat JC, Bezzine S, El Feki A. The protective
effect of Malva sylvestris on rat kidney damaged by vanadium. Lipids
Health Dis. 2011;10:65.
24. Mohamadi Yarijani Z, Godini A, Madani SH, Najafi H. Reduction of
cisplatin-induced renal and hepatic side effects in rat through antioxidative
and anti-inflammatory properties of Malva sylvestris L. extract. Biomed
Pharmacother. 2018;106:1767–74.
25. Mustafa A, Ali M. New steroidal lactones and homomonoterpenic glucoside
from fruits of Malva sylvestris L. Acta Pol Pharm. 2011;68:393–401.
26. Najafi H, Mohamadi Yarijani Z, Changizi-Ashtiyani S, et al. Protective
effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute
kidney and remote liver injury. PLoS ONE. 2017;12:270.
27. Nasiri E, Hosseinimehr SJ, Azadbakht M, et al. Effect of Malva sylvestris
cream on burn injury and wounds in rats. Avicenna J Phytomed. 2015;5:
341–54.
28. Pirbalouti AG, Azizi S, Koohpayeh A, Hamedi B. Wound healing activity
of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats.
Acta Pol Pharm. 2010;67:511–6.
29. Prudente AS, Loddi AM, Duarte MR, et al. Preclinical anti-inflammatory
aspects of a cuisine and medicinal millennial herb: Malva sylvestris L. Food
Chem Toxicol. 2013;58:324–31.
30. Prudente AS, Sponchiado G, Mendes DAGB, et al. Preclinical efficacy
assessment of Malva sylvestris on chronic skin inflammation. Biomed
Pharmacother. 2017;93:852–60.
31. Qin H, Qin J, Hu J, Huang H, Ma L. Malva sylvestris attenuates cognitive
deficits in a repetitive mild traumatic brain injury rat model by reducing
neuronal degeneration and astrocytosis in the hippocampus. Med Sci Monit.
2017;23:6099–106.
32. Romojaro A, Botella MÁ, Obón C, Pretel MT. Nutritional and antioxidant
properties of wild edible plants and their use as potential ingredients in the
modern diet. Int J Food Sci Nutr. 2013;64:944–52.
33. Saad AB, Rjeibi I, Alimi H, et al. Lithium induced, oxidative stress and
related damages in testes and heart in male rats: the protective effects of
Malva sylvestris extract. Biomed Pharmacother. 2017;86:127–35.
1136 Malva sylvestris L.

34. Samavati V, Manoochehrizade A. Polysaccharide extraction from Malva

sylvestris and its antioxidant activity. Int J Biol Macromol. 2013;60:427–36.
35. Tuttolomondo T, Licata M, Leto C, et al. Popular uses of wild plant species
for medicinal purposes in the Nebrodi Regional Park (North-Eastern Sicily,
Italy). J Ethnopharmacol. 2014;157:21–37.
36. Usami A, Kashima Y, Marumoto S, Miyazawa M. Characterization of
aroma-active compounds in dry flower of Malva sylvestris L. by GC-MS-O
analysis and OAV calculations. J Oleo Sci. 2013;62:563–70.
37. Veshkurova O, Golubenko Z, Pshenichnov E, et al. Malvone A, a phytoalexin
found in Malva sylvestris (family Malvaceae). Phytochemistry. 2006;67:
2376–9.
38. Zuo H, Li Y, Cui Y, An Y. Cardioprotective effect of Malva sylvestris L. in
myocardial ischemic/reprefused rats. Biomed Pharmacother. 2017;95:679–84.
Marrubium vulgare L.
(Lamiaceae)

(Syns.: M. apulum Ten.; M. hamatum Kunth; M. uncinatum Stokes)

Abstract
It is a perennial aromatic herb, a native of Europe and Asia (India and Iran) and
has been naturalized in other parts of the world, including the United States.
Theophrastus described two kinds of it, and Dioscorides, Pliny and Hippocrates
considered it stimulant, expectorant, deobstruent, carminative and local anodyne.
Europeans reputed it as a remedy for chronic bronchitis with copious expectora-
tion, and as a stomachic tonic for dyspepsia. The ancients used the expressed
juice with honey, both internally and as a local application to foul ulcers and
diseased mucous surfaces. Avicenna and other Arab physicians followed
accounts of its properties described by Dioscorides, and called it Hashishat-el-
kalb, because the dogs always urinate after smelling this herb. It is reported to
possess expectorant, diaphoretic, vasodilator and diuretic properties. Its seeds are
carminative, anti-inflammatory, stomachic, deobstruent, lithotriptic, aphrodisiac,
and strengthen kidneys and urinary bladder; for hemorrhoids, the seeds are used
with wine. In Brazilian folk medicine it is used in the treatment of several
diseases, including gastrointestinal disorders. The second kind described by
Muslim writers is called Baluti or black horehound and botanically identified as
Ballota nigra. Various other species of the genus Marrubium are traditionally
used to treat diseases like asthma, pulmonary infections, inflammation and
hypotension, as cholagogue and as sedative and analgesic. The diterpene
(marrubiin), flavonoids, phenylpropanoid esters, tannins, and sterols have been
reported from the plant. A phenylethanoid glycoside, marruboside, a terpenoid
with significant antihepatotoxic activity, designated as marrubic acid, and a
methoxylated flavone, ladanein have been isolated from aerial parts. Aqueous
extract ameliorated CP-hepatotoxicity in rats, and lowered SBP of SHRs, but not
of normotensive rats, and also inhibited contractile responses of rat aorta to
noradrenaline and to KCl. The decoction of the plant significantly decreased
dextrose-induced hyperglycemia, and lowered blood glucose, total lipids, TGs,
and TC levels of diabetic rats. Supplementation with infusion of dry leaves of

© Springer Nature Switzerland AG 2020 1137

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_122
1138 Marrubium vulgare L.

patients with type-2 diabetes not fully responding to conventional treatment

additionally reduced plasma glucose by 0.64%, and TC and TGs by 4.16% and
5.78%, respectively.

Keywords





Farasiyun Gandana pahari Karaderme Khanak Malrove Malrubio






Marrochemin Marroio Ōu xià zhì cǎo shǔ White horehound

Vernaculars: Urd.: Farasiyun, Hashishat-el-kalb (dog’s herb); Hin.: Gandana

pahari, Kurras Arabi; Ara.: Farasiyun, Hashishat-el-kalb, Zaqoom; Chi.: 欧夏至草属,
Ōu xià zhì cǎo shǔ; Cze.: Jablečník obecný; Dut.: Malrove, Witte malrove; Eng.: East
Indian peppermint, White horehound; Fin.: Hurtanminttu, Valkohurtanminttu;
Fre.: Bonhomme, Herbe vierge, Marrochemin, Marrube, Marrube blanc, Marrube
commun, Marrube des champs, Marrube officinal; Ger.: Gemeiner andorn, Gewöhn-
licher andorn, Gewöhnlicher andornmalrove; Ita.: Erba apiola, Marrubio, Marrubio
comune, Mentastro, Robbio; Per.: Khanak; Por.: Erva-virgem, Incenso, Marroio,
Marroio-branco, Marroio-de-frança, Marroio-vulgar, Marrolho; Rus.: Šandra oby-
knovennaja; Spa.: Alcar, Berrumbi, Camarruego, Juanrubio, Malrubio, Malva de sapo,
Manrubio, Manrubio blanco, Marrubio blanco; Swe.: Kransborre; Tur.: Karaderme.
Description: It is a perennial aromatic herb, a native of Europe and Asia (India and
Iran) and has been naturalized in other parts of the world, including the United
States. It grows to a height of about 90 cm; stem branching, quadrangular and
covered with a white felt. Leaves are opposite, petiolate, somewhat heart-shaped, or
rounded at the base, obtuse, serrate or coarsely crenate, pale-green and downy
above and hoary beneath. Flowers are small, white, axillary with wooly whorls, and
bloom from June to August. Achenes four, dark-brown; odor somewhat aromatic
and musky (after storage the aroma may disappear), taste pungent and bitter
(Figs. 1, 2 and 3).XL
Actions and Uses: Theophrastus described two kinds of it, and Dioscorides, Pliny
and Hippocrates considered it stimulant, expectorant, deobstruent, carminative and
local anodyne. Europeans reputed it as a remedy for chronic bronchitis with copious
expectoration, and as a stomachic tonic for dyspepsia. The ancients used the
expressed juice with honey, both internally and as a local application to foul ulcers
and diseased mucous surfaces.XL Avicenna and other Arab physicians followed
accounts of its properties described by Dioscorides, and called it Hashishat-el-kalb,
because the dogs always urinate after smelling this herb. It is reported to possess
expectorant, diaphoretic, vasodilator and diuretic properties. The second kind
described by Muslim writers is called Baluti or black horehound and botanically
identified as Ballota nigra. GhaniL mentioned it (temperament, hot 2° & dry 2°)
deobstruent, anti-inflammatory, aphrodisiac, stomachic, laxative, diuretic, emme-
nagogue anthelmintic, and useful for hemorrhoids. Its seeds are carminative,
anti-inflammatory, stomachic, deobstruent, lithotriptic, aphrodisiac, and strengthen
Marrubium vulgare L. 1139

Fig. 1 Marrubium vulgare, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Marrubium_vulgare_-_K%C3%B6hler%
E2%80%93s_Medizinal-Pflanzen-224.jpg

Fig. 2 Marrubium vulgare, Young Foliage, Raul654, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Marrubium_vulgare.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
1140 Marrubium vulgare L.

Fig. 3 Marrubium vulgare, Flowers, Stan Shebs, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Marrubium_vulgare_7.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

kidneys and urinary bladder; for hemorrhoids, the seeds are used with wine.
KabeerudinLXXVII described seeds especially useful for hemorrhagic and dry piles;
squeezed water of its green leaves is used to make pills with other drugs for the
treatment of piles. As an alterative, it is used in chronic rheumatism, jaundice,
chronic hepatitis, phthisis, amenorrhea and cachectic conditions,LXXXI,CV and an
infusion is used as stimulant, expectorant, and resolvent in the treatment of coughs,
bronchitis, dyspepsia, and hepatitis.CV Various other species of the genus Marru-
bium are traditionally used to treat diseases like asthma, pulmonary infections,
inflammation and hypotension, as cholagogue and as sedative and analgesic [30]. In
Brazilian folk medicine it is used in the treatment of several diseases, including
gastrointestinal disorders [41]. It has widely been used for the control of type-2
diabetes in traditional medicines of Algeria [6], in the western Anti-Atlas Provinces
of Morocco [4], of Spain [37], and Mexico [21, 38], where it is one of the most
versatile species used medicinally [23], and also used mainly in the northwestern
part of Mexico (Sonora) for the empirical treatment of gastrointestinal disorders
[35]. It is also one of the commonly used plants in the traditional medicine of
Bosnia and Herzegovina [34], and the aerial parts are official in Hungarian Phar-
macopoeia VII [44]. Whole plant is emmenagogue and uterine stimulant [24], and
was reported active against 37 Sarcoma [5]. As a cough remedy it has been used in
Europe for over 400 years, and due to its choleretic properties it also improves
digestion. In 1990, the German Commission E approved it for the treatment of
bronchial catarrh and dyspepsia with loss of appetite.
Marrubium vulgare L. 1141

Phytoconstituents: The diterpene (marrubiin), flavonoids (apigenin, luteolin,

quercetin, isoquercitrin, ladanein, chrysoeriol, or vitexin, apigerin 7-glycoside,
luteoline 7-glycoside, quercetin 3-glycoside and quercetin 3-rhamnoglycoside) [26,
36], phenylpropanoid esters (acteoside, forsythoside B, arenarioside, ballotetroside,
alyssonoide, marruboside, and acethyl marruboside), tannins (proanthocyanidins,
catechin and epicatechin, condensed tannins), and sterols have been reported from
the plant [36]. A phenylethanoid glycoside, marruboside [40], a terpenoid with
significant antihepatotoxic activity, designated as marrubic acid [1], and a
methoxylated flavone, ladanein [2] have been isolated from aerial parts. Three
secondary metabolites, 11-oxomarrubiin, vulgarcoside A and 3-hydroxyapigenin-4′-
O-(6″-O-p-coumaroyl)-b-D-glucopyranoside, were isolated from the whole plant
[42]. Furanic labdane diterpenes are accumulated in greatest amounts in leaves and
flowers [25]. Premarrubiin, a diterpenoid [20], volatile oil, resin, and fat have also
been isolated from the plant.
Pharmacology: Ethanol extract of flowering tops in a dose of 100 mg/kg orally
produced 29% inhibition of carrageenan-induced inflammation in rats [28].
Marrubiin also exerted a nonspecific inhibitory effect on proinflammatory agent-
induced microvascular extravasation [43]. Hydroalcohol extracts of roots and aerial
parts significantly antagonized in vitro actions of ACh, bradykinin, PGE2, his-
tamine and oxytocin with selectivity for cholinergic contractions [41]. Hydroal-
cohol extract and marrubiin also exhibited significant analgesic activity [11, 12].
Methanol extract and marrubiin were significantly gastroprotective against ethanol-
and indomethacin-induced gastric ulcers; the high dose of the extract being
equivalent to omeprazole and better than cimetidine, with a significant increase in
pH and mucus production. Methanol extract also significantly inhibited growth of
H. pylori [35], and EO being active against a number of Gram-positive bacteria
[47]. Total phenolic and flavonoid contents of leaves samples collected from dif-
ferent locations in northwest Algeria varied [8], so did the antifungal activity of
flavonoid extracts against A. niger and C. albicans, but the antifungal activity was
highly significant and even exceeding to that of amphotericin, fluconazole, terbi-
nafine and econazole nitrate [7].
Aqueous extract ameliorated CP-hepatotoxicity in rats [17], and lowered SBP of
SHRs, but not of normotensive rats, and also inhibited contractile responses of rat
aorta to noradrenaline and to KCl [14]. Furanic labdane diterpenes, marrubenol and
marrubiin, were identified as the most active compounds for this effect [15].
Methanol extract significantly lowered TC, LDL-C, and TGs of triton-induced
hyperlipidemic mice [22], protected myocardium against isoproterenol-induced
acute MI, and the effect was suggested to be due to its antioxidant activities [46].
Aqueous fraction of the methanol extract protected against I/R-induced arrhythmias
and infarct size of isolated rat heart [19]. Cahen [9] was the first to report that the
plant exhibits hypoglycemic activity in rabbits. The decoction of the plant signif-
icantly decreased dextrose-induced hyperglycemia [38], and significantly lowered
blood glucose [6, 31], total lipids, TGs, and TC levels of diabetic rats [6]. Aqueous
and methanol extracts of leaves exhibit significant in vitro antioxidant activity
1142 Marrubium vulgare L.

[18, 29, 45]. The EO possesses expectorant and vasodilatory activities, and stim-
ulates bronchial mucosal secretion.CXXXXIII The protein extract exhibited in vitro
immunostimulatory activity [10].
Clinical Studies: In a double-blind study, 21 Mexican patients with type-2 dia-
betes not fully responding to conventional treatment were added infusion of dry
leaves as adjunct to their treatment for 21-days. Plasma glucose level was addi-
tionally reduced by 0.64%, and TC and TGs by 4.16% and 5.78%, respectively
[21].
Mechanism of Action: Most of the pharmacological effects are attributed to its
total phenolic and flavonoid contents. 6-Octadecynoic acid, a fatty acid with a triple
bond has been identified in the methanol extract as an agonist of PPARc [32]. The
glycosidic phenylpropanoid esters, acteoside, forsythoside B, and arenarioside
inhibit Cox-2 enzyme more than Cox-1 [39]. Secondary metabolites also exhibit
moderate to low level inhibition of NO production, and vulgarcoside A moderately
inhibited proinflammatory cytokine TNF-a [42]. Marrubenol inhibits contraction of
smooth muscle by blocking L-type calcium channels [16], and also improves
endothelial function in SHRs [13]. The gastroprotection is related to the activity of
NO and endogenous sulfhydryls [33].
Human A/Es, Allergy and Toxicity: It is not suitable for people with hot-
temperament, causes headache and produces confusion.LXXVII
Animal Toxicity: Aqueous extract does not cause any significant toxicity. Mar-
rubiin is reported to have antiarrhythmic properties in smaller doses, but may induce
cardiac irregularities in large doses. Marrubiin oral LD50 in rats was reported
370 mg/kg [27]. Single oral daily dose of 1,000 mg/kg of hydroethanol leaf extract
to nonpregnant and pregnant rats for 19-days significantly reduced RBCs, hemat-
ocrit, Hb, and MCV, and significantly decreased implantation of fetuses [3].
Commentary: There are no formal studies on various significant effects of the
herb in clinical settings. The anti-inflammatory and antifungal activities, in addition
to antidiabetic and effects on respiratory system should be of interest for clinical
studies.

References
1. Ahmed B, Masoodi MH, Siddique AH, Khan S. A new monoterpene acid
from Marrubium vulgare with potential antihepatotoxic activity. Nat Prod
Res. 2010;24:1671–80.
2. Alkhatib R, Joha S, Cheok M, et al. Activity of ladanein on leukemia cell
lines and its occurrence in Marrubium vulgare. Planta Med. 2010;76:86–7.
3. Aouni R, Ben Attia M, Jaafoura MH, Bibi-Derbel A, Haouari M. Effects of
the hydroethanolic extract of Marrubium vulgare in female rats. Asian Pac J
Trop Med. 2017;10:160–4.
Marrubium vulgare L. 1143

4. Barkaoui M, Katiri A, Boubaker H, Msanda F. Ethnobotanical survey of

medicinal plants used in the traditional treatment of diabetes in Chtouka Ait
Baha and Tiznit (Western Anti-Atlas), Morocco. J Ethnopharmacol. 2017;
198:338–50.
5. Belkin M, Fitzgerald DB. Tumor-damaging capacity of plant materials.
V. Miscellaneous plants. J Natl Cancer Inst. 1953;13:607.
6. Boudjelal A, Henchiri C, Siracusa L, et al. Compositional analysis and in vivo
antidiabetic activity of wild Algerian Marrubium vulgare L. infusion.
Fitoterapia. 2012;83:286–92.
7. Bouterfas K, Mehdadi Z, Aouad L, et al. Does the sampling locality
influence on the antifungal activity of the flavonoids of Marrubium vulgare
against Aspergillus niger and Candida albicans? J Mycol Med. 2016;26:
201–11 (Article in French).
8. Bouterfas K, Mehdadi Z, Elaoufi MM, Latreche A, Benchiha W. Antiox-
idant activity and total phenolic and flavonoids content variations of leaves
extracts of white Horehound (Marrubium vulgare Linné) from three
geographical origins. Ann Pharm Fr. 2016;74:453–62.
9. Cahen R. Pharmacologic spectrum of Marrubium vulgare L. C R Soc Biol
(Paris). 1970;164:1467–72.
10. Daoudi A, Aarab L, Abdel-Sattar E. Screening of immunomodulatory
activity of total and protein extracts of some Moroccan medicinal plants.
Toxicol Ind Health. 2013;29:245–53.
11. De Jesus RA, Cechinel-Filho V, Oliveira AE, Schlemper V. Analysis of the
antinociceptive properties of marrubiin isolated from Marrubium vulgare.
Phytomedicine. 2000;7:111–5.
12. De Souza MM, de Jesus RA, Cechinel-Filho V, Schlemper V. Analgesic
profile of hydroalcoholic extract obtained from Marrubium vulgare.
Phytomedicine. 1998;5:103–7.
13. El Bardai S, Lyoussi B, Wibo M, Morel N. Comparative study of the
antihypertensive activity of Marrubium vulgare and of the dihydropyridine
calcium antagonist amlodipine in spontaneously hypertensive rat. Clin Exp
Hypertens. 2004;26:465–74.
14. El Bardai S, Lyoussi B, Wibo M, Morel N. Pharmacological evidence of
hypotensive activity of Marrubium vulgare and Foeniculum vulgare in
spontaneously hypertensive rat. Clin Exp Hypertens. 2001;23:329–43.
15. El Bardai S, Morel N, Wibo M, et al. The vasorelaxant activity of marrubenol
and marrubiin from Marrubium vulgare. Planta Med. 2003;69:75–7.
16. El-Bardai S, Wibo M, Hamaide MC, et al. Characterisation of marrubenol, a
diterpene extracted from Marrubium vulgare, as an L-type calcium channel
blocker. Br J Pharmacol. 2003;140:1211–6.
17. Ettaya A, Dhibi S, Samout N, Elfeki A, Hfaiedh N. Hepatoprotective
activity of white horehound (Marrubium vulgare) extract against cyclophos-
phamide toxicity in male rats. Can J Physiol Pharmacol. 2016;94:441–7.
1144 Marrubium vulgare L.

18. Firuzi O, Javidnia K, Gholami M, et al. Antioxidant activity and total phenolic
content of 24 Lamiaceae species growing in Iran. Nat Prod Commun.
2010;5:261–4.
19. Garjani A, Tila D, Hamedeyazdan S, et al. An investigation on cardiopro-
tective potential of Marrubium vulgare aqueous fraction against ischaemia-
reperfusion injury in isolated rat heart. Folia Morphol (Warsz). 2017;76:
361–71.
20. Henderson MS, McCrindle R. Premarrubiin. A diterpenoid from Marrubium
vulgare. J Chem Soc C. 1969;15:2014–5.
21. Herrera-Arellano A, Aguilar-Santamaría L, García-Hernández B, et al.
Clinical trial of Cecropia obtusifolia and Marrubium vulgare leaf extracts on
blood glucose and serum lipids in type 2 diabetics. Phytomedicine. 2004;11:
561–6.
22. Ibrahim AY, Hendawy SF, Elsayed AA, Omer EA. Evaluation of
hypolipidemic Marrubium vulgare effect in Triton WR-1339-induced
hyperlipidemia in mice. Asian Pac J Trop Med. 2016;9:453–9.
23. Juárez-Vázquez MD, Carranza-Álvarez C, Alonso-Castro AJ, et al. Eth-
nobotany of medicinal plants used in Xalpatlahuac, Guerrero. México.
J Ethnopharmacol. 2013;148:521–7.
24. Kchouk M, Chadli A. On the abortive properties of white horehound
(Marrubium vulgare L.). Arch Inst Pasteur Tunis. 1963;40:129–32.
25. Knöss W, Zapp J. Accumulation of furanic labdane diterpenes in
Marrubium vulgare and Leonurus cardiaca. Planta Med. 1998;64:357–61.
26. Kowalewski Z, Marlawska I. Flavonoid compounds in the herb of
Marrubium vulgare. Herba Pol (Poland). 1978;24:183.
27. Krejci I, Zadina R. Planta Med. 1959;7:1.
28. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal
plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
29. Matkowski A, Piotrowska M. Antioxidant and free radical scavenging activities
of some medicinal plants from the Lamiaceae. Fitoterapia. 2006;77:346–53.
30. Meyre-Silva C, Cechinel-Filho V. A review of the chemical and pharmaco-
logical aspects of the genus marrubium. Curr Pharm Des. 2010;16:3503–18.
31. Novaes AP, Rossi C, Poffo C, et al. Preliminary evaluation of the hypoglycemic
effect of some Brazilian medicinal plants. Therapie. 2001;56:427–30.
32. Ohtera A, Miyamae Y, Nakai N, et al. Identification of 6-octadecynoic acid
from a methanol extract of Marrubium vulgare L. as a peroxisome
proliferator-activated receptor c agonist. Biochem Biophys Res Commun.
2013;440:204–9.
33. Paula de Oliveira A, Santin JR, Lemos M, et al. Gastroprotective activity of
methanol extract and marrubiin obtained from leaves of Marrubium vulgare
L. (Lamiaceae). J Pharm Pharmacol. 2011;63:1230–7.
34. Redzić SS. The ecological aspect of ethnobotany and ethnopharmacology of
population in Bosnia and Herzegovina. Coll Antropol. 2007;31:869–90.
Marrubium vulgare L. 1145

35. Robles-Zepeda RE, Velázquez-Contreras CA, Garibay-Escobar A, et al.

Antimicrobial activity of Northwestern Mexican plants against Helicobacter
pylori. J Med Food. 2011;14:1280–3.
36. Rodríguez Villanueva J, Martín Esteban J, Rodríguez Villanueva L.
A reassessment of the Marrubium vulgare L. herb’s potential role in
diabetes mellitus type 2: first results guide the investigation toward new
horizons. Medicines (Basel). 2017;4:E57.
37. Rodríguez Villanueva J, Martín Esteban J. An insight into a blockbuster
phytomedicine; Marrubium vulgare L. herb. More of a myth than a reality?
Phytother Res. 2016;30:1551–8.
38. Román Ramos R, Alarcón-Aguilar F, Lara-Lemus A, Flores-Saenz JL.
Hypoglycemic effect of plants used in Mexico as antidiabetics. Arch Med
Res. 1992;23:59–64.
39. Sahpaz S, Garbacki N, Tits M, Bailleul F. Isolation and pharmacological
activity of phenylpropanoid esters from Marrubium vulgare. J Ethnophar-
macol. 2002;79:389–92.
40. Sahpaz S, Hennebelle T, Bailleul F. Marruboside, a new phenylethanoid
glycoside from Marrubium vulgare L. Nat Prod Lett. 2002;16:195–9.
41. Schlemper V, Ribas A, Nicolau M, Cechinel Filho V. Antispasmodic effects
of hydroalcoholic extract of Marrubium vulgare on isolated tissues.
Phytomedicine. 1996;3:211–6.
42. Shaheen F, Rasoola S, Shah ZA, et al. Chemical constituents of Marrubium
vulgare as potential inhibitors of nitric oxide and respiratory burst. Nat Prod
Commun. 2014;9:903–6.
43. Stulzer HK, Tagliari MP, Zampirolo JA, et al. Antioedematogenic effect of
marrubiin obtained from Marrubium vulgare. J Ethnopharmacol. 2006;108:
379–84.
44. Telek E, Tõth L, Botz L, Máthé I. Chemical tests with Marrubium species.
Official data on Marubii herba in Pharmacopoeia Hungarica VII. Acta
Pharm Hung. 1997;67:31–7.
45. VanderJagt TJ, Ghattas R, VanderJagt DJ, et al. Comparison of the total
antioxidant content of 30 widely used medicinal plants of New Mexico. Life
Sci. 2002;70:1035–40.
46. Yousefi K, Soraya H, Fathiazad F, et al. Cardioprotective effect of
methanolic extract of Marrubium vulgare L. on isoproterenol-induced acute
myocardial infarction in rats. Indian J Exp Biol. 2013;51:653–60.
47. Zarai Z, Kadri A, Ben Chobba I, et al. The in-vitro evaluation of
antibacterial, antifungal and cytotoxic properties of Marrubium vulgare L.
essential oil grown in Tunisia. Lipids Health Dis. 2011;10:161.
Matricaria chamomilla L.
(Asteraceae/Compositae)

(Syns.: M. recutita L.; Chamomilla recutita (L.) Rausch.; C. vulgaris Koch)

Abstract
A plant native and naturalized in north India, Persia, West Asia, Australia,
Germany, Hungary, France, Russia, Yugoslavia, and Brazil. Chamomile use
dates back to centuries, it was known to ancient Egyptians, Greeks, and Romans,
was mentioned by Hippocrates, Galen, and Asclepius; it exerts calming,
carminative, and spasmolytic effects. Chamomile preparations are chiefly used
for hay fever, inflammation, muscle spasms, menstrual disorders, insomnia,
ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids.
Besides being used as a mild sedative and for digestion, chamomile essential oils
are used extensively in perfumery, cosmetic creams, hair and skin preparations,
and in aromatherapy. Persian writers opined that the odor of the flowers induces
sleep and drives away noxious insects, and that bathing the genitals with
chamomile tea has a powerful aphrodisiac effect. The disinfectant, antiseptic and
powerful antiphlogistic action causes constriction of the dilated capillaries due to
inflammation. The herb also reportedly doubles the amount of biliary secretions.
Though, Hindu physicians or Sanskrit writers did not mention this plant in their
Materia Medica, it is used in India in flatulent colic, dyspepsia, chlorosis,
amenorrhea, and during convalescence from acute febrile and other diseases.
More than 120 chemical constituents have been identified in chamomile flower
as secondary metabolites, including 28 terpenoids and 36 flavonoids. Aqueous
extract significantly decreased blood glucose and amylase activity and increased
serum insulin levels of diabetic rats, and showed a synergistic effect with
oregano. In an open-label, two-phase RCT, treatment with chamomile extract of
U.S. patients with moderate to severe General Anxiety Disorder (GAD) for up to
8-weeks, clinically meaningful reduction in GAD symptoms with a response rate
comparable to conventional anxiolytic drug therapy was observed. Treatment of

Both Anthemis nobilis and Matricaria chamomilla are used as Chamomile and share the same
vernacular names, though Ghauri et al. [23] established that the Babunah widely used in Unani
medicine is Matricaria chamomilla.
© Springer Nature Switzerland AG 2020 1147
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_123
1148 Matricaria chamomilla L.

three 14–16-year-old male psychiatric outpatients with baseline ADHD,

improved their hyperactivity, inattention and immaturity factors while using
chamomile tea.

Keywords




Alman papatyası Babunah Babunaj Camomila Echtkamille

German




chamomile Kamamil Matricaire Mu ju Sońbhal

Vernaculars: Urd.: Babunah; Hin.: Babune-ke-phul, Sonamoti, Sońbhal; Ben.:

Babunphul; Mar.: Babuna-cha-phula; Tam.: Chaman duppu, Shimai-chamantippu;
Tel.: Chamanti-pushpamu, Sima; Mal.: Shima-jeventi-pushpam; Ara.: Babunaj,
Shajrat-el-kafur, Tuffah-ul-arz; Chi.: Kau-kiuh-hwa, Mu ju; Dut.: Echte kamille,
Kamamil; Eng.: Chamomile, Genuine chamomile, German chamomile, Hungarian
chamomile, Scented mayweed, Wild chamomile; Fre.: Camomille ordinaire,
Camomille sauvage, Camomille vraie, Matricaire, Matricaire chamomille, Matricaire
tronquée, Petite camomille; Ger.: Echtkamille, Echte kamille, Kleine kamille; Ita.:
Camomilla commune, Capomilla; Jap.: Kamirure, Kamitsure, Kamomairu, Kamo-
mîru; Per.: Babunah, Karnanak; Por.: Camomila, Camomila-alemã, Camomila-
da-alemanha, Camomila-dos-alemães, Camomila-vulgar, Mançanila, Margaça-das-
boticas; Spa.: Camomilla, Manzanilla bastarda, Manzanilla común, Manzanilla de
aragón, Manzanilla del país, Manzanilla fina, Manzanilla loca, Margaza; Tur.: Alman
papatyası.
Description: A plant native and naturalized in north India, Persia, West Asia,
Australia, Germany, Hungary, France, Russia, Yugoslavia, and Brazil. The flow-
erheads are 12–18 mm in diameter, and have a flattish involucre, with two or three
rows of small oblong-linear, obtuse scales having the membranous margin. The
receptacle is at first convex, but becomes strongly conical and hollow, and is free
from chaff. Ray-florets are about fifteen in number, soon reflexed white, ligulate-
oblong, with two notches at the ape and enclosing the bifid style, but no stamens.
Numerous yellow disk-florets are tubular, five-toothed, somewhat glandular, her-
maphrodite, and have the anthers united into a tube through which the bifid style
projects. Achenes are small, curved, finely five-ribbed on the inner surface,
brownish, without pappus, but with a slightly elevated margin at the apex. German-
chamomile flowers have a peculiar aromatic odor and a bitter aromatic taste. They
are easily distinguished from allied composite plants by their smooth, conical and
hollow disks, which shrink very considerably on drying.XL Flowers should be
collected near full bloom stage during March-April season for best quality [71]
(Figs. 1, 2 and 3).
Actions and Uses: Chamomile use dates back to centuries, it was known to ancient
Egyptians, Greeks, and Romans, was mentioned by Hippocrates, Galen, and Ascle-
pius [31]; it exerts calming, carminative, and spasmolytic effects [3]. Chamomile
preparations are chiefly used for hay fever, inflammation, muscle spasms, menstrual
disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and
Matricaria chamomilla L. 1149

Fig. 1 Matricaria chamomilla, Plants, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Matricaria_recutita_001.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Matricaria chamomilla, Flower (Close-up), Alina Zienowicz, WikimediaCommons; Share-

Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Matricaria_recutita_
2008_07_06.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

hemorrhoids [21, 45]. Besides being used as a mild sedative and for digestion,
chamomile essential oils are used extensively in perfumery, cosmetic creams, hair and
skin preparations, and in aromatherapy [29, 76]. Ibn al-BaitarLXIX described it anti-
inflammatory, laxative, diaphoretic, diuretic, lithotriptic, antiflatulence, spasmolytic,
1150 Matricaria chamomilla L.

Fig. 3 Matricaria chamomilla, Dried Flowers as sold in the U.S., Prof. Akbar, Original

nervine tonic, and beneficial in liver pain and jaundice. Ibn Jazlah used it for treatment
of epilepsy, and al-Kindi used it in a strong dressing for spleen, and to relax liver and
stomach.LIII Arab Muslim physicians ascribed to it the properties of stimulant,
attenuant and discutient. Persian writers opined that the odor of the flowers induces
sleep and drives away noxious insects, and that bathing the genitals with chamomile
(temperament, hot 2° and dry 1°) tea has a powerful aphrodisiac effect.XL Unani
physicians use it externally to resolve inflammations and indurations, and sprains;
internally for diuresis, and menstruation, and as sitz bath to expel baby and pla-
centa.LXXVII The disinfectant, antiseptic and powerful antiphlogistic action causes
constriction of the dilated capillaries due to inflammation. The herb also reportedly
doubles the amount of biliary secretions.CV Though, Hindu physicians or Sanskrit
writers did not mention this plant in their Materia Medica, it is used in India in flatulent
colic, dyspepsia, chlorosis, amenorrhea, and during convalescence from acute febrile
and other diseases. The warm infusion is used in colic, biliary derangement, periodic
headache and in confirmed drunkards and heavy gluttons. Cold infusion is a stom-
achic tonic, and given in indigestion, flatulence and summer diarrhea. Fomentation
with chamomile flowers is also a very soothing application to relieve local colicky
pains. The oil is a stimulant and antispasmodic and used internally to relieve reflex
cough, pulmonary catarrh, diarrhea of children, spasmodic asthma, whooping cough,
and in dysmenorrhea and hysteria.LXXXI It is one of the plants known for antith-
rombtic property in Persian traditional medicine, and is used to treat blood clot dis-
orders [47]. Eye washing with chamomile tea is a Spanish folk remedy to treat
conjunctivitis and other ocular diseases [78]. It is one of the most frequently used
plants in southwestern Serbian folk medicine [63], by Hispanic families in the San
Luis Valley of Colorado [4], by the Mexican family physicians, health workers and
patients [60, 80], and by the population of the Atlantic Coast of Colombia for colic
[27].
Matricaria chamomilla L. 1151

Phytoconstituents: More than 120 chemical constituents have been identified in

chamomile flower as secondary metabolites, including 28 terpenoids and 36 fla-
vonoids [72]. Methanol extract contains high concentration of apigenin-7-O-glu-
coside, along with several polyphenolic constituents, including caffeic acid,
luteolin, and luteolin-7-O-glucoside [18, 58]. Flavonoids in chamomile are thought
to be responsible for its health promoting and anticancer activities [13, 74].
Flavonoids breakdown in the alimentary canal to release the aglycones, that are
metabolized in liver by methylation or by conjugation with gluconate or sulfate
[13]. In addition to herniarin and umbelliferone, two other coumarin glycosides and
one aglycone skimmin (umbelliferone-7-O-b-D-glucoside), daphnin (daphnetin-7-
O-b-D-glucoside) and daphnetin (7,8-dihydroxy-coumarin) were isolated from the
leaves [55]. Chamomile flowers contain 0.24–2% EO that is blue in color, and is
often referred to as blue oil; blue color of the oil is due to the presence of
sesquiterpenes. European Pharmacopoeia recommends that chamomile should
contain no less than 4 mL/kg of the EO [17]. The EO chiefly contains sesquiterpene
derivatives (75–90%) and traces of monoterpenes; b-farnesene, terpene alcohol
(farnesol), chamazulene, a-bisabolol, and a-bisabolol oxides A and a-bisabolol
oxides B [3, 20, 44, 54, 72]. Chamazulene contents vary depending on the origin
and age of the material; storage of flowers also decreases its contents [72]. Blue oil
hydrodistilled from flowerheads from Serbia contained a-bisabolol oxide A
(21.5%), a-bisabolol oxide B (25.5%) and (Z)-spiroether (cis-en-yn-spiroether)
(10.3%) as the major compounds [83]; whereas yield of oil of aerial parts was 0.7%
(v/w), and trans-b-farnesene was the major component (43.5%) of a Dutch origin
M. chamomilla oil [73]. Major compounds identified in EO from Iran were
a-bisabolol (56.86%), trans-trans-farnesol (15.64%), cis-b-farnesene (7.12%),
guaiazulene (4.24%), a-cubebene (2.69%), a-bisabolol oxide A (2.19%) and
chamazulene (2.18%) [82]. Chamomile oil from Nepal contained (E)-b-famesene
(42.2%), a-bisabolol oxide A (22.3%), (E,E)-a-famesene (8.3%), cis-bicycloether
(5.0%), a-bisabolol oxide B (4.5%), and a-bisabolone oxide A (4.0%) as the main
components, representing the (E)-b-farnesene chemotype [62]. Besides chamazu-
lene, (−)-a-bisabolol plays significant role in its healing effects as anti-inflammatory,
antiallergic, antispasmodic, antibacterial, antipyretic, ulcer-protective, and antifun-
gal [21]. Quantity of (−)-a-bisabolol is not always correlated with the quantity of
total EO [22].
Pharmacology: Aqueous extract (300 mg/kg) significantly decreased blood glu-
cose and amylase activity and increased serum insulin levels of diabetic rats, and
showed a synergistic effect with oregano [56]. Ethanol extract of aerial parts
significantly reduced postprandial hyperglycemia and oxidative stress, and aug-
mented the antioxidant system of diabetic rats [11]. Administration of hot water
extract to diabetic rats for 21-days also significantly lowered blood glucose [35].
Coadministration of a standardized extract containing 0.3% flavonoid, apigenin
with morphine inhibits development of morphine dependence and precipitation of
withdrawal syndrome in rats [26]. Apigenin reduced locomotor activity in rats; the
sedative effect was not antagonized by the benzodiazepine antagonist flumazenil
[16, 87]. Ethanol plant extract exhibited significant antinociceptive effect in rats and
1152 Matricaria chamomilla L.

a synergistic effect with diclofenac, but the combination caused significant gastric
damage [52]; it was also synergistic with diclofenac and indomethacin for their
anti-inflammatory effect [51]. Freeze-dried extract suppressed both carrageenan-
induced inflammation and leukocyte infiltration [67]. Matricaria oil produced sig-
nificant reduction of hyperalgesia and edema in rats both prophylactically and
therapeutically, but more effective prophylactically [83]. Topical application of
chamomile extract accelerated burn [34], and incisional wounds healing [32, 33].
Two-weeks application of the aqueous extract in petroleum jelly improved atopic
dermatitis-like lesions in mice [53]. Contrary to the allergenicity, a single oral
administration of the ethyl acetate extract or EO shows a remarkable antipruritic
effect in mice [38]. Aqueous extract exhibited in vitro antioxidant activity [8, 9],
and chamazulene inhibited LPO [59]. Aqueous infusion also showed uterotonic
effect in isolated rabbit and guinea pig uterine horns [68].
The plant significantly inhibits ROS generation from H. pylori-infected gastric
epithelial cells [86], and pretreatment with hydroethanol extract attenuates ethanol-
induced gastric damage in rats [7, 12], and produces antiulcerogenic activity in rats
with reduced acid output and increased mucin secretion, increase in PGE2 release
and a decrease in leukotrienes [37]. Aqueous extract significantly protected against
paraquat-hepatotoxicity, improving liver antioxidant capacity [81]. Aqueous and
methanol flower extracts caused minimal growth inhibition of normal cells, but a
significant decrease in cell viability and apoptosis of various human cancer cell
lines [74]; methanol fraction demonstrating higher response in inhibiting cell
growth and inducing apoptosis [75]. Ethanol extract of aerial parts also produced
anti-invasive and antimigrative effects on breast cancer cells [49].
Ethanol extract inhibited in vitro growth of poliovirus-2 [79, 85], and was active
against S. aureus strains [70]. Antibacterial activity of EO varies, probably due to
variations in their chemical constituents. While the EO from Brazil was reported
active against strains of S. aureus, C. albicans and C. krusei [50], Iranian oil
inhibited 92.5% growth of A. niger [82], and EO from Germany was also reported
virucidal to aciclovir-sensitive and aciclovir-resistant HSV-1 and HSV-2 [39, 40];
EO from Serbia exhibited relatively weak antibacterial activity against Gram-
positive bacteria (S. aureus, S. epidermidis, B. subtilis) [73], and EO from Ethiopia
showed weaker if any antimicrobial activity against S. typhi, S. paratyphi,
S. typhimurium, Shigella species, P. aeruginosa, S. aureus, and E. coli, two Tri-
chophyton spp. and two Aspergillus spp. [46]. Matricaria chamomilla gel in aqueous
base (25%) also significantly inhibited growth of C. albicans and E. faecalis [57].
Clinical Studies: In an open-label, two-phase RCT, treatment with chamomile
extract 1,500 mg/day of U.S. patients with moderate to severe GAD for up to
8-weeks, clinically meaningful reduction in GAD symptoms with a response rate
comparable to conventional anxiolytic drug therapy was observed [36]. In the
follow-up, after twelve-weeks open-label treatment, when patients were randomized
in a double-blind manner to placebo or continued with chamomile extract, patients
in placebo group relapsed [43]. Treatment of three 14–16-year-old male Italian
psychiatric outpatients with baseline ADHD, improved their hyperactivity, inat-
tention and immaturity factors while using chamomile tea [48]. Chamomile
Matricaria chamomilla L. 1153

improved sleep quality of elderly Iranian people admitted to nursing homes, after
four-weeks of treatment [1]. Chamomile tea caused deep sleep in 10 out of 12
patients preparing to undergo cardiac catheterization [28]. In a double-blind, ran-
domized comparative trial, chamomile extract significantly relieved PMS symptoms
in Iranian students, better than mefenamic acid [66], and significantly relieved mild
to moderate mastalgia associated with menstrual cycle [61].
Topical application of chamomile oil in patients with knee osteoarthritis sig-
nificantly reduced patients’ need for acetaminophen for pain relief [69], and sig-
nificantly improved symptoms and functionality in cases of severe carpal tunnel
syndrome [30]. Topical application of chamomile extract on weeping dermabra-
sions significantly decreased weeping wound area and increased drying [24]. Twice
daily rinse with a mouthwash consisting of 1% aqueous flower extract by Brazilian
patients undergoing orthodontic treatment, significantly reduced plaque and gin-
gival bleeding [25].
Mechanism of Action: Aqueous and ethanol extracts significantly inhibited
in vitro rat brain glutamic acid decarboxylase activity, the enzyme that catalyzes
conversion of glutamate to GABA [6]. Apigenin also reduced GABA-activated Cl−
currents in a dose-dependent fashion in cultured cells [5]. Therefore, GABA-ergic
system is likely not involved in the sedative effect of apigenin. Mechanism of action
by which it exerts its CNS effects is still unknown. Virucidal activity of the EO is
due to interruption of the adsorption of the herpes viruses [39, 40].
Human A/Es, Allergy and Toxicity: Allergic reactions from acute rhinitis, rhino-
conjunctivitis, urticaria, contact dermatitis, asthma, angioedema to anaphylactic
reactions in individuals hypersensitive to Chamomile or other plants of Compositae
family (cross-sensitivity) have been reported [14, 19, 41, 64, 77, 78, 84]. Pollens
present in chamomile tea are responsible for the allergic reactions and
cross-reactivity [78]. Washing eyes with Chamomile tea caused allergic conjunc-
tivitis [78]. Ingestion of chamomile-tea by an 8-year-old atopic Spanish boy pre-
cipitated a severe anaphylactic reaction [77], and a 38-year-old Caucasian male
developed severe anaphylaxis with generalized urticaria, angioedema and severe
dyspnea, one hour after consuming Chamomile tea [2]. Individuals with known
hypersensitivity to plants of Compositae family (ragweed, chrysanthemum, mar-
igold, daisy, etc.) should avoid using chamomile-containing products to reduce the
likelihood of an allergic reaction [3]. Patients with asthma and/or rhinitis have also
shown cross-reactivity between Artemisia vulgaris and M. chamomilla [15].
The FDA, however, classifies the oil and extract of both German and Roman
chamomile as substances Generally Regarded As Safe (GRAS).
Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interactions: Ethanol extract significantly
inhibits human CYP3A4 [10], while the EO and its constituents, chamazulene,
cis-spiroether and trans-spiroether are potent in vitro inhibitors of CYP1A2, but
also inhibit CYP3A4, CYP2C9 and CYP2D6; the CYP2D6 is significantly inhib-
ited by both chamazulene and a-bisabolol [21]. A 70-year-old woman on warfarin
suffered from multiple internal hemorrhages after using chamomile products to
1154 Matricaria chamomilla L.

relieve upper respiratory symptoms, possibly due to coumarins present in chamo-

mile, but doubtful due to their different chemical configuration [42, 65]. Drug
interactions are possible with drugs metabolized by CYP450s.
Commentary: Chamomile use by the masses for relaxation (sedation), as sleep aid
and for anxiety disorders is a testament of its effectiveness and corroborated by a
limited number of clinical studies. Nevertheless, more RCTs are needed to firmly
establish its clinical uses. Also, physicians should be aware and warn patients about
the possibility of its interactions with drugs like warfarin, and cross-allergy with
other plants of the Compositae family.

References
1. Abdullahzadeh M, Matourypour P, Naji SA. Investigation effect of oral
chamomilla on sleep quality in elderly people in Isfahan: a randomized
control trial. J Educ Health Promot. 2017;6:53.
2. Andres C, Chen WC, Ollert M, et al. Anaphylactic reaction to camomile tea.
Allergol Int. 2009;58:135–6.
3. Anonymous. Matricaria chamomilla (German chamomile)—monograph.
Altern Med Rev. 2008;13:58–62.
4. Appelt GD. Pharmacological aspects of selected herbs employed in Hispanic
folk medicine in the San Luis Valley of Colorado, USA: I. Ligusticum porteri
(osha) and Matricaria chamomilla (manzanilla). J Ethnopharmacol. 1985;
13:51–5.
5. Avallone R, Zanoli P, Puia G, et al. Pharmacological profile of apigenin, a
flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol.
2000;59:1387–94.
6. Awad R, Levac D, Cybulska P, et al. Effects of traditionally used anxiolytic
botanicals on enzymes of the gamma-aminobutyric acid (GABA) system.
Can J Physiol Pharmacol. 2007;85:933–42.
7. Bezerra SB, Leal LK, Nogueira NA, Campos AR. Bisabolol-induced
gastroprotection against acute gastric lesions: role of prostaglandins, nitric
oxide, and KATP+ channels. J Med Food. 2009;12:1403–6.
8. Bhaskaran N, Shukla S, Kanwal R, Srivastava JK, Gupta S. Induction of
heme oxygenase-1 by chamomile protects murine macrophages against
oxidative stress. Life Sci. 2012;90:1027–33.
9. Bhaskaran N, Srivastava JK, Shukla S, Gupta S. Chamomile confers
protection against hydrogen peroxide-induced toxicity through activation of
Nrf2-mediated defense response. Phytother Res. 2013;27:118–25.
10. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation
of human cytochrome P450 3A4 inhibition by selected commercial herbal
extracts and tinctures. Phytomedicine. 2000;7:273–82.
11. Cemek M, Kağa S, Simşek N, et al. Antihyperglycemic and antioxidative
potential of Matricaria chamomilla L. in streptozotocin-induced diabetic
rats. Nat Med (Tokyo). 2008;62:284–93.
Matricaria chamomilla L. 1155

12. Cemek M, Yilmaz E, Büyükokuroğlu ME. Protective effect of Matricaria

chamomilla on ethanol-induced acute gastric mucosal injury in rats. Pharm
Biol. 2010;48:757–63.
13. Chen J, Lin H, Hu M. Metabolism of flavonoids via enteric recycling: role
of intestinal disposition. J Pharmacol Exp Ther. 2003;304:1228–35.
14. de Jong NW, Vermeulen AM, van Wijk RG, de Groot H. Occupational
allergy caused by flowers. Allergy. 1998;53:204–9.
15. de la Torre Morín F, Sánchez Machín I, García Robaina JC, et al. Clinical
cross-reactivity between Artemisia vulgaris and Matricaria chamomilla
(chamomile). J Investig Allergol Clin Immunol. 2001;11:118–22.
16. Della Loggia R, Tubaro A, Redaelli C. Evaluation of the activity on the
mouse CNS of several plant extracts and a combination of them. Riv
Neurol. 1981;51:297–310 (Italian).
17. European Pharmacopoeia. 5th ed. European directorate for the quality of
medicines of the Council of Europe. Strasbourg, France; 1996:1976–1977.
18. Fonseca FN, Tavares MF, Horvath C. Capillary electrochromatography of
selected phenolic compounds of Chamomilla recutita. J Chromatogr A.
2007;1154:390–9.
19. Foti C, Nettis E, Panebianco R, et al. Contact urticaria from Matricaria
chamomilla. Contact Derm. 2000;42:360–1.
20. Ganzera M, Schneider P, Stuppner H. Inhibitory effects of the essential oil
of chamomile (Matricaria recutita) and its major constituents on human
cytochrome P450 enzymes. Life Sci. 2006;78:856–61.
21. Gardiner P. Complementary, holistic, and integrative medicine: chamomile.
Pediatr Rev. 2007;28:16–8.
22. Gasic O, Lukic V, Nikolic A. Chemical study of Matricaria chamomilla
L-II. Fitoterapia. 1983;54:51–5.
23. Ghauri IG, Malih S, Ahmed I. Correct scientific name of “Babuna” used
widely as a drug in Unani system of medicine. Pak J Sci Ind Res. 1984;27:
20–3.
24. Glowania HJ, Raulin C, Swoboda M. Effect of chamomile on wound
healing—a clinical double-blind study. Z Hautkr. 1987;62:1267–71 (German).
25. Goes P, Dutra CS, Lisboa MR, et al. Clinical efficacy of a 1% Matricaria
chamomile L. mouthwash and 0.12% chlorhexidine for gingivitis control in
patients undergoing orthodontic treatment with fixed appliances. J Oral Sci.
2016;58:569–74.
26. Gomaa A, Hashem T, Mohamed M, Ashry E. Matricaria chamomilla
extract inhibits both development of morphine dependence and expression
of abstinence syndrome in rats. J Pharmacol Sci. 2003;92:50–5.
27. Gómez-Estrada H, Díaz-Castillo F, Franco-Ospina L, et al. Folk medicine in
the northern coast of Colombia: an overview. J Ethnobiol Ethnomed.
2011;7:27.
28. Gould L, Reddy CV, Gomprecht RF. Cardiac effects of chamomile tea.
J Clin Pharmacol. 1973;13:475–9.
1156 Matricaria chamomilla L.

29. Gowda TNV, Farooqi AA, Subbaiah T, Raju B. Influence of plant density,
nitrogen and phosphorus on growth, yield and essential oil content of chamomile
(Matricaria chamomilla Linn.). Indian Perfumers. 1991;35:168–72.
30. Hashempur MH, Lari ZN, Ghoreishi PS, et al. A pilot randomized
double-blind placebo-controlled trial on topical chamomile (Matricaria
chamomilla L.) oil for severe carpal tunnel syndrome. Complement Ther
Clin Pract. 2015;21:223–8.
31. Isaac O. Recent progress in chamomile research-medicines of plant origin in
modern therapy. 1st ed. Czecho-Slovakia: Prague Press; 1989.
32. Jarrahi M, Vafaei AA, Taherian AA, et al. Evaluation of topical Matricaria
chamomilla extract activity on linear incisional wound healing in albino
rats. Nat Prod Res. 2008;22:1197–202.
33. Jarrahi M, Vafaei AA, Taherian AA, et al. Evaluation of topical Matricaria
chamomilla extract activity on linear incisional wound healing in albino
rats. Nat Prod Res. 2010;24:697–702.
34. Jarrahi M. An experimental study of the effects of Matricaria chamomilla
extract on cutaneous burn wound healing in albino rats. Nat Prod Res. 2008;
22:422–7.
35. Kato A, Minoshima Y, Yamamoto J, et al. Protective effects of dietary
chamomile tea on diabetic complications. J Agric Food Chem. 2008;56:
8206–11.
36. Keefe JR, Mao JJ, Soeller I, Li QS, Amsterdam JD. Short-term open-label
chamomile (Matricaria chamomilla L.) therapy of moderate to severe
generalized anxiety disorder. Phytomedicine. 2016;23:1699–705.
37. Khayyal MT, El-Ghazaly MA, Kenawy SA, et al. Antiulcerogenic effect of
some gastrointestinally acting plant extracts and their combination.
Arzneimittelforschung. 2001;51:545–53.
38. Kobayashi Y, Takahashi R, Ogino F. Antipruritic effect of the single oral
administration of German chamomile flower extract and its combined effect
with antiallergic agents in ddY mice. J Ethnopharmacol. 2005;101:308–12.
39. Koch C, Reichling J, Kehm R, et al. Efficacy of anise oil, dwarf-pine oil and
chamomile oil against thymidine-kinase-positive and thymidine-kinase-
negative herpesviruses. J Pharm Pharmacol. 2008;60:1545–50.
40. Koch C, Reichling J, Schneele J, Schnitzler P. Inhibitory effect of essential
oils against herpes simplex virus type 2. Phytomedicine. 2008;15:71–8.
41. Krauskopf J, Adámková D. 3 Cases of simultaneous contact hypersensi-
tivity to wild chamomile (Matricaria chamomilla) and Frullania tamarisci.
Cesk Dermatol. 1975;50:299–302 (Czech).
42. Majerus PW, Tollefsen DM. Anticoagulant, thrombolytic, and antiplatelet
drugs. In: Hardman JG, Limbird LE, Molinoff PB, Gilman AG, editors.
Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th ed.
New York, NY: McGraw-Hill; 2001. p. 1519–38.
43. Mao JJ, Xie SX, Keefe JR, et al. Long-term chamomile (Matricaria
chamomilla L.) treatment for generalized anxiety disorder: a randomized
clinical trial. Phytomedicine. 2016;23:1735–42.
Matricaria chamomilla L. 1157

44. Marczal G, Petri G. Composition of essential oils from native Hungarian

camomile. Acta Pharm Hung. 1989;59:145–56.
45. McKay DL, Blumberg JB. A review of the bioactivity and potential health
benefits of chamomile tea (Matricaria recutita L.). Phytother Res. 2006;
20:519–30.
46. Mekonnen A, Yitayew B, Tesema A, Taddese S. In vitro antimicrobial activity
of essential oil of Thymus schimperi, Matricaria chamomilla, Eucalyptus
globulus, and Rosmarinus officinalis. Int J Microbiol. 2016;2016:9545693.
47. Memariani Z, Moeini R, Hamedi SS, Gorji N, Mozaffarpur SA. Medicinal
plants with antithrombotic property in Persian medicine: a mechanistic
review. J Thromb Thrombolysis. 2018;45:158–79.
48. Niederhofer H. Observational study: Matricaria chamomilla may improve
some symptoms of attention-deficit hyperactivity disorder. Phytomedicine.
2009;16:284–6.
49. Nikseresht M, Kamali AM, Rahimi HR, et al. The hydroalcoholic extract of
Matricaria chamomilla suppresses migration and invasion of human breast
cancer MDA-MB-468 and MCF-7 cell lines. Pharmacognosy Res. 2017;9:
87–95.
50. Nogueira JC, Diniz Mde F, Lima EO. In vitro antimicrobial activity of
plants in acute otitis externa. Braz J Otorhinolaryngol. 2008;74:118–24.
51. Ortiz MI, Cariño-Cortés R, Ponce-Monter HA, et al. Synergistic interaction
of Matricaria chamomilla extract with diclofenac and indomethacin on
carrageenan-induced paw inflammation in rats. Drug Dev Res. 2017;78:
360–7.
52. Ortiz MI, Fernández-Martínez E, Soria-Jasso LE, et al. Isolation, identifi-
cation and molecular docking as cyclooxygenase (COX) inhibitors of the
main constituents of Matricaria chamomilla L. extract and its synergistic
interaction with diclofenac on nociception and gastric damage in rats.
Biomed Pharmacother. 2016;78:248–56.
53. Ortiz-Bautista RJ, García-González LL, Ocádiz-González MA, et al. Matri-
caria chamomilla (aqueous extract) improves atopic dermatitis-like lesions
in a murine model. Rev Med Inst Mex Seguro Soc. 2017;55:587–93 (Article
in Spanish).
54. Padula LZ, Rondina RV, Coussio JD. Quantitative determination of essential
oil, total azulenes and chamazulene in German chamomile (Matricaria
chamomilla) cultivated in Argentina. Planta Med. 1976;30:273–80.
55. Petruľová-Poracká V, Repčák M, Vilková M, Imrich J. Coumarins of
Matricaria chamomilla L.: aglycones and glycosides. Food Chem. 2013;
141:54–9.
56. Prasanna R, Ashraf EA, Essam MA. Chamomile and oregano extracts
synergistically exhibit antihyperglycemic, antihyperlipidemic, and renal
protective effects in alloxan-induced diabetic rats. Can J Physiol Pharmacol.
2017;95:84–92.
57. Rahman H, Chandra A. Microbiologic evaluation of matricaria and chlorhex-
idine against E. faecalis and C. albicans. Indian J Dent. 2015;6:60–4.
1158 Matricaria chamomilla L.

58. Redaelli C, Formentini L, Santaniello E. Reversed-phase high-performance

liquid chromategraphy analysis of apigenin and its glucosides in flowers of
Matricaria chamomilla and chamomile extracts. Planta Med. 1981;42:288–92.
59. Rekka EA, Kourounakis AP, Kourounakis PN. Investigation of the effect of
chamazulene on lipid peroxidation and free radical processes. Res Commun
Mol Pathol Pharmacol. 1996;92:361–4.
60. Rodriguez-Fragoso L, Reyes-Esparza J, Burchiel SW, et al. Risks and
benefits of commonly used herbal medicines in Mexico. Toxicol Appl
Pharmacol. 2008;227:125–35.
61. Saghafi N, Rhkhshandeh H, Pourmoghadam N, et al. Effectiveness of
Matricaria chamomilla (chamomile) extract on pain control of cyclic
mastalgia: a double-blind randomised controlled trial. J Obstet Gynaecol.
2018;38:81–4.
62. Satyal P, Shrestha S, Setzer WN. Composition and bioactivities of an (e)-
b-farnesene chemotype of chamomile (Matricaria chamomilla) essential oil
from Nepal. Nat Prod Commun. 2015;10:1453–7.
63. Savikin K, Zdunić G, Menković N, et al. Ethnobotanical study on traditional
use of medicinal plants in southwestern Serbia, Zlatibor district. J Ethnophar-
macol. 2013;146:803–10.
64. Scala G. Acute, short-lasting rhinitis due to camomile-scented toilet paper in
patients allergic to Compositae. Int Arch Allergy Immunol. 2006;139:330–1.
65. Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla.
CMAJ. 2006;174:1281–2.
66. Sharifi F, Simbar M, Mojab F, Majd HA. Comparison of the effects of
Matricaria chamomila (chamomile) extract and mefenamic acid on the
intensity of premenstrual syndrome. Complement Ther Clin Pract. 2014;
20:81–8.
67. Shipochliev T, Dimitrov A, Aleksandrova E. Anti-inflammatory action of a
group of plant extracts. Vet Med Nauki. 1981;18:87–94 (Bulgarian).
68. Shipochliev T. Uterotonic action of extracts from a group of medicinal
plants [Bulgarian]. Veterinarnomeditsinski Nauki. 1981;18:94–8.
69. Shoara R, Hashempur MH, Ashraf A, et al. Efficacy and safety of topical
Matricaria chamomilla L. (chamomile) oil for knee osteoarthritis: a
randomized controlled clinical trial. Complement Ther Clin Pract. 2015;21:
181–7.
70. Silva NC, Barbosa L, Seito LN, Fernandes A Jr. Antimicrobial activity and
phytochemical analysis of crude extracts and essential oils from medicinal
plants. Nat Prod Res. 2012;26:1510–4.
71. Singh A. Cultivation of Matricaria chamomilla. In: Atal CK, Kapur BM,
editors. Cultivation and utilization of medicinal and aromatic plants.
Regional Research Laboratory (CSIR), Jammu-Tawi; 1982, p. 653–8.
72. Singh O, Khanam Z, Misra N, Srivastava MK. Chamomile (Matricaria
chamomilla L.): an overview. Pharmacogn Rev. 2011;5:82–95.
Matricaria chamomilla L. 1159

73. Soković M, Glamočlija J, Marin PD, Brkić D, van Griensven LJ. Antibac-
terial effects of the essential oils of commonly consumed medicinal herbs
using an in vitro model. Molecules. 2010;15:7532–46.
74. Srivastava JK, Gupta S. Antiproliferative and apoptotic effects of
chamomile extract in various human cancer cells. J Agric Food Chem. 2007;
55:9470–8.
75. Srivastava JK, Gupta S. Extraction, characterization, stability and biological
activity of flavonoids isolated from chamomile flowers. Mol Cell Pharma-
col. 2009;1:138.
76. Srivastava JK, Shankar E, Gupta S. Chamomile: a herbal medicine of the
past with bright future. Mol Med Rep. 2010;3:895–901.
77. Subiza J, Subiza JL, Hinojosa M, et al. Anaphylactic reaction after the
ingestion of chamomile tea: a study of cross-reactivity with other composite
pollens. J Allergy Clin Immunol. 1989;84:353–8.
78. Subiza J, Subiza JL, Marisa A, et al. Allergic conjunctivitis to chamomile
tea. Ann Allergy. 1990;65:127–32.
79. Suganda AG, Amoros M, Girre L, Fauconnier B. Inhibitory effects of some
crude and semipurified extracts of indigenous French plants on the multi-
plication of human herpesvirus 1 and poliovirus 2 in cell culture. J Nat Prod.
1983;46:626–32 (French).
80. Taddei-Bringas GA, Santillana-Macedo MA, Romero-Cancio JA, Romero-
Téllez MB. Acceptance and use of medicinal plants in family medicine.
Salud Publica Mex. 1999;41:216–20 (Spanish).
81. Tavakol HS, Farzad K, Fariba M, et al. Hepatoprotective effect of
Matricaria chamomilla L. in paraquat induced rat liver injury. Drug Res
(Stuttg). 2015;65:61–4.
82. Tolouee M, Alinezhad S, Saberi R, et al. Effect of Matricaria chamomilla
L. flower essential oil on the growth and ultrastructure of Aspergillus niger
van Tieghem. Int J Food Microbiol. 2010;139:127–33.
83. Tomić M, Popović V, Petrović S, et al. Antihyperalgesic and antiedematous
activities of bisabolol-oxides-rich matricaria oil in a rat model of inflamma-
tion. Phytother Res. 2014;28:759–66.
84. van Ketel WG. Allergy to Matricaria chamomilla. Contact Derm. 1987;
16:50–1.
85. Vilaginès P, Delaveau P, Vilaginès R. Inhibition of poliovirus replication by
an extract of Matricaria chamomilla (L). C R Acad Sci III. 1985;301:289–
94 (French).
86. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and cyto-
protective effects of selected Pakistani medicinal plants in Helicobacter
pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
87. Zanoli P, Avallone R, Baraldi M. Behavioral characterisation of the
flavonoids apigenin and chrysin. Fitoterapia. 2000;71 Suppl 1:S117–23.
Melia azedarach L.
(Meliaceae)

(Syns.: M. japonica G. Don.; M. sempevirens Swartz; M. toosendan Sieb. et Zucc.)

Abstract
It is an ornamental deciduous tree often found on street sides in warmer
countries, such as India, China, Indonesia, Iran, Syria, Guiana, Madagascar, and
Antilles. It is one of the most commonly used plants for various diseases,
especially skin diseases, by tribal people throughout the world. Fresh leaves
boiled in water are used by women to grow and strengthen their hair. The plant
has deobstruent, resolvent and alexipharmic properties. Flowers and leaves are
applied as poultice to relieve nervous headaches, and internally, the leaves’ juice
is administered as anthelmintic, antilithic, diuretic and emmenagogue, and is
thought to resolve cold swellings, and expel the humours which give rise to
them. The bark and leaves are used externally and internally in leprosy and
scrofula. A poultice of flowers kills lice and cures eruptions of the scalp. The
fruit is poisonous, but nevertheless is prescribed in leprosy and scrofula, and is
worn as a necklace to avert contagious diseases. The root bark was in the
secondary list of United States Pharmacopoeia as anthelmintic. The flowers,
leaves and fruits are recommended in Iranian traditional medicine as a remedy to
normalize temperament in elderly, for brain obstruction, intestinal worms,
kidney stones, leprosy, vitiligo, purulent sores, as an antidote to toxins, diuretic,
emmenagogue, hair growth inducer and to kill lice. A series of limonoids,
triterpenes, steroids and flavonoids and limonoid glycosides, including salannin,
meldenin, melianoninol, melianol, meliandiol, vanillin, vanillic acid, ring C-seco
limonoids, lignanes, and tirucallane triterpenoids have been isolated from the
fruits. Methanol flower extract healed S. aureus caused skin infection in rabbits,
an effect that was comparable to neomycin. The fruit extract showed higher
antibacterial effect against Gram-negative bacteria, while the leaf extract was
more effective on C. albicans. Various bark extracts have shown significant
in vitro antibacterial activities against a number of pathogenic bacteria. Fresh
green leaves extracts contain an antiviral factor that inhibits replication of several

© Springer Nature Switzerland AG 2020 1161

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_124
1162 Melia azedarach L.

animal viruses, protects neonatal mice against Tacaribe virus inoculation-

induced lethal encephalitis, and protects offspring of nursing mothers from
developing viral encephalitis.

Keywords






Agrión Azédarach Azufeifo Bakayen Chinaberry Dharek Haralshajr





Liàn Mahanimba Tespih ağacı

Vernaculars: Urd.: Bakayen; Hin.: Bakayen, Dharek, Ghora neem; San.: Arishta,
Himadruma, Mahanimba, Parvatanimba vraksha; Ben.: Bakarjam, Ghora-nim,
Hebbevu, Maha-nimb; Mal.: Malaivembu, Malai-veppam; Mar.: Bakana-nimb,
Goru-nima, Vilayati-nimb; Tam.: Kattu vembhu, Malaivembu, Malai-veppam;
Tel.: Konda-vepa, Nimbarun, Turukavepa, Vepa-manu; Ara.: Habb-ul-ban, Har-
alshajr, Harbeet, Shajratal-harra; Chi.: 楝树, Chuan lian, Chuan liang zi, Ku-lian,
Kulianpi, Liàn, Tz’u-hua shu; Cze.: Zederach hladký; Dan.: Paternostertræ; Dut.:
Galbessen, Kralenboom, Paternosterboom; Eng.: Cape syringa, Chinaberry tree,
Chinese um árbol de los rosarios brella tree, Persian lilac, Pride of India; Fre.:
Acacie d’Égypte, Arbre à chapelets, Azédarach, Cornier des Indes, Faux sycomore,
Laurier grec, Lilas de Perse, Lilas des Antilles, Lilas des Indes, Margousier,
Patenôtre; Ger.: Indischer zedrachbaum, Paternosterbaum, Persischer flieder,
Zedarachbaum; Ita.: Albero da rosari, Albero dei paternostri, Albero della pazienza,
Perlaro, Sicomoro falso; Jap.: Sendan; Kor.: Meol gu seul na mu; Maly.: Mul-
layvempu; Nep.: Bakenu, Khaibasi; Per.: Aaraatos takhak, Azad derakht, Taghak,
Tak, Zanzalakht; Pol.: Miotla; Por.: Agrião, Amargoseira, Amargoseira-bastarda,
Amargoseira-do-himaláia, Azufeifo, Árvore-santa, Árvore-dos-rosários, Azedar-
aque, Cinamomo, Falso-sicómoro, Jazmim-de-caiena (Br.), Lilás-das-índias, Mélia-
dos-himaláias, Sicómoro-bastardo; Spa.: Agriaz, Agrión, Árbol de cuentas, Árbol
del paraíso, Árbol de los rosarios, Bolillero, Canelo, Cinamomo, Falso sicomoro,
Jaboncillo, Lilo de China, Lilo de Persia, Jacinta; Swe.: Zedrak; Tag.: Bagalunga,
Balgango, Paraiso; Tha.: Hian, Lian, Lian bai yai; Tur.: Tesbih ağacı, Tespih
ağacı; Vie.: Cây xoan, Sâ dông.
Description: It is an ornamental deciduous tree often found on street sides in
warmer countries, such as India, China, Indonesia, Iran, Syria, Guiana, Madagascar,
and Antilles. It grows up to 20 m tall; leaves are long-petioled, two or three-times
compound alternate, pinnate, leaflets are dark green above and lighter green below,
opposite, glabrous when mature, oval-lanceolate, acuminate, margin irregularly
dentate. Flowers grow in clusters, are small, odoriferous, elongate, purple, 1 cm
long with five pale purple or liliac petals (April–May); fruit a glabrous drupe,
marble-sized, light-yellow at maturity and gradually becoming wrinkled and almost
white (September to October).LXXIX Fresh root-bark is thick and rather spongy, the
Melia azedarach L. 1163

Fig. 1 Melia azedarach, Leaves, Flowers and Berries, Anna Anichkova, WikimediaCommons;
Share Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Melia_azeda
rach_01434.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Melia azedarach, Berries, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Indian_Grey_Hornbill_(Ocyceros_birostris)_
eating_Bakain_(Melia_Azadirachta)_berries_at_Roorkee,_Uttarakhand_W_IMG_9016.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

external surface scabrous and warty, of a dark-brown color with irregular ridges; the
inner surface is white, taste acrid, nauseous, astringent and slightly bitter.XL It is
very similar to neem (Azadirachta indica) except that its fruit pulp is not bitter like
that of neem1 (Figs. 1 and 2).
Actions and Uses: It is one of the most commonly used plants for various diseases,
especially skin diseases, by tribal people throughout the world [1, 7, 35, 46]. Fresh
leaves boiled in water are used by women to grow and strengthen their hair.LXIX
The plant has deobstruent, resolvent and alexipharmic properties. Flowers and

1
Tayyab M: Personal Communication.
1164 Melia azedarach L.

leaves are applied as poultice to relieve nervous headaches, and internally, the
leaves’ juice is administered as anthelmintic, antilithic, diuretic and emmenagogue,
and is thought to resolve cold swellings, and expel the humours which give rise to
them. The bark and leaves are used externally and internally in leprosy and
scrofula.XXI,LXXXI,CV A poultice of flowers kills lice and cures eruptions of the scalp.
The fruit is poisonous, but nevertheless is prescribed in leprosy and scrofula, and is
worn as a necklace to avert contagious diseases. The root bark has a bitter, nauseous
taste and yields its virtues to boiling water. One hundred ten (110 g) of fresh bark
boiled in about a liter of water until the volume was reduced to half; the dose for a
child was one tablespoonful every three hours until the bowel and stomach were
cleared, or twice daily for several days followed by a cathartic.XL Unani physicians
describe it as blood purifier, analgesic, antihemorrhoidal, wound healer, anthel-
mintic, antipyretic for chronic fevers and antiperiodic; and use the leaves and bark in
diseases like leprosy and leucoderma, and externally the leaves decoction for
fomentation and poultice for boils and sores. Bark decoction is used to kill and expel
intestinal worms.LXXVII Externally, the seed oil is used as an antiseptic for indolent
sores and ulcers, for rheumatism and skin diseases such as ringworm and scabies,
and internally, the oil is used in malaria fever and leprosy [28], as antidiabetic,
spermicidal, and antifertility agent [44]. Leaves juice is also used in the Philippines
as anthelmintic, antilithic, diuretic and emmenagogue.CXVII The flowers, leaves and
fruits are recommended in Iranian traditional medicine as a remedy to normalize
temperament in elderly, for brain obstruction, intestinal worms, kidney stones,
leprosy, vitiligo, purulent sores, as an antidote to toxins, diuretic, emmenagogue, hair
growth inducer and to kill lice [25]. Fruit powder is insecticide against flies,LXXXVIII
and the root is considered anthelmintic by Ethiopians [31],LXXIX while the bark was
considered vermifuge in the Philippines.LVI In Indo-China, seeds were recommended
for typhoid fever and retention of urine [17]. The root bark was included in the official
Pharmacopoeias of the United States and Mexico.XV In traditional Chinese medicine,
it is used orally and topically as an antiparasitic and antifungal agent [40]; the roots
and barks of M. azedarach and M. toosendan are known as Kulianpi; and are
described as bitter, ‘cold’ and slightly toxic. They are indicated for the treatment of
ascariasis, oxyuriasis, erysipelas, rubella, scabies and tinea favosa. Powdered
Kulianpi, mixed with vinegar is used externally for scabies.XVIII
Phytoconstituents: A series of limonoids, triterpenes, steroids and flavonoids and
limonoid glycosides, including salannin, meldenin [49, 50], melianoninol, melianol,
melianone, meliandiol, vanillin, vanillic acid [22, 32, 48], 3-deacetyl-4′-demethyl-
salannin, 3-deacetyl-28-oxosalannin, and 1-detigloylohchinolal [38], ring C-seco
limonoids [63, 64], lignanes: pinoresinol, bis-epi-pinoresinol, hemicetal and diacid
[11], and tirucallane triterpenoids [2, 62] have been isolated from the fruits. Steroids
[56], triterpenoids and sterol [61], and flavonoid glycosides, including quercetin
3-O-rutinoside, kaempferol 3-O-robinobioside and kaempferol 3-O-rutinoside [30]
have been isolated from the leaves. Triterpenoids, steroids [21, 57]; limonoids, and
sesquiterpenoid [58] have also been isolated from the bark. Azadirachtin-type
Melia azedarach L. 1165

limonoids, meliacarpinin D, melianin B, highly cytotoxic sendanin-type limo-

noids [19, 20, 24, 52], and trichilin-type limonoids, including meliatoxin B1,
trichilin H, trichilin D and 1,12-diacetyltrichilin B [53] have been reported from the
root bark. Chemical constituents of the seeds include b-sitosterol, vanillin, benzoic
acid, vanillic acid, daucosterol, a-D-glucopyranose, limonoid glycosides: 6,11-diacetoxy-
7-oxo-14b,15b-epoxymeliacin (1,5-diene-3-O-b-D-glucopyranoside) and scopoletin,
melianol, meliacin, meliacarpin, meliartenin hydroxyl-3-methoxcinnamaldehyde and
(+-) pinoresinol [12, 13]. Kulianpi is reported to contain toosendanin, margoside,
kaempferol, resin, tannin, n-triacontane, b-sitosterol, and the triterpene kulinone. Seeds
yield 60% of a fatty oil comprising stearic, palmitic, lauric, valerianic, and butyric acids,
and traces of a sulfurated essential oil.XVIII
Pharmacology: Methanol flower extract healed S. aureus caused skin infection in
rabbits, an effect that was comparable to neomycin [47]. The fruit extract showed
higher antibacterial effect against Gram-negative bacteria, while the leaf extract was
more effective on C. albicans [37]. Various bark extracts have shown significant
antibacterial activities against a number of pathogenic bacteria [59]. Fresh green leaves
extracts contain an antiviral factor that inhibits replication of several animal viruses
[5, 18, 54, 55], protects neonatal mice against Tacaribe virus inoculation-induced
lethal encephalitis, and protects offspring of nursing mothers from developing viral
encephalitis [6]. Meliacine is identified as the compound possessing antiviral activity
that inhibits HSV-1 replication [3], exerts a strong antiviral action on corneal HSV-1
inoculation in mice [4, 10, 41], and has a protective effect against genital herpetic
infection in mice [39]. Hydroethanol leaf extract showed pediculicidal activity, killing
all lice faster than 1% permethrin [45]. Ethanol leaf extract also possesses significant
in vitro radical scavenging activity, and protects cells against oxidative damage [34].
Hexane leaf and seed extracts exhibited significant antipyretic activity in rabbits,
comparable to aspirin [23, 29].
Ethanol leaf extract in a dose of 100 mg/kg daily for 21-days caused complete
loss of libido in male rats [14], and ethanol root extract and its chloroform fraction
interrupted pregnancy in 75% of female rats [26, 27]. Seed extract also increases
preimplantation, post-implantation and total prenatal mortalities during early and
late stages of gestation in rats [33]. However, 50% ethanol and acetone extracts of
leaf showed no anti-implantation activity in rats [42]. The fruit extracts showed
activity against tapeworms and hookworms better than piperazine phosphate and
hexylresorcinol, respectively [51]. Methanol extracts of leaves and seeds are strong
larvicidal, pupicidal, adulticidal, and repellent to mosquito [15, 36], so is the
hydroalcohol extract of the leaves [43]. Aqueous leaf extract showed strong anti-
complementary activity, but did not affect phagocytic activity of PMNL [9].
Treatment of mice with the aqueous extract diminished production of antibodies
and inhibited graft vs host and delayed type hypersensitivity reactions [16].
Human A/Es, Allergy and Toxicity: Melia azedarach pollens have been reported
to cause respiratory allergy [8]. Eating fruits is described as a fatal poison; causes
vomiting, asphyxation, dizziness, coma and death. Consumption of six to nine
1166 Melia azedarach L.

fruits, 30–40 seeds, or 400 g of the bark are considered toxic to human in Chinese
medicine. Poisoning may cause gastrointestinal, cardiovascular, respiratory, or
neurological effects; general weakness, myalgia, numbness, and ptosis are the
presenting symptoms, which may occur within 4–6 h after ingestion [40]. Children
have died from eating berries and adults from making a brew out of leaves.
A resinous poison is in the fruit-pulp, but the amount varies with the strain and
growing conditions. Irritant activity of the plant is evident in causing vomiting
and constipation or diarrhea. Difficulty in breathing, weakening heart activity, and
nervous depression or excitement and paralysis may develop. Symptoms may occur
for several hours and death may take place within a few days.CXXXV The epiderm of
the bark is more toxic and should be discarded.
Animal Toxicity: Oral administration of aqueous and alcoholic extracts of flowers
and berries caused mild CNS depression but were nontoxic up to a dose of
1,500 mg/kg in mice and rats. Intravenously, LD50 of aqueous extract of berries in
mice and rats were 700 and 925 mg/kg, respectively; and of flowers extract 395 and
580 mg/kg, respectively [60].
Commentary: Despite many clinical uses in traditional medicines, no RCTs are
reported in the published literature, except from China on fresh Kulianpi decoction
being very effective against ascariasis infestation in both adults and children.XVIII

References
1. Abbasi AM, Khan MA, Ahmad M, et al. Ethnopharmacological application
of medicinal plants to cure skin diseases and in folk cosmetics among the
tribal communities of North-West Frontier Province, Pakistan. J Ethnophar-
macol. 2010;128:322–35.
2. Akihisa T, Pan X, Nakamura Y, et al. Limonoids from the fruits of Melia
azedarach and their cytotoxic activities. Phytochemistry. 2013;89:59–70.
3. Alché LE, Barquero AA, Sanjuan NA, Coto CE. An antiviral principle
present in a purified fraction from Melia azedarach L. leaf aqueous extract
restrains herpes simplex virus type 1 propagation. Phytother Res. 2002;
16:348–52.
4. Alché LE, Berra A, Veloso MJ, Coto CE. Treatment with meliacine, a plant
derived antiviral, prevents the development of herpetic stromal keratitis in
mice. J Med Virol. 2000;61:474–80.
5. Andrei GM, Coto CE, de Torres RA. Assays of cytotoxicity and antiviral
activity of crude and semipurified extracts of green leaves of Melia azedarach
L. Rev Argent Microbiol. 1985;17:187–94 (Spanish).
6. Andrei GM, Lampuri JS, Coto CE, de Torres RA. An antiviral factor from
Melia azedarach L. prevents Tacaribe virus encephalitis in mice. Experi-
entia. 1986;42:843–5.
Melia azedarach L. 1167

7. Ayyanar M, Ignacimuthu S. Ethnobotanical survey of medicinal plants

commonly used by Kani tribals in Tirunelveli hills of Western Ghats. India.
J Ethnopharmacol. 2011;134:851–64.
8. Baena-Cagnani CE, Patiño CM, Cáceres MS. Pollinosis: some immunologic
and regional considerations and the description of Melia azedarach
respiratory allergy. Allergol Immunopathol (Madr). 1987;15:393–7.
9. Benencia F, Courrèges MC, Massouh EJ, Coulombié FC. Effect of Melia
azedarach L. leaf extracts on human complement and polymorphonuclear
leukocytes. J Ethnopharmacol. 1994;41:53–7.
10. Bueno CA, Lombardi MG, Sales ME, Alché LE. A natural antiviral and
immunomodulatory compound with antiangiogenic properties. Microvasc
Res. 2012;84:235–41.
11. Cabral MM, Garcia ES, Kelecom A. Lignanes from the Brazilian Melia
azedarach, and their activity in Rhodnius prolixus (Hemiptera, Reduviidae).
Mem Inst Oswaldo Cruz. 1995;90:759–63.
12. Carpinella MC, Ferrayoli CG, Palacios SM. Antifungal synergistic effect of
scopoletin, a hydroxycoumarin isolated from Melia azedarach L. fruits.
J Agric Food Chem. 2005;53:2922–7.
13. Chong XT, Tian GZ, Cheng ZL, Yao QQ. Study on chemical constituents
of the seed of Melia azedarach L. Food Drug. 2009;11:30–1.
14. Choudhary DN, Singh JN, Verma SK, Singh BP. Antifertility effects of leaf
extracts of some plants in male rats. Indian J Exp Biol. 1990;28:714–6.
15. Coria C, Almiron W, Valladares G, et al. Larvicide and oviposition
deterrent effects of fruit and leaf extracts from Melia azedarach L. on Aedes
aegypti (L.) (Diptera: Culicidae). Bioresour Technol. 2008;99:3066–70.
16. Courrèges MC, Benencia F, Coulombié FC, Coto CE. In vitro and in vivo
activities of Melia azedarach L. aqueous leaf extracts on murine lympho-
cytes. Phytomedicine. 1998;5:47–53.
17. Crevost CH, Petelot A. Catalogue des Produits de l’indo-Chine (Plantas
Medicinales). Bull Econ IndoChine. 1934;37.
18. Descalzo AM, Coto C. Inhibition of the pseudorabies virus (Suis herpesvirus 1)
by an antiviral agent isolated from the leaves of Melia azedarach. Rev Argent
Microbiol. 1989;21:133–40 (Spanish).
19. Fukuyama Y, Nakaoka M, Yamamoto T, Takahashi H, Minami H.
Degraded and oxetane-bearing limonoids from the roots of Melia
azedarach. Chem Pharm Bull. 2006;54:1219–22.
20. Fukuyama Y, Ogawa M, Takahashi H, Minami H. Two new meliacarpinins
from the roots of Melia azedarach. Chem Pharm Bull (Tokyo). 2000;48:
301–3.
21. Ge JJ, Wang LT, Chen P, et al. Two new tetracyclic triterpenoids from the
barks of Melia azedarach. J Asian Nat Prod Res. 2016;18:20–5.
22. Han J, Lin WH, Xu RS, et al. Studies on the chemical constituents of Melia
azedarach L. Yao Xue Xue Bao. 1991;26:426–9 (Chinese).
23. Ikram M, Khattak SG, Gilani SN. Antipyretic studies on some indigenous
Pakistani medicinal plants: II. J Ethnopharmacol. 1987;19:185–92.
1168 Melia azedarach L.

24. Itokawa H, Qiao ZS, Hirobe C, Takeya K. Cytotoxic limonoids and

tetranortriterpenoids from Melia azedarach. Chem Pharm Bull (Tokyo).
1995;43:1171–5.
25. Jafari S, Saeidnia S, Hajimehdipoor H, et al. Cytotoxic evaluation of Melia
azedarach in comparison with, Azadirachta indica and its phytochemical
investigation. Daru. 2013;21:37.
26. Keshri G, Bajpai M, Lakshmi V, et al. Role of energy metabolism in the
pregnancy interceptive action of Ferula assafoetida and Melia azedarach
extracts in rat. Contraception. 2004;70:429–32.
27. Keshri G, Lakshmi V, Singh MM. Pregnancy interceptive activity of Melia
azedarach Linn. in adult female Sprague-Dawley rats. Contraception.
2003;68:303–6.
28. Khan AV, Ahmed QU, Mir MR, et al. Antibacterial efficacy of the seed
extracts of Melia azedarach against some hospital isolated human
pathogenic bacterial strains. Asian Pac J Trop Biomed. 2011;1:452–5.
29. Khattak SG, Gilani SN, Ikram M. Antipyretic studies on some indigenous
Pakistani medicinal plants. J Ethnopharmacol. 1985;14:45–51.
30. Kumazawa S, Kubota S, Yamamoto H, et al. Antiangiogenic activity of
flavonoids from Melia azedarach. Nat Prod Commun. 2013;12:1719–20.
31. Lemordant D. Contribution a l’ethnobotanique Ethiopienne. J Agric Trop
Bot Appl. 1971;18:1–35; 18:142–79.
32. Liu HB, Zhang CR, Dong SH, et al. Limonoids and triterpenoids from the
seeds of Melia azedarach. Chem Pharm Bull (Tokyo). 2011;59:1003–7.
33. Mandal R, Dhaliwal PK. Antifertility effect of Melia azedarach Linn.
(dharek) seed extract in female albino rats. Indian J Exp Biol. 2007;45:
853–60.
34. Marimuthu S, Balakrishnan P, Nair S. Phytochemical investigation and
radical scavenging activities of Melia azedarach and its DNA protective
effect in cultured lymphocytes. Pharm Biol. 2013;51:1331–40.
35. Mavundza EJ, Maharaj R, Finnie JF, et al. An ethnobotanical survey of
mosquito repellent plants in uMkhanyakude district, KwaZulu-Natal
province, South Africa. J Ethnopharmacol. 2011;137:1516–20.
36. Nathan SS, Savitha G, George DK, et al. Efficacy of Melia azedarach L.
extract on the malarial vector Anopheles stephensi Liston (Diptera:
Culicidae). Bioresour Technol. 2006;97:1316–23.
37. Orhan IE, Guner E, Ozcelik B, et al. Assessment of antimicrobial, insecticidal
and genotoxic effects of Melia azedarach L. (chinaberry) naturalized in
Anatolia. Int J Food Sci Nutr. 2012;63:560–5.
38. Pan X, Matsumoto M, Nakamura Y, et al. Three new and other limonoids
from the hexane extract of Melia azedarach fruits and their cytotoxic
activities. Chem Biodivers. 2014;11:987–1000.
39. Petrera E, Coto CE. Therapeutic effect of meliacine, an antiviral derived
from Melia azedarach L., in mice genital herpetic infection. Phytother Res.
2009;23:1771–7.
Melia azedarach L. 1169

40. Phua DH, Tsai WJ, Ger J, et al. Human Melia azedarach poisoning. Clin
Toxicol (Phila). 2008;46:1067–70.
41. Pifarré MP, Berra A, Coto CE, Alché LE. Therapeutic action of meliacine, a
plant-derived antiviral, on HSV-induced ocular disease in mice. Exp Eye
Res. 2002;75:327–34.
42. Prakash AO. Potentialities of some indigenous plants for antifertility
activity. Int J Crude Drug Res. 1986;24:19–24.
43. Prophiro JS, Rossi JC, Pedroso MF, et al. Leaf extracts of Melia azedarach
Linnaeus (Sapindales: Meliaceae) act as larvicide against Aedes aegypti
(Linnaeus, 1762) (Diptera: Culicidae). Rev Soc Bras Med Trop. 2008;41:
560–4.
44. Roop JK, Dhaliwal PK, Guraya SS. Extracts of Azadirachta indica and
Melia azedarach seeds inhibit folliculogenesis in albino rats. Braz J Med
Biol Res. 2005;38:943–7.
45. Rutkauskis JR, Jacomini D, Temponi LG, et al. Pediculicidal treatment
using ethanol and Melia azedarach L. Parasitol Res. 2015;114:2085–91.
46. Saikia AP, Ryakala VK, Sharma P, et al. Ethnobotany of medicinal plants
used by Assamese people for various skin ailments and cosmetics.
J Ethnopharmacol. 2006;106:149–57.
47. Saleem R, Ahmed SI, Shamim SM, et al. Antibacterial effect of Melia
azedarach flowers on rabbits. Phytother Res. 2002;16:762–4.
48. Shahwar D, Raza MA, Shafiq-Ur-Rehman, et al. An investigation of
phenolic compounds from plant sources as trypsin inhibitors. Nat Prod Res.
2012;26:1087–93.
49. Srivastava SD. Further constituent from the seeds of Melia azedarach.
Planta Med. 1987;53:100–1.
50. Srivastava SD. Limonoids from the seeds of Melia azedarach. J Nat Prod.
1986;49:56–61.
51. Szewczuk VD, Mongelli ER, Pomilio AB. In vitro anthelmintic activity of
Melia azedarach naturalized in Argentina. Phytother Res. 2006;20:993–6.
52. Takeya K, Qiao ZS, Hirobe C, Itokawa H. Cytotoxic azadirachtin-type
limonoids from Melia azedarach. Phytochemistry. 1996;42:709–12.
53. Takeya K, Quio ZS, Hirobe C, Itokawa H. Cytotoxic trichilin-type
limonoids from Melia azedarach. Bioorg Med Chem. 1996;4:1355–9.
54. Wachsman MB, Coto CE. Susceptibility of picornaviruses++ to an antiviral
of plant origin (meliacin). Rev Argent Microbiol. 1995;27:33–7 (Spanish).
55. Wachsman MB, Damonte EB, Coto CE, de Torres RA. Antiviral effects of
Melia azedarach L. leaves extracts on Sindbis virus-infected cells. Antiviral
Res. 1987;8:1–12.
56. Wu SB, Ji YP, Zhu JJ, et al. Steroids from the leaves of Chinese Melia
azedarach and their cytotoxic effects on human cancer cell lines. Steroids.
2009;74:761–5.
57. Wu SB, Bao QY, Wang WX, et al. Cytotoxic triterpenoids and steroids
from the bark of Melia azedarach. Planta Med. 2011;77:922–8.
1170 Melia azedarach L.

58. Yuan CM, Zhang Y, Tang GH, et al. Cytotoxic limonoids from Melia
azedarach. Planta Med. 2013;79:163–8.
59. Zahoor M, Ahmed M, Naz S, Ayaz M. Cytotoxic, antibacterial and anti-
oxidant activities of extracts of the bark of Melia azedarach (China Berry).
Nat Prod Res. 2015;29:1170–2.
60. Zakir-ur-Rahman, Ahmad S, Qureshi S, et al. Toxicological studies of Melia
azedarach L. (flowers and berries). Pak J Pharm Sci. 1991;4:153–8.
61. Zhang WM, Liu JQ, Peng XR, et al. Triterpenoids and sterols from the
leaves and twigs of Melia azedarach. Nat Prod Bioprospect. 2014;4:
157–62.
62. Zhou F, Ma X, Li Z, et al. Four new tirucallane triterpenoids from the fruits
of Melia azedarach and their cytotoxic activities. Chem Biodivers. 2016;
13:1738–46.
63. Zhou H, Hamazaki A, Fontana JD, et al. Cytotoxic limonoids from Brazilian
Melia azedarach. Chem Pharm Bull (Tokyo). 2005;53:1362–5.
64. Zhou H, Hamazaki A, Fontana JD, et al. New ring C-seco limonoids from
Brazilian Melia azedarach and their cytotoxic activity. J Nat Prod. 2004;67:
1544–7.
Melilotus officinalis (L.) Pall.
(Fabaceae/Leguminosae)

(Syns.: M. arenarius Grecescu; M. arvensis Wallr.; M. neglectus Ten.; M. pallidus

Ser.; M. alba Medik.)

Abstract
It is a legume species native to Persia and India, and naturalized in North
America, Africa and Australia. Muslim writers described two kinds of melilot,
but both plants look alike except for their fruits. Fruits of one are crescent-
shaped with small roundish seeds something like fenugreek, while the fruits of
other variety are much smaller and only slightly curved; both have fenugreek-
like odor. The best fruit for medicinal purposes is hard, yellowish-white, and
aromatic with yellow seeds. Greeks (Dioscorides) held the plant in high esteem
and the Muslim physicians followed their footstep. The pods with seeds (fruits)
are considered suppurative, and slightly astringent, and used as plaster to resolve
tumors and cold swellings. Fruits are described as anti-inflammatory, analgesic,
diuretic and emmenagogue, lactogenic, and strengthen internal organs, such as
liver and spleen. Head massage of its oil improves mental acuity, intelligence,
amnesia, and melancholy. It contains flavonoids and phenolic compounds with
iron-chelating and antioxidant properties. An extract of the plant containing
0.25% coumarin produced anti-inflammatory effect on turpentine oil-induced
inflammation in rabbits, and methanol extract exhibited significant antioxidant
activity and chelated iron overload in rats. Treatment with a coumarin extract for
six-months was effective in 79% Italian patients in reducing lymphedema
post-lymphadenectomy due to breast cancer, though with a modest decrease of
5% in upper arm circumference but improvement in symptoms in more than
50% patients. It has also been tested in combination with other drugs for patients
with chronic venous insufficiency.

Keywords





Ackerhonigklee Aspurk Cǎo mù xi Iklilul-malik Kokulu yonca Meliloto






Nakhuna Rohtomesikkä Sötväppling Yellow sweet clover

© Springer Nature Switzerland AG 2020 1171

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_125
1172 Melilotus officinalis (L.) Pall.

Vernaculars: Urd.: Iklilul-Malik, Nakhuna; Hin.: Aspurk; San.: Sprkka; Ben.:

Banpiring, Tairapa sano malya; Mar.: Aklula mulka, Iklilul-mulk; Ara.: Iklilul-
malik; Chi.: Cǎo mù xi; Dan.: Mark-stenkløver; Dut.: Akkerhoningklaver, Citro-
engele honingklaver; Eng.: Field melilot, Ribbed melilot, Yellow melilot, Yellow
sweet clover; Fin.: Rohtomesikkä; Fre.: Couronne royale, Mélilot des champs,
Mélilot jaune, Mélilot officinal, Trèfle des mouches; Ger.: Ackerhonigklee, Echter
honigklee, Echter steinklee, Gebräuchlicher honigklee, Gelber steinklee; Ita.:
Meliloto comune, Meliloto giallo, Trifoglio delle mosche; Jap.: Seiyou ebira hagi,
Shinagawahagi; Kor.: Me li lo teu; Per.: Giah-i-kaisar; Pol.: Nostrzyk zólty; Por.:
Meliloto, Meliloto-amarelo, Trevo-de-cheiro; Rus.: Donnik zheltyi; Spa.: Corona
de rey, Corona real, Coronilla real, Hierba de los caminos, Meliloto, Meliloto
amarillo, Meliloto de los campos, Trébol de olor amarillo, Trébol de San Juan;
Swe.: Sötväppling; Tur.: Kokulu yonca.
Description: It is a legume species native to Persia and India, and naturalized in
North America, Africa and Australia. Muslim writers described two kinds of
melilot, but both plants look alike except for their fruits. Fruits of one are crescent-
shaped with small roundish seeds something like fenugreek, while the fruits of
other variety are much smaller and only slightly curved; both have fenugreek-like
odor. The best fruit for medicinal purposes is hard, yellowish-white, and aromatic
with yellow seeds. Dymock et al.XL mentioned it as Trigonella uncata Boiss and
have described them as small sickle-shaped, greyish-yellow pods with a beak
slightly curved outward, distance from base to apex 12 mm, length of pod round the
curve about 25 mm; it is grooved on both sides, and divided by a central partition
into two cells, each of which contains a single row of small greyish-yellow
rhomboidal seeds, deeply notched on one side. Sweet clover honey is reputed for
medicinal properties, as the plant serves as a major source of nectar for domestic
honey bees as hives near sweet clover fields (Figs. 1 and 2).
Actions and Uses: Greeks (Dioscorides) held the plant in high esteem and the
Muslim physicians followed their footstep. The pods with seeds (fruits) are con-
sidered suppurative, and slightly astringent, and used as plaster to resolve tumors
and cold swellings.XL Fruits (temperament, hot 1° and dry 1°) are described as anti-
inflammatory, analgesic, diuretic and emmenagogue, lactogenic, and strengthen
internal organs, such as liver and spleen. Head massage of its oil improves mental
acuity, intelligence, amnesia, and melancholy.L,LXXVII Ibn Jazlah considered it a
good stomachic and useful in reducing swelling of joints.LIII Dried leaves and
flowers have been used in Europe for the treatment of arthritis, brachialgia, bron-
chitis, hemorrhoids, and rheumatism.XCIV In Indian traditional medicines it is used
in colic, diarrhea, dysmenorrhea, rheumatism, scrofula and syphilis, and its dihy-
drocoumarin is narcotic that initially stimulates the heart, followed by great
depression.LXXXI NadkarniCV mentioned its use in swellings and bowel complaints.
M. officinalis is approved for venous circulatory disorder in Europe since Nov.
2005 by the HMPC of the European Medicines Agency.
Melilotus officinalis (L.) Pall. 1173

Fig. 1 Melilotus officinalis, Plant, AnRo0002, WikimediaCommons; 1.0 Universal CC0 1.0,
https://commons.wikimedia.org/wiki/File:20140613Melilotus_officinalis.jpg; https://creativecommons.
org/publicdomain/zero/1.0/deed.en

Fig. 2 Melilotus officinalis, Bee on the Flower, Ivar Leidus, WikimediaCommons; ShareAlike
4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Bombus_lapidarius_-_
Melilotus_officinalis_-_Tallinn.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
1174 Melilotus officinalis (L.) Pall.

Phytoconstituents: It contains flavonoids and phenolic compounds with iron-

chelating and antioxidant properties [10]. a-tocopherol, b-carotene and fatty acids
[3], dihydrocoumarin [7], malilotus-saponin O2, soyasaponin I, astragaloside VIII,
wistariasaponin D [4], soyasapogenols B & E, coumarins, kaempferol, quercetin [5]
and melilotigenin [6] have been reported from aerial parts. Malilotus-saponin I was
isolated from the roots [11].
Pharmacology: An extract of the plant containing 0.25% coumarin produced
anti-inflammatory effect on turpentine oil-induced inflammation in rabbits [9], and
methanol extract exhibited significant antioxidant activity and chelated iron over-
load in rats [10]. Pretreatment with M. officinalis extract significantly decreased
oxidative stress and restricted brain infract volume and neurological deficit in rats
with acute cerebral ischemia [13].
Clinical Studies: Treatment with a coumarin extract for six-months was effective
in 79% Italian patients in reducing lymphedema post-lymphadenectomy due to
breast cancer, though with a modest decrease of 5% in upper arm circumference but
improvement in symptoms in more than 50% patients [8]. It has also been tested in
combination with other drugs for patients with chronic venous insufficiency [1, 2].
In an earlier study, 76 Italian patients with lymphedema of lower limbs treated daily
for 6–8-weeks with coumarin (60 mg), gingko biloba (40 mg) and melilotus
(40 mg) showed very significant improvement both in functional symptoms and
physical signs of edema and episodes of infection [12].
Human A/Es, Allergy and Toxicity: In humans, a nonspecific harm to testes has
been described.LXXVII Also, doses of 2–4 g may cause nausea, giddiness, depression,
vomiting and drowsiness.XL
Animal Toxicity: In dogs, even 400–600 mg may cause great or even fatal
depression.XL
Commentary: Results of clinical studies in lymphedema and venous efficiency are
very encouraging, probably why it has been approved for venous circulatory dis-
order by the European Medicines Agency. The plant also holds promise for more
clinical studies in inflammatory conditions, and as an effective, safe and inexpen-
sive iron chelator.

References
1. Cataldi A, Gasbarro V, Viaggi R, et al. Effectiveness of the combination of
alpha tocopherol, rutin, melilotus, and Centella asiatica in the treatment of
patients with chronic venous insufficiency. Minerva Cardioangiol. 2001;49:
159–63 (Italian).
2. Consoli A. Chronic venous insufficiency: an open trial of FLEBS Crema.
Minerva Cardioangiol. 2003;51:411–6 (Italian).
Melilotus officinalis (L.) Pall. 1175

3. Elgersma A, Søegaard K, Jensen SK. Fatty acids, a-tocopherol, b-carotene,

and lutein contents in forage legumes, forbs, and a grass-clover mixture.
J Agric Food Chem. 2013;61:11913–20.
4. Hirakawa T, Okawa M, Kinjo J, et al. A new oleanene glucuronide obtained
from the aerial parts of Melilotus officinalis. Chem Pharm Bull (Tokyo).
2000;48:286–7.
5. Kang SS, Lim C-H, Lee SY. Arch Pharm Res. 1987;10:9.
6. Kang SS, Woo WS. Melilotigenin, a new sapogenin from Melilotus offi-
cianalis. J Nat Prod. 1988;51:335–8.
7. Olaharski AJ, Rine J, Marshall BL, et al. The flavoring agent dihydro-
coumarin reverses epigenetic silencing and inhibits sirtuin deacetylases.
PLoS Genet. 2005;1:e77.
8. Pastura G, Mesiti M, Saitta M, et al. Lymphedema of the upper extremity in
patients operated for carcinoma of the breast: clinical experience with
coumarinic extract from Melilotus officinalis. Clin Ter. 1999;150:403–8
(Italian).
9. Pleşca-Manea L, Pârvu AE, Pârvu M, et al. Effects of Melilotus officinalis
on acute inflammation. Phytother Res. 2002;16:316–9.
10. Sheikh NA, Desai TR, Tirgar PR. Investigation into iron chelating and
antioxidant potential of Melilotus officinalis in iron dextran induced iron
overloaded Sprague Dawley rat model. Drug Res (Stuttg). 2016;66:618–27.
11. Udayama M, Kinjo J, Yoshida N, et al. A new oleanene glucuronide having
a branched-chain sugar from Melilotus officinalis. Chem Pharm Bull
(Tokyo). 1998;46:526–7.
12. Vettorello G, Cerreta G, Derwish A, et al. Contribution of a combination of
alpha and beta benzopyrones, flavonoids and natural terpenes in the
treatment of lymphedema of the lower limbs at the 2D stage of the surgical
classification. Minerva Cardioangiol. 1996;44:447–55 (Italian).
13. Zhao GC, Yuan YL, Chai FR, Ji FJ. Effect of Melilotus officinalis extract on
the apoptosis of brain tissues by altering cerebral thrombosis and inflam-
matory mediators in acute cerebral ischemia. Biomed Pharmacother.
2017;89:1346–52.
Melissa officinalis L.
(Lamiaceae)

Abstract
The plant is naturalized in many countries, and is widely cultivated in northern
Mediterranean region, Central Asia, China, Europe and North America for its
medicinal value as herbal tea. Imported variety from Persia was used for
hypochondriacal affections, and was also a domestic remedy in Europe for
febrile affections. It is refrigerant and cardiotonic and it protects heart from black
bile unlike any other drug. It is useful in anxiety and palpitation, and application
of its leaves’ water (juice) is beneficial in eczema and bilious boils; it attracts
honey bees. Its traditional uses have been recorded mostly in European
countries, Mediterranean region and the Middle East countries. Old European
reference books on medicinal herbs document its memory-improving properties,
and during the middle ages a recommendation by Paracelsus that the balm would
completely revivify a man and for ‘all complaints supposed to proceed from a
disordered state of the nervous system’ helped extend its widespread use
throughout Europe. Currently it is used in traditional European medicines to treat
insomnia, anxiety, psychiatric conditions, migraines, gastric disorders, hyper-
tension and bronchial afflictions, and as antibacterial agent, but more widely
used as a mild sedative and sleep aid. It is predominantly sold in combination
with other herbs, most often combined with Valeriana officinalis as sleep aid to
improve quality of poor sleepers. Its decoctions are also used as functional
beverages in Portugal. In Italian folk medicine it is used for nervous complaints,
lower abdominal disorders and for the treatment of Herpes simplex lesions. The
plant contains volatile compounds, triterpenoids, phenolic acids and flavonoids.
More than 100 chemical constituents have been identified in M. officinalis, the
chief ones include citral, linalool, geraniol, b-caryophyllene oxide, phenolic
acid, tannins, rosmarinic acid and caffeic acid. In double-blinded, balanced
crossover RCTs, healthy volunteers receiving a single low dose of a standardized
leaf extract showed significant improvement in mathematical processing speed,
without affecting accuracy, and a higher dose ameliorated negative mood effects

© Springer Nature Switzerland AG 2020 1177

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_126
1178 Melissa officinalis L.

of laboratory-induced psychological stress with significant increase in self-rated

calmness and reduced alertness.

Keywords






Acemotu Appiastro Badranjboya Baqlat-el-utrujiya Baume Citronmelisse





Citraria Lemon balm Touroudjan Xiāng fēng huā

Vernaculars: Urd.: Badranjboya; Alg.: Bararendjabouya, Tindjan, Touroudjan;

Ara.: Baqlat-el-utrujiya, Hashisha al namal, Munardah, Rihan al limun, Turijan;
Chi.: 香蜂花, Xiāng fēng huā; Cze.: Meduňka; Dan.: Citronmelisse, Hjertensfryd;
Dut.: Bijenkruid, Citroenkruid, Citroenmelisse; Eng.: Bee balm, Lemon balm,
Mountain balm; Fin.: Sitruunamelissa; Fre.: Baume, Herbe citron, Mélisse, Mélisse
citronelle, Mélisse officinale, Piment des abeilles; Ger.: Frauenkraut, Garten-
melisse, Herzkraut, Herztrost, Melisse, Mutterkraut, Zitronenmelisse; Gre.:
Melissa, Melissohorto, Melissophyllon, Melittaina; Hun.: Anyaméhfű, Citrom-
szagú mézfü, Macskaméz, Melissza, Mézfű, Orvosi citromfű; Ita.: Appiastro,
Cedronella, Citronella, Erba limona, Limoncina, Melissa vera; Jap.: Kousui hakka,
Remonbâmu, Seiyou yama hakka; Kor.: Me ri sa, Re mon bam; Nor.: Sitron-
melisse; Per.: Badrangboya, Badranjboya, Farandj moschk; Pol.: Melisa lekarska;
Por.: Anafes, Chá-da-frança, Cidreira, Citronela-menor, Coroa-de-rei, Erva-
cidreira, Limonete; Rus.: Limonnik, Melissa lekarstvennaia; Spa.: Albedarumbre,
Apiastro, Balsamito major, Cedrón, Cidronela, Citraria, Hierba limonera, Hoja de
limón, Limoncillo, Melisa, Pasto de abejas, Té de calazo, Tolongina, Torongil,
Toronjil cidrado, Toronjil de limón, Toronjiña abejera; Swe.: Citronmeliss, Hjär-
tansfröjd, Melissört; Tur.: Acemotu, Kovan otu, Limon nanesi, Limon otu, Melisa
otu, Oğulotu.
Description: The plant is naturalized in many countries, and is widely cultivated in
northern Mediterranean region, Central Asia, China, Europe and North America for
its medicinal value as herbal tea. There is a dispute in the identity of what is known
as Badranjboya in India. It was imported into India from Persia. Dymock et al.XL
mentioned it as Melissa officinalis, the Apiastrum of Dioscorides and Theophrastus;
the ‘Balm Gentle of our gardens loved by bees.’ Their description of the plant is
reproduced here: “calyx striated, 5-fid, and not colored; seeds four, naked, brown,
3-angled, nearly smooth, a white patch on each side of the hilum; flowers in axillary
clusters of about 6, upon a short peduncle; leaves ovate, margin deeply dentate,
somewhat hairy. The drug is much broken and consists chiefly of stem and fruits;
the former is quadrangular, much larger than that of Zúfah, of a purplish tint.”
When fresh it has a pleasant lemon odor, which is lost in the dried plant.XL Some
have described Nepeta cataria as badranjboya. Khory and KatrakLXXXI have also
described Melissa officinalis as badranjboya. M. officinalis and Nepeta cataria do
not share any features except that both plants have quadrangular stems and belong
Melissa officinalis L. 1179

to the same family, otherwise they look completely different plants. Both plants
have been described here under Badranjboya as the vernacular name, and both have
been comprehensively analyzed chemically (Figs. 1 and 2).

Fig. 1 Melissa officinalis, Plant, P. Wagner, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Melissa_officinalis1.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Melissa officinalis, Flowers, Gideaon Pisanty, WikimediaCommons; 3.0 Unported CC BY

3.0, https://commons.wikimedia.org/wiki/File:Melissa_officinalis_1.jpg; https://creativecommons.
org/licenses/by/3.0/deed.en
1180 Melissa officinalis L.

Actions and Uses: Imported variety from Persia was used for hypochondriacal
affections, and was also a domestic remedy in Europe for febrile affections.XL Ibn
al-BaitarLXIX said that Galen did not describe it in his book. It is refrigerant and
cardiotonic and it protects heart from black bile unlike any other drug. It is useful in
anxiety and palpitation, and application of its leaves’ water (juice) is beneficial in
eczema and bilious boils; it attracts honey bees. Its traditional uses have been
recorded mostly in European countries, Mediterranean region and the Middle East
countries [56]. Old European reference books on medicinal herbs document its
memory-improving properties [52, 53], and during the middle ages a recommen-
dation by Paracelsus that the balm would completely revivify a man and for ‘all
complaints supposed to proceed from a disordered state of the nervous system’
helped extend its widespread use throughout Europe.LV Currently it is used in
traditional European medicines to treat insomnia, anxiety, psychiatric conditions,
migraines, gastric disorders, hypertension and bronchial afflictions [24], and as
antibacterial agent, but more widely used as a mild sedative and sleep aid [37]. It is
predominantly sold in combination with other herbs, most often combined with
Valeriana officinalis as sleep aid to improve quality of poor sleepers [20]. Its
decoctions are also used as functional beverages in Portugal [14]. In Italian folk
medicine it is used for nervous complaints, lower abdominal disorders and for the
treatment of Herpes simplex lesions [42]. The plant is cultivated in some parts of
Iran, and its leaves are used in Iranian folk medicine as digestive, antispasmodic,
carminative, sedative, analgesic, tonic and diuretic, and for functional gastroin-
testinal disorders [45]. However, Joharchi and Amiri [31] reported that aerial parts
of Asperugo procumbens, Dracocephalum moldavica, Hymenocrater elegans,
Hymenocrater bituminosus, Hymenocrater calycinus, and Hymenocrater platyste-
gius are also sold in Iran as Badranjbuyeh. In Algerian traditional medicine, it is
used for the treatment of nervousness, headaches, indigestion, colic, cardiac failure
and depression [1]. Brazilians also use it to treat neurological disorders [51]. In
Unani medicine, aerial parts (temperament, hot 2° and dry 2°) are described as
refrigerant, cardiotonic, concoctive of black bile, blood purifier, resolvent, and
rubefacient, and used in the treatment of epilepsy, paralysis, palsy and to strengthen
heart; externally, it is used as paste in arthritis and mastitis.LXXVII
Phytoconstituents: The plant contains volatile compounds, triterpenoids, phenolic
acids and flavonoids [56]. More than 100 chemical constituents have been identified
in M. officinalis, the chief ones include citral, linalool, geraniol, b-caryophyllene
oxide, phenolic acid, tannins, rosmarinic acid and caffeic acid [2]. Flavonoids:
luteolin, luteolin 7-O-b-D-glucopyranoside, apigenin 7-O-b-D-glucopyranoside,
luteolin 7-O-b-D-glucuronopyranoside, luteolin 3′-O-b-D-glucuronopyranoside,
luteolin 7-O-b-D-glucopyranoside-3′O-b-D-glucuronopyranoside [50], luteolin 3′-
O-b-D-glucuronide [27], quadranoside III, salvianic acid A, and rosmarinic acid
[43], have been isolated from leaves. Six polyphenolic compounds: caftaric acid,
caffeic acid, p-cumaric acid, ferulic acid, luteolin and apigenin were identified in the
leaves of the plant grown in Romania [25], and the EO from leaves contained citral
(neral and geranial) (16.10%), citronellal (3.76%) and trans-caryophyllene (3.57%)
Melissa officinalis L. 1181

as the main components [24]. Spiridon et al. [60] reported major phenolic acids in
plants growing in Romania as ferulic, rosmarinic, p-coumaric and caffeic acid, and
predominant flavonoids in the form of glucosides as quercetin, apigenin and
kaempherol. Protocatechuyl aldehyde, serratagenic acid, vanillin, 2a,3b-dihydroxy-
urs-12-en-28-oic acid, ursolic acid, oleanolic acid, daucosterol, 2a,3b,23,29-
tetrahydroxyolean-12-en-28-oic acid-29-O-b-D-glucopyranoside, luteolin-7-O-b-D-
glucoside, b-stitosterol and palmitic acid from the leaves have also been isolated
[30]. A total of 106 compounds have been identified in the EO; predominant ones
are geranial and neral, which are comparable in oil from one- and two-year-old
plants. However, the contents of citronellal, geraniol, and geranyl acetate are much
higher in two-year-old plants than the oil from younger plants [47]. Thirty-six
compounds accounting for 94.10% of the total oil were identified in the EO of
M. officinalis grown in Algeria, with geranial (44.20%) and neral (30.20%) being
the major components [1]. Quinic acid, fructose, glucose and c-tocopherol, with
phenolic compounds (rosmarinic acid and lithospermic acid A) were reported as the
most abundant compounds in a functional beverage, that also shows significant
antimicrobial activity against P. aeruginosa and S. typhimurium, and the fungus,
P. funiculosum [14]. Rosmarinic acid content in commercial tinctures made from
dried plant material was reportedly significantly higher (2.96–22.18 mg/mL) than
in the tincture made from fresh plant (  0.92 mg/mL) [54]. Yield of fresh and dry
aerial parts and the oil yield from them is maximum if the plant was harvested at
160 days after planting in the Doon Valley of Uttarakhand state of India. Major
constituents of the EO were geranial (24.53%) and neral (18.80%), followed by
trans-caryophyllene (7.70%) [57].
Pharmacology: Crude extracts and isolated pure compounds exhibit numerous
pharmacological effects, out of which only anxiolytic, antiviral and antispasmodic
activities, as well as its effects on mood, cognition and memory have been validated
in clinical trials [56]. Hydroalcohol extract showed peripheral analgesic effect,
induced sleep in mice treated with a subhypnotic dose of pentobarbital and
potentiated pentobarbital-induced sleep [23, 59]. Methanol and ethanol extracts
produced anxiolytic effects [28, 61], and methanol extract inhibited rat brain GABA
transaminase; rosmarinic acid was identified as partly responsible for this effect
[10, 17, 28]. However, López et al. [40] reported MAO-A inhibiting activity of
methanol extract and no inhibition of AChE. Ethanol extract (i.p.) significantly
enhanced learning and memory of naïve rats, significantly ameliorated scopolamine-
induced learning deficit, and inhibited AChE activity in hippocampal region [49,
58]. Aqueous extract and rosmarinic acid exhibited substantial antidepression-like
activity in rats but the type of neurotransmitter involved in this effect could not be
determined [39]. Various studies have shown that M. officinalis possesses marked
antioxidant activity due to the presence of high amounts of flavonoids, rosmarinic
acid and gallic acid [45]. Aqueous, methanol, and ethanol extracts, and the EO,
all exhibited strong antioxidative activity against various pro-oxidation agents [41,
44, 51]. Ethanol leaf extract produced significant analgesic effect in several models
of chemical pain, through muscarinic and nicotinic receptors and the L-arginine-NO
1182 Melissa officinalis L.

pathway; the rosmarinic acid appears to be responsible for the antinociceptive effect
[24]; the EO also exhibits potential anti-inflammatory activity [12]. The EO very
highly inhibited in vitro activities of AChE and BChE; however, none of the single
components of the oil was as active as the oil [48]. The oil at low concentrations was
an effective hypoglycemic, enhanced glucose uptake and metabolism in the liver and
adipose tissue, and inhibited liver gluconeogenesis [16], and relieved hyperalgesia of
diabetic neuropathy in rats [26]. Hydroalcohol extract and EO were also cytotoxic to
several human cancer cell lines [29, 55].
Aqueous extract produced an entirely endothelium-dependent in vitro vasore-
laxation that was abolished by pretreatment with L-NAME, indicating involvement
of NO [21], and mildly protected against I/R-induced lethal ventricular arrhythmias
in rats [32, 34]; the hydroalcohol extract also protected against CaCl2-induced
cardiac arrhythmias in rats [3]. Aqueous extract administration to rats for a week
prolonged QRS interval, with no significant effect on RR interval, amplitude of
ECG waves, HR and BP [33]. The extract reduced serum TC, total lipids,
transaminases, and LPO in liver tissue, and increased GSH levels of hyperlipidemic
rats [11, 64].
Aqueous extract showed potent anti-HIV-1 and HIV-1 reverse transcriptase
inhibitory activity [63]. Virucidal and growth inhibitory effects of extracts and the
EO have been reported against HSV type-1 [7, 8, 19] and HSV-2 [6, 42]. Essential
oil exhibited significant growth inhibitory activity against S. aureus, B. subtilis,
L. monocytogenes, K. pneumonia, E. coli, P. aeruginosa, C. albicans, and
S. cerevisiae [1], against MDR strain of Sh. sonei, and significant antifungal activity
against Trichophyton species [44]. An extract also produced gastric antiulcer activity
in rats, with reduced acid output and increased mucin secretion, increase in PGE2
release and a decrease in LTs [38].
Clinical Studies: In double-blinded, balanced crossover RCTs, healthy volunteers
receiving a single low dose of a standardized leaf extract showed significant
improvement in mathematical processing speed, without affecting accuracy, and a
higher dose ameliorated negative mood effects of laboratory-induced psychological
stress with significant increase in self-rated calmness and reduced alertness [35, 36].
A single dose (1,600 mg) of encapsulated dried leaf powder also improved memory
performance and increased ‘calmness,’ but the speed of memory task performance
was decreased, and rapid visual information processing task was increased with
decreasing doses [37]. Iranian patients (65–80 years old) with mild to moderate
Alzheimer’s disease treated with an ethanol leaf extract, standardized to contain at
least 500 ug citral/ml, for 4-months had significant improvement in cognition, in a
double-blinded RCT [4]. However, there was no significant difference between
Melissa oil aromatherapy, donepezil or placebo on the Alzheimer’s-related agita-
tion, after 12-weeks treatment [13]. A lemon balm (Melissa) infusion prepared like
a tea and used for 30-days by radiology staff constantly exposed to low-dose
radiation, significantly improved plasma levels of antioxidant enzymes, and con-
spicuously reduced plasma DNA damage, myeloperoxidase, and LPO [65].
Treatment of Italian volunteers with mild-to-moderate anxiety disorder and sleep
Melissa officinalis L. 1183

disturbances, with a standardized commercial leaf extract Cyracos® for 15-days,

ameliorated anxiety-associated symptoms and insomnia, with 19/20 subjects
responding to treatment, and 14/20 achieving full remission [15]. An aqueous
lyophilized leaf extract (500 mg twice daily) administered for 14-days to 55 Iranian
volunteer adults suffering from benign palpitations, significantly reduced the fre-
quency of palpitation episodes and its associated anxiety [5]. Treatment of young
high school girls suffering from PMS, with an ‘essence’ of M. officinalis (600 mg
bid) for three consecutive menstrual cycles significantly reduced intensity of PMS
symptoms, compared to placebo [2]. In healthy Japanese volunteers, peak serum
concentration of rosmarinic acid reached after one hour of the extract administration
in fasted state; food intake delayed the time but the AUC increased [46]. Topical
application of a dried extract significantly protected German patients against HSV
infections, most effectively if initiated in the early stages of infection [62].
Mechanism of Action: AChE inhibitory activity, stimulation of the ACh and
GABAA receptors, as well as inhibition of matrix metalloproteinase-2 are the main
mechanisms proposed for the widely discussed neurological effects of this plant
[56]. Aqueous extract significantly inhibits in vitro GABA-transaminase activity
[9]. Rosmarinic acid is suggested to be responsible for antinociceptive effect [22].
Human A/Es, Allergy and Safety: A 30-year-old Turkish patient suffered from
symptoms of restlessness, tremor, distractibility, and sweating, after discontinuing
consumption of lemon balm tea, which the patient used to relieve anxiety symp-
toms, but increased it from one cup a day to four cups a day over a period of two
months (typical example of ‘little is good, more is better’) before abruptly dis-
continuing it. The case raises the question: does a regular consumption of lemon
balm tea cause dependence, that would precipitate withdrawal symptoms after
stopping its consumption? [18]. Rosmarinic acid supplementation does not affect
liver, kidney, or blood cell function parameters in healthy individuals [46].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: The frequency of use as a sleep aid and limited RCTs for other
uses, especially the improvement in learning and memory faculties warrant more
systematic clinical trials to establish dosage forms, dosing range, and provide
credibility for its use. Nonetheless, limited clinical trials and anecdotal patients’
testimonies who have used the herb point to a positive trend as an anxiolytic and
sleep aid.

References
1. Abdellatif F, Boudjella H, Zitouni A, Hassani A. Chemical composition and
antimicrobial activity of the essential oil from leaves of Algerian Melissa
officinalis L. EXCLI J. 2014;13:772–81.
1184 Melissa officinalis L.

2. Akbarzadeh M, Dehghani M, Moshfeghy Z, et al. Effect of Melissa

officinalis capsule on the intensity of premenstrual syndrome symptoms in
high school girl students. Nurs Midwifery Stud. 2015;4:e27001.
3. Akhondali Z, Dianat M, Radan M. Negative chronotropic and antidysrhyth-
mic effects of hydroalcoholic extract of lemon balm (Melissa officinalis L.) on
CaCl2-induced arrhythmias in rats. Electron Physician. 2015;7:971–6.
4. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis
extract in the treatment of patients with mild to moderate Alzheimer’s disease:
a double blind, randomised, placebo controlled trial. J Neurol Neurosurg
Psychiatry. 2003;74:863–6.
5. Alijaniha F, Naseri M, Afsharypuor S, et al. Heart palpitation relief with
Melissa officinalis leaf extract: double blind, randomized, placebo controlled
trial of efficacy and safety. J Ethnopharmacol. 2015;164:378–84.
6. Allahverdiyev A, Duran N, Ozguven M, Koltas S. Antiviral activity of the
volatile oils of Melissa officinalis L. against Herpes simplex virus type-2.
Phytomedicine. 2004;11:657–61.
7. Astani A, Navid MH, Schnitzler P. Attachment and penetration of
acyclovir-resistant Herpes simplex virus are inhibited by Melissa officinalis
extract. Phytother Res. 2014;28:1547–52.
8. Astani A, Reichling J, Schnitzler P. Melissa officinalis extract inhibits
attachment of Herpes simplex virus in vitro. Chemotherapy. 2012;58:70–7.
9. Awad R, Levac D, Cybulska P, et al. Effects of traditionally used anxiolytic
botanicals on enzymes of the gamma-aminobutyric acid (GABA) system.
Can J Physiol Pharmacol. 2007;85:933–42.
10. Awad R, Muhammad A, Durst T, Trudeau VL, Arnason JT. Bioassay-
guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro
measure of GABA transaminase activity. Phytother Res. 2009;23:1075–81.
11. Bolkent S, Yanardag R, Karabulut-Bulan O, Yesilyaprak B. Protective role of
Melissa officinalis L. extract on liver of hyperlipidemic rats: a morphological
and biochemical study. J Ethnopharmacol. 2005;99:391–8.
12. Bounihi A, Hajjaj G, Alnamer R, Cherrah Y, Zellou A. In vivo potential
anti-inflammatory activity of Melissa officinalis L. essential oil. Adv Phar-
macol Sci. 2013;2013:101759.
13. Burns A, Perry E, Holmes C, et al. A double-blind placebo-controlled randomized
trial of Melissa officinalis oil and donepezil for the treatment of agitation in
Alzheimer’s disease. Dement Geriatr Cogn Disord. 2011;31:158–64.
14. Carocho M, Barros L, Calhelha RC, et al. Melissa officinalis L. decoctions
as functional beverages: a bioactive approach and chemical characterization.
Food Funct. 2015;6:2240–8.
15. Cases J, Ibarra A, Feuillère N, Roller M, Sukkar SG. Pilot trial of Melissa
officinalis L. leaf extract in the treatment of volunteers suffering from mild-
to-moderate anxiety disorders and sleep disturbances. Med J Nutrition
Metab. 2011;4:211–8.
Melissa officinalis L. 1185

16. Chung MJ, Cho SY, Bhuiyan MJ, Kim KH, Lee SJ. Antidiabetic effects of
lemon balm (Melissa officinalis) essential oil on glucose- and lipid-regulating
enzymes in type 2 diabetic mice. Br J Nutr. 2010;104:180–8.
17. Dastmalchi K, Ollilainen V, Lackman P, et al. Acetylcholinesterase
inhibitory guided fractionation of Melissa officinalis L. Bioorg Med Chem.
2009;17:867–71.
18. Demirci K, Akgönül M, Demirdaş A, Akpınar A. Does Melissa officinalis
cause withdrawal or dependence? Med Arch. 2015;69:60–1.
19. Dimitrova Z, Dimov B, Manolova N, et al. Antiherpes effect of Melissa
officinalis L. extracts. Acta Microbiol Bulg. 1993;29:65–72.
20. Dressing H, Riemann D, Löw H, et al. Insomnia: are valerian/balm com-
binations of equal value to benzodiazepine? Therapiewoche. 1992;42:726–36.
21. Ersoy S, Orhan I, Turan NN, et al. Endothelium-dependent induction of
vasorelaxation by Melissa officinalis L. ssp. officinalis in rat isolated
thoracic aorta. Phytomedicine. 2008;15:1087–92.
22. Guginski G, Luiz AP, Silva MD, et al. Mechanisms involved in the
antinociception caused by ethanolic extract obtained from the leaves of
Melissa officinalis (lemon balm) in mice. Pharmacol Biochem Behav.
2009;93:10–16.
23. Hajhashemi V, Safaei A. Hypnotic effect of Coriandrum sativum, Ziziphus
jujuba, Lavandula angustifolia and Melissa officinalis extracts in mice. Res
Pharm Sci. 2015;10:477–84.
24. Hăncianu M, Aprotosoaie AC, Gille E, et al. Chemical composition and
in vitro antimicrobial activity of essential oil of Melissa officinalis L. from
Romania. Rev Med Chir Soc Med Nat Iasi. 2008;112:843–7.
25. Hanganu D, Vlase L, Filip L, et al. The study of some polyphenolic
compounds from Melissa officinalis L. (Lamiaceae). Rev Med Chir Soc
Med Nat Iasi. 2008;112:525–9.
26. Hasanein P, Riahi H. Antinociceptive and antihyperglycemic effects of
Melissa officinalis essential oil in an experimental model of diabetes. Med
Princ Pract. 2015;24:47–52.
27. Heitz A, Carnat A, Fraisse D, Carnat AP, Lamaison JL. Luteolin 3′-
glucuronide, the major flavonoid from Melissa officinalis subsp. officinalis.
Fitoterapia. 2000;71:201–2.
28. Ibarra A, Feuillere N, Roller M, Lesburgere E, Beracochea D. Effects of
chronic administration of Melissa officinalis L. extract on anxiety-like
reactivity and on circadian and exploratory activities in mice. Phytomedicine.
2010;17:397–403.
29. Jahanban-Esfahlan A, Modaeinama S, Abasi M, Abbasi MM, Jahanban-
Esfahlan R. Antiproliferative properties of Melissa officinalis in different
human cancer cells. Asian Pac J Cancer Prev. 2015;16:5703–7.
30. Ji ZY, Yang YX, Zhuang FF, Yan FL, Wang CH. Chemical constituents
from Melissa officinalis leaves. Zhong Yao Cai. 2015;38:510–3.
1186 Melissa officinalis L.

31. Joharchi MR, Amiri MS. Taxonomic evaluation of misidentification of

crude herbal drugs marketed in Iran. Avicenna J Phytomed. 2012;2:105–12.
32. Joukar S, Asadipour H, Sheibani M, Najafipour H, Dabiri S. The effects of
Melissa officinalis (Lemon Balm) pretreatment on the resistance of the heart
to myocardial injury. Pharm Biol. 2016;54:1005–13.
33. Joukar S, Asadipour H. Evaluation of Melissa officinalis (Lemon Balm)
effects on heart electrical system. Res Cardiovasc Med. 2015;4:e27013.
34. Joukar S, Zarisfi Z, Sepehri G, Bashiri A. Efficacy of Melissa officinalis in
suppressing ventricular arrhythmias following ischemia-reperfusion of the
heart: a comparison with amiodarone. Med Princ Pract. 2014;23:340–5.
35. Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced
stress in humans after acute administration of Melissa officinalis (Lemon
Balm). Psychosom Med. 2004;66:607–13.
36. Kennedy DO, Scholey AB, Tildesley NT, Perry EK, Wesnes KA.
Modulation of mood and cognitive performance following acute adminis-
tration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav.
2002;72:953–64.
37. Kennedy DO, Wake G, Savelev S, et al. Modulation of mood and cognitive
performance following acute administration of single doses of Melissa
officinalis (Lemon balm) with human CNS nicotinic and muscarinic
receptor-binding properties. Neuropsychopharmacology. 2003;28:1871–81.
38. Khayyal MT, El-Ghazaly MA, Kenawy SA, et al. Antiulcerogenic effect of
some gastrointestinally acting plant extracts and their combination.
Arzneimittelforschung. 2001;51:545–53.
39. Lin SH, Chou ML, Chen WC, et al. A medicinal herb, Melissa officinalis L.
ameliorates depressive-like behavior of rats in the forced swimming test via
regulating the serotonergic neurotransmitter. J Ethnopharmacol. 2015;175:
266–72.
40. López V, Martín S, Gómez-Serranillos MP, et al. Neuroprotective and
neurological properties of Melissa officinalis. Neurochem Res. 2009;34:
1955–61.
41. Martins EN, Pessano NT, Leal L, et al. Protective effect of Melissa
officinalis aqueous extract against Mn-induced oxidative stress in chroni-
cally exposed mice. Brain Res Bull. 2012;87:74–9.
42. Mazzanti G, Battinelli L, Pompeo C, et al. Inhibitory activity of Melissa
officinalis L. extract on Herpes simplex virus type 2 replication. Nat Prod
Res. 2008;22:1433–40.
43. Mencherini T, Picerno P, Scesa C, Aquino R. Triterpene, antioxidant, and
antimicrobial compounds from Melissa officinalis. J Nat Prod. 2007;70:
1889–94.
44. Mimica-Dukic N, Bozin B, Sokovic M, Simin N. Antimicrobial and antioxidant
activities of Melissa officinalis L. (Lamiaceae) essential oil. J Agric Food Chem.
2004;52:2485–9.
Melissa officinalis L. 1187

45. Miraj S, Rafieian-Kopaei, Kiani S. Melissa officinalis L.: a review study

with an antioxidant prospective. J Evid Based Complementary Altern Med.
2017;22:385–94.
46. Noguchi-Shinohara M, Ono K, Hamaguchi T, et al. Pharmacokinetics, safety
and tolerability of Melissa officinalis extract which contained rosmarinic
acid in healthy individuals: a randomized controlled trial. PLoS ONE. 2015;
10:e0126422.
47. Nurzyńska-Wierdak R, Bogucka-Kocka A, Szymczak G. Volatile con-
stituents of Melissa officinalis leaves determined by plant age. Nat Prod
Commun. 2014;9:703–6.
48. Orhan I, Kartal M, Kan Y, Sener B. Activity of essential oils and individual
components against acetyl- and butyrylcholinesterase. Z Naturforsch C.
2008;63:547–53.
49. Ozarowski M, Mikolajczak PL, Piasecka A, et al. Influence of the Melissa
officinalis leaf extract on long-term memory in scopolamine animal model
with assessment of mechanism of action. Evid Based Complement Alternat
Med. 2016;2016:9729818.
50. Patora J, Klimek B. Flavonoids from lemon balm (Melissa officinalis L.,
Lamiaceae). Acta Pol Pharm. 2002;59:139–43.
51. Pereira RP, Fachinetto R, de Souza Prestes A, et al. Antioxidant effects of
different extracts from Melissa officinalis, Matricaria recutita and Cymbo-
pogon citratus. Neurochem Res. 2009;34:973–83.
52. Perry EK, Pickering AT, Wang WW, et al. Medicinal plants and Alzheimer’s
disease: from ethnobotany to phytotherapy. J Pharm Pharmacol. 1999;51:
527–34.
53. Perry EK, Pickering AT, Wang WW, et al. Medicinal plants and Alzheimer’s
disease: integrating ethnobotanical and contemporary scientific evidence.
J Altern Complement Med. 1998;4:419–28.
54. Sanchez-Medina A, Etheridge CJ, Hawkes GE, et al. Comparison of rosmarinic
acid content in commercial tinctures produced from fresh and dried lemon
balm (Melissa officinalis). J Pharm Pharm Sci. 2007;10:455–63.
55. Saraydin SU, Tuncer E, Tepe B, et al. Antitumoral effects of Melissa
officinalis on breast cancer in vitro and in vivo. Asian Pac J Cancer Prev.
2012;13:2765–70.
56. Shakeri A, Sahebkar A, Javadi B. Melissa officinalis L.—a review of its
traditional uses, phytochemistry and pharmacology. J Ethnopharmacol.
2016;188:204–28.
57. Singh S, Haider SZ, Chauhan NK, et al. Effect of time of harvesting on yield
and quality of Melissa officinalis L. in Doon Valley. India. Indian J Pharm
Sci. 2014;76:449–52.
58. Soodi M, Naghdi N, Hajimehdipoor H, Choopani S, Sahraei E. Memory-
improving activity of Melissa officinalis extract in naïve and scopolamine-
treated rats. Res Pharm Sci. 2014;9:107–14.
1188 Melissa officinalis L.

59. Soulimani R, Fleurentin J, Mortier F, et al. Neurotropic action of the

hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med.
1991;57:105–9.
60. Spiridon I, Colceru S, Anghel N, et al. Antioxidant capacity and total
phenolic contents of oregano (Origanum vulgare), lavender (Lavandula
angustifolia) and lemon balm (Melissa officinalis) from Romania. Nat Prod
Res. 2011;25:1657–61.
61. Taiwo AE, Leite FB, Lucena GM, et al. Anxiolytic and antidepressant-like
effects of Melissa officinalis (lemon balm) extract in rats: influence of
administration and gender. Indian J Pharmacol. 2012;44:189–92.
62. Wölbling RH, Leonhardt K. Local therapy of herpes simplex with dried
extract from Melissa officinalis. Phytomedicine. 1994;1:25–31.
63. Yamasaki K, Nakano M, Kawahata T, et al. Anti-HIV-1 activity of herbs in
Labiatae. Biol Pharm Bul. 1998;21:829–33.
64. Zarei A, Changizi Ashtiyani S, Taheri S, Rasekh F. Comparison between
effects of different doses of Melissa officinalis and atorvastatin on the
activity of liver enzymes in hypercholesterolemia rats. Avicenna J Phy-
tomed. 2014;4:15–23.
65. Zeraatpishe A, Oryan S, Bagheri MH, et al. Effects of Melissa officinalis L.
on oxidative status and DNA damage in subjects exposed to long-term
low-dose ionizing radiation. Toxicol Ind Health. 2011;27:205–12.
Mesua ferrea L.
(Clusiaceae/Calophyllaceae)

(Syns.: M. coromandelina Wight; M. nagassarium (Burm.f.) Kosterm.; M. pedunculata

Wight; M. roxburghii Wight; M. speciosa Choisy; M. sclerophylla Thw.)

Abstract
A small tree that is indigenous to Sri Lanka, Himalayas, Assam, Bengal,
Andamans and Myanmar. It is claimed that if the anthers are soaked in water at
night, filtered in the morning and taken with honey for few days, it would stop
bleeding from piles and shrink them. It is also mentioned beneficial for cold
stomach and liver. Dried blossoms are prescribed by Hindu physicians as adjunct
to medicinal oils on account of their fragrance, astringent and stomachic
properties; powdered and mixed with ghee (purified butter) they are recom-
mended by most of the later Hindu writers in bleeding piles and burning of the
feet. Fruits contain an oleoresin and a very fragrant, pale-yellow color essential
oil. A series of 4-alkyl and 4-phenyl 5,7-dihydroxycoumarins from the blossoms
have been isolated. Methanol extract of the whole flower was bactericidal for
S. Typhimurium, and also inhibited growth of V. cholera and E. coli. Various
seed extracts also exhibited potent protective effect against formaldehyde and
adjuvant-induced arthritis in rats.

Keywords
Bois d’anis

Champeryah

Cobra’s saffron Kaliuas

Nagakesara






Nagasbaum Nágchampa Narae-kaiser Narmushk Rautaviiriö

Vernaculars: Urd.: Narmushk; Hin.: Gajapushpam, Nagakesara, Nagchampa,

Nagesar, Nagkesar; San.: Champeryah, Kanjalkama, Nãga, Nãgakesara, Nãgapushpa;
Ben.: Nagesar; Mal.: Churuli, Nagachampakam, Nagapoovu, Penaga, Vainavu, Veila;
Mar.: Nagchafa, Nágchampa, Thorlachampa; Tam.: Cheru-nagapu, Iravum, Irul-
maram, Mallaynangai, Nagecuram, Naka, Sirunagappoo, Tadinangu, Veillutta-
champakam; Tel.: Chikati manu, Nagakesara, Nagashappu; Ara.: Mushk-al-raman,
Narae-kaiser; Bur.: Gungen, Kant kaw, Kengan; Chi.: 莫拉, 喃木波朗; Eng.: Ceylon
ironwood, Cobra’s saffron, Indian rose chestnut; Fin.: Rautaviiriö; Fre.: Arbre de fer

© Springer Nature Switzerland AG 2020 1189

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_127
1190 Mesua ferrea L.

d’Annam, Bois d’anis, Bois de fer, Mesua naghas; Ger.: Nagasbaum; Per.: Narmushk;
Sin.: Diya na, Na’ in; Tag.: Kaliuas.
Description: Mesua ferrea is indigenous to Sri Lanka, Himalayas, Assam, Bengal,
Andamans and Myanmar. A small, 15 m high tree that grows near streams and in
marshes in the southwest of Sri Lanka, and is called Diya Na in Sinhalese language,
and is the National Tree of Sri Lanka. Young leaves are red to yellowish-pink on
slender, terete and glabrous branches. Bisexual flowers with four white petals are
4–7.5 cm in diameter, and contain numerous orange-yellow stamens, that are used
medicinally in Unani medicine; while in Ayurveda, the dried floral buds, dried
fruiting inflorescence of Cinnamomum wightii and dried fruits of Dillenia pentagyna
are all used as nagkesar in different regions of India [1] (Figs. 1, 2, 3 and 4).
Actions and Uses: It is claimed that if the anthers are soaked in water at night,
filtered in the morning and taken with honey for few days, it would stop bleeding
from piles and shrink them.LXXVII It is also mentioned beneficial for cold stomach
and liver.LXIX Dried blossoms are prescribed by Hindu physicians as adjunct to
medicinal oils on account of their fragrance, astringent and stomachic properties;
powdered and mixed with ghee (purified butter) they are recommended by most of
the later Hindu writers in bleeding piles and burning of the feet. Unani physicians use
the anthers (temperament, hot 2° and dry 2°) of the stamens and stigmas, and regard
them as stomach and intestinal anti-inflammatory, astringent, cardiac refrigerant,
sedative and beneficial for hemorrhoids, tonic for liver, stomach and intestines,
intestinal anthelmintic, and as sexual stimulant.LXXVII Bark is mildly astringent and

Fig. 1 Mesua ferrea, Tree, Southeast Sri Lanka, Benvda, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:MesuaFerrea_IronWood.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Mesua ferrea L. 1191

Fig. 2 Mesua ferrea, Flower, Earlysalad, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Mesua_ferrea_flower.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Mesua ferrea, Fertilized Flower, Earlysalad, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Base_of_the_Mesua_ferrea_
flower_having_dropped_most_of_the_petals.jpg; https://creativecommons.org/licenses/by-sa/3.0/
deed.en
1192 Mesua ferrea L.

Fig. 4 Mesua ferrea, Raw Fruit, Prasobhgs, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA 3.0, https://commons.wikimedia.org/wiki/File:%E0%B4%A8%E0%B4%BE%E0%B4%
97%E0%B4%AA%E0%B5%8D%E0%B4%AA%E0%B5%82%E0%B4%B5%E0%B5%81%E0%
B5%8D.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

feebly aromatic, but not bitter; and combined with ginger is used as a sudorific, wrote
Dymock et al.XL Dried blossoms, root and bark are aromatic, bitter and sudorific, while
the unripe fruits are aromatic and purgative; the dried blossoms or flower buds are used
in the treatment of dysentery, and the oil is applied to rheumatic joints.LXXXI,CV
In addition to treatment of bleeding piles, it is used in Ayurveda for fever and renal
diseases [2], and due to its antiseptic, anti-inflammatory, antiasthmatic and anti-
allergic activities, it is a component of several Ayurvedic immune-boosting formula-
tions [3, 4].
Phytoconstituents: Fruits contain an oleoresin and a very fragrant, pale-yellow
color essential oil.LXXXI A series of 4-alkyl and 4-phenyl 5,7-dihydroxycoumarins
from the blossoms have been isolated [9].
Pharmacology: Methanol extract of the whole flower was bactericidal for
S. Typhimurium [7], and also inhibited growth of V. cholera and E. coli [6]. Methanol
leaf extract exhibited significant antibacterial activity against S. aureus, Bacillus
spp., L. arabinosus, E. coli, Shigellae and Proteus spp [5]. The leaf and fruit extracts
also showed significant bacteriostatic activity against S. aureus [2]. Methanol root
bark extract possesses high antioxidant activity and exhibited antimicrobial activity
against Gram-positive bacteria, B. cereus, MSSA, and MRSA [8]. Various seed
Mesua ferrea L. 1193

extracts exhibit a potent protective effect against formaldehyde and adjuvant-induced

arthritis in rats [4].
Human A/Es, Allergy and Toxicity: Not suitable for people with hot tempera-
ment.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This plant has not been investigated enough for its pharmacological
effects based on its traditional uses. Also, there are no formal clinical studies reported
in mainstream journals.

References
1. Anandakumar A, Balasubramanian M, Muralidharan R. Nagakesara—a
comparative pharmacognosy. Anc Sci Life. 1986;5:263–8.
2. Aruldass CA, Marimuthu MM, Ramanathan S, Mansor SM, Murugaiyah V.
Effects of Mesua ferrea leaf and fruit extracts on growth and morphology of
Staphylococcus aureus. Microsc Microanal. 2013;19:254–60.
3. Chahar MK, Sanjaya Kumar DS, Lokesh T, Manohara KP. In-vivo antiox-
idant and immunomodulatory activity of mesuol isolated from Mesua ferrea
L. seed oil. Int Immunopharmacol. 2012;13:386–91.
4. Jalalpure SS, Mandavkar YD, Khalure PR, et al. Antiarthritic activity of
various extracts of Mesua ferrea Linn. seed. J Ethnopharmacol. 2011;138:
700–4.
5. Mazumder R, Dastidar SG, Basu SP, Mazumder A, Kumar S. Emergence of
Mesua ferrea Linn. leaf extract as a potent bactericide. Anc Sci Life.
2003;22:160–5.
6. Mazumder R, Dastidar SG, Basu SP, Mazumder A, Singh SK. Antibacterial
potentiality of Mesua ferrea Linn. flowers. Phytother Res. 2004;18:824–6.
7. Mazumder R, Dastidar SG, Basu SP, Mazumder A. Effect of Mesua ferrea
Linn. flower extract on Salmonella. Indian J Exp Biol. 2005;43:566–8.
8. Teh SS, Ee GC, Mah SH, et al. In vitro cytotoxic, antioxidant, and
antimicrobial activities of Mesua beccariana (Baill.) Kosterm., Mesua ferrea
Linn., and Mesua congestiflora extracts. Biomed Res Int. 2013;2013:517072.
9. Verotta L, Lovaglio E, Vidari G, et al. 4-Alkyl- and 4-phenylcoumarins from
Mesua ferrea as promising multidrug resistant antibacterials. Phytochemistry.
2004;65:2867–79.
Momordica charantia L.
(Cucurbitaceae)

Abstract
It is a climbing, nearly or quite smooth, annual vine that is widely grown in Asia
(especially Indian subcontinent), Africa, and in central Europe. Hindu physicians
in India used the whole plant combined with cinnamon, long pepper, rice and the
oil of Hydnocarpus wightiana as an external application in scabies and other
skin diseases. Fruits and leaves were used as anthelmintic, and externally applied
in leprosy. Leaves juice was also rubbed in burning sole of the feet, and with
black pepper was rubbed around the orbit as a cure for night blindness. Muslim
physicians found it useful in rheumatism and gout, and in diseases of the liver
and spleen, and as anthelmintic. Outer fruit coat and seeds, but not the fruit pulp,
are cathartic, producing gastroenteritis with vomiting and diarrhea, the
symptoms persisting for long periods. In Turkish folk medicine, mature fruits
are used externally for wound healing and orally for the treatment of gastric
ailments including peptic ulcers. It is part of the traditional diet of Okinawa
Island (Japan) residents, is used to manage diabetes by Mauritian population,
and a tea prepared from a wild variety, known as Cerasee is traditionally used
for the treatment of diabetes mellitus in the West Indies and Central America. In
Cuba and Puerto Rico, the plant is also used for the treatment of diabetes
mellitus, wounds refractive to other treatments, skin diseases, chronic stomach
ulcers, and for sterility in women. Whole plant is used in the management of
depressive illness in traditional African medicine. Fruits are a good source of
iron, calcium and phosphorus, contain substances with antidiabetic properties,
such as charantin (a ribosome-inactivating peptide), vicine, and polypeptide-P,
and other nonspecific bioactive components such as antioxidants. Lycopene is
the major carotinoid of ripe seeds, and its concentration increases about 100-fold
from the immature to the ripe stage. Drinking of homogenized water suspension
of the pulp significantly reduced both fasting and postprandial serum glucose
levels of NIDDM patients, and the fruit juice significantly improved glucose

© Springer Nature Switzerland AG 2020 1195

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_128
1196 Momordica charantia L.

tolerance of Sri Lankan NIDDM patients. Addition of powdered fruit to standard

therapy of newly diagnosed or poorly controlled type-2 diabetes patients with
HbA1c levels between 7 and 9%, lowered HbA1c, but no significant improve-
ment in mean FBS, TC, and body weight.

Keywords



Balsamagurk Bálsamo Balsempeer
Bitter melon
Concombre amer




Karavella Karela Ku gua Margose

Niga uri

Vernaculars: Urd.: Karela; Hin.: Karela; San.: Karavella, Sushavi; Ben.: Karala,
Korola, Karolla, Ucche (Bangladesh); Guj.: Karelân; Mal.: Kayppayka,
Pandi-pavel, Pavayka; Mar.: Karala, Karle; Tam.: Paagharkaai, Pākal, Pava-kai,
Pavakkapchedi; Tel.: Kaakarakaya, Kakara-chettu; Bur.: Kyethinkhathee; Chi.:
苦瓜, Ku gua, Lai pu tao, Liang gua; Dan.: Balsamaeble, Balsamagurk; Dut.:
Balsempeer, Springkomkommer; Eng.: African cucumber, Balsam apple, Balsam
pear, Bitter gourd, Bitter melon, Bitter squash; Fin.: Karvaskurkku; Fre.: Con-
combre amer, Margose, Margose amère, Momordique à feuilles de vigne, Pomme
de merveille; Ger.: Balsambirne, Bittere springgurke, Bitterer balsamkürbis; Ind.:
Paré, Paria, Peria katak, Peparé; Ita.: Momordica amara, Pomo balsam, Pomo
meraviglia; Jap.: Niga uri, Tsuru reishi; Nep.: Karelaa, Tito karelaa; Per.:
Khyarchamber talkh, Simahang; Por.: Melão-de-são-caetano, Saint Cajetan’s
melon (Br.); Sin.: Karavila, Karawila, Pakal, Pavakai; Spa.: Archucha, Balsamina,
Bálsamo, Calabaza africana, Cundeamor, Estropajo, Jaiva (Mexican); Swe.:
Bittergurka; Tag.: Ampalaya, Ampalia, Apalaya, Margoso; Tha.: Maha, Mara,
Phakha; Vie.: La khoqua (leaves).
Description: It is a climbing, nearly or quite smooth, annual vine that is widely
grown in Asia (especially Indian subcontinent), Africa, and in central Europe. It has
simple tendrils up to 20 cm long. Leaves are rounded, 2.5–10 cm in diameter, cut
nearly to the base into five or seven, oblong-ovate, variously toothed and lobed, and
heart-shaped at the base sections. Flowers are axillary; male flower is about 12 mm
long, and is peduncled with a rounded, green, about 1 cm long bract approximately
in the middle. Fruit, in cultivated form, is oblong, cylindric, 15–25 cm in length,
pointed at both ends, ribbed and wrinkled; while in wild forms, it is ovoid and
2–4 cm long. Seeds are oblong, compressed, 10–13 mm long and corrugated at the
margins (Figs. 1, 2 and 3).CXVII
Actions and Uses: Hindu physicians in India used the whole plant combined with
cinnamon, long pepper, rice and the oil of Hydnocarpus wightiana as an external
application in scabies and other skin diseases. Fruits and leaves were used as
anthelmintic, and externally applied in leprosy. One hundred ml of the leaves juice
used to be given in bilious affections as an emetic and purgative, alone or combined
with aromatics. Leaves juice was also rubbed in burning sole of the feet, and with
black pepper was rubbed around the orbit as a cure for night blindness. Muslim
physicians found it useful in rheumatism and gout, and in diseases of the liver and
Momordica charantia L. 1197

Fig. 1 Momordica charantia, Plant (Vine), H. Zell, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Momordica_charantia_001.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

spleen, and as anthelmintic.XL In Unani medicine, fruit and leaves (temperament,

hot 3° and dry 3°) are considered good for persons of phlegmatic constitution, and
are beneficial in intestinal worms, and phlegmatic diseases, such as rheumatism,
cold gout, inflammation of spleen, ascites, cough, and asthma.LXXVII Fruit pulp,
leaves juice and seeds are anthelmintic; fruit is also tonic and alterative, and used in
rheumatism, gout and diseases of the liver and spleen. Whole plant powder is used
for dusting over leprous and other intractable ulcers.LXXXI Outer fruit coat and
seeds, but not the fruit pulp, are cathartic, producing gastroenteritis with vomiting
and diarrhea, the symptoms persisting for long periods.CXXXV In Turkish folk
medicine, mature fruits are used externally for wound healing and orally for the
treatment of gastric ailments including peptic ulcers [49, 188]. It is part of the
traditional diet of Okinawa Island (Japan) residents [120], is used to manage dia-
betes by Mauritian population [103], and a tea prepared from a wild variety of
M. charantia, known as Cerasee is traditionally used for the treatment of diabetes
mellitus in the West Indies and Central America [18]. Diabetic patients in Pam-
panga, the Philippines, generally use bitter melon to manage their diabetes [146];
and the juice expressed from green fruits is used to treat chronic colitis and bacillary
dysentery. One teaspoonful of leaves juice is used daily for children’s cough. The
sap of the leaves is used as parasiticide and the fruit macerated in oil as a vulnerary.
In Cuba and Puerto Rico, the plant is used for the treatment of diabetes mellitus,
wounds refractive to other treatments, skin diseases, chronic stomach ulcers, and for
1198 Momordica charantia L.

Fig. 2 Momordica charantia, Fruit of Indian Variety, Flying Toaster, WikimediaCommons; 3.0
Unported CC BY 3.0, https://commons.wikimedia.org/wiki/File:Bittermelloncloseup.jpg; https://
creative commons.org/licenses/by/3.0/deed.en

Fig. 3 Momordica charantia, Fruits of Chinese Variety, Prof. Akbar, Original

sterility in women.LVI,CXVII It is one of the most frequently used medicinal plants

by the Caribs of Guatemala [56]. Whole plant is used in the management of
depressive illness in traditional African medicine [68]. Leaves are also one of the
most frequently used folk medicines for intestinal parasites by the population of
the Atlantic Coast of Colombia [57], and one of the most important local medici-
nal plants in Togo (West Africa), where it is extensively used in the treatment of
Momordica charantia L. 1199

gastrointestinal and viral diseases [22]. From the above accounts it appears that
initially this plant or any of its parts were not used for diabetes by organized
traditional medicines, including both the Unani and Ayurveda of India, as its use for
diabetes is mentioned only from Mauritius, the Philippines, West Indies, Central
America, Cuba and Puerto Rico.
Phytoconstituents: Fruits are a good source of iron, calcium and phosphorus,
contain substances with antidiabetic properties, such as charantin (a ribosome-
inactivating peptide) [132], vicine, and polypeptide-P, and other nonspecific bioac-
tive components such as antioxidants [81]. Indian variety (on dry basis) was found
to contain moisture 90.4%, total ash 7.31%, acid insoluble ash 0.97%, total alka-
loids 0.03%, free acids 8.11% and mucilage 6.25%. Ash contained Cl, SO4, PO4,
Fe, Mg, Na, and K; 5HT was detected in the acetone extract of fresh fruits. Fol-
lowing amino acids were found in both the dried and fresh fruits; glutamic acid,
alanine, b-alanine, phenylalanine, proline and a-aminobutyric acid. Toxic and
nontoxic lectins, momordin and momordica agglutinin have also been isolated [93].
Bitter gourd pulp of Indian variety contains higher amounts of phenolics and fla-
vonoids than the seeds; whereas the seeds contain higher amounts of total protein,
total fat and crude fiber than the pulp [131]. Fruits [82, 187], seeds [100], stems [90,
192], and leaves [192], contain cucurbitane-type triterpenoids [96]. From seeds,
bidesmoside triterpenoid saponins have also been isolated [99]. Leaves contain
triterpene glycosides, momordicins I and II that possess anthelmintic property [22].
5-HT [47], diosgenine and b-sitosterol have estrogenic properties, and act as
stimulants of uterus; whereas charantine, a sterol glycoside, causes uterine hem-
orrhage and abortion in rabbits [113], and inhibition of fetal development in rats
[180]. Cucurbitacine-like triterpenes also possess potent cytotoxic activity [50].
Cucurbitane-type triterpene, karavilagenins from dried fruits of Sri Lankan variety
[117], and triterpene glycosides, goyaglycosides [97, 114], momordicosides [89,
91, 97, 98, 114, 125], kuguaosides [64], taiwacin A and B [94], charantosides [11],
karavilosides [117], oleanane-type triterpene saponins (goyasaponins) [114], and
tetracyclic triterpenoids from fruits of Japanese M. charantia [79] have been iso-
lated. Vincine, mycose, momordicoside A and B were reported from the unripe
fruits of M. charantia grown in China [182].
Lycopene is the major carotinoid of ripe seeds, and its concentration increases
about 100-fold from the immature to the ripe stage [147]. Peptides with antilipolytic
and lipogenic activities have been isolated from decorticated seeds [122, 123], and
fruits [121]. A compound, initially identified as MAP 30 (Momordica Anti-HIV
Protein), isolated from seeds and fruits, exhibited inhibition of cell-free HIV-1
infection and replication [87], and antitumor activities [177]. A similar protein
(MRK29) with HIV-1 reverse transcriptase inhibitory activity was reported from
ripe fruits and seeds of Thai bitter gourd [72]. Trichosanthin, a-momorcharin and
b-momorcharin from seeds were identified as abortifacient proteins [189]. Other
compounds isolated from seeds include vacine, mycose, momorcharaside A and B
[193]. Seeds EO contained twenty-five components, with trans-nerolidol, apiole,
cis-dihydrocarveol and germacrene D being the major constituents [27]. Processing
1200 Momordica charantia L.

of bitter melon of Sri Lankan variety by sun drying, oven drying, and freeze drying,
decreased moisture content from 92 to 9.5–10.2%, while frying lowered moisture
content to 0.8% and increased lipid content from 3.6 to 67%; protein content and
momordicosides K and L remained unaffected by the treatments [48].
Pharmacology: Freeze-dried fruit powder supplemented diet for 6-weeks did not
significantly lower blood glucose in diabetic rats [137] and those fed cholesterol-
enriched diets, but produced a consistent decrease in serum glucose in rats fed
cholesterol-free diets [71]. Dried fruits in higher than 1g/kg dose to normal and
diabetic rabbits significantly lowered blood glucose [9], and fruit pulp juice caused
significant hypoglycemic effect in glucose-fed normal rats, but had no significant
effect in IDDM diabetic rats [13], whereas, Lin et al. [95] reported significant
decrease in fasting and postprandial serum glucose of diabetic mice after 21-days
treatment with fruit juice. Karunanayake et al. [74] also found no significant effect
on glucose tolerance after 30-days treatment of diabetic rats with the juice; whereas,
a significant increase in the number of b-cells in fruit juice-treated diabetic rats was
reported [7]. Water fruit decoction, though, significantly reduced FBG in normo-
glycemic [75], and hyperglycaemic animals [29], significantly reduced blood glu-
cose and improved glucose tolerance in diabetic rats, without increase in serum
insulin [85], prevented cataract formation in diabetic rats [162], reduced glycemic
response to both oral and intraperitoneal glucose, without altering insulin level in
normal mice, an indication of its effect independent of intestinal glucose absorption,
suggestive of extrapancreatic effect [45]; however, potently stimulated insulin
release from b-cell rich pancreatic islets isolated from obese-hyperglycemic mice
[178]. Maximum antihyperglycemic effect of water extract occurred at week 3 and
significant fall of 70% at the end of 4-months in alloxanized rats, whereas a 22%
decrease in plasma glucose occurred in STZ-diabetic mice [141], and completely
prevented development of cataract in alloxan dibetic rats [142]. Water macerated
fruit juice also highly significantly lowered FBG of diabetic rats, reduced oxidative
stress and increased levels of GSH and SOD of diabetic rats [30, 101], and sub-
stantially prevented hyperglycemia and hyperinsulinemia in high fructose-diet
fed rats [174]. Daily feeding of fruit (200 mg/kg) to diabetic mice for 40-days
significantly reduced plasma glucose, polyuria, and urinary albumin levels [59].
Two-weeks treatment of rats with fruit juice before induction of diabetes and
continued postdiabetes for three-weeks significantly reduced serum glucose, TC,
TGs, and insulin resistance, while significantly increasing serum insulin, HDL-C,
and total antioxidant capacity levels [102]. It also effectively ameliorated hyper-
glycemia, hyperleptinemia, hyperinsulinemia, and hypertriglyceridemia, reduced
levels of FFA, and reversed fructose diet-induced hypoadiponectinemia in rats
[156]. Water fruit extract did not affect blood glucose of normal KK-Ay mice, but
significantly lowered blood glucose and serum hyperinsulinemia of diabetic mice
after five-weeks of oral administration [111, 112], and 4-weeks treatment of dia-
betic rats caused a significant decrease in BP, TC and TGs levels [1], decreased
LPO [169], and improved antioxidant enzymes activities [168]. Water extract
powder of fresh unripe fruits reduced FBG by 48% of diabetic rats, comparable to
Momordica charantia L. 1201

glibenclamide [175]. Water fruits extract of Jamaican variety did not show hypo-
glycemic or antihyperglycemic activity but significantly improved glucose toler-
ance of normoglycaemic rats [28]. Freeze-dried juice with high fat-diet lowered
visceral fat mass, serum insulin and leptin, improved insulin resistance, but raised
serum FFA of rats [37]. The juice and alcohol extract significantly decreased serum
glucose in normal and diabetic rats, and significantly lowered serum urea, crea-
tinine, ALT, AST, ALP, TC and TGs in diabetic rats [2]. Whole plant extract also
significantly lowered blood glucose in normoglycemic and diabetic rats [129].
Oral ethanol fruit extract significantly lowered FBG of rats [31], and via i.p. route
of both normal and diabetic mice [77], and acetone extract normalized blood sugar
and cholesterol of diabetic rats after 15 to 30-days of oral treatment, and the effect
persisted for 15-days after discontinuation of the treatment [159, 160]. Ethanol fruit
extract also significantly lowered blood glucose close to normal fasting level in
alloxan diabetic rats [73], and a commercially standardized ethanol extract powder
treatment of diabetic rats markedly reduced blood glucose, HbA1c, TC, TGs, and
increased insulin level, comparable to glibenclamide [51], and improved insulin
sensitivity, glucose tolerance and insulin signaling in high-fat diet-induced insulin
resistance [161]. Treatment of neonatally-induced diabetic rats with ethanol fruit
pulp extract for 28-days doubled the pancreatic islet size, total b-cell area and the
number of b-cells [61]. Diabetic rabbits treated with granules of concentrated
ethanol fruit extract had significantly lowered serum glucose after 72 h [10]. In
diabetic rats, alcohol extract reduced plasma glucose by 26%, while metformin
reduced it by 40-50% [150]. A single dose of methanol extract of Ugandan variety
showed dose-dependent hypoglycemic effect in diabetic rats [127]. Methanol extract
of Thai bitter gourd fruit also decreased blood glucose of diabetic rats [63], and
protein extracted from fruit-pulp markedly decreased plasma glucose in both normal
and diabetic rats, and increased glucose uptake into myocytes and adipocytes [190].
Thirty-days treatment with methanol fruit extract significantly decreased TGs and
LDL, and increased HDL levels [33], of high fat diet-fed diabetic rats [36]. Water
seed extract also significantly reduced blood glucose, HbA1c, LDH, G-6-Pase,
fructose-1,6-bisphosphatase and glycogen phosphorylase, and increased levels of
Hb, glycogen and activities of hexokinase and glycogen synthase of diabetic rats
[152]. Water methanol seed extract and D-(+)-trehalose, isolated from them, sig-
nificantly inhibited a-glucosidase activity [108].
All parts of bitter melon reduced TC, TGs and LDL levels of hypercholes-
terolemic rats [119]. Methanol extract reduced body weight and serum cholesterol
in male Sprague-Dawley rats [185]. Treatment of diabetic rats with fruit extract
over a 10-week period reversed diabetes-induced increases in plasma nonesterified
cholesterol, TGs and phospholipids [8]. Bitter gourd oil in diet substantially
reduced free cholesterol, but no significant change in TC of rats [128]. Feeding diets
containing three Japanese varieties of bitter melon, did not appreciably affect food
intake or growth of rats; however, the Koimidori variety was most effective in
lowering hepatic TGs, compared to the Powerful-Reishi, and Hyakunari varieties
[153]. Administration of freeze-dried juice caused a decrease in tissue fat accu-
mulation, mediated, in part, by enhanced sympathetic activity and lipolysis [38].
1202 Momordica charantia L.

Diet of obese mice supplementated with bitter melon reduced body fat and insulin
level, and restored overproduction of energy and nutrient metabolism [23, 58], and
decreased serum lipids [107, 176], fasting glucose, insulin, and serum lipids, and
suppressed proinflammatory cytokines in high-fat diet fed rats [17]. Supplementing
bitter melon to high-fructose diet of rats during gestation and lactation could
offset the adverse effects on lipid metabolism and antioxidant status in adult
offspring [40].
Fruit extract possesses significant NO scavenging activity [69], and fruit extract
pretreatment prevented stress-induced LPO in rats, and increased levels of GSH and
activity of CAT [35]. Lyophilized fruit juice significantly reduced high-fat
diet-induced brain oxidative stress, and ameliorated BBB disruptive changes, and
neuroinflammatory markers in mice [120], and I/R induced neuronal injury in dia-
betic mice [104]. Pretreatment with ethanol fruit extract attenuated chronic unpre-
dictable stress-induced changes in the levels of monoamines in cortex, hypothalamus,
and hippocampus regions of brain, and plasma corticosterone level [78]. Methanol
extract also exhibited antidepressant and anxiolytic activities in mice [68]. Ethanol
fruit extract of Brazilian variety exhibited highly significant free radical scavenging
activity (FRSA) [149], and ethanol extract of Malaysian variety showed stronger
antioxidant activity than the water extract, with strong correlation to the presence of
total phenol contents [139]. The FRSA of the fruits was reportedly increased after
boiling, compared to the cold macerate [14]. Ng et al. [124] also reported improved
total antioxidant activity of Chinese bitter melon after boiling in water. Seed extract
for 30-days significantly decreased FBG, hepatic and renal TBARS and hydroper-
oxides, and increased GSH, SOD, CAT, GPx and GST in the liver and kidney of
diabetic rats [151].
Crude methanol fruits (of Tanzanian origin) extract significantly inhibited growth
of P. aeruginosa, E. coli, C. albicans and S. aureus [115]; Pseudomonas spp. were
the more susceptible food-borne pathogens [140]. Ethanol leaf extract of Puerto
Rican variety exhibited significant bactericidal activity against M. tuberculosis [52],
and Brazilian fruit ethanol extract potentiated the effect of aminoglycosides against
MRSA strain SA358 [43]. A 30 kDa protein isolated from seeds and fruits inhibited
cell-free HIV-1 infection and replication [86, 87], and HIV-1 integrase [86], and in
combination improved the efficacy of low pharmacological doses of weak anti-HIV
drugs, dexamethasone and indomethacin [25]; it was also more potent than acyclovir
against acyclovir-resistant strains of HSV-1 and HSV-2 [26]. Despite claims of
antimalarial activity, both water and ethanol extracts were ineffective in mice
infected with P. berghei [173]. Ethanol [60, 130] and methanol fruit extracts
exhibited gastric-ulcer protective effect, and inhibited standard strain and clinical
isolates of H. pylori [12, 188]. Water leaf extract also exhibited antidiarrheal
potential in castor oil-induced diarrhea [19]. Topical application of fruit powder
ointment, an olive oil extract and olive oil fruit macerate to wounds in rabbits [134],
in normal [138] and diabetic rats significantly enhanced wound healing [66, 67,
166]. Oral ethanol fruit extract exhibited analgesic and antipyretic effects in mice and
rats, respectively [133], significantly attenuated nerve transection-induced neuro-
pathic pain in rats [70], and water extract inhibited LPS-induced PGE2 production
Momordica charantia L. 1203

by a macrophage cell line [65]. Dietary bitter gourd may induce both intestinal and
systemic anti-inflammatory responses, as it decreases the number of lymphocytes,
increases the population of Th cells and NK cells, and increases the Ig production of
lymphocytes [105].
Topical application of whole fruit extract during peri-initiation and tumor pro-
motion stages significantly reduced tumor burden, cumulative number of papillo-
mas and the percent incidence of mice bearing papillomas [158]. Both fruits and
leaves extracts produced similar effects on skin papillomas in mice [4]; and fruit
extract on forestomach papillomagenesis [46], and the leaves extract improved
survival of mice inoculated with prostate cancer cells [135], and reversed MDR of
human cervical carcinoma cells due to modulation of P-glycoprotein [92]. Hot
water fruit extract significantly activated liver enzymes GST, GPx and CAT, that
are involved in biotransformation and detoxification of the carcinogen [54], and
effectively prevented spontaneous mammary tumorigenesis and uterine adeno-
myosis in SHN virgin mice [116]. Crude fruit extract was heat-stable and possessed
both cytostatic and cytotoxic activities to human leukemic lymphocytes without
affecting viability of normal human lymphocyte cells [164]. Co-treatment with
bitter melon extract and cisplatin counteracted cisplatin-resistance and markedly
attenuated growth of human immortalized epithelial ovarian cells and mouse
ovarian xenograft tumor [191]. Methanol extract exhibited apoptotic effect on
nasopharyngeal carcinoma, gastric adenocarcinoma, colorectal carcinoma, and lung
adenocarcinoma cell lines [88]. Water seed extract also showed marked cytotoxicity
toward human embryonic kidney and colon tumor cells [41]. While rats fed ground
freeze-dried Thai bitter melon were reported to increase AOM-induced colon
tumors in rats [83], dietary supplementation with seed oil significantly reduced the
incidence and multiplicity of AOM-induced colonic adenocarcinoma in rats [80].
Petroleum ether, benzene and alcohol seed extracts showed simultaneously
antispermatogenic antisteroidogenic and androgenic activities in different organs of
rats [118]; the alcohol extract being the most effective, and produced abnormal
morphological changes in sperms [55]. Methanol seed extract also produced
reversible histological alterations in prostate and testes of Sprague-Dawley rats
[24], whereas ethanol seed extract markedly reduced daily sperm production,
motility and viability, and suppressed seminal and plasma testosterone levels of
male Wistar rats [171]. Water leaf extract also significantly reduced both estrogen
and plasma progesterone levels of rats [3].
Clinical Studies: Drinking of homogenized water suspension of the pulp signifi-
cantly reduced both fasting and postprandial serum glucose levels of NIDDM
patients [5], and the fruit juice significantly improved glucose tolerance of Sri
Lankan NIDDM patients [179]. Single oral dose of freeze-dried fruit to healthy
overweight Canadian men prior to an oral glucose challenge, did not affect plasma
glucose/insulin levels, energy expenditure, and appetite scores, compared to con-
trols [76]. However, in Taiwanese adults of both sexes with MetS, supplementation
with lyophilized wild bitter-gourd powder, 4.8 g daily for three-months signifi-
cantly decreased MetS incidence rate [170]. A modest hypoglycemic effect and a
1204 Momordica charantia L.

significant reduction in fructosamine level was reported in Thai patients with type-2
diabetes after treatment with 2 g/day of bitter melon for four-weeks [53]. In a
double-blinded RCT at the Philippine General Hospital, involving 40 patients with
either newly diagnosed or poorly controlled type-2 diabetes with HbA1c levels
between 7% and 9%, addition of powdered fruit in capsules to standard therapy for
3-months lowered HbA1c, but no significant improvement in mean FBS, TC, and
body weight [44]. An insulin-like compound obtained from fruits as well as from
tissue cultures showed a consistent hypoglycemic effect in patients with diabetes
mellitus; the onset of action was within 30–60 min with the peak effect 6-hrs after
the administration of the dose [20].
Mechanism of Action: The extracts are suggested to lower blood glucose and
affect activities of enzymes of glucose metabolism, by depressing glucose synthesis
through inhibition of G-6-Pase and fructose-1,6-bisphosphatase and by enhancing
glucose oxidation through activation of G-6-PD [155], and increasing glycogen
synthesis [150]. Bitter-melon also increases expression of GLUT4 in skeletal
muscle [109], and prevents insulin resistence through modulation of NF-jB and
JNK pathways [186]. It significantly increases hepatic protein contents of AMPK,
which is a major cellular regulator of lipid and glucose metabolism, and reduces
expression of PEPCK and glucose production [157], repairs damaged b-cells,
increases insulin levels, enhances insulin sensitivity, and stimulates synthesis and
release of thyroid hormones [34]. Glutathione metabolism and GST distribution in
various tissues of diabetic rats is also suggested to play a role in the antihyper-
glycemic effect [143]. Major cucurbutanoids have shown in vivo hypoglycemic
effects [62]; triterpenoids, such as charantin, p-insulin and 9cis-11trans-13trans-
conjugated linolenic acid [148] are the potential hypoglycemic components and the
underlying mechanism of their action involves AMPK [39]. 9cis,11trans,13trans-
conjugated linolenic acid, isolated from wild bitter gourd, with higher concentration
in seeds than in the flesh, was identified as a PPARa activator [42]. Ethyl acetate
extract of whole fruit also activated PPARa, equivalent to a known standard ligand
of PPARa [32], and crude methanol and water extracts significantly inhibited
a-glucosidase activity [103]. Fruit juice also significantly reduced Na+- and K+-
dependent absorptions of glucose by the brush border membrane of jejunum, and
stimulated glucose uptake into skeletal muscles of diabetic rats [6]. Protein extract
exerted both insulin secretagogue and insulinomimetic activities to lower blood
glucose in vivo [190].
Decreased intestinal cholesterol absorption via inhibition of pancreatic choles-
terol esterase, and micelle formation may play a role in lowering cholesterol
level [163]. It also decreases intestinal reabsorption of bile acids, and increases
conversion of cholesterol to bile acids [107], decreases hepatic triacylglycerol
synthesis and enhances fatty acid oxidation [154]. Fruits and seeds were suggested to
contain components resembling insulin in inhibiting hormone-induced lipolysis
[181]. Antinociceptive effect reportedly critically involves PPAR-c agonistic, anti-
inflammatory, and antioxidative activities [70]. Its anticancer effects are also exerted
through activation of AMPK [191].
Momordica charantia L. 1205

Human A/Es, Allergy and Interactions with Antidiabetic Drugs: Bitter-melon

may cause additive hypoglycemic effects when used with other glucose-lowering
agents; adverse effects reported include headaches, and hypoglycemic coma and
convulsions in children [21]. Dose of chlorpropamide had to be reduced in a
Pakistani diabetic woman, who was being treated with diet and chlorpropamide, as
her severe glycosuria disappeared after eating a curry containing garlic and Karela
[16]. A 22-year-old Turkish man developed atrial fibrillation with rapid ventricular
response after consuming two tablespoonful of crushed bitter-gourd juice three
times a day for two days for dyspeptic symptoms; the patient recovered without
sequelae after stopping using the juice [49]. Treatment of NIDDM patients with
carbon tetrachloride and benzene soft extract plus half doses of metformin or
glibenclamide or both in combination for 7-days also caused greater hypoglycemia
than that caused by full doses of oral hypoglycemics [167].
Animal Toxicity: Supplementation of diet of normal adult rats with dried bitter-
gourd for 8-weeks did not affect food intake, growth and organ weights, or
hematological parameters, except a significant decrease in serum cholesterol levels
of rats receiving 0.5% bitter-gourd [136]. Water extract of unripe fruit administered
to rats during 2nd week of pregnancy caused multiple congenital malformations in
the litter [172]. Alpha-momorcharin, in overdose, may cause immunogenicity and
immunotoxicity, and organic liver lesions in animals [110]. LD50 of bitter-gourd
juice and alcohol extract by subcutaneous route in mice were reported to be 919 and
3,623 mg/kg, respectively [2]; whereas, ethanol fruit extract up to a dose of
4,000 mg/kg i.p. to mice was nontoxic, but repeated administration of 500 mg/kg
for 7-days caused nephrotoxicity [106]. Oral fruit juice and the seed extract to male
Sprague-Dawley rats, at a daily dose of 1 ml/100 g body weight for 30-days sig-
nificantly increased serum gamma-glutamyl transferase and ALP concentrations,
without significant histopathological changes in the liver [165].
CYP450 and Potential for Drug-Herb Interactions: Coadministration of
methanol extract and rosiglitazone in diabetic rats produced significantly higher
hypoglycemic effect, compared to either drug used alone [126]. Water extract in
combination with glimepiride potently produced hypoglycemic and antihyper-
glycemic effects without causing severe hypoglycemia in normal rats [183]. The
fruit extract in combination with sodium orthovanadate also exhibited pronounced
hypolipidemic and hypoglycemic effects in diabetic rats [184]. Rats fed diets
containing 12.5% Thai bitter-gourd fruits for 2-weeks strongly enhanced GST
activity 1.6-fold, and markedly reduced levels of most phase I reactions, whereas
Chinese bitter-gourd feeding had no effect on GST activity [84]. Karela fruit juice
did not consistently reverse effects of diabetes on drug-metabolizing enzymes in
rats [144]. However, the same authors reported karela-juice feeding reversing
effects of chronic diabetes on P450-dependent monooxygenase activities [145].
Appiah-Opong et al. [15] reported water extract of whole plant, leaf, stem and root
inhibiting recombinant human CYP1A2 and CYP2C9 expressed in E. coli.
1206 Momordica charantia L.

Commentary: Blood glucose and lipids lowering effects of bitter gourd have been
extensively investigated in animals; however, despite much anecdotal clinical
evidence and animal studies, blinded randomized clinical trials are lacking or the
results are inconsistent. Also, diversity in effects of different varieties, their parts
and extracts are factors to be resolved to establish the clinical validity in diabetes of
this common vegetable.

References
1. Abas R, Othman F, Thent ZC. Effect of Momordica charantia fruit extract
on vascular complication in type 1 diabetic rats. Excli J. 2015;14:179–89.
2. Abd El Sattar El Batran S, El-Gengaihi SE, El Shabrawy OA. Some
toxicological studies of Momordica charantia L. on albino rats in normal
and alloxan diabetic rats. J Ethnopharmacol. 2006;108:236–42.
3. Adewale OO, Oduyemi OI, Ayokunle O. Oral administration of leaf
extracts of Momordica charantia affect reproductive hormones of adult
female Wistar rats. Asian Pac J Trop Biomed. 2014;4 Suppl 1:S521–4.
4. Agrawal RC, Beohar T. Chemopreventive and anticarcinogenic effects of
Momordica charantia extract. Asian Pac J Cancer Prev. 2010;11:371–5.
5. Ahmad N, Hassan MR, Halder H, Bennoor KS. Effect of Momordica
charantia (Karolla) extracts on fasting and postprandial serum glucose
levels in NIDDM patients. Bangladesh Med Res Counc Bull. 1999;25:11–3.
6. Ahmed I, Adeghate E, Cummings E, et al. Beneficial effects and
mechanism of action of Momordica charantia juice in the treatment of
streptozotocin-induced diabetes mellitus in rat. Mol Cell Biochem. 2004;
261:63–70.
7. Ahmed I, Adeghate E, Sharma AK, et al. Effects of Momordica charantia
fruit juice on islet morphology in the pancreas of the streptozotocin-
diabetic rat. Diabetes Res Clin Pract. 1998;40:145–51.
8. Ahmed I, Lakhani MS, Gillett M, et al. Hypotriglyceridemic and
hypocholesterolemic effects of antidiabetic Momordica charantia (karela)
fruit extract in streptozotocin-induced diabetic rats. Diabetes Res Clin
Pract. 2001;51:155–61.
9. Akhtar MS, Athar MA, Yaqub M. Effect of Momordica charantia on
blood glucose level of normal and alloxan diabetic rabbits. Planta Med.
1981;42:205–12.
10. Akhtar N, Khan BA, Majid A, et al. Pharmaceutical and biopharmaceutical
evaluation of extracts from different plant parts of indigenous origin for
their hypoglycemic responses in rabbits. Acta Pol Pharm. 2011;68:919–25.
11. Akihisa T, Higo N, Tokuda H, et al. Cucurbitane-type triterpenoids from
the fruits of Momordica charantia and their cancer chemopreventive
effects. J Nat Prod. 2007;70:1233–9.
Momordica charantia L. 1207

12. Alam S, Asad M, Asdaq SM, Prasad VS. Antiulcer activity of methanolic
extract of Momordica charantia L. in rats. J Ethnopharmacol. 2009;123:
464–9.
13. Ali L, Khan AK, Mamun MI, et al. Studies on hypoglycemic effects of fruit
pulp, seed, and whole plant of Momordica charantia on normal and
diabetic model rats. Planta Med. 1993;59:408–12.
14. Ansari NM, Houlihan L, Hussain B, Pieroni A. Antioxidant activity of five
vegetables traditionally consumed by South-Asian migrants in Bradford,
Yorkshire, UK. Phytother Res. 2005;19:907–11.
15. Appiah-Opong R, Commandeur JN, Axson C, Vermeulen NP. Interactions
between cytochromes P450, glutathione S-transferases and Ghanaian
medicinal plants. Food Chem Toxicol. 2008;46:3598–603.
16. Aslam M, Stockley IH. Interaction between curry ingredient (Karela) and
drug (Chlorpropamide). Lancet. 1979;1:607.
17. Bai J, Zhu Y, Dong Y. Response of gut microbiota and inflammatory
status to bitter melon (Momordica charantia L.) in high fat diet induced
obese rats. J Ethnopharmacol. 2016;194:717–26.
18. Bailey CJ, Day C, Turner SL, Leatherdale BA. Cerasee, a traditional
treatment for diabetes. Studies in normal and streptozotocin diabetic mice.
Diabetes Res. 1985;2:81–4.
19. Bakare RI, Magbagbeola OA, Akinwande AI, Ebuehi OA. Effect of
aqueous leaf extract of Momordica charantia on intestinal enzyme
activities in diarrhoeagenic mice. Nig Q J Hosp Med. 2010;20:24–8.
20. Baldwa VS, Bhandari CM, Pangaria A, Coyal RK. Clinical trial in patients
with diabetes mellitus of an insulin-like compound obtained from plant
source. Upsala J Med Sci (Sweden). 1977;82:39–41.
21. Basch E, Gabardi S, Ulbricht C. Bitter melon (Momordica charantia): a
review of efficacy and safety. Am J Health Syst Pharm. 2003;60:356–9
(Review).
22. Beloin N, Gbeassor M, Akpagana K, et al. Ethnomedicinal uses of
Momordica charantia (Cucurbitaceae) in Togo and relation to its phyto-
chemistry and biological activity. J Ethnopharmacol. 2005;96:49–55.
23. Bian HX, Wu ZY, Bao B, et al. 1H NMR-based metabolic study reveals
the improvements of bitter melon (Momordica charantia) on energy
metabolism in diet-induced obese mouse. Pharm Biol. 2016;54:3103–12.
24. Boetse YO, Ikechukwu DF, Olugbenga OA, et al. Histomorphological
alterations in the prostate gland and epithelium of seminiferous tubule of
Sprague-Dawley rats treated with methanolic extract of Momordica
charantia Seeds. Iran J Med Sci. 2011;36:266–72.
25. Bourinbaiar AS, Lee-Huang S. Potentiation of anti-HIV activity of
anti-inflammatory drugs, dexamethasone and indomethacin, by MAP30,
the antiviral agent from bitter melon. Biochem Biophys Res Commun.
1995;208:779–85.
26. Bourinbaiar AS, Lee-Huang S. The activity of plant-derived antiretroviral
proteins MAP30 and GAP31 against herpes simplex virus in vitro.
Biochem Biophys Res Commun. 1996;219:923–9.
1208 Momordica charantia L.

27. Braca A, Siciliano T, D’Arrigo M, Germanò MP. Chemical composition

and antimicrobial activity of Momordica charantia seed essential oil.
Fitoterapia. 2008;79:123–5.
28. Burnett A, McKoy ML, Singh P. Investigation of the blood glucose
lowering potential of the Jamaican Momordica charantia (Cerasee) fruit in
Sprague-Dawley rats. West Indian Med J. 2015;64:315–9.
29. Cakici I, Hurmoğlu C, Tunçtan B, et al. Hypoglycaemic effect of
Momordica charantia extracts in normoglycaemic or cyproheptadine-
induced hyperglycaemic mice. J Ethnopharmacol. 1994;44:117–21.
30. Chandra A, Mahdi AA, Singh RK, et al. Effect of Indian herbal hypo-
glycemic agents on antioxidant capacity and trace elements content in
diabetic rats. J Med Food. 2008;11:506–12.
31. Chandrasekar B, Mukherjee B, Mukherjee SK. Blood sugar lowering
potentiality of selected Cucurbitaceae plants of Indian origin. Indian J Med
Res. 1989;90:300–5.
32. Chao CY, Huang CJ. Bitter gourd (Momordica charantia) extract activates
peroxisome proliferator-activated receptors and upregulates the expression
of the acyl CoA oxidase gene in H4IIEC3 hepatoma cells. J Biomed Sci.
2003;10:782–91.
33. Chaturvedi P, George S, Milinganyo M, Tripathi YB. Effect of Momordica
charantia on lipid profile and oral glucose tolerance in diabetic rats.
Phytother Res. 2004;18:954–6.
34. Chaturvedi P. Antidiabetic potentials of Momordica charantia: multiple
mechanisms behind the effects. J Med Food. 2012;15:101–7.
35. Chaturvedi P. Bitter melon protects against lipid peroxidation caused by
immobilization stress in albino rats. Int J Vitam Nutr Res. 2009;79:48–56.
36. Chaturvedi P. Role of Momordica charantia in maintaining the normal levels
of lipids and glucose in diabetic rats fed a high-fat and low-carbohydrate
diet. Br J Biomed Sci. 2005;62:124–6.
37. Chen Q, Chan LL, Li ET. Bitter melon (Momordica charantia) reduces
adiposity, lowers serum insulin and normalizes glucose tolerance in rats
fed a high fat diet. J Nutr. 2003;133:1088–93.
38. Chen Q, Li ET. Reduced adiposity in bitter melon (Momordica charantia)
fed rats is associated with lower tissue triglyceride and higher plasma
catecholamines. Br J Nutr. 2005;93:747–54.
39. Cheng HL, Huang HK, Chang CI, et al. A cell-based screening identifies
compounds from the stem of Momordica charantia that overcome insulin
resistance and activate AMP-activated protein kinase. J Agric Food Chem.
2008;56:6835–43.
40. Ching RH, Yeung LO, Tse IM, et al. Supplementation of bitter melon to
rats fed a high-fructose diet during gestation and lactation ameliorates
fructose-induced dyslipidemia and hepatic oxidative stress in male
offspring. J Nutr. 2011;141:1664–72.
Momordica charantia L. 1209

41. Chipps ES, Jayini R, Ando S, et al. Cytotoxicity analysis of active

components in bitter melon (Momordica charantia) seed extracts using
human embryonic kidney and colon tumor cells. Nat Prod Commun. 2012;
7:1203–8.
42. Chuang CY, Hsu C, Chao CY, et al. Fractionation and identification of 9c,
11t, 13t-conjugated linolenic acid as an activator of PPARalpha in bitter
gourd (Momordica charantia L.). J Biomed Sci. 2006;13:763–72.
43. Coutinho HD, Costa JG, Falcão-Silva VS, et al. Effect of Momordica
charantia L. in the resistance to aminoglycosides in methicilin-resistant
Staphylococcus aureus. Comp Immunol Microbiol Infect Dis. 2010;33:
467–71.
44. Dans AM, Villarruz MV, Jimeno CA, et al. The effect of Momordica
charantia capsule preparation on glycemic control in type 2 diabetes
mellitus needs further studies. J Clin Epidemiol. 2007;60:554–9.
45. Day C, Cartwright T, Provost J, Bailey CJ. Hypoglycaemic effect of
Momordica charantia extracts. Planta Med. 1990;56:426–9.
46. Deep G, Dasgupta T, Rao AR, Kale RK. Cancer preventive potential of
Momordica charantia L. against benzo(a)pyrene induced fore-stomach
tumourigenesis in murine model system. Indian J Exp Biol. 2004;42:319–22.
47. Dhalla NS, Gupta KC, Sastry MS, Malhotra CL. Chemical composition of
the fruit of Momordica charantia. Indian J Pharmacol. 1961;23:128–9.
48. Donya A, Hettiarachchy N, Liyanage R, et al. Effects of processing
methods on the proximate composition and momordicosides K and L
content of bitter melon vegetable. J Agric Food Chem. 2007;55:5827–33.
49. Erden I, Ordu S, Erden EC, Caglar SO. A case of atrial fibrillation due to
Momordica charantia (bitter melon). Ann Saudi Med. 2010;30:86–7.
50. Farnsworth NR, Bingel AS, Cordell GA, et al. Potential value of plants as
sources of new antifertility agents. II. J Pharmaceut Sci. 1975;64:717–53.
51. Fernandes NP, Lagishetty CV, Panda VS, Naik SR. An experimental
evaluation of the antidiabetic and antilipidemic properties of a standardized
Momordica charantia fruit extract. BMC Complement Altern Med.
2007;7:29.
52. Frame AD, Ríos-Olivares E, De Jesús L, et al. Plants from Puerto Rico
with anti-Mycobacterium tuberculosis properties. P R Health Sci J. 1998;
17:243–52.
53. Fuangchan A, Sonthisombat P, Seubnukarn T, et al. Hypoglycemic effect
of bitter melon compared with metformin in newly diagnosed type 2
diabetes patients. J Ethnopharmacol. 2011;134:422–8.
54. Ganguly C, De S, Das S. Prevention of carcinogen-induced mouse skin
papilloma by whole fruit aqueous extract of Momordica charantia. Eur J
Cancer Prev. 2000;9:283–8.
55. Girini MM, Ahamed RN, Aladakatti RH. Effect of graded doses of
Momordica charantia seed extract on rat sperm: scanning electron
microscope study. J Basic Clin Physiol Pharmacol. 2005;16:53–66.
1210 Momordica charantia L.

56. Girón LM, Freire V, Alonzo A, Cáceres A. Ethnobotanical survey of the

medicinal flora used by the Caribs of Guatemala. J Ethnopharmacol.
1991;34:173–87.
57. Gómez-Estrada H, Díaz-Castillo F, Franco-Ospina L, et al. Folk medicine
in the northern coast of Colombia: an overview. J Ethnobiol Ethnomed.
2011;7:27.
58. Gong ZG, Zhang J, Xu YJ. Metabolomics reveals that Momordica
charantia attenuates metabolic changes in experimental obesity. Phytother
Res. 2017;31:296–302.
59. Grover JK, Vats V, Rathi SS, Dawar R. Traditional Indian antidiabetic
plants attenuate progression of renal damage in streptozotocin induced
diabetic mice. J Ethnopharmacol. 2001;76:233–8.
60. Gürbüz I, Akyüz C, Yeşilada E, Sener B. Antiulcerogenic effect of
Momordica charantia L. fruits on various ulcer models in rats. J Ethnophar-
macol. 2000;71:77–82.
61. Hafizur RM, Kabir N, Chishti S. Modulation of pancreatic b-cells in
neonatally streptozotocin-induced type 2 diabetic rats by the ethanolic
extract of Momordica charantia fruit pulp. Nat Prod Res. 2011;25:353–67.
62. Harinantenaina L, Tanaka M, Takaoka S, et al. Momordica charantia
constituents and antidiabetic screening of the isolated major compounds.
Chem Pharm Bull (Tokyo). 2006;54:1017–21.
63. Higashino H, Suzuki A, Tanaka Y, Pootakham K. Hypoglycemic effects of
Siamese Momordica charantia and Phyllanthus urinaria extracts in
streptozotocin-induced diabetic rats (the 1st report). Nippon Yakurigaku
Zasshi. 1992;100:415–21 (Japanese).
64. Hsiao PC, Liaw CC, Hwang SY, et al. Antiproliferative and hypoglycemic
cucurbitane-type glycosides from the fruits of Momordica charantia.
J Agric Food Chem. 2013;61:2979–86.
65. Huang CJ, Wu MC. Differential effects of foods traditionally regarded as
‘heating’ and ‘cooling’ on prostaglandin E(2) production by a macrophage
cell line. J Biomed Sci. 2002;9:596–606.
66. Hussan F, Teoh SL, Muhamad N, Mazlan M, Latiff AA. Momordica
charantia ointment accelerates diabetic wound healing and enhances
transforming growth factor-b expression. J Wound Care. 2014;23:400,
402, 404–7.
67. İlhan M, Bolat IE, Süntar İ, et al. Topical application of olive oil macerate
of Momordica charantia L. promotes healing of excisional and incisional
wounds in rat buccal mucosa. Arch Oral Biol. 2015;60:1708–13.
68. Ishola IO, Akinyede AA, Sholarin AM. Antidepressant and anxiolytic
properties of the methanolic extract of Momordica charantia Linn.
(Cucurbitaceae) and its mechanism of action. Drug Res (Stuttg).
2014;64:368–76.
69. Jagetia GC, Baliga MS. The evaluation of nitric oxide scavenging activity
of certain Indian medicinal plants in vitro: a preliminary study. J Med
Food. 2004;7:343–8.
Momordica charantia L. 1211

70. Jain V, Pareek A, Paliwal N, et al. Antinociceptive and antiallodynic

effects of Momordica charantia L. in tibial and sural nerve transection-
induced neuropathic pain in rats. Nutr Neurosci. 2014;17:88–96.
71. Jayasooriya AP, Sakono M, Yukizaki C, et al. Effects of Momordica
charantia powder on serum glucose levels and various lipid parameters in
rats fed with cholesterol-free and cholesterol-enriched diets. J Ethnophar-
macol. 2000;72:331–6.
72. Jiratchariyakul W, Wiwat C, Vongsakul M, et al. HIV inhibitor from Thai
bitter gourd. Planta Med. 2001;67:350–3.
73. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
74. Karunanayake EH, Jeevathayaparan S, Tennekoon KH. Effect of
Momordica charantia fruit juice on streptozotocin-induced diabetes in
rats. J Ethnopharmacol. 1990;30:199–204.
75. Karunanayake EH, Welihinda J, Sirimanna SR, Sinnadorai G. Oral
hypoglycemic activity of some medicinal plants of Sri Lanka. J Ethnophar-
macol. 1984;11:223–31.
76. Kasbia GS, Arnason JT, Imbeault P. No effect of acute, single dose oral
administration of Momordica charantia Linn., on glycemia, energy expendi-
ture and appetite: a pilot study in nondiabetic overweight men. J Ethnophar-
macol. 2009;126:127–33.
77. Kavimani S, Ilango R, Gupta M, Majumdar UK. Hypoglycaemic action of
Momordica charantia in normal and diabetic mice. Anc Sci Life. 1997;
17:32–5.
78. Kavitha N, Babu SM, Rao ME. Influence of Momordica charantia on
oxidative stress-induced perturbations in brain monoamines and plasma
corticosterone in albino rats. Indian J Pharmacol. 2011;43:424–8.
79. Kimura Y, Akihisa T, Yuasa N, et al. Cucurbitane-type triterpenoids from
the fruit of Momordica charantia. J Nat Prod. 2005;68:807–9.
80. Kohno H, Yasui Y, Suzuki R, et al. Dietary seed oil rich in conjugated
linolenic acid from bitter melon inhibits azoxymethane-induced rat colon
carcinogenesis through elevation of colonic PPARgamma expression and
alteration of lipid composition. Int J Cancer. 2004;110:896–901.
81. Krawinkel MB, Keding GB. Bitter gourd (Momordica charantia): a
dietary approach to hyperglycemia. Nutr Rev. 2006;64:331–7 (Review).
82. Kuanhuta W, Aree T, Pornpakakul S, Sawasdee P. Novel cucurbitane
triterpenoids and anticholinesterase activities of constituents from
Momordica charantia L. Nat Prod Commun. 2014;9:765–9.
83. Kupradinun P, Tepsuwan A, Tantasi N, et al. Anticlastogenic and
anticarcinogenic potential of Thai bitter gourd fruits. Asian Pac J Cancer
Prev. 2011;12:1299–305.
84. Kusamran WR, Ratanavila A, Tepsuwan A. Effects of neem flowers,
Thai and Chinese bitter gourd fruits and sweet basil leaves on hepatic
monooxygenases and glutathione S-transferase activities, and in vitro
1212 Momordica charantia L.

metabolic activation of chemical carcinogens in rats. Food Chem Toxicol.

1998;36:475–84.
85. Leatherdale BA, Panesar RK, Singh G, et al. Improvement in glucose
tolerance due to Momordica charantia (karela). Br Med J (Clin Res Ed).
1981;6:1823–4.
86. Lee-Huang S, Huang PL, Huang PL, et al. Inhibition of the integrase of
human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins
MAP30 and GAP31. Proc Natl Acad Sci U S A. 1995;92:8818–22.
87. Lee-Huang S, Huang PL, Nara PL, et al. MAP 30: a new inhibitor of
HIV-1 infection and replication. FEBS Lett. 1990;272:12–8.
88. Li CJ, Tsang SF, Tsai CH, et al. Momordica charantia extract induces
apoptosis in human cancer cells through caspase- and mitochondria-
dependent pathways. Evid Based Complement Alternat Med. 2012;2012:
261971.
89. Li QY, Chen HB, Liu ZM, et al. Cucurbitane triterpenoids from
Momordica charantia. Magn Reson Chem. 2007;45:451–6.
90. Li YC, Xu XJ, Yang J, et al. One new 19-nor cucurbitane-type triterpenoid
from the stems of Momordica charantia. Nat Prod Res. 2016;30:973–8.
91. Liao YW, Chen CR, Kuo YH, et al. Cucurbitane-type triterpenoids from the
fruit pulp of Momordica charantia. Nat Prod Commun. 2012;7:1575–8.
92. Limtrakul P, Khantamat O, Pintha K. Inhibition of P-glycoprotein activity
and reversal of cancer multidrug resistance by Momordica charantia
extract. Cancer Chemother Pharmacol. 2004;54:525–30.
93. Lin JY, Hou MJ, Chen YC. Isolation of toxic and nontoxic lectins from the
bitter pear melon Momordica charantia Linn. Toxicon. 1978;16:653–60.
94. Lin KW, Yang SC, Lin CN. Antioxidant constituents from the stems and
fruits of Momordica charantia. Food Chem. 2011;127:609–14.
95. Lin X, Shen X, Long Z, Yang Q. Effects of cactus, alove veral, Momorcica
charantia on reducing the blood glucose of diabetic mice. Wei Sheng Yan
Jiu. 2001;30:203–5 (Chinese).
96. Liu JQ, Chen JC, Wang CF, Qiu MH. New cucurbitane triterpenoids
and steroidal glycoside from Momordica charantia. Molecules. 2009;14:
4804–13.
97. Liu Y, Ali Z, Khan IA. Cucurbitane-type triterpene glycosides from the
fruits of Momordica charantia. Planta Med. 2008;74:1291–4.
98. Ma J, Whittaker P, Keller AC, et al. Cucurbitane-type triterpenoids from
Momordica charantia. Planta Med. 2010;76:1758–61.
99. Ma L, Yu AH, Sun LL, et al. Two new bidesmoside triterpenoid saponins
from the seeds of Momordica charantia L. Molecules. 2014;19:2238–46.
100. Ma L, Yu AH, Sun LL, et al. Two new cucurbitane triterpenoids from the
seeds of Momordica charantia. J Asian Nat Prod Res. 2014;16:476–82.
101. Mahdi AA, Chandra A, Singh RK, et al. Effect of herbal hypoglycemic
agents on oxidative stress and antioxidant status in diabetic rats. Indian J
Clin Biochem. 2003;18:8–15.
Momordica charantia L. 1213

102. Mahmoud MF, El Ashry FE, El Maraghy NN, Fahmy A. Studies on the
antidiabetic activities of Momordica charantia fruit juice in streptozotocin-
induced diabetic rats. Pharm Biol. 2017;55:758–65.
103. Mahomoodally MF, Subratty AH, Gurib-Fakim A, et al. Traditional
medicinal herbs and food plants have the potential to inhibit key carbohy-
drate hydrolyzing enzymes in vitro and reduce postprandial blood glucose
peaks in vivo. Sci World J. 2012;2012:285284.
104. Malik ZA, Singh M, Sharma PL. Neuroprotective effect of Momordica
charantia in global cerebral ischemia and reperfusion induced neuronal
damage in diabetic mice. J Ethnopharmacol. 2011;133:729–34.
105. Manabe M, Takenaka R, Nakasa T, Okinaka O. Induction of anti-
inflammatory responses by dietary Momordica charantia L. (bitter gourd).
Biosci Biotechnol Biochem. 2003;67:2512–7.
106. Mardani S, Nasri H, Hajian S, et al. Impact of Momordica charantia
extract on kidney function and structure in mice. J Nephropathol. 2014;
3:35–40.
107. Matsui S, Yamane T, Takita T, et al. The hypocholesterolemic activity of
Momordica charantia fruit is mediated by the altered cholesterol- and bile
acid-regulating gene expression in rat liver. Nutr Res. 2013;33:580–5.
108. Matsuur H, Asakawa C, Kurimoto M, Mizutani J. Alpha-glucosidase
inhibitor from the seeds of balsam pear (Momordica charantia) and the
fruit bodies of Grifola frondosa. Biosci Biotechnol Biochem. 2002;66:
1576–8.
109. McCarty MF. Does bitter melon contain an activator of AMP-activated
kinase? Med Hypotheses. 2004;63:340–3.
110. Meng Y, Liu B, Lei N, et al. Alpha-momorcharin possessing high immuno-
genicity, immunotoxicity and hepatotoxicity in SD rats. J Ethnopharmacol.
2012;139:590–8.
111. Miura T, Itoh C, Iwamoto N, et al. Hypoglycemic activity of the fruit of the
Momordica charantia in type 2 diabetic mice. J Nutr Sci Vitaminol
(Tokyo). 2001;47:340–4.
112. Miura T, Itoh Y, Iwamoto N, et al. Suppressive activity of the fruit of
Momordica charantia with exercise on blood glucose in type 2 diabetic
mice. Biol Pharm Bull. 2004;27:248–50.
113. Morton JF. The balsam pear—an edible, medicinal and toxic plant. Econ
Bot. 1967;21:57–68.
114. Murakami T, Emoto A, Matsuda H, Yoshikawa M. Medicinal foodstuffs. XXI.
Structures of new cucurbitane-type triterpene glycosides, goyaglycosides-a,
-b, -c, -d, -e, -f, -g, and -h, and new oleanane-type triterpene saponins, goyas-
aponins I, II, and III, from the fresh fruit of Japanese Momordica charantia
L. Chem Pharm Bull (Tokyo). 2001;49:54–63.
115. Mwambete KD. The in vitro antimicrobial activity of fruit and leaf crude
extracts of Momordica charantia: a Tanzania medicinal plant. Afr Health
Sci. 2009;9:34–9.
1214 Momordica charantia L.

116. Nagasawa H, Watanabe K, Inatomi H. Effects of bitter melon (Momordica

charantia L.) or ginger rhizome (Zingiber offifinale Rosc) on spontaneous
mammary tumorigenesis in SHN mice. Am J Chin Med. 2002;30:195–205.
117. Nakamura S, Murakami T, Nakamura J, et al. Structures of new
cucurbitane-type triterpenes and glycosides, karavilagenins and karavilo-
sides, from the dried fruit of Momordica charantia L. Sri Lanka. Chem
Pharm Bull (Tokyo). 2006;54:1545–50.
118. Naseem MZ, Patil SR, Patil SR, et al. Antispermatogenic and androgenic
activities of Momordica charantia (Karela) in albino rats. J Ethnopharma-
col. 1998;61:9–16.
119. Naz R, Anjum FM, Butt MS, Mahr-Un-Nisa. Dietary supplementation of
bitter gourd reduces the risk of hypercholesterolemia in cholesterol fed
Sprague Dawley rats. Pak J Pharm Sci. 2016;29:1565–70.
120. Nerurkar PV, Johns LM, Buesa LM, et al. Momordica charantia (bitter melon)
attenuates high-fat diet-associated oxidative stress and neuro-inflammation.
J Neuroinflammation. 2011;8:64.
121. Ng TB, Wong CM, Li WW, Yeung HW. Acid-ethanol extractable
compounds from fruits and seeds of the bitter gourd Momordica charantia:
effects on lipid metabolism in isolated rat adipocytes. Am J Chin Med.
1987;15:31–42.
122. Ng TB, Wong CM, Li WW, Yeung HW. Insulin-like molecules in
Momordica charantia seeds. J Ethnopharmacol. 1986;15:107–17.
123. Ng TB, Wong CM, Li WW, Yeung HW. Peptides with antilipolytic and
lipogenic activities from seeds of the bitter gourd Momordica charantia
(family Cucurbitaceae). Gen Pharmacol. 1987;18:275–81.
124. Ng ZX, Chai JW, Kuppusamy UR. Customized cooking method improves
total antioxidant activity in selected vegetables. Int J Food Sci Nutr. 2011;
62:158–63.
125. Nguyen XN, Phan VK, Chau VM, et al. Cucurbitane-type triterpene
glycosides from the fruits of Momordica charantia. Magn Reson Chem.
2010;48:392–6.
126. Nivitabishekam SN, Asad M, Prasad VS. Pharmacodynamic interaction of
Momordica charantia with rosiglitazone in rats. Chem Biol Interact.
2009;177:247–53.
127. Nkambo W, Anyama NG, Onegi B. In vivo hypoglycemic effect of
methanolic fruit extract of Momordica charantia L. Afr Health Sci. 2013;
13:933–9.
128. Noguchi R, Yasui Y, Suzuki R, et al. Dietary effects of bitter gourd oil on
blood and liver lipids of rats. Arch Biochem Biophys. 2001;396:207–12.
129. Ojewole JA, Adewole SO, Olayiwola G. Hypoglycaemic and hypotensive
effects of Momordica charantia Linn. (Cucurbitaceae) whole-plant aque-
ous extract in rats. Cardiovasc J S Afr. 2006;17:227–32.
130. Ozbakiş Dengiz G, Gürsan N. Effects of Momordica charantia L.
(Cucurbitaceae) on indomethacin-induced ulcer model in rats. Turk J
Gastroenterol. 2005;16:85–8.
Momordica charantia L. 1215

131. Padmashree A, Sharma GK, Semwal AD, Bawa AS. Studies on the
antioxygenic activity of bitter gourd (Momordica charantia) and its
fractions using various in vitro models. J Sci Food Agric. 2011;91:776–82.
132. Parkash A, Ng TB, Tso WW. Purification and characterization of
charantin, a napin-like ribosome-inactivating peptide from bitter gourd
(Momordica charantia) seeds. J Pept Res. 2002;59:197–202.
133. Patel R, Mahobia N, Upwar N, et al. Analgesic and antipyretic activities of
Momordica charantia Linn. fruits. J Adv Pharm Technol Res. 2010;1:415–8.
134. Pişkin A, Altunkaynak BZ, Tümentemur G, et al. The beneficial effects of
Momordica charantia (bitter gourd) on wound healing of rabbit skin.
J Dermatolog Treat. 2014;25:350–7.
135. Pitchakarn P, Ogawa K, Suzuki S, et al. Momordica charantia leaf extract
suppresses rat prostate cancer progression in vitro and in vivo. Cancer Sci.
2010;101:2234–40.
136. Platel K, Shurpalekar KS, Srinivasan K. Influence of bitter gourd
(Momordica charantia) on growth and blood constituents in albino rats.
Nahrung. 1993;37:156–60.
137. Platel K, Srinivasan K. Effect of dietary intake of freeze dried bitter gourd
(Momordica charantia) in streptozotocin induced diabetic rats. Nahrung.
1995;39:262–8.
138. Prasad V, Jain V, Girish D, Dorle AK. Wound-healing property of
Momordica charantia L. fruit powder. J Herb Pharmacother. 2006;6:105–15.
139. Qader SW, Abdulla MA, Chua LS, et al. Antioxidant, total phenolic content
and cytotoxicity evaluation of selected Malaysian plants. Molecules. 2011;
16:3433–43.
140. Rakholiya K, Vaghela P, Rathod T, Chanda S. Comparative study of
hydroalcoholic extracts of Momordica charantia L. against food borne
pathogens. Indian J Pharm Sci. 2014;76:148–56.
141. Rathi SS, Grover JK, Vats V. The effect of Momordica charantia and
Mucuna pruriens in experimental diabetes and their effect on key
metabolic enzymes involved in carbohydrate metabolism. Phytother Res.
2002;16:236–43.
142. Rathi SS, Grover JK, Vikrant V, Biswas NR. Prevention of experimental
diabetic cataract by Indian Ayurvedic plant extracts. Phytother Res. 2002;
16:774–7.
143. Raza H, Ahmed I, John A. Tissue specific expression and immunohisto-
chemical localization of glutathione S-transferase in streptozotocin induced
diabetic rats: modulation by Momordica charantia (karela) extract. Life
Sci. 2004;74:1503–11.
144. Raza H, Ahmed I, Lakhani MS, et al. Effect of bitter melon (Momordica
charantia) fruit juice on the hepatic cytochrome P450-dependent monooxy-
genases and glutathione S-transferases in streptozotocin-induced diabetic
rats. Biochem Pharmacol. 1996;52:1639–42.
145. Raza H, Ahmed I, John A, Sharma AK. Modulation of xenobiotic
metabolism and oxidative stress in chronic streptozotocin-induced diabetic
1216 Momordica charantia L.

rats fed with Momordica charantia fruit extract. J Biochem Mol Toxicol.
2000;14:131–9.
146. Reyes BA, Bautista ND, Tanquilut NC, et al. Antidiabetic potentials of
Momordica charantia and Andrographis paniculata and their effects on
estrous cyclicity of alloxan-induced diabetic rats. J Ethnopharmacol. 2006;
105:196–200.
147. Rodriguez DB, Lee TC, Chichester CO. Comparative study of the
carotenoid composition of the seeds of ripening Momordica charantia and
tomatoes. Plant Physiol. 1975;56:626–9.
148. Rudá-Kučerová J, Kotolová H, Koupý D. Effectiveness of phytotherapy in
supportive treatment of type 2 diabetes mellitus III Momordica
(Momordica charantia). Ceska Slov Farm. 2015;64:126–32 (Czech).
149. Santos AK, Costa JG, Menezes IR, et al. Antioxidant activity of five
Brazilian plants used as traditional medicines and food in Brazil.
Pharmacogn Mag. 2010;6:335–8.
150. Sarkar S, Pranava M, Marita R. Demonstration of the hypoglycemic action
of Momordica charantia in a validated animal model of diabetes.
Pharmacol Res. 1996;33:1–4.
151. Sathishsekar D, Subramanian S. Antioxidant properties of Momordica
Charantia (bitter gourd) seeds on streptozotocin-induced diabetic rats.
Asia Pac J Clin Nutr. 2005;14:153–8.
152. Sekar DS, Sivagnanam K, Subramanian S. Antidiabetic activity of
Momordica charantia seeds on streptozotocin induced diabetic rats.
Pharmazie. 2005;60:383–7.
153. Senanayake GV, Maruyama M, Shibuya K, et al. The effects of bitter
melon (Momordica charantia) on serum and liver triglyceride levels in
rats. J Ethnopharmacol. 2004;91:257–62.
154. Senanayake GV, Fukuda N, Nshizono S, et al. Mechanisms underlying
decreased hepatic triacylglycerol and cholesterol by dietary bitter melon
extract in the rat. Lipids. 2012;47:495–503.
155. Shibib BA, Khan LA, Rahman R. Hypoglycaemic activity of Coccinia
indica and Momordica charantia in diabetic rats: depression of the
hepatic gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-
bisphosphatase and elevation of both liver and red-cell shunt enzyme
glucose-6-phosphate dehydrogenase. Biochem J. 1993;292(Pt 1):267–70.
156. Shih CC, Lin CH, Lin WL, Wu JB. Momordica charantia extract on
insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed
rats. J Ethnopharmacol. 2009;123:82–90.
157. Shih CC, Shlau MT, Lin CH, Wu JB. Momordica charantia ameliorates
insulin resistance and dyslipidemia with altered hepatic glucose production
and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice.
Phytother Res. 2014;28:363–71.
158. Singh A, Singh SP, Bamezai R. Momordica charantia (Bitter Gourd) peel,
pulp, seed and whole fruit extract inhibits mouse skin papillomagenesis.
Toxicol Lett. 1998;94:37–46.
Momordica charantia L. 1217

159. Singh N, Gupta M, Sirohi P. Varsha: Effects of alcoholic extract of

Momordica charantia (Linn.) whole fruit powder on the pancreatic islets
of alloxan diabetic albino rats. J Environ Biol. 2008;29:101–6.
160. Singh N, Tyagi SD, Agarwal SC. Effects of long term feeding of acetone
extract of Momordica charantia (whole fruit powder) on alloxan diabetic
albino rats. Indian J Physiol Pharmacol. 1989;33:97–100.
161. Sridhar MG, Vinayagamoorthi R, Arul Suyambunathan V, et al. Bitter
gourd (Momordica charantia) improves insulin sensitivity by increasing
skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in
high-fat-fed rats. Br J Nutr. 2008;99:806–12.
162. Srivastava Y, Venkatakrishna-Bhatt H, Verma Y. Effect of Momordica
charantia Linn. pomous aqueous extract on cataractogenesis in murrin
alloxan diabetics. Pharmacol Res Commun. 1988;20:201–9.
163. Su J, Wang H, Ma C, et al. Hypocholesterolaemic mechanism of bitter
melon aqueous extracts via inhibition of pancreatic cholesterol esterase and
reduction of cholesterol micellar solubility. Int J Food Sci Nutr. 2016;67:
20–8.
164. Takemoto DJ, Kresie R, Vaughn D. Partial purification and characteriza-
tion of a guanylate cyclase inhibitor with cytotoxic properties from the
bitter melon (Momordica charantia). Biochem Biophys Res Commun.
1980;94:332–9.
165. Tennekoon KH, Jeevathayaparan S, Angunawala P, et al. Effect of
Momordica charantia on key hepatic enzymes. J Ethnopharmacol. 1994;
44:93–7.
166. Teoh SL, Latiff AA, Das S. The effect of topical extract of Momordica
charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with
diabetes induced by streptozotocin. Clin Exp Dermatol. 2009;34:815–22.
167. Tongia A, Tongia SK, Dave M. Phytochemical determination and
extraction of Momordica charantia fruit and its hypoglycemic potentiation
of oral hypoglycemic drugs in diabetes mellitus (NIDDM). Indian J
Physiol Pharmacol. 2004;48:241–4.
168. Tripathi UN, Chandra D. Antihyperglycemic and antioxidative effect of
aqueous extract of Momordica charantia pulp and Trigonella foenum
graecum seed in alloxan-induced diabetic rats. Indian J Biochem Biophys.
2010;47:227–33.
169. Tripathi UN, Chandra D. The plant extracts of Momordica charantia and
Trigonella foenum-graecum have antioxidant and antihyperglycemic
properties for cardiac tissue during diabetes mellitus. Oxid Med Cell
Longev. 2009;2:290–6.
170. Tsai CH, Chen EC, Tsay HS, Huang CJ. Wild bitter gourd improves
metabolic syndrome: a preliminary dietary supplementation trial. Nutr J.
2012;11:4.
171. Tumkiratiwong P, Ploypattarapinyo R, Pongchairerk U, Thong-Asa W.
Reproductive toxicity of Momordica charantia ethanol seed extracts in
male rats. Iran J Reprod Med. 2014;12:695–704.
1218 Momordica charantia L.

172. Uche-Nwachi EO, McEwen C. Teratogenic effect of the water extract of

bitter gourd (Momordica charantia) on the Sprague Dawley rats. Afr J
Tradit Complement Altern Med. 2009;7:24–33.
173. Ueno HM, Doyama JT, Padovani CR, Salata E. Effect of Momordica
charantia L. in mice infected with Plasmodium berghei. Rev Soc Bras
Med Trop. 1996;29:455–60 (Portuguese).
174. Vikrant V, Grover JK, Tandon N, et al. Treatment with extracts of
Momordica charantia and Eugenia jambolana prevents hyperglycemia and
hyperinsulinemia in fructose fed rats. J Ethnopharmacol. 2001;76:139–43.
175. Virdi J, Sivakami S, Shahani S, et al. Antihyperglycemic effects of three
extracts from Momordica charantia. J Ethnopharmacol. 2003;88:107–11.
176. Wang J, Ryu HK. The effects of Momordica charantia on obesity and lipid
profiles of mice fed a high-fat diet. Nutr Res Pract. 2015;9:489–95.
177. Wang YX, Neamati N, Jacob J, et al. Solution structure of anti-HIV-1 and
antitumor protein MAP30: structural insights into its multiple functions.
Cell. 1999;99:433–42.
178. Welihinda J, Arvidson G, Gylfe E, et al. The insulin releasing activity of
the tropical plant Momordica charantia. Acta Biol Med Ger (East Ger.).
1982;41:1229–40.
179. Welihinda J, Karunanayake EH, Sheriff MH, Jayasinghe KS. Effect of
Momordica charantia on the glucose tolerance in maturity onset diabetes.
J Ethnopharmacol. 1986;17:277–82.
180. West ME, Sidrak GH, Street SP. The antigrowth properties of extracts
from Momordica charantia. West Ind Med J. 1971;20:25–34.
181. Wong CM, Yeung HW, Ng TB. Screening of Trichosanthes kirilowii,
Momordica charantia and Cucurbita maxima (family Cucurbitaceae) for
compounds with antilipolytic activity. J Ethnopharmacol. 1985;13:313–21.
182. Xie H, Huang S, Deng H, et al. Study on chemical components of
Momordica charantia. Zhong Yao Cai. 1998;21:458–9 (Chinese).
183. Yadav M, Lavania A, Tomar R, et al. Complementary and comparative
study on hypoglycemic and antihyperglycemic activity of various extracts
of Eugenia jambolana seed, Momordica charantia fruits, Gymnema
sylvestre, and Trigonella foenum graecum seeds in rats. Appl Biochem
Biotechnol. 2010;160:2388–400.
184. Yadav UC, Moorthy K, Baquer NZ. Combined treatment of sodium
orthovanadate and Momordica charantia fruit extract prevents alterations
in lipid profile and lipogenic enzymes in alloxan diabetic rats. Mol Cell
Biochem. 2005;268:111–20.
185. Yama OE, Osinubi AA, Noronha CC, Okanlawon AO. Effect of
methanolic seed extract of Momordica charantia on body weight and
serum cholesterol level of male Sprague-Dawley rats. Nig Q J Hosp Med.
2010;20:209–13.
Momordica charantia L. 1219

186. Yang SJ, Choi JM, Park SE, et al. Preventive effects of bitter melon
(Momordica charantia) against insulin resistance and diabetes are associ-
ated with the inhibition of NF-jB and JNK pathways in high-fat-fed
OLETF rats. J Nutr Biochem. 2015;26:234–40.
187. Yen PH, Dung DT, Nhiem NX, et al. Cucurbitane-type triterpene
glycosides from the fruits of Momordica charantia. Nat Prod Commun.
2014;9:383–6.
188. Yeşilada E, Gürbüz I, Shibata H. Screening of Turkish antiulcerogenic
folk remedies for anti-Helicobacter pylori activity. J Ethnopharmacol.
1999;66:289–93.
189. Yeung HW, Li WW, Feng Z, et al. Trichosanthin, alpha-momorcharin and
beta-momorcharin: identity of abortifacient and ribosome-inactivating
proteins. Int J Pept Protein Res. 1988;31:265–8.
190. Yibchok-Anun S, Adisakwattana S, Yao CY, et al. Slow acting protein
extract from fruit pulp of Momordica charantia with insulin secretagogue
and insulinomimetic activities. Biol Pharm Bull. 2006;29:1126–31.
191. Yung MM, Ross FA, Hardie DG, et al. Bitter melon (Momordica
charantia) extract inhibits tumorigenicity and overcomes cisplatin-
resistance in ovarian cancer cells through targeting AMPK signaling
cascade. Integr Cancer Ther. 2016;15:376–89.
192. Zhao GT, Liu JQ, Deng YY, et al. Cucurbitane-type triterpenoids from the
stems and leaves of Momordica charantia. Fitoterapia. 2014;95:75–82.
193. Zhu ZJ, Zhong ZC, Luo ZY, Xiao ZY. Studies on the active constituents of
Momordica charantia L. Yao Xue Xue Bao. 1990;25:898–903 (Chinese).
Moringa oleifera Lam.
(Moringaceae)

(Syns.: M. pterygosperma Gaetern.nom.illeg; Guilandina moringa L.;

Hyperanthera moringa (L.) Vahl.)

Abstract
A fast-growing, deciduous tree, native of the Indian subcontinent, but cultivated in
all tropical and subtropical regions of the world. All parts of the tree are used as
highly nutritive vegetable in many countries, particularly in India, Pakistan, the
Philippines, Thailand, Hawaii and African countries. The flowers, leaves, pods and
gum are used in the treatment of phlegmatic diseases, such as cough, asthma,
arthritis, backache, paralysis and inflammation of spleen. Internally, the leaves,
flowers and pods are carminative, diuretic, anthelmintic, and appetizer, and the
seeds are aphrodisiac; externally, the leaves are used as anti-inflammatory and
analgesic. In most regions of Senegal, it is cultivated as the second most commonly
used leafy vegetable, and was the most cited plant used by diabetic patients in
Dakar and northern Tanzania, and used to treat diabetic patients by the Bapedi
traditional healers in the Limpopo Province of South Africa. It is distributed in all
ecological zones of Nigeria and is used in the treatment of body pains and
weakness, fever, asthma, cough, blood pressure, arthritis, diabetes, epilepsy,
wound, hemorrhage, chronic anemia, malaria and skin infections, and for terminal
illnesses such as HIV/AIDs infections and cancer. In Ghana, it is used as galac-
tagogue in mothers of preterm infants and to manage heart diseases, inflamma-
tions, dyspepsia and eye complaints. In Cameroon traditional medicine, leaves are
used to treat syphilis, typhoid, diarrhea, epilepsy, prostate cancer, HIV/AIDS,
malnutrition, fever, headaches, nerve pain and diabetes, and in Benin as food
supplements for HIV patients and as antipyretic and antibiotic. Leaves contain
phenolic acids, flavonoids, glucoside, kaempferol 3-O-a-rhamnoside, procyani-
dins, caffeoyl quinic acid a-glucosides, marumosides A and B, tannins, saponins,
essential nutrients, such as, vitamins, minerals, amino acids, b-carotene, lutein,
antioxidants, and omega 3 and 6 fatty acids. Administration of leaf powder to
young fasting healthy Thai volunteers, dose-dependently increased serum insulin

© Springer Nature Switzerland AG 2020 1221

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_129
1222 Moringa oleifera Lam.

levels without affecting blood glucose levels. Daily supplementation with 7 g

leaves powder to postmenopausal Indian women for three-months significantly
lowered FBG level and significantly increased Hb, serum retinol and ascorbic acid
levels, and improved activities of antioxidative enzymes.

Keywords




Behennødtræ Ben ailée Benboom Drumstick-tree
Habulbau
La mu




Moringa Shajanah Sobhanjana Sonjhna

Vernaculars: Urd.: Sonjhna; Hin.: Munagaa, Sahinjan, Saijan, Segve, Sengva,

Shajanah, Shajian; San.: Akshiva, Dansha-mula-sveta, Jiksna gandha, Mochak,
Shigru, Shobhana-jana, Shrigree, Sigru murngi, Sobhanjana; Ben.: Munga ara,
Shajina, Sohanjana, Sojna; Guj.: Midho saragavo, Seeng ni phali; Mal.: Morunna,
Murina, Muringa, Muringai, Muringakka (fruit), Murunna; Mar.: Bododi, Shegta,
Shevga, Soigut, Sujna; Tam.: Murungai, Murungai maram (tree); Tel.: Doonsha,
Mula, Mulaga, Mulakkaya, Mulana, Munaga, Sveta maricha; Ara.: Habulbau;
Bur.: Daintha, Dandalonbin; Chi.: La mu, Lat mok; Cze.: Moringa olejná; Dan.:
Behennødtræ; Dut.: Benboom, Moringaboom, Peperwortel boom; Eng.: Benzolive
tree (USA), Drumstick-tree, Horse-radish tree, Miracle tree; Fre.: Arbre de la vie,
Ben ailé, Ben ailée, Ben oléifère, Bois quénique, Moringa; Ger.: Behenbaum,
Behennussbaum, Meerrettichbaum, Moringa, Pferderettichbaum; Hun.: Lóretekfa;
Ita.: Been, Bemen, Moringa; Jap.: Marungai, Wasabi no ki; Maly.: Benzolive,
Kaylor, Kelor, Marango, Mlonge, Mulangay, Ramoongie, Saijihan, Sajna; Nep.:
Sajiwan, Sitachini, Swejan; Per.: Ban, Sajna; Por.: Acácia branca, Moringa,
Muringueiro; Sin.: Moo rin guu, Murunga (bean/pod), Murunga gasa (tree); Spa.:
Marango, Naranjo (Mexico); Tag.: Kalamungay (leaves), Kalúñgai, Kamalúñgai,
Malóñgai, Malúñgai; Tha.: Ka naeng doing, Ma khon kom, Ma rum (bean/pod);
Vie.: Chùm ngây.
Description: A native of the Indian subcontinent, but cultivated in all tropical and
subtropical regions of the world. A fast-growing, deciduous tree reaching a height of
8 m or less; leaves are alternate, usually thrice pinnate, 25–50 cm long, with three
to nine, thin, ovate to elliptic 1–2 cm leaflets. Flowers are fragrant, surrounded by
five unequal, thinly veined, yellowish-white petals. The pod is 15–30 cm long,
pendulous, three-angled, and nine ribbed, containing three-angled seeds (Figs. 1, 2
and 3).CXVII
Actions and Uses: All parts of the tree are used as highly nutritive vegetable in many
countries, particularly in India, Pakistan, the Philippines, Thailand, Hawaii and
African countries [31, 78]. The flowers, leaves, pods and gum are used in the treat-
ment of phlegmatic diseases, such as cough, asthma, arthritis, backache, paralysis and
inflammation of spleen. Internally, the leaves, flowers and pods (temperament, hot 3°
and dry 3°) are carminative, diuretic, anthelmintic, and appetizer, and the seeds are
aphrodisiac; externally, the leaves are used as anti-inflammatory and analgesic.
A pickle is made of raw pods by boiling them, then mixed with mustard oil, salt and
Moringa oleifera Lam. 1223

Fig. 1 Moringa oleifera, Tree in Dakawa, Tanzania, Prof. Chen Hualin, WikimediaCommons; Share-
Alike 4.0 International CC BY-SA 4.0, https://en.wikipedia.org/wiki/Moringa_oleifera#/media/File:
The_tree_and_seedpods_of_Moringa_oleifera.JPG; https://creativecommons.org/licenses/by-sa/4.0/
deed.en

Fig. 2 Moringa oleifera, Flowers, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Sonjna_(Moringa_oleifera)_at_Jayanti,_Du
ars,_West_Bengal_W_IMG_5249.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

rai (Brassica juncea) and left in the sun for a few days, and used in patients with
paralysis, palsy, arthritis, backache, loss of appetite and stomachache.LXXVII Seeds
are acrid and stimulant and the bark is emmenagogue and abortifacient; seed oil is
used for topical application in rheumatism, and the EO of the root is used externally as
a rubefacient.CV Bark is abortifacient and is a good substitute for laminaria to dilate
1224 Moringa oleifera Lam.

Fig. 3 Moringa oleifera, Fruits (Pods), Krish Dulal, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Moringa_oleifera_pods_NP.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

cervical os.LXXXI Since all parts of the plant possess medicinal properties they are
used in African countries in the treatment of ascites, rheumatic and joint pains,
venomous bites and pneumonia [84], to prevent and treat inflammation, infectious
diseases, cardiovascular, gastrointestinal, hematological and hepatorenal disorders
[83]. In most regions of Senegal, it is cultivated as the second most commonly used
leafy vegetables [73], and was the most cited plant used by diabetic patients in Dakar
[36] and northern Tanzania [67], and used to treat diabetic patients by the Bapedi
traditional healers in the Limpopo Province of South Africa [108]. It is recommended
as the health promoter and for the prevention and treatment of chronic hyperglycemia
and dyslipidemia [75]. It is distributed in all ecological zones of Nigeria and is used in
the treatment of body pains and weakness, fever, asthma, cough, blood pressure,
arthritis, diabetes, epilepsy, wound, hemorrhage, chronic anemia, malaria and skin
infections, and for terminal illnesses such as HIV/AIDs infections and cancer [96]. In
Ghana, it is used as galactagogue in mothers of preterm infants and to manage heart
diseases, inflammations, dyspepsia and eye complaints [15]. In Cameroon traditional
medicine, leaves are used to treat syphilis, typhoid, diarrhea, epilepsy, prostate
cancer, HIV/AIDS [38], malnutrition, fever, headaches, nerve pain and diabetes, and
in Benin as food supplements for HIV patients and as antipyretic and antibiotic [65].
Ancient Egyptians used the oil for its cosmetic value and in skin preparation [66]. In
traditional Thai medicine, leaves are used to treat dysentery [34], and as cardiotonic
[30]. In the Philippines, young leaves are used as galactagogue; the roots decoction is
used to cleanse sores and ulcers and also in delirious patients,CXVII and for diseases of
the circulatory system by the indigenous people of Batan Island [4].
Phytoconstituents: Methanol leaves extract showed the presence of alkaloids,
anthraquinones, flavonoids, coumarins, polyphenols, sterols, tannins, triterpenes
and saponins [38]. Leaves contain phenolic acids (caffeic acid, chlorogenic acid,
Moringa oleifera Lam. 1225

ellagic acid, gallic acid), flavonoids (apigenin, epicatechin, kaempferol, luteolin,

myricetin, rutin, quercetin, quercetin 3-O-b-glucoside), glucoside, kaempferol
3-O-a-rhamnoside, procyanidins [16, 66, 72], caffeoyl quinic acid a-glucosides [59],
marumosides A and B [107], tannins, saponins, essential nutrients, such as, vitamins
(A, B1, B2, B3, C, E), minerals (Ca, Mn, Fe, Cu, P, Mg, Zn), amino acids,
b-carotene, lutein, antioxidants, and omega 3 and 6 fatty acids [3, 20, 40, 46, 60, 66].
Fresh leaves are a rich source of kaempferol [18], contain approximately 200 mg/100
g of vitamin C, greater than orange; in dried leaves vitamin C content is lower than in
the fresh leaves, dropping to 18.7 to 140 mg/100 g of dry weight [55]. Young fruits
have high protein content, fair source of calcium and iron, and high in phosphorus
content.CXVII Ethanol extract of flowers collected in the month of December from
Oman, showed the presence of tannins, alkaloids, flavonoids, cardiac glycosides,
terpenoids, steroids and carbohydrates [12]. Methanol leaves extract from Nigeria
contained flavonoids, terpenoids, glycosides, tannins and saponins [5], while
methanol seed extract showed the presence of saponins, tannins, terpenes, alkaloids,
flavonoids, carbohydrates, and cardiac glycosides [9], and the EO mainly contained
monoterpenoids (81.8%) with a-phellandrene (25.2%) and p-cymene (24.9%) being
the major compounds [87]. Stem bark contains alkaloids (moringine and mor-
inginine), vanillin, b-sitosterol, b-sitostenone, 4-hydroxymellin, octacosanoic acid,
phenolics and procyanidins [74]. From ethanol extract of seeds from the Philippines,
O-ethyl-4-(a-L-rhamnosyloxybenzyl carbamate, 4(a-L-rhamnosyloxy)-benzyl isothio-
cyanate, niazimicin, niazirin, b-sitosterol, glycerol-1-(9-octadecanoate),3-O-(6′-O-
oleoyl-b-D-glucopyranosyl)-b-sitosterol, and b-sitosterol-3-O-b-D-glucopyranoside
were isolated [49].
Pharmacology: Leaves aqueous extract significantly decreased FBG, oral glucose
challenge in normal [53] and diabetic rats [2, 53], and significantly increased
activities of antioxidant enzymes and GSH levels [54, 126]. Methanol leaf extract
inhibited weight loss, significantly improved glucose tolerance and increased serum
insulin levels, and reduced serum TG, TC, and LDL-C, and increased HDL-C of
diabetic rats [88]. Pods methanol extract also significantly reduced serum glucose
and increased antioxidant levels in pancreatic tissue of diabetic rats [51]. Ethanol
bark extract prevented both acute and chronic dexamethasone-induced insulin
resistance and hypertriglyceridemia in rats [115]. Supplementation of seed powder
(50 and 100 mg/kg) in diet of diabetic rats ameliorated increase in FBG and HbA1c
[13]. Very high-fat diet supplemented with 5% aqueous leaf concentrate rich in
isothiocyanates, to C57BL/6L mice significantly improved glucose tolerance and
insulin signalling, reduced plasma insulin, leptin, resistin, and cholesterol, and
prevented the development of fatty liver disease [125].
Methanol leaves extract exhibited significant analgesic effect in i.p. doses of 300
and 400 mg/kg in rats with Freund’s adjuvant-induced arthritis, comparable to 5 mg
dose of indomethacin [71], and significant analgesic, anti-inflammatory and
antioxidant activities with oral dosing [5]. Oral pretreatment with hydroalcohol seed
extract effectively controlled acetic acid-induced colitis in rats [77], protected guinea
pigs against ACh-induced bronchoconstriction and airway inflammation [69],
1226 Moringa oleifera Lam.

inhibited in vitro histamine release from mast cells [70], and reduced histamine
release from sensitized guinea pig lungs [48], significantly reduced adjuvant-induced
arthritis, serum levels of Rheumatoid Factor, TNF-a, IL-1, and IL-6, and reduced
oxidative stress in rats [68]. Ethanol flower extract exhibited moderate antioxidant
activity, but significant anti-inflammatory activity comparable to diclofenac sodium
[12]. Oral aqueous root extract markedly inhibited carrageenan-induced edema,
similar in extent to indomethacin [84], and hydroalcohol bark extract dose-
dependently reduced E. coli-induced pyrexia in rabbits [8]. Various cultivars show
different degree of antioxidant activity, the cultivar from Thailand showed the
strongest antioxidant activity [83]. Aqueous extracts of both tender and mature
leaves possess strong antioxidant activity [30, 118], protect against CP-induced
nephrotoxicity and oxidative stress [120]; the seed aqueous extract also protects
against high-fat diet-induced oxidative stress [32]. Cold ethanol leaf extract
offers significant protection against APAP-nephrotoxicity in mice [58]. Aqueous
and methanol leaf extracts are also reported to stimulate cellular and humoral
immunity [63, 85].
Pretreatment with ethanol leaf extract protected against brain damage due to
focal ischemic stroke in rats [62], protected mice against PTZ-induced convulsion,
possibly mediated through enhancement of GABA activity [19], decreased oxida-
tive stress, potentiated cognition and protected against neurotoxic chemical chal-
lenge [119], and synergistically potentiated antidepressant effect of fluoxetine in
mice [61]. Chronic treatment with ethanol leaf extract restored monoamines levels
of brain regions of rats, perturbed due to i.c.v. infusion of colchicine, to near control
levels [44]. Pretreatment of rats with aqueous root extract was also protective
against penicillin-induced convulsions and markedly reduced locomotor activity;
chronic treatment significantly increased 5-HT and decreased DA level in cerebral
cortex [104], and potentiated pentobarbitone-induced sleeping time in rats through
5-HT [103].
Diet supplemented with seed powder did not modify BP of SHRs, but reduced
nocturnal HR and improved cardiac diastolic function, and significantly reduced left
ventricular fibrosis [100]; though ethanol extract of whole pods exhibited signifi-
cant hypotensive activity [41]. Ethanol leaves extract (i.p.) also attenuated devel-
opment of monocrotaline-induced pulmonary hypertension in rats via direct
vasodilatation and increase in antioxidant activity [27]. Pretreatment with lyophi-
lized hydroalcohol leaves extract for 30-days significantly protected against
myocardiac damage and biochemical perturbations caused by isoproterenol-induced
MI in rats [81]; polyphenolic fraction of leaves offered the same protection and
decreased oxidative stress [93]. Diet of hypercholesterolemic rabbits supplemented
with leaves significantly lowered serum TC, phospholipid, TG, VLDL, LDL-C, and
cholesterol to phospholipid ratio [76]; crude leaf aqueous extract also significantly
lowered cholesterol of hypercholesterolemic rats and rabbits [30, 45].
Fresh leaves juice and aqueous seed extract inhibited growth of S. aureus and
P. aeruginosa [25], hot ethanol leaf extract was active against E. coli, B. subtilis,
M. phlei, B. cereus, and S. aureus [92], cold aqueous and ethanol leaf extracts were
active against S. aureus, E. faecalis, V. parahaemolyticus and A. caviae [95], cold
Moringa oleifera Lam. 1227

ethanol leaf extract was also active against S. epidermidis, S. pyogenes and P. acnes
[102], and acetone leaf extract active against K. pneumoniae [83]. Ethanol leaf
extract inhibited growth of dematophytes, T. mentagrophytes, T. rubrum, E. floc-
cosum, and M. canis [29]. Cold aqueous and ethanol seed extracts inhibited growth
of S. aureus, V. cholerae and E. coli [124], and cold methanol leaf extract was
significantly active against E. coli and K. pneumoniae [38]. The EO was active
against dermatophytes, including T. rubrum and T. mentagrophytes [86]. Signifi-
cant wound healing effect of aqueous leaf extract in rats was reported by Rathi et al.
[101], and topical application of an ointment containing aqueous fraction of
methanol leaf extract enhanced wound healing in diabetic rats [80]. However,
aqueous leaf extract was not effective as antimicrobial or immune-boosting agent to
enhance healing of wounds infected with MRSA in rats [39].
Supplementation of diet with the leaves for sixteen-weeks protected mice against
sodium arsenite renal and hepatotoxicity [114]. Powdered pods administered to mice
in diet for 14-days also significantly reversed DMBA-hepatotoxicity [111]. Ethanol
leaf extract enhanced recovery from hepatotoxicity of antitubercular drugs, isoni-
azid, rifampicin and pyrazinamide in rats [94], protected against APAP-[42, 110],
CCl4- [117] and Cd chloride-hepatotoxicity [123], and high-fat diet-induced non-
alcoholic fatty liver damage [33], by strengthening antioxidant enzymes system [43].
Hamza [52] also reported seed extract significantly protective against CCl4-hepa-
totoxicity in rats. Leaves supplemented diet for 21-days was conspicuously pro-
tective against nickel sulphate-nephrotoxicity in rats [6]. Aqueous-ethanol leaf
extract highly significantly reduced LPO in gentamicin-induced nephrotoxicity in
rabbits [90], and the hydroethanol extract of pods also protected against DMBA
renal toxicity [112], oxidative stress and renal carcinogenesis [113], prevented
AOM-induced colon carcinogenesis [24], and on topical application significantly
protected against DMBA-induced skin papillomas in mice [22]. Aqueous leaf extract
inhibited growth of pancreatic cell lines and synergistically enhanced cytotoxic
effect of cisplatin on Panc-1 cells [21]. A number of studies on extracts of leaves,
bark, and pods exhibited in vitro anticancer activity against epithelial, leukemic,
breast, colorectal, lung, prostate, esophageal, and hepatocellular carcinoma HepG2
cell lines [10, 11, 35, 56, 57, 121, 122].
Fresh leaf juice and ethanol root bark extract exhibited considerable gastric
antiulcer activity in rats [28, 105]. Hot water seed infusion significantly inhibited
ACh-induced contraction of isolated duodenum, inhibited carrageenan-induced paw
edema and exhibited diuretic activity in rats [26]. Aqueous extract administration to
rats for 4-weeks improved their body energy stores and tissue antioxidant capacity
and reduced tissue build-up of lactic acid during exercise [65], and seed powder
attenuated arsenic-induced oxidative stress in rats [50]. Hydroethanol leaf extract
improved sexual performance in stress-exposed rats, increased serum testosterone
level, and suppressed PDE-5 activity, and decreased serum corticosterone level
[98], and protected rats against testicular toxicity of chromium [106] and CP [82],
reduced LPO and improved antioxidant enzymatic activities; similarly, oil protected
against mercury chloride testicular toxicity [1]. Aqueous leaf extract even protected
against deleterious effects of mobile phone electromagnetic radiation on fertility in
1228 Moringa oleifera Lam.

rats [23]. Hydroethanol leaf extract orally administered from 5th to 10th day of
gestation caused 100% abortions in rats [109]. Aqueous root extract showed some
antiprogestational activity in ovariectomized rats [116], and its anti-implantation
activity was reported to be due to uterus being nonreceptive to fertilized eggs [99].
Orally administered methanol seed extract for three-weeks, significantly increased
sexual activity in normal and diabetic rats [47].
Clinical Studies: In a randomized comparative trial of thirty Indian patients with
UTI, two-third patients were cured and one-third improved after treatment with an
aqueous bark extract for three-weeks, compared to 46% cured and 26% improved in
the standard antibiotic treatment group [74]. Administration of leaf powder in
capsules to ten young fasting healthy Thai volunteers dose-dependently increased
serum insulin levels without affecting blood glucose levels [14]. Daily supple-
mentation with 7 g leaves powder to thirty postmenopausal Indian women for
three-months significantly lowered FBG level and significantly increased Hb, serum
retinol and ascorbic acid levels, and improved activities of antioxidative enzymes
compared to untreated controls [64]. In an open, noncomparative trial, treatment of
mild-to-moderate asthmatic Indian patients with powdered dried seed kernels, in a
dose of 3 g for 3-weeks, significantly improved symptoms and severity of asthmatic
attacks with a significant increase in Hb values and significant reduction in ESR [7].
Mechanism of Action: HMG-CoA reductase inhibitory potency of M. oleifera
extract was similar to pravastatin, that possibly results in reduced cholesterol
biosynthesis [37]. Its antioxidant activity was credited for many of its observed
pharmacological effects.
Human A/Es, Allergy and Toxicity: A case of occupational asthma has been
reported from France [97].
Animal Toxicity: A single oral dose of 5,000 mg/kg of aqueous leaf extract and
repeat doses up to 1,000 mg/kg for 14-days to rats were nonlethal and nontoxic
[15]. Oral LD50 of aqueous and ethanol leaf extracts in mice were reported to be
1,585 mg/kg [17], and more than 6,400 mg/kg, respectively [19]. Median lethal
dose of methanol seed extract in rat was 3,873 mg/kg; subacute toxicity study
showed significant increase in serum transaminases and body weight at daily dose
of 1,600 mg/kg [9]. Subacute toxicity studies on methanol leaf extract administered
to rats in a daily dose of 200 mg/kg or more for 5–8-weeks caused renal and hepatic
damage [89, 91].
CYP450 and Potential for Drug-Herb Interactions: Methanol and aqueous leaf
extracts showed significant in vitro CYP3A4 inhibitory effects [79], that might
result in interactions with conventional prescription drugs metabolized by CYP3A4.
Commentary: Pharmacological studies evidently show a wide-spectrum of ben-
eficial effects of all parts of this common tropical tree, and regular consumption of it
as a vegetable could contribute to the maintenance of health. However, its uti-
lization as a medicinal plant would require extensive controlled clinical trials to
Moringa oleifera Lam. 1229

objectively establish effectiveness for various conditions. This author, though,

witnessed the effective use of the decoction of its flowers as a household remedy for
inflammation.

References
1. Abarikwu SO, Benjamin S, Ebah SG, Obilor G, Agbam G. Oral
administration of Moringa oleifera oil but not coconut oil prevents
mercury-induced testicular toxicity in rats. Andrologia. 2017;49.
2. Abd El Latif A, El Bialy Bel S, Mahboub HD, Abd Eldaim MA. Moringa
oleifera leaf extract ameliorates alloxan-induced diabetes in rats by
regeneration of b cells and reduction of pyruvate carboxylase expression.
Biochem Cell Biol. 2014;92:413–9.
3. Abdull Razis AF, Ibrahim MD, Kntayya SB. Health benefits of Moringa
oleifera. Asian Pac J Cancer Prev. 2014;15:8571–6.
4. Abe R, Ohtani K. An ethnobotanical study of medicinal plants and
traditional therapies on Batan Island, the Philippines. J Ethnopharmacol.
2013;145:554–65.
5. Adedapo AA, Falayi OO, Oyagbemi AA. Evaluation of the analgesic,
anti-inflammatory, antioxidant, phytochemical and toxicological properties
of the methanolic leaf extract of commercially processed Moringa oleifera
in some laboratory animals. J Basic Clin Physiol Pharmacol. 2015;26:
491–9.
6. Adeyemi OS, Elebiyo TC. Moringa oleifera supplemented diets prevented
nickel-induced nephrotoxicity in Wistar rats. J Nutr Metab. 2014;2014:
958621.
7. Agrawal B, Mehta A. Antiasthmatic activity of Moringa oleifera Lam: a
clinical study. Indian J Pharmacol. 2008;40:28–31.
8. Ahmad S, Shah SM, Alam MK, et al. Antipyretic activity of hydroalco-
holic extracts of Moringa oleifera in rabbits. Pak J Pharm Sci. 2014;27:
931–4.
9. Ajibade TO, Arowolo R, Olayemi FO. Phytochemical screening and
toxicity studies on the methanol extract of the seeds of Moringa oleifera.
J Complement Integr Med. 2013;10.
10. Akanni EO, Adedeji AL, Adedosu OT, Olaniran OI, Oloke JK. Chemo-
preventive and antileukemic effects of ethanol extracts of Moringa oleifera
leaves on wistar rats bearing benzene induced leukemia. Curr Pharm
Biotechnol. 2014;15:563–8.
11. Al-Asmari AK, Albalawi SM, Athar MT, et al. Moringa oleifera as an
anticancer agent against breast and colorectal cancer cell lines. PLoS ONE.
2015;10:e0135814.
12. Alhakmani F, Kumar S, Khan SA. Estimation of total phenolic content,
in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa
oleifera. Asian Pac J Trop Biomed. 2013;3:623–7.
1230 Moringa oleifera Lam.

13. Al-Malki AL, El Rabey HA. The antidiabetic effect of low doses of
Moringa oleifera Lam. seeds on streptozotocin induced diabetes and
diabetic nephropathy in male rats. Biomed Res Int. 2015;2015:381040.
14. Anthanont P, Lumlerdkij N, Akarasereenont P, Vannasaeng S, Sriwi-
jitkamol A. Moringa oleifera leaf increases insulin secretion after single
dose administration: a preliminary study in healthy subjects. J Med Assoc
Thai. 2016;99:308–13.
15. Asiedu-Gyekye IJ, Frimpong-Manso S, Awortwe C, Antwi DA, Nyarko AK.
Micro- and macroelemental composition and safety evaluation of the
nutraceutical Moringa oleifera leaves. J Toxicol. 2014;2014:786979.
16. Atawodi SE. Nigerian foodstuffs with prostate cancer chemopreventive
polyphenols. Infect Agent Cancer. 2011;6 Suppl. 2:S9.
17. Awodele O, Oreagba IA, Odoma S, da Silva JA, Osunkalu VO.
Toxicological evaluation of the aqueous leaf extract of Moringa oleifera
Lam. (Moringaceae). J Ethnopharmacol. 2012;139:330–6.
18. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and
antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr.
2005;56:287–91.
19. Bakre AG, Aderibigbe AO, Ademowo OG. Studies on neuropharmaco-
logical profile of ethanol extract of Moringa oleifera leaves in mice.
J Ethnopharmacol. 2013;149:783–9.
20. Barminas JT, Charles M, Emmanuel D. Mineral composition of non-
conventional leafy vegetables. Plant Foods Hum Nutr. 1998;53:29–36.
21. Berkovich L, Earon G, Ron I, et al. Moringa oleifera aqueous leaf extract
downregulates nuclear factor-kappaB and increases cytotoxic effect of
chemotherapy in pancreatic cancer cells. BMC Complement Altern Med.
2013;13:212.
22. Bharali R, Tabassum J, Azad MR. Chemomodulatory effect of Moringa
oleifera, Lam, on hepatic carcinogen metabolising enzymes, antioxidant
parameters and skin papillomagenesis in mice. Asian Pac J Cancer Prev.
2003;4:131–9.
23. Bin-Meferij MM, El-Kott AF. The radioprotective effects of Moringa
oleifera against mobile phone electromagnetic radiation-induced infertility
in rats. Int J Clin Exp Med. 2015;8:12487–97.
24. Budda S, Butryee C, Tuntipopipat S, et al. Suppressive effects of Moringa
oleifera Lam. pod against mouse colon carcinogenesis induced by
azoxymethane and dextran sodium sulfate. Asian Pac J Cancer Prev.
2011;12:3221–8.
25. Cáceres A, Cabrera O, Morales O, Mollinedo P, Mendia P. Pharmacological
properties of Moringa oleifera. 1: preliminary screening for antimicrobial
activity. J Ethnopharmacol. 1991;33:213–6.
26. Cáceres A, Saravia A, Rizzo S, et al. Pharmacologic properties of Moringa
oleifera. 2: screening for antispasmodic, anti-inflammatory and diuretic
activity. J Ethnopharmacol. 1992;36:233–7.
Moringa oleifera Lam. 1231

27. Chen KH, Chen YJ, Yang CH, et al. Attenuation of the extract from
Moringa oleifera on monocrotaline-induced pulmonary hypertension in
rats. Chin J Physiol. 2012;55:22–30.
28. Choudhary MK, Bodakhe SH, Gupta SK. Assessment of the antiulcer
potential of Moringa oleifera root-bark extract in rats. J Acupunct
Meridian Stud. 2013;6:214–20.
29. Chuang PH, Lee CW, Chou JY, et al. Antifungal activity of crude extracts
and essential oil of Moringa oleifera Lam. Bioresour Technol. 2007;98:
232–6.
30. Chumark P, Khunawat P, Sanvarinda Y, et al. The in vitro and ex vivo
antioxidant properties, hypolipidaemic and antiatherosclerotic activities of
water extract of Moringa oleifera Lam. leaves. J Ethnopharmacol. 2008;
116:439–46.
31. D’souza J, Kulkarni AR. Comparative studies on nutritive values of tender
foliage of seedlings and mature plants of Moringa oleifera Lam. J Econ
Taxon Bot. 1993;17:479–85.
32. Das N, Ganguli D, Dey S. Moringa oleifera Lam. seed extract prevents fat
diet induced oxidative stress in mice and protects liver cell-nuclei from
hydroxyl radical mediated damage. Indian J Exp Biol. 2015;53:794–802.
33. Das N, Sikder K, Ghosh S, Fromenty B, Dey S. Moringa oleifera Lam.
leaf extract prevents early liver injury and restores antioxidant status in
mice fed with high-fat diet. Indian J Exp Biol. 2012;50:404–12.
34. Dholvitayakhun A, Cushnie TP, Trachoo N. Antibacterial activity of three
medicinal Thai plants against Campylobacter jejuni and other foodborne
pathogens. Nat Prod Res. 2012;26:356–63.
35. Diab KA, Guru SK, Bhushan S, Saxena AK. In vitro anticancer activities
of Anogeissus latifolia, Terminalia bellerica, Acacia catechu and Moringa
oleiferna Indian Plants. Asian Pac J Cancer Prev. 2015;16:6423–8.
36. Dièye AM, Sarr A, Diop SN, et al. Medicinal plants and the treatment of
diabetes in Senegal: survey with patients. Fundam Clin Pharmacol. 2008;
22:211–6.
37. Duangjai A, Ingkaninan K, Limpeanchob N. Potential mechanisms of
hypocholesterolaemic effect of Thai spices/dietary extracts. Nat Prod Res.
2011;25:341–52.
38. Dzotam JK, Touani FK, Kuete V. Antibacterial and antibiotic-modifying
activities of three food plants (Xanthosoma mafaffa Lam., Moringa oleifera
(L.) Schott and Passiflora edulis Sims.) against multidrug-resistant
(MDR) Gram-negative bacteria. BMC Complement Altern Med. 2016;16:9.
39. Eyarefe OD, Idowu A, Afolabi JM. Healing potentials of oral Moringa
Oleifera leaves extract and tetracycline on methicillin resistant Staphylo-
coccus aureus infected wounds of Wistar rats. Niger J Physiol Sci. 2015;
30:73–8.
40. Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution
of glucosinolates and isothiocyanates among plants. Phytochem. 2001;56:
5–51.
1232 Moringa oleifera Lam.

41. Faizi S, Siddiqui BS, Saleem R, et al. Hypotensive constituents from the
pods of Moringa oleifera. Planta Med. 1998;64:225–8.
42. Fakurazi S, Hairuszah I, Nanthini U. Moringa oleifera Lam. prevents
acetaminophen induced liver injury through restoration of glutathione
level. Food Chem Toxicol. 2008;46:2611–5.
43. Fakurazi S, Sharifudin SA, Arulselvan P. Moringa oleifera hydroethanolic
extracts effectively alleviate acetaminophen-induced hepatotoxicity in
experimental rats through their antioxidant nature. Molecules. 2012;17:
8334–50.
44. Ganguly R, Guha D. Alteration of brain monoamines and EEG wave
pattern in rat model of Alzheimer’s disease and protection by Moringa
oleifera. Indian J Med Res. 2008;128:744–51.
45. Ghasi S, Nwobodo E, Ofili JO. Hypocholesterolemic effects of crude
extract of leaf of Moringa oleifera Lam. in high-fat diet fed wistar rats.
J Ethnopharmacol. 2000;69:21–5.
46. Girija V, Sharada D, Pushpamma P. Bioavailability of thiamine, riboflavin
and niacin from commonly consumed green leafy vegetables in the rural
areas of Andhra Pradesh in India. Int J Vitam Nutr Res. 1982;52:9–13.
47. Goswami SK, Inamdar MN, Dethe SM, et al. Erectogenic and aphrodisiac
property of Moringa oleifera: involvement of soluble epoxide hydrolase
enzyme. Phytother Res. 2016;30:1119–27.
48. Goyal BR, Goyal RK, Mehta AA. Investigation into the mechanism of
antiasthmatic action of Moringa oleifera. J Diet Suppl. 2009;6:313–27.
49. Guevara AP, Vargas C, Sakurai H, et al. An antitumor promoter from
Moringa oleifera Lam. Mutat Res. 1999;440:181–8.
50. Gupta R, Kannan GM, Sharma M, Flora SJS. Therapeutic effects of
Moringa oleifera on arsenic-induced toxicity in rats. Environ Toxicol
Pharmacol. 2005;20:456–64.
51. Gupta R, Mathur M, Bajaj VK, et al. Evaluation of antidiabetic and
antioxidant activity of Moringa oleifera in experimental diabetes. J Dia-
betes. 2012;4:164–71.
52. Hamza AA. Ameliorative effects of Moringa oleifera Lam. seed extract on
liver fibrosis in rats. Food Chem Toxicol. 2010;48:345–55.
53. Jaiswal D, Kumar Rai P, Kumar A, Mehta S, Watal G. Effect of Moringa
oleifera Lam. leaves aqueous extract therapy on hyperglycemic rats.
J Ethnopharmacol. 2009;123:392–6.
54. Jaiswal D, Rai PK, Mehta S, et al. Role of Moringa oleifera in regulation of
diabetes-induced oxidative stress. Asian Pac J Trop Med. 2013;6:426–32.
55. Joshi P, Mehta D. Effect of dehydration on the nutritive value of drumstick
leaves. J Metabolomics Syst Biol. 2010;1:5–9.
56. Jung IL. Soluble extract from Moringa oleifera leaves with a new
anticancer activity. PLoS ONE. 2014;9:95492.
57. Jung IL, Lee JH, Kang SC. A potential oral anticancer drug candidate,
Moringa oleifera leaf extract, induces the apoptosis of human hepatocel-
lular carcinoma cells. Oncol Lett. 2015;10:1597–604.
Moringa oleifera Lam. 1233

58. Karthivashan G, Kura AU, Arulselvan P, Md Isa N, Fakurazi S. The

modulatory effect of Moringa oleifera leaf extract on endogenous
antioxidant systems and inflammatory markers in an acetaminophen-
induced nephrotoxic mice model. Peer J. 2016;4:e2127.
59. Kashiwada Y, Ahmed FA, Kurimoto S, et al. New a-glucosides of caffeoyl
quinic acid from the leaves of Moringa oleifera Lam. J Nat Med. 2012;66:
217–21.
60. Kasolo JN, Bimenya GS, Ojok L, et al. Phytochemicals and uses of
Moringa oleifera leaves in Ugandan rural communities. J Med Plants Res.
2010;4:753–7.
61. Kaur G, Invally M, Sanzagiri R, Buttar HS. Evaluation of the antidepres-
sant activity of Moringa oleifera alone and in combination with fluoxetine.
J Ayurveda Integr Med. 2015;6:273–9.
62. Kirisattayakul W, Wattanathorn J, Tong-Un T, et al. Cerebroprotective
effect of Moringa oleifera against focal ischemic stroke induced by middle
cerebral artery occlusion. Oxid Med Cell Longev. 2013;2013:951415.
63. Kurokawa M, Wadhwani A, Kai H, et al. Activation of cellular immunity
in herpes simplex virus type 1-infected mice by the oral administration of
aqueous extract of Moringa oleifera Lam. leaves. Phytother Res. 2016;30:
797–804.
64. Kushwaha S, Chawla P, Kochhar A. Effect of supplementation of
drumstick (Moringa oleifera) and amaranth (Amaranthus tricolor) leaves
powder on antioxidant profile and oxidative status among postmenopausal
women. J Food Sci Technol. 2014;51:3464–9.
65. Lamou B, Taiwe GS, Hamadou A, et al. Antioxidant and antifatigue
properties of the aqueous extract of Moringa oleifera in rats subjected to
forced swimming endurance test. Oxid Med Cell Longev. 2016;2016:
3517824.
66. Leone A, Spada A, Battezzati A, et al. Cultivation, genetic, ethnophar-
macology, phytochemistry and pharmacology of Moringa oleifera leaves:
an overview. Int J Mol Sci. 2015;16:12791–835.
67. Lunyera J, Wang D, Maro V, et al. Comprehensive kidney disease
assessment for risk factors, epidemiology, knowledge, and attitudes (CKD
AFRiKA) study: traditional medicine practices among community mem-
bers with diabetes mellitus in Northern Tanzania: an ethnomedical survey.
BMC Complement Altern Med. 2016;16:282.
68. Mahajan SG, Mali RG, Mehta AA. Protective effect of ethanolic extract of
seeds of Moringa oleifera Lam. against inflammation associated with
development of arthritis in rats. J Immunotoxicol. 2007;4:39–47.
69. Mahajan SG, Mehta AA. Effect of Moringa oleifera Lam. seed extract on
ovalbumin-induced airway inflammation in guinea pigs. Inhal Toxicol.
2008;20:897–909.
70. Mahajan SG, Mehta AA. Inhibitory action of ethanolic extract of seeds of
Moringa oleifera Lam. on systemic and local anaphylaxis. J Immunotox-
icol. 2007;4:287–94.
1234 Moringa oleifera Lam.

71. Manaheji H, Jafari S, Zaringhalam J, Rezazadeh S, Taghizadfarid R.

Analgesic effects of methanolic extracts of the leaf or root of Moringa
oleifera on complete Freund’s adjuvant-induced arthritis in rats. Zhong Xi
Yi Jie He Xue Bao. 2011;9:216–22.
72. Manguro LO, Lemmen P. Phenolics of Moringa oleifera leaves. Nat Prod
Res. 2007;21:56–68.
73. Mathieu G, Meissa D. Traditional leafy vegetables in Senegal: diversity
and medicinal uses. Afr J Tradit Complement Altern Med. 2007;4:469–75.
74. Maurya SK, Singh AK. Clinical efficacy of Moringa oleifera Lam. stems
bark in urinary tract infections. Int Sch Res Notices. 2014;2014:906843.
75. Mbikay M. Therapeutic potential of Moringa oleifera leaves in chronic
hyperglycemia and dyslipidemia: a review. Front Pharmacol. 2012;3:24.
76. Mehta K, Balaraman R, Amin AH, Bafna PA, Gulati OD. Effect of fruits of
Moringa oleifera on the lipid profile of normal and hypercholesterolaemic
rabbits. J Ethnopharmacol. 2003;86:191–5.
77. Minaiyan M, Asghari G, Taheri D, Saeidi M, Nasr-Esfahani S. Anti-
inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced
acute colitis in rats. Avicenna J Phytomed. 2014;4:127–36.
78. Mokkhasmit M, Swasdimongkol K, Ngarmwathana W, Permphiphat U.
Pharmacological evaluation of Thai medicinal plants. J Med Assoc Thai.
1971;54:490–504.
79. Monera TG, Wolfe AR, Maponga CC, Benet LZ, Guglielmo J. Moringa
oleifera leaf extracts inhibit 6b-hydroxylation of testosterone by CYP3A4.
J Infect Dev Ctries. 2008;2:379–83.
80. Muhammad AA, Arulselvan P, Cheah PS, Abas F, Fakurazi S. Evaluation
of wound healing properties of bioactive aqueous fraction from Moringa
oleifera Lam. on experimentally induced diabetic animal model. Drug Des
Devel Ther. 2016;10:1715–30.
81. Nandave M, Ojha SK, Joshi S, Kumari S, Arya DS. Moringa oleifera leaf
extract prevents isoproterenol-induced myocardial damage in rats: evidence
for an antioxidant, antiperoxidative, and cardioprotective intervention.
J Med Food. 2009;12:47–55.
82. Nayak G, Vadinkar A, Nair S, et al. Sperm abnormalities induced by
prepubertal exposure to cyclophosphamide are effectively mitigated by
Moringa oleifera leaf extract. Andrologia. 2016;48:125–36.
83. Ndhlala AR, Mulaudzi R, Ncube B, et al. Antioxidant, antimicrobial and
phytochemical variations in thirteen Moringa oleifera Lam. cultivars.
Molecules. 2014;19:10480–94.
84. Ndiaye M, Dieye AM, Mariko F, et al. Contribution to the study of the
anti-inflammatory activity of Moringa oleifera (moringaceae). Dakar Med.
2002;47:210–2 (Article in French).
85. Nfambi J, Bbosa GS, Sembajwe LF, Gakunga J, Kasolo JN. Immunomod-
ulatory activity of methanolic leaf extract of Moringa oleifera in Wistar
albino rats. J Basic Clin Physiol Pharmacol. 2015;26:603–11.
Moringa oleifera Lam. 1235

86. Nwosu MO, Okafor JI. Preliminary studies of the antifungal activities of
some medicinal plants against Basidiobolus and some other pathogenic
fungi. Mycoses. 1995;38:191–5.
87. Ogunbinu AO, Flamini G, Cioni PL, Adebayo MA, Ogunwande IA.
Constituents of Cajanus cajan (L.) Millsp., Moringa oleifera Lam.,
Heliotropium indicum L. and Bidens pilosa L. from Nigeria. Nat Prod
Commun. 2009;4:573–8.
88. Olayaki LA, Irekpita JE, Yakubu MT, Ojo OO. Methanolic extract of
Moringa oleifera leaves improves glucose tolerance, glycogen synthesis
and lipid metabolism in alloxan-induced diabetic rats. J Basic Clin Physiol
Pharmacol. 2015;26:585–93.
89. Omobowale TO, Oyagbemi AA, Abiola JO, et al. Effect of chronic
administration of methanol extract of Moringa oleifera on some biochem-
ical indices in female Wistar rats. Niger J Physiol Sci. 2014;29:107–11.
90. Ouédraogo M, Lamien-Sanou A, Ramdé N, et al. Protective effect of
Moringa oleifera leaves against gentamicin-induced nephrotoxicity in
rabbits. Exp Toxicol Pathol. 2013;65:335–9.
91. Oyagbemi AA, Omobowale TO, Azeez IO, et al. Toxicological evalua-
tions of methanolic extract of Moringa oleifera leaves in liver and kidney
of male Wistar rats. J Basic Clin Physiol Pharmacol. 2013;24:307–12.
92. Pal SK, Mukherjee PK, Saha K, Pal M, Saha BP. Antimicrobial action of
the leaf extract of Moringa oleifera Lam. Anc Sci Life. 1995;14:197–9.
93. Panda S. Butanolic fraction of Moringa oleifera Lam. (Moringaceae)
attenuates isoprotrenol-induced cardiac necrosis and oxidative stress in
rats: an EPR study. Excli J. 2015;14:64–74.
94. Pari L, Kumar NA. Hepatoprotective activity of Moringa oleifera on
antitubercular drug-induced liver damage in rats. J Med Food. 2002;5:
171–7.
95. Peixoto JR, Silva GC, Costa RA, et al. In vitro antibacterial effect of
aqueous and ethanolic Moringa leaf extracts. Asian Pac J Trop Med. 2011;
4:201–4.
96. Popoola JO, Obembe OO. Local knowledge, use pattern and geographical
distribution of Moringa oleifera Lam. (Moringaceae) in Nigeria. J Ethno-
pharmacol. 2013;150:682–91.
97. Poussel M, Penven E, Richard C, et al. Occupational asthma to “the
miracle tree” (Moringa oleifera): first description. J Allergy Clin Immunol
Pract. 2015;3:813–4.
98. Prabsattroo T, Wattanathorn J, Iamsaard S, et al. Moringa oleifera extract
enhances sexual performance in stressed rats. J Zhejiang Univ Sci B. 2015;
16:179–90.
99. Prakash AO, Pathak S, Shukla S, Mathur R. Uterine histoarchitecture
during pre and post-implantation periods of rats treated with aqueous
extract of Moringa oleifera Lam. Acta Eur Fertil. 1987;18:129–35.
1236 Moringa oleifera Lam.

100. Randriamboavonjy JI, Loirand G, Vaillant N, et al. Cardiac protective

effects of Moringa oleifera seeds in spontaneous hypertensive rats. Am J
Hypertens. 2016;29:873–81.
101. Rathi BS, Bodhankar SL, Baheti AM. Evaluation of aqueous leaves extract
of Moringa oleifera Linn. for wound healing in albino rats. Indian J Exp
Biol. 2006;44:898–901.
102. Rattanasena P. Antioxidant and antibacterial activities of vegetables and
fruits commonly consumed in Thailand. Pak J Biol Sci. 2012;15:877–82.
103. Ray K, Hazra R, Debnath PK, Guha D. Role of 5-hydroxytryptamine in
Moringa oleifera induced potentiation of pentobarbitone hypnosis in
albino rats. Indian J Exp Biol. 2004;42:632–5.
104. Ray K, Hazra R, Guha D. Central inhibitory effect of Moringa oleifera root
extract: possible role of neurotransmitters. Indian J Exp Biol. 2003;41:
1279–84.
105. Ruckmani K, Kavimani S, Jayakar B, Anandan R. Antiulcer activity of the
alkali preparation of the root and fresh leaf juice of Moringa oleifera Lam.
Anc Sci Life. 1998;17:220–3.
106. Sadek KM. Chemotherapeutic efficacy of an ethanolic Moringa oleifera
leaf extract against chromium-induced testicular toxicity in rats. Androlo-
gia. 2014;46:1047–54.
107. Sahakitpichan P, Mahidol C, Disadee W, Ruchirawat S, Kanchanapoom T.
Unusual glycosides of pyrrole alkaloid and 4′-hydroxyphenylethanamide
from leaves of Moringa oleifera. Phytochemistry. 2011;72:791–5.
108. Semenya S, Potgieter M, Erasmus L. Ethnobotanical survey of medicinal
plants used by Bapedi healers to treat diabetes mellitus in the Limpopo
Province, South Africa. J Ethnopharmacol. 2012;141:440–5.
109. Sethi N, Nath D, Shukla SC, Dyal R. Abortifacient activity of a medicinal
plant “Moringa oleifera” in rats. Anc Sci Life. 1988;7:172–4.
110. Sharifudin SA, Fakurazi S, Hidayat MT, et al. Therapeutic potential of
Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in
rats. Pharm Biol. 2013;51:279–88.
111. Sharma V, Paliwal R, Janmeda P, Sharma S. Chemopreventive efficacy of
Moringa oleifera pods against 7,12-dimethylbenz[a]anthracene induced
hepatic carcinogenesis in mice. Asian Pac J Cancer Prev. 2012;13:2563–9.
112. Sharma V, Paliwal R, Janmeda P, Sharma S. Renoprotective effects of
Moringa oleifera pods in 7,12-dimethylbenz [a] anthracene-exposed mice.
Zhong Xi Yi Jie He Xue Bao. 2012;10:1171–8.
113. Sharma V, Paliwal R. Potential chemoprevention of 7,12-dimethylbenz[a]
anthracene induced renal carcinogenesis by Moringa oleifera pods and its
isolated saponin. Indian J Clin Biochem. 2014;29:202–9.
114. Sheikh A, Yeasmin F, Agarwal S, et al. Protective effects of Moringa
oleifera Lam. leaves against arsenic-induced toxicity in mice. Asian Pac J
Trop Biomed. 2014;4 Suppl. 1:S353–8.
Moringa oleifera Lam. 1237

115. Sholapur HN, Patil BM. Effect of Moringa oleifera bark extracts on
dexamethasone-induced insulin resistance in rats. Drug Res (Stuttg).
2013;63:527–31.
116. Shukla S, Mathur R, Prakash AO. Antifertility profile of the aqueous
extract of Moringa oleifera roots. J Ethnopharmacol. 1988;22:51–62.
117. Singh D, Arya PV, Aggarwal VP, Gupta RS. Evaluation of antioxidant and
hepatoprotective activities of Moringa oleifera Lam. leaves in carbon
tetrachloride-intoxicated rats. Antioxidants (Basel). 2014;3:569–91.
118. Sreelatha S, Padma PR. Antioxidant activity and total phenolic content of
Moringa oleifera leaves in two stages of maturity. Plant Foods Hum Nutr.
2009;64:303–11.
119. Sutalangka C, Wattanathorn J, Muchimapura S, Thukham-mee W. Moringa
oleifera mitigates memory impairment and neurodegeneration in ani-
mal model of age-related dementia. Oxid Med Cell Longev. 2013;2013:
695936.
120. Taha NR, Amin HA, Sultan AA. The protective effect of Moringa oleifera
leaves against cyclophosphamide-induced urinary bladder toxicity in rats.
Tissue Cell. 2015;47:94–104.
121. Tiloke C, Phulukdaree A, Chuturgoon AA. The antiproliferative effect of
Moringa oleifera crude aqueous leaf extract on human esophageal cancer
cells. J Med Food. 2016;19:398–403.
122. Tiloke C, Phulukdaree A, Chuturgoon AA. The antiproliferative effect of
Moringa oleifera crude aqueous leaf extract on cancerous human alveolar
epithelial cells. BMC Complement Altern Med. 2013;13:226.
123. Toppo R, Roy BK, Gora RH, Baxla SL, Kumar P. Hepatoprotective
activity of Moringa oleifera against cadmium toxicity in rats. Vet World.
2015;8:537–40.
124. Viera GH, Mourão JA, Angelo AM, Costa RA, Vieira RH. Antibacterial
effect (in vitro) of Moringa oleifera and Annona muricata against Gram
positive and Gram negative bacteria. Rev Inst Med Trop Sao Paulo.
2010;52:129–32.
125. Waterman C, Rojas-Silva P, Tumer TB, et al. Isothiocyanate-rich Moringa
oleifera extract reduces weight gain, insulin resistance, and hepatic
gluconeogenesis in mice. Mol Nutr Food Res. 2015;59:1013–24.
126. Yassa HD, Tohamy AF. Extract of Moringa oleifera leaves ameliorates
streptozotocin-induced diabetes mellitus in adult rats. Acta Histochem.
2014;116:844–54.
Myristica fragrans Houtt.
(Myristicaceae)

(Syn.: M. moschata Thunb.)

Abstract
The tree is endemic to the Maluku Province of Indonesia, India, Sri Lanka,
Zanjibar, Indochina, Taiwan, and Malaysia. The small, dark colored, dry and very
light fruit (described as seed by many) with a very thin fragrant skin that is easily
broken, is used medicinally. The fragrant thin skin of nutmeg is called mace and is
used independently. Ibn-al-Baitar quoted various authorities that it is astringent,
digestive, improves functions of stomach, spleen and liver (cirrhosis), relieves
flatulence, and is beneficial for halitosis. Avicenna described it as antiemetic and
beneficial for eyesight and oliguria. It is especially useful in indigestion and
diarrhea due to decreased retentive strength of intestines in patients with ‘cold and
wet’ temperament. Muslim physicians in India describe nutmeg and mace as
stimulating, narcotic, digestive, tonic and aphrodisiac, useful in diarrhea of
cholera, especially when roasted; also, in obstruction of the liver and spleen.
A paste made with nutmeg was used in nervous headache and palsy, and applied
around the eyes was thought to strengthen eyesight. Ibn Jazlah called the peels of
the tree as the most useful medicinally. Nutmeg contains volatile oil comprised of
alkyl benzene derivatives, terpenes and myristic acid, d- and l-a-pinene, sabinene,
d-camphene, dipentene, elemicin and isoelemicin, safrole, eugenol, geraniol,
d-borneol, and l-terpineol; also 4% myristicin, which is toxic and narcotic. Behav-
ioral effects of nutmeg have varied by the type of extract and the route of
administration. Oral administration of methanol, dichloromethane (DE), and hexane
(HE) extracts caused a significant increase in locomotor activity, and i.p. adminis-
tration of DE and HE produced significant reduction in rectal and core body
temperature in mice. Myristica seed extract potently reduced TC, LDL-C, lowered
cholesterol/phospholipid ratio, and significantly elevated HDL-C, and prevented
accumulation of cholesterol, phospholipids and TGs in liver, heart and aorta, and
dissolved aortic atheromatous plaques by 75% of hypercholesterolemic rabbits. In a
double-blind RCT, topical application of nutmeg oil was not significantly different
in improving symptoms in diabetic painful neuropathy and neuropathic pain than
placebo.
© Springer Nature Switzerland AG 2020 1239
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_130
1240 Myristica fragrans Houtt.

Keywords







Bicuiba Basbasah Jayephal Javitri Joz-boya Mace Macis Muskatnuß




Nutmeg Róu dóu kóu

Vernaculars: Urd.: Javitri (Mace), Jayephal (Nutmeg); Hin.: Japatri, Javitri,

Jayephal; San.: Jati-kosha, Jati-pattri (Mace), Jatiphala (Nutmeg), Jati-phalam,
Jati-sara, Majja-sara (Nutmeg), Malathi-phalam, Shaluka; Ben.: Jayatri (Mace),
Jayephal, Jotri nuez moscada (Mace); Guj.: Jāyapatrī (mace), Jāyaphaḷa; Mal.:
Jatikka (Nutmeg), Jatipattiri (Mace); Mar.: Jayapatri, Jayephal; Tam.: Jadikai
(Nutmeg), Jadipattiri (Mace), Jathikkai; Tel.: Jaji-kaya (Nutmeg), Japatri (Mace);
Ara.: Basbasah (Mace), Jouz-bua, Joz-at-teeb; Bur.: Zadeikpo, Zadi-phu; Chi.:
Róu dóu kóu, Rou dou kou yi (Mace), Yu guo hua (Mace); Cze.: Muškátový květ
(Mace), Muškátový ořech; Dan.: Muskatblomme (Mace), Muskatnød; Dut.: Foelie
(Mace), Nootmuskaat, Nootmuskaatboom; Eng.: Mace, Nutmeg; Fin.: Muskot-
tikukka (Mace), Muskottipähkinä; Fre.: Fleur de muscade, Macis (Mace), Muscade
(Nutmeg), Noix de muscade; Ger.: Macis, Muskatblüte, Muskatnuß (Nutmeg),
Muskatnußbaum (Nutmeg tree); Gre.: Moschokarido anthos; Hun.: Szerecsendió
virág (Mace); Ind.: Fuli (Mace), Pala (Nutmeg), Sekar pala; Ita.: Mace, Noce
moscata (Nutmeg); Jap.: Meesu (mace), Mirisutika, Natsume, Natsumegu; Kor.:
Meisu (Mace); Maly.: Buah pala, Bunga pala, Kambang pala; Nep.: Jaaiipatrii
(Mace), Jayaphal; Nor.: Muskatblomme, Muskatnøtt; Per.: Basbaseh (Mace),
Gauz-i-buya (fragrant nut), Joz-boya (Nutmeg); Pol.: Gałka muszkatołowa,
Muszkat; Por.: Bicuiba, Muscadeira, Noz moscada (Br.); Rus.: Matsis (Mace);
Sin.: Sadikka (Nutmeg), Vasa-vasi (Mace); Spa.: Macia, Macis, Miristica, Mos-
cada, Moscadero, Nuez de bauda, Nuez de especias; Swe.: Muskotblomma (Mace),
Muskotnöt, Muskott; Tag.: Duguan; Tha.: Dok chan thet (Mace), Look chan thet;
Tur.: Besbase (Mace), Küçük hindistan cevizi; Vie.: Đậu khấu, Nhục đậu khấu.
Description: It is endemic to the Maluku Province of Indonesia, India, Sri Lanka,
Zanjibar, Indochina, Taiwan, and Malaysia. A 10–15 m tall tree with glabrous,
alternate leaves, nearly coriaceous, oval, elliptical or lanceolate, base acute or more
or less rounded, tip acuminate, 5–15 cm long by 3–7 cm wide. Inflorescence
axillary; flowers dioecious. The small, dark colored, dry and very light fruit (de-
scribed as seed by many) with a very thin fragrant skin that is easily broken, is used
medicinally. The fragrant thin skin of nutmeg is called mace (Bisbasah) and is used
independently. The fruits (seeds) are globular-oval-ellipsoidal, 26–30 mm long by
21–24 mm wide, cross section shows mottled surface. The odor is aromatic and
tastes strongly pungent.LXXIX The fruit is marked by a furrow which passes round
it, and by which at maturity its thick fleshy pericarp splits into two pieces,
exhibiting in its interior a single seed, enveloped in a fleshy foliaceous mantle or
arillus, of fine crimson hue, which is mace. The dark-brown, shining ovate seed is
marked with impressions corresponding to the lobes of the arillus; and on one side,
which is of paler hue and slightly flattened, a line indicating the raphe may be
observed (Figs. 1 and 2).XL
Myristica fragrans Houtt. 1241

Fig. 1 Myristica fragrans, Unripe Fruit on a Tree, Dinesh Valke, WikimediaCommons; ShareAlike
2.0 Generic CC BY-SA 2.0, https://commons.wikimedia.org/wiki/File:Jayaphal_(Konkani-_%E0%
A4%9C%E0%A4%BE%E0%A4%AF%E0%A4%AB%E0%A4%B3)_(6935056401).jpg; https://
creativecommons.org/licenses/by-sa/2.0/deed.en

Fig. 2 Myristica fragrans, Nutmeg Fruit and Mace, Prof. Akbar, Original

Actions and Uses: Ibn-al-BaitarLXIX quoted various authorities that it is astringent,

digestive, improves functions of stomach, spleen and liver (cirrhosis), relieves
flatulence, and is beneficial for halitosis. Avicenna described it as antiemetic and
beneficial for eyesight and oliguria. It is especially useful in indigestion and diarrhea
due to decreased retentive strength of intestines in patients with ‘cold and wet’
temperament. Muslim physicians in India describe nutmeg and mace as stimulating,
narcotic, digestive, tonic and aphrodisiac, useful in diarrhea of cholera, especially
when roasted; also, in obstruction of the liver and spleen. A paste made with nutmeg
was used in nervous headache and palsy, and applied around the eyes was thought to
1242 Myristica fragrans Houtt.

strengthen eyesight.XL Ibn Jazlah called the peels of the tree as the most useful
medicinally.LIII In Unani medicine, it (temperament, hot 2° and dry 2°) is used in the
treatment of weakened heart, decreased libido, weak digestion, flatulence, and
diarrhea; externally, it is used as a paste for arthritis, paralysis, and headache.LXXVII
Tayyab1 recommended 500 mg powdered mace in honey for chronic cough with
sticky sputum, urinary incontinence, and leucorrhea. NadkarniCV described nutmeg
useful in jaundice, and mace as stomachic, digestive, carminative, antidiarrheal, and
aphrodisiac. In Ayurveda, nutmeg is said to possess antidiarrheal activity [15]; in
small doses it stimulates gastric juice secretion promoting digestion, increasing
appetite, relieving intestinal spasm and flatulence.LXXIX Mace is used in Indonesian
folk medicine as aromatic, stomachic, analgesic, and as a remedy for rheumatism
[40], and traditionally used by the people of Maluku Province (known as Spice
Islands) of Indonesia to treat diarrhea, mouth sores, and insomnia; its reported
hallucinogenic or other psychoactive properties, other than a mild sedative action,
have been discredited [63], and in Malaysia, nutmeg is used to treat epilepsy [1].
Nutmeg is contained in 100% of the multi-ingredient formulae that are used to treat
imbalance of rLung, one of the three humors in Tibetan medicine, whose imbalance
is considered the source of mental disorders [2]. Macelignan possesses antibacterial,
anti-inflammatory, anticancer, antidiabetes, hepatoprotective and neuroprotective
activities [42]. The seeds (nutmeg, essential oil 5–15%) are used as a flavor and
carminative.CXXXXI
Phytoconstituents: Nutmeg contains volatile oil comprised of alkyl benzene
derivatives, terpenes and myristic acid [13, 21], d- and l-a-pinene, sabinene,
60–80% d-camphene, 8% dipentene, 2% elemicin and isoelemicin, 0.6% safrole,
eugenol, geraniol, d-borneol, and l-terpineol; also 4% myristicin, which is toxic and
narcotic.CXXXXI Essential oil obtained by supercritical carbon dioxide extraction
showed the presence of 48 compounds with myristic acid, myristicin, terpinen-4-ol,
a-pinene and safrole being the major compounds; whereas b-pinene, terpinen-4-ol,
a-pinene, c-terpinene and b-phellandrene were the main components out of 38
compounds identified in the EO obtained by steam distillation [45]. However, EO
obtained by hydrodistillation was reported by Soni et al. [58] to mostly contain
c-terpinolene, p-cymene, thymol and b-pinene. Sabinene and a-pinene were
identified as the constituents responsible for the characteristic nutmeg odor [5].
Lignans, mesodihydroguaiaretic acid and otobaphenol [65], tetrahydrofuroguaiacin
B, saucernetindiol, verrucosin, nectandrin B, nectandrin A, fragransin C, and gal-
bacin [37], have been isolated from nutmeg. Fifteen compounds including myris-
ticin, methyleugenol, safrole, dehydrodiisoeugenol, guaiacin and myrisisolignan
were identified by Yang et al. [66] from nutmeg, and trimyristin was isolated by
Lugemwa [27]. Diarylbutane lignans and aryltetralin lignan were isolated from
methanol extract of seeds [25]. Malabaricone B and C, the resorcinols isolated from
mace possess strong antifungal and antibacterial activities [39]. Mace also contains
trace elements in decreasing order: Se > Zn> Mg > Fe > Ca > Mn and > Pb [69].

1
Tayyab M: Personal Communication.
Myristica fragrans Houtt. 1243

In Chinese medicine, nutmegs are processed by soaking in water and roasting with
bran. The EOs obtained from processed and unprocessed nutmeg differ both
qualitatively and quantitatively. In the processed nutmeg oil, thirteen new com-
ponents are detected while four components are lost. Quantitatively methyleugenol
and methylisoeugenol are increased, while the amounts of myristicin and safrol are
decreased in the processed nutmeg oil [68].
Pharmacology: Behavioral effects of nutmeg have varied by the type of extract
and the route of administration. Oral administration of methanol, dichloromethane
(DE), and hexane (HE) extracts caused a significant increase in locomotor activity,
and i.p. administration of DE and HE produced significant reduction in rectal and
core body temperature in mice [12]. n-Hexane extract and trimyristin exhibited
anxiogenic activity and trimyristin antagonized the anxiolytic effect of diazepam,
ondansetron, and buspirone [57]; myristicin was also found to promote anxiogen-
esis and antagonized anxiolytic effect of midazolam in rats [26]. n-Hexane extract
also elicited a significant antidepressant-like effect in mice that was postulated to
involve adrenergic, dopaminergic, and serotonergic systems [10]. n-Hexane extract
orally administered for three successive days significantly improved learning and
memory of young and aged mice, and also reversed scopolamine- and diazepam-
induced impairment in learning and memory of young mice [41], and significantly
decreased AChE activity in brains of mice [9]; also, hydroalcohol extract in vitro
inhibited AChE activity by 50% [35]. Essential oil administered by inhalation to
mice also significantly decreased locomotor activity [34].
Methanol mace extract inhibited growth of twenty strains of H. pylori with an
MIC of 12.5 mcg/ml [3], while methanol seed extract inhibited growth of 15 strains
of H. pylori with an MIC of 12.5 mcg/ml [30], and showed strong antibacterial
activity against MDR S. typhi [47]. Nutmeg extract in vitro inhibited human rotavirus
growth by 90%, an organism responsible for diarrhea in infants and young children
[14]. The volatile oil shows antibacterial activity against a broad range of organisms
[11], against E. coli, P. vulgaris, K. pneumoniae, S. aureus, B. subtilis and B.
megaterium [58]. Nutmeg and mace extracts and macelignan strongly inhibit growth
of S. mutans and other oral microorganisms, such as S. sobrinus, S. salivarius, S.
sanguis, L. acidophilus, L. casei and A. viscosus [7, 50, 67]. Malabaricone C strongly
inhibits P. gingivalis growth, an organism involved in periodontal disease [54].
Myristicin and trimyristin also show significant antibacterial activity [36].
Myristica seed extract potently reduced TC, LDL-C, lowered cholesterol/
phospholipid ratio, and significantly elevated HDL-C, and prevented accumulation
of cholesterol, phospholipids and TGs in liver, heart and aorta, and dissolved aortic
atheromatous plaques by 75% of hypercholesterolemic rabbits [46, 51]. Macelig-
nan, a dual agonist for PPARa/c, significantly improved glucose and insulin-
tolerance and reduced serum levels of glucose, insulin, TGs, and FFA, and TGs
levels in skeletal muscle and liver of db/db obese mice [17]. Phenylpropanoid
compounds, 4-allyl-2,6-dimethoxyphenol, terpinene-4-ol, and a-terpineol exhibited
significant antioxidant activity [29]. Myristicin exhibited extraordinarily potent
hepatoprotective activity against LPS plus d-galactosamine-induced hepatotoxicity
1244 Myristica fragrans Houtt.

in rats [32]; macelignan also protected against cisplatin-hepatotoxicity [56]. Crude

nutmeg suspension, petroleum ether and ethanol extracts are reported to show
antidiarrheal activity and increase intestinal tone [15, 44]. Nutmeg extract (i.p.) also
significantly produced gastric antiulcer effects in rabbits [19]. Nutmeg possesses
strong reducing power and superoxide radical scavenging activity [64]; the oil
shows significant in vitro antioxidant and antiangiogenic activities [43], and
macelignans are reported to protect against oxidative damage [55]. Pretreatment of
mice with alcohol extract protects against radiation induced biochemical alterations,
decreases the increased testicular LPO and acid phosphatase activity, and increases
depleted hepatic GSH and alkaline phosphatase activity [52]. Ethanol nutmeg
extract (oral) increased libido and overall sexual behavior of mice [60, 61].
Methanol mace extract and one of its fractions produced marked and lasting
anti-inflammatory effect, comparable approximately to that of indomethacin [40].
Chloroform nutmeg extract exhibited anti-inflammatory, analgesic and antithrom-
botic activities [38], and the methanol extract inhibited NO production and
iNOS mRNA expression in LPS-stimulated macrophages [62]. Oral treatment with
macelignan attenuated eosinophilic airway inflammation and airway hyper-
responsiveness in mice [53], and reduced LPS-induced hippocampal microglial
activation and hippocampal-dependent spatial memory impairments of rats [28].
Mace administered in diet to mice reduced both the incidence and average number
of chemically-induced skin papillomas [20], and uterine cervix carcinogenesis of
mice [18]. Mace replenished significantly decreased levels of serum trace elements
in MCA-induced uterine cervix tumors, that could be directly or indirectly
responsible for its antitumor activity [69]. Methanol nutmeg extract also induced
in vitro apoptosis of Jurkat leukemia T cell line [6].
Clinical Studies: In a double-blind RCT, topical application of nutmeg oil was not
significantly different in improving symptoms in diabetic painful neuropathy and
neuropathic pain than placebo [33].
Human A/Es, Allergy and Toxicity: Occupational allergies and asthma due to
exposure to nutmeg dust have been reported [49]. Harmless in normal use, dried
seed kernel is sometimes ground and self-administered in large amount (more than
one nutmeg) as a cheap recreational drug.CXXXV In man 6–7 mg/kg of myristicin
may be enough to cause psychological effects. However, it is unlikely that
myristicin present in EOs and spices in food would cause adverse effects in humans
[16]. Nutmeg use as a cheap recreational drug has increased over the years [23], that
has resulted in acute nutmeg poisoning due to intentional use of high doses. Cases
of intoxication have occurred after ingestion of about 5 g, corresponding to 1–2 mg
myristicin/kg body weight, or more of nutmeg [13, 16, 31]. Individuals inten-
tionally abusing nutmeg are more likely to be between the ages of 13 and 20; the
intoxication results only in moderate clinical effects, and no death has ever been
reported even after use of 50 g nutmeg [4, 8, 13]. Symptoms may appear 6 h after
ingestion of at least 10 g of nutmeg; patient may present with anxiety, restlessness,
agitation, palpitations, drowsiness, nausea, dizziness, thirst, and dry mouth; some
may complain of stomachache and dizziness. Patients recover without any treatment
Myristica fragrans Houtt. 1245

or sequelae [8, 24]. Even patients using as high as 20–80 g of powdered nutmeg had
never faced a life-threatening situation. A 13-year-old girl suffered from visual,
auditory, and tactile hallucinations, nausea, gagging, hot/cold sensations, blurred
vision, headache, and drowsiness after ingesting 15–24 g of nutmeg over a 3-h
period and smoked and shared 2 joints of marijuana. Still, her vital signs and
laboratory tests remained normal and she fully recovered in a couple days [48]. The
only fatal case of a 55-year-old woman in whom myristicin (4 lg/ml) was detected
at autopsy probably died due to the combined toxic effects of flunitrazepam
(0.072 lg/ml) and nutmeg. Myristicin blood level of 2 lg/ml have been detected 8 h
after ingestion of approximately 14–21 g of nutmeg powder [59].
Animal Toxicity: Orally administered myristicin to rats at a dose of 10 mg/kg did
not cause any toxicity [16].
CYP450 and Potential for Drug-Herb Interactions: Nutmeg volatile oil induces
hepatic microsomal CYP450 in mice [70]. However, nutmeg is also reported to
significantly inhibit in vitro human CYP2C9 activity [22].
Commentary: Use of nutmeg as a spice is prevalent and historically it has also
been used medicinally, especially for GIT and CNS afflictions. However, in light of
the available cheaper and effective alternatives, unless clinical studies prove it
substantially useful, it does not hold big promise as a medicine.

References
1. Abdullah JM. Interesting asian plants: their compounds and effects on
electrophysiology and behaviour. Malays J Med Sci. 2011;18:1–4.
2. Antonio RL, Kozasa EH, Galduróz JC, et al. Formulas used by Tibetan
doctors at Men-Tsee-Khang in India for the treatment of neuropsychiatric
disorders and their correlation with pharmacological data. Phytother Res.
2013;27:552–63.
3. Bhamarapravati S, Pendland SL, Mahady GB. Extracts of spice and food
plants from Thai traditional medicine inhibit the growth of the human
carcinogen Helicobacter pylori. In Vivo. 2003;17:541–4.
4. Carstairs SD, Cantrell FL. The spice of life: an analysis of nutmeg
exposures in California. Clin Toxicol (Phila). 2011;49:177–80.
5. Chatterjee S, Gupta S, Variyar SP. Comparison of essential oils obtained
from different extraction techniques as an aid in identifying aroma significant
compounds of nutmeg (Myristica fragrans). Nat Prod Commun. 2015;10:
1443–6.
6. Chirathaworn C, Kongcharoensuntorn W, Dechdoungchan T, et al. Myris-
tica fragrans Houtt. methanolic extract induces apoptosis in a human
leukemia cell line through SIRT1 mRNA downregulation. J Med Assoc
Thai. 2007;90:2422–8.
1246 Myristica fragrans Houtt.

7. Chung JY, Choo JH, Lee MH, Hwang JK. Anticariogenic activity of
macelignan isolated from Myristica fragrans (nutmeg) against Streptococ-
cus mutans. Phytomedicine. 2006;13:261–6.
8. Demetriades AK, Wallman PD, McGuiness A, Gavalas MC. Low cost, high
risk: accidental nutmeg intoxication. Emerg Med J. 2005;22:223–5.
9. Dhingra D, Parle M, Kulkarni SK. Comparative brain cholinesterase-
inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid,
and metrifonate in mice. J Med Food. 2006;9:281–3.
10. Dhingra D, Sharma A. Antidepressant-like activity of n-hexane extract of
nutmeg (Myristica fragrans) seeds in mice. J Med Food. 2006;9:84–9.
11. Dorman HJ, Deans SG. Antimicrobial agents from plants: antibacterial
activity of plant volatile oils. J Appl Microbiol. 2000;88:308–16.
12. El-Alfy AT, Wilson L, ElSohly MA, Abourashed EA. Towards a better
understanding of the psychopharmacology of nutmeg: activities in the
mouse tetrad assay. J Ethnopharmacol. 2009;126:280–6.
13. Forrester MB. Nutmeg intoxication in Texas, 1998–2004. Hum Exp Toxicol.
2005;24:563–6.
14. Gonçalves JL, Lopes RC, Oliveira DB, et al. In vitro antirotavirus activity of
some medicinal plants used in Brazil against diarrhea. J Ethnopharmacol.
2005;99:403–7.
15. Grover JK, Khandkar S, Vats V, et al. Pharmacological studies on Myristica
fragrans—antidiarrheal, hypnotic, analgesic and hemodynamic (blood pres-
sure) parameters. Methods Find Exp Clin Pharmacol. 2002;24:675–80.
16. Hallström H, Thuvander A. Toxicological evaluation of myristicin. Nat
Toxins. 1997;5:186–92.
17. Han KL, Choi JS, Lee JY, et al. Therapeutic potential of peroxisome
proliferators-activated receptor-alpha/gamma dual agonist with alleviation
of endoplasmic reticulum stress for the treatment of diabetes. Diabetes.
2008;57:737–45.
18. Hussain SP, Rao AR. Chemopreventive action of mace (Myristica fragrans,
Houtt.) on methylcholanthrene-induced carcinogenesis in the uterine cervix
in mice. Cancer Lett. 1991;56:231–4.
19. Jan M, Faqir F, Hamida, Mughal MA. Comparison of effects of extract of
Myristica fragrans and verapamil on the volume and acidity of carbachol
induced gastric secretion in fasting rabbits. J Ayub Med Coll Abbottabad.
2005;17:69–71.
20. Jannu LN, Hussain SP, Rao AR. Chemopreventive action of mace
(Myristica fragrans Houtt.) on DMBA-induced papillomagenesis in the
skin of mice. Cancer Lett. 1991;56:59–63.
21. Janssen J, Lackman G. Nutmeg oil: identification and quantification of its
most active constituents as inhibitors of platelet aggregation. J Ethnophar-
macol. 1990;29:179–88.
22. Kimura Y, Ito H, Hatano T. Effects of mace and nutmeg on human
cytochrome P450 3A4 and 2C9 activity. Biol Pharm Bull. 2010;33:1977–82.
Myristica fragrans Houtt. 1247

23. Kresanek J, Plackova S, Caganova B, Klobusicka Z. Drug abuse in Slovak

Republic. Przegl Lek. 2005;62:357–60.
24. Krol CG, Janssen MJ. Unusual use of nutmeg. Ned Tijdschr Geneeskd.
2010;154:A2214 (Dutch).
25. Kwon HS, Kim MJ, Jeong HJ, et al. Low-density lipoprotein (LDL)-
antioxidant lignans from Myristica fragrans seeds. Bioorg Med Chem Lett.
2008;18:194–8.
26. Leiter E, Hitchcock G, Godwin S, et al. Evaluation of the anxiolytic
properties of myristicin, a component of nutmeg, in the male Sprague-
Dawley rat. AANA J. 2011;79:109–14.
27. Lugemwa FN. Extraction of betulin, trimyristin, eugenol and carnosic acid
using water-organic solvent mixtures. Molecules. 2012;17:9274–82.
28. Ma J, Hwang YK, Cho WH, et al. macelignan attenuates activations of
mitogen-activated protein kinases and nuclear factor kappa B induced by
lipopolysaccharide in microglial cells. Biol Pharm Bull. 2009;32:1085–90.
29. Maeda A, Tanimoto S, Abe T, et al. Chemical constituents of Myristica
fragrans Houttuyn seed and their physiological activities. Yakugaku Zasshi.
2008;128:129–33.
30. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of
Helicobacter pylori to botanical extracts used traditionally for the treatment
of gastrointestinal disorders. Phytother Res. 2005;19:988–91.
31. McKenna A, Nordt SP, Ryan J. Acute nutmeg poisoning. Eur J Emerg Med.
2004;11:240–1.
32. Morita T, Jinno K, Kawagishi H, et al. Hepatoprotective effect of myristicin
from nutmeg (Myristica fragrans) on lipopolysaccharide/d-galactosamine-
induced liver injury. J Agric Food Chem. 2003;51:1560–5.
33. Motilal S, Maharaj RG. Nutmeg extracts for painful diabetic neuropathy: a
randomized, double-blind, controlled study. J Altern Complement Med.
2013;19:347–52.
34. Muchtaridi Subarnas A, Apriyantono A, Mustarichie R. Identification of
compounds in the essential oil of nutmeg seeds (Myristica fragrans Houtt.)
that inhibit locomotor activity in mice. Int J Mol Sci. 2010;11:4771–81.
35. Mukherjee PK, Kumar V, Houghton PJ. Screening of Indian medicinal
plants for acetylcholinesterase inhibitory activity. Phytother Res. 2007;21:
1142–5.
36. Narasimhan B, Dhake AS. Antibacterial principles from Myristica fragrans
seeds. J Med Food. 2006;9:395–9.
37. Nguyen PH, Le TV, Kang HW, et al. AMP-activated protein kinase
(AMPK) activators from Myristica fragrans (nutmeg) and their antiobesity
effect. Bioorg Med Chem Lett. 2010;20:4128–31.
38. Olajide OA, Ajayi FF, Ekhelar AI, et al. Biological effects of Myristica
fragrans (nutmeg) extract. Phytother Res. 1999;13:344–5.
39. Orabi KY, Mossa JS, el-Feraly FS. Isolation and characterization of two
antimicrobial agents from mace (Myristica fragrans). J Nat Prod. 1991;54:
856–9.
1248 Myristica fragrans Houtt.

40. Ozaki Y, Soedigdo S, Wattimena YR, Suganda AG. Anti-inflammatory

effect of mace, aril of Myristica fragrans Houtt., and its active principles.
Jpn J Pharmacol. 1989;49:155–63.
41. Parle M, Dhingra D, Kulkarni SK. Improvement of mouse memory by
Myristica fragrans seeds. J Med Food. 2004;7:157–61.
42. Paul S, Hwang JK, Kim HY, et al. Multiple biological properties of
macelignan and its pharmacological implications. Arch Pharm Res. 2013;
36:264–72.
43. Piaru SP, Mahmud R, Abdul Majid AM, Mahmoud Nassar ZD. Antioxidant
and antiangiogenic activities of the essential oils of Myristica fragrans and
Morinda citrifolia. Asian Pac J Trop Med. 2012;5:294–8.
44. Pillai NR, Lillykutty L. Antidiarrhoel potential of Myristica frangrans seed
extracts. Anc Sci Life. 1991;11:74–7.
45. Qiu Q, Zhang G, Sun X, Liu X. Study on chemical constituents of the
essential oil from Myristica fragrans Houtt. by supercritical fluid extraction
and steam distillation. Zhong Yao Cai. 2004;27:823–6 (Article in Chinese).
46. Ram A, Lauria P, Gupta R, Sharma VN. Hypolipidaemic effect of Myristica
fragrans fruit extract in rabbits. J Ethnopharmacol. 1996;55:49–53.
47. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
48. Sangalli BC, Chiang W. Toxicology of nutmeg abuse. J Toxicol Clin
Toxicol. 2000;38:671–8.
49. Sastre J, Olmo M, Novalvos A, et al. Occupational asthma due to different
spices. Allergy. 1996;51:117–20.
50. Shafiei Z, Shuhairi NN, Md Fazly Shah Yap N, et al. Antibacterial activity
of Myristica fragrans against oral pathogens. Evid Based Complement
Alternat Med. 2012;2012:825362.
51. Sharma A, Mathur R, Dixit VP. Prevention of hypercholesterolemia and
atherosclerosis in rabbits after supplementation of Myristica fragrans seed
extract. Indian J Physiol Pharmacol. 1995;39:407–10.
52. Sharma M, Kumar M. Radioprotection of Swiss albino mice by Myristica
fragrans Houtt. J Radiat Res (Tokyo). 2007;48:135–41.
53. Shin K, Chung HC, Kim DU, et al. Macelignan attenuated allergic lung
inflammation and airway hyperresponsiveness in murine experimental
asthma. Life Sci. 2013;92:1093–9.
54. Shinohara C, Mori S, Ando T, Tsuji T. Arg-gingipain inhibition and
antibacterial activity selective for Porphyromonas gingivalis by malabari-
cone C. Biosci Biotechnol Biochem. 1999;63:1475–7.
55. Sohn JH, Han KL, Choo JH, Hwang JK. Macelignan protects HepG2 cells
against tertbutylhydroperoxide-induced oxidative damage. BioFactors. 2007;
29:1–10.
56. Sohn JH, Han KL, Kim JH, et al. Protective effects of macelignan on
cisplatin-induced hepatotoxicity is associated with JNK activation. Biol
Pharm Bull. 2008;31:273–7.
Myristica fragrans Houtt. 1249

57. Sonavane GS, Sarveiya VP, Kasture VS, Kasture SB. Anxiogenic activity of
Myristica fragrans seeds. Pharmacol Biochem Behav. 2002;71:239–44.
58. Soni R, Sharma G, Jasuja ND. Essential oil yield pattern and antibacterial
and insecticidal activities of Trachyspermum ammi and Myristica fragrans.
Scientifica (Cairo). 2016;2016:1428194.
59. Stein U, Greyer H, Hentschel H. Nutmeg (myristicin) poisoning—report on
a fatal case and a series of cases recorded by a poison information centre.
Forensic Sci Int. 2001;118:87–90.
60. Tajuddin, Ahmad S, Latif A, et al. An experimental study of sexual function
improving effect of Myristica fragrans Houtt. (nutmeg). BMC Complement
Altern Med. 2005;5:16.
61. Tajuddin, Ahmad S, Latif A, Qasmi IA. Aphrodisiac activity of 50%
ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium
aromaticum (L.) Merr. & Perry. (clove) in male mice: a comparative study.
BMC Complement Altern Med. 2003;3:6.
62. Tezuka Y, Irikawa S, Kaneko T, et al. Screening of Chinese herbal drug
extracts for inhibitory activity on nitric oxide production and identification
of an active compound of Zanthoxylum bungeanum. J Ethnopharmacol.
2001;77:209–17.
63. Van Gils C, Cox PA. Ethnobotany of nutmeg in the Spice Islands.
J Ethnopharmacol. 1994;42:117–24.
64. Yadav AS, Bhatnagar D. Modulatory effect of spice extracts on
iron-induced lipid peroxidation in rat liver. BioFactors. 2007;29:147–57.
65. Yang S, Na MK, Jang JP, et al. Inhibition of protein tyrosine phosphatase
1B by lignans from Myristica fragrans. Phytother Res. 2006;20:680–2.
66. Yang XW, Huang X, Ahmat M. New neolignan from seed of Myristica
fragrans. Zhongguo Zhong Yao Za Zhi. 2008;33:397–402.
67. Yanti, Rukayadi Y, Kim KH, Hwang JK. In vitro anti-biofilm activity of
macelignan isolated from Myristica fragrans Houtt. against oral primary
colonizer bacteria. Phytother Res. 2008;22:308–12.
68. Yuan ZM, Wang J, Lv J, Jia TZ. Comparing analysis of components in
volatile oils of nutmeg and prepared nutmeg by GC-MS. Zhongguo Zhong
Yao Za Zhi. 2006;31:737–9.
69. Zhang C, Qi X, Shi Y, et al. Estimation of trace elements in mace (Myristica
fragrans Houtt.) and their effect on uterine cervix cancer induced by
methylcholanthrene. Biol Trace Elem Res. 2012;149:431–4.
70. Zhao R, Wang W, Zhao L, Li Z, Wang J. Effect of volatile oil from nutmeg
on liver microsomal cytochrome P450 in mice. Zhongguo Zhong Yao Za
Zhi. 2009;34:447–9.
Myrtus communis L.
(Myrtaceae)

Abstract
An evergreen shrub, native to Europe, Mediterranean region, North Africa, West
Asia and India. In Rome, the plant was supposed not only to inspire love, but to
maintain it. Before pepper was known, myrtle was used as a spice to season food,
and wine was flavored with them. Myrtle enjoyed a prominent place in the writings
of Hippocrates, Dioscorides, Pliny, Galen and the Arabian physicians. Galen said
that its leaves, stems, fruits and the juice are equally astringent. According to Pliny,
berries were used in dysentery, and as an application to indolent ulcers and
inflamed eyes; and in wine are antidote to poison of mushrooms. Avicenna in his
legendary book Canon of Medicine mentioned it as one of the drugs for the
treatment of abnormal uterine bleeding. Fresh or dried fruits are diuretic and
beneficial in hemoptysis and cystitis; seeds are tonic for intestines and urinary
bladder, and relieve foul smell from gums and mouth (halitosis). In the Ethiopian
folk medicine, it is suggested to aid sleep, and also used as sedative-hypnotic in
Iranian traditional medicine. In the Mediterranean region, especially in Sardinia, it
is used as a flavoring agent for alcoholic beverages. Both leaves and the berries
contain high levels of total phenolic content, responsible for their antioxidant
property. Berries are also a rich source of minerals, such as Ca, K, Mg, Na and
P. Administration of ethanol-water extract of aerial parts did not affect blood
glucose of normal mice, but administered 30 min before STZ, abolished initial
hyperglycemic phase without affecting the second phase, and if the dose was
repeated at 24 and 30 h, it did not allow hyperglycemia to develop until after 48 h.
Essential oil of Ethiopian origin did not produce hypnosis but potentiated
pentobarbital sleeping time in mice, and ethanol leaf extract exerted anxiolytic,
myorelaxant and hypnotic effects. In a double-blind RCT, myrtle fruit syrup for
7-days during menstrual period for three consecutive periods in women suffering
from menometrorrhagia, significantly reduced the bleeding. In a double-blinded
RCT, freeze-dried aqueous extract of myrtle fruits was as effective as omeprazole
in relieving symptoms of GERD.

© Springer Nature Switzerland AG 2020 1251

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_131
1252 Myrtus communis L.

Keywords







Aass Arrayán Asbiri Maatoru Mersin Murad Murteira Myrte Myrtle



Xiang tao mu

Vernaculars: Urd.: Aass, Marteen, Moorad; Hin.: Baragasha, Murad, Sata Sova,
Vilayati mehndi (leaves); San.: Gandhamalati; Ben.: Bilatimehedi, Sutra-sowa,
Velayti mehndi; Mal.: Mirṟṟas kam’myūṇisaṁ; Mar.: Firangimethi, Murt; Tam.:
Cativam, Kulinaval, Sadevam, Tev, Tevam; Tel.: Chitti jama; Ara.: Ahmam, Arri-
hane, Asbiri, Aselmûn, Habb-el-aass (berries), Hadass (South Arabia), Halmuch,
HoumblassIsmar, Isfaren, Mirsin, Raihan (North Africa); Chi.: 香桃木, Xiang tao
mu; Dan.: Myrte; Dut.: Gewone mirt, Mirt, Mirte; Eng.: Myrtle; Fre.: Herbe du lagui,
Myrte, Myrte commun, Myrte juif, Nerte; Ger.: Brautmyrte, Gewöhnliche myrte,
Myrte; Gre.: Mirtia, Myrtos; Ita.: Mirto, Mirto comune, Mortella; Jap.: Ginbaika,
Iwai no ki, Maatoru; Per.: Barg-e-murad (leaves); Por.: Gorreiro, Mata-pulgas, Mirta,
Mirto, Mitra, Murta, Murteira, Murtinheira, Murtinhos, Trovisco, Trovisco-fêmea,
Trovisqueiro; Rus.: Mirt, Myrt; Spa.: Arrayán, Arrayán blanco, Arrayán común,
Arrayán morisco, Astruc, Mata gallinas, Mirto, Murtal, Murtera, Murtonera; Swe.:
Myrten; Tur.: Mersin.
Description: It is native to Europe, Mediterranean region, North Africa, West Asia
and India. Evergreen shrub, grows wild throughout the Mediterranean region; berries
black, pear-shaped, and slightly sweet; seeds yellowish-white, hard, kidney-shaped,
and 6, 8 or 12 in number; taste bland; leaves small, lanceolate, and dotted, margins
revolute, very agreeably aromatic when bruised.LXXXI Ibn al-BaitarLXIX described it
as an evergreen tree that is usually found in the Arabian mountains and plains, with
white fragrant flowers, that has a fruit which becomes darker on ripening and is sweet
with a little bitterness, and is also called Quntus (Figs. 1, 2 and 3).
Actions and Uses: In Rome, the plant was supposed not only to inspire love, but to
maintain it. Before pepper was known, myrtle was used as a spice to season food, and
wine was flavored with them. Myrtle enjoyed a prominent place in the writings of
Hippocrates, Dioscorides, Pliny, Galen and the Arabian physicians. Galen said that its
leaves, stems, fruits and the juice are equally astringent. According to Pliny, berries
were used in dysentery, and as an application to indolent ulcers and inflamed eyes; and
in wine are antidote to poison of mushrooms. They also cure scorpion bites,
inflammation of bladder, headaches, abscesses, aphthae, leucorrhea and other mucous
discharges; juice is diuretic, but constipates. An ointment made with it cures skin
eruptions and darkens hair. Dried leaves in powder form arrest sweats; in fomentations
check the white flux, correct prolapses of the womb and rectum, and are employed to
cure ulcers, burns, erysipelas, otorrhea, alopecia, and eruptions of the skin, to arrest
hemorrhage, and as application to lentigo, pterygium, panaris, condylomata, and
swelled testicles. A wine made from the berries was used for most of these purposes
and was regarded as tonic.XL Avicenna in his legendary book Canon of Medicine
mentioned it as one of the drugs for the treatment of abnormal uterine bleeding [42].
Quoting Idrisi, Ghāfiqī mentioned Marziyanij as a synonym; and in the Jewish book
Myrtus communis L. 1253

Fig. 1 Myrtus communis, Yellow Variety Ripe Myrtle Berries, Giancarlo Dessi, WikimediaCom-
mons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Myrtus_
communis4.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Myrtus communis, Blue (Black) Variety Myrtle Berries, Javier Martin, WikimediaCommons,
https://commons.wikimedia.org/wiki/File:Myrtus_communis_Fruits_Closeup_DehesaBoyalPuertol
lano.jpg

Talmud, it is reported that people danced in front of the bridal procession holding
myrtle in their hands.LIII Ibn al-BaitarLXIX quoted Galen that it has opposite qualities
but the earthy cold element is dominant, and its leaves, stems, fruits and juice are all
astringent. Fresh or dried fruits are diuretic and beneficial in hemoptysis and cystitis;
seeds are tonic for intestines and urinary bladder, and relieve foul smell from gums
and mouth (halitosis). KabeeruddinLXXVII described fruits (temperament, cold 1° and
1254 Myrtus communis L.

Fig. 3 Myrtus communis, Black Berries, Giancarlo Dessi, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Myrtus_communis_10.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

dry 2°) as astringent, styptic, antidiaphoretic, stomachic and cardiotonic, and the
leaves as analgesic and drying, that blacken and strengthen hair. Fruit syrup is used in
the treatment of diarrhea, to stop bleeding, for palpitations, and to strengthen stomach
and heart; the leaves are applied as paste or poultice on inflammations and headache.
In Turkish folk medicine, myrtle leaves and their volatile oil are used to lower blood
glucose level in type-2 diabetic patients [47, 55]. Fragrant volatile oil from leaves is
antiseptic and rubefacient, and is used in affections of respiratory organs and bladder,
and as topical application in rheumatic affections.CV In folk medicines of many
countries, fruits (berries) are used in the treatment of various infectious diseases,
including diarrhea and dysentery; while leaves are used as antiseptic and
anti-inflammatory agents, as mouthwash for treatment of candidiasis, for wound
healing, and in urinary diseases [17, 20, 35], and for the treatment of respiratory
disorders, diarrhea and hemorrhoids [15]. Khory and KatrakLXXXI stated that in small
doses it aids digestion, and is used to check profuse expectoration in chronic fetid
bronchitis, gangrene of the lungs, whooping cough, asthma, and chronic inflammation
of the bladder and urethra. It is an important plant in Tunisian Pharmacopoeia, and
myrtle berry is used for its astringent, tonic, and antiseptic properties to treat diarrhea,
GIT disorders, and hemorrhoids [30]. In the Ethiopian folk medicine, it is suggested to
aid sleep [12], and also used as sedative-hypnotic in Iranian traditional medicine [25].
In the Mediterranean region, especially in Sardinia, it is used as a flavoring agent for
alcoholic beverages [51].
Phytoconstituents: Both leaves and the berries contain high levels of total phenolic
content [5, 28, 43, 56, 60], responsible for their antioxidant property. Berries are also a
rich source of minerals, such as Ca, K, Mg, Na and P [24]. Hydroalcohol leaf extract
contains galloylglucosides, ellagitannins, galloylquinic acids and flavonol glycosides
[50], and leaf extracts are also reported to contain significantly higher amount of total
Myrtus communis L. 1255

phenolic compounds than berry extracts [5]. Acylphloroglucinols, myrtucommulone-A

and myrtucommulone-B [53], dimeric nonprenylated acylphloroglucinol, semimyr-
tucommulone [7], hydrolyzable tannins (oenothein B, eugeniflorin D, tellimagrandins I
and II), polyphenolic compounds (gallic acid and quinic acid 3,5-di-O-gallate), and
myricetin glycosides (myricetins 3-O-b-D-xyloside, 3-O-b-D-galactoside, 3-O-b-D-
galactoside 6″-O-gallate, and 3-O-a-L-rhamnoside) [63] have been isolated from the
leaves. In traditional medicines, myrtle is consumed as an infusion or decoction; main
constituents in Tunisian myrtle leaves infusions were 1,8-cineole (42.58–51.39%),
a-terpineol (9.45–9.72%), methyl eugenol (6.69–7.11%), and linalool (5.91–6.06%)
[39]. While EO from Morocco showed the presence of myrtenyl acetate, 1,8-cineole
and a-pinene, and lacked significant antibacterial activity against food pathogens [19],
essential oil offruits offour genotypes of myrtle growing in Turkey had high amounts of
oxygenated monoterpenes, representing 73.02–83.83% of the oil, and 1,8-cineole
(29.20–31.40%), linalool (15.67–19.13%), a-terpineol (8.40–18.43%), a-pinene (6.04–
20.71%), and geranyl acetate (3.98–7.54%) as the major constituents [33]. Myrtle leaves
from Egypt contained phenolic compounds: gallic acid, methyl gallate, myricetin-
3-O-b-glucoside, myricetin-3-O-2-rhamnopyranoside, quercetin-3-O-b-galactoside,
quercitrin, ellagic acid, myricetin, quercetin and quercetin-3-O-b-glucopyranoside [45].
Polyphenol composition of Corsican myrtus berries consisted of two phenolic acids,
four flavanols, three flavonols and five flavonol glycosides; major compounds being
myricetin-3-O-arabinoside and myricetin-3-O-galactoside [9]. Chemical analysis of
Iranian myrtle leaves EO showed the presence of 70 components; 1,8-cineole, a-pinene,
linalool, bornyl acetate, a-terpineol, linalyl acetate and limonene in descending order
being the major components [34], whereas Nabavizadeh et al. [44] reported 1,8-cineole
(28.62%), a-pinene (17.8%), linalool (17.55%), and geranyl acetate (6.3%) as the major
compounds, and geraniol (1.6%), a-humulene (1.5%), eugenol (1.3%), isobutylisobu-
tyrate (0.8%), and methyl chavicol (0.5%) as the minor components of leaves EO; that
was effective against E. faecalis, S. aureus and C. albicans. Essential oil from wild
myrtle growing in southwest Iran contained a-pinene (22.3–55.2%), 1,8-cineole (8.7–
43.8%) and linalool (6.4–14.5%) as the major components [48].
Essential oil obtained from myrtle leaves collected from southernmost and
northern point of the Montenegro coastline, showed monoterpenes as the predominant
compounds; a-pinene, linalool, 1,8-cineole, and myrtenyl acetate being the major
constituents, with significant variation in a-pinene and myrtenyl acetate contents [40].
However, major compounds in the EO from leaves and berries, collected from
different places in Sardinia, Corsica and northeastern Algeria, were a-pinene,
1,8-cineole, linalool, a-terpineol, and limonene, with higher limonene content, and
myrtenyl acetate being conspicuous by its absence [14, 16, 59, 65], a-pinene (50.8 and
33.6%), 1,8-cineole (21.9 and 13.3%), linalool (2.7 and 14.8%), and linalyl acetate
(0.5 and 9.5%) were reported as major monoterpene derivatives in two samples of EOs
from Algeria [15]; whereas, Berka-Zougali et al. [11] reported only a-pinene and
1,8-cineole as the major compounds of Algerian myrtle leaf EO. Tunisian oil
was bactericidal to L. monocytogenes and strongly active against other food patho-
gens; myrtenyl acetate (20.75%), 1,8-cineol (16.55%), a-pinene (15.59%), linalool
1256 Myrtus communis L.

(13.30%), limonene (8.94%), linalyl acetate (3.67%), geranyl acetate (2.99%), and
a-terpineol (2.88%) were found to be the major components out of 17 compounds
[10]. Oils obtained from dark blue fruits of a Tunisian myrtle variety showed higher
percentages of a-terpineol, a-pinene, linalool, methyl eugenol, and geraniol, while the
white berries oil contained myrtenyl acetate as the major compound [38]. Methanol
extract of wildly grown myrtle fruits in Turkey contained oleic acid as the dominant
fatty acid, followed by palmitic and stearic acid [56].
Pharmacology: Intragastric administration of ethanol-water extract (2 g/kg) of
aerial parts did not affect blood glucose of normal mice, but administered 30 min
before STZ, abolished initial hyperglycemic phase without affecting the second phase,
and if the dose was repeated at 24 and 30 h, it did not allow hyperglycemia to develop
until after 48 h [20]. Turkish myrtle leaves EO did not affect blood glucose of nor-
moglycemic rabbits either in a single or multiple doses, but caused a good hypo-
glycemic effect after an oral glucose load in normal rabbits, and in diabetic animals.
Repeated administration once daily for one-week significantly lowered blood glucose
by 51% in diabetic rabbits, without affecting serum insulin concentrations but sig-
nificantly reduced serum TGs [55]. Aqueous-methanol leaves extract orally admin-
istered to diabetic rats for 28-days ameliorated changes in lipid profile, markedly
increased GSH content and decreased LPO level [47]. Aqueous leaf extract strongly
inhibited a-glucosidase activity [46].
Essential oil of Ethiopian origin did not produce hypnosis per se but potentiated
pentobarbital sleeping time in mice [12], and ethanol leaf extract (i.p.) exerted anxi-
olytic, myorelaxant and hypnotic effects [25]. Significant anti-inflammatory activity
of leaf extracts, EO, and myrtucommulone has been reported [3, 6, 37, 52]. The EO,
alcohol and aqueous leaf extracts, myricetin 3-O-b-glucopyranoside, myricetin
3-O-/-rhamnopyranoside and gallic acid showed significant antihyperglycemic,
anti-inflammatory and antinociceptive effects in rats [45]. Low dose of an aqueous
extract and high dose of methanol extract of berries were significantly more protective
against ethanol-induced gastric ulcers in rats than omeprazole [58], whereas ethanol
extract strongly inhibited secretion of IL-8 from H. pylori-infected gastric epithelial
cells [64]. Myrtle berry aqueous extract protected against esophageal reflux damage in
rats [31], and castor oil-induced intestinal fluid accumulation and diarrhea [29, 30];
methanol leaves extract also protected against castor oil-induced diarrhea in mice [57].
Aqueous leaf extract showed significant antibacterial activity against P. aerugi-
nosa isolated from burn patients [4]. A crude extract was reported bactericidal to
S. aureus, P. mirabilis and P. vulgaris [2]. The EO also showed significant activity
against E. coli, S. aureus and C. albicans [62], clinical isolates of C. albicans,
C. tropicalis and C. parapsilosis, with 24-h MIC90 of 2 µg/ml compared to MIC90 of
0.5 µg/ml of amphotericin B [18], and showed synergistic activity with amphotericin
B against C. albicans and Aspergillus spp. [34]. Myrtle oil also strongly inhibited
growth of oral pathogens, P. gingivalis [26], S. mutans, 20 strains of S. pyogenes,
A. actinomycetemcomitans and C. albicans [21], and both sensitive and MDR
M. tuberculosis with an MIC of 0.17% [65]. Combination of subinhibitory concen-
trations of EOs from Serbia with ciprofloxacin or polymyxin B synergistically
Myrtus communis L. 1257

reduced growth of MDR A. baumannii wound isolates [1]. Two samples of EO from
Algeria were strongly active against C. neoformans, E. floccosum, M. canis, and
T. rubrum [15]. Methanol seed extract was also substantially active against S. aureus,
B. cereus and B. bronchiseptica [13]. Myrtucommulone A is also strongly active
against many clinically relevant MDR bacteria [7], and significantly inhibited growth
of S. aureus, S. albus, strains of B. subtilis, B. pumilus, S. faecalis and C. diphtheria.
Concentrations as low as 0.5 µg/ml inhibited growth of B. subtilis, but addition of 10
and 20 µg/ml to the culture medium completely inhibited growth of S. aureus and
B. subtilis, respectively [53]. Ethanol leaf extract also showed significant activity
against P. falciparum [54].
Clinical Studies: In a double-blind RCT, administration of myrtle fruit syrup for
7-days during menstrual period for three consecutive periods in 30 Iranian women
suffering from menometrorrhagia, significantly reduced the bleeding [49]. In a
6-week, double-blinded RCT, freeze-dried aqueous extract of myrtle fruits was as
effective as omeprazole in relieving symptoms of GERD [66]. In a double-blinded
RCT of 120 married Iranian women aged 18–40 years suffering from bacterial
vaginosis, were treated with either metronidazole gel (0.75%) alone or with ethanol
myrtle leaf extract (2%) added to the metronidazole gel base for 5 nights. Myrtle group
had a better response than metronidazole gel alone with no relapse, while 30% of
patients in metronidazole alone group experienced relapse during three-weeks follow
up [36]. In a blinded RCT, a paste containing myrtle, applied during episodes of
recurrent aphthous stomatitis, significantly reduced ulcer size, pain severity, erythema
and exudation, and improved overall oral health [8]. Topical application of leaf
macerate on skin warts produced more rapid response than salicylic acid with fewer
side effects [23]. Two young Iranian girls with warts on their hands, neck and faces,
topically treated their warts only on hands and neck with myrtle leaves macerated in
water for twenty-days, and had their facial warts also completely cured [41].
Mechanism of Action: Anti-inflammatory effect of the leaves is due to potent
suppression by myrtucommulone and semimyrtucommulone of the biosynthesis of
eicosanoids by direct inhibition of COX-1 and 5-LOX [22]. Topical anti-inflammatory
activity of EO is due to reduced leukocyte migration to the damaged tissue, serum IL-6
and TNF-a, and myeloperoxidase activity [37]. Myrtucommulone was reported to be
the first natural product to inhibit microsomal PGE2 synthase-1 that efficiently sup-
presses PGE2 synthesis without significant inhibition of COX enzymes [32]. Anal-
gesic activity of the aqueous and ethanol extracts of aerial parts was suggested to be
mediated by opioid receptors, as it was inhibited by naloxone [27].
Human A/Es, Allergy and Toxicity: No known or reported human A/Es or
toxicity.
Animal Toxicity: Oral LD50 of aqueous and ethanol extracts of aerial parts in
mice were reported to be 473 mg and 790 mg/kg, respectively [27]. Acute oral
toxic doses of the leaves EO in rats and mice were 3.7 ml/kg, and 2.2 ml/kg,
respectively [61]. However, by subcutaneous route the volatile oil, alcohol and
1258 Myrtus communis L.

aqueous leaf extracts were practically nontoxic to mice, as they caused no mortality
or toxicity symptoms [45].
Commentary: Constituents of EO from Myrtle leaves vary both qualitatively and
quantitatively depending upon geographical location of the plant, and sometimes
within the same country. However, EO possesses significant antimicrobial and
anti-inflammatory activities, though clinical trials are warranted. Myrtucommulone
was recognized as the first natural product to inhibit microsomal PGE2 synthase-1
that efficiently suppresses PGE2 synthesis without significant inhibition of COX
enzymes. These activities could be further explored. Leaves and the berries also
possess significant antimicrobial activities, even against many clinically relevant
MDR bacteria. Only formal studies in clinically relevant states would establish the
medicinal value of this familiar plant.

References
1. Aleksic V, Mimica-Dukic N, Simin N, Nedeljkovic NS, Knezevic P. Syner-
gistic effect of Myrtus communis L. essential oils and conventional antibiotics
against multidrug resistant Acinetobacter baumannii wound isolates. Phy-
tomedicine. 2014;21:1666–74.
2. Alem G, Mekonnen Y, Tiruneh M, Mulu A. In vitro antibacterial activity of
crude preparation of myrtle (Myrtus communis) on common human pathogens.
Ethiop Med J. 2008;46:63–9.
3. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory
activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26:
163–8.
4. Al-Saimary IE, Bakr SS, Jaffar T, et al. Effects of some plant extracts and
antibiotics on Pseudomonas aeruginosa isolated from various burn cases.
Saudi Med J. 2002;23:802–5.
5. Amensour M, Sendra E, Abrini J, et al. Total phenolic content and antioxidant
activity of myrtle (Myrtus communis) extracts. Nat Prod Commun. 2009;
4:819–24.
6. Amira S, Dade M, Schinella G, Ríos JL. Anti-inflammatory, antioxidant,
and apoptotic activities of four plant species used in folk medicine in the
Mediterranean basin. Pak J Pharm Sci. 2012;25:65–72.
7. Appendino G, Bianchi F, Minassi A, et al. Oligomeric acylphloroglucinols
from myrtle (Myrtus communis). J Nat Prod. 2002;65:334–8.
8. Babaee N, Mansourian A, Momen-Heravi F, et al. The efficacy of a paste
containing Myrtus communis (Myrtle) in the management of recurrent aphthous
stomatitis: a randomized controlled trial. Clin Oral Investig. 2010;14:65–70.
9. Barboni T, Cannac M, Massi L, et al. Variability of polyphenol compounds in
Myrtus communis L. (Myrtaceae) berries from Corsica. Molecules. 2010;15:
7849–60.
Myrtus communis L. 1259

10. Ben Hsouna A, Hamdi N, Miladi R, Abdelkafi S. Myrtus communis essential

oil: chemical composition and antimicrobial activities against food spoilage
pathogens. Chem Biodivers. 2014;11:571–80.
11. Berka-Zougali B, Ferhat MA, Hassani A, et al. Comparative study of
essential oils extracted from Algerian Myrtus communis L. leaves using
microwaves and hydrodistillation. Int J Mol Sci. 2012;13:4673–95.
12. Birhanie MW, Walle B, Rebba K. Hypnotic effect of the essential oil from
the leaves of Myrtus communis on mice. Nat Sci Sleep. 2016;8:267–75.
13. Bonjar GH. Antibacterial screening of plants used in Iranian folkloric
medicine. Fitoterapia. 2004;75:231–5.
14. Bouzabata A, Boussaha F, Casanova J, Tomi F. Composition and chemical
variability of leaf oil of Myrtus communis from northeastern Algeria. Nat
Prod Commun. 2010;5:1659–62.
15. Bouzabata A, Cabral C, Gonçalves MJ, et al. Myrtus communis L. as source
of a bioactive and safe essential oil. Food Chem Toxicol. 2015;75:166–72.
16. Bouzabata A, Castola V, Bighelli A, et al. Chemical variability of Algerian
Myrtus communis L. Chem Biodivers. 2013;10:129–37.
17. Cakir A. Essential oil and fatty acid composition of Hippophae rhamnoides
L. (Sea Buckthorn) and Myrtus communis L. from Turkey. Biochem Syst
Ecol. 2004;3:809–16.
18. Cannas S, Molicotti P, Ruggeri M, et al. Antimycotic activity of Myrtus
communis L. towards Candida spp. from isolates. J Infect Dev Ctries. 2013;
7:295–8.
19. Cherrat L, Espina L, Bakkali M, et al. Chemical composition and antioxidant
properties of Laurus nobilis L. and Myrtus communis L. essential oils from
Morocco and evaluation of their antimicrobial activity acting alone or in
combined processes for food preservation. J Sci Food Agric. 2014;94:
1197–204.
20. El-Fellah MS, Akhter MH, Khan MT. Antihyperglycemic effect of an extract
of Myrtus communis in streptozotocin-induced diabetes in mice. J Ethnophar-
macol. 1984;11:275–81.
21. Fani MM, Kohanteb J, Araghizadeh A. Inhibitory activity of Myrtus
communis oil on some clinically isolated oral pathogens. Med Princ Pract.
2014;23:363–8.
22. Feisst C, Franke L, Appendino G, Werz O. Identification of molecular
targets of the oligomeric nonprenylated acylphloroglucinols from Myrtus
communis and their implication as anti-inflammatory compounds. J Phar-
macol Exp Ther. 2005;315:389–96.
23. Ghadami Yazdi E, Minaei MB, Hashem Dabaghian F, et al. Efficacy of
Myrtus communis L. and Descurainia sophia L. versus salicylic acid for
wart treatment. Iran Red Crescent Med J. 2014;16:e16386.
24. Hacıseferoğulları H, Ozcan MM, Arslan D, Unver A. Biochemical
compositional and technological characterizations of black and white
myrtle (Myrtus communis L.) fruits. J Food Sci Technol. 2012;49:82–8.
1260 Myrtus communis L.

25. Hajiaghaee R, Faizi M, Shahmohammadi Z, et al. Hydroalcoholic extract of

Myrtus communis can alter anxiety and sleep parameters: a behavioural and
EEG sleep pattern study in mice and rats. Pharm Biol. 2016;54:2141–8.
26. Hedayati A, Khosropanah H, Bazargani A, Abed M, Emami A. Assessing
the antimicrobial effect of the essential oil of Myrtus communis on the
clinical isolates of Porphyromonas gingivalis: an in vitro study. Jundisha-
pur J Nat Pharm Prod. 2013;8:165–8.
27. Hosseinzadeh H, Khoshdel M, Ghorbani M. Antinociceptive, anti-inflam-
matory effects and acute toxicity of aqueous and ethanolic extracts of Myrtus
communis L. aerial parts in mice. J Acupunct Meridian Stud. 2011;4:242–7.
28. Ines S, Ines B, Wissem B, et al. In vitro antioxidant and antigenotoxic
potentials of 3,5-O-di-galloylquinic acid extracted from Myrtus communis
leaves and modulation of cell gene expression by H2O2. J Appl Toxicol.
2012;32:333–41.
29. Jabri MA, Rtibi K, Ben-Said A, et al. Antidiarrhoeal, antimicrobial and antiox-
idant effects of myrtle berries (Myrtus communis L.) seeds extract. J Pharm
Pharmacol. 2016;68:264–74.
30. Jabri MA, Rtibi K, Sakly M, Marzouki L, Sebai H. Role of gastrointestinal
motility inhibition and antioxidant properties of myrtle berries (Myrtus
communis L.) juice in diarrhea treatment. Biomed Pharmacother. 2016;84:
1937–44.
31. Jabri MA, Tounsi H, Rtibi K, et al. Ameliorative and antioxidant effects of
myrtle berry seed (Myrtus communis) extract during reflux-induced
esophagitis in rats. Pharm Biol. 2016;25:1–11 (Epub ahead of print).
32. Koeberle A, Pollastro F, Northoff H, Werz O. Myrtucommulone, a natural
acylphloroglucinol, inhibits microsomal prostaglandin E(2) synthase-1. Br J
Pharmacol. 2009;156:952–61.
33. Kordali S, Usanmaz A, Cakir A, Komaki A, Ercisli S. Antifungal and
herbicidal effects of fruit essential oils of four Myrtus communis genotypes.
Chem Biodivers. 2016;13:77–84.
34. Mahboubi M, Ghazian Bidgoli F. In vitro synergistic efficacy of combi-
nation of amphotericin B with Myrtus communis essential oil against
clinical isolates of Candida albicans. Phytomedicine. 2010;17:771–4.
35. Mansouri S, Foroumadi A, Ghaneie T, Najar AG. Antibacterial activity of
the crude extracts and fractionated constituents of Myrtus communis. Pharm
Biol. 2001;39:399–401.
36. Masoudi M, Miraj S, Rafieian-Kopaei M. Comparison of the effects of
Myrtus communis L, Berberis vulgaris and metronidazole vaginal gel alone
for the treatment of bacterial vaginosis. J Clin Diagn Res. 2016;10:QC04–7.
37. Maxia A, Frau MA, Falconieri D, et al. Essential oil of Myrtus communis
inhibits inflammation in rats by reducing serum IL-6 and TNF-alpha. Nat
Prod Commun. 2011;6:1545–8.
38. Messaoud C, Boussaid M. Myrtus communis berry color morphs: a compar-
ative analysis of essential oils, fatty acids, phenolic compounds, and
antioxidant activities. Chem Biodivers. 2011;8:300–10.
Myrtus communis L. 1261

39. Messaoud C, Laabidi A, Boussaid M. Myrtus communis L. infusions: the

effect of infusion time on phytochemical composition, antioxidant, and
antimicrobial activities. J Food Sci. 2012;77:C941–7.
40. Mimica-Dukić N, Bugarin D, Grbović S, et al. Essential oil of Myrtus
communis L. as a potential antioxidant and antimutagenic agents. Molecules.
2010;15:2759–70.
41. Minaei MB, Ghadami Yazdi E, Ebrahim Zadeh Ardakani M, et al. First case
report: treatment of the facial warts by using Myrtus communis L. topically
on the other part of the body. Iran Red Crescent Med J. 2014;16:e13565.
42. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal
plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
43. Montoro P, Tuberoso CI, Piacente S, et al. Stability and antioxidant activity
of polyphenols in extracts of Myrtus communis L. berries used for the
preparation of myrtle liqueur. J Pharm Biomed Anal. 2006;41:1614–9.
44. Nabavizadeh M, Abbaszadegan A, Gholami A, et al. Chemical constituent
and antimicrobial effect of essential oil from Myrtus communis leaves on
microorganisms involved in persistent endodontic infection compared to
two common endodontic irrigants: an in vitro study. J Conserv Dent. 2014;
17:449–53.
45. Nassar MI, Aboutabl el-SA, Ahmed RF, et al. Secondary metabolites and
bioactivities of Myrtus communis. Pharmacognosy Res. 2010;2:325–9.
46. Onal S, Timur S, Okutucu B, Zihnioğlu F. Inhibition of alpha-glucosidase
by aqueous extracts of some potent antidiabetic medicinal herbs. Prep
Biochem Biotechnol. 2005;35:29–36.
47. Ozkol H, Tuluce Y, Dilsiz N, Koyuncu I. Therapeutic potential of some
plant extracts used in Turkish traditional medicine on streptozocin-induced
type 1 diabetes mellitus in rats. J Membr Biol. 2013;246:47–55.
48. Pirbalouti AG, Mirbagheri H, Hamedi B, Rahimi E. Antibacterial activity of
the essential oils of myrtle leaves against Erysipelothrix rhusiopathiae.
Asian Pac J Trop Biomed. 2014;4:S505–9.
49. Qaraaty M, Kamali SH, Dabaghian FH, et al. Effect of myrtle fruit syrup on
abnormal uterine bleeding: a randomized double-blind, placebo-controlled
pilot study. Daru. 2014;22:45.
50. Romani A, Coinu R, Carta S, et al. Evaluation of antioxidant effect of
different extracts of Myrtus communis L. Free Radic Res. 2004;38:97–103.
51. Rosa A, Melis MP, Deiana M, et al. Protective effect of the oligomeric
acylphloroglucinols from Myrtus communis on cholesterol and human low
density lipoprotein oxidation. Chem Phys Lipids. 2008;155:16–23.
52. Rossi A, Di Paola R, Mazzon E, et al. Myrtucommulone from Myrtus
communis exhibits potent anti-inflammatory effectiveness in vivo. J Phar-
macol Exp Ther. 2009;329:76–86.
53. Rotstein A, Lifshitz A, Kashman Y. Isolation and antibacterial activity of
acylphloroglucinols from Myrtus communis. Antimicrob Agents Chemother.
1974;6:539–42.
1262 Myrtus communis L.

54. Sangian H, Faramarzi H, Yazdinezhad A, et al. Antiplasmodial activity of

ethanolic extracts of some selected medicinal plants from the northwest of
Iran. Parasitol Res. 2013;112:3697–701.
55. Sepici A, Gürbüz I, Cevik C, Yesilada E. Hypoglycaemic effects of myrtle oil
in normal and alloxan-diabetic rabbits. J Ethnopharmacol. 2004;93:311–8.
56. Serce S, Ercisli S, Sengul M, et al. Antioxidant activities and fatty acid
composition of wild grown myrtle (Myrtus communis L.) fruits. Pharma-
cogn Mag. 2010;6:9–12.
57. Sisay M, Engidawork E, Shibeshi W. Evaluation of the antidiarrheal activity
of the leaf extracts of Myrtus communis Linn. (Myrtaceae) in mice model.
BMC Complement Altern Med. 2017;17:103.
58. Sumbul S, Ahmad MA, Asif M, et al. Evaluation of Myrtus communis Linn.
berries (common myrtle) in experimental ulcer models in rats. Hum Exp
Toxicol. 2010;29:935–44.
59. Tuberoso CI, Barra A, Angioni A, et al. Chemical composition of volatiles
in Sardinian myrtle (Myrtus communis L.) alcoholic extracts and essential
oils. J Agric Food Chem. 2006;54:1420–6.
60. Tuberoso CI, Boban M, Bifulco E, et al. Antioxidant capacity and vasodilatory
properties of Mediterranean food: the case of Cannonau wine, myrtle berries
liqueur and strawberry-tree honey. Food Chem. 2013;140:686–91.
61. Uehleke H, Brinkschulte-Freitas M. Oral toxicity of an essential oil from
myrtle and adaptive liver stimulation. Toxicol. 1979;12:335–42.
62. Yadegarinia D, Gachkar L, Rezaei MB, et al. Biochemical activities of Iranian
Mentha piperita L. and Myrtus communis L. essential oils. Phytochemistry.
2006;67:1249–55.
63. Yoshimura M, Amakura Y, Tokuhara M, Yoshida T. Polyphenolic com-
pounds isolated from the leaves of Myrtus communis. Nat Med (Tokyo). 2008;
62:366–8.
64. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and
cytoprotective effects of selected Pakistani medicinal plants in Helicobacter
pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
65. Zanetti S, Cannas S, Molicotti P, et al. Evaluation of the antimicrobial
properties of the essential oil of Myrtus communis L. against clinical strains
of Mycobacterium spp. Interdiscip Perspect Infect Dis. 2010;2010. Pii:
931530.
66. Zohalinezhad ME, Hosseini-Asl MK, Akrami R, et al. Myrtus communis L.
freeze-dried aqueous extract versus omeprazol in gastrointestinal reflux
disease: a double-blind randomized controlled clinical trial. J Evid Based
Complementary Altern Med. 2016;21:23–9.
Nageia nagi (Thunb.) Kuntze
(Podocarpaceae)

(Formerly Known as Myrica nagi)

Abstract
It is a slow-growing hardy tree, native to China, Taiwan, and Japan; also found in
India, Korea, Malaysia and Vietnam. According to Nighantas, the bark (M. nagi) is
useful in diseases caused by deranged phlegm, such as fever, asthma, gonorrhea,
piles, cough, and other affections of the throat. A bark decoction is a valuable
remedy in asthma, diarrhea and diuresis; powdered or in the form of lotion the bark
is applied to putrid sores; pessaries made of it promote uterine action. Other authors
described the bark as stimulant, alterative, aromatic, diaphoretic, and astringent,
and used in fevers, catarrh of the intestinal mucous membranes, diarrhea, dysentery,
scrofula, chronic gonorrhea, catarrh of the lungs and asthma; powder topically
applied to strengthen gums and to putrid sores, and as a poultice for bruises, sprains
and fractures. Fresh fruit juice exhibited significant antioxidant activity. Topical
application of bark EO also exhibited significant anti-inflammatory activity in mice.
Since two different species, belonging to different families (Nageia nagi, formerly
known as Myrica nagi belongs to Podocarpaceae family and is also listed as
synonym for Myrica esculenta that belongs to Myricaceae family), are called by the
same vernaculars, it is essential first to establish their identities in local languages
and botanically before any pharmacological activities are assigned to them.

Keywords



Aziri Bayberry Box myrtle
Cham-poi
Kaiphal
Kandula
Kâtaphala



Kumuda Nagi Zhu bai

Vernaculars: Urd.: Kaifal, Kaiphal; Hin.: Kaiphal, Katphal, Kâtaphala; San.: Kat-
aphala, Kumbhi-paki, Kumbli, Kumuda, Mahakumbhi, Somavalka, Sriparnika; Ben.:
Kâiphala; Mal.: Marutam-toli; Mar.: Kâiphala, Kayaphala; Tam.: Marudam-pattai;
Tel.: Kaidaryamu; Ara.: Aziri, Dar-u-sheeshaan, Ud-el-bark; Chi.: 竹柏, Cham-pú,

© Springer Nature Switzerland AG 2020 1263

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_132
1264 Nageia nagi (Thunb.) Kuntze

Zhai ye zhu bai, Zhu bai; Eng.: Asian bayberry, Box myrtle, Broad-leaf podocarpus;
Jap.: Nagi, Naki; Per.: Dar-u-sheeshaan, Kandula; Tag.: Cham-poi.
Description: It is a slow-growing hardy tree, native to China, Taiwan, and Japan;
also found in India, Korea, Malaysia and Vietnam; 15–20 m tall. Leaves lanceolate,
5–20 cm long, 2–6 cm wide, arranged subopposite on branches, light-green when
new, and as they age become dark green and glossy. Branches also start out as green
but as they age they become reddish-brown and peel in small layers. Red or green
colored, thick, aromatic and bitter bark. According to Ayurveda, it has two varieties
based on the color of flower: Shwet (white) and Rakta (red). Myrica esculenta and
M. Nagi (Nageia nagi) are two separate species and belong to different families [5],
but some authors have used them interchangeably or as synonyms, and described both
of them as Box myrtle and Bayberry. All published studies available on PubMed and
reported here are on M. esculenta (Figs. 1 and 2).
Actions and Uses: According to Nighantas, the bark (M. Nagi) is useful in diseases
caused by deranged phlegm, such as fever, asthma, gonorrhea, piles, cough, and other
affections of the throat. A bark decoction is a valuable remedy in asthma, diarrhea and
diuresis; powdered or in the form of lotion the bark is applied to putrid sores; pessaries
made of it promote uterine action. A prescription consisting of powdered equal parts of
bark of M. Nagi, tubers of Cyperus rotundus, root of Picrorrhiza kurroa, Curcuma
zedoaria, galls of Pistacia integerrima, and root of Saussurea lappa, is used in doses of
2 g with ginger juice and honey in affections of throat, cough and asthma.XL Other
authors described the bark as stimulant, alterative, aromatic, diaphoretic, and astrin-
gent, and used in fevers, catarrh of the intestinal mucous membranes, diarrhea,
dysentery, scrofula, chronic gonorrhea, catarrh of the lungs and asthma; powder
topically applied to strengthen gums and to putrid sores, and as a poultice for bruises,
sprains and fractures.LXXXI In Ayurveda, M. esculenta bark is used in the treatment of
asthma and bronchitis [7].LXXXIV,CV In Unani medicine, the bark (temperament, hot 2°
and dry 2°) is described as resolvent, astringent, carminative, nervine tonic, antiseptic,
expectorant and styptic. Its powder mixed with sesame seed oil is massaged in cases of
paralysis, palsy, arthritis, pain and tremors.LXXVII Bark decoction is used to wash
wounds and internally in gonorrhea, and the powder mixed with honey is used in
tonsillitis and pharyngitis.1 In Vietnamese folk medicine, the bark is used to treat
catarrhal fever, cough, sore throat, and skin diseases [6]. The edible fruits are also a very
rich source of total phenolics and a natural source of antioxidant/nutraceuticals [4].
Phytoconstituents: Phytoconstituents reported here are from M. esculenta. Aqueous
bark extract showed the presence of carbohydrates, proteins, tannins, glycosides and
mucilage; and the alcohol extract was positive for sterols, resins and traces of volatile
oil [10]. The bark contains a glycoside, quercitin, b-sitosterol, taraxerol and triter-
pindiol [1], gallic acid, myricanol, myricanone, epigallocatechin 3-O-gallate,
prodelphinidin dimmers: epigallocatechin-(4b!8)-epigallocatechin3-O-gallate and

1
Tayyab M: Personal Communication.
Nageia nagi (Thunb.) Kuntze 1265

Fig. 1 Nageia nagi, Leaves and Seed Cones, Keisotyou, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Podocarpus_nagi_nagi01.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Nageia nagi, Fruits of Kaiphal Plant (Nepal), Ram Prasad Joshi, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:%E0%A4%
95%E0%A4%BE%E0%A4%AB%E0%A4%B2.jpg; https://creativecommons.org/licenses/by-sa/3.
0/deed.en

3-O-galloylepigallocatechin-(4b!8)-epigallocatechin 3-O-gallate and a hydro-

lysable tannin castalagin [11]. Myricitrin and glycosides from the bark, and flavone-
4′-hydroxy-3′,5,5′-trimethoxy-7-O-b-I-D-glucopyranosy)(1!4)-a-L-rhamnopyrano-
side; flavone-3′,4′-dihydroxy-6-methoxy-7-O-a-L-rhamnopyranoside; b-sitosterol,
b-sitosterol-b-D-glucopyranoside and quercetin were reported from the leaves of
1266 Nageia nagi (Thunb.) Kuntze

M. esculenta [3]. Myresculoside, (1S,2S,4R)-2-hydroxy-1,8-cineole b-D-glucopyr-

anoside, corchoionoside C, roseoside, myricanol, 5-O-b-D-glucopyranosylmyricanol,
arjunolic acid, arjunglucoside, 3-epi-ursonic acid, 3-O-(E)-caffeoylursonic acid,
myricetin, and myricitrin were also reported from the leaves [6]. Fruits of M. Escu-
lenta also have a significant amount of total phenolic and flavonoid contents, and
possess significant antioxidant activity [9]. The EO of stem bark contains n-hexa-
decanol, eudesmol acetate, palmitic acid, cis-b-caryophyllene, n-pentadecanol and
n-octadecanol [2].
Pharmacology: Pretreatment with ethanol extract of aerial parts of M. esculenta
significantly inhibited rise in plasma exudation and eosinophil accumulation in acetic
acid-induced allergic pleurisy and vascular permeability in mice [7]. Ethyl acetate and
aqueous bark extracts inhibited carrageenan-induced rat paw edema 27 and 22%
respectively, compared to aspirin (28%), and also significantly reduced histamine-
induced paw edema [8]. Fresh fruit juice of both M. esculenta and M. nagi exhibited
significant antioxidant activity, and M. esculenta fruit juice had almost 90% in vitro
DPPH scavenging activity [5]. Topical application of bark EO also exhibited
significant anti-inflammatory activity in mice, and antimicrobial activity against
B. pumilus, S. aureus, S. epidermidis, E. coli, P. aeruginosa, C. albicans, A. niger and
S. cerevisiae [2].
Human A/Es, Allergy and Toxicity: It is reportedly harmful to liver and
spleen.LXXVII
Animal Toxicity: LD50 (i.p.) of ethyl acetate and aqueous bark extracts in mice
was reported to be 1,000 mg/kg [8].
Commentary: Since two different species, belonging to different families (Nageia
nagi, formerly known as Myrica nagi belongs to Podocarpaceae family and is also
listed as sysnonym for Myrica esculenta that belongs to Myricaceae family), are called
by the same vernaculars, it is essential first to establish their identities in local lan-
guages and botanically before any pharmacological activities are assigned to them.
According to the published reports, bark seems to have significant anti-inflammatory
and antibacterial activities, fruits of both plants possess antioxidant activity. However,
in the absence of proper identification and more pharmacological studies and clinical
trials no conclusion about the utility of this or these plants can be drawn.

References
1. Agarwal KP, Ray AC, Dhar ML. Triterpenses from the bark of Myrica escu-
lenta Buch-Ham. Indian J Pharm. 1963;I:28.
2. Agnihotri S, Wakode S, Ali M. Essential oil of Myrica esculenta Buch.
Ham.: composition, antimicrobial and topical anti-inflammatory activities.
Nat Prod Res. 2012;26:2266–9.
3. Bamola A, Semwal DK, Semwal S, Rawat U. Flavonoid glycosides from
Myrica esculenta leaves. J Indian Chem Soc. 2009;86:535–6.
Nageia nagi (Thunb.) Kuntze 1267

4. Bhatt ID, Rawat S, Badhani A, Rawal RS. Nutraceutical potential of selected

wild edible fruits of the Indian Himalayan region. Food Chem. 2017;215:
84–91.
5. Goyal AK, Mishra T, Bhattacharya M, Kar P, Sen A. Evaluation of
phytochemical constituents and antioxidant activity of selected actinorhizal
fruits growing in the forests of Northeast India. J Biosci. 2013;38:797–803.
6. Nguyen XN, Phan VK, Chau VM, et al. A new monoterpenoid glycoside
from Myrica esculenta and the inhibition of angiotensin I-converting
enzyme. Chem Pharm Bull (Tokyo). 2010;58:1408–10.
7. Patel K, Rao Nj, Gajera V, et al. Antiallergic activity of stem bark of
Myrica esculenta Buch.-Ham. (Myricaceae). J Young Pharm. 2010;2:74–8.
8. Patel T, Dudhpejiya A, Sheath N. Anti-inflammatory activity of Myrica
nagi Linn. bark. Anc Sci Life. 2011;30:100–3.
9. Rawat S, Jugran A, Giri L, Bhatt ID, Rawal RS. Assessment of antioxidant
properties in fruits of Myrica esculenta: a popular wild edible species in Indian
Himalayan region. Evid Based Complement Alternat Med. 2011;2011:
512787.
10. Singh J, Lan VK, Trivedi VP. Pharmacognostic evaluation of katphala (The
bark of Myrica esculenta Buch–Ham). Anc Sci Life. 1986;6:85–7.
11. Sun D, Zhao Z, Wong H, Foo LY. Tannins and other phenolics from Myrica
esculenta bark. Phytochemistry. 1982;21:579–83.
Nardostachys jatamansi (D. Don) DC
(Caprifoliaceae)

(Syns.: N. chinensis Batalin; N. grandiflora DC; Patrinia jatamansi (Jones) D. Don.)

Abstract
An alpine perennial herb found in the Himalayas, and Europe. This plant has
been used by Hindu physicians since ancient times and is mentioned by Sushruta
in a prescription for epilepsy (6th Cent. B.C.), and is considered a nervine tonic
and carminative, and an aromatic adjunct in the preparation of aromatic oils and
ghritas (butters). In Ayurveda, the rhizome/root is highly esteemed as incense
and the powder is used to treat mental disorders, hyperlipidemia, hypertension,
and convulsions, and as a bitter tonic and antispasmodic, and is also mentioned
to be useful in cancers. Infusion of fresh roots is employed in the treatment of
spasmodic hysterical affections, especially palpitation of heart, nervous head-
ache, chorea, and flatulence; also useful in menopausal disturbances, hys-
teroepilepsy, and other nervous and convulsive ailments. Dioscorides described
it under the name Nardin, and ancient Hindu writers also named it Gangitis,
because the Ganges flowed from the foot of the mountain where the plant grew.
Two sesquiterpenoids, jatamols A and B, neolignans and lignans from the roots,
valeranone (also known as yatamanson), three terpenoid identified as jatamansic
acid, nardal, and nardin, a terpenoid ester, and two sesquiterpenoids were isolated
from rhizomes. Its sedative and depressant actions were first reported in 1957.
Acute oral administration of alcoholic extract did not change brain levels of NE
and DA, but caused a significant increase in 5-HT, 5-HIAA, and GABA levels.
However, a 15-days treatment caused a significant increase in the levels of all
monoamines and inhibitory amino acids. Ethanol extract significantly improved
learning and memory in young mice and reversed diazepam-, scopolamine-, and
aging-induced amnesia of mice. Powdered roots, daily for one month, modestly
but statistically significantly improved the latency to falling asleep, duration and
undisturbed restful sleep in Indian patients with primary insomnia of up to 5 years
duration.

© Springer Nature Switzerland AG 2020 1269

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_133
1270 Nardostachys jatamansi (D. Don) DC

Keywords





Balchhad Bhutakesi Echte narde Gan song Indian valerian
Jatamasi





Muskroot Nard indien Nardeen Sunbulutteeb

Vernaculars: Urd.: Balchhad, Sunbulutteeb; Hin.: Balachadi, Chhar, Jatamasi,

Kalichada, Sumbul; San.: Bhytajata, Bhutakesi, Jatamansi, Mishi, Pisita, Tapasvini;
Ben.: Jhatamanasi; Mal.: Jetamanchi; Mar.: Balacharea, Jhatamansi; Tam.: Jata-
mashi; Tel.: Jetamamshi, Jatamsi; Ara.: Nardeen, Sunbul-al-asafeer, Sunbul-utteeb;
Chi.: Gan song (sweet pine); Eng.: Indian spikenard, Indian valerian, Muskroot,
True spikenard; Fre.: Nard de l’Himalaya, Nard indien; Ger.: Echte Narde,
Indischer baldrian; Maly.: Jeta-manchi; Per.: Sumbul-e-hindi, Sumbuluttib.
Description: An alpine perennial herb found in the Himalayas (India, Nepal,
Bhutan), and Europe, with a thick fragrant stem, surrounded at the base with the
remains of old leaves. Leaves opposite, 3–9 cm long, oblong, glabrous or lightly
pubescent, the cauline leaves sessile. Inflorescence a terminal, capitate panicle
consisting of cymes, provided with opposite bracts. Flowers reddish, somewhat
irregular; fruit dry, topped with the indehiscent calyx, villous. Root has aromatic
odor, tastes sweet and slightly bitter.LXXIX Rhizomes occur in short pieces about the
thickness of little finger, of a dark-grey color and surmounted by a bundle of
reddish-brown fibers that are produced by an accumulation of the skeletons of
leaves, and are matted together forming a kind of network. Odor is heavy and
peculiar like a mixture of valerian and patchouli, taste bitter and aromatic.XL,LXXXI
Best quality is fresh, light in weight, bigger in size, reddish, slightly bitter, dries
tongue on chewing and very aromatic (Fig. 1).LXIX
Actions and Uses: This plant has been used by Hindu physicians since ancient
times and is mentioned by Sushruta in a prescription for epilepsy (6th Cent. B.C.),
and is considered a nervine tonic and carminative, and an aromatic adjunct in the
preparation of aromatic oils and ghritas (butters). In Ayurveda, the rhizome/root is
highly esteemed as incense and the powder is used to treat mental disorders,
hyperlipidemia, hypertension, and convulsions [15, 20], and as a bitter tonic and
antispasmodic [10], and is also mentioned to be useful in cancers [12]. Infusion of
fresh roots is employed in the treatment of spasmodic hysterical affections, espe-
cially palpitation of heart, nervous headache, chorea, and flatulence; also useful in
menopausal disturbances, hysteroepilepsy, and other nervous and convulsive ail-
ments.CV Dioscorides described it under the name Nardin, and ancient Hindu
writers also named it Gangitis, because the Ganges flowed from the foot of the
mountain where the plant grew. The author of Makhzan-al-Adwiya, mentioned it as
deobstruent, stimulant, emmenagogue, and diuretic, and recommended it in various
disorders of digestive and respiratory organs, and as a nervine tonic in hysteria; and
also, to promote growth and blackness of hair.XL Powdered root (temperament, hot
1° and dry 2°) is antidiarrheal, diuretic, antinauseant, antiflatulence, anxiolytic, and
useful for diseases of kidneys and liver, especially jaundice.LXIX Unani physicians
consider it beneficial for persons of phlegmatic constitution, it acts as brain, heart
Nardostachys jatamansi (D. Don) DC 1271

Fig. 1 Nardostachys jatamansi, Illustration, Joseph Dalton Hooker, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Nardostachys_grandiflora.jpg

and nerve tonic, aphrodisiac, anti-inflammatory, deobstruent, carminative, antispas-

modic, detergent, astringent, emmenagogue, stomach and liver stimulant, and used
in epilepsy, tremors, digestive weakness, and hysteria.LXXVII A paste is used to
clear facial skin, and improve complexion.LXXVII Green leaves are also refrigerant,
stomachic, diuretic and emmenagogue, and the roots/rhizomes are tonic for heart,
liver and brain, diuretic, remove obstructions in jaundice and stones in kidneys.L
In Korea, it has been used as a remedy for stomach and skin ailments [4].
Phytoconstituents: Two sesquiterpenoids, jatamols A and B, neolignans and lig-
nans from the roots [8, 9], valeranone (also known as yatamanson) [34], three
terpenoid identified as jatamansic acid, nardal, and nardin [18], a terpenoid ester
[11], and two sesquiterpenoids [33] were isolated from rhizomes. More sesquiter-
penoids, kanshone J and K [46], kanshone D, kanshones L-N, nardosinanone G,
narchinol A, nardoaristolone B, 7-methoxydesoxonarchinol, and nardosdaucanol
from Korea [45], and three sesquiterpenoid dimers, dinardokanshones C–E, and
monomeric sesquiterpenoids, isonardoeudesmols A–D and nardoeudesmol D from
China have been isolated from roots/rhizomes [44]. Roots also contain 1–2%
essential oil.
1272 Nardostachys jatamansi (D. Don) DC

Pharmacology: Bose et al. [10] first reported its sedative and depressant actions in
1957. Prabhu et al. [29] showed that acute oral administration of alcoholic extract
did not change brain levels of NE and DA, but caused a significant increase in
5-HT, 5-HIAA, and GABA levels in rat brain. However, a 15-days treatment
caused a significant increase in the levels of all monoamines and inhibitory amino
acids. Ethanol extract significantly increased seizure threshold against MES with
minimal neurotoxicity, but was ineffective against PTZ-induced seizures; and in
combination with phenytoin significantly increased protective index of phenytoin
in a synergistic action in rats [30]. Ethanol extract also significantly and dose-
dependently corrects the 6-OHDA-caused deficits in locomotor activity and mus-
cular coordination, and prevents increased LPO and significant depletion of GSH
content in the substantia nigra, and restores level of DA and its metabolites and
activities of antioxidant enzymes [1]; and ameliorates reserpine-induced catalepsy
and orofacial dyskinesia in rats [28]. Aqueous extract also significantly reduced
catalepsy score, and restored antioxidant enzymes levels to normal in haloperidol-
induced catalepsy in rats [31]. Ethanol extract significantly improved learning and
memory in young mice and reversed diazepam-, scopolamine-, and aging-induced
amnesia of mice [20]. The extract was also protective against chronic stress-induced
impairments in hippocampus-dependent learning and memory behavior in rats [21].
Methanol extract has shown in vitro antioxidant and AChE inhibitory activities
[26, 27, 43]. Antidepressant-like effect of ethanol extract, comparable to imipra-
mine and sertraline was observed in mice, with a decrease in whole brain MAO-A
and MAO-B activities and an increase in monoamines levels [13]. Pretreatment of
rats with ethanol extract significantly reversed stress-induced elevation of LPO and
NO levels and decreased CAT activity in the brain; inhibited the incidence and
reversed alterations in biochemical parameters/markers of stress-induced gastric
ulceration [23, 24]; and mitigated cold restraint-induced oxidative stress and
monoamines levels in cerebral cortex, hippocampus and hypothalamus of rats [25].
Anxiolytic effect of 7-days treatment of mice with an extract (unidentified) was
antagonized by co-treatment with flumazenil or picrotoxin, signifying involvement
of GABA-ergic complex [32]. Due to its antioxidant activity, 15-days pretreatment
of rats significantly decreased neuronal cell death and attenuated alternations
induced by cerebral I/R [35]. Valeronone, one active sesquiterpene in N. jatamansi,
exhibits activities typical for tranquilizers [34].
Methanol extracts of roots/rhizomes and their fractions possess significant
antiproliferative potential in estrogen receptor (ER)-negative breast carcinoma cells,
which is mediated through cell cycle perturbation and proapoptotic effects [12].
Pretreatment of mice with i.p. injections of aqueous root extract completely pro-
tected against STZ-induced hyperglycemia and hypoinsulinemia, and maintained
normal insulin secretion of cytokine-treated b-cells in response to glucose [39]. An
extract significantly lowered blood glucose, HbA1c, plasma insulin and lipids in
diabetic C57BL/KsJ-db/db mice [47]. Aqueous extract treatments of mice 1 h after
or before, inhibited LPS-induced endotoxin shock and generation of inflammatory
mediators, such as IL-1b, IL-6, TNF-a, and IFN-a/b [3, 7]. Antioxidant and
free radical scavenging activities have also been observed in vitro [14, 16, 38].
Nardostachys jatamansi (D. Don) DC 1273

Pretreatment with N. jatamansi extract significantly prevented reduction in the

antioxidant enzymes and LPO levels, restored enzymes activity and lipid peroxides
to near normal levels [40], and significantly maintained the lipid status and the
activities of lipid metabolizing enzymes in doxorubicin-induced cardiac damage in
rats [41]. Ethanol rhizome extract protected against thioacetamide-hepatoxicity [2],
attenuated cerulein-induced acute pancreatitis [4], choline-deficient diet supple-
mented with ethionine-induced severe acute pancreatitis [5], and alcoholic chronic
pancreatitis [6]. Ethanol extract of whole plant also elevated HDL-C/TC ratio, and
significantly reduced ratio of TC/phospholipids in hyperlipidemic rats [15]. The
rhizomes/roots extract is also reported to exhibit antiandrogenic activity in PCOS
rat model [36], and the rhizomes/roots and their EO exhibited significant antifungal
and antibacterial activities [22, 37]. Significant diuretic activity of aqueous extract
in rats had also been reported [19].
Clinical Studies: In a comparative study of N. jatamansi and Valeriana wallchii in
Indian patients with primary insomnia of up to 5 years duration (15 in each group),
powdered roots of both drugs, 4 g with milk after meals were administered thrice
daily for a month. N. jatamansi powder modestly but statistically significantly
improved the latency to falling asleep, duration and undisturbed restful sleep, while
improvement by Valeriana was better. No adverse effects were reported or recorded
[42].
Mechanism of Action: Antidepressant-like effect may involve decrease in MAO-A
and MAO-B activities and increase in monoamines levels [13]; whereas anxiolytic
effect is likely mediated via GABA-ergic system [13, 32], and antiamnesic effect
could result from AChE inhibitory effect [26, 27, 43]. Increased expression of
AMPK and GLUT-4 in skeletal muscles, and decreased expression of liver glucose-
6-phosphatase and phosphoenolpyruvate carboxykinase in diabetic mice are sug-
gested mechanisms to decrease insulin-resistance [47]. 7-Methoxydesoxonarchinol,
kanshone N, and narchinol A inhibit LPS-stimulated NO production, proinflam-
matory mediators, PGE2, iNOS, and COX-2, as well as proinflammatory cytokines,
such as IL-1b, IL-12 and TNF-a, and activation of the NF-jB signaling pathway in
LPS-stimulated BV2 microglial cells [46].
Human A/Es, Allergy and Toxicity: There are no human A/Es or toxicities
reported in the published literature, except being harmful for the kidneys.LXXVII
Animal Toxicity: Oral LD50 of valeranone in rats and mice was more than
3,160 mg/kg [34]. Aqueous and hydroalcoholic extracts showed in vitro genotoxic
potential in hepG2 cells [17].
Commentary: In Unani medicine, it is described as beneficial for persons of
phlegmatic constitution, and all nervous system diseases are considered to be due to
phlegmatic disorders; also, in Ayurveda, it is used to treat mental disorders and
convulsions. Pharmcological studies also corroborate some of these effects. How-
ever, despite being an important and widely used plant in Indian systems of
1274 Nardostachys jatamansi (D. Don) DC

medicine, there are no reports available in the published literature about any
organized clinical trials (except one nonrandomized and nonblinded small study on
insomnia) on the roots/rhizomes or any of their ‘active’ constituents.

References
1. Ahmad M, Yousuf S, Khan MB, et al. Attenuation by Nardostachys
jatamansi of 6-hydroxydopamine-induced parkinsonism in rats: behavioral,
neurochemical, and immunohistochemical studies. Pharmacol Biochem
Behav. 2006;83:150–60.
2. Ali S, Ansari KA, Jafry MA, et al. Nardostachys jatamansi protects against
liver damage induced by thioacetamide in rats. J Ethnopharmacol. 2000;71:
359–63.
3. Bae GS, Heo KH, Choi SB, et al. Beneficial effects of fractions of
Nardostachys jatamansi on lipopolysaccharide-induced inflammatory
response. Evid Based Complement Altern Med. 2014;2014:837835.
4. Bae GS, Park HJ, Kim DY, et al. Nardostachys jatamansi protects against
cerulein-induced acute pancreatitis. Pancreas. 2010;39:520–9.
5. Bae GS, Park KC, Koo BS, et al. Nardostachys jatamansi inhibits severe
acute pancreatitis via mitogen-activated protein kinases. Exp Ther Med.
2012;4:533–7.
6. Bae GS, Park KC, Koo BS, et al. The inhibitory effects of Nardostachys
jatamansi on alcoholic chronic pancreatitis. BMB Rep. 2012;45:402–7.
7. Bae GS, Seo SW, Kim MS, et al. The roots of Nardostachys jatamansi
inhibits lipopolysaccharide-induced endotoxin shock. J Nat Med. 2011;65:
63–72.
8. Bagchi A, Oshima Y, Hikino H. Jatamols A and B: sesquiterpenoids of
Nardostachys jatamansi roots1. Planta Med. 1991;57:282–3.
9. Bagchi A, Oshima Y, Hikino H. Neolignans and lignans of Nardostachys
jatamansi roots1. Planta Med. 1991;57:96–7.
10. Bose BC, Gupta SS, Bhatnagar JN, Vijyavargiya R. Nardostachys
Jatamansi DC: its sedative and depressant action as estimated by Warburg
technique. Indian J Med Sci. 1957;11:803–7.
11. Chatterjee A, Basak B, Saha M, et al. Structure and stereochemistry of
nardostachysin, a new terpenoid ester constituent of the rhizomes of
Nardostachys jatamansi. J Nat Prod. 2000;63:1531–3.
12. Chaudhary S, Chandrashekar KS, Pai KS, et al. Evaluation of antioxidant
and anticancer activity of extract and fractions of Nardostachys jatamansi
DC. in breast carcinoma. BMC Complement Altern Med. 2015;15:50.
13. Dhingra D, Goyal PK. Inhibition of MAO and GABA: probable mecha-
nisms for antidepressant-like activity of Nardostachys jatamansi DC. in
mice. Indian J Exp Biol. 2008;46:212–8.
Nardostachys jatamansi (D. Don) DC 1275

14. Dhuna K, Dhuna V, Bhatia G, et al. Cytoprotective effect of methanolic extract

of Nardostachys jatamansi against hydrogen peroxide induced oxidative
damage in C6 glioma cells. Acta Biochim Pol. 2013;60:21–31.
15. Dixit VP, Jain P, Joshi SC. Hypolipidaemic effects of Curcuma longa L and
Nardostachys jatamansi DC. in triton-induced hyperlipidaemic rats. Indian
J Physiol Pharmacol. 1988;32:299–304.
16. Dugaheh MA, Meisami F, Torabian Z, Sharififar F. Antioxidant effect and
study of bioactive components of Valeriana sisymbriifolia and Nar-
dostachys jatamansii in comparison to Valeriana officinalis. Pak J Pharm
Sci. 2013;26:53–8.
17. Etebari M, Zolfaghari B, Jafarian-Dehkordi A, Rakian R. Evaluation of
DNA damage of hydroalcoholic and aqueous extract of Echium amoenum
and Nardostachys jatamansi. J Res Med Sci. 2012;17:782–6.
18. Gottumukkala VR, Annamalai T, Mukhopadhyay T. Phytochemical inves-
tigation and hair growth studies on the rhizomes of Nardostachys jatamansi
DC. Pharmacogn Mag. 2011;7:146–50.
19. Gujral ML, Saxena PN, Mishra SS. An experimental study of the comparative
activity of Indigenous diuretics. J Indian Med Assoc. 1955;25:49.
20. Joshi H, Parle M. Nardostachys jatamansi improves learning and memory
in mice. J Med Food. 2006;9:113–8.
21. Karkada G, Shenoy KB, Halahalli H, Karanth KS. Nardostachys jata-
mansi extract prevents chronic restraint stress-induced learning and memory
deficits in a radial arm maze task. J Nat Sci Biol Med. 2012;3:125–32.
22. Kumar VP, Chauhan NS, Padh H, Rajani M. Search for antibacterial and
antifungal agents from selected Indian medicinal plants. J Ethnopharmacol.
2006;107:182–8.
23. Lyle N, Bhattacharyya D, Sur TK, et al. Stress modulating antioxidant effect
of Nardostachys jatamansi. Indian J Biochem Biophys. 2009;46:93–8.
24. Lyle N, Gomes A, Sur T, et al. The role of antioxidant properties of
Nardostachys jatamansi in alleviation of the symptoms of the chronic
fatigue syndrome. Behav Brain Res. 2009;202:285–90.
25. Lyle N, Chakrabarti S, Sur T, et al. Nardostachys jatamansi protects against
cold restraint stress induced central monoaminergic and oxidative changes
in rats. Neurochem Res. 2012;37:2748–57.
26. Mathew M, Subramanian S. In vitro screening for anticholinesterase and
antioxidant activity of methanolic extracts of ayurvedic medicinal plants
used for cognitive disorders. PLoS ONE. 2014;9:e86804.
27. Mukherjee PK, Kumar V, Houghton PJ. Screening of Indian medicinal
plants for acetylcholinesterase inhibitory activity. Phytother Res. 2007;21:
1142–5.
28. Patil RA, Hiray YA, Kasture SB. Reversal of reserpine-induced orofacial
dyskinesia and catalepsy by Nardostachys jatamansi. Indian J Pharmacol.
2012;44:340–4.
1276 Nardostachys jatamansi (D. Don) DC

29. Prabhu V, Karanth KS, Rao A. Effects of Nardostachys jatamansi on bio-

genic amines and inhibitory amino acids in the rat brain. Planta Med. 1994;
60:114–7.
30. Rao VS, Rao A, Karanth KS. Anticonvulsant and neurotoxicity profile of
Nardostachys jatamansi in rats. J Ethnopharmacol. 2005;102:351–6.
31. Rasheed AS, Venkataraman S, Jayaveera KN, et al. Evaluation of toxicolog-
ical and antioxidant potential of Nardostachys jatamansi in reversing
haloperidol-induced catalepsy in rats. Int J Gen Med. 2010;3:127–36.
32. Razack S, Kandikattu HK, Venuprasad MP, et al. Anxiolytic actions of
Nardostachys jatamansi via GABA benzodiazepine channel complex mech-
anism and its biodistribution studies. Metab Brain Dis. 2018 (Epub ahead
of print).
33. Rekha K, Rao RR, Pandey R, et al. Two new sesquiterpenoids from the
rhizomes of Nardostachys jatamansi. J Asian Nat Prod Res. 2013;15:111–6.
34. Rucker G, Tautges J, Sieck A, Wenzl H, Graf E. Isolation and pharma-
codynamic activity of the sesquiterpene valeranone from Nardostachys
jatamansi DC. Arzneimforsch. 1978;28:7–13 (German).
35. Salim S, Ahmad M, Zafar KS, et al. Protective effect of Nardostachys jatamansi
in rat cerebral ischemia. Pharmacol Biochem Behav. 2003;74:481–6.
36. Sandeep PM, Bovee TF, Sreejith K. Antiandrogenic activity of Nardostachys
jatamansi DC. and Tribulus terrestris L. and their beneficial effects on
polycystic ovary syndrome-induced rat models. Metab Syndr Relat Disord.
2015;13:248–54.
37. Sarbhoy AK, Varshney JL, Maheshwari ML, Saxena DB. Efficacy of some
essential oils and their constituents on few ubiquitous molds. Zentralbl
Bakteriol Naturwiss. 1978;133:723–5.
38. Sharma SK, Singh AP. In vitro antioxidant and free radical scavenging
activity of Nardostachys jatamansi DC. J Acupunct Meridian Stud. 2012;5:
112–8.
39. Song MY, Bae UJ, Lee BH, et al. Nardostachys jatamansi extract protects
against cytokine-induced beta-cell damage and streptozotocin-induced
diabetes. World J Gastroenterol. 2010;16:3249–57.
40. Subashini R, Yogeeta S, Gnanapragasam A, Devaki T. Protective effect of
Nardostachys jatamansi on oxidative injury and cellular abnormalities during
doxorubicin-induced cardiac damage in rats. J Pharm Pharmacol. 2006;58:
257–62.
41. Subashini R, Ragavendran B, Gnanapragasam A, et al. Biochemical study
on the protective potential of Nardostachys jatamansi extract on lipid profile
and lipid metabolizing enzymes in doxorubicin intoxicated rats. Pharmazie.
2007;62:382–7.
42. Toolika E, Bhat NP, Shetty SK. A comparative clinical study on the effect of
Tagara (Valeriana wallichii DC.) and Jatamansi (Nardostachys jata-
mansi DC.) in the management of Anidra (primary insomnia). Ayu. 2015;36:
46–9.
Nardostachys jatamansi (D. Don) DC 1277

43. Vinutha B, Prashanth D, Salma K, et al. Screening of selected Indian medicinal

plants for acetylcholinesterase inhibitory activity. J Ethnopharmacol. 2007;
109:359–63.
44. Wu HH, Deng X, Zhang H, et al. Dinardokanshones C-E, isonardoeudesmols
A-D and nardoeudesmol D from Nardostachys jatamansi DC. Phytochemistry.
2018;150:50–9.
45. Yoon CS, Kim DC, Park JS, et al. Isolation of novel sesquiterpeniods and
antineuroinflammatory metabolites from Nardostachys jatamansi. Mole-
cules. 2018;23. pii: E2367.
46. Yoon CS, Kim KW, Lee SC, Kim YC, Oh H. Antineuroinflammatory
effects of sesqui-terpenoids isolated from Nardostachys jatamansi. Bioorg
Med Chem Lett. 2018;28:140–4.
47. You HN, Park MH, Hwang SY, Han JS. Nardostachys jatamansi DC. extract
alleviates insulin resistance and regulates glucose metabolism in C57BL/
KsJ-db/db mice through the AMP-activated protein kinase signaling pathway.
J Med Food. 2018;21:324–31.
Nepeta cataria L.
(Lamiaceae)

(Syns.: N. bodinieri Vaniot; N. ceretana Sennen; N. citriodora Dumort.;

N. laurentii Sennen)

Abstract
It is native of southeast Europe, southwest Asia and western temperate
Himalayas, and is naturalized in the United States, and many other countries. Ibn
al-Baitar quoting Dioscorides and other authors described it as a grass that smells
like orange, and mentioned the Greek names as Malsoonan and Maletana. As
cardiotonic being its main property it is useful for angina, and protection of heart
from diseases and the effects of black-bile vapors; and being useful in all
phlegmatic and black-bile originated diseases (Avicenna). It is also useful for
discomfort, anxiety and stress (Rhazes). Above all a digestive herb, catnip
relieves all abdominal cramps, flatulence and intestinal pain. It expels winds and
reduces discomfort without impeding normal digestive processes. It is used in
Wales to stop persistent coughs and hiccups; and is prescribed as a safe yet
efficient pain killer, especially suitable for children’s aches and pains. The scent
of the volatile oil responsible for characteristic stimulatory response in cats is
due to the presence of nepetalactones, the major chemical components of catnip
constituting 70–99% of the volatile oil (especially cis-trans-nepetalactone).
Interestingly, the effects in cats are produced only when it is smelled, not when it
is administered orally. Nepetalactone is somewhat similar in its chemical
structure to the valepotriates, the sedative principle of valerian, which may be
responsible for its use as sleeping aid. Catnip oil and nepetalic acid significantly
increase hexobarbital-induced sleeping time in mice, and decrease performance
of rats trained on a Sidman avoidance schedule, but develop behavioral tolerance
after daily injections of catnip oil. Myorelaxant activity of the EO, mediated
possibly through dual inhibition of calcium channels and PDE, has also been
reported.

Keywords
Badranjboya

Baqlatul-rehan Cataire

Cataria

Catnip

Catswort




Chikumahakka Kattekruid Kattmynta Katzenminze

© Springer Nature Switzerland AG 2020 1279
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_134
1280 Nepeta cataria L.

Vernaculars: Urd.: Badranjboya,1 Billi-lotan; Ara.: Baqlatul-rehan, Baqlatul-

utrujiya, Habaqur-rehani, Hashishat-assanoor, Utraji-arrahia; Chi.: 荆芥; Cze.:
Šanta kočičí; Dan.: Katteurt; Dut.: Kattenkruid, Wild kattenkruid; Eng.: Catmint,
Catnip, Catswort; Fin.: Aitokissanminttu; Fre.: Cataire, Chataire, Herbe aux chats,
Menthe de chat, Népéta chataire, Népéta des chats; Ger.: Echte katzenminze,
Gewöhnliche katzenmelisse, Katzenminze; Gre.: Maletana, Malsoonan; Hun.:
Illatos macskamenta; Ita.: Cataria, Erba dei gatti, Erba gattaia, Gattaia commune,
Menta dei gatti; Jap.: Chikumahakka, Inuhakka, Kyattonippu; Nor.: Kattemynte;
Per.: Badrangboya, Badranjboya; Pol.: Kocimiętka właściwa; Por.: Catária,
Erva-dos-gatos, Erva-gateira, Nêveda-dos-gatos, Urtiga-morta; Spa.: Cataria, Gat-
era tuberose, Hierba de los gatos, Hierba gatera, Manrubios, Manruego, Meagatos,
Menta de gato, Menta de gatos, Merruegos, Nepeta; Swe.: Kattmynta.
Description: Nepeta cataria is native of southeast Europe, southwest Asia and
western temperate Himalayas, and is naturalized in the United States, and many
other countries. The identity of what is known as Badranjboya in Unani medicine
(not of Nepeta cataria) is in dispute. Dymock et al.XL mentioned Badranjboya as
Melissa officinalis, the Apiastrum of Dioscorides and Theophrastus; the Balm
Gentle of our gardens loved by bees, whereas Nepeta hindustana is described as
Badranjboya and Kazwan in Ibn al-Baitar’s Urdu language translation.LXIX The
name Badranjboya is an Arabized form of a Persian word meaning
“citron-scented.”LIII Dymock et al.XL mentioned that it was imported into India
from Persia, and their description of the plant has been mentioned under Melissa
officinalis. Badranjboya is called billi lotan in Urdu, meaning that the cats love it,
and Khory and KatrakLXXXI provided description of both Nepeta cataria and
Melissa officinalis in almost identical terms, and Dymock et al.XL did not describe
Nepeta cataria in their Pharmacographia Indica. Except that both plants have
quadrangular stems and belong to the same family, they do not share other features
and look completely different plants. As mentioned under Melissa officinalis, both
plants with Badranjboya as the vernacular name are described separately in this
book. Khory and KatrakLXXXI described it as a perennial herb, growing up to a
height of 100 cm; the stem is quadrangular, branching and hoary; leaves hairy,
5 cm long, triangular, ovate, cordate and serrate. It is a common inhabitant of
hedges and waste places, with a downy stem which at the height of summer bears a
spike of small and hooded white or liliac-colored flowers in axillary clusters of
about 6, upon a short peduncle that grows in crowded whorls. They described the
odor, mint-like, taste bitter, aromatic, and camphoraceous. However, Kabeerud-
dinLXXVII described leaves to smell like orange. Leaves are deltoid-oval with
double layers of palisade, petiole about as long as blade, stem hollow in the middle;
leaves, petioles and stems contain glandular and uniseriate, multicellular
non-glandular hairs [19]. Cats are extremely attractive to the curious scent of the
volatile oil in the plant, causing them to cavort playfully while attempting to

1
Both Melissa officinalis and Nepeta cataria are known as Badranjboya.
Nepeta cataria L. 1281

Fig. 1 Nepeta cataria, Leaves, Forest & Kim Starr, WikimediaCommons; 3.0 Unported CC BY
3.0, https://commons.wikimedia.org/wiki/File:Starr_070906-8819_Nepeta_cataria.jpg; https://creative-
commons.org/licenses/by/3.0/deed.en

Fig. 2 Nepeta cataria, Flowers, D. Gordon E. Robertson, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Catnip_flowers.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
1282 Nepeta cataria L.

saturate their entire bodies with the plants distinctive aroma; cats and other crea-
tures also eat it for its medicinal virtues (Figs. 1 and 2).
Actions and Uses: Ibn al-BaitarLXIX quoting Dioscorides and other authors
described it as a grass that smells like orange, and mentioned the Greek names as
Malsoonan and Maletana. As cardiotonic being its main property it is useful for
angina, and protection of heart from diseases and the effects of black-bile vapors; and
being useful in all phlegmatic and black-bile originated diseases (Avicenna). It is
also useful for discomfort, anxiety and stress (Rhazes). In Unani medicine (tem-
perament, hot 1° and dry 1° by Ghani; hot 2° and dry 2° by Kabeeruddin), cardiac
refrigerant and cardiotonic activities are its most useful properties; other effects
include strengthening of mental acuity, memory and intelligence, aphrodisiac,
anti-inflammatory, stomachic, antispasmodic, bronchodilator, and analgesic for
arthritis (as a poultice or paste),L,LXXVII whereas N. hindustana is described as a
potent antidote for poisons, especially for scorpion poison.LXIX Tayyab2 regarded it
antispasmodic, cardiotonic, blood purifier and munzij (concoctive) of phlegm
and black bile, and used it for melancholy. Leaves and flowering tops are aromatic,
carminative, diaphoretic, refrigerant (cooling), emmenagogue, tonic, antiseptic, and
stimulant, and useful in infantile colic, chlorosis, amenorrhea and hysteria
[19].LXXXI Above all a digestive herb, catnip relieves all abdominal cramps, flatu-
lence and intestinal pain. It expels winds and reduces discomfort without impeding
normal digestive processes. It is used in Wales to stop persistent coughs and hiccups;
and is prescribed as a safe yet efficient pain killer, especially suitable for children’s
aches and pains. The dosage is one or two tablespoonfuls daily of the standard
infusion prepared from whole plant above ground. Painful menstruation is relieved
with this herb which will also induce restful sleep if taken before going to bed.XXVI
Catnip was once rather widely used in medicine, primarily as a carminative or
digestive aid and as a tonic. Hot tea taken at bedtime was also recommended as sleep
aid. It is still one of the most commonly used home remedies to relieve colic in
children by African-Americans [20], and its traditional uses also include treatment of
inflammation [18].
Phytoconstituents: The scent of the volatile oil responsible for characteristic
stimulatory response in cats is due to the presence of nepetalactones [22], the major
chemical components of catnip constituting 70–99% of the volatile oil (especially
cis-trans-nepetalactone). Interestingly, the effects in cats are produced only when it
is smelled, not when it is administered orally [21]. Fractionation of the commercial
sample of catnip oil showed the presence of 40% nepetalactone and 43% nepetalic
acid [8]. Nepetalactone is somewhat similar in its chemical structure to the vale-
potriates, the sedative principle of valerian [11], which may be responsible for its
use as sleeping aid.CXXXXIII Volatile oil of leaves and flowering tops [19] also
contain geranyl acetate, citronellyl acetate, citronellol, and geraniol [3]. Thirty
volatile components were identified in EO from Iran, representing 99.7% of the EO
[6]. Gilani et al. [7], however, reported 1,8-cineol (21%), a-humulene (14.4%),

2
Tayyab M: Personal Communication.
Nepeta cataria L. 1283

a-pinene (10.4%) and geranyl acetate (8.2%) as the four major components among
the 27 identified in the oil. Another analysis of the EOs from Iran obtained at
different stages of the plant development indicated that 4a-a,7-a,7a-b-nepetalactone
(55–58%) and 4a-a,7-b,7a-a-nepetalactone (30–31.2%) were the major compounds
at all developmental stages [26]. Ethanol extract of the plant tested positive for
tannins, carbohydrates, glycosides and flavonoids; and tests were positive for
steroids and terpenoids in petroleum ether and chloroform extracts [14]. Ursolic
acid, daucosterol (b-sitosterol 3-O-b-D-glucoside), small amounts of b-sitosterol,
campesterol, a-amyrin and b-amyrin [10], and luteolin 7-O-glucuronide, luteolin
7-O-glucurono-(1!6)-glucoside, apigenin 7-O-glucuronide as well as free agly-
cones luteolin and apigenin have been isolated from N. cataria var. citriodora,
called the lemon catnip [13].
Pharmacology: Catnip oil and nepetalic acid significantly increase hexobarbital-
induced sleeping time in mice, and decrease performance of rats trained on a
Sidman avoidance schedule, but develop behavioral tolerance after daily injections
of catnip oil [8]. However, when the whole plant was fed to mice as 10% of the
normal diet for 2 h/day for 1 or 7-days, there was an increase in stereotypical
behavior and susceptibility to seizures, and decrease in sodium pentobarbital-
induced sleeping time on acute dosing. Long-term exposure caused tolerance to
stereotypic behavior, catalepsy and sleeping time, and increased susceptibility to
picrotoxin- and strychnine-induced seizures [12].
Myorelaxant activity of the EO, mediated possibly through dual inhibition of
calcium channels and PDE, has been reported [7]. Caffeoyl phenylethanoid gly-
cosides teucrioside, verbascoside and lamiuside A (teupolioside), isolated from
N. cataria, inhibited calcineurin both in the presence and absence of calmodulin,
suggesting a direct interaction with calcineurin [18]. Extracts successively extracted
in 70% ethanol, petroleum ether and chloroform exhibited potent antioxidant
activity, while ethyl acetate and ethanol successive extraction showed moderate or
low reducing activities [14]. A diethyl ether extract reportedly showed antimicrobial
activity against fungi and Gram-positive bacteria [15]. Essential oil was active
against eleven bacteria, and twelve fungi and a yeast, C. albicans [1], against
food-borne pathogens, and oral pathogens [25, 26].
Leaves fed in chow to male rats increased penile erection, decreased general
activity and slightly improved sexual behavior, by an action on dopaminergic sys-
tems [4]. Hatch [9] had reported increased pleasure behavior in cats, and catnip oil is
also a mosquito repellant [2, 5, 17, 23, 24]. Most of the radioactivity (86–94%) was
recovered in the urine when radiolabelled cis, trans-nepetalactone, the biologically
active component of catnip, was administered to domestic cat [21].
Human A/Es, Allergy and Toxicity: A toddler developed signs of central nervous
system depression after given a high dose of the plant [16].
Animal Toxicity: LD50 of catnip oil, the nepetalactone-enriched fraction, and
nepetalic acid in mice were 1,300 mg/kg, 1,550 mg/kg and 1,050 mg/kg, respec-
tively [8].
1284 Nepeta cataria L.

Commentary: A known sedative and used as sleep aid in both European and
Asian cultures for long still lacks objective clinical trials for any of its purported
effects.

References
1. Adiguzel A, Ozer H, Sokmen M, et al. Antimicrobial and antioxidant activity
of the essential oil and methanol extract of Nepeta cataria. Pol J Microbiol.
2009;58:69–76.
2. Amer A, Mehlhorn H. Repellency effect of forty-one essential oils against
Aedes, Anopheles, and Culex mosquitoes. Parasitol Res. 2006;99:478–90.
3. Baranauskiene R, Venskutonis RP, Demyttenaere JC. Sensory and instru-
mental evaluation of catnip (Nepeta cataria L.) aroma. J Agric Food Chem.
2003;51:3840–8.
4. Bernardi MM, Kirsten TB, Lago JH, et al. Nepeta cataria L. var. citriodora
(Becker) increases penile erection in rats. J Ethnopharmacol. 2011;137:
1318–22.
5. Bernier UR, Furman KD, Kline DL, et al. Comparison of contact and spatial
repellency of catnip oil and N,N-diethyl-3-methylbenzamide (deet) against
mosquitoes. J Med Entomol. 2005;42:306–11.
6. Emami SA, Asili J, Hossein Nia S, et al. Growth inhibition and apoptosis
induction of essential oils and extracts of Nepeta cataria L. on human pro-
static and breast cancer cell lines. Asian Pac J Cancer Prev. 2016;17:
125–30.
7. Gilani AH, Shah AJ, Zubair A, et al. Chemical composition and mechanisms
underlying the spasmolytic and bronchodilatory properties of the essential oil
of Nepeta cataria L. J Ethnopharmacol. 2009;121:405–11.
8. Harney JW, Barofsky IM, Leary JD. Behavioral and toxicological studies of
cyclopentanoid monoterpenes from Nepeta cataria. Lloydia. 1978;41:
367–74.
9. Hatch RC. Effect of drugs on catnip (Nepeta cataria)-induced pleasure
behavior in cats. Am J Vet Res. 1972;33:143–55.
10. Klimek B, Modnicki D. Terpenoids and sterols from Nepeta cataria L. var.
citriodora (Lamiaceae). Acta Pol Pharm. 2005;62:231–5.
11. Kuklinski M. Deutsche Apotheker-Zeitung. 1969;109:114.
12. Massoco CO, Silva MR, Gorniak SL, et al. Behavioral effects of acute and
long-term administration of catnip (Nepeta cataria) in mice. Vet Hum
Toxicol. 1995;37:530–3.
13. Modnicki D, Tokar M, Klimek B. Flavonoids and phenolic acids of Nepeta
cataria L. var. citriodora (Becker) Balb. (Lamiaceae). Acta Pol Pharm. 2007;
64:247–52.
14. Naguib AM, Ebrahim ME, Aly HF, et al. Phytochemical screening of Nepeta
cataria extracts and their in vitro inhibitory effects on free radicals and
carbohydrate-metabolising enzymes. Nat Prod Res. 2012;26:2196–8.
Nepeta cataria L. 1285

15. Nostro A, Cannatelli MA, Crisafi G, Alonzo V. The effect of Nepeta cataria
extract on adherence and enzyme production of Staphylococcus aureus.
Int J Antimicrob Agents. 2001;18:583–5.
16. Osterhoudt KC, Lee SK, Callahan JM, Henretig FM. Catnip and the
alteration of human consciousness. Vet Hum Toxicol. 1997;39:373–5.
17. Polsomboon S, Grieco JP, Achee NL, et al. Behavioral responses of catnip
(Nepeta cataria) by two species of mosquitoes, Aedes aegypti and Anopheles
harrisoni, in Thailand. J Am Mosq Control Assoc. 2008;24:513–9.
18. Prescott TA, Veitch NC, Simmonds MS. Direct inhibition of calcineurin by
caffeoyl phenyl-ethanoid glycosides from Teucrium chamaedrys and
Nepeta cataria. J Ethnopharmacol. 2011;137:1306–10.
19. Sarkar M, Rashmi R, Vikramaditya, Varma PN. Pharmacognosy of Nepeta
cataria. Anc Sci Life. 1995;14:225–34.
20. Smitherman LC, Janisse J, Mathur A. The use of folk remedies among
children in an urban black community: remedies for fever, colic, and teething.
Pediatrics. 2005;115:e297–304.
21. Waller GR, Price GH, Mitchell ED. Feline attractant, cis, trans-nepetalactone:
metabolism in the domestic cat. Science. 1969;164:1281–2.
22. Wang M, Cheng KW, Wu Q, Simon JE. Quantification of nepetalactones in
catnip (Nepeta cataria L.) by HPLC coupled with ultraviolet and mass
spectrometric detection. Phytochem Anal. 2007;18:157–60.
23. Webb CE, Russell RC. Is the extract from the plant catmint (Nepeta cataria)
repellent to mosquitoes in Australia? J Am Mosq Control Assoc. 2007;23:
351–4.
24. Zhu J, Zeng X, Yanma, Liu T, et al. Adult repellency and larvicidal activity
of five plant essential oils against mosquitoes. J Am Mosq Control Assoc.
2006;22:515–22.
25. Zomorodian K, Saharkhiz MJ, Rahimi MJ, et al. Chemical composition and
antimicrobial activities of essential oil of Nepeta cataria L. against common
causes of oral infections. J Dent (Tehran). 2013;10:329–37.
26. Zomorodian K, Saharkhiz MJ, Shariati S, et al. Chemical composition and
antimicrobial activities of essential oils from Nepeta cataria L. against
common causes of food-borne infections. ISRN Pharm. 2012;2012:591953.
Nigella sativa L.
(Ranunculaceae)

(Syns.: N. indica Roxb. ex Flem.; N. truncata Viv.)

Abstract
The plant is native to south and southwest Mediterranean countries, and India,
and widely cultivated in the Mediterranean and Middle Eastern countries, south
Europe, and southwest Asia. Medicinal usage of black seeds dates back to the
ancient Egyptians, Greeks, and Romans. Black cumin seeds were found in the
tomb of the Egyptian Pharaoh, Tutankhamen, and were also recovered in
northcentral Turkey from a pilgrim flask of the Old Hittite period of Boyali
Höyük (Mound), dating from around 1650 B.C. Hippocrates and Dioscorides
mentioned it as Melanthion and Pliny called it Gith. It is extensively used both as
a spice and as a medicine. Muslim physicians of Unani medicine in India describe
it as heating, attenuant, suppurative, detergent and diuretic, and believe that it
increases menstrual flow and secretion of milk, and stimulates uterine activity. In
Arab countries, Europe and Iran, the seeds and oil are also traditionally used in
the treatment of asthma, hypertension, diabetes, inflammation, tumor, cough,
bronchitis, headache, eczema, fever, dizziness, gastrointestinal disturbances,
impotence, painful menstruation, flu, and as carminative, diuretic and antipar-
asitic agent. Aqueous seed extract tested positive for alkaloids, flavonoids,
saponins, anthraquinones, and tannins, and methanol extract showed the presence
of alkaloids, phenolic compounds, flavonoids, proteins, carbohydrates, saponins,
lipids, sterols and tannins. Ninteen phenolic compounds were identified from
ethanol extract of seeds. Seed-supplemented diet of normal rats produced a
homogenous cardiac hypertrophy and enhanced cardiac contractility. Seeds
supplemented diet also significantly decreased TC, LDL-C and TG in normal and
hypercholesterolemic rats. Aqueous seed extract (i.v.) lowered MABP with a
significant decrease in HR in normal rats, that was partly dependent on
endothelium. Both aqueous and macerated extracts significantly reduced HR and
contractility on isolated guinea pig heart due to calcium channel blocking effect
that was greater than nifedipine. Powdered seeds twice daily to Bangladeshi
healthy elderly volunteers for nine-weeks significantly enhanced memory,

© Springer Nature Switzerland AG 2020 1287

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_135
1288 Nigella sativa L.

attention and cognition, and stabilized mood, decreased anxiety and modulated
cognition in healthy adolescent male volunteers.

Keywords





Black cumin Caminho-reto Çöreotu Hab-es-sauda Hei xian hao Kalonji






Krishnajiraka Narduszaad Neguilla Saatschwarzkümmel

Vernaculars: Urd.: Kalonji; Hin.: Kalajira, Kalonji, Mangrail; San.: Aranyajeer-

aka, Karavi, Krishnajiraka, Sushavi, Upakunchika; Ben.: Kalojira, Mugrela; Mal.:
Karinchirakam, Karun jiragam; Mar.: Kalejire, Kelanji, Mangrela; Tam.: Karun-
jiragam, Karun-shiragam; Tel.: Nalla-jilakara, Ullithnam; Ara.: Al syuniz (Iran,
Yemen), Basdas (Morocco), Habbatus-sauda, Hab-es-sauda, Habbat-ul-barakah
(seeds of blessing), Shivneez; Bur.: Samon-ne, Satmung; Chi.: 栽 培黑种草, Hak
Jung Chou, Hei xian hao, Zai pei hei zhong cao; Cze.: Černucha, Černý kmín; Dan.:
Sortkommen; Dut.: Kruidboek, Narduszaad (seeds), Zwarte komijn; Eng.: Black
caraway, Black cumin, Black seed, Fennel flower, Nutmeg flower; Fre.: Cheveux de
vénus, Cumin noir, Herbe aux épices, Nielle cultivée, Nigelle, Poivrette; Ger.:
Saatschwarzkümmel, Schwarzkümmel, Zwiebelsame; Gre.: Melanthion; Ita.:
Cuminella, Damigella aromatic, Erba spezie, Gittaione, Melanzio; Jap.: Kuro
tanetsou, Nigera; Kor.: Beul raeg ku min, Dae hoe hyang; Lat.: Panacea; Maly.:
Jintam hitam; Nep.: Mugrelo, Mungrelo; Nor.: Svartkarve; Per.: Siyah daneh,
Shuniz; Pol.: Czarnuszka siewna; Por.: Caminho-reto (Br.), Cominho-negro,
Cominho-preto, Nigela; Rus.: Chernushka posevnaia; Sin.: Kalu duru; Spa.: Ajenuz
común, Arañuel, Neguilla; Swe.: Svartkummin; Tha.: Thian dam; Tur.: Çörek otu,
Çöreotu; Vie.: Thì là đen.
Description: The plant is native to south and southwest Mediterranean countries,
and India, and widely cultivated in the Mediterranean and Middle Eastern countries,
south Europe, and southwest Asia. It is an annual flowering plant that grows to a
height of 20–30 cm, with finely divided linear leaves; flowers are delicate and
usually colored pale blue and white, with five to ten petals. Seeds are triangular,
black, 3 mm long, contained in a large caraway fruit that has an inflated cap-
sule composed of three to seven united follicles, each containing numerous seeds;
the umblical end being smaller than the other, testa rough; inside the testa is a white
oily kernel with a strong aromatic odor. When rubbed, seeds diffuse a pleasant odor
of lemons, with a slight soupcon of carrot (Figs. 1 and 2).XL
Actions and Uses: Medicinal usage of black seeds dates back to the ancient
Egyptians, Greeks, and Romans; the Prophet Muhammad (PBUH) is quoted to have
said “Use Black seed regularly, since it is a cure for every disease except death” [71].
Black cumin seeds were found in the tomb of the Egyptian Pharaoh, Tutankha-
men,CLVI and were also recovered in northcentral Turkey from a pilgrim flask of the
Old Hittite period of Boyali Höyük (Mound), dating from around 1650 B.C [182].
Hippocrates and Dioscorides mentioned it as Melanthion and Pliny called it Gith. It
is extensively used both as a spice and as a medicine. Muslim physicians of Unani
Nigella sativa L. 1289

Fig. 1 Nigella sativa, Plant, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA
3.0, https://commons.wikimedia.org/wiki/File:Nigella_sativa_001.JPG; https://creativecommons.
org/licenses/by/3.0/deed.en

Fig. 2 Nigella sativa, Seeds, Prof. Akbar, Original

medicine in India describe it as heating, attenuant, suppurative, detergent and

diuretic, and believe that it increases menstrual flow and secretion of milk, and
stimulates uterine activity. They prescribe it for a variety of disorders caused due to
cold humours, and credit it with anthelmintic property. Earlier clinical trials showed
a dose of 10–20 g produced marked emmenagogue effect in dysmenorrhea, and in
larger doses caused abortion. In doses of 10–40 g of powdered seeds raised body
temperature, increased pulse rate, stimulated all secretions, especially of the kidneys
1290 Nigella sativa L.

and skin.XL Continuous use of black seeds is diuretic, galactagogue and emmena-
gogue. Topical application of ground seeds mixed with vinegar cures pimples and
boils. Seven seeds soaked in woman’s milk for an hour and then used as snuff is
extremely beneficial in jaundice.LXIX KabeeruddinLXXVII described seeds (temper-
ament, hot 2° and dry 2°; Al-Baitar quoted Galen to describe the temperament in 3°)
as expectorant, carminative, stomachic, emmenagogue, anthelmintic, and analgesic,
and used in the treatment of bronchial asthma, digestive weakness, jaundice, ascites,
arthritis and amenorrhea. Externally, seeds are detergent and used for vitiligo,
eczema, alopecia, and pimples; its oil is used as massage for paralysis, palsy and
backache. Hindu physicians also regard seeds as aromatic, diuretic, diaphoretic,
antibilious, stomachic, stimulant, carminative, digestive, anthelmintic and emme-
nagogueCV and use them with other aromatics and Plumbago root in dyspepsia, loss
of appetite, diarrhea and intermittent fevers. A decoction of seeds is given after
delivery to stimulate uterine contraction and to stimulate milk secretion.LXXXI In
Arab countries, Europe and Iran, the seeds and oil are also traditionally used in the
treatment of asthma, hypertension, diabetes, inflammation, tumor, cough, bronchitis,
headache, eczema, fever, dizziness, gastrointestinal disturbances, impotence, painful
menstruation, flu, and as carminative, diuretic and antiparasitic agent [18]. It is one
of the most frequently used plants to treat diabetes in the Moroccan folk medicine
[172, 192], and almost three-quarter Jordanian diabetic patients use them as adjunct
to conventional therapy and 80% of them with the knowledge of their physicians
[166]. It is one of the medicinal plants that have been promoted on industrial scale in
Egypt for several decades [185].
Phytoconstituents: Aqueous seed extract tested positive for alkaloids, flavonoids,
saponins, anthraquinones, and tannins [33], and methanol extract showed the pres-
ence of alkaloids, phenolic compounds, flavonoids, proteins, carbohydrates, sapo-
nins, lipids, sterols and tannins [8]. Nineteen phenolic compounds: apigenin, caftaric
acid, caffeic acid, chlorogenic acid, cichoric acid, p-coumaric acid, ferulic acid,
fisetin, gentisic acid, hyperoside, isoquercitrin, kaempferol, luteolin, myricetin, pat-
uletin, quercitrin, quercetin, rutin, and sinapic acid were identified from ethanol
extract of seeds [197]. Indazole-type alkaloids, nigellidine [20], 17-O-(b-D-gluco-
pyranosyl)-4-O-methylnigellidine, nigelanoid, 8b 4-O-methylnigellidine, 8b
nigeglanine, 14 and 4-O-methylnigeglanine [208], dolabellane-type diterpene alka-
loids, nigellamines A1, A2, B1 and B2 [153] nigellamines A3, A4, A5, and C [154],
triterpene saponin (a-hederin) [134], steroidal glucoside [147], and glycosylated
triterpene [146] have also been isolated from seeds. Trans-anethole (38.3%),
p-cymene (14.8%), limonene (4.3%), and carvone (4.0%) were identified as major
compounds out of thirty-two compounds identified in seed VO [163], but Mah-
moudvand et al. [140] reported thymoquinone (TQ) (42.4%), p-cymene (14.1%),
carvacrol (10.3%) and longifolene (6.1%) as the major components, whereas,
p-cymene (37.3%) and TQ (13.7%) were found as the major components out of 20
identified in the steam distilled VO, all from Iran. Thymoquinone and p-cymene were
identified as the major constituents of thirty-eight volatile compounds of seed oil from
Turkey; levels of these compounds decreased with roasting of seeds [130].
Nigella sativa L. 1291

Thymoquinone (62.17%), carvacrol (16.84%), 2-methyl-5-prop-2-enyldihydroquinone

(8.29%), dihydrothymoquinone (6.99%), monoterpenes (3.11%) and terpini-4-en-1-ol
(2.07%) were identified as major constituents of seed VO from Morocco [10]. Seed VO
from India, obtained by SCCD, contained forty-seven volatile compounds, of which TQ,
dithymoquinone, thymohydroquinone and thymol were the major phenolic compounds
that varied depending upon extraction method [195]. Quercetin-3-O-a-L rhamnopyra-
noside, quercetin-7-O-b-D-glucopyranoside, tauroside E, and sapindoside B were
reported as potential antidepressant constituents in methanolic extract of defatted seeds
[71]. Seed fixed oil contained linoleic acid (55.6%) as the major fatty acid, followed by
oleic acid (23.4%), and palmitic acid (12.5%) as the major saturated fatty acid [163, 173].
Sterols derived from oil of Sudanese variety were identified as cholesterol, campesterol,
stigmasterol, b-sitosterol and a-spinasterol [178].
Pharmacology: Seed-supplemented diet of normal rats produced a homogenous
cardiac hypertrophy and enhanced cardiac contractility [17, 65, 203]. Aqueous seed
extract (i.v.) lowered MAP with a significant decrease in HR in normal rats, that
was partly dependent on endothelium [95]. Both aqueous and macerated extracts
significantly reduced HR and contractility on isolated guinea pig heart due to
calcium channel blocking effect that was greater than nifedipine [49, 189]. Volatile
oil (i.v.) also decreased arterial BP and HR of anesthetized rats, that were antag-
onized by cyproheptadine, hexamethonium, atropine and pretreatment with reser-
pine [63]; the vasorelaxant effect of the oil was not mediated by NO and was
independent of endothelium [53]. Aqueous extract (i.p.) produced significant
diuresis coupled with natriuresis and kaliuresis in rats [33], and dichloromethane
extract to SHRs for 15-days caused significant diuresis with natriuresis and sig-
nificantly lowered MAP [211]. Volatile oil (i.p.) prevented hematological toxicity,
decreased elevated HR and glucose concentration, and preserved islet b-cells in
cadmium-treated rats [57]. Hydroalcohol extract treatment of diabetic rats for
six-weeks significantly reduced rat aortic rings reactivity to vasoconstrictors, and
increased to vasodilator agents [2]. Isolated heart from rats, administered seed
powder for 12-weeks, were more resistant to oxidative stress and damage due to I/R
injury [188]. Pretreatment with TQ also reduced the heart infarct size due to I/R
injury in anesthetized rats [84].
Seeds supplemented diet significantly decreased TC, LDL-C and TG in normal
rats [131], and in hypercholesterolemic rats [160]. Powdered seeds to rats with
fructose-induced metabolic syndrome, highly significantly reduced serum LDL-C
and TGs and improved antioxidant enzymes activities [29], and both seed powder
and VO significantly reduced TC and LDL-C and enhanced HDL-C levels, and
significantly inhibited aortic plaque formation in hypercholesterolemic rabbits [28].
Thymoquinone also protected against methionine-induced hyperhomocysteinemia
and biochemical changes [72]. Aqueous extract inhibited sodium-dependent glucose
transport across isolated rat jejunum, and improved glucose-tolerance in rats, com-
parable to metformin [145]; reduced blood glucose and MDA, increased GSH and
prevented LPO-induced liver damage in diabetic rabbits [149]. Ethanol extract sig-
nificantly reduced blood glucose, lipids, plasma insulin of diabetic rats and improved
1292 Nigella sativa L.

antioxidant enzymes [116]. Petroleum ether extract caused significant reduction in

food intake and a transient weight loss, lowered plasma levels of insulin and TGs and
higher HDL-C in normal rats after four-weeks treatment [137]. Fixed and VO sig-
nificantly decreased oxidative stress in diabetic rats [120, 191], and VO significantly
reduced blood glucose and increased phagocytic activity of peritoneal macrophages
of diabetic hamsters [76, 77], and caused partial regeneration/proliferation of pan-
creatic b-cells in diabetic rats [124], the hypoglycemic effect may have an extra-
pancreatic component to stimulated insulin release [68].
Aqueous (AE) and methanol extracts of defatted seeds exhibited potent CNS
depressant and analgesic effects [27]; the AE also showed anxiolytic activity in rats
[40], and the VO produced antidepressant effect with increased brain 5-HT and
decreased 5-HT turnover [170]. Volatile oil pretreatment for 20-days improved
learning and memory of normal rats [175], and repeated administration attenuated
development of tolerance and dependence to morphine [5]. Volatile oil also
effectively prevented brain oxidative injury due to seizures better than valproate
[74, 107], both VO and TQ ameliorated brain ischemia and spinal cord injury-
induced oxidative damage [99, 119], and diabetic neuropathy [125]. Petroleum
ether and chloroform extracts also ameliorated brain ischemia-induced oxidative
damage and improved brain antioxidant enzymes [12]. Hydroalcohol extract
protected against seizure-induced neuronal damage and memory impairment [187,
200], scopolamine-induced memory deficit, decreased brain AChE activity [97],
and hypothyroidism-associated learning and memory impairment during neonatal
and juvenile growth in rats [45]. Volatile oil significantly protected against
haloperidol-induced EPS-like effects including movement disorders and oral
dyskinesia in rats [142].
Seeds supplemented diet protected against lead acetate-[78], and isoniazid-
hepatotoxicity [93, 111], and ethanol and methanol seed extracts protected against
acute APAP-hepatoxicity [6, 135]. Water suspension and extract of seeds protected
against CCl4-hepatotoxicity [15, 112], so did both the fixed oil [198] and VO [30,
148, 198]. Fixed and VO also protected against ethanol-induced oxidative stress
and liver damage in rats [58, 171]. VO completely protected against d-galactosa-
mine hepatotoxicity [69], alleviated CCl4-induced suppression of CYP2B,
CYP3A2, CYP2C11 and CYP1A2 [106], decreased LPO, liver enzymes and
increased antioxidant enzymes [118, 123], protected liver against the effects of
hypervitaminosis A [31], and against I/R injury [205]. Thymoquinone was the only
constituent of VO that could efficiently protect against chemically-induced hepatic
damage [144]. Powdered seeds lowered serum creatinine with no effect on kidney
architecture in normal rats [59], and protected against I/R injury of kidneys [158,
159]. Ethanol extract significantly reduced number of EG-induced calcium oxalate
deposits in rats’ kidneys [86], ameliorated cisplatin-nephrotoxicity [88, 98],
APAP-nephrotoxicity [52], and caused significant uricosuric, diuretic and natri-
uretic effect with minimal kaliuresis [197]. The oil significantly ameliorated
gentamicin-nephrotoxicity in rats [19, 179, 202], sodium nitrite-nephrotoxicity [14],
diabetic-nephropathy [209], attenuated bromobenzene-induced hepatorenal injury
Nigella sativa L. 1293

[90], significantly normalized physiological parameters and prevented APAP-

induced structural changes in kidneys [9], protected against I/R injury of kidneys
[44, 94, 206], attenuated cyclosporine-induced oxidative stress and nephron-toxicity
[199]. Thymoquinone significantly protected rats from doxorubicin-hyperlipidemic
nephropathy [34], gentamicin-nephrotoxicity [186], and significantly decreased
number and size of EG-induced renal calculi in rats [87]. An extract is also reported
to protect from cisplatin-induced falls in Hb levels and WBC counts [161].
Aqueous seed extract possesses both analgesic and anti-inflammatory activities
[16], and ethanol extract (i.p.) exhibited potent and prolonged anti-inflammatory
activity in rats [42], and analgesic activity in mice [43]. Oral VO exhibited anal-
gesic activity, blocked by naloxone [3], but only i.p. dose exhibited significant
anti-inflammatory effect [89]. Significant analgesic effect, not reversed by naloxone,
was elicited by both oral and i.p. polyphenols, but only i.p. dose reduced
carrageenan-induced paw edema [81]. Thymoquinone (i.p.) attenuated OVA-
induced airway inflammation in mice [1, 62], suppressed adjuvant-induced arthritis
in rats [193], and potently inhibited formation of LTs in blood cells [67, 143]. Fixed
oil to normal rats for 12-weeks significantly decreased serum TC, TG, and glucose
levels, and leukocytes and platelets counts [210], and the methanol soluble portion
of it inhibited AA-induced platelet aggregation and blood coagulation [73]. Both
fixed oil and TQ inhibit COX and 5-LOX pathways in rat stimulated peritoneal
leukocytes. However, inhibition by fixed oil was greater than was expected from its
TQ content [102]. Seeds, VO and TQ significantly reduced gastric ulcers and
gastric mucosal histamine, and significantly increased GSH level, mucin content
and free acidity [51, 66, 121, 122]; they also protected against I/R-induced gastric
oxidative stress and lesions [64]. While the oil decreased proinflammatory
cytokines, LDH, TG, and TC in TNBSA-induced colitis in rats [108], TQ did not
show any anti-inflammatory effects on TNBSA colitis in mice [113]. Hexane seed
extract and TQ significantly improved symptoms and immune parameters in
OVA-induced allergic diarrhea in BALB/c-mice [61].
Aqueous extract was more effective against MDR Gram-negative isolates than
the Gram-positive ones [155], and C. albicans [128]. Inhibition of growth of S.
aureus by aqueous infusion of ground seeds from Hadramout (Yemen) was more
effective than with seeds from Ethiopia, but no effect on E. coli or Enterobacter
[37]. Ethanol extract showed inhibitory effect on MRSA [92], and ether extract
significantly inhibited growth of S. aureus, P. aeruginosa, E. coli, and C. albicans;
the ether extract showed synergistic activity with streptomycin and gentamicin, and
additive effect with spectinomycin, erythromycin, tobramycin, doxycycline, chlo-
ramphenicol, nalidixic acid, ampicillin, lincomycin and sulfamethoxazole-
trimethoprim [91]. Volatile oil was significantly active against S. aureus, and
moderately active against E. coli, S. typhi, P. aeruginosa, B. subtilis and C. albicans
[196], and strongly active against A. fumigatus [110], on dermatophytes, M. canis,
M. gypseum and T. mentagrophytes [140]. Thymohydroquinone potently inhibited
growth of B. subtilis, S. aureus [70], and of T. mentagrophytes, M. canis and
M. gypseum [140]. Volatile oil (i.p.) to BALB/c mice strikingly inhibited murine
CMV titers in spleen and liver, with increased serum level of IFN-c [181].
1294 Nigella sativa L.

Ethanol extract to male rats for 60-days significantly increased weight of testes
and epididymidis, sperm count, epididymal sperm reserve, daily sperm production,
testosterone and LH [168], oil also produced significantly higher percentage of
motile, normal and live sperm [54], improved semen quality and moderated
chlorpyrifos-induced reproductive toxicity [156]. Seeds supplemented diet signifi-
cantly increased testosterone level and ameliorated deleterious effects of heat on
spermatogenesis and antioxidant status in male mice [150], and low dose seeds and
their methanol extract exerted prominent estrogenic effects on reproductive organs
of ovariectomized rats [169]. Hexane extract to female rats on days 1–10
post-coitum prevented pregnancy [127]. Both aqueous and ethanol extracts sig-
nificantly increased milk production in rats [7, 101]. Volatile oil inhibited spon-
taneous and oxytocin induced contractions of rat and guinea pig uterine smooth
muscle [32].
Seeds exerted antiproliferative, proapoptotic, cytotoxic, antimutagenic, anti-
metastatic, and NK cytotoxic activity enhancing effects against various primary
cancer cell lines [141]. Seeds supplemented diet inhibitd DNA damage in
AOM-induced colon cancer in rats [23], and significantly suppressed ferric
nitrilotriacetate-induced oxidative stress, hyperproliferative response and renal car-
cinogenesis in rats [129]. A seed extract delayed onset of DMBA-induced skin
papillomas and MCA-induced soft tissue sarcoma in mice [184]. Injection of VO into
tumor also significantly inhibited solid tumor development [10], and VO inhibited
DMH-induced colon carcinogenesis of rats in the post-initiation stage with sup-
pression of cell proliferation in the colonic mucosa [183]. Thymoquinone and seed
oil decreased expression of the Brca1, Brca2, Id-1 and P53 mutations in mammary
tissues of female rats with DMBA-induced breast cancer, and reduced activities of
tumor markers [138], and TQ blocked tumor angiogenesis in a xenograft human
prostate cancer in mouse [204]. Thymoquinone also inhibited DNA synthesis, pro-
liferation, and viability of cancerous prostate epithelial cells by downregulating
androgen receptors and E2F-1, a regulator of cell proliferation and viability, without
affecting the noncancerous cells [126], and prevented B(a)P-induced forestomach
carcinogenesis and MCA-induced fibrosarcoma tumors [35, 36].
Clinical Studies: In healthy Iranian volunteers, aged 34–63 years, 2.5 mL of oil
twice daily for eight-weeks significantly lowered both SBP and DBP from baseline
and compared to placebo group [75], and a seed extract for two-months signifi-
cantly reduced both SBP and DBP, TC and LDL-C in mildly hypertensive patients
[56]. Treatment of Indonesian men, 30–45 years old with central obesity, with
seeds 750 mg twice daily for three-months highly significantly reduced body
weight and waist circumference with an insignificant reduction in serum free
testosterone, SBP and DBP, compared to placebo [55]. Meta-analysis of eleven
RCTs involving 860 hypertensive or normotensive subjects reported a mean
decrease in SBP from 132.85 to 125.19 mmHg and from 82.63 to 77.74 mmHg in
DBP after a mean treatment duration of 8.3 weeks with N. sativa [177]. In an RCT,
hypercholesterolemic Iranian patients treated with 2 g of seed powder daily for
four-weeks had a significant decrease in TC, LDL-C and TGs, but no significant
Nigella sativa L. 1295

effect on FBG [174], and administration of powdered seed in a dose of 3 g/day for
8-weeks to healthy postmenopausal Emarati women significantly improved blood
oxidants and antioxidants balance [157], whereas postmenopausal Malaysian
women with MetS treated with seeds powder 1 g daily after breakfast for
two-months showed no significant reduction in body weight but a significant fall in
FBG, TC, LDL-C, and TG, and increased HDL-C [104, 105]. Perimenopausal
Malaysian women treated with 800 mg of seed powder twice daily for
twelve-weeks showed significant improvement in prevalence and severity of
menopausal symptoms and LDL-C, but no significant differences in TC, TG and
HDL-C [136]. However, consumption of bread containing seeds for two-months by
patients of either sex with MetS did not have any significant effects on TC, LDL-C,
TG, HDL, APO-A, APO-B and CRP [151]. Supplementation of powdered seeds
(2 g daily) to young sedentary overweight Iranian women coupled with aerobic
exercise for eight-weeks synergistically lowered TC, LDL-C, TG, and BMI, and
increased HDL, compared to aerobic training alone [79]. Obese premenopausal
Iranian women with BMI between 30 and 35 kg m2 treated with seed oil (1 g
before each meal) and low calorie-diet for eight-weeks, had significant reduction in
body weight and waist circumference, and significant decline in LDL-C and TG
levels [139], increased SOD levels, but no significant changes in LPO, GPx, and
total antioxidant capacity compared to placebo group [162]. A meta-analysis of
seventeen RCTs concluded that supplementation with N. sativa resulted in an
average reduction of 15.6 mg/dL of TC, 14.1 mg/dL of LDL-C, and 20.6 mg/dL of
TG; seed oil lowered TC and LDL-C better than seed powder, however, increase in
HDL-C levels was observed only with seed powder [176]. Supplementation of
Saudi patients of either sex with uncontrolled type-2 diabetes with HbA1c > 7%,
with an optimal dose of 2 g/day of seeds powder as an adjunct to oral antidiabetic
drugs for twelve-weeks, had significant reduction in TC, LDL-C, and TGs, and
significant increase in HDL-C/LDL-C ratio [39, 115]; continuing the treatment for
one-year also significantly reduced insulin-resistance, improved antioxidant defense
capacity [114], significantly decreased HbA1c, improved LV systolic function and
protected from diastolic dysfunction [38].
The number of swollen joints and the duration of morning stiffness in Egyptian
female patients with rheumatoid arthritis improved after oral treatment with seed oil
capsules 500 mg twice daily for a month [82]. Similar results were reported in
Iranian female patients with rheumatoid arthritis treated with the oil for eight-weeks
that also reported reduced oxidative stress [85]. Topical application of seed oil
provided significant relief from cyclic mastalgia, comparable to topical diclofenac
use [103]. Application of VO to vitiligo patches for six-months significantly
improved patches on upper extremities, trunk, head, and neck than fish oil [83], and
VO application twice daily significantly improved hand eczema, similar to the
application of betamethasone [207].
Powdered seeds (500 mg) twice daily to Bangladeshi healthy elderly volunteers
for nine-weeks significantly enhanced memory, attention and cognition [46], and
stabilized mood, decreased anxiety and modulated cognition in healthy adolescent
male volunteers [47]. Aqueous extract (40 mg/kg tid) for four-weeks as an adjunct
1296 Nigella sativa L.

to anticonvulsant therapy in children aged 13 months to 13 years old with refrac-

tory epilepsy, significantly decreased frequency of seizures [11]. Iranian infertile
men with abnormal semen quality treated with 2.5 ml of seed oil twice daily for two
months significantly improved sperm morphology, count, motility and semen
volume [132].
Adult Saudi patients suffering from dyspeptic symptoms and positive for
H. pylori infection, comparatively treated either with conventional triple-therapy or
with seeds plus omeprazole, equally improved dyspepsia symptoms but did not
show better anti H. pylori effect than the triple-therapy [180]. In another study of
functional dyspepsia in Iranian patients, daily dose of seed oil (5 ml) mixed with
honey for eight-weeks significantly improved dyspeptic symptoms and significantly
lowered H. pylori infection compared to placebo group [152].
Boiled seed extract to Iranian asthmatic patients as an adjunct to asthma therapy
improved asthma symptoms and decreased usage of rescue inhaler, oral b-agonists,
oral and inhaled corticosteroid, and oral theophylline at the end of 45-days study
period [48]. The time of onset of bronchodilatory effect was 30 min, and lasted for
150 min, similar but less than the effect of theophylline [50]. Volatile oil treatment
in a dose of 40–80 mg/kg/day improved subjective feeling score in a total of 152
German patients with allergic diseases: allergic rhinitis, bronchial asthma, and
atopic eczema, over the course of the treatment [117]. Iranian patients with allergic
rhinitis treated with VO for 30-days improved their nasal mucosal congestion, nasal
itching, runny nose, sneezing attacks, turbinate hypertrophy, and mucosal pallor
[164]. Similarly, Turkish patients sensitive to house dustmites with allergic rhinitis
receiving immunotherapy supplemented with seed (2 g/day orally) for 30-days
showed a significant increase in CD8 counts compared to patients receiving only
specific immunotherapy [109]. Two weeks topical application of VO in Turkish
geriatric patients with nasal dryness and related symptoms, significantly improved
nasal dryness, obstruction and crusting [167].
A 46-years old Nigerian sero-positive HIV patient with multiple papular pruritic
lesions, administered by an herbalist 10 ml concoction of seeds twice daily,
reportedly had his pruritic lesions cleared by 20th day and became seronegative
after six-months treatment, and remained so for twenty-four months of follow-up
without further treatment [165]. The seed oil (450 mg tid) administered to Egyptian
patients with positive HCV infection with chronic liver disease or liver cirrhosis
significantly improved HCV viral load, improved clinical symptoms, oxidative
stress, and reduced blood glucose in those with diabetes [41]. Ethanol extract also
significantly decreased viral load and ameliorated altered liver function in HCV
patients [4]. A single oral dose of ground seeds at 40 mg/kg to children with natural
cestodal infection reduced percentage of fecal eggs per gram counts on days 7 and
15, equivalent to 50 mg/kg dose of niclosamide [13].
Mechanism of Action: Anticancer activity involves proapoptotic, cytotoxic, and
enhancing NK cytotoxic activity effects, that utilizes iNOS signaling as the
major signaling pathway [141]. Anticonvulsant activity of TQ is suggested to be
Nigella sativa L. 1297

through an opioid receptor-mediated increase in GABAergic tone [100], whereas,

antidepressant-like effect is due to increased brain 5-HT and decreased 5-HT
turnover [170]. Decreased hepatic gluconeogenesis, and increased insulin secretion
contribute to its hypoglycemic effect [76, 77].
Human A/Es, Allergy and Toxicity: Use of topical preparations containing black
seed oil has resulted in allergic contact dermatitis in German patients [190, 213],
and a 53-year-old French woman developed systematic erythematous plaques with
vesicles and bullous lesions after ingesting and topically using black seed oil for
two-weeks [80].
Animal Toxicity: Powdered seeds supplemented diet of rats, 1 g/kg daily for
28-days did not affect liver enzymes or cause other toxicity [60]. Oral aqueous,
methanol and chloroform extracts up to a dose of 21 g/kg were nonlethal and
nontoxic to mice except that methanol and chloroform extracts significantly
decreased animals weight [201]. Aqueous extract to male Sprague-Dawley rats for
14-days significantly increased serum ALT (SGPT) concentration without any
changes in hepatocytes [194]. Ethanol extract was nontoxic, but aqueous extract
was toxic to Brine shrimp [96]. LD50 (i.p.) of aqueous and ethanol seed extracts
were reported to be 4,230 and 4,900 mg/kg, respectively [101]; whereas, oral and
i.p. single dose LD50 values of fixed oil in mice were 28.8 and 2.06 ml/kg,
respectively [212].
CYP450 and Potential for Drug-Herb Interactions: Black seed aqueous extract
significantly inhibited CYP2D6 and CYP3A4 in human liver microsomes and in
healthy human volunteers [22], and concurrent administration significantly reduced
phenytoin elimination in dogs [25], reduced AUC, Cmax and half-life of sildenafil
in beagle dogs [26], significantly decreased Cmax and AUC of cyclosporine [21],
but did not affect pharmcokinetics of carbamazepine in rabbits [24]. The extract
also strongly inhibited rat CYP2C11 gene expression [133].
Commentary: This is one of the most extensively studied medicinal plants.
Results of a number of RCTs, regarding effects of black seeds on blood pressure
and lipids were encouraging, and positive outcomes of other clinical trials were also
promising. However, many of these trials have not been reproduced in larger
numbers and in diverse populations to validate their results.

References
1. Abbas AT, Abdel-Aziz MM, Zalata KR. Abd Al-Galel Tel-D. Effect of
dexamethasone and Nigella sativa on peripheral blood eosinophil count,
IgG1 and IgG2a, cytokine profiles and lung inflammation in murine model
of allergic asthma. Egypt J Immunol. 2005;12:95–102.
2. Abbasnezhad A, Niazmand S, Mahmoudabady M, et al. Nigella sativa seed
decreases endothelial dysfunction in streptozotocin-induced diabetic rat
aorta. Avicenna J Phytomed. 2016;6:67–76.
1298 Nigella sativa L.

3. Abdel-Fattah AM, Matsumoto K, Watanabe H. Antinociceptive effects of

Nigella sativa oil and its major component, thymoquinone, in mice. Eur J
Pharmacol. 2000;400:89–97.
4. Abdel-Moneim A, Morsy BM, Mahmoud AM, Abo-Seif MA, Zanaty MI.
Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in
HCV patients in Egypt. EXCLI J. 2013;12:943–55.
5. Abdel-Zaher AO, Abdel-Rahman MS. ELwasei FM. Blockade of nitric
oxide overproduction and oxidative stress by Nigella sativa oil attenuates
morphine-induced tolerance and dependence in mice. Neurochem Res.
2010;35:1557–65.
6. Adam GO, Rahman MM, Lee SJ, et al. Hepatoprotective effects of Nigella
sativa seed extract against acetaminophen-induced oxidative stress. Asian
Pac J Trop Med. 2016;9:221–7.
7. Agrawala IP, Achar MV, Tamankar BP. Galactogogue action of Nigella
sativa. Indian J Med Sci. 1971;25:535–7.
8. Ahmad A, Husain A, Mujeeb M, et al. Physicochemical and phytochem-
ical standardization with HPTLC fingerprinting of Nigella sativa L. seeds.
Pak J Pharm Sci. 2014;27:1175–82.
9. Ahmed OG, El-Mottaleb NA. Renal function and arterial blood pressure
alterations after exposure to acetaminophen with a potential role of Nigella
sativa oil in adult male rats. J Physiol Biochem. 2013;69:1–13.
10. Ait Mbarek L, Ait Mouse H, Elabbadi N, et al. Antitumor properties of
black seed (Nigella sativa L.) extracts. Braz J Med Biol Res. 2007;40:
839–47.
11. Akhondian J, Parsa A, Rakhshande H. The effect of Nigella sativa L.
(black cumin seed) on intractable pediatric seizures. Med Sci Monit. 2007;
13:CR555–9.
12. Akhtar M, Maikiyo AM, Najmi AK, et al. Neuroprotective effects of
chloroform and petroleum ether extracts of Nigella sativa seeds in stroke
model of rat. J Pharm Bioallied Sci. 2013;5:119–25.
13. Akhtar MS, Riffat S. Field trial of Saussurea lappa roots against
nematodes and Nigella sativa seeds against cestodes in children. J Pak
Med Assoc. 1991;41:185–7.
14. Al-Gayyar MM, Hassan HM, Alyoussef A, et al. Nigella sativa oil
attenuates chronic nephrotoxicity induced by oral sodium nitrite: effects on
tissue fibrosis and apoptosis. Redox Rep. 2016;21:50–60.
15. Al-Ghamdi MS. Protective effect of Nigella sativa seeds against carbon
tetrachloride-induced liver damage. Am J Chin Med. 2003;31:721–8.
16. Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity
of Nigella sativa. J Ethnopharmacol. 2001;76:45–8.
17. Al-Hariri MT, Yar T, Bamosa AO, El-Bahai MN. Effects of two-months
Nigella sativa supplementation on cardiac hemodynamics and adrenergic
responsiveness. J Pak Med Assoc. 2009;59:363–8.
18. Ali BH, Blunden G. Pharmacological and toxicological properties of
Nigella sativa. Phytother Res. 2003;17:299–305.
Nigella sativa L. 1299

19. Ali BH. The effect of Nigella sativa oil on gentamicin nephrotoxicity in
rats. Am J Chin Med. 2004;32:49–55.
20. Ali Z, Ferreira D, Carvalho P, et al. Nigellidine-4-O-sulfite, the first sulfated
indazole-type alkaloid from the seeds of Nigella sativa. J Nat Prod. 2008;
71:1111–2.
21. Al-Jenoobi FI, Al-Suwayeh SA, Muzaffar I, et al. Effects of Nigella sativa
and Lepidium sativum on cyclosporine pharmacokinetics. Biomed Res Int.
2013;2013:953520.
22. Al-Jenoobi FI, Al-Thukair AA, Abbas FA, et al. Effect of black seed on
dextromethorphan O- and N-demethylation in human liver microsomes
and healthy human subjects. Drug Metab Lett. 2010;4:51–5.
23. Al-Johar D, Shinwari N, Arif J, et al. Role of Nigella sativa and a number
of its antioxidant constituents towards azoxymethane-induced genotoxic
effects and colon cancer in rats. Phytother Res. 2008;22:1311–23.
24. Alkharfy KM, Al-Jenoobi FI, Alam MA, et al. Lepidium sativum but not
Nigella sativa affects carbamazepine disposition in an animal model. Drug
Metab Lett. 2013;7:47–51.
25. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium
sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin
pharmacokinetics in beagle dogs. Phytother Res. 2013;27:1800–4.
26. Al-Mohizea AM, Ahad A, El-Maghraby GM, et al. Effects of Nigella
sativa, Lepidium sativum and Trigonella foenum-graecum on sildenafil
disposition in beagle dogs. Eur J Drug Metab Pharmacokinet. 2015;40:
219–24.
27. Al-Naggar TB, Gómez-Serranillos MP, Carretero ME, Villar AM. Neu-
ropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol.
2003;88:63–8.
28. Al-Naqeep G, Al-Zubairi AS, Ismail M, Amom ZH, Esa NM. Antiathero-
genic potential of Nigella sativa seeds and oil in diet-induced hyperc-
holesterolemia in rabbits. Evid Based Complement Alternat Med. 2011;
2011:213628.
29. Al-Rasheed N, Al-Rasheed N, Bassiouni Y, Faddah L, Mohamad AM.
Potential protective effects of Nigella sativa and Allium sativum against
fructose-induced metabolic syndrome in rats. J Oleo Sci. 2014;63:839–48.
30. Al-Seeni MN, El Rabey HA, Zamzami MA, Alnefayee AM. The
hepatoprotective activity of olive oil and Nigella sativa oil against CCl4
induced hepatotoxicity in male rats. BMC Complement Altern Med.
2016;16:438.
31. Al-Suhaimi EA. Hepatoprotective and immunological functions of Nigella
sativa seed oil against hypervitaminosis A in adult male rats. Int J Vitam
Nutr Res. 2012;82:288–97.
32. Aqel M, Shaheen R. Effects of the volatile oil of Nigella sativa seeds on
the uterine smooth muscle of rat and guinea pig. J Ethnopharmacol.
1996;52:23–6.
1300 Nigella sativa L.

33. Asif M, Jabeen Q, Abdul Majid AM, Atif M. Diuretic activity of aqueous
extract of Nigella sativa in albino rats. Acta Pol Pharm. 2015;72:129–35.
34. Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM. The
influence of thymoquinone on doxorubicin-induced hyperlipidemic nephro-
pathy in rats. Toxicology. 2000;143:219–26.
35. Badary OA, Al-Shabanah OA, Nagi MN, et al. Inhibition of benzo(a)
pyrene-induced forestomach carcinogenesis in mice by thymoquinone.
Eur J Cancer Prev. 1999;8:435–40.
36. Badary OA, Gamal El-Din AM. Inhibitory effects of thymoquinone against
20-methylcholanthrene-induced fibrosarcoma tumorigenesis. Cancer Detect
Prev. 2001;25:362–8.
37. Bakathir HA, Abbas NA. Detection of the antibacterial effect of Nigella
sativa ground seeds with water. Afr J Tradit Complement Altern Med.
2011;8:159–64.
38. Bamosa A, Kaatabi H, Badar A, et al. Nigella sativa: a potential natural
protective agent against cardiac dysfunction in patients with type 2 diabetes
mellitus. J Family Community Med. 2015;22:88–95.
39. Bamosa AO, Kaatabi H, Lebdaa FM, Elq AM, Al-Sultanb A. Effect
of Nigella sativa seeds on the glycemic control of patients with type 2
diabetes mellitus. Indian J Physiol Pharmacol. 2010;54:344–54.
40. Bano F, Ahmed A, Parveen T, Haider S. Anxiolytic and hyperlocomotive
effects of aqueous extract of Nigella sativa L. seeds in rats. Pak J Pharm
Sci. 2014;27(5 Spec no):1547–52.
41. Barakat EM, El Wakeel LM, Hagag RS. Effects of Nigella sativa on
outcome of hepatitis C in Egypt. World J Gastroenterol. 2013;19:2529–36.
42. Bashir MU, Qureshi HJ, Saleem T. Comparison of anti-inflammatory
activity of Nigella sativa and diclofenac sodium in albino rats. J Ayub
Med Coll Abbottabad. 2015;27:523–6.
43. Bashir MU, Qureshi HJ. Analgesic effect of Nigella sativa seeds extract on
experimentally induced pain in albino mice. J Coll Physicians Surg Pak.
2010;20:464–7.
44. Bayrak O, Bavbek N, Karatas OF, et al. Nigella sativa protects against
ischaemia/reperfusion injury in rat kidneys. Nephrol Dial Transplant. 2008;
23:2206–12.
45. Beheshti F, Hosseini M, Shafei MN, et al. The effects of Nigella sativa
extract on hypothyroidism-associated learning and memory impairment
during neonatal and juvenile growth in rats. Nutr Neurosci. 2016;1–11.
46. Bin Sayeed MS, Asaduzzaman M, Morshed H, et al. The effect of Nigella
sativa Linn. seed on memory, attention and cognition in healthy human
volunteers. J Ethnopharmacol. 2013;148:780–6.
47. Bin Sayeed MS, Shams T, Fahim Hossain S, et al. Nigella sativa L. seeds
modulate mood, anxiety and cognition in healthy adolescent males.
J Ethnopharmacol. 2014;152:156–62.
Nigella sativa L. 1301

48. Boskabady MH, Javan H, Sajady M, Rakhshandeh H. The possible

prophylactic effect of Nigella sativa seed extract in asthmatic patients.
Fundam Clin Pharmacol. 2007;21:559–66.
49. Boskabady MH, Shafei MN, Parsaee H. Effects of aqueous and macerated
extracts from Nigella sativa on guinea pig isolated heart activity. Pharmazie.
2005;60:943–8.
50. Boskabady MH, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella
sativa in airways of asthmatic patients. Phytomedicine. 2010;17:707–13.
51. Bukhari MH, Khalil J, Qamar S, et al. Comparative gastroprotective effects
of natural honey, Nigella sativa and cimetidine against acetylsalicylic acid
induced gastric ulcer in albino rats. J Coll Physicians Surg Pak. 2011;21:
151–6.
52. Canayakin D, Bayir Y, Kilic Baygutalp N, et al. Paracetamol-induced
nephrotoxicity and oxidative stress in rats: the protective role of Nigella
sativa. Pharm Biol. 2016;54:2082–91.
53. Cherkaoui-Tangi K, Israili ZH, Lyoussi B. Vasorelaxant effect of essential
oil isolated from Nigella sativa L. seeds in rat aorta: proposed mechanism.
Pak J Pharm Sci. 2016;29:1–8.
54. Cho Ping N, Hashim NH, Hasan Adli DS. Effects of Nigella sativa (Habbatus
sauda) oil and nicotine chronic treatments on sperm parameters and testis
histological features of rats. Evid Based Complement Alternat Med.
2014;2014:218293.
55. Datau EA, Wardhana, Surachmanto EE, et al. Efficacy of Nigella sativa on
serum free testosterone and metabolic disturbances in central obese male.
Acta Med Indones. 2010;42:130–4.
56. Dehkordi FR, Kamkhah AF. Antihypertensive effect of Nigella sativa seed
extract in patients with mild hypertension. Fundam Clin Pharmacol. 2008;
22:447–52.
57. Demir H, Kanter M, Coskun O, et al. Effect of black cumin (Nigella sativa)
on heart rate, some hematological values, and pancreatic beta-cell damage
in cadmium-treated rats. Biol Trace Elem Res. 2006;110:151–62.
58. Develi S, Evran B, Betül Kalaz E, Koçak-Toker N, Erata GÖ. Protective
effect of Nigella sativa oil against binge ethanol-induced oxidative stress
and liver injury in rats. Chin J Nat Med. 2014;12:495–9.
59. Dollah MA, Parhizkar S, Izwan M. Effect of Nigella sativa on the kidney
function in rats. Avicenna J Phytomed. 2013;3:152–8.
60. Dollah MA, Parhizkar S, Latiff LA, Bin Hassan MH. Toxicity effect of
Nigella sativa on the liver function of rats. Adv Pharm Bull. 2013;3:97–102.
61. Duncker SC, Philippe D, Martin-Paschoud C, et al. Nigella sativa (black
cumin) seed extract alleviates symptoms of allergic diarrhea in mice,
involving opioid receptors. PLoS ONE. 2012;7:e39841.
62. El Mezayen R, El Gazzar M, Nicolls MR, et al. Effect of thymoquinone on
cyclooxygenase expression and prostaglandin production in a mouse
model of allergic airway inflammation. Immunol Lett. 2006;106:72–81.
1302 Nigella sativa L.

63. El Tahir KE, Ashour MM, al-Harbi MM. The cardiovascular actions of the
volatile oil of the black seed (Nigella sativa) in rats: elucidation of the
mechanism of action. Gen Pharmacol. 1993;24:1123–31.
64. El-Abhar HS, Abdallah DM, Saleh S. Gastroprotective activity of Nigella
sativa oil and its constituent, thymoquinone, against gastric mucosal injury
induced by ischaemia/reperfusion in rats. J Ethnopharmacol. 2003;84:251–8.
65. El-Bahai MN, Al-Hariri MT, Yar T, Bamosa AO. Cardiac inotropic and
hypertrophic effects of Nigella sativa supplementation in rats. Int J Cardiol.
2009;131:e115–7.
66. El-Dakhakhny M, Barakat M, El-Halim MA, Aly SM. Effects of Nigella
sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnophar-
macol. 2000;72:299–304.
67. El-Dakhakhny M, Madi NJ, Lembert N, Ammon HP. Nigella sativa oil,
nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase
products in polymorphonuclear leukocytes from rats. J Ethnopharmacol.
2002;81:161–4.
68. El-Dakhakhny M, Mady N, Lembert N, Ammon HP. The hypoglycemic
effect of Nigella sativa oil is mediated by extrapancreatic actions. Planta
Med. 2002;68:465–6.
69. El-Dakhakhny M, Mady NI, Halim MA. Nigella sativa L. oil protects
against induced hepatotoxicity and improves serum lipid profile in rats.
Arzneimittelforschung. 2000;50:832–6.
70. El-Fatatry HM, El-Alfy TS, Toama MA. Isolation and structure assign-
ment of an antimicrobial principle from the volatile oil of Nigella sativa L.
seeds. Pharmazie. 1975;30:111–3.
71. Elkhayat ES, Alorainy MS, El-Ashmawy IM, Fat’hi S. Potential antide-
pressant constituents of Nigella sativa seeds. Pharmacogn Mag. 2016;12:
S27–31.
72. El-Saleh SC, Al-Sagair OA, Al-Khalaf MI. Thymoquinone and Nigella
sativa oil protection against methionine-induced hyperhomocysteinemia in
rats. Int J Cardiol. 2004;93:19–23.
73. Enomoto S, Asano R, Iwahori Y, et al. Hematological studies on black cumin
oil from the seeds of Nigella sativa L. Biol Pharm Bull. 2001;24:307–10.
74. Ezz HS, Khadrawy YA, Noor NA. The neuroprotective effect of curcumin
and Nigella sativa oil against oxidative stress in the pilocarpine model of
epilepsy: a comparison with valproate. Neurochem Res. 2011;36:2195–204.
75. Fallah Huseini H, Amini M, Mohtashami R, et al. Blood pressure
lowering effect of Nigella sativa L. seed oil in healthy volunteers: a
randomized, double-blind, placebo-controlled clinical trial. Phytother Res.
2013;27:1849–53.
76. Fararh KM, Atoji Y, Shimizu Y, et al. Mechanisms of the hypoglycaemic and
immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced
diabetic hamsters. Res Vet Sci. 2004;77:123–9.
Nigella sativa L. 1303

77. Fararh KM, Atoji Y, Shimizu Y, Takewaki T. Isulinotropic properties of

Nigella sativa oil in streptozotocin plus nicotinamide diabetic hamster. Res
Vet Sci. 2002;73:279–82.
78. Farrag AR, Mahdy KA, Abdel Rahman GH, Osfor MM. Protective effect
of Nigella sativa seeds against lead-induced hepatorenal damage in male
rats. Pak J Biol Sci. 2007;10:2809–16.
79. Farzaneh E, Nia FR, Mehrtash M, Mirmoeini FS, Jalilvand M. The effects of
8-week Nigella sativa supplementation and aerobic training on lipid profile
and VO2 max in sedentary overweight females. Int J Prev Med. 2014;5:
210–6.
80. Gelot P, Bara-Passot C, Gimenez-Arnau E, et al. Bullous drug eruption
with Nigella sativa oil. Ann Dermatol Venereol. 2012;139:287–91 (Article
in French).
81. Ghannadi A, Hajhashemi V, Jafarabadi H. An investigation of the analgesic
and anti-inflammatory effects of Nigella sativa seed polyphenols. J Med
Food. 2005;8:488–93.
82. Gheita TA, Kenawy SA. Effectiveness of Nigella sativa oil in the
management of rheumatoid arthritis patients: a placebo-controlled study.
Phytother Res. 2012;26:1246–8.
83. Ghorbanibirgani A, Khalili A, Rokhafrooz D. Comparing Nigella sativa
oil and fish oil in treatment of vitiligo. Iran Red Crescent Med J. 2014;16:
e4515.
84. Gonca E, Kurt Ç. Cardioprotective effect of thymoquinone: a constituent
of Nigella sativa L., against myocardial ischemia/reperfusion injury and
ventricular arrhythmias in anaesthetized rats. Pak J Pharm Sci. 2015;28:
1267–73.
85. Hadi V, Kheirouri S, Alizadeh M, Khabbazi A, Hosseini H. Effects of Nigella
sativa oil extract on inflammatory cytokine response and oxidative stress
status in patients with rheumatoid arthritis: a randomized, double-blind,
placebo-controlled clinical trial. Avicenna J Phytomed. 2016;6:34–43.
86. Hadjzadeh MA, Khoei A, Hadjzadeh Z, Parizady M. Ethanolic extract of
Nigella sativa L. seeds on ethylene glycol-induced kidney calculi in rats.
Urol J. 2007;4:86–90.
87. Hadjzadeh MA, Mohammadian N, Rahmani Z, Rassouli FB. Effect of
thymoquinone on ethylene glycol-induced kidney calculi in rats. Urol J.
2008;5:149–55.
88. Hadjzadeh MA, Keshavarzi Z, Tabatabaee Yazdi SA, et al. Effect of alcoholic
extract of Nigella sativa on cisplatin-induced toxicity in rat. Iran J Kidney
Dis. 2012;6:99–104.
89. Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a
potent analgesic and anti-inflammatory drug. Phytother Res. 2004;18:195–9.
90. Hamed MA, El-Rigal NS, Ali SA. Effects of black seed oil on resolution of
hepatorenal toxicity induced by bromobenzene in rats. Eur Rev Med
Pharmacol Sci. 2013;17:569–81.
1304 Nigella sativa L.

91. Hanafy MS, Hatem ME. Studies on the antimicrobial activity of Nigella
sativa seed (black cumin). J Ethnopharmacol. 1991;34:275–8.
92. Hannan A, Saleem S, Chaudhary S, Barkaat M, Arshad MU. Antibacterial
activity of Nigella sativa against clinical isolates of methicillin resistant
Staphylococcus aureus. J Ayub Med Coll Abbottabad. 2008;20:72–4.
93. Hassan AS, Ahmed JH, Al-Haroon SS. A study of the effect of Nigella
sativa (Black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits.
Indian J Pharmacol. 2012;44:678–82.
94. Havakhah S, Sadeghnia HR, Hajzadeh MA, et al. Effect of Nigella sativa on
ischemia-reperfusion induced rat kidney damage. Iran J Basic Med Sci.
2014;17:986–92.
95. Hebi M, Zeggwagh N, Hajj L, Bouhali BE, Eddouks M. Cardiovascular
effect of Nigella sativa L. aqueous extract in normal rats. Cardiovasc Hematol
Disord Drug Targets. 2016;16:47–55.
96. Hilmi Y, Abushama MF, Abdalgadir H, Khalid A, Khalid H. A study of
antioxidant activity, enzymatic inhibition and in vitro toxicity of selected
traditional Sudanese plants with antidiabetic potential. BMC Complement
Altern Med. 2014;14:149.
97. Hosseini M, Mohammadpour T, Karami R, et al. Effects of the hydroalco-
holic extract of Nigella sativa on scopolamine-induced spatial memory
impairment in rats and its possible mechanism. Chin J Integr Med. 2015;21:
438–44.
98. Hosseinian S, Khajavi Rad A, Hadjzadeh MA, et al. The protective effect
of Nigella sativa against cisplatin-induced nephrotoxicity in rats. Avicenna J
Phytomed. 2016;6:44–54.
99. Hosseinzadeh H, Parvardeh S, Asl MN, et al. Effect of thymoquinone and
Nigella sativa seeds oil on lipid peroxidation level during global cerebral
ischemia-reperfusion injury in rat hippocampus. Phytomedicine. 2007;14:
621–7.
100. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the
major constituent of Nigella sativa seeds, in mice. Phytomedicine. 2004;
11:56–64.
101. Hosseinzadeh H, Tafaghodi M, Mosavi MJ, Taghiabadi E. Effect of
aqueous and ethanolic extracts of Nigella sativa seeds on milk production
in rats. J Acupunct Meridian Stud. 2013;6:18–23.
102. Houghton PJ, Zarka R, de las Heras B, Hoult JR. Fixed oil of Nigella
sativa and derived thymoquinone inhibit eicosanoid generation in leuko-
cytes and membrane lipid peroxidation. Planta Med. 1995;61:33–6.
103. Huseini HF, Kianbakht S, Mirshamsi MH, Zarch AB. Effectiveness of
topical Nigella sativa seed oil in the treatment of cyclic mastalgia: a
randomized, triple-blind, active, and placebo-controlled clinical trial.
Planta Med. 2016;82:285–8.
104. Ibrahim RM, Hamdan NS, Mahmud R, et al. A randomised controlled trial
on hypolipidemic effects of Nigella sativa seeds powder in menopausal
women. J Transl Med. 2014;12:82.
Nigella sativa L. 1305

105. Ibrahim RM, Hamdan NS, Ismail M, et al. Protective effects of Nigella
sativa on metabolic syndrome in menopausal women. Adv Pharm Bull.
2014;4:29–33.
106. Ibrahim ZS, Ishizuka M, Soliman M, et al. Protection by Nigella sativa
against carbon tetrachloride-induced downregulation of hepatic cyto-
chrome P450 isozymes in rats. Jpn J Vet Res. 2008;56:119–28.
107. Ilhan A, Gurel A, Armutcu F, et al. Antiepileptogenic and antioxidant
effects of Nigella sativa oil against pentylenetetrazol-induced kindling in
mice. Neuropharmacology. 2005;49:456–64.
108. Isik F, Tunali Akbay T, Yarat A, et al. Protective effects of black cumin
(Nigella sativa) oil on TNBSA-induced experimental colitis in rats. Dig
Dis Sci. 2011;56:721–30.
109. Işik H, Cevikbaş A, Gürer US, et al. Potential adjuvant effects of Nigella
sativa seeds to improve specific immunotherapy in allergic rhinitis patients.
Med Princ Pract. 2010;19:206–11.
110. Islam SK, Ahsan M, Hassan CM, Malek MA. Antifungal activities of the
oils of Nigella sativa seeds. Pak J Pharm Sci. 1989;2:25–8.
111. Jaswal A, Sharma M, Raghuvanshi S, et al. Therapeutic efficacy of
Nigella sativa Linn. against antituberculosis drug-induced hepatic injury
in Wistar Rats. J Environ Pathol Toxicol Oncol. 2016;35:59–71.
112. Jaswal A, Shukla S. Therapeutic efficacy of Nigella sativa Linn. seed
extract against CCl4 induced hepatic injury in Wistar rats. Indian J Exp
Biol. 2015;53:44–50.
113. Juhás S, Cikos S, Czikková S, et al. Effects of borneol and thymoquinone
on TNBS-induced colitis in mice. Folia Biol (Praha). 2008;54:1–7.
114. Kaatabi H, Bamosa AO, Badar A, et al. Nigella sativa improves glycemic
control and ameliorates oxidative stress in patients with type 2 diabetes
mellitus: placebo-controlled participant blinded clinical trial. PLoS ONE.
2015;10:e0113486.
115. Kaatabi H, Bamosa AO, Lebda FM, Al Elq AH, Al-Sultan AI. Favorable
impact of Nigella sativa seeds on lipid profile in type 2 diabetic patients.
J Family Community Med. 2012;19:155–61.
116. Kaleem M, Kirmani D, Asif M, et al. Biochemical effects of Nigella sativa
L. seeds in diabetic rats. Indian J Exp Biol. 2006;44:745–8.
117. Kalus U, Pruss A, Bystron J, et al. Effect of Nigella sativa (black seed) on
subjective feeling in patients with allergic diseases. Phytother Res. 2003;17:
1209–14.
118. Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella
sativa L. and Urtica dioica L. on lipid peroxidation, antioxidant enzyme
systems and liver enzymes in carbon tetrachloride-treated rats. World J
Gastroenterol. 2005;11:6684–8.
119. Kanter M, Coskun O, Kalayci M, et al. Neuroprotective effects of Nigella
sativa on experimental spinal cord injury in rats. Hum Exp Toxicol. 2006;
25:127–33.
1306 Nigella sativa L.

120. Kanter M, Coskun O, Korkmaz A, Oter S. Effects of Nigella sativa on

oxidative stress and beta-cell damage in streptozotocin-induced diabetic
rats. Anat Rec A Discov Mol Cell Evol Biol. 2004;279:685–91.
121. Kanter M, Coskun O, Uysal H. The antioxidative and antihistaminic effect
of Nigella sativa and its major constituent, thymoquinone on ethanol-
induced gastric mucosal damage. Arch Toxicol. 2006;80:217–24.
122. Kanter M, Demir H, Karakaya C, Ozbek H. Gastroprotective activity of
Nigella sativa L. oil and its constituent, thymoquinone against acute alcohol-
induced gastric mucosal injury in rats. World J Gastroenterol. 2005;11:
6662–6.
123. Kanter M, Meral I, Dede S, et al. Effects of Nigella sativa L. and Urtica dioica
L. on lipid peroxidation, antioxidant enzyme systems and some liver enzymes
in CCl4-treated rats. J Vet Med A Physiol Pathol Clin Med. 2003;50:264–8.
124. Kanter M, Meral I, Yener Z, et al. Partial regeneration/proliferation of the
beta-cells in the islets of Langerhans by Nigella sativa L. in streptozotocin-
induced diabetic rats. Tohoku J Exp Med. 2013;201:213–9.
125. Kanter M. Effects of Nigella sativa and its major constituent, thymo-
quinone on sciatic nerves in experimental diabetic neuropathy. Neurochem
Res. 2008;33:87–96.
126. Kaseb AO, Chinnakannu K, Chen D, et al. Androgen receptor and E2F-1
targeted thymoquinone therapy for hormone-refractory prostate cancer.
Cancer Res. 2007;67:7782–8.
127. Keshri G, Singh MM, Lakshmi V, Kamboj VP. Postcoital contraceptive
efficacy of the seeds of Nigella sativa in rats. Indian J Physiol Pharmacol.
1995;39:59–62.
128. Khan MA, Ashfaq MK, Zuberi HS, et al. The in vivo antifungal activity of the
aqueous extract from Nigella sativa seeds. Phytother Res. 2003;17:183–6.
129. Khan N, Sultana S. Inhibition of two stage renal carcinogenesis, oxidative
damage and hyperproliferative response by Nigella sativa. Eur J Cancer
Prev. 2005;14:159–68.
130. Kiralan M. Volatile compounds of black cumin seeds (Nigella sativa L.)
from microwave-heating and conventional roasting. J Food Sci. 2012;77:
C481–4.
131. Kocyigit Y, Atamer Y, Uysal E. The effect of dietary supplementation of
Nigella sativa L. on serum lipid profile in rats. Saudi Med J. 2009;30:893–6.
132. Kolahdooz M, Nasri S, Modarres SZ, Kianbakht S, Huseini HF. Effects of
Nigella sativa L. seed oil on abnormal semen quality in infertile men: a
randomized, double-blind, placebo-controlled clinical trial. Phytomedicine.
2014;21:901–5.
133. Korashy HM, Al-Jenoobi FI, Raish M, et al. Impact of herbal medicines like
Nigella sativa, Trigonella foenum-graecum, and Ferula asafoetida, on
Cytochrome P450 2C11 gene expression in rat liver. Drug Res (Stuttg).
2015;65:366–72.
Nigella sativa L. 1307

134. Kumara SS, Huat BT. Extraction, isolation and characterisation of antitumor
principle, alpha-hederin, from the seeds of Nigella sativa. Planta Med.
2001;67:29–32.
135. Kushwah DS, Salman MT, Singh P, Verma VK, Ahmad A. Protective
effects of ethanolic extract of Nigella sativa seed in paracetamol induced
acute hepatotoxicity in vivo. Pak J Biol Sci. 2014;17:517–22.
136. Latiff LA, Parhizkar S, Dollah MA, Hassan ST. Alternative supplement for
enhancement of reproductive health and metabolic profile among peri-
menopausal women: a novel role of Nigella sativa. Iran J Basic Med Sci.
2014;17:980–5.
137. Le PM, Benhaddou-Andaloussi A, Elimadi A, et al. The petroleum ether
extract of Nigella sativa exerts lipid-lowering and insulin-sensitizing
actions in the rat. J Ethnopharmacol. 2004;94:251–9.
138. Linjawi SA, Khalil WK, Hassanane MM, Ahmed ES. Evaluation of the
protective effect of Nigella sativa extract and its primary active component
thymoquinone against DMBA-induced breast cancer in female rats. Arch
Med Sci. 2015;11:220–9.
139. Mahdavi R, Namazi N, Alizadeh M, Farajnia S. Effects of Nigella sativa oil
with a low-calorie diet on cardiometabolic risk factors in obese women: a
randomized controlled clinical trial. Food Funct. 2015;6:2041–8.
140. Mahmoudvand H, Sepahvand A, Jahanbakhsh S, Ezatpour B, Ayatollahi
Mousavi SA. Evaluation of antifungal activities of the essential oil and
various extracts of Nigella sativa and its main component, thymoquinone
against pathogenic dermatophyte strains. J Mycol Med. 2014;24:e155–61.
141. Majdalawieh AF, Fayyad MW. Recent advances on the anticancer properties
of Nigella sativa, a widely used food additive. J Ayurveda Integr Med.
2016;7:173–80.
142. Malik T, Hasan S, Pervez S, Fatima T, Haleem DJ. Nigella sativa oil reduces
extrapyramidal symptoms (EPS)-like behavior in haloperidol-treated rats.
Neurochem Res. 2016;41:3386–98.
143. Mansour M, Tornhamre S. Inhibition of 5-lipoxygenase and leukotriene
C4 synthase in human blood cells by thymoquinone. J Enzyme Inhib Med
Chem. 2004;19:431–6.
144. Mansour MA, Ginawi OT, El-Hadiyah T, et al. Effects of volatile oil
constituents of Nigella sativa on carbon tetrachloride-induced hepatotox-
icity in mice: evidence for antioxidant effects of thymoquinone. Res
Commun Mol Pathol Pharmacol. 2001;110:239–51.
145. Meddah B, Ducroc R, El Abbes Faouzi M, et al. Nigella sativa inhibits
intestinal glucose absorption and improves glucose tolerance in rats.
J Ethnopharmacol. 2009;121:419–24.
146. Mehta BK, Mehta P, Gupta M. A new naturally acetylated triterpene saponin
from Nigella sativa. Carbohydr Res. 2009;344:149–51.
147. Mehta BK, Pandit V, Gupta M. New principles from seeds of Nigella sativa.
Nat Prod Res. 2009;23:138–48.
1308 Nigella sativa L.

148. Meral I, Kanter M. Effects of Nigella sativa L. and Urtica dioica L. on

selected mineral status and hematological values in CCl4-treated rats. Biol
Trace Elem Res. 2003;96:263–70.
149. Meral I, Yener Z, Kahraman T, Mert N. Effect of Nigella sativa on glucose
concentration, lipid peroxidation, antioxidant defence system and liver
damage in experimentally-induced diabetic rabbits. J Vet Med A Physiol
Pathol Clin Med. 2001;48:593–9.
150. Mohajeri D, Kaffashi Elahi R. Effects of Nigella sativa on heat-induced
testis damage in mouse. Bratisl Lek Listy. 2015;116:264–9.
151. Mohtashami A, Mahaki B, Azadbakht L, Entezari MH. Effects of bread
with Nigella sativa on lipid profiles, apolipoproteins and inflammatory
factor in metabolic syndrome patients. Clin Nutr Res. 2016;5:89–95.
152. Mohtashami R, Huseini HF, Heydari M, et al. Efficacy and safety of
honey-based formulation of Nigella sativa seed oil in functional dyspepsia:
a double blind randomized controlled clinical trial. J Ethnopharmacol.
2015;175:147–52.
153. Morikawa T, Xu F, Kashima Y, et al. Novel dolabellane-type diterpene
alkaloids with lipid metabolism promoting activities from the seeds of Nigella
sativa. Org Lett. 2004;6:869–72.
154. Morikawa T, Xu F, Ninomiya K, et al. Nigellamines A3, A4, A5, and C,
new dolabellane-type diterpene alkaloids, with lipid metabolism-promoting
activities from the Egyptian medicinal food black cumin. Chem Pharm Bull
(Tokyo). 2004;52:494–7.
155. Morsi NM. Antimicrobial effect of crude extracts of Nigella sativa on
multiple antibiotics-resistant bacteria. Acta Microbiol Pol. 2000;49:63–74.
156. Mosbah R, Yousef MI, Maranghi F, Mantovani A. Protective role of Nigella
sativa oil against reproductive toxicity, hormonal alterations, and oxidative
damage induced by chlorpyrifos in male rats. Toxicol Ind Health.
2016;32:1266–77.
157. Mostafa RM, Moustafa YM, Mirghani Z, AlKusayer GM, Moustafa KM.
Antioxidant effect of garlic (Allium sativum) and black seeds (Nigella
sativa) in healthy postmenopausal women. SAGE Open Med. 2013;24:
2050312113517501.
158. Mousavi G, Mohajeri D. Effect of ground black seeds (Nigella sativa L.)
on renal tubular cell apoptosis induced by ischemia/reperfusion injury in
the rats. Iran J Basic Med Sci. 2014;17:1032–5.
159. Mousavi G. Study on the effect of black cumin (Nigella sativa Linn.) on
experimental renal ischemia-reperfusion injury in rats. Acta Cir Bras. 2015;
30:542–50.
160. Muneera KE, Majeed A, Naveed AK. Comparative evaluation of Nigella
sativa (Kalonji) and simvastatin for the treatment of hyperlipidemia and in
the induction of hepatotoxicity. Pak J Pharm Sci. 2015;28:493–8.
161. Nair SC, Salomi MJ, Panikkar B, Panikkar KR. Modulatory effects of
Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in
mice. J Ethnopharmacol. 1991;31:75–83.
Nigella sativa L. 1309

162. Namazi N, Mahdavi R, Alizadeh M, Farajnia S. Oxidative stress responses

to Nigella sativa oil concurrent with a low-calorie diet in obese women: a
randomized, double-blind controlled clinical trial. Phytother Res.
2015;29:1722–8.
163. Nickavar B, Mojab F, Javidnia K, Amoli MA. Chemical composition of
the fixed and volatile oils of Nigella sativa L. from Iran. Z Naturforsch.
2003;58:629–31.
164. Nikakhlagh S, Rahim F, Aryani FH, et al. Herbal treatment of allergic
rhinitis: the use of Nigella sativa. Am J Otolaryngol. 2011;32:402–7.
165. Onifade AA, Jewell AP, Adedeji WA. Nigella sativa concoction induced
sustained sero-reversion in HIV patient. Afr J Tradit Complement Altern
Med. 2013;10:332–5.
166. Otoom SA, Al-Safi SA, Kerem ZK, Alkofahi A. The use of medicinal herbs
by diabetic Jordanian patients. J Herb Pharmacother. 2006;6:31–41.
167. Oysu C, Tosun A, Yilmaz HB, et al. Topical Nigella sativa for nasal
symptoms in elderly. Auris Nasus Larynx. 2014;41:269–72.
168. Parandin R, Yousofvand N, Ghorbani R. The enhancing effects of alcoholic
extract of Nigella sativa seed on fertility potential, plasma gonadotropins
and testosterone in male rats. Iran J Reprod Med. 2012;10:355–62.
169. Parhizkar S, Latiff LA, Parsa A. Effect of Nigella sativa on reproductive
system in experimental menopause rat model. Avicenna J Phytomed.
2016;6:95–103.
170. Perveen T, Haider S, Zuberi NA, et al. Increased 5-HT levels following
repeated administration of Nigella sativa L. (Black Seed) oil produce
antidepressant effects in rats. Sci Pharm. 2012;82:161–70.
171. Pourbakhsh H, Taghiabadi E, Abnous K, et al. Effect of Nigella sativa fixed
oil on ethanol toxicity in rats. Iran J Basic Med Sci. 2014;17:1020–31.
172. Rachid H, Chevassus H, Nmila R, et al. Nigella sativa seed extracts
enhance glucose-induced insulin release from rat-isolated Langerhans
islets. Fundam Clin Pharmacol. 2004;18:525–9.
173. Ramadan MF, Mörsel JT. Characterization of phospholipid composition of
black cumin (Nigella sativa L.) seed oil. Nahrung. 202;46:240–4.
174. Sabzghabaee AM, Dianatkhah M, Sarrafzadegan N, Asgary S, Ghannadi A.
Clinical evaluation of Nigella sativa seeds for the treatment of hyperlipi-
demia: a randomized, placebo controlled clinical trial. Med Arch. 2012;66:
198–200.
175. Sahak MK, Mohamed AM, Hashim NH, Hasan Adli DS. Nigella sativa oil
enhances the spatial working memory performance of rats on a radial arm
maze. Evid Based Complement Alternat Med. 2013;2013:180598.
176. Sahebkar A, Beccuti G, Simental-Mendía LE, Nobili V, Bo S. Nigella
sativa (black seed) effects on plasma lipid concentrations in humans: a
systematic review and meta-analysis of randomized placebo-controlled
trials. Pharmacol Res. 2016;106:37–50.
1310 Nigella sativa L.

177. Sahebkar A, Soranna D, Liu X, et al. A systematic review and meta-analysis

of randomized controlled trials investigating the effects of supplementation
with Nigella sativa (black seed) on blood pressure. J Hypertens. 2016;34:
2127–35.
178. Salama RB. Sterols in the seed oil of Nigella sativa. Planta Med. 1973;24:
375–7.
179. Saleem U, Ahmad B, Rehman K, et al. Nephroprotective effect of vitamin
C and Nigella sativa oil on gentamicin associated nephrotoxicity in rabbits.
Pak J Pharm Sci. 2012;25:727–30.
180. Salem EM, Yar T, Bamosa AO, et al. Comparative study of Nigella
Sativa and triple therapy in eradication of Helicobacter Pylori in patients
with nonulcer dyspepsia. Saudi J Gastroenterol. 2010;16:207–14.
181. Salem ML, Hossain MS. Protective effect of black seed oil from Nigella
sativa against murine cytomegalovirus infection. Int J Immunopharmacol.
2000;22:729–40.
182. Salih B, Sipahi T, Dönmez EO. Ancient nigella seeds from Boyali Höyük
in northcentral Turkey. J Ethnopharmacol. 2009;124:416–20.
183. Salim EI, Fukushima S. Chemopreventive potential of volatile oil from
black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis.
Nutr Cancer. 2003;45:195–202.
184. Salomi MJ, Nair SC, Panikkar KR. Inhibitory effects of Nigella sativa and
saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr Cancer.
1991;16:67–72.
185. Sayed MD. Traditional medicine in health care. J Ethnopharmacol. 1980;2:
19–22.
186. Sayed-Ahmed MM, Nagi MN. Thymoquinone supplementation prevents
the development of gentamicin-induced acute renal toxicity in rats. Clin
Exp Pharmacol Physiol. 2007;34:399–405.
187. Seghatoleslam M, Alipour F, Shafieian R, et al. The effects of Nigella
sativa on neural damage after pentylenetetrazole induced seizures in rats.
J Tradit Complement Med. 2015;6:262–8.
188. Seif AA. Nigella sativa attenuates myocardial ischemic reperfusion injury
in rats. J Physiol Biochem. 2013;69:937–44.
189. Shafei MN, Boskabady MH, Parsaee H. Effect of aqueous extract from
Nigella sativa L. on guinea pig isolated heart. Indian J Exp Biol. 2005;43:
635–9.
190. Steinmann A, Schätzle M, Agathos M, Breit R. Allergic contact dermatitis
from black cumin (Nigella sativa) oil after topical use. Contact Dermatitis.
1997;36:268–9.
191. Sultan MT, Butt MS, Karim R, et al. Effect of Nigella sativa fixed and
essential oils on antioxidant status, hepatic enzymes, and immunity in
streptozotocin induced diabetes mellitus. BMC Complement Altern Med.
2014;14:193.
Nigella sativa L. 1311

192. Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B. Ethnopharmacological

survey of plants used in the traditional treatment of hypertension and
diabetes in southeastern Morocco (Errachidia province). J Ethnopharmacol.
2007;110:105–17.
193. Tekeoglu I, Dogan A, Ediz L, et al. Effects of thymoquinone (volatile oil of
black cumin) on rheumatoid arthritis in rat models. Phytother Res. 2007;
21:895–7.
194. Tennekoon KH, Jeevathayaparan S, Kurukulasooriya AP, Karunanayake
EH. Possible hepatotoxicity of Nigella sativa seeds and Dregea volubilis
leaves. J Ethnopharmacol. 1991;31:283–9.
195. Tiruppur Venkatachallam SK, Pattekhan H, Divakar S, Kadimi US. Chemi-
cal composition of Nigella sativa L. seed extracts obtained by supercritical
carbon dioxide. J Food Sci Technol. 2010;47:598–605.
196. Toama MA, El-Alfy TS, El-Fatatry HM. Antimicrobial activity of the
volatile oil of Nigella sativa Linneaus seeds. Antimicrob Agents Chemo-
ther. 1974;6:225–6.
197. Toma CC, Olah NK, Vlase L, Mogoșan C, Mocan A. Comparative studies
on polyphenolic composition, antioxidant and diuretic effects of Nigella
sativa L. (Black Cumin) and Nigella damascena L. (Lady-in-a-Mist) seeds.
Molecules. 2015;20:9560–74.
198. Türkdoğan MK, Ozbek H, Yener Z, et al. The role of Urtica dioica and
Nigella sativa in the prevention of carbon tetrachloride-induced hepato-
toxicity in rats. Phytother Res. 2003;17:942–6.
199. Uz E, Bayrak O, Uz E, et al. Nigella sativa oil for prevention of chronic
cyclosporine nephrotoxicity: an experimental model. Am J Nephrol. 2008;
28:517–22.
200. Vafaee F, Hosseini M, Hassanzadeh Z, et al. The effects of Nigella sativa
hydroalcoholic extract on memory and brain tissues oxidative damage after
repeated seizures in rats. Iran J Pharm Res. 2015;14:547–57.
201. Vahdati-Mashhadian N, Rakhshandeh H, Omidi A. An investigation on
LD50 and subacute hepatic toxicity of Nigella sativa seed extracts in mice.
Pharmazie. 2005;60:544–7.
202. Yaman I, Balikci E. Protective effects of Nigella sativa against gentamicin-
induced nephrotoxicity in rats. Exp Toxicol Pathol. 2010;62:183–90.
203. Yar T, El-Hariri M, El-Bahai MN, Bamosa AO. Effects of Nigella sativa
supplementation for one month on cardiac reserve in rats. Indian J Physiol
Pharmacol. 2008;52:141–8.
204. Yi T, Cho SG, Yi Z, et al. Thymoquinone inhibits tumor angiogenesis and
tumor growth through suppressing AKT and extracellular signal-regulated
kinase signaling pathways. Mol Cancer Ther. 2008;7:1789–96.
205. Yildiz F, Coban S, Terzi A, et al. Nigella sativa relieves the deleterious effects
of ischemia reperfusion injury on liver. World J Gastroenterol. 2008;14:
5204–9.
206. Yildiz F, Coban S, Terzi A, et al. Protective effects of Nigella sativa against
ischemia-reperfusion injury of kidneys. Ren Fail. 2010;32:126–31.
1312 Nigella sativa L.

207. Yousefi M, Barikbin B, Kamalinejad M, et al. Comparison of therapeutic

effect of topical nigella with betamethasone and eucerin in hand eczema.
J Eur Acad Dermatol Venereol. 2013;27:1498–504.
208. Yuan T, Nahar P, Sharma M, et al. Indazole-type alkaloids from Nigella
sativa seeds exhibit antihyperglycemic effects via AMPK activation
in vitro. J Nat Prod. 2014;77:2316–20.
209. Yusuksawad M, Chaiyabutr N. Restoration of renal hemodynamics and
functions during black cumin (Nigella sativa) administration in strepto-
zotocin-induced diabetic rats. J Exp Pharmacol. 2011;4:1–7.
210. Zaoui A, Cherrah Y, Alaoui K, et al. Effects of Nigella sativa fixed oil on
blood homeostasis in rat. J Ethnopharmacol. 2002;79:23–6.
211. Zaoui A, Cherrah Y, Lacaille-Dubois MA, et al. Diuretic and hypotensive
effects of Nigella sativa in the spontaneously hypertensive rat. Therapie.
2000;55:379–82 (French).
212. Zaoui A, Cherrah Y, Mahassini N, et al. Acute and chronic toxicity of
Nigella sativa fixed oil. Phytomedicine. 2002;9:69–74.
213. Zedlitz S, Kaufmann R, Boehncke WH. Allergic contact dermatitis from
black cumin (Nigella sativa) oil-containing ointment. Contact Dermatitis.
2002;46:188.
Ocimum basilicum L.
(Lamiaceae)

(Syns.: O. americanum Jacq.; O. barrelieri Roth; O. bullatum Lam.; O. thyrsiflorum L.;

Plectranthus barrelieri (Roth) Spreng.)

Abstract
The herb is native to India, but thrives in hot and dry conditions, such as
southern Europe, the southern states of the U.S., and Australia. In southern Italy,
it is called Bacia-nicola and was worn in the waist or bossom by young girls and
in the hair by married women; the youth would stick a sprig of it above the ear
when they go out courting. In Crete it is a sign of mourning, and is cultivated in
window gardens. In Europe, sweet basil is used as a potherb for seasoning of
foods like that of thyme and sage. Ibn al-Baitar described it as Badrooj and said it
is aphrodisiac, diuretic, galactagogue, antiflatulent, and anti-inflammatory, and its
poultice is useful in scorpion and python bites. Seeds are beneficial in flatulence,
oliguria, and epilepsy. He quotes Rhazes that this drug produces bile and its
excessive use causes blindness. Leaves juice is dropped into the ear to relieve
earache. In Indian traditional medicine, basil has been used for the treatment of
anxiety, diabetes, cardiovascular diseases, headaches, nerve pain, neurodegen-
erative disorders, as anticonvulsant and anti-inflammatory. Seeds are used in
traditional Iranian medicine for the treatment of IBD. It is one of the widely used
medicinal plants in Morocco to reduce plasma cholesterol and the risk of
atherosclerosis-related diseases, and also used in traditional Uyghur medicine for
the treatment and prevention of cardiovascular diseases. The plant is traditionally
used as a repellent for mosquitoes and houseflies in the Arribes del Duero Natural
Park of western Spain, and is effectively used by the indigenes of Bolifamba
region in Cameroon for personal protection against mosquito and other insect
bites. Aqueous extract showed the presence of reducing sugars, cardiac
glycosides, tannins, saponins, glycosides, flavonoids and steroids, while the
ethanol extract indicated the presence of phenolic compounds and flavonoids;
rosmarinic acid being the principal phenolic compound. Aqueous leaf extract
markedly lowered TC, LDL-C and TGs in hyperlipidemic rats without
significantly affecting HDL-C, and inhibited ADP- and thrombin-induced platelet
aggregation. Pretreatment of mice with ethyl acetate leaf extract markedly

© Springer Nature Switzerland AG 2020 1313

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_136
1314 Ocimum basilicum L.

reduced cerebral infarct size after BCA occlusion-induced global cerebral

ischemia, and attenuated impairment of short-term memory and motor
coordination.

Keywords




Alfábega Babui tulsi Badrooj Basilicum
Fesleğen
Luo le
Mebôki




Shahasfaram Sweet basil Vishva-tulasi

Vernaculars: Urd.: Badrooj; Hin.: Babui tulsi, Jangli tulsi, Nazbo, Subzah; San.:
Manjariki, (seeds, Rehan), Varavara, Vishva-tulasi; Ben.: Baboi tulsi, Debunsha,
Khubkalam, Nazbo, Subja; Guj.: Damaro, Damro, Nasabo; Mal.: Paccha,
Ram-tulasi, Tirunitri, Trunitru-rachcha; Mar.: Babi tulsi, Nazbo, Subja; Tam.:
Karandai, Thiruneetrupachilai, Tirnut-patchi, Tirunitrupachchai; Tel.: Bhu-tulasi,
Kukkatulasi, Vibudi-patri; Ara.: Háabaq nabatái, Habaqa, Hauk, Raihan, Saatar
hindi, Shahsafaram; Bur.: Pinsein; Chi.: 罗勒, Luo le; Cze.: Bazalka pravá; Dan.:
Basilik, Basilikum; Dut.: Basilicum, Bazielkruid, Tuinbasilicum; Eng.: St. Joseph’s
wort, Sweet basil, Thai basil; Fin.: Basilika; Fre.: Basilic, Basilie cultive, Basilic
des jardins, Herbe royale, Oranger des savetiers, Pistou; Ger.: Basilienkraut,
Basilikum, Gartenbasilienkraut, Königskraut; Gre.: Vasilikos; Ind.: Daun kemangi;
Ita.: Bacianicola, Basilico; Jap.: Bajiru, Mebôki; Maly.: Kemangi, Ruku-ruku,
Tiru-nitru; Nep.: Baavarii phuul; Nor.: Basilikum; Per.: Daban-shab, Habak-i-
kirmani, Firunjmushk, Nazbu, Rehan, Shahasperham; Por.: Alfavaca, Basilicão,
Manjericão, Manjerico-de-folhas-grandes, Manjericão-grande; Spa.: Albahaca,
Alfábega, Alhábega, Hierba de los reyes, Hierba de salitre; Swe.: Basilica; Tag.:
Albanáka, Balanoi, Pansi-pansi, Solási; Tha.: Horapa, Horapha, Kaphrau, Kaprao;
Tur.: Fesleğen, Feslien; Vie.: Cây húng quế, Cây rau é, É tía, É trắng, Húng giỏi,
Húng quế, Lá quế, Rau quế.
Description: A native to India, but thrives in hot and dry conditions, such as
southern Europe, the southern states of the U.S., and Australia. The herb is erect
and glabrous, 30–130 cm tall; leaves light-green, glossy, 3–11 cm long, 1–6 cm
wide, petiolate, ovate, oblong, narrowed at the base, slightly toothed; pedicle cili-
ated; flowers small and white, in simple racemes; seeds of a brown color or black,
no odor; taste oily and slightly pungent. When moistened with water, seeds become
coated with semi-opaque mucilage (Figs. 1 and 2).LXXXI
Actions and Uses: In southern Italy, it is called Bacia-nicola and was worn in the
waist or bossom by young girls and in the hair by married women; the youth would
stick a sprig of it above the ear when they go out courting. In Crete it is a sign of
mourning, and is cultivated in window gardens. In Europe, sweet basil is used as a
potherb for seasoning of foods like that of thyme and sage.XL Ibn al-BaitarLXIX
described it as Badrooj and said it is aphrodisiac, diuretic, galactagogue, antiflat-
ulent, and anti-inflammatory, and its poultice is useful in scorpion and python bites.
Seeds are beneficial in flatulence, oliguria, and epilepsy. He quotes Rhazes that this
drug produces bile and its excessive use causes blindness. Leaves are fragrant and
Ocimum basilicum L. 1315

Fig. 1 Ocimum basilicum, Basil Plant, Castielli, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Basil-Basilico-Ocimum_basilicum-albahaca.
jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Ocimum basilicum, Basil Leaves, Henna, WikimediaCommons; ShareAlike 1.0 Generic CC
BY-SA 1.0, https://commons.wikimedia.org/wiki/File:Basilic-spice.jpg; https://creativecommons.
org/licenses/by/1.0/deed.en

aromatic, and used for flavoring food, diaphoretic, mucilaginous, carminative and
stimulant; given in intestinal fluxes, gonorrhea, catarrh, and to relieve pains after
parturition, during cold stage of intermittent fever and to allay vomiting; leaves
juice is dropped into the ear to relieve earache.LXXXI,CV Seeds are mucilaginous,
demulcent, aphrodisiac, and diuretic, and soaked in water form a mucilaginous jelly
that with added sugar serves as an excellent drink in catarrh, chronic diarrhea,
dysentery, gonorrhea, nephritis, cystitis and internal piles.CV In Unani medicine,
seeds are considered deobstruent, carminative, and stimulant, and are valued much
when taken whole due to their mucilaginous properties; when crushed they are said
to be astringent.XL Leaves (temperament, hot 2° and dry 1°) decoction strengthens
1316 Ocimum basilicum L.

stomach and causes diuresis and menstruation. A syrup made with seeds is bene-
ficial in heart weakness and palpitation.LXXVII In Indian traditional medicine, basil
has been used for the treatment of anxiety, diabetes, cardiovascular diseases,
headaches, nerve pain, neurodegenerative disorders, as anticonvulsant and
anti-inflammatory [11]. Seeds are also used in traditional Iranian medicine for the
treatment of IBD [57, 60]. It is one of the widely used medicinal plants in Morocco
to reduce plasma cholesterol and the risk of atherosclerosis-related diseases [5], and
also used in traditional Uyghur medicine for the treatment and prevention of car-
diovascular diseases [76]. One of the most commonly used plants in the traditional
medicine of Aquismón, San Luis Potosí, México [35], and is used for the treatment
of GI disorders such as diarrhea in Mexican traditional medicine [79]. The plant is
traditionally used as a repellent for mosquitoes and houseflies in the Arribes del
Duero Natural Park (Salamanca-Zamora) of western Spain [29], and is effectively
used by the indigenes of Bolifamba region in Cameroon for personal protection
against mosquito and other insect bites, and offers effective protection under field
conditions [48]. Leaves infusion or decoction is used as a carminative and stimulant
in the Philippines.CXVII
Phytoconstituents: Aqueous extract showed the presence of reducing sugars,
cardiac glycosides, tannins, saponins, glycosides, flavonoids and steroids [20],
while the ethanol extract indicated the presence of phenolic compounds (5.36%)
and flavonoids (1.86%); rosmarinic acid (15.74%) being the principal phenolic
compound [25]. Sweet basil has several chemotypes or cultivars that differ in their
EO composition. A total of 149 compounds were identified in commercially
available oils on the Serbian market or isolated from plant material cultivated in
Serbia [56]. Leaf age and its position are also a factor that influence the composition
of EO. There is higher concentration of EO and eugenol levels in younger than in
older leaves, and older leaves predominantly have methyleugenol and lower levels
of linalool [26]. Yield of EO from an Omani variety was three-times higher in
spring than in winter or summer. Major components were identified as l-linalool,
geraniol, 1,8-cineole, p-allylanisole and dl-limonene, and b-farnesene was
exclusively present in oils extracted during winter and spring [4]. Linalool and
methyl chavicol (estragole) are the two major volatile compounds in fresh or dried
basil [85]; linalool is the active nematicidal compound [13]. Phenylpropanoids
(65.2–77.6%) constituted the major proportion of EO composition of basil from
northern India; methyl chavicol, linalool, bicyclogermacrene and a-terpineol being
the major components [53]. Major constituents in fresh leaves from western Ghats
of India, a different chemotype, were methyl cinnamate, linalool, b-elemene and
camphor [36]. Rosmarinic acid was the predominant phenolic acid present in both
flowers and leaves from Iran [33]. Linalool, (Z)-cinnamic acid methyl ester, cyclo-
hexene, a-cadinol, 2,4-diisopropenyl-1-methyl-1-vinylcyclohexane, 3,5-pyridine-
dicarboxylic acid, 2,6-dimethyl-diethyl ester, b-cubebene, guaia-1(10),11-diene,
cadinene, (E)-cinnamic acid methyl ester and b-guaiene were the main constituents
reported in the EO of O. basilicum var. pilosum from China [86], and Wang et al.
[81] reported 1,7-dimethyl-1,6-octadien-3-ol as the main constituent in EO,
Ocimum basilicum L. 1317

accounting for 29.87%. Phenolic compounds and flavonoids were reported in

leaves from Finland [18]. Linalool (54.95%), methylchavicol (11.98%), methyl-
cinnamat (7.24%) and linolen (0.14%) were identified as the component of EO from
Bulgaria [55], while linalool (54.4%), eugenol (9.6%), and methyl eugenol (7.6%)
were the major components of EO from Turkey [19], and methylchavicol was
reported as the major compound (93.0% and 74.9%, respectively) in sweet basil oil
from Thailand and Greece [27, 80]. Estragole is never found in Greek Genovese
and purple basil types, but occurs in Napoletano type [44]. Major components of
EO from Iran were methylchavicol (42.8%), geranial (13.0%), neral (12.2%) and
b-caryophyllene (7.2%) [55], whereas EO from Egypt contained linalool (48.4%),
1,8-cineol (12.2%), eugenol (6.6%), methyl cinnamate (6.2%), a-cubebene (5.7%),
caryophyllene (2.5%), b-ocimene (2.1%) and a-farnesene (2.0%) as the main
components [21]. Fifty-seven compounds were identified in leaf EO from Ban-
gladesh, of which methylchavicol (36.7%), gitoxigenin (9.3%), trimethoquinol
(10.3%), b-guaiene (3.7%), aciphyllene (3.4%), alizarin (3.2%), naphthaline
(2.2%), (-)-caryophyllene (2.0%), and mequinol (1.6%) were reported as the major
compounds [31]. Nineteen constituents were identified in EO from Burkina Faso,
representing 94.6% of the total oil; linalool (57%) and eugenol (19.2%) were major
constituents; a-cadinol (3.2%), b-ocimene (2.7%), trans-a-bergamotene (2.7%),
1,8-cineole (1.7%), c-cadinene (1.6%), germacrene A (1.1%) and bicyclogerma-
crene (1%) as the minor constituents [8]. However, in another publication by the
same authors, a-terpineol (59.78%) and b-caryophyllene (10.54%) were reported as
the major constituents of EO from Burkina Faso [9]. Basilol, ocimol, basilimoside,
betulinic acid, oleanolic acid, two terpenoids, p-formylphenyl 3b-hydroxyolean-
12-en-28-oate, and 2-methoxy-4-carbomethoxyphenyl3b-hydroxy-lup-20(29)-en-
28-oate, and a steroidal glycoside [67], and cinnamic acid esters [68] were isolated
from aerial parts. Microwave dried leaves retained higher percentage of volatile
compounds (eucalyptol, linalool, eugenol, and methyl eugenol), and larger
chlorophyll pigments than leaves air dried by traditional method [17].
Pharmacology: Pretreatment of mice with ethyl acetate leaf extract markedly
reduced cerebral infarct size after BCA occlusion-induced global cerebral ischemia,
and attenuated impairment of short-term memory and motor coordination [11].
Hydroalcohol extract of fresh basil significantly increased memory retention and
memory retrieval in mice after electric shock [66], significantly prolonged duration
of pentobarbital-induced sleep in mice, comparable to diazepam [7], and both the
extract and EO decreased motor activity and showed anxiolytic and sedative effects
in mice; EO being more effective [55]. Hydromethanol extract showed potent
antioxidant activity, reduced brain AChE activity and reversed scopolamine-
induced memory deficit in mice [73]. The EO from Turkey potently inhibited
activities of AChE and BChE; however, individual components of the oil were not
as active as the oil [51]. Both EO and estragole, the most dominant oil component
from Egypt exhibited significant anti-AChE activity, comparable to that of
physostigmine [24]. Aqueous, ethanol, acetone, ethyl acetate, butanol and methanol
1318 Ocimum basilicum L.

extracts [30, 34, 37, 84], and EO [9, 43] showed significant antioxidant activity.
Rosmarinic acid was determined to be the major antioxidant compound [34].
Cold ethanol leaf extract showed activity against E. coli, S. paratyphi and Sh.
dysenterae [49], and potent activity against P. falciparum [32]. Methanol extract
inhibited growth of P. aeruginosa, Shigella sp., L. monocytogenes, S. aureus, two
different strains of E. coli [38], and V. cholerae [64]. Hossain et al. [31] reported
both methanol extract and EO highly active against B. cereus, B. subtilis,
B. megaterium, S. aureus, L. monocytogenes, E. coli, Sh. boydii, S. dysenteriae,
V. mimicus, V. parahaemolyticus, and S. typhi. Aqueous and ethanol extracts
exhibited broad-spectrum antiviral activity [14]; aqueous extract potently inhibited
HIV-1 and HIV-1 reverse transcriptase [83]. Active constituents, ursolic acid was
strongly active against HSV-1, ADV-8, coxsackievirus B1 and enterovirus 71, and
apigenin was highly active against HSV-2, ADV-3, and Hep B surface antigen [14].
The EO exhibits broad-spectrum antibacterial (against B. subtilis, S. aureus,
S. mutans, and E. faecalis) and antifungal (against E. floccosum, M. gypseum, and
S. schenckii) activities [58], against standard strain of E. coli and 60 other clinical
isolate strains of E. coli, including ESbetaL-positive bacteria [69]. Essential oil
from Omani basil showed strong antifungal activity against A. niger, A. fumigatus,
P. italicum and R. stolonifer [4]. The oil also inhibited growth of T. vaginalis
trophozoites with an MIC of 30 lg/ml after 24 h, and 10 lg/ml after 96 h incu-
bation [22]. The EO was active against MDR clinical isolates of Staphylococcus,
Enterococcus and Pseudomonas [50], strongly active against strains of K. pneu-
moniae producing ESbetaL-enzyme [52], zoonotic enteropathogens Salmonella
spp., E. coli, C. perferingens, and C. jejunii [82], highly active against S. enteritidis
[61], active against acid-tolerant food microflora [42], and modestly active against
L. monocytogenes, L. innocua S. aureus [47]. Soković et al. [74] reported that sweet
basil oil from Serbia significantly inhibited growth of M. flavus, B. subtilis,
S. aureus, S. epidermidis, S. enteritidis, S. typhimurium, and E. coli; whereas
twenty-four clinical isolates of S. aureus were reported resistant to EO from Greek
basil [3]. EO from Burkina Faso was most active against E. faecalis, E. areogenes,
S. typhimurium and E. coli [8]. The EO also significantly cured or healed otitis
media caused by S. pneumoniae and H. influenzae in rats [40], inhibited growth of
P. acnes with an MIC of 2% [80], significantly inhibited A. flavus mycelial growth
and aflatoxin B1 production by it [21], demonstrated antigiardial activity; linalool
killed 100% parasites (G. lamblia) after 1 h of incubation [16], and showed
antileishmania activity [65]. Essential oil from Brazil was reported ineffective
against fluconazole-resistant and fluconazole-susceptible Candida spp.: C. albicans,
C. dubliniensis, C. tropicalis, C. glabrata, and C. krusei [54], and the EO from
Nigeria inhibited growth of K. pneumoniae, P. vulgaris, S. viridians, S. albus and at
very high concentration of P. aeruginosa [1].
Both EO and its main component, estragole are significantly effective against
acute and chronic inflammation [62]. Powdered aerial parts and their aqueous and
methanol extracts exhibited protective effect against aspirin-induced gastric ulcers
in rats [2]; the fixed oil and tincture also showed significant anti-inflammatory
Ocimum basilicum L. 1319

activity [10, 70], and the fixed oil protected against gastric ulceration induced by
various ulcerogenic challenges in rats [71]. Both aqueous and methanol leaf extracts
inhibit cholera toxin-induced intestinal secretion in rats [79]; the oil also inhibits
castor oil-induced diarrhea in rats and protects against acetic acid-induced colitis
[60]; the linolenic acid present in the oil blocks both the COX and LOX pathways
of AA metabolism [72], and Umar et al. [76] reported that basil extracts simulta-
neously inhibit COX-2 and stimulate endothelial COX-1.
Aqueous leaf extract markedly lowered TC, LDL-C and TGs in triton-induced
hyperlipidemic rats without significantly affecting HDL-C [5], and inhibited ADP-
and thrombin-induced platelet aggregation [6, 75]. Ethanol extract reduced lipid
accumulation in human macrophages and reduced foam cell formation [12], strongly
protected rats against isoproterenol-induced MI [25], and lowered both SBP and
DBP in renovascular hypertensive rats, improved renal function and decreased levels
of angiotensin II and endothelin-1 [77]. Ethanol leaf extract shows significant anti
LPO and potent antioxidant effects, significant protection against CCl4- and H2O2
[45] and sodium arsenite-hepatotoxicity [28], and was highly effective in reducing
tumor incidence in B(a)P-induced forestomach and DMBA-initiated skin papillo-
magenesis [15]. Alcoholic aqueous extract also reduced tumor volume and improved
survival rate of mice in chemically-induced melanoma [46]. Concurrent treatment
with aqueous basil extract protects against cadmium-induced testicular toxicity in
rats [63].
Mechanism of Action: Inhibition of a-glucosidase and a-amylase activities may
play a role in its antidiabetic (hypoglycemic) activity [20].
Human A/Es, Allergy and Toxicity: Patients are reported to have developed
severe allergic reaction after eating pasta sauce containing basil [78], and allergic
contact dermatitis developed in some workers handling basil [39]. It is considered
harmful for eyesight.LXXVII
Animal Toxicity: Single oral dose of 2,000 mg/kg of hydroalcohol extract of aerial
parts to rats was nonlethal and nontoxic; the extract administered in a dose of
500 mg/kg daily for 45-days also caused no mortality but reduced LDL-C, VLDL-C
and TGs and increased HDL-C levels [59]. LD50 (i.p.) in mice of hydroalcohol leaf
extract from Iran was reported to be 2,400 mg/kg [7]. Oral administration of EO to rats
at a dose >1,500 mg/kg/day for 14 consecutive days caused significant functional
damages to stomach and liver [23].
Potential for Drug-Herb Interactions: Feeding sweet basil leaves in diet to rats
for 2-weeks caused a significant increase in levels of GST and all phase I enzymes
[41], whereas hydroalcohol extract of fresh leaves significantly augmented phase II
enzyme activity and inhibited phase I enzyme activity, and significantly decreased
LPO and LDH activities in mice [15].
1320 Ocimum basilicum L.

Commentary: Basil and its EO possess potent broad-spectrum antimicrobial and

neuroprotective effects based on their pharmacological profiles and documented in
traditional uses. Nevertheless, there are no formal clinical studies (RCTs) reported
in contemporary literature, a major scientific lacuna for the medicinal use of this
important plant.

References
1. Ahonkhai I, Ba A, Edogun O, Mu U. Antimicrobial activities of the volatile
oils of Ocimum bacilicum L. and Ocimum gratissimum L. (Lamiaceae)
against some aerobic dental isolates. Pak J Pharm Sci. 2009;22:405–9.
2. Akhtar MS, Munir M. Evaluation of the gastric antiulcerogenic effects of
Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats. J Ethno-
pharmacol. 1989;27:163–76.
3. Alexopoulos A, Kimbaris AC, Plessas S, et al. Antibacterial activities of
essential oils from eight Greek aromatic plants against clinical isolates of
Staphylococcus aureus. Anaerobe. 2011;17:399–402.
4. Al-Maskri AY, Hanif MA, Al-Maskari MY, et al. Essential oil from Ocimum
basilicum (Omani Basil): a desert crop. Nat Prod Commun. 2011;6:1487–90.
5. Amrani S, Harnafi H, Bouanani Nel H, et al. Hypolipidaemic activity of
aqueous Ocimum basilicum extract in acute hyperlipidaemia induced by triton
WR-1339 in rats and its antioxidant property. Phytother Res. 2006;20:1040–5.
6. Amrani S, Harnafi H, Gadi D, et al. Vasorelaxant and antiplatelet aggregation
effects of aqueous Ocimum basilicum extract. J Ethnopharmacol. 2009;125:
157–62.
7. Askari VR, Baradaran Rahimi V, Ghorbani A, Rakhshandeh H. Hypnotic
effect of Ocimum basilicum on pentobarbital-induced sleep in mice. Iran
Red Crescent Med J. 2016;18:e24261.
8. Bassolé IH, Lamien-Meda A, Bayala B, et al. Composition and antimicrobial
activities of Lippia multiflora Moldenke, Mentha piperita L. and Ocimum
basilicum L. essential oils and their major monoterpene alcohols alone and in
combination. Molecules. 2010;15:7825–39.
9. Bayala B, Bassole IH, Gnoula C, et al. Chemical composition, antioxidant,
anti-inflammatory and antiproliferative activities of essential oils of plants
from Burkina Faso. PLoS ONE. 2014;9:e92122.
10. Benedec D, Pârvu AE, Oniga I, et al. Effects of Ocimum basilicum L.
extract on experimental acute inflammation. Rev Med Chir Soc Med Nat
Iasi. 2007;111:1065–9.
11. Bora KS, Arora S, Shri R. Role of Ocimum basilicum L. in prevention of
ischemia and reperfusion-induced cerebral damage and motor dysfunctions in
mice brain. J Ethnopharmacol. 2011;137:1360–5.
12. Bravo E, Amrani S, Aziz M, et al. Ocimum basilicum ethanolic extract
decreases cholesterol synthesis and lipid accumulation in human macro-
phages. Fitoterapia. 2008;79:515–23.
Ocimum basilicum L. 1321

13. Chatterjee A, Sukul NC, Laskar S, Ghoshmajumdar S. Nematicidal principles

from two species of lamiaceae. J Nematol. 1982;14:118–20.
14. Chiang LC, Ng LT, Cheng PW, et al. Antiviral activities of extracts and
selected pure constituents of Ocimum basilicum. Clin Exp Pharmacol
Physiol. 2005;32:811–6.
15. Dasgupta T, Rao AR, Yadava PK. Chemomodulatory efficacy of basil leaf
(Ocimum basilicum) on drug metabolizing and antioxidant enzymes, and on
carcinogen-induced skin and forestomach papillomagenesis. Phytomedicine.
2004;11:139–51.
16. de Almeida I, Alviano DS, Vieira DP, et al. Antigiardial activity of Ocimum
basilicum essential oil. Parasitol Res. 2007;101:443–52.
17. Di Cesare LF, Forni E, Viscardi D, Nani RC. Changes in the chemical
composition of basil caused by different drying procedures. J Agric Food
Chem. 2003;51:3575–81.
18. Dorman HJ, Hiltunen R. Ocimum basilicum L.: phenolic profile and anti-
oxidant-related activity. Nat Prod Commun. 2010;5:65–72.
19. Duman AD, Telci I, Dayisoylu KS, et al. Evaluation of bioactivity of
linalool-rich essential oils from Ocimum basilucum and Coriandrum
sativum varieties. Nat Prod Commun. 2010;5:969–74.
20. El-Beshbishy H, Bahashwan S. Hypoglycemic effect of basil (Ocimum
basilicum) aqueous extract is mediated through inhibition of a-glucosidase
and a-amylase activities: an in vitro study. Toxicol Ind Health. 2012;28:
42–50.
21. El-Soud NH, Deabes M, El-Kassem LA, Khalil M: Chemical composition
and antifungal activity of Ocimum basilicum L. essential oil. Open Access
Maced J Med Sci. 2015;3:374–9.
22. Ezz Eldin HM, Badawy AF. In vitro anti-Trichomonas vaginalis activity of
Pistacia lentiscus mastic and Ocimum basilicum essential oil. J Parasit Dis.
2015;39:465–73.
23. Fandohan P, Gnonlonfin B, Laleye A, et al. Toxicity and gastric tolerance of
essential oils from Cymbopogon citratus, Ocimum gratissimum and Oci-
mum basilicum in Wistar rats. Food Chem Toxicol. 2008;46:2493–7.
24. Farag MA, Ezzat SM, Salama MM, Tadros MG, Serya RA. Antiacetyl-
cholinesterase activity of essential oils and their major constituents from
four Ocimum species. Z Naturforsch C. 2016;71:393–402.
25. Fathiazad F, Matlobi A, Khorrami A, et al. Phytochemical screening and
evaluation of cardioprotective activity of ethanolic extract of Ocimum
basilicum L. (basil) against isoproterenol induced myocardial infarction in
rats. Daru. 2012;20:87.
26. Fischer R, Nitzan N, Chaimovitsh D, et al. Variation in essential oil
composition within individual leaves of sweet basil (Ocimum basilicum L.)
is more affected by leaf position than by leaf age. J Agric Food Chem. 2011;59:
4913–22.
1322 Ocimum basilicum L.

27. Fitsiou E, Mitropoulou G, Spyridopoulou K, et al. Phytochemical profile and

evaluation of the biological activities of essential oils derived from the Greek
aromatic plant species Ocimum basilicum, Mentha spicata, Pimpinella anisum
and Fortunella margarita. Molecules. 2016;21. pii: E1069.
28. Gbadegesin MA, Odunola OA. Aqueous and ethanolic leaf extracts of Oci-
mum basilicum (sweet basil) protect against sodium arsenite-induced hepa-
totoxicity in Wistar rats. Niger J Physiol Sci. 2010;25:29–36.
29. González JA, García-Barriuso M, Gordaliza M, Amich F. Traditional
plant-based remedies to control insect vectors of disease in the Arribes del
Duero (western Spain): an ethnobotanical study. J Ethnopharmacol. 2011;138:
595–601.
30. Gülçin I, Elmastaş M, Aboul-Enein HY. Determination of antioxidant and
radical scavenging activity of basil (Ocimum basilicum L. Family Lami-
aceae) assayed by different methodologies. Phytother Res. 2007;21:354–61.
31. Hossain MA, Kabir MJ, Salehuddin SM, et al. Antibacterial properties of
essential oils and methanol extracts of sweet basil Ocimum basilicum oc-
curring in Bangladesh. Pharm Biol. 2010;48:504–11.
32. Inbaneson SJ, Sundaram R, Suganthi P. In vitro antiplasmodial effect of
ethanolic extracts of traditional medicinal plant Ocimum species against
Plasmodium falciparum. Asian Pac J Trop Med. 2012;5:103–6.
33. Javanmardi J, Khalighi A, Kashi A, et al. Chemical characterization of basil
(Ocimum basilicum L.) found in local accessions and used in traditional
medicines in Iran. J Agric Food Chem. 2002;50:5878–83.
34. Jayasinghe C, Gotoh N, Aoki T, Wada S. Phenolics composition and
antioxidant activity of sweet basil (Ocimum basilicum L.). J Agric Food
Chem. 2003;51:4442–9.
35. Josabad Alonso-Castro A, Jose Maldonado-Miranda J, Zarate-Martinez A,
et al. Medicinal plants used in the Huasteca Potosina. México. J Ethnophar-
macol. 2012;143:292–8.
36. Kathirvel P, Ravi S. Chemical composition of the essential oil from basil
(Ocimum basilicum Linn.) and its in vitro cytotoxicity against HeLa and
HEp-2 human cancer cell lines and NIH 3T3 mouse embryonic fibroblasts. Nat
Prod Res. 2012;26:1112–8.
37. Kaurinovic B, Popovic M, Vlaisavljevic S, Trivic S. Antioxidant capacity
of Ocimum basilicum L. and Origanum vulgare L. extracts. Molecules. 2011;
16:7401–14.
38. Kaya I, Yigit N, Benli M. Antimicrobial activity of various extracts of Oci-
mum basilicum L. and observation of the inhibition effect on bacterial cells by
use of scanning electron microscopy. Afr J Tradit Complement Altern Med.
2008;5:363–9.
39. Kiec-Swierczynska M, Krecisz B, Chomiczewska D, Swierczynska-
Machura D, Palczynski C. Occupational allergic contact dermatitis caused
by basil (Ocimum basilicum). Contact Dermatitis. 2010;63:365–7.
Ocimum basilicum L. 1323

40. Kristinsson KG, Magnusdottir AB, Petersen H, Hermansson A. Effective

treatment of experimental acute otitis media by application of volatile fluids
into the ear canal. J Infect Dis. 2005;191:1876–80.
41. Kusamran WR, Ratanavila A, Tepsuwan A. Effects of neem flowers, Thai and
Chinese bitter gourd fruits and sweet basil leaves on hepatic monooxygenases
and glutathione S-transferase activities, and in vitro metabolic activation of
chemical carcinogens in rats. Food Chem Toxicol. 1998;36:475–84.
42. Lachowicz KJ, Jones GP, Briggs DR, et al. The synergistic preservative
effects of the essential oils of sweet basil (Ocimum basilicum L.) against
acid-tolerant food microflora. Lett Appl Microbiol. 1998;26:209–14.
43. Lee KG, Shibamoto T. Determination of antioxidant potential of volatile
extracts isolated from various herbs and spices. J Agric Food Chem. 2002;
50:4947–52.
44. Maggio A, Roscigno G, Bruno M, De Falco E, Senatore F. Essential-oil
variability in a collection of Ocimum basilicum L. (Basil) cultivars. Chem
Biodivers. 2016;13:1357–68.
45. Meera R, Devi P, Kameswari B, et al. Antioxidant and hepatoprotective
activities of Ocimum basilicum Linn. and Trigonella foenum-graecum Linn.
against H2O2 and CCL4 induced hepatotoxicity in goat liver. Indian J Exp
Biol. 2009;47:584–90.
46. Monga J, Sharma M, Tailor N, Ganesh N. Antimelanoma and radiopro-
tective activity of alcoholic aqueous extract of different species of Ocimum
in C(57)BL mice. Pharm Biol. 2011;49:428–36.
47. Nguefack J, Budde BB, Jakobsen M. Five essential oils from aromatic
plants of Cameroon: their antibacterial activity and ability to permeabilize
the cytoplasmic membrane of Listeria innocua examined by flow cytometry.
Lett Appl Microbiol. 2004;39:395–400.
48. Ntonifor NN, Ngufor CA, Kimbi HK, Oben BO. Traditional use of indigenous
mosquito-repellents to protect humans against mosquitoes and other insect
bites in a rural community of Cameroon. East Afr Med J. 2006;83:553–8.
49. Omoregbe RE, Ikuebe OM, Ihimire IG. Antimicrobial activity of some
medicinal plants extracts on Escherichia coli, Salmonella paratyphi and
Shigella dysenteriae. Afr J Med Med Sci. 1996;25:373–5.
50. Opalchenova G, Obreshkova D. Comparative studies on the activity of basil—
an essential oil from Ocimum basilicum L.—against multidrug resistant
clinical isolates of the genera Staphylococcus, Enterococcus and Pseudomonas
by using different test methods. J Microbiol Methods. 2003;54:105–10.
51. Orhan I, Kartal M, Kan Y, Sener B. Activity of essential oils and individual
components against acetyl- and butyrylcholinesterase. Z Naturforsch C. 2008;
63:547–53.
52. Orhan IE, Ozcelik B, Kan Y, Kartal M. Inhibitory effects of various essential
oils and individual components against extended-spectrum beta-lactamase
(ESBL) produced by Klebsiella pneumoniae and their chemical compositions.
J Food Sci. 2011;76:M538–46.
1324 Ocimum basilicum L.

53. Padalia RC, Verma RS. Comparative volatile oil composition of four Oci-
mum species from northern India. Nat Prod Res. 2011;25:569–75.
54. Pozzatti P, Scheid LA, Spader TB, et al. In vitro activity of essential oils
extracted from plants used as spices against fluconazole-resistant and
fluconazole-susceptible Candida spp. Can J Microbiol. 2008;54:950–6.
55. Rabbani M, Sajjadi SE, Vaezi A. Evaluation of anxiolytic and sedative effect
of essential oil and hydroalcoholic extract of Ocimum basilicum L. and
chemical composition of its essential oil. Res Pharm Sci. 2015;10:535–43.
56. Radulović NS, Blagojević PD, Miltojević AB. a-Linalool-a marker com-
pound of forged/ synthetic sweet basil (Ocimum basilicum L.) essential oils.
J Sci Food Agric. 2013;93:3292–303.
57. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J Gastro-
enterol. 2010;16:4504–14.
58. Rao BR, Kotharia SK, Rajput DK, et al. Chemical and biological diversity in
fourteen selections of four Ocimum species. Nat Prod Commun. 2011;6:
1705–10.
59. Rasekh HR, Hosseinzadeh L, Mehri S, et al. Safety assessment of Ocimum
basilicum hydroalcoholic extract in Wistar rats: acute and subchronic
toxicity studies. Iran J Basic Med Sci. 2012;15:645–53.
60. Rashidian A, Roohi P, Mehrzadi S, Ghannadi AR, Minaiyan M. Protective
effect of Ocimum basilicum essential oil against acetic acid-induced colitis
in rats. J Evid Based Complementary Altern Med. 2016;21:NP36–42.
61. Rattanachaikunsopon P, Phumkhachorn P. Antimicrobial activity of basil
(Ocimum basilicum) oil against Salmonella enteritidis in vitro and in food.
Biosci Biotechnol Biochem. 2010;74:1200–4.
62. Rodrigues LB, Oliveira Brito Pereira Bezerra Martins A, Cesário FR, et al.
Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum
essential oil and its main compound estragole: in vivo mouse models. Chem
Biol Interact. 2016;257:14–25.
63. Sakr SA, Nooh HZ. Effect of Ocimum basilicum extract on cadmium-induced
testicular histomorphometric and immunohistochemical alterations in albino
rats. Anat Cell Biol. 2013;46:122–30.
64. Sánchez E, García S, Heredia N. Extracts of edible and medicinal plants
damage membranes of Vibrio cholerae. Appl Environ Microbiol. 2010;76:
6888–94.
65. Sanchez-Suarez J, Riveros I, Delgado G. Evaluation of the leishmanicidal
and cytotoxic potential of essential oils derived from ten Colombian plants.
Iran J Parasitol. 2013;8:129–36.
66. Sarahroodi S, Esmaeili S, Mikaili P, et al. The effects of green Ocimum
basilicum hydroalcoholic extract on retention and retrieval of memory in
mice. Anc Sci Life. 2012;31:185–9.
67. Siddiqui BS, Aslam H, Ali ST, et al. Two new triterpenoids and a steroidal
glycoside from the aerial parts of Ocimum basilicum. Chem Pharm Bull
(Tokyo). 2007;55:516–9.
Ocimum basilicum L. 1325

68. Siddiqui BS, Aslam H, Begum S, Ali ST. New cinnamic acid esters from
Ocimum basilicum. Nat Prod Res. 2007;21:736–41.
69. Sienkiewicz M, Łysakowska M, Pastuszka M, Bienias W, Kowalczyk E. The
potential of use basil and rosemary essential oils as effective antibacterial
agents. Molecules. 2013;18:9334–51.
70. Singh S. Comparative evaluation of anti-inflammatory potential of fixed oil
of different species of Ocimum and its possible mechanism of action.
Indian J Exp Biol. 1998;36:1028–31.
71. Singh S. Evaluation of gastric antiulcer activity of fixed oil of Ocimum
basilicum Linn. and its possible mechanism of action. Indian J Exp Biol.
1999;37:253–7.
72. Singh S. Mechanism of action of anti-inflammatory effect of fixed oil of
Ocimum basilicum Linn. Indian J Exp Biol. 1999;37:248–52.
73. Singh V, Kahol A, Singh IP, Saraf I, Shri R. Evaluation of antiamnesic
effect of extracts of selected Ocimum species using in-vitro and in-vivo
models. J Ethnopharmacol. 2016;193:490–9.
74. Soković M, Glamočlija J, Marin PD, Brkić D, van Griensven LJ. Antibac-
terial effects of the essential oils of commonly consumed medicinal herbs
using an in vitro model. Molecules. 2010;15:7532–46.
75. Tohti I, Tursun M, Umar A, et al. Aqueous extracts of Ocimum basilicum
L. (sweet basil) decrease platelet aggregation induced by ADP and thrombin
in vitro and rats arteriovenous shunt thrombosis in vivo. Thromb Res.
2006;118:733–9.
76. Umar A, Zhou W, Abdusalam E, et al. Effect of Ocimum basilicum L. on
cyclooxygenase isoforms and prostaglandins involved in thrombosis.
J Ethnopharmacol. 2014;152:151–5.
77. Umar A, Imam G, Yimin W, et al. Antihypertensive effects of Ocimum
basilicum L. (OBL) on blood pressure in renovascular hypertensive rats.
Hypertens Res. 2010;33:727–30.
78. Vartholomaios S, Pitsios C, Mikos N, et al. Allergy to basil, a Lamiaceae herb.
J Investig Allergol Clin Immunol. 2007;17:348–9.
79. Velázquez C, Calzada F, Torres J, et al. Antisecretory activity of plants used to
treat gastrointestinal disorders in Mexico. J Ethnopharmacol. 2006;103:66–70.
80. Viyoch J, Pisutthanan N, Faikreua A, et al. Evaluation of in vitro antimicrobial
activity of Thai basil oils and their microemulsion formulas against
Propionibacterium acnes. Int J Cosmet Sci. 2006;28:125–33.
81. Wang T, Cui SY, Hu XL, Lu RH. Study on the constituents of volatile oil
from Ocimum basilicum. Zhongguo Zhong Yao Za Zhi. 2003;28:740–2
(Chinese).
82. Wannissorn B, Jarikasem S, Siriwangchai T, Thubthimthed S. Antibacterial
properties of essential oils from Thai medicinal plants. Fitoterapia. 2005;76:
233–6.
83. Yamasaki K, Nakano M, Kawahata T, et al. Anti-HIV-1 activity of herbs in
Labiatae. Biol Pharm Bull. 1998;21:829–33.
1326 Ocimum basilicum L.

84. Yeşiloğlu Y, Sit L. Antioxidant properties of various solvent extracts from

purple basil. Spectrochim Acta A Mol Biomol Spectrosc. 2012;95:100–6.
85. Yousif AN, Scaman CH, Durance TD, Girard B. Flavor volatiles and
physical properties of vacuum-microwave- and air-dried sweet basil
(Ocimum basilicum L.). J Agric Food Chem. 1999;47:4777–81.
86. Zhang JW, Li SK, Wu WJ. The main chemical composition and in vitro
antifungal activity of the essential oils of Ocimum basilicum Linn. var.
pilosum (Willd.) Benth. Molecules. 2009;14:273–8.
Ocimum gratissimum L.
(Lamiaceae)

(Syns.: O. suave Willd.; O. dalabaense A. Chev.; O. superbum Busc. & Muschl.;

O. trichodon Baker ex Gürke; O. viride Willd.)

Abstract
A plant native to Sri Lanka, India, Iran, Africa, and Madagaskar, and naturalized
worldwide. The leaves have a remarkably grateful lemon odor and taste. Baths
and fumigations prepared with the plant are used in the treatment of rheumatism
and paralysis. Unani medicine physicians of India consider it cardiorefrigerant,
cardiotonic, brain tonic, anti-inflammatory, antiseptic, diuretic, carminative,
astringent, and deobstruent; and use it to treat cardiac weakness, palpitation, cold
and cough, gastrointestinal disorders and fevers. In India, it is generally combined
with other expectorants in cough mixtures; and an infusion of seeds is used in
urinary disorders, such as gonorrhea, scanty and burning micturition. In Nigeria,
the plant is used to facilitate childbirth and to reduce the associated pain, is
believed to possess curative properties for measles among the local populace of
Ogun State in southwest Nigeria, and is one of the component plants in herbal
decoctions used by Nigerian traditional herbal medicine practitioners for the
treatment of diabetes. The plant is used in Brazilian traditional medicine to treat
painful conditions, and in the northeast of Brazil, for digestive problems. The
plant is grown and used in traditional medicine of São Tomé (a Caribbean Island
nation), as a febrifuge and for the treatment of respiratory diseases. Analysis of
volatile oils of aerial parts collected from three different geographical locations,
Nepal, Tajikistan, and Yemen, showed six chemotypes: linalool, eugenol,
estragole, methyl eugenol, 1,8-cineole, and geraniol. Aqueous extract adminis-
tration for 4-weeks significantly lowered FBG of diabetic rats, and significantly
increased PCV, RBC count, and Hb, and methanol leaf extract reduced plasma
glucose both in normal and diabetic rats. Various leaf extracts were very active
against Sh. dysenteriae and to a lesser extent against E. coli, P. shigelloides, and
S. typhi. Aqueous extract inhibited growth of clinical isolates of Sh. dysenteriae,
Sh. flexneri, Sh. sonnei and Sh. boydii, and MDR S. typhi. One clinical trial of the
EO for acne reported results equivalent to conventional treatments.

© Springer Nature Switzerland AG 2020 1327

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_137
1328 Ocimum gratissimum L.

Keywords





Ajeka Alfavacão Basilic africain Bantulsi Baumbasilikum Clove basil






Ding xiang luo le Firanjmishk Indo mebouki Orégano cimarrón

Vernaculars: Urd.: Firanjmishk, Rehan; Hin.: Banjari, Bantulsi, Ram tulsi,; San.:
Ajeka, Ajvalla, Barbara, Vantulasi, Varvara; Ben.: Rama tulsi, Ramtulshi; Guj.:
Avachibavachi, Ramtulasi; Mal.: Kattei-tulluva, Kattutrittavu; Mar.: Rama tulsi;
Tam.: Elumichai thulasi, Elumicham-tolashi, Peruntulasi; Tel.: Nimma-tulasi; Ara.:
Faranjmushk; Chi.: Ding xiang luo le; Dut.: Boombasilicum; Eng.: African basil,
Clove basil, Russian basil, Shrubby basil, Wild basil; Fre.: Basilic à fleurs
jaune-verdâtre-pâle, Basilic africain, Basilic-arbre, Basilic à thymol, Basilic de-
Ceylon, Romba; Ger.: Afrikanisches basilikum, Baumbasilikum; Ita.: Basilico
cespuglioso; Jap.: Indo mebouki; Nep.: Tulasii, Van tulasii; Nig.: Ahigbu, Ahinji,
Dai doya tagida, Efirin, Ihiri eziza, Nchuanwu, Ntion; Per.: Balanki-khurd (seeds),
Palang-mishk, Raihan-e-qaranfali; Por.: Alfavaca-cravo, Alfavacão, Louro-cheiroso
and Manjericão-indiano (Br.); Sin.: Tankay; Spa.: Albahaca cimarrona, Clavo
canela, Orégano cimarrón; Tag.: Balanoi; Tha.: Horapha chang, Ka phrao yuan,
Kaprao-chang, Niam yira.
Description: A plant native to Sri Lanka, India, Iran, Africa, and Madagaskar, and
naturalized worldwide. Dymock et al.XL stated that this plant has wrongly been
identified with Firanjmushk of Persia, because the seeds imported from Persia
under that name bear no resemblance to the seeds of O. basilicum. The plant from
which these seeds (Faranjmishk) are obtained was described by Persian medical
writers as having a clove-like odor, on which account it is often called Qaranfal-
i-bustani, ‘garden clove.’ O. gratissimum’s stem is erect, woody, perennial, from a
little over 1 m to about 2.5 m tall; bark ash-colored; branches opposite, erect,
4-sided, when young smooth, glossy and green; leaves opposite, long-petioled,
drooping, oblong, ventricose, remotely serrate, pointed, smooth on both sides, often
15 cm long, including the petiole, which is about a third of the whole; racemes
terminal, pretty long, rigidly erect, with the verticals of 6 flowers pretty close; bracts
short-petioled, reflexed, cordate lanceolate; calyx upper lip marked with three
nerves; corolla short, scarcely larger than the calyx, pale-yellow underneath,
oblong, concave and entire; filaments longer than the corolla, with a large tuft of
dark yellow hairs on the joints of the large pair near the base (Fig. 1).XL
Actions and Uses: The leaves have a remarkably grateful lemon odor and taste.
Baths and fumigations prepared with the plant are used in the treatment of rheuma-
tism and paralysis. A decoction of mucilaginous seeds is used as a demulcent.XL
Unani medicine physicians of India consider it (temperament, hot 2° and dry 2°)
cardiorefrigerant, cardiotonic, brain tonic, antiseptic, anti-inflammatory, diuretic,
carminative, astringent, and deobstruent; and use it to treat cardiac weakness,
palpitation, cold and cough, gastrointestinal disorders and fevers.LXIX,LXXVII
NadkarniCV described it styptic, stimulant, demulcent, diuretic and carminative, and
in India, it is generally combined with other expectorants in cough mixtures; and an
Ocimum gratissimum L. 1329

Fig. 1 Ocimum gratissimum, Leaves and Fruits, Forest & Kim Starr, http://www.starr-
environmental.com/plants/images/image/?q=030202-0053, WikimediaCommons; 3.0 Unported
CC BY 3.0, https://commons.wikimedia.org/wiki/File:Starr_030202-0053_Ocimum_gratissimum.
jpg; https://creativecommons.org/licenses/by/3.0/deed.en

infusion of seeds is used in urinary disorders, such as gonorrhea, scanty and burning
micturition.LXXXI,CV In Nigeria, the plant is used to facilitate childbirth and to reduce
the associated pain [7], is believed to possess curative properties for measles among
the local populace of Ogun State in southwest Nigeria [75], and is one of the com-
ponent plants in herbal decoctions used by Nigerian traditional herbal medicine
practitioners for the treatment of diabetes [17, 22], and also used in the treatment of
diarrhea, as a febrifuge and component of antimalaria remedies, mosquito/insect
repellant, stomachic and general tonic, antiseptic, in wound dressing, skin infections,
conjunctivitis and bronchitis [58]. The plant is used in Brazilian traditional medicine
to treat painful conditions [66], and in the northeast Brazil for digestive problems
[70]. The plant is grown and used in traditional medicine of São Tomé (a Caribbean
Island nation), as a febrifuge and for the treatment of respiratory diseases [42].
Phytoconstituents: Analysis of volatile oils of aerial parts collected from three
different geographical locations, Nepal, Tajikistan, and Yemen, showed six
chemotypes: linalool, eugenol, estragole, methyl eugenol, 1,8-cineole, and geraniol
[72]. Phenylpropanoids (65.2–77.6%) constitute the major proportion of EO com-
position of O. gratissimum from northern India; eugenol (75–77%), 1,8-cineole,
germacrene D and b-caryophyllene being the major constituents [32, 64]. Dubey
et al. [16] described an Indian chemotype, with a high level of ethyl cinnamate
with significant antifungal activity. Chemical composition of the EO also varied
1330 Ocimum gratissimum L.

according to the season in which the plant was collected in Brazil; however, eugenol
and 1,8-cineole were found to be the most abundant compounds in oils from all
seasons, and sesquiterpenes had the greatest relative percentage in EO from Spring
season [20]. Leaves EO from Rwanda contained 35% thymol and 11% eugenol, but
the oil from plant cultivated in Rwanda of seeds procured from Cameroon, consisted
of 47% thymol and only 0.3% eugenol [53]; whereas, major compounds in the
leaves EO from São Tomé were thymol (48.1%) and P-cymene (12.5%) [42]. Major
constituents of the oil from Cameroon were reported to be c-terpinene (21.9%),
b-phellandrene (21.1%), limonene (11.4%) and thymol (11.2%) [77]. However,
p-cymene (28.08–53.82%), thymol (3.32–29.13%), c-terpinene (1.11–10.91%),
a-thujene (3.37–10.77%), and b-myrcene (4.24–8.28%) were the major components
of leaves EO from Benin, that also varied according to the time of collection of the
plant [33].
Pharmacology: Various leaf extracts were very active against Sh. dysenteriae and to
a lesser extent against E. coli, P. shigelloides, and S. typhi [26]. Aqueous extract
inhibited growth of clinical isolates of Sh. dysenteriae, Sh. flexneri, Sh. sonnei and Sh.
boydii [29, 30], MDR S. typhi [4], and was effective against Poliovirus and HSV-1
[45]. Aqueous and ethanol extracts were also significantly active against clinical
isolates of MRSA [5], and ethanol extract against clinical isolates of S. aureus, E. coli,
P. mirabilis and P. aeruginosa, and C. albicans [54]. Methanol extract showed
antifungal activity against C. neoformans and C. albicans [10], and chloroform
extract and eugenol against C. neoformans [36], while Silva et al. [74] reported 100%
growth inhibition of dermatophytes, M. canis, M. gypseum, T. rubrum and T. men-
tagrophytes by hexane extract from Brazil, and subinhibitory concentration of hexane
extract enhanced norfloxacin activity against MDR strains of S. aureus [15]. How-
ever, Chah et al. [12] reported no growth inhibition by methanol extract of wound
isolate strains of S. aureus, E. coli, P. aeruginosa, Proteus spp., and Shigella
spp. The EO possesses broad-spectrum significant antibacterial activity against
S. aureus, B. subtilis, E. coli [31], against S. mutans, and E. faecalis, and antifungal
activity against E. floccosum, M. gypseum, and S. schenckii [71], against L. mono-
cytogenes, and L. innocua [51], Sh. flexineri, S. enteritidis, Klebsiella sp., and
P. mirabilis [47], P. aeruginosa and P. mirabilis [43], fungicidal to C. albicans,
C. krusei, C. parapsilosis and C. tropicalis [46], against mycotoxin producing fungi,
F. moniliforme, A. flavus and A. fumigates [50], A. ochraceus, P. expansum and
P. verrucosum [52], dermatophytes [38], including T. rubrum and T. mentagrophytes
[55], and T. mentagrophytes var. interdigitale [31]. Joshi [32] reported EO
highly active against S. marcescens, and its main constituent, eugenol effective only
against S. aureus. EO from Nigeria inhibited growth of K. pneumoniae, P. vulgaris,
S. viridians, S. albus and at very high concentration of P. aeruginosa [2]. Antibac-
terial activity of the EOs from Benin varied to the time of collection of the plant. The
EOs of the full-flowering plants collected at 7 am showed most fungicidal activity
against C. albicans; whereas oil obtained from plants at the pre-flowering stage
collected at 7 am was most active against S. aureus [33]. The EO also showed
Ocimum gratissimum L. 1331

significant larvicidal activity against Aedes aegypti, the major vector of dengue fever
[11], leishmanicidal activity [80], and significant antimalarial activity [77]. Methanol
extract and the oil are potently active against L. chagasi [10, 59].
Successive extracts in petroleum ether and methanol exhibited anticonvulsant
and anxiolytic-like activities [58]. Pentobarbital-induced sleeping duration in mice
was increased by EO, and the oil obtained during Spring season (from Brazil)
protected animals against MES-induced seizures [20]. Eugenol, 1,8-cineole and
trans-caryophyllene, as principal compounds of the EO, however, are not effective
as anticonvulsant individually or in combination, but prolong sleeping time in
combination [21]. Pretreatment with ethanol extract significantly attenuated focal
I/R caused brain oxidative stress, LPO and neurological deficits, and reduced
cerebral infarct size [9]. Pretreatment with chloroform extract effectively amelio-
rated cobalt chloride-induced cardiac and renal toxicity in rats, lowered BP, reduced
MI, renal tubular necrosis and inflammation [3]. Aqueous leaf extract effectively
protected myocardiac cells from hydrogen peroxide-induced cell death [35]. Bolus
(i.v.) injection of EO or eugenol caused an immediate decrease in mean aortic
pressure and HR of normal [34] and hypertensive rats [28]; pretreatment with either
methylatropine or hexamethonium reduced the bradycardia without affecting the
hypotension [34]. The EO also produced in vitro vasorelaxation [69].
Aqueous extract administration for 4-weeks significantly lowered FBG of dia-
betic rats [17, 73], and significantly increased PCV, RBC count, and Hb [73], and
methanol leaf extract reduced plasma glucose both in normal and diabetic rats [1].
Aqueous leaf extract, EO and its components eugenol and myrcene exhibit sig-
nificant analgesic [8, 65, 66, 70, 76], and anti-inflammatory activities [76]. Anal-
gesic effect of EO was antagonized by naloxone, indicating an opioid receptors
involvement [65]. Aqueous extract and the EO also exhibited spasmolytic effect [8,
39, 40], inhibited castor oil-induced diarrhea [57], decreased gastric acid secretion
and ulceration, and increased gastric mucus secretion in rats [56]; ethanol extract
also increased gastric mucus secretion [60]. Aqueous leaf extract efficiently pro-
tected against CCl4-hepatotoxicity [14], and cirrhosis-related cardiac hypertrophy
in rats [37]; and administered to rats daily for 4-weeks significantly increased
activities of plasma and hepatic CAT and SOD enzymes [25]. Methanol extract
attenuated alcohol-induced oxidative stress, increased levels of GSH and improved
activities of antioxidant enzymes [23], prevented free radical damage to liver and
protected it from oxidative stress [13]. Leaves EO also demonstrated significant
antioxidant capacity that was correlated with the amount of eugenol [79]; however,
eugenol showed weaker antioxidant activity than the oil [32]. Aqueous leaf extract
reduced tumor size and neoangiogenesis in experimental breast cancer, and
inhibited proliferation, migration, and induction of COX-2 protein in breast cancer
cells [48, 49], inhibited proliferation of several cancer cell lines, especially prostate
adenocarcinoma cells [18]. Alcoholic aqueous extract also reduced tumor volume
and survival rate of mice in chemically-induced melanoma [44].
1332 Ocimum gratissimum L.

Topical application of methanol leaf extract and EO to wounds in rabbits

facilitated healing [62, 63]. A 30% (v/v) volatile oil concentration in olive oil base
lotion exhibited an average mosquito repellency of more than 95% [61]. Mucilage
extracted from the seeds was comparable to acacia as a pharmaceutical binder [6].
Clinical Studies: One clinical trial of the EO for acne reported results equivalent to
conventional treatments [41]. In a parallel, double-blind RCT, a mouth rinse con-
taining O. gratissimum significantly reduced plaque and gingivitis comparable to
chlorhexidine digluconate [67]. Another crossover, double-blind clinical study
reported significant inhibition of plaque regrowth by a mouthrinse containing 10%
O. gratissimum solution, but lesser than 0.12% chlorhexidine digluconate [68].
Mechanism of Action: Calcium channel blockade is suggested to be responsible
for hypotensive effect of EO and eugenol [27], and cholinergic system has been
suggested to be involved in the neurobehavioural effects [24].
Human A/Es, Allergy and Toxicity: It reduces production of semen.LXXVII
Animal Toxicity: LD50 (i.p.) of aqueous leaf extract in mice was 1,265 mg/kg
body weight [76], while methanol leaf extract was nonlethal to mice up to an oral
dose of 5,000 mg/kg [58]. Oral EO to rats, 1,500 mg/kg/day for 14 consecutive
days did not cause any adverse effects [19], and rats administered with oil-treated
diet for sixty-days also exhibited no physical or biochemical signs of toxicity [78].
Commentary: There are some clinical studies on the antimicrobial effects, but a
lot needs to be done to clinically evaluate other aspects of this commonly used plant
with promising potentials.

References
1. Aguiyi JC, Obi CI, Gang SS, Igweh AC. Hypoglycaemic activity of Ocimum
gratissimum in rats. Fitoterapia. 2000;71:444–6.
2. Ahonkhai I, Ba A, Edogun O, Mu U. Antimicrobial activities of the volatile
oils of Ocimum bacilicum L. and Ocimum gratissimum L. (Lamiaceae)
against some aerobic dental isolates. Pak J Pharm Sci. 2009;22:405–9.
3. Akinrinde AS, Oyagbemi AA, Omobowale TO, Asenuga ER, Ajibade TO.
Alterations in blood pressure, antioxidant status and caspase 8 expression in
cobalt chloride-induced cardiorenal dysfunction are reversed by Ocimum
gratissimum and gallic acid in Wistar rats. J Trace Elem Med Biol. 2016;
36:27–37.
4. Akinyemi KO, Mendie UE, Smith ST, et al. Screening of some medicinal
plants used in southwest Nigerian traditional medicine for anti-Salmonella
typhi activity. J Herb Pharmacother. 2005;5:45–60.
5. Akinyemi KO, Oladapo O, Okwara CE, et al. Screening of crude extracts of
six medicinal plants used in southwest Nigerian unorthodox medicine for
antimethicillin resistant Staphylococcus aureus activity. BMC Complement
Altern Med. 205;5:6.
Ocimum gratissimum L. 1333

6. Anroop B, Ghosh B, Parcha V, Vasanti S. Studies on Ocimum gratissi-

mum seed mucilage: evaluation of binding properties. Int J Pharm. 2006;
325:191–3.
7. Attah AF, O’Brien M, Koehbach J, et al. Uterine contractility of plants used
to facilitate childbirth in Nigerian ethnomedicine. J Ethnopharmacol. 2012;
143:377–82.
8. Aziba PI, Bass D, Elegbe Y. Pharmacological investigation of Ocimum
gratissimum in rodents. Phytother Res. 1999;13:427–9.
9. Bora KS, Shri R, Monga J. Cerebroprotective effect of Ocimum gratissi-
mum against focal ischemia and reperfusion-induced cerebral injury. Pharm
Biol. 2011;49:175–81.
10. Braga FG, Bouzada ML, Fabri RL, et al. Antileishmanial and antifungal
activity of plants used in traditional medicine in Brazil. J Ethnopharmacol.
2007;111:396–402.
11. Cavalcanti ES, Morais SM, Lima MA, Santana EW. Larvicidal activity of
essential oils from Brazilian plants against Aedes aegypti L. Mem Inst
Oswaldo Cruz. 2004;99:541–4.
12. Chah KF, Eze CA, Emuelosi CE, Esimone CO. Antibacterial and wound
healing properties of methanolic extracts of some Nigerian medicinal plants.
J Ethnopharmacol. 2006;104:164–7.
13. Chaturvedi R, George S, John A. Preventive and protective effects of wild
basil in ethanol-induced liver toxicity in rats. Br J Biomed Sci. 2007;64:
10–2.
14. Chiu CC, Huang CY, Chen TY, et al. Beneficial effects of Ocimum
gratissimum aqueous extract on rats with CCl(4)-induced acute liver injury.
Evid Based Complement Alternat Med. 2012;2012:736752.
15. Coutinho HD, Matias EF, Santos KK, et al. Modulation of the norfloxacin
resistance in Staphylococcus aureus by Croton campestris A. and Ocimum
gratissimum L. Biomedica. 2011;31:608–12.
16. Dubey NK, Tiwari TN, Mandin D, et al. Antifungal properties of Ocimum
gratissimum essential oil (ethyl cinnamate chemotype). Fitoterapia. 2000;
71:567–9.
17. Egesie UG, Adelaiye AB, Ibu JO, Egesie OJ. Safety and hypoglycaemic
properties of aqueous leaf extract of Ocimum gratissimum in streptozotocin
induced diabetic rats. Niger J Physiol Sci. 2006;21:31–5.
18. Ekunwe SI, Thomas MS, Luo X, et al. Potential cancer-fighting Ocimum
gratissimum (OG) leaf extracts: increased antiproliferation activity of
partially purified fractions and their spectral fingerprints. Ethn Dis. 2010;20:
S1–S12, S16.
19. Fandohan P, Gnonlonfin B, Laleye A, et al. Toxicity and gastric tolerance of
essential oils from Cymbopogon citratus, Ocimum gratissimum and Oci-
mum basilicum in Wistar rats. Food Chem Toxicol. 2008;46:2493–7.
20. Freire CM, Marques MO, Costa M. Effects of seasonal variation on the
central nervous system activity of Ocimum gratissimum L. essential oil.
J Ethnopharmacol. 2006;105:161–6.
1334 Ocimum gratissimum L.

21. Galindo LA, Pultrini Ade M, Costa M. Biological effects of Ocimum

gratissimum L. are due to synergic action among multiple compounds
present in essential oil. J Nat Med. 2010;64:436–41.
22. Gbolade AA. Inventory of antidiabetic plants in selected districts of Lagos
State, Nigeria. J Ethnopharmacol. 2009;121:135–9.
23. George S, Chaturvedi P. A comparative study of the antioxidant properties
of two different species of Ocimum of southern Africa on alcohol-induced
oxidative stress. J Med Food. 2009;12:1154–8.
24. Ibironke GF, Modupe OG. Noncholinergic dependent mechanism of
Ocimum gratissimum induced neurobehavioural alterations in mice. Afr J
Med Sci. 2015;44:213–20.
25. Ighodaro OM, Ebuehi OA. Aqueous leaf extract of Ocimum gratissimum
potentiates activities of plasma and hepatic antioxidant enzymes in rats.
Nig Q J Hosp Med. 2009;19:106–9.
26. Ilori M, Sheteolu AO, Omonigbehin EA, Adeneye AA. Antidiarrhoeal
activities of Ocimum gratissimum (Lamiaceae). J Diarrhoeal Dis Res. 1996;
14:283–5.
27. Interaminense LF, Jucá DM, Magalhães PJ, et al. Pharmacological evidence
of calcium-channel blockade by essential oil of Ocimum gratissimum and its
main constituent, eugenol, in isolated aortic rings from DOCA-salt hyper-
tensive rats. Fundam Clin Pharmacol. 2007;21:497–506.
28. Interaminense LF, Leal-Cardoso JH, Magalhães PJ, et al. Enhanced
hypotensive effects of the essential oil of Ocimum gratissimum leaves and
its main constituent, eugenol, in DOCA-salt hypertensive conscious rats.
Planta Med. 2005;71:376–8.
29. Iwalokun BA, Gbenle GO, Adewole TA, Akinsinde KA. Shigellocidal
properties of three Nigerian medicinal plants: Ocimum gratissimum, Termi-
nalia avicennoides, and Momordica balsamina. J Health Popul Nutr. 2001;
19:331–5.
30. Iwalokun BA, Gbenle GO, Adewole TA, et al. Effects of Ocimum gratis-
simum L. essential oil at subinhibitory concentrations on virulent and
multidrug-resistant Shigella strains from Lagos. Nigeria. APMIS. 2003;111:
477–82.
31. Janssen AM, Scheffer JJ, Ntezurubanza L, Baerheim Svendsen A. Antimi-
crobial activities of some Ocimum species grown in Rwanda. J Ethnophar-
macol. 1989;26:57–63.
32. Joshi RK. Chemical composition, in vitro antimicrobial and antioxidant
activities of the essential oils of Ocimum gratissimum, O. sanctum and their
major constituents. Indian J Pharm Sci. 2013;75:457–62.
33. Kpadonou Kpoviessi BG, Ladekan EY, Kpoviessi DS, et al. Chemical
variation of essential oil constituents of Ocimum gratissimum L. from Benin,
and impact on antimicrobial properties and toxicity against Artemia salina
leach. Chem Biodivers. 2012;9:139–50.
Ocimum gratissimum L. 1335

34. Lahlou S, Interaminense Lde F, Leal-Cardoso JH, et al. Cardiovascular

effects of the essential oil of Ocimum gratissimum leaves in rats: role of the
autonomic nervous system. Clin Exp Pharmacol Physiol. 2004;31:219–25.
35. Lee MJ, Chen HM, Tzang BS, et al. Ocimum gratissimum aqueous extract
protects H9c2 myocardiac cells from H2O2-induced cell apoptosis through
Akt signalling. Evid Based Complement Alternat Med. 2011;2011. pii:
578060.
36. Lemos Jde A, Passos XS, Fernandes Ode F, et al. Antifungal activity from
Ocimum gratissimum L. towards Cryptococcus neoformans. Mem Inst
Oswaldo Cruz. 2005;100:55–8.
37. Li PC, Chiu YW, Lin YM, et al. Herbal supplement ameliorates cardiac
hypertrophy in rats with CCl4-induced liver cirrhosis. Evid Based Comple-
ment Alternat Med. 2012;2012:139045.
38. Lima EO, Gompertz OF, Giesbrecht AM, Paulo MQ. In vitro antifungal
activity of essential oils obtained from officinal plants against dermato-
phytes. Mycoses. 1993;36:333–6.
39. Madeira SV, Matos FJ, Leal-Cardoso JH, Criddle DN. Relaxant effects of
the essential oil of Ocimum gratissimum on isolated ileum of the guinea pig.
J Ethnopharmacol. 2002;81:1–4.
40. Madeira SV, Rabelo M, Soares PM, et al. Temporal variation of chemical
composition and relaxant action of the essential oil of Ocimum gratissimum
L. (Labiatae) on guinea-pig ileum. Phytomedicine. 2005;12:506–9.
41. Martin KW, Ernst E. Herbal medicines for treatment of bacterial infections:
a review of controlled clinical trials. J Antimicrob Chemother. 2003;51:
241–6 (Review).
42. Martins AP, Salgueiro LR, Vila R, et al. Composition of the essential oils of
Ocimum canum, O. gratissimum and O. minimum. Planta Med. 1999;65:
187–9.
43. Matasyoh LG, Matasyoh JC, Wachira FN, et al. Antimicrobial activity of
essential oils of Ocimum gratissimum L. from different populations of
Kenya. Afr J Tradit Complement Altern Med. 2008;5:187–93.
44. Monga J, Sharma M, Tailor N, Ganesh N. Antimelanoma and radiopro-
tective activity of alcoholic aqueous extract of different species of Ocimum
in C(57)BL mice. Pharm Biol. 2011;49:428–36.
45. Moura-Costa GF, Nocchi SR, Ceole LF, et al. Antimicrobial activity of
plants used as medicinals on an indigenous reserve in Rio das Cobras,
Paraná. Brazil. J Ethnopharmacol. 2012;143:631–8.
46. Nakamura CV, Ishida K, Faccin LC, et al. In vitro activity of essential oil
from Ocimum gratissimum L. against four Candida species. Res Microbiol.
2004;155:579–86.
47. Nakamura CV, Ueda-Nakamura T, Bando E, et al. Antibacterial activity of
Ocimum gratissimum L. essential oil. Mem Inst Oswaldo Cruz. 1999;94:
675–8.
1336 Ocimum gratissimum L.

48. Nangia-Makker P, Tait L, Shekhar MP, et al. Inhibition of breast tumor

growth and angiogenesis by a medicinal herb: Ocimum gratissimum. Int J
Cancer. 2007;121:884–94.
49. Nangia-Makker P, Raz T, Tait L, et al. Ocimum gratissimum retards breast
cancer growth and progression and is a natural inhibitor of matrix
metalloproteases. Cancer Biol Ther. 2013;14:417–27.
50. Nguefack J, Leth V, Amvam Zollo PH, Mathur SB. Evaluation of five
essential oils from aromatic plants of Cameroon for controlling food spoilage
and mycotoxin producing fungi. Int J Food Microbiol. 2004;94:329–34.
51. Nguefack J, Budde BB, Jakobsen M. Five essential oils from aromatic
plants of Cameroon: their antibacterial activity and ability to permeabilize
the cytoplasmic membrane of Listeria innocua examined by flow cytometry.
Lett Appl Microbiol. 2004;39:395–400.
52. Nguefack J, Dongmo JB, Dakole CD, et al. Food preservative potential of
essential oils and fractions from Cymbopogon citratus, Ocimum gratissi-
mum and Thymus vulgaris against mycotoxigenic fungi. Int J Food
Microbiol. 2009;131:151–6.
53. Ntezurubanza L, Scheffer JJ, Svendsen AB. Composition of the essential oil
of Ocimum gratissimum grown in Rwanda. Planta Med. 1987;53:421–3.
54. Nweze EI, Eze EE. Justification for the use of Ocimum gratissimum L. in
herbal medicine and its interaction with disc antibiotics. BMC Complement
Altern Med. 2009;9:37.
55. Nwosu MO, Okafor JI. Preliminary studies of the antifungal activities of
some medicinal plants against Basidiobolus and some other pathogenic
fungi. Mycoses. 1995;38:191–5.
56. Ofem OE, Eno AE, Antai AB. Gastric acid antisecretory, antiulcerogenic
and mucogenic effects of aqueous leaves extract of Ocimum gratissimum in
rats. Niger J Physiol Sci. 2012;27:41–7.
57. Offiah VN, Chikwendu UA. Antidiarrhoeal effects of Ocimum gratissimum
leaf extract in experimental animals. J Ethnopharmacol. 1999;68:327–30.
58. Okoli CO, Ezike AC, Agwagah OC, Akah PA. Anticonvulsant and anxi-
olytic evaluation of leaf extracts of Ocimum gratissimum, a culinary herb.
Pharmacognosy Res. 2010;2:36–40.
59. Oliveira VC, Moura DM, Lopes JA, et al. Effects of essential oils from
Cymbopogon citratus (DC) Stapf., Lippia sidoides Cham., and Ocimum gratis-
simum L. on growth and ultrastructure of Leishmania chagasi promastigotes.
Parasitol Res. 2009;104:1053–9.
60. Onasanwo SA, Omolaso BO, Ukoha N. Ocimum grastissimum extract
inhibits stimulated acid secretion by carbachol and induces gastric mucus
secretion. Afr J Med Med Sci. 2012;41(Suppl):35–8.
61. Oparaocha ET, Iwu I, Ahanakuc JE. Preliminary study on mosquito
repellent and mosquitocidal activities of Ocimum gratissimum (L.) grown
in eastern Nigeria. J Vector Borne Dis. 2010;47:45–50.
Ocimum gratissimum L. 1337

62. Orafidiya LO, Agbani EO, Abereoje OA, et al. An investigation into the
wound-healing properties of essential oil of Ocimum gratissimum Linn.
J Wound Care. 2003;12:331–4.
63. Osuagwu FC, Oladejo OW, Imosemi IO, et al. Wound healing activities of
methanolic extracts Ocimum gratissimum leaf in Wistar rats—a preliminary
study. Afr J Med Med Sci. 2004;33:23–6.
64. Padalia RC, Verma RS. Comparative volatile oil composition of four Oci-
mum species from northern India. Nat Prod Res. 2011;25:569–75.
65. Paula-Freire LI, Andersen ML, Molska GR, et al. Evaluation of the antinoci-
ceptive activity of Ocimum gratissimum L. (Lamiaceae) essential oil and its
isolated active principles in mice. Phytother Res. 2013;27:1220–4.
66. Paula-Freire LI, Molska GR, Andersen ML, Carlini EL. Ocimum gratis-
simum essential oil and its isolated compounds (eugenol and myrcene)
reduce neuropathic pain in mice. Planta Med. 2016;82:211–6.
67. Pereira SL, de Oliveira JW, Angelo KK, et al. Clinical effect of a mouth
rinse containing Ocimum gratissimum on plaque and gingivitis control.
J Contemp Dent Pract. 2011;12:350–5.
68. Pimenta MS, Lobo NS, Vieira VC, et al. Effect of Ocimum gratissimum in
mouthrinses on de novo plaque formation. A randomized clinical trial. Braz
Dent J. 2016;27:646–51 (Article in Portuguese).
69. Pires AF, Madeira SV, Soares PM, et al. The role of endothelium in the
vasorelaxant effects of the essential oil of Ocimum gratissimum in aorta and
mesenteric vascular bed of rats. Can J Physiol Pharmacol. 2012;90:1380–5.
70. Rabelo M, Souza EP, Soares PM, et al. Antinociceptive properties of the
essential oil of Ocimum gratissimum L. (Labiatae) in mice. Braz J Med Biol
Res. 2003;36:521–4.
71. Rao BR, Kotharia SK, Rajput DK, et al. Chemical and biological diversity
in fourteen selections of four Ocimum species. Nat Prod Commun. 2011;6:
1705–10.
72. Sharopov FS, Satyal P, Ali NA, et al. The essential oil compositions of
Ocimum basilicum from three different regions: Nepal, Tajikistan, and
Yemen. Chem Biodivers. 2016;13:241–8.
73. Shittu ST, Oyeyemi WA, Lasisi TJ, et al. Aqueous leaf extract of Ocimum
gratissimum improves hematological parameters in alloxan-induced diabetic
rats via its antioxidant properties. Int J Appl Basic Med Res. 2016;6:96–100.
74. Silva MR, Oliveira JG Jr, Fernandes OF, et al. Antifungal activity of
Ocimum gratissimum towards dermatophytes. Mycoses. 2005;48:172–5.
75. Sonibare MA, Moody JO, Adesanya EO. Use of medicinal plants for the
treatment of measles in Nigeria. J Ethnopharmacol. 2009;122:268–72.
76. Tanko Y, Magaji GM, Yerima M, et al. Antinociceptive and anti-inflammatory
activities of aqueous leaves extract of Ocimum gratissimum (Labiate) in
rodents. Afr J Tradit Complement Altern Med. 2008;5:141–6.
1338 Ocimum gratissimum L.

77. Tchoumbougnang F, Zollo PH, Dagne E, Mekonnen Y. In vivo antimalarial

activity of essential oils from Cymbopogon citratus and Ocimum gratissi-
mum on mice infected with Plasmodium berghei. Planta Med. 2005;71:20–3.
78. Tiwari TN, Varma J, Dubey NK, et al. Pharmacological evaluation of some
bioactive plant products on albino rats. Hindustan Antibiot Bull. 1998;40:
38–41.
79. Trevisan MT, Vasconcelos Silva MG, Pfundstein B, et al. Characterization of
the volatile pattern and antioxidant capacity of essential oils from different
species of the genus Ocimum. J Agric Food Chem. 2006;54:4378–82.
80. Ueda-Nakamura T, Mendonça-Filho RR, Morgado-Díaz JA, et al. Antileish-
manial activity of eugenol-rich essential oil from Ocimum gratissimum.
Parasitol Int. 2006;55:99–105.
Ocimum tenuiflorum L.
(Lamiaceae)

(Syn.: O. sanctum L.)

Abstract
An erect, herbaceous or half-woody plant, that is native to India but pantropic in
distribution. This immortal plant is the most sacred plant in Hindu religion, which
contains in itself every perfection, cures every ill, and purifies and guides to the
heavenly paradise those who worship it. The plant is mentioned in Charak
Samhita and Susruta Samhita, the oldest Indian medical texts. Every part of the
plant finds its medicinal use in one form or the other. Charak described it as
curative of Kapha and Vata. All parts are recommended for the treatment of
bronchitis, bronchial asthma, malaria, diarrhea, dysentery, skin diseases, arthritis,
painful eye diseases, chronic fever, and insect bites. It is also reported to possess
antifertility, anticancer, antidiabetic, antifungal, antimicrobial, cardioprotective,
analgesic, antispasmodic and adaptogenic activities. Tulsi protects body against
physical, chemical, metabolic and psychological stresses, against industrial
pollutants and heavy metals, improves memory and cognitive functions, and
normalizes blood glucose, BP and lipid levels. It is believed that daily use of Tulsi
leaves on empty stomach increases immunity, and twenty-one fresh leaves
ground into paste with yogurt (curd) and used 2–3 times a day with honey on
empty stomach prevent cancer and improve memory. In the Philippines, the
decocted leaves are used for aromatic baths, and decoction of roots and leaves is
claimed to be useful for gonorrhea. Leaves and stems contain saponins,
triterpenoids, flavonoids, and tannins; the phenolic compounds include ros-
marinic acid, propanoic acid, apigenin, cirsimaritin, isothymusin and isothy-
monin. Supplementation of diet with leaf powder of diabetic rats significantly
reduced FBG, TC, TGs, phospholipids and total lipids, and improved antioxidant
status. Adding fresh leaves to the diet significantly decreased serum TC, TGs,
phospholipid and LDL-C and increased HDL-C and total fecal sterol contents of
normal, and hypercholesterolemic rabbits. Leaf extract also exhibited significant
blood sugar-lowering activity in normal and diabetic rats. In a crossover single
blind RCT, treatment of Indian NIDDM patients with leaves reduced fasting

© Springer Nature Switzerland AG 2020 1339

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_138
1340 Ocimum tenuiflorum L.

and postprandial blood glucose levels during treatment. Aqueous extract twice
daily after meal to patients suffering from GAD, significantly ameliorated anxiety
symptoms and relieved the associated stress.

Keywords
Badruj

Basilic sacré

Heiliges basilikum Holy basil

Kâlâ tulsi





Kamimebouki Manjericão-pequeno Sheng luo le Tulasi Tulsi

Vernaculars: Urd.: Tulsi; Hin.: Barandâ, Kâlâ tulsi, Krishna tulasii; San.: Ajaka,
Arjaka, Bharati, Divya, Krishnamul, Paranasa, Surasa, Tulasi, Vishnu-priya, Vrandi;
Ben.: Jiuli, Jiyal, Kalotulsi, Krishna tulasi; Guj.: Tulasi; Mal.: Krishnatulasi, Kun-
nakam, Nallatulluva Tulasi, Shiva-tulasi; Mar.: Kâlâ tulasi, Tulshi; Tam.: Alungai,
Karuntulasi, Kuli mitan, Thulasi; Tel.: Brynda, Gaggera, Gaggerachettu, Gumpina,
Krushnatulasi, Oddhi, Tulasi; Ara.: Badruj, Dohsh, Schadjant; Bur.: Kala-pinsein,
Lun, Pinsein-net; Chi.: Sheng luo le; Dut.: Heilige basilicum, Thaise basilicum;
Eng.: Holy basil, Monks’ basil, Purple-stalked basil; Fre.: Basilic sacré, Basilic sacré
à feuilles vertes, Basilic thaïlandais, Basilie saint; Ger.: Heiliges basilikum, Indis-
ches basilikum; Ita.: Basilico sacro; Jap.: Bajiru hoorii, Kamimebouki; Maly.:
Kemangi, Selasih merah, Selasih siam; Nep.: Krisna; Por.: Manjericão-pequeno,
Manjericão-santo, Tulase (Br.); Sin.: Madurutala; Spa.: Albahaca morada; Tag.:
Sulasi; Tha.: Ka phrao, Ka phrao daeng khon; Vie.: Húng quế, Rau quế.
Description: This is an erect, herbaceous or half-woody, branched plant, up to a
meter high, that is native to India but pantropic in distribution. The stem and
younger parts are covered with spreading hairs; leaves are oblong-ovate and 2–
4.5 cm long, with pointed or blunt tips and somewhat toothed margins. Flowers are
pink or purplish, about 7 mm long, and borne on racemes 5–14 cm long. The calyx
at the time of flowering is about 3 mm long and somewhat larger in fruit; the two
lower teeth are long-awned, the upper one broadly-oblong, and the lateral ones are
very broad. Corolla is very small, scarcely longer than calyx. The nutlets are
somewhat rounded or broadly oblong, slightly compressed, and nearly smooth
(Figs. 1, 2 and 3).CXVII
Actions and Uses: This immortal plant is the most sacred plant in Hindu religion,
which contains in itself every perfection, cures every ill, and purifies and guides to
the heavenly paradise those who worship it.XL The plant is mentioned in Charak
Samhita and Susruta Samhita, the oldest Indian medical texts. Every part of the plant
finds its medicinal use in one form or the other. Charak described it as curative of
Kapha and Vata [67]. All parts are recommended for the treatment of bronchitis,
bronchial asthma, malaria, diarrhea, dysentery, skin diseases, arthritis, painful eye
diseases, chronic fever, and insect bites [92]. It is also reported to possess antifer-
tility, anticancer, antidiabetic, antifungal, antimicrobial, cardioprotective, analgesic,
antispasmodic and adaptogenic activities [11, 90]. Tulsi protects body against
physical, chemical, metabolic and psychological stresses, against industrial pollu-
tants and heavy metals, improves memory and cognitive functions, and normalizes
Ocimum tenuiflorum L. 1341

Fig. 1 Ocimum tenuiflorum, Plant, Gouranga, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Ocimum_tenuiflorum2.jpg

Fig. 2 Ocimum tenuiflorum, Leaf Close Up, Forest & Kim Starr, WikimediaCommons; 3.0
Unported CC BY 3.0, https://commons.wikimedia.org/wiki/File:Starr_080117-1577_Ocimum_
tenuiflorum.jpg; https://creativecommons.org/licenses/by/3.0/deed.en
1342 Ocimum tenuiflorum L.

Fig. 3 Ocimum tenuiflorum, Inflorescence, Muhammad Mahdi Karim, WikimediaCommons;

GNU Free Documentation License 1.2. GNU Version 1.2 only, https://commons.wikimedia.org/
wiki/File:Holy_Basil_flowers.jpg; https://commons.wikimedia.org/wiki/Commons:GNU_Free_
Documentation_License,_version_1.2

blood glucose, BP and lipid levels [22]. Eugenol is regarded as the active constituent
largely responsible for its therapeutic potentials [92]. In Ayurveda, leaves are anti-
catarrhal, expectorant, fragrant and aromatic, and ground with water are applied to
boils; an infusion of leaves is used in malaria, and as stomachic in gastric diseases of
children and hepatic affections. Patients suffering from skin diseases, such as ring-
worm, itches, leprosy, impurity of blood, should drink leaves juice and also apply by
itself or preferably mixed with lemon juice as a paste for radical cure.LXXXIV,CV
Leaves juice is dropped in the ear for earache; the seeds are mucilaginous and
demulcent, and are used as a remedy in genitourinary disorders.LXXXIV It is believed
that daily use of Tulsi leaves on empty stomach increases immunity [79], and
twenty-one fresh leaves ground into paste with yogurt (curd) and used 2–3 times a
day with honey on empty stomach prevent cancer and improve memory [67]. Seeds
contain a pale-yellow colored fixed oil that produces anti-inflammatory activity due
to inhibition of AA metabolism and antihistaminic activity, and antipyretic and
analgesic activities due to PG inhibition. Leaves EO possesses anticoagulant,
immunomodulatory, chemopreventive, hypotensive, hypolipidemic and antioxidant
activities [134]. The plant is used as mosquito repellant in India and South Africa;
Ocimum tenuiflorum L. 1343

dried plant’s decoction is a domestic remedy for croup, catarrh, bronchitis, and for
diarrhea.CV In the Philippines, the decocted leaves are used for aromatic baths, and
decoction of roots and leaves is claimed to be useful for gonorrhea.LVI
Phytoconstituents: Leaves and stems contain saponins, triterpenoids, flavonoids
(orientin, vicenin), and tannins; the phenolic compounds include rosmarinic acid,
propanoic acid, apigenin, cirsimaritin, isothymusin and isothymonin [61, 90], cir-
silineol, and significant amounts of eugenol [61], ocimumosides A and B, and
ocimarin [41], neolignan derivatives [141], and a tetracyclic triterpenoid with
antidiabetic and antilipidemic activities [88, 89]. Leaves also contain significant
amount of Zn, Mn, and Na [108], but results of another study reported only trace
amounts of Cu, Ni, Zn, K, and Na [84]. Leaf EO contains eugenol, euginal (eugenic
acid), urosolic acid, carvacrol, linalool, limatrol, caryophyllene, and methyl carvicol
(estragol) [90]. Eugenol and linalool are considered active constituents of EO that
are responsible for its nematicidal activity [17], and it also strongly inhibits (97%)
COX-1 activity [61]; presence of linolenic acid imparts its antibacterial activity
against S. aureus [134]. Phenylpropanoids (65.2–77.6%) constitute major propor-
tion of the EO composition of O. tenuiflorum from northern India; eugenol,
b-elemene, b-caryophyllene and germacrene D, being the major components [86].
O. tenuiflorum contains the highest content (2.02%) of ursolic acid of the Ocimum
species grown in northeastern Brazil [125]. Joshi [51] reported methyl eugenol
(92.4%) as the principal constituent of EO, comprising 98.9% of the total oil;
eugenol (2.4%) and b-caryophyllene (1.3%) were the minor constituents. However,
Saharkhiz et al. [102] collected aerial parts of cultivated plant in Iran at different
stages of growth, and reported highest EO yield at the full flowering stage and
eugenol as the main compound of floral budding and at the full flowering devel-
opmental stages. Eugenol (41.5%), c-caryophyllene (23.7%) and methyl eugenol
(11.8%) were reported as the major compounds in holy basil oil from Thailand
[147]. Leaves fixed oil showed the presence of five fatty acids: stearic, palmitic,
oleic, linoleic and linolenic acids [127]; a-linolenic acid was the major fatty acid of
the fixed oil [137]. Phenylpropanoid compounds including eugenol and methyl
eugenol were the major constituents of EO from Thailand [139].
Pharmacology: Dhar et al. [26] initially reported hypoglycemic effect of ethanol
leaf extract in rats and antispasmodic activity on isolated guinea pig ileum, whereas
potentiation of hexobarbitone-induced narcosis by aqueous extract, and adaptogenic
or antistress activity were reported by Bhargava and Singh [14]. Later, CNS
depressant and dopaminergic effects were reported [104]. Supplementation of diet
with leaf powder (1%) of diabetic rats significantly reduced FBG [94, 115], TC,
TGs, phospholipids and total lipids [94], and improved antioxidant status [115].
Adding fresh leaves to the diet significantly decreased serum TC, TGs, phospho-
lipid and LDL-C and increased HDL-C and total fecal sterol contents of normal [23,
110], and of hypercholesterolemic rabbits [65]. Leaf extract exhibited significant
blood sugar-lowering activity in normal and STZ-diabetic rats [19]. Aqueous leaf
extract reduced blood sugar of diabetic rabbits by 33% for two and a half hours
[109], significantly reduced FBG, serum lipids, LPO products, improved glucose
1344 Ocimum tenuiflorum L.

tolerance and antioxidant status in rats [16, 45, 48, 71]. Aqueous leaf extract also
protected liver and aortic tissue from hypercholesterolemia-induced oxidative
damage in male albino rabbits and rats [30, 32, 138], and ethanol extract provided
significant protection against cadmium-, DMBA- and diabetes-induced oxidative
stress in rats [47, 75, 96]. Aqueous extract also significantly prevented selenite-
induced cataract in rats [43], and effectively inhibited aldose reductase activity [44].
Leaves reduced cholesterol levels, and lowered restraint stress-induced elevated
LDH and ALP in rats but no hypoglycemic effect [113]. Ethanol extract also
produced a marked fall in blood sugar [21, 54, 83, 145], significantly increased
activities of carbohydrate-metabolizing enzymes to near normal [83], delayed the
development of insulin-resistance [101], improved antioxidant status [81], and
decreased serum cortisol concentration of diabetic rats [33]. Ethanol extract and its
aqueous, butanol and ethyl acetate fractions stimulated insulin secretion from
perfused rat pancreas, isolated rat islets and a clonal rat b-cell line [46]. Chloroform
extract also significantly decreased elevated serum glucose, TC, TG, and LDL-C
levels of diabetic rats [89]. Seed oil administered for four-weeks significantly
decreased LPO, TC, triacylglycerol, LDL-C and VLDL-C of hypercholesterolemic
rabbits [42], and leaves fixed oil decreased blood glucose, serum lipids and levels of
serum creatinine, and increased insulin levels of diabetic rats [137]. Essential and
fixed oils of leaves also protect heart against adverse effects of hypercholes-
terolemia by lowering lipids and countering oxidative stress [139, 140]. However,
seed oil administered to diabetic rabbits for two-weeks did not show any significant
hypoglycemic effect [42].
Aqueous and ethanol extracts ameliorated experimentally-induced cognitive and
memory impairment in mice and rats [34, 50]. Aqueous extract also exhibited
significant anxiolytic and antidepressant activities in restraint stress-induced anxiety
and depression in rats [142]. Ethanol leaf extract also produced significant anxi-
olytic activity in mice, comparable to diazepam [18, 20] but less than alprazolam
[12], and prevented noise exposure-induced stress-caused increase in corticos-
teroids level [52, 112], decreased brain neurotransmitters content [100, 106, 111],
oxidative stress [107], protected against chronic restraint stress-induced cardiac
changes [136], and leukopenia in rats [8]. Pretreatment with Tulsi significantly
protected against chronic (15 days) cerebral hypoperfusion-induced functional
(memory) and structural deficit [4, 149]. Commercial EO exhibited AChE inhibi-
tory activity and eugenol was a potent AChE inhibitor [28]. Fresh leaf homogenate
pretreatment of rats for 30-days significantly protected against isoproterenol-
induced MI, and increased basal myocardial antioxidant enzymes [135]. Pre- and
co-treatment with hydroalcohol leaf extract also protected against isoproterenol-
induced MI in rats [118], but did not protect against apoptotic effects of I/R injury
in rats [78]. Increased levels of inflammation mediators, 5-LOX, COX-2, LTB4 and
TXB2 in isoproterenol-induced MI in rats were significantly reduced by methanol
leaf extract [60]. Fixed oil also exhibited hypotensive, anticoagulant, and CNS
depressant effects [133].
Pretreatment with leaf extracts protected against experimental gastric ulcers in
rats by reducing acid, increasing mucous secretion and cytoprotection [27, 37, 73],
Ocimum tenuiflorum L. 1345

and significantly increased antioxidant activity [57]. Aqueous extract counteracts

meloxicam toxicity in liver and gastrointestinal tract [70]. Fixed oil also exhibits
significant antiulcer, LOX inhibitory, histamine antagonistic and antisecretory
activities [130]. Diet supplemented with powdered leaves prevents hepatotoxicity
of simultaneously administered antitubercular drugs (Isoniazid + Rifampicin +
Pyrazinamide) in guinea pigs [1]. Ethanol leaf extract also significantly protects
against APAP-hepatotoxicity in rats [69], and protects against mercury chloride-
induced nephrotoxicity and hepatotoxicity in mice [119, 120]. Aqueous leaf extract,
at 10 mg/kg/day (i.p.) for 5 consecutive days provided maximum survival against
whole-body exposure to gamma radiation-induced lethality in albino mice [25], and
significantly attenuated radiation induced depletion of GSH and increase in LPO
[24]; pretreatment with isolated flavonoids, orientin and vicenin, also offered
similar protection [144].
Godhwani et al. [35] reported significant anti-inflammatory and analgesic effects,
and a short-lived antipyretic activity of methanol extract and the aqueous suspen-
sion of powdered leaves in rats; it also significantly attenuated chronic neuropathic
pain and decreased oxidative stress in rats [58, 59, 82]. Fixed oil exhibited sig-
nificant anti-inflammatory activity in rats [126, 129, 132], inhibited both COX and
LOX pathways [129], and inhibited increase in vascular/capillary permeability and
leucocytes migration [128]. The triglyceride fraction of fixed oil exhibits better
anti-inflammatory and analgesic activities than the oil [127]. Ethanol and aqueous
leaf extracts also significantly promoted wound healing [121, 122, 143], upregu-
lated TNF-a [36], increased activity of antioxidant enzymes [87, 121, 122], and
helped overcome dexamethasone’s wound healing suppression in rats [143].
Methanol extract shows moderate antibacterial activity against MDR S. typhi
[97], and growth of isolates of S. Typhi resistant to both chloramphenicol and
trimethoprim was significantly inhibited by ethanol leaf extract [74]. Ethanol leaf
extract also exhibited excellent activity against P. falciparum [49], significantly
inhibited growth of clinical isolates of b-lactamase producing MRSA and MSSA
[7], E. coli, K. pneumonia, and P. aeruginosa [117], was bactericidal to E. faecalis
at 40% concentration [39], and active against periodontal pathogens, S. mutans [2,
68], and A. actinomycetemcomitans [29, 72]. Cold aqueous and ethanol leaf extracts
showed significant antifungal activity against T. mentagrophytes, and moderate
activity against T. rubrum, M. gypseum, M. nanum and E. floccosum [10]. Methanol
extract exhibited modest activity against S. aureus and E. coli [146], but significant
activity against S. mutans [77], and the hexane extract inhibited growth of clinical
isolates of N. gonorrhoeae [124]; eugenol was identified as the active constituent
[123]. The EO exhibits broad-spectrum antibacterial activity against B. subtilis, S.
aureus, S. mutans and E. faecalis, and antifungal activity against E. floccosum, M.
gypseum, and S. schenckii [98], inhibits growth of P. acnes with an MIC of 3%
[147], also significant activity against A. niger and S. faecalis, while methyl
eugenol was significantly active against P. aeruginosa [51], E. faecalis [85], and
effectively inhibited growth of C. albicans and C. tropicalis [63, 150]. The oil
inhibits morphological transition in C. albicans and reduces their virulence by
decreasing secretion of hydrolytic enzymes involved in the early stage of infection
1346 Ocimum tenuiflorum L.

[64]. Aerial parts EO obtained at full flowering stage showed potent fungistatic and
fungicidal activities against A. fumigatus, A. clavatus, A. flavus and A. orizae, and
marked antibacterial activity against Sh. flexneri and B. cereus [102]. Treatment of
K. pneumoniae-infected mice with Tulsi oil for 30-days significantly decreased
bacterial load [103]. Seed oil also exhibited significant activity against oral fungal
pathogens, C. albicans, C. krusei, C. tropicalis, C. parapsilosis, C. glabrata and
C. dubliniensis [38], and antibacterial activity against S. aureus, B. pumilus and
P. aeruginosa [131].
Supplementation of diet with Tulsi leaves significantly decreased incidence of
B[a]P-induced carcinomas of stomach and 3′MeDAB-induced hepatomas in mice
[9], and seed oil-supplemented diet also significantly delayed onset and reduced
20-MCA-induced tumor incidence and volume, and increased survival of mice [91].
Topical application of ethanol leaf extract at peri-initiation or post-initiation stage
significantly reduced DMBA-induced skin tumor incidence in mice [93, 99].
Topical application of fresh leaf paste, aqueous extract and ethanol extract, and oral
administration of the extracts also significantly reduced incidence of DMBA-
induced papillomas and squamous cell carcinomas of hamster buccal pouch, and
increased survival rate; oral administration of the aqueous extract being the most
effective [55]. Ethanol leaf extract also reduced incidence of MNNG-induced
gastric carcinomas in rats [76]. Tumor volume and survival rate in chemically-
induced melanoma of mice was significantly reduced by oral administration of the
50% alcoholic aqueous extract [80].
Antifertility activity of aqueous leaf extract in male rats had earlier been reported
[13, 56, 114, 148]. Administration of Tulsi leaves extract to male rats in doses
of 200 mg/kg and 400 mg/kg daily for 15-days significantly decreased sexual
behavioral score [53], and benzene extract treatment (250 mg/kg) for 48-days
reversibly decreased total sperm count, sperm motility, and forward velocity [5];
there was no implantation in female rats mated with the treated male rats [6].
Rabbits supplemented in diet 2 g of fresh leaves daily for 30-days also produced a
significant decrease in sperm count, and serum FSH and LH levels; though, serum
testosterone levels were markedly increased [116].
Clinical Studies: In a crossover single blind RCT, treatment of Indian NIDDM
patients with leaves reduced fasting and postprandial blood glucose levels by 17.6%
and 7.3%, respectively, during treatment [3]. Aqueous extract to patients suffering
from GAD in a dose of 500 mg twice daily after meal significantly ameliorated
anxiety symptoms and relieved the associated stress and depression [15]. Healthy
adult Indian volunteers administered 300 mg of ethanol leaf extract daily in a
capsule or a placebo for 30-days showed significant cognition-enhancing effect of
the extract [105], and healthy volunteers treated with ethanol leaf extract for
four-weeks also showed levels of IFN-c and IL-4, and percentages of T-helper and
NK-cells significantly increased [79]. In a comparative, blinded clinical trial, a Tulsi
mouth rinse composed of ethanol leaf extract suspended in polyethylene glycol and
sterile water was equally effective in reducing plaque and gingivitis as chlorhexi-
dine [40].
Ocimum tenuiflorum L. 1347

Mechanism of Action: Analgesic activity of alcohol extract is suggested to be

mediated both centrally and peripherally [66], whereas anti-inflammatory effects are
mediated through inhibition of both COX and LOX enzymes [129]. Blood glucose
lowering effect could be the result of increased activities of carbohydrate-
metabolizing enzymes [83], and insulinotropic effect [46]. Antioxidant [81, 107,
137, 138], and AChE inhibitory [28, 34] activities may contribute to its CNS
effects. Antifungal activity against C. albicans and C. tropicalis [63, 150], was due
to disruption of ergosterol biosynthesis; linalool was identified responsible for this
activity [62].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: A single oral dose of 50% ethanol leaf extract up to 2,000 mg/kg
and repeated daily dosing up to 800 mg/kg for 28-days were nonlethal and nontoxic
to mice [31]. Aqueous-methanol extract also produced no significant changes in
hematological, pathological and biochemical parameters in rats after being orally
administered daily for 28-days up to a dose of 1,000 mg/kg [95]. LD50 of seed fixed
oil in rats was 42.5 ml/kg and chronic administration of oil to rats in a dose of
3 ml/kg daily was nontoxic [134].
Commentary: Surprisingly, an important plant like holy basil that has religious
significance, enjoys long history of diverse medicinal uses and has shown signifi-
cant pharmacological effects in animals, has not sufficiently been clinically evalu-
ated in RCTs. Significant anticancer activities by all forms of the plant and other
useful activities warrant investigations for clinical applications.

References
1. Adhvaryu MR, Reddy N, Parabia MH. Effects of four Indian medicinal
herbs on isoniazid-, rifampicin- and pyrazinamide-induced hepatic injury
and immunosuppression in guinea pigs. World J Gastroenterol. 2007;13:
3199–205.
2. Agarwal P, Nagesh L. Murlikrishnan: Evaluation of the antimicrobial
activity of various concentrations of Tulsi (Ocimum sanctum) extract
against Streptococcus mutans: an in vitro study. Indian J Dent Res. 2010;
21:357–9.
3. Agrawal P, Rai V, Singh RB. Randomized placebo-controlled, single blind
trial of holy basil leaves in patients with noninsulin-dependent diabetes
mellitus. Int J Clin Pharmacol Ther. 1996;34:406–9.
4. Ahmad A, Khan MM, Raza SS, et al. Ocimum sanctum attenuates oxidative
damage and neurological deficits following focal cerebral ischemia/reper-
fusion injury in rats. Neurol Sci. 2012;33:1239–47.
5. Ahmed M, Ahamed RN, Aladakatti RH, Ghosesawar MG. Reversible
antifertility effect of benzene extract of Ocimum sanctum leaves on sperm
parameters and fructose content in rats. J Basic Clin Physiol Pharmacol.
2002;13:51–9.
1348 Ocimum tenuiflorum L.

6. Ahmed M, Nazeer Ahamed R, Aladakatti RH. Effect of benzene extract

of Ocimum sanctum leaves on cauda epididymis of albino rats. J Basic
Clin Physiol Pharmacol. 2009;20:29–41.
7. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant
extracts on clinical isolates of beta-lactamase producing methicillin
resistant Staphylococcus aureus. J Basic Microbiol. 2005;45:106–14.
8. Archana R, Namasivayam A. Effect of Ocimum sanctum on noise induced
changes in neutrophil functions. J Ethnopharmacol. 2000;73:81–5.
9. Aruna K, Sivaramakrishnan VM. Anticarcinogenic effects of some Indian
plant products. Food Chem Toxicol. 1992;30:953–6.
10. Balakumar S, Rajan S, Thirunalasundari T, Jeeva S. Antifungal activity of
Ocimum sanctum Linn. (Lamiaceae) on clinically isolated dermatophytic
fungi. Asian Pac J Trop Med. 2011;4:654–7.
11. Baliga MS, Jimmy R, Thilakchand KR, et al. Ocimum sanctum L. (Holy
Basil or Tulsi) and its phytochemicals in the prevention and treatment of
cancer. Nutr Cancer. 2013;65 Suppl 1:26–35.
12. Bathala LR, Rao ChV, Manjunath S, et al. Efficacy of Ocimum sanctum
for relieving stress: a preclinical study. J Contemp Dent Pract. 2012;13:
782–6.
13. Batta SK, Santhakumari G. The antifertility effect of Ocimum sanctum and
Hibiscus rosa-sinensis. Indian J Med Res. 1971;59:777–81.
14. Bhargava KP, Singh N. Antistress activity of Ocimum sanctum Linn.
Indian J Med Res. 1981;73:443–8.
15. Bhattacharyya D, Sur TK, Jana U, Debnath PK. Controlled programmed
trial of Ocimum sanctum leaf on generalized anxiety disorders. Nepal Med
Coll J. 2008;10:176–9.
16. Chandra A, Mahdi AA, Singh RK, et al. Effect of Indian herbal hypo-
glycemic agents on antioxidant capacity and trace elements content in
diabetic rats. J Med Food. 2008;11:506–12.
17. Chatterjee A, Sukul NC, Laskar S, Ghoshmajumdar S. Nematicidal princi-
ples from two species of lamiaceae. J Nematol. 1982;14:118–20.
18. Chatterjee M, Verma P, Maurya R, Palit G. Evaluation of ethanol leaf extract
of Ocimum sanctum in experimental models of anxiety and depression.
Pharm Biol. 2011;49:477–83.
19. Chattopadhyay RR. A comparative evaluation of some blood sugar
lowering agents of plant origin. J Ethnopharmacol. 1999;67:367–72.
20. Chattopadhyay RR. Anxiolytic activity of Ocimum sanctum leaf extract.
Anc Sci Life. 1994;14:108–11.
21. Chattopadhyay RR. Hypoglycemic effect of Ocimum sanctum leaf extract
in normal and streptozotocin diabetic rats. Indian J Exp Biol. 1993;31:
891–3.
22. Cohen MM. Tulsi—Ocimum sanctum: a herb for all reasons. J Ayurveda
Integr Med. 2014;5:251–9.
Ocimum tenuiflorum L. 1349

23. Dahiya K, Sethi J, Dhankhar R, et al. Effect of Ocimum sanctum on homo-

cysteine levels and lipid profile in healthy rabbits. Arch Physiol Biochem.
2011;117:8–11.
24. Devi PU, Ganasoundari A. Modulation of glutathione and antioxidant
enzymes by Ocimum sanctum and its role in protection against radiation
injury. Indian J Exp Biol. 1999;37:262–8.
25. Devi PU, Ganasoundari A. Radioprotective effect of leaf extract of Indian
medicinal plant Ocimum sanctum. Indian J Exp Biol. 1995;33:205–8.
26. Dhar MM, Dhawan BN, Mehrotra BN, Roy C. Screening of Indian plants
for biological activity. Part I. Indian J Exp Biol. 1968;6:232–47.
27. Dharmani P, Kuchibhotla VK, Maurya R, et al. Evaluation of antiulcero-
genic and ulcer- healing properties of Ocimum sanctum Linn. J Ethnophar-
macol. 2004;93:197–206.
28. Dohi S, Terasaki M, Makino M. Acetylcholinesterase inhibitory activity
and chemical composition of commercial essential oils. J Agric Food
Chem. 2009;57:4313–8.
29. Eswar P, Devaraj CG, Agarwal P. Antimicrobial activity of Tulsi {Ocimum
Sanctum (Linn.)} extract on a periodontal pathogen in human dental plaque:
an in vitro study. J Clin Diagn Res. 2016;10:ZC53–56.
30. Gamboa-Gómez C, Salgado LM, González-Gallardo A, et al. Consump-
tion of Ocimum sanctum L. and Citrus paradisi infusions modulates lipid
metabolism and insulin resistance in obese rats. Food Funct. 2014;5:
927–35.
31. Gautam MK, Goel RK. Toxicological study of Ocimum sanctum Linn.
leaves: hematological, biochemical, and histopathological studies. J Toxi-
col. 2014;2014:135654.
32. Geetha RK, Vasudevan DM. Inhibition of lipid peroxidation by botanical
extracts of Ocimum sanctum: in vivo and in vitro studies. Life Sci. 2004;
76:21–8.
33. Gholap S, Kar A. Hypoglycaemic effects of some plant extracts are possibly
mediated through inhibition in corticosteroid concentration. Pharmazie. 2004;
59:876–8.
34. Giridharan VV, Thandavarayan RA, Mani V, et al. Ocimum sanctum
Linn. leaf extracts inhibit acetylcholinesterase and improve cognition in
rats with experimentally induced dementia. J Med Food. 2011;14:912–9.
35. Godhwani S, Godhwani JL, Vyas DS. Ocimum sanctum: an experimental
study evaluating its anti-inflammatory, analgesic and antipyretic activity in
animals. J Ethnopharmacol. 1987;21:153–63.
36. Goel A, Kumar S, Singh DK, Bhatia AK. Wound healing potential of
Ocimum sanctum Linn. with induction of tumor necrosis factor-alpha.
Indian J Exp Biol. 2010;48:402–6.
37. Goel RK, Sairam K, Dorababu M, et al. Effect of standardized extract
of Ocimum sanctum Linn. on gastric mucosal offensive and defensive
factors. Indian J Exp Biol. 2005;43:715–21.
1350 Ocimum tenuiflorum L.

38. Gopalkrishna AH, Seshagiri M, Muddaiah S, Shashidara R. In vitro

antifungal activity of different components of Centratherum anthelminti-
cum and Ocimum sanctum seed oils and their synergism against oral
pathogenic fungi. J Dent Res Dent Clin Dent Prospects. 2016;10:92–8.
39. Gupta A, Duhan J, Tewari S, et al. Comparative evaluation of antimicro-
bial efficacy of Syzygium aromaticum, Ocimum sanctum and Cinnamo-
mum zeylanicum plant extracts against Enterococcus faecalis: a prelimi-
nary study. Int Endod J. 2013;46:775–83.
40. Gupta D, Bhaskar DJ, Gupta RK, et al. A randomized controlled clinical
trial of Ocimum sanctum and chlorhexidine mouthwash on dental plaque
and gingival inflammation. J Ayurveda Integr Med. 2014;5:109–16.
41. Gupta P, Yadav DK, Siripurapu KB, et al. Constituents of Ocimum sanc-
tum with antistress activity. J Nat Prod. 2007;70:1410–6.
42. Gupta S, Mediratta PK, Singh S, et al. Antidiabetic, antihypercholestero-
laemic and antioxidant effect of Ocimum sanctum (Linn.) seed oil. Indian J
Exp Biol. 2006;44:300–4.
43. Gupta SK, Srivastava S, Trivedi D, et al. Ocimum sanctum modulates
selenite-induced cataractogenic changes and prevents rat lens opacifica-
tion. Curr Eye Res. 2005;30:583–91.
44. Halder N, Joshi S, Gupta SK. Lens aldose reductase inhibiting potential of
some indigenous plants. J Ethnopharmacol. 2003;86:113–6.
45. Halim EM, Mukhopadhyay AK. Effect of Ocimum sanctum (Tulsi) and
vitamin E on biochemical parameters and retinopathy in streptozotocin
induced diabetic rats. Indian J Clin Biochem. 2006;21:181–8.
46. Hannan JM, Marenah L, Ali L, et al. Ocimum sanctum leaf extracts
stimulate insulin secretion from perfused pancreas, isolated islets and
clonal pancreatic beta-cells. J Endocrinol. 2006;189:127–36.
47. Husain I, Chander R, Saxena JK, Mahdi AA, Mahdi F. Antidyslipidemic
effect of Ocimum sanctum leaf extract in streptozotocin induced diabetic
rats. Indian J Clin Biochem. 2015;30:72–7.
48. Hussain EH, Jamil K, Rao M. Hypoglycaemic, hypolipidemic and antioxi-
dant properties of Tulsi (Ocimum sanctum Linn.) on streptozotocin induced
diabetes in rats. Indian J Clin Biochem. 2001;16:190–4.
49. Inbaneson SJ, Sundaram R, Suganthi P. In vitro antiplasmodial effect of
ethanolic extracts of traditional medicinal plant Ocimum species against
Plasmodium falciparum. Asian Pac J Trop Med. 2012;5:103–6.
50. Joshi H, Parle M. Evaluation of nootropic potential of Ocimum sanctum
Linn. in mice. Indian J Exp Biol. 2006;44:133–6.
51. Joshi RK. Chemical composition, in vitro antimicrobial and antioxidant
activities of the essential oils of Ocimum gratissimum, O. sanctum and
their major constituents. Indian J Pharm Sci. 2013;75:457–62.
52. Jothie Richard E, Illuri R, Bethapudi B, et al. Antistress activity of
Ocimum sanctum: possible effects on hypothalamic-pituitary-adrenal axis.
Phytother Res. 2016;30:805–14.
Ocimum tenuiflorum L. 1351

53. Kantak NM, Gogate MG. Effect of short-term administration of Tulsi

(Ocimum sanctum Linn.) on reproductive behaviour of adult male rats.
Indian J Physiol Pharmacol. 1992;36:109–11.
54. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
55. Karthikeyan K, Ravichandran P, Govindasamy S. Chemopreventive effect
of Ocimum sanctum on DMBA-induced hamster buccal pouch carcino-
genesis. Oral Oncol. 1999;35:112–9.
56. Kasinathan S, Ramakrishnan S, Basu SL. Antifertility effect of Ocimum
sanctum L. Indian J Exp Biol. 1972;10:23–5.
57. Kath RK, Gupta RK. Antioxidant activity of hydroalcoholic leaf extract of
Ocimum sanctum in animal models of peptic ulcer. Indian J Physiol
Pharmacol. 2006;50:391–6.
58. Kaur G, Bali A, Singh N, Jaggi AS. Ameliorative potential of Ocimum
sanctum in chronic constriction injury-induced neuropathic pain in rats. An
Acad Bras Cienc. 2015;87:417–29.
59. Kaur G, Jaggi AS, Singh N. Exploring the potential effect of Oci-
mum sanctum in vincristine-induced neuropathic pain in rats. J Brachial
Plex Peripher Nerve Inj. 2010;5:3.
60. Kavitha S, John F, Indira M. Amelioration of inflammation by phenolic
rich methanolic extract of Ocimum sanctum Linn. leaves in isoproterenol
induced myocardial infarction. Indian J Exp Biol. 2015;53:632–40.
61. Kelm MA, Nair MG, Strasburg GM, DeWitt DL. Antioxidant and
cyclooxygenase inhibitory phenolic compounds from Ocimum sanctum
Linn. Phytomedicine. 2000;7:7–13.
62. Khan A, Ahmad A, Akhtar F, et al. Ocimum sanctum essential oil and its
active principles exert their antifungal activity by disrupting ergosterol
biosynthesis and membrane integrity. Res Microbiol. 2010;161:816–23.
63. Khan A, Ahmad A, Manzoor N, Khan LA. Antifungal activities of
Ocimum sanctum essential oil and its lead molecules. Nat Prod Commun.
2010;5:345–9.
64. Khan A, Ahmad A, Xess I, Khan LA, Manzoor N. Ocimum sanctum
essential oil inhibits virulence attributes in Candida albicans. Phyto-
medicine. 2014;21:448–52.
65. Khanna N, Arora D, Halder S, et al. Comparative effect of Ocimum sanc-
tum, Commiphora mukul, folic acid and ramipril on lipid peroxidation
in experimentally-induced hyperlipidemia. Indian J Exp Biol. 2010;48:
299–305.
66. Khanna N, Bhatia J. Antinociceptive action of Ocimum sanctum (Tulsi) in
mice: possible mechanisms involved. J Ethnopharmacol. 2003;88:293–6.
67. Khosla MK. Sacred Tulsi (Ocimum sanctum L.) in traditional medicine
and pharmacology. Anc Sci Life. 1995;15:53–61.
1352 Ocimum tenuiflorum L.

68. Kochikar Pai R, Bhat SS, Salman A, Chandra J. Use of an extract of Indian
sacred plant Ocimum sanctum as an anticariogenic agent: an in vitro study.
Int J Clin Pediatr Dent. 2015;8:99–101.
69. Lahon K, Das S. Hepatoprotective activity of Ocimum sanctum alcoholic
leaf extract against paracetamol-induced liver damage in albino rats.
Pharmacognosy Res. 2011;3:13–8.
70. Mahaprabhu R, Bhandarkar AG, Jangir BL, et al. Ameliorative effect of
Ocimum sanctum on meloxicam induced toxicity in wistar rats. Toxicol
Int. 2011;18:130–6.
71. Mahdi AA, Chandra A, Singh RK, et al. Effect of herbal hypoglycemic
agents on oxidative stress and antioxidant status in diabetic rats. Indian J
Clin Biochem. 2003;18:8–15.
72. Mallikarjun S, Rao A, Rajesh G, Shenoy R, Pai M. Antimicrobial efficacy
of Tulsi leaf (Ocimum sanctum) extract on periodontal pathogens: an
in vitro study. J Indian Soc Periodontol. 2016;20:145–50.
73. Mandal S, Das DN, De K, et al. Ocimum sanctum Linn.—a study on
gastric ulceration and gastric secretion in rats. Indian J Physiol Pharmacol.
1993;37:91–2.
74. Mandal S, Mandal MD, Pal NK. Enhancing chloramphenicol and
trimethoprim in vitro activity by Ocimum sanctum Linn. (Lamiaceae) leaf
extract against Salmonella enterica serovar Typhi. Asian Pac J Trop Med.
2012;5:220–4.
75. Manikandan P, Murugan RS, Abbas H, et al. Ocimum sanctum Linn.
(Holy Basil) ethanolic leaf extract protects against 7,12-dimethylbenz(a)
anthracene-induced genotoxicity, oxidative stress, and imbalance in
xenobiotic-metabolizing enzymes. J Med Food. 2007;10:495–502.
76. Manikandan P, Vidjaya Letchoumy P, Prathiba D, Nagini S. Proliferation,
angiogenesis and apoptosis-associated proteins are molecular targets for
chemoprevention of MNNG-induced gastric carcinogenesis by ethano-
lic Ocimum sanctum leaf extract. Singapore Med J. 2007;48:645–51.
77. Mistry KS, Sanghvi Z, Parmar G, Shah S. The antimicrobial activity of
Azadirachta indica, Mimusops elengi, Tinospora cardifolia, Ocimum
sanctum and 2% chlorhexidine gluconate on common endodontic patho-
gens: an in vitro study. Eur J Dent. 2014;8:172–7.
78. Mohanty I, Arya DS, Gupta SK. Effect of Curcuma longa and Oci-
mum sanctum on myocardial apoptosis in experimentally induced myocar-
dial ischemic-reperfusion injury. BMC Complement Altern Med. 2006;6:3.
79. Mondal S, Varma S, Bamola VD, et al. Double-blinded randomized
controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum
Linn.) leaf extract on healthy volunteers. J Ethnopharmacol. 2011;136:
452–6.
80. Monga J, Sharma M, Tailor N, Ganesh N. Antimelanoma and radiopro-
tective activity of alcoholic aqueous extract of different species of Ocimum
in C(57)BL mice. Pharm Biol. 2011;49:428–36.
Ocimum tenuiflorum L. 1353

81. Muralikrishnan G, Pillai SK, Shakeel F. Protective effects of Ocimum

sanctum on lipid peroxidation and antioxidant status in streptozotocin-
induced diabetic rats. Nat Prod Res. 2012;26:474–8.
82. Muthuraman A, Diwan V, Jaggi AS, et al. Ameliorative effects of Ocimum
sanctum in sciatic nerve transection-induced neuropathy in rats. J Ethno-
pharmacol. 2008;120:56–62.
83. Narendhirakannan RT, Subramanian S, Kandaswamy M. Biochemical
evaluation of antidiabetogenic properties of some commonly used Indian
plants on streptozotocin-induced diabetes in experimental rats. Clin Exp
Pharmacol Physiol. 2006;33:1150–7.
84. Narendhirakannan RT, Subramanian S, Kandaswamy M. Mineral content
of some medicinal plants used in the treatment of diabetes mellitus. Biol
Trace Elem Res. 2005;103:109–15.
85. Navin M, Ajay L, Naseem S, et al. Preliminary ex-vivo and an animal
model evaluation of Ocimum sanctum’s essential oil extract for its
antibacterial and anti-inflammatory properties. Oral Health Dent Manag.
2013;12:174–9.
86. Padalia RC, Verma RS. Comparative volatile oil composition of
four Ocimum species from northern India. Nat Prod Res. 2011;25:569–75.
87. Panda S, Kar A. Ocimum sanctum leaf extract in the regulation of thyroid
function in the male mouse. Pharmacol Res. 1998;38:107–10.
88. Patil R, Patil R, Ahirwar B, Ahirwar D. Isolation and characterization of
antidiabetic component (bioactivity-guided fractionation) from Ocimum
sanctum L. (Lamiaceae) aerial part. Asian Pac J Trop Med. 2011;4:278–82.
89. Patil RN, Patil RY, Ahirwar B, Ahirwar D. Evaluation of antidiabetic and
related actions of some Indian medicinal plants in diabetic rats. Asian Pac J
Trop Med. 2011;4:20–3.
90. Pattanayak P, Behera P, Das D, Panda SK. Ocimum sanctum Linn.
A reservoir plant for therapeutic applications: an overview. Pharmacogn
Rev. 2010;4:95–105.
91. Prakash J, Gupta SK. Chemopreventive activity of Ocimum sanctum seed
oil. J Ethnopharmacol. 2000;72:29–34.
92. Prakash P, Gupta N. Therapeutic uses of Ocimum sanctum Linn. (Tulsi)
with a note on eugenol and its pharmacological actions: a short review.
Indian J Physiol Pharmacol. 2005;49:125–31.
93. Prashar R, Kumar A, Banerjee S, Rao AR. Chemopreventive action by an
extract from Ocimum sanctum on mouse skin papillomagenesis and its
enhancement of skin glutathione S-transferase activity and acid soluble
sulfhydryl level. Anticancer Drugs. 1994;5:567–72.
94. Rai V, Iyer U, Mani UV. Effect of Tulasi (Ocimum sanctum) leaf powder
supplementation on blood sugar levels, serum lipids and tissue lipids in
diabetic rats. Plant Foods Hum Nutr. 1997;50:9–16.
1354 Ocimum tenuiflorum L.

95. Raina P, Chandrasekaran CV, Deepak M, Agarwal A, Ruchika KG.

Evaluation of subacute toxicity of methanolic/aqueous preparation of aerial
parts of O. sanctum in Wistar rats: clinical, haematological, biochemical
and histopathological studies. J Ethnopharmacol. 2015;175:509–17.
96. Ramesh B, Satakopan VN. Antioxidant activities of hydroalcoholic extract
of Ocimum sanctum against cadmium induced toxicity in rats. Indian J
Clin Biochem. 2010;25:307–10.
97. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
98. Rao BR, Kotharia SK, Rajput DK, et al. Chemical and biological diversity
in fourteen selections of four Ocimum species. Nat Prod Commun. 2011;
6:1705–10.
99. Rastogi S, Shukla Y, Paul BN, et al. Protective effect of Ocimum sanctum
on 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene and aflatoxin
B1 induced skin tumorigenesis in mice. Toxicol Appl Pharmacol. 2007;
224:228–40.
100. Ravindran R, Rathinasamy SD, Samson J, Senthilvelan M. Noise-stress-
induced brain neurotransmitter changes and the effect of Ocimum sanctum
(Linn.) treatment in albino rats. J Pharmacol Sci. 2005;98:354–60.
101. Reddy SS, Karuna R, Baskar R, Saralakumari D. Prevention of insulin
resistance by ingesting aqueous extract of Ocimum sanctum to
fructose-fed rats. Horm Metab Res. 2008;40:44–9.
102. Saharkhiz MJ, Kamyab AA, Kazerani NK, et al. Chemical compositions
and antimicrobial activities of Ocimum sanctum L. essential oils at
different harvest stages. Jundishapur J Microbiol. 2014;8:e13720.
103. Saini A, Sharma S, Chhibber S. Induction of resistance to respiratory tract
infection with Klebsiella pneumoniae in mice fed on a diet supplemented
with Tulsi (Ocimum sanctum) and clove (Syzgium aromaticum) oils.
J Microbiol Immunol Infect. 2009;42:107–13.
104. Sakina MR, Dandiya PC, Hamdard ME, Hameed A. Preliminary psy-
chopharmacological evaluation of Ocimum sanctum leaf extract. J Ethno-
pharmacolgy. 1990;28:143–50.
105. Sampath S, Mahapatra SC, Padhi MM, Sharma R, Talwar A. Holy basil
(Ocimum sanctum Linn.) leaf extract enhances specific cognitive param-
eters in healthy adult volunteers: a placebo-controlled study. Indian J
Physiol Pharmacol. 2015;59:69–77.
106. Samson J, Sheela Devi R, Ravindran R, Senthilvelan M. Biogenic amine
changes in brain regions and attenuating action of Ocimum sanctumin
noise exposure. Pharmacol Biochem Behav. 2006;83:67–75.
107. Samson J, Sheeladevi R, Ravindran R. Oxidative stress in brain and anti-
oxidant activity of Ocimum sanctum in noise exposure. Neurotoxicology.
2007;28:679–85.
Ocimum tenuiflorum L. 1355

108. Samudralwar DL, Garg AN. Minor and trace elemental determination in
the Indian herbal and other medicinal preparations. Biol Trace Elem Res.
1996;54:113–21.
109. Santoshkumari KS, Devi KS. Hypoglycemic effect of a few medicinal
plants. Anc Sci Life. 1990;9:221–3.
110. Sarkar A, Lavania SC, Pandey DN, Pant MC. Changes in the blood lipid
profile after administration of Ocimum sanctum (Tulsi) leaves in the
normal albino rabbits. Indian J Physiol Pharmacol. 1994;38:311–2.
111. Sembulingam K, Sembulingam P, Namasivayam A. Effect of Ocimum
sanctum Linn. on the changes in central cholinergic system induced by
acute noise stress. J Ethnopharmacol. 2005;96:477–82.
112. Sembulingam K, Sembulingam P, Namasivayam A. Effect of Ocimum
sanctum Linn. on noise induced changes in plasma corticosterone level.
Indian J Physiol Pharmacol. 1997;41:139–43.
113. Sen P, Maiti PC, Puri S, et al. Mechanism of antistress activity of
Ocimum sanctum Linn., eugenol and Tinospora malabarica in experi-
mental animals. Indian J Exp Biol. 1992;30:592–6.
114. Seth SD, Johri N, Sundaram KR. Antispermatogenic effect of Ocimum
sanctum. Indian J Exp Biol. 1981;19:975–6.
115. Sethi J, Sood S, Seth S, Talwar A. Evaluation of hypoglycemic and
antioxidant effect of Ocimum sanctum. Indian J Clin Biochem. 2004;
19:152–5.
116. Sethi J, Yadav M, Sood S, et al. Effect of Tulsi (Ocimum Sanctum Linn.)
on sperm count and reproductive hormones in male albino rabbits. Int J
Ayurveda Res. 2010;1:208–10.
117. Sharma A, Chandraker S, Patel VK, Ramteke P. Antibacterial activity of
medicinal plants against pathogens causing complicated urinary tract
infections. Indian J Pharm Sci. 2009;71:136–9.
118. Sharma M, Kishore K, Gupta SK, et al. Cardioprotective potential
of Ocimum sanctum in isoproterenol induced myocardial infarction in rats.
Mol Cell Biochem. 2001;225:75–83.
119. Sharma MK, Kumar M, Kumar A. Ocimum sanctum aqueous leaf extract
provides protection against mercury induced toxicity in Swiss albino mice.
Indian J Exp Biol. 2002;40:1079–82.
120. Sharma MK, Kumar M, Kumar A. Protection against mercury-induced renal
damage in Swiss albino mice by Ocimum sanctum. Environ Toxicol
Pharmacol. 2005;19:161–7.
121. Shetty S, Udupa S, Udupa L, Somayaji N. Wound healing activity
of Ocimum sanctum Linn. with supportive role of antioxidant enzymes.
Indian J Physiol Pharmacol. 2006;50:163–8.
122. Shetty S, Udupa S, Udupa L. Evaluation of antioxidant and wound healing
effects of alcoholic and aqueous extract of Ocimum sanctum Linn. in rats.
Evid Based Complement Alternat Med. 2008;5:95–101.
1356 Ocimum tenuiflorum L.

123. Shokeen P, Bala M, Singh M, Tandon V. In vitro activity of eugenol, an

active component from Ocimum sanctum, against multiresistant and
susceptible strains of Neisseria gonorrhoeae. Int J Antimicrob Agents.
2008;32:174–9.
124. Shokeen P, Ray K, Bala M, Tandon V. Preliminary studies on activity of
Ocimum sanctum, Drynaria quercifolia, and Annona squamosa against
Neisseria gonorrhoeae. Sex Transm Dis. 2005;32:106–11.
125. Silva MG, Vieira IG, Mendes FN, et al. Variation of ursolic acid content
in eight Ocimum species from northeastern Brazil. Molecules. 2008;13:
2482–7.
126. Singh S, Majumdar DK, Rehan HM. Evaluation of anti-inflammatory
potential of fixed oil of Ocimum sanctum (Holybasil) and its possible
mechanism of action. J Ethnopharmacol. 1996;54:19–26.
127. Singh S, Majumdar DK, Yadav MR. Chemical and pharmacological studies
on fixed oil of Ocimum sanctum. Indian J Exp Biol. 1996;34:1212–5.
128. Singh S, Majumdar DK. Effect of Ocimum sanctum fixed oil on vascular
permeability and leucocytes migration. Indian J Exp Biol. 1999;37:1136–8.
129. Singh S, Majumdar DK. Evaluation of anti-inflammatory activity of fatty
acids of Ocimum sanctum fixed oil. Indian J Exp Biol. 1997;35:380–3.
130. Singh S, Majumdar DK. Evaluation of the gastric antiulcer activity of fixed
oil of Ocimum sanctum (Holy Basil). J Ethnopharmacol. 1999;65:13–9.
131. Singh S, Malhotra M, Majumdar DK. Antibacterial activity of Ocimum
sanctum L. fixed oil. Indian J Exp Biol. 2005;43:835–7.
132. Singh S, Nair V, Jain S, Gupta YK. Evaluation of anti-inflammatory
activity of plant lipids containing alpha-linolenic acid. Indian J Exp Biol.
2008;46:453–6.
133. Singh S, Rehan HM, Majumdar DK. Effect of Ocimum sanctum fixed oil
on blood pressure, blood clotting time and pentobarbitone-induced
sleeping time. J Ethnopharmacol. 2001;78:139–43.
134. Singh S, Taneja M, Majumdar DK. Biological activities of Ocimum sanc-
tum L. fixed oil—an overview. Indian J Exp Biol. 2007;45:403–12.
135. Sood S, Narang D, Dinda AK, Maulik SK. Chronic oral administration of
Ocimum sanctum Linn. augments cardiac endogenous antioxidants and
prevents isoproterenol-induced myocardial necrosis in rats. J Pharm
Pharmacol. 2005;57:127–33.
136. Sood S, Narang D, Thomas MK, et al. Effect of Ocimum sanctum Linn. on
cardiac changes in rats subjected to chronic restraint stress. J Ethnophar-
macol. 2006;108:423–7.
137. Suanarunsawat T, Anantasomboon G, Piewbang C. Antidiabetic and
antioxidative activity of fixed oil extracted from Ocimum sanctum L.
leaves in diabetic rats. Exp Ther Med. 2016;11:832–40.
138. Suanarunsawat T, Ayutthaya WD, Songsak T, et al. Lipid-lowering and
antioxidative activities of aqueous extracts of Ocimum sanctum L. leaves
in rats fed with a high- cholesterol diet. Oxid Med Cell Longev.
2011;2011:962025.
Ocimum tenuiflorum L. 1357

139. Suanarunsawat T, Boonnak T, Na Ayutthaya WD, Thirawarapan S.

Antihyperlipidemic and cardioprotective effects of Ocimum sanctum L.
fixed oil in rats fed a high fat diet. J Basic Clin Physiol Pharmacol.
2010;21:387–400.
140. Suanarunsawat T, Devakul Na Ayutthaya W, Songsak T, et al. Antioxi-
dant activity and lipid-lowering effect of essential oils extracted from
Ocimum sanctum L. leaves in rats fed with a high cholesterol diet. J Clin
Biochem Nutr. 2010;46:52–9.
141. Suzuki A, Shirota O, Mori K, et al. Leishmanicidal active constituents
from Nepalese medicinal plant Tulsi (Ocimum sanctum L.). Chem Pharm
Bull (Tokyo). 2009;57:245–51.
142. Tabassum I, Siddiqui ZN, Rizvi SJ. Effects of Ocimum sanctum and
Camellia sinensis on stress-induced anxiety and depression in male albino
Rattus norvegicus. Indian J Pharmacol. 2010;42:283–8.
143. Udupa SL, Shetty S, Udupa AL, Somayaji SN. Effect of Ocimum sanc-
tum Linn. on normal and dexamethasone suppressed wound healing.
Indian J Exp Biol. 2006;44:49–54.
144. Uma Devi P, Ganasoundari A, Rao BS, Srinivasan KK. In vivo radiopro-
tection by ocimum flavonoids: survival of mice. Radiat Res. 1999;151:
74–8.
145. Vats V, Grover JK, Rathi SS. Evaluation of antihyperglycemic and
hypoglycemic effect of Trigonella foenum-graecum Linn., Ocimum sanc-
tum Linn. and Pterocarpus marsupium Linn. in normal and alloxanized
diabetic rats. J Ethnopharmacol. 2002;79:95–100.
146. Vijayalakshmi S, Arunkumar V, Anju D, et al. Comparative antimicrobial
activities of Emblica officinalis and Ocimum sanctum. Anc Sci Life. 2007;
27:1–6.
147. Viyoch J, Pisutthanan N, Faikreua A, et al. Evaluation of in vitro
antimicrobial activity of Thai basil oils and their microemulsion formulas
against Propionibacterium acnes. Int J Cosmet Sci. 2006;28:125–33.
148. Vohora SB, Garg SK, Chaudhury RR. Antifertility screening of plants. 3.
Effect of six indigenous plants on early pregnancy in albino rats. Indian J
Med Res. 1969;57:893–9.
149. Yanpallewar SU, Rai S, Kumar M, Acharya SB. Evaluation of antioxidant
and neuroprotective effect of Ocimum sanctum on transient cerebral
ischemia and long-term cerebral hypoperfusion. Pharmacol Biochem Behav.
2004;79:155–64.
150. Zomorodian K, Ghadiri P, Saharkhiz MJ, et al. Antimicrobial activity of
seven essential oils from Iranian aromatic plants against common causes of
oral infections. Jundishapur J Microbiol. 2015;8:e17766.
Operculina turpethum (L.) Silva Manso
(Convolvulaceae)

(Syns.: Ipomoea turpethum R.Br.; I. anceps L.; Merremia turpethum (L.) Shah &
Bhatt.)

Abstract
A perennial climber, the plant is pantropic in distribution, but especially found in
India, China, Sri Lanka, and Australia. Two varieties, white and black, are
mentioned in the literature; some using them interchangeably without any
distinction. White variety is commonly used as a cathartic and laxative, resem-
bling jalap in its action; the black variety is drastic in action and not generally used
medicinally. The rhizomes/roots are soft phlegm-purgative, and with zingiber
thick sputum purgative, and used for the treatment of phlegmatic and nervous
diseases, such as arthritis, gout, sciatica, paralysis, palsy, asthma and cough. It is
especially used as a purgative in cases of ascites, and in the presence of intestinal
worms. In Ayurveda, the root powder is used for the treatment of rheumatism,
flatulence, paralysis, scorpion sting and snakebite; it is also used in skin
disorders such as vitiligo. Root is also reported as anti-inflammatory/antipyretic,
and useful in the treatment of ulcers, tumors, neurological disorders, and dysmen-
orrhea, in liver disorders, and has anthelmintic properties. Roots contain alkaloids,
flavonoids, phenols, glycosidic resin, coumarins, turpethin, a and b rhamnose,
fructose, scopoletin, b-sitosterol, betulin, lupeol, essential oil, gum and sugar.
Ethanol root extract restored RBC and WBC counts, and Hb content due to NDMA
hematological toxicity in mice, and protected against APAP-, and NDMA-
hepatotoxicity in rats and mice, and also exhibited moderate antioxidant and
radical scavenging activities. Methanol and hydroalcohol extracts of stem bark
exhibited significant gastric ulcer preventive and protective activities.

Keywords
Fuusen asagao
He guo teng
Indian jalap
Nishotra
Nisoth
Pitohri

Turbith vegetal
Turbud
Turpeth

© Springer Nature Switzerland AG 2020 1359

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_139
1360 Operculina turpethum (L.)

Vernaculars: Urd.: Jalapa, Nisoth, Turbud; Hin.: Nagpatr, Nakpatra, Nisoth,

Panila, Pitohri, Tera; San.: Kalameshi, Kalaparni, Nandi, Nishotra, Tihudi, Triputa,
Trivrit, Trivrutha, Trivrutt; Ben.: Dhud-kalmi, Teori, Tevudi; Mal.: Chivakavera,
Ochani, Sarala, Sivata, Tigade, Tribhandi, Trikolpakkonna; Mar.: Nishottara,
Nisottar, Phutkari; Tam.: Adimbu, Caralam, Civatai, Gunakandi, Kumbham,
Kumpncan, Paganrai, Shivadai, Sivadaiver; Tel.: Ettategada, Nallategada, Tegada
(triangular), Trivrut tellatega; Ara.: Hud-ul-zangi, Turbud; Chi.: 盒果藤, He guo
teng; Eng.: Indian jalap, St. Thomas lidpod, Turpeth; Fre.: Turbith vegetal; Ger.:
Turpeth-trichterwinde; Jap.: Fuusen asagao; Rus.: Operkulina turpet; Tag.: Bang-
bangau, Burakan, Kamokamotihan.
Description: The plant is pantropic in distribution, but especially found in India,
China, Sri Lanka, and Australia. A perennial climber, that exudates a milky juice,
reaches a length of 5 m or more; stems are often purplish, very long, twining and
much twisted, prominently 2- to 4-angled, and narrowly winged; leaves are entire,
ovate, 5–15 cm long, narrowing to a pointed tip, and broad, somewhat heart-shaped
or straight at the base. Inflorescence have few straight flowers that are borne in the
axils of leaves. Sepals are green and ovate to oblong-ovate; the outer two, 2–3 cm
long, are larger than the inner three, and hairy, and somewhat fleshy. Corolla is
white, bell-shaped, and about 4 cm long, with the limb 4 cm wide. Capsule is
rounded, 1–1.5 cm in diameter, and contains normally 4 black, smooth seeds.CXVII
Roots are long, slender, fleshy, and much branched. Black variety of root is powerful
drastic, bitter with a sharp sweet taste, while the white variety is moderately cathartic
and red. The best is whitish, thin, not heavy, and easily breakable, and its powder is
also white; old loses its strength and feels very light.LXIX It is called Tihudi or Trivrit
in Ayurveda due to the triangular shape of its stem [5] (Fig. 1).

Fig. 1 Operculina turpethum, Leaves and Flowers, J.M. Garg, WikimediaCommons; ShareAlike
4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Operculina_turpethum_
(Nisottar)_in_Kawal,_AP_W_IMG_2210.jpg; https://creativecommons.org/licenses/by-sa/4.0/
Operculina turpethum (L.) 1361

Actions and Uses: Two varieties, white and black, are mentioned in the literature;
some using them interchangeably without any distinction. White variety is com-
monly used as a cathartic and laxative, resembling jalap in its action;LXXXIV the
black variety is drastic in action and not generally used medicinally.CV The
rhizomes/roots (temperament, hot 2° and dry 2°) are soft phlegm-purgative, and
with zingiber thick sputum purgative, and used for the treatment of phlegmatic and
nervous diseases, such as arthritis, gout, sciatica, paralysis, palsy, asthma and
cough.XL,LXIX,LXXVII It is especially used as a purgative in cases of ascites, and in
the presence of intestinal worms.L It purifies stomach and uterus,CV and combined
with three myrobalans, long pepper, ginger, Hyoscyamus niger and Beliospermum
montanum, it forms an ideal laxative, useful in melancholia, gout, dropsy, and
leprosy.CV It is particularly beneficial in rheumatic and paralytic affections.LXXXI
Powdered ginger and dried, powdered root bark are beneficial in obesity.1 In
Ayurveda, the root powder is used for the treatment of rheumatism, flatulence,
paralysis, scorpion sting and snakebite; it is also used in skin disorders such as
vitiligo, and cervical lymphadenitis, fistulas, constipation, chronic gout, fever,
bronchitis, hemorrhoids, ulcers, tumors, obesity, jaundice, herpes, and to induce
lacrimation [5]. Root is also reported as anti-inflammatory/antipyretic,LXXX and
useful in the treatment of ulcers, tumors, neurological disorders, and dysmenor-
rhea,IX in liver disorders, and has anthelmintic properties [9]. MortonC mentioned
its uses for constipation, colitis, dysentery, gastritis, inflammation, sluggishness,
colic, and sores; whereas GrieveLV described it as an excellent purge in rheumatism,
and used with wormwood or calomel as a vermifuge for children. In the Philippines,
either pulverized root or alcoholic tincture is used as a drastic purgative.CXVII
Phytoconstituents: Roots contain alkaloids, flavonoids, phenols, glycosidic resin,
coumarins, turpethin, a and b rhamnose, fructose, scopoletin, b-sitosterol, betulin,
lupeol, essential oil [10, 13], gum and sugar; other compounds include turpethinic
acids A–E, cycloartenol, lanosta-5-ene,24-methylene-d-5-lanosterol, acrylamide,
stigma-5,22dien-3-O-b-D-glucopyrano-side, b-sitosterol-b-D-glucoside, 22,23-dihydro-
a-spinosterol-b-D-glucoside, and salicylic acid [5]. It is a source of convolvulin which
causes sneezing.CXXXII Dammarane-type saponins, operculinosides A–D, glycosidic
acids, turpethic acids A–C, and resin glycosides, turpethosides A and B, were reported
from aerial parts [3, 4]. Black turpeth yielded glucose, rhamnose, fructose, and
scopoletin [8].
Pharmacology: Ethanol root extract restored RBC and WBC counts, and Hb
content due to hematological toxicity of NDMA in mice [11], and protected against
APAP- [7], and NDMA- hepatotoxicity in rats and mice [1, 12], and also exhibited
moderate antioxidant and radical scavenging activities [10]. Methanol and hydroal-
cohol extracts of stem bark exhibited significant gastric ulcer preventive and pro-
tective activities [6]. Methanol stem extract for 45-days significantly reduced tumor
size and LPO activity, and increased antioxidants level in DMBA-induced breast
cancer-bearing rats [2]. Resin rich methanol extract of white turpeth exhibited potent

1
Tayyab M: Personal Communication.
1362 Operculina turpethum (L.)

antibacterial activity against B. subtilis and S. aureus, and significant activity against
M. luteus, E. faecalis and Gram-negative bacterial strains E. coli, P. aeruginosa,
S. typhi, and Sh. dysenteriae [15].
Human A/Es, Allergy and Toxicity: Since it causes watery diarrhea, that may
result in dehydration.XL,LXIX,LXXVII
Animal Toxicity: Oral LD50 of ethanol extract of white variety in mice was
reported to be 1,917 mg/kg [11], whereas ethanol extract of roots of black variety
was nontoxic and nonlethal to mice up to a dose of 5,000 mg/kg [14].
Commentary: An important and widely used herb in traditional Indian medicines
for the treatment of phlegmatic diseases, such as arthritis, gout, sciatica, paralysis,
and asthma, but lacks any reported RCTs.

References
1. Ahmad R, Ahmed S, Khan NU, Hasnain AU. Operculina turpethum at-
tenuates N-nitrosodimethylamine induced toxic liver injury and clasto-
genicity in rats. Chem Biol Interact. 2009;181:145–53.
2. Anbuselvam C, Vijayavel K, Balasubramanian MP. Protective effect of
Operculina turpethum against 7,12-dimethyl benz(a)anthracene induced
oxidative stress with reference to breast cancer in experimental rats. Chem
Biol Interact. 2007;168:229–36.
3. Ding W, Jiang ZH, Wu P, et al. Resin glycosides from the aerial parts
of Operculina turpethum. Phytochemistry. 2012;81:165–74.
4. Ding W, Zeng F, Xu L, et al. Bioactive dammarane-type saponins from
Operculina turpethum. J Nat Prod. 2011;74:1868–74.
5. Gupta S, Ved A. Operculina turpethum (Linn.) Silva Manso as a medicinal
plant species: a review on bioactive components and pharmacological
properties. Pharmacogn Rev. 2017;11:158–66.
6. Ignatius V, Narayanan M, Subramanian V, Periyasamy BM. Antiulcer activity
of indigenous plant Operculina turpethum Linn. Evid Based Complement
Alternat Med. 2013;2013:272134.
7. Kumar SV, Sujatha C, Syamala J, Nagasudha B, Mishra SH. Protective
effect of root extract of Operculina turpethum Linn. against paracetamol-
induced hepatotoxicity in rats. Indian J Pharm Sci. 2006;68:32–5.
8. Shah CS, Qadry JS, Krishnamurthy TN. Sugars and coumarins in black
turpeth (Ipomoea turpethum). Indian J Pharm. 1972;34:126.
9. Sharma V, Singh M. Operculina turpethum as a panoramic herbal medicine.
Int J Pharm Sci Res. 2012;3:1–5.
10. Sharma V, Singh M. In vitro radical scavenging activity and phytochemical
screening for evaluation of the antioxidant potential of Operculina
turpethum root extract. J Pharm Res. 2012;5:783–7.
Operculina turpethum (L.) 1363

11. Sharma V, Singh M. Ameliorative effects of Operculina turpethum and its

isolated stigma-5,22dien-3-o-b-D-glucopyranoside on the hematological
parameters of male mice exposed to N-nitrosodimethylamine, a potent
carcinogen. Toxicol Int. 2014;21:29–36.
12. Sharma V, Singh M. Attenuation of N-nitrosodimethylamine induced
hepatotoxicity by Operculina turpethum in Swiss Albino mice. Iran J Basic
Med Sci. 2014;17:73–80.
13. Shareef H, Mahmood S, Farrukh U, Ahmed A, Rizwani GH. In vitro anti-
microbial and phytochemical activity of Operculina turpethum L. Inventi
Impact Ethnopharmacol. 2010;1:50–3.
14. Shareef H, Rizwani GH, Mandukhail SR, Watanabe N, Gilani AH. Studies
on antidiarrhoeal, antispasmodic and bronchodilator activities of Oper-
culina turpethum Linn. BMC Complement Altern Med. 2014;14:479.
15. Shuaib M, Ali A, Ali M, Panda BP, Ahmad MI. Antibacterial activity of
resin rich plant extracts. J Pharm Bioallied Sci. 2013;5:265–9.
Paeonia officinalis L.; Paeonia emodi Royle
(Paeoniaceae)

Abstract
A native to France, Switzerland and Italy, its roots known as Common Paeony or
Garden Paeony , is grown in gardens for its flowers. This drug is the female Paeony
of Dioscorides, and was held in great esteem by the ancients as a valuable remedy
in uterine obstructions, colic, bilious obstructions, dropsy, epilepsy, convulsions
and hysteria. Dioscorides described two kinds of Paeony, male (P. corallina) and
female (P. officinalis); these are also the two kinds described by the Arabic and
Persian writers. Ud-e-Saleeb means “wood of the cross” because the wood on
section shows two lines crossing each other like a cross. Galen described its acrid
qualities and emmenagogue virtues, and its use as an astringent in diarrhea. In
Galen’s time, a superstition prevailed that Paeony root enclosed in a bag and hung
around a child’s neck both prevented epileptic attacks and cured them. According
to Pliny the Elder, the name Paeonia is derived from Paeon, the physician of the
gods, who was the first to discover this plant. Hippocrates mentioned the use of
seeds in uterine obstruction. It is considered emmenagogue in Italy. Paeonia
spp. are also mentioned by Avicenna in his legendary book Canon of Medicine for
the treatment of abnormal uterine bleeding. Roots contain alkaloids, tannins,
saponins, glycosides, flavonoids, terpenes, steroids, carbohydrates and proteins.
Monoterpene galactosides, paeonins A and B, isolated from the roots are potent
LOX inhibitors. Treatment of high-fat diet-induced dyslipidemic rats with
hydroalcoholic and aqueous extracts significantly lowered TC, LDL-C, TGs and
atherogenic index, while HDL-C, SOD, and GPx were significantly elevated.
Aqueous infusion of roots significantly ameliorated CCl4-hepatotoxicity in rats.

Keywords



Chandra Duo-hua-shao-yao Fawania Garden Paeony

Peonia selvatica





Pfingstrose Pione Sinksbloem Ud salap Ud saleeb

Both P. emodi and P. officinalis are described as Ud-e-saleeb in Unani books; though the plants
look similar but differ in flowers.
© Springer Nature Switzerland AG 2020 1365
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_140
1366 Paeonia officinalis L.; Paeonia emodi Royle

Vernaculars: Urd.: Ood saleeb, Ud saleeb; Hin.: Ud salap; San.: Chandra; Mar.:
Ud-salam; Ara.: Fawania, Ud-e-saleeb; Chi.: Duo-hua-shao-yao; Dut.: Sinksbloem,
Tuin-pioen; Eng.: Garden peony, Peony rose; Fre.: Fleur aux convulsions, Fleur de
Saint Georges, Pione, Pivoine des jardins, Pivoine femelle, Pivoine officinale, Rose
de la pentecôte, Rose de Notre-Dame: Ger.: Echte pfingstrose, Gebräuchliche
königsblume, Pfingstrose, Puthanchen; Ita.: Paeonia selvatica, Peonia selvatica.
Description: A native to France, Switzerland and Italy, its roots known as Com-
mon Paeony or Garden Paeony, is grown in gardens for its flowers.CXII An herba-
ceous perennial growing to 60–70 cm tall and wide; leaves divided into 9 leaflets,
and bowl-shaped deep-pink or deep-red flowers, 10–13 cm in diameter, blooms in
late spring. Dried tubers are 2.5–7 cm in length and 1.2–2 cm in diameter, tapering
to a point at both ends; external surface is brown and channelled longitudinally; the
interior is starchy and white. Cortex is hard and gritty, and of a yellowish color; taste
slightly acrid and the central starchy portion is almost tasteless. The roots consist of
oblong tubercles attached by a stout fiber to a rhizome (Figs. 1 and 2).XL
Actions and Uses: This drug is the female Paeony of Dioscorides, and was held in
great esteem by the ancients as a valuable remedy in uterine obstructions, colic,
bilious obstructions, dropsy, epilepsy, convulsions and hysteria. Dioscorides
described two kinds of Paeony, male (P. corallina) and female (P. officinalis); these
are also the two kinds described by the Arabic and Persian writers. Ud-e-Saleeb
means “wood of the cross” because the wood on section shows two lines crossing
each other like a cross. Galen described its acrid qualities and emmenagogue virtues,
and its use as an astringent in diarrhea. In Galen’s time, a superstition prevailed that
Paeony root enclosed in a bag and hung around a child’s neck prevented epileptic
attacks and also cured them. According to Pliny the Elder, the name Paeonia is
derived from Paeon, the physician of the gods, who was the first to discover this plant.
Hippocrates mentioned the use of seeds in uterine obstruction.XL It is considered

Fig. 1 Paeonia emodi, Plant with Flower at Kew Gardens, Dinkum, WikimediaCommons; Share-
Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Paeonia_emodi_-_
Kew_Gardens.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Paeonia officinalis L.; Paeonia emodi Royle 1367

Fig. 2 Paeonia officinalis, Plant with Flowers at Botanical Garden Alpin du Lautaret, Meneerke
Bloem, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wiki
media.org/wiki/File:Paeonia_officinalis_01.JPG; https://creativecommons.org/licenses/by-sa/3.0/
deed.en

emmenagogue in Italy.CXII Paeonia spp. are also mentioned by Avicenna in his

legendary book Canon of Medicine for the treatment of abnormal uterine
bleeding [5]. KabeeruddinLXXVII described the male variety as Ud-e-Saleeb (tem-
perament, hot 3° and dry 3°) that has astringent, vessels deobstruent, resolvent,
emollient, detergent, analgesic, diuretic and emmenagogue properties; and used in
the treatment of brain and nervous diseases, such as epilepsy, tremors, palsy,
paralysis, mania, hallucination (waswas), encephalitis, and hysteria (Ikhtanaq-
ur-rahm), but especially useful for epilepsy. GrieveLV also described it as alterative,
antispasmodic, deobstruent, depurative, emmenagogue, tonic, emetic, and used for
convulsions, diarrhea, dropsy, epilepsy, epistaxis, hemorrhage, lunacy, neurosis,
pimples, intestinal and liver ailments, spasms, splenosis, tumors, uterosis, varices and
wounds. As alterative, it is used in syphilis, torpor of liver and ascites, but its great
repute is as emmenagogue in dysmenorrhea and amenorrhea. As antispasmodic it is
used in biliary, intestinal and renal colics; and in the treatment of hysteria, epilepsy,
palpitation, asthma and convulsive affections.LXXXI P. emodi root is also reportedly
used to treat hypertension, palpitations, and asthma [3], such as the indigenous
community of the Dir Lower district in northwest Khyber Pakhtunkhwa province of
Pakistan use aqueous decoction to treat hypertension [2]. The root combined with
bruised leaves of Melia is a favorite remedy for bruises, and sprains.CV Dried root
bark of P. suffruticosa (Mu-Tan-Pi) is described as a superior drug in TCM, and is
1368 Paeonia officinalis L.; Paeonia emodi Royle

mainly used for inflammation, pain, stagnant blood, and gynecological disorders; and
dried, cork-removed root of P. lactiflora (Pai-Shao) is used in the treatment of
gastrospasm, neuralgia, and painful, irregular menstruation.LXVI
Phytoconstituents: Oleanolic acid, betulinic acid, ethyl gallate, methyl grevillate
and 1,5-dihydroxy-3-methylanthraquinone, and a b-glucuronidase inhibiting triter-
pene, named emodinol have been reported from roots of P. emodi [7, 8]. Monoter-
pene galactosides, paeonins A and B, isolated from the roots are potent LOX
inhibitors [9]. Roots also contain alkaloids, tannins, saponins, glycosides, flavo-
noids, terpenes, steroids, carbohydrates and proteins [1]; 4–15% glucose, 8–14%
saccharose, 14–20% starch, 2% metarabinic acid, 1% organic acids, tannic acid,
calcium oxalate, 0.4% EO, benzoic acid, and esters, glutamine, arginine, paeo-
niafloureszine and tannin.XXXVIII Fruits contain oligostilbene and monoterpene
galactoside, paeoninol and paeonin C [10].
Pharmacology: Treatment of high-fat diet-induced dyslipidemic rats with hydro-
alcoholic and aqueous extracts of P. emodi significantly lowered TC, LDL-C, TGs
and atherogenic index, while HDL-C, SOD, and GPx were significantly elevated
[11]. Aqueous infusion of P. officinalis roots significantly ameliorated CCl4-
hepatotoxicity in rats [1]. Ghayur et al. [3] also reported cardiosuppressant,
vasodilatory, antiplatelet, and tracheal and airway relaxant activities of ethanol root
extract. Methanol, n-hexane, chloroform, ethyl acetate and aqueous fraction of
P. emodi root show significant antibacterial activity against E. coli, K. pneumoniae,
P. aeruginosa, S. aureus, S. typhi, S. epidermidis and MRSA, and antifungal
activity against A. flavus, A. fumigatus, A. niger and F. solani [6]. Pretreatment with
aqueous extract of P. officinalis protected against CCl4-hepatotoxicity [1]. Tubers of
P. emodi are reported to show uterine stimulant activity [4].
Human A/E, Allergy and Toxicity: In large doses the drug may cause headache,
giddiness and vomiting,CV and KabeeruddinLXXVII warns about its nonspecific
harmful effects in pregnant women.
Animal Toxicity: Aqueous infusion of the P. officinalis root was nontoxic and
nonlethal to rats up to an oral dose of 2,000 mg/kg [1].
Commentary: One of the widely used drugs in Indian traditional medicines,
especially in Unani medicine, but has been scantily investigated pharmacologically
and none clinically.

References
1. Ahmad F, Tabassum N. Preliminary phytochemical, acute oral toxicity and
antihepatotoxic study of roots of Paeonia officinalis Linn. Asian Pac J Trop
Biomed. 2013;3:64–8.
2. Ahmad L, Semotiuk A, Zafar M, et al. Ethnopharmacological documen-
tation of medicinal plants used for hypertension among the local commu-
nities of DIR Lower, Pakistan. J Ethnopharmacol. 2015;175:138–46.
Paeonia officinalis L.; Paeonia emodi Royle 1369

3. Ghayur MN, Gilani AH, Rasheed H, et al. Cardiovascular and airway

relaxant activities of peony root extract. Can J Physiol Pharmacol. 2008;
86:793–803.
4. Misra MB, Dikshit BB, Mishra SS, Misra RK. A preliminary pharmacology
of Paeonia emodi Wall. Indian J Med Sci. 1968;22:463–5.
5. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal
plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
6. Mufti FU, Ullah H, Bangash A, et al. Antimicrobial activities of Aerva
javanica and Paeonia emodi plants. Pak J Pharm Sci. 2012;25:565–9.
7. Nawaz HR, Malik A, Khan PM, et al. A novel beta-glucuronidase inhibiting
triterpenoid from Paeonia emodi. Chem Pharm Bull (Tokyo). 2000;48:
1771–3.
8. Riaz N, Anis I, Aziz-ur-Rehman, et al. Emodinol, beta-glucuronidase
inhibiting triterpene from Paeonia emodi. Nat Prod Res. 2003;17:247–51.
9. Riaz N, Anis I, Malik A, et al. Paeonins A and B, lipoxygenase inhibiting
monoterpene galactosides from Paeonia emodi. Chem Pharm Bull (Tokyo).
2003;51:252–4.
10. Riaz N, Malik A, Rehman AU, et al. Lipoxygenase inhibiting and antioxi-
dant oligostilbene and monoterpene galactoside from Paeonia emodi.
Phytochemistry. 2004;65:1129–35.
11. Zargar BA, Masoodi MH, Ahmed B, Ganie SA. Antihyperlipidemic and
antioxidant potential of Paeonia emodi Royle against high-fat diet induced
oxidative stress. ISRN Pharmacol. 2014;2014:182362.
Pandanus odorifer (Forssk.) Kuntze
(Pandanaceae)

(Syns.: P. odoratissimus C.L.; P. tectorius Park.; P. spurious Miq.)

Abstract
It is a palm-like small branched dioecious tree or shrub, which usually grows in
the tropics and few warm temperate regions, at the very edge of the sea and near
coastal forests in southeast Asia, including the Philippines and Indonesia, Papua
New Guinea and northern Australia, and throughout the Pacific Ocean beaches
and Hawaii. According to Nighantas, the plant has bitter-sweet, light and pungent
properties and removes phlegmatic humors; Muslim physicians consider it car-
diacal, cephalic and aphrodisiacal. The wood ashes promote wound healing, and
the seeds strengthen heart and liver. Razi said it cures leprosy and smallpox. In
Unani medicine, the fragrant distillate (kewra water) or syrup made with it is
described as cardiorefrigerant and cardiotonic, and is very beneficial in epidemic
diseases, such as small pox, measles, and typhoid fever; also used for palpitation
and anxiety (wahshat). In Ayurveda, various parts of the plant such as leaves,
root, flowers, and oils are also used as anthelmintic, tonic, stomachic, digestive
and in the treatment of jaundice and various liver disorders, and stress related
disorders. In Hawaii, chewed flowers (by the mother) are given to ten to sixty
days old babies to relieve constipation, and the roots are useful for mothers
weakened due to large number of births, and for those with chest pain. It contains
alkaloids, phenolic compounds, glycosides, lignans and isoflavones, coumestrol,
steroids, carbohydrates, proteins, amino acids, vitamins and other nutrients.
Hydroethanol leaf extract reversed stress-induced physiological and biochemical
changes, indicating a significant adaptogenic activity, and also protected mice
against experimental convulsions and death. Methanol leaf extract reduced
spontaneous motor activity, motor coordination and prolonged pentobarbital
sodium-induced sleeping time in mice.

Keywords


Al-kâdi Bai toey
Baquais
Fragrant screw pine
Hala
Keora
Kétaka



Kewra Qi ye lan
Schraubenbaum
© Springer Nature Switzerland AG 2020 1371
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_141
1372 Pandanus odorifer (Forssk.) Kuntze

Vernaculars: Urd.: Keora, Kewra; Hin.: Gagan-dhul, Jambala, Kewra; San.:

Dhúli-pushpika, Kétaka, Ketaki; Ben.: Kea, Keora, Ketaki, Keya; Guj.: Ketak,
Kevda; Mal.: Kainari, Kaitha, Ketaki, Tázha; Mar.: Kegad, Ketaki, Kevada; Tam.:
Kedagai, Ramba, Talambu, Talamchedi, Talum, Tazhambu, Tázhan-chedi, Thaaz-
hai; Tel.: Gájangi, Gedaga, Ketaki, Mogali-chettu, Mogheli; Ara.: Al-kâdi, Kadar;
Bur.: Tsatthap; Chi.: 露兜樹, Lu dou shu (Taiwan), Qi ye lan; Eng.: Fragrant screw
pine, Kaldera bush, Umbrella tree; Fre.: Baquais, Pandanus, Vacouet; Ger.: Chi-
nesischer schraubenbaum, Schraubenbaum, Schraubenpalme; Haw.: Hala; Ind.:
Daun pandan, Pandan wangi; Ita.: Ananasso della cina; Jap.: Adan; Maly.: Pandan
wangi; Nep.: Kerada, Tarika; Per.: Gulkiri, Gul-i-kabadi, Kádi; Sin.: Rampa,
Rampe, Rampeh; Tag.: Pandán-mabango; Tha.: Bai toey, Panae-wo-nging, Toei,
Toey-hom; Vie.: Cây cơm nếp, Dứa gỗ, Dứa thơm, Lá dứa.
Description: It is a palm-like small branched dioecious tree or shrub, which
usually grows in the tropics and few warm temperate regions, at the very edge of
the sea and near coastal forests in southeast Asia, including the Philippines and
Indonesia, extending eastward through Papua New Guinea and northern Australia,
and throughout the Pacific Ocean beaches and Hawaii. About 30–40 species of
Pandanus are widely distributed in India in the coastal districts of Orissa, Andhra
Pradesh, Tamil Nadu, and in some parts of Uttar Pradesh [3]. The tree is rugged,
tough and strong, grows very high with branches spreading far apart in all direc-
tions; leaves are glaucous-green, 180–240 cm long, 5 cm wide, ensiform, caudate
acuminate, coriaceous, with spines on the margins and on the midrib; the trunk rests
on its tubular roots above the ground. Flowers are in large clusters enveloped with
long white and very fragrant leaves, lined with sharp spikes.LXXVI In the Philip-
pines, it is planted in pots that does not grow over one meter.CXVII There are two
types of it, male and female. Female tree has yellow flowers, while male tree has
white and strong-smelling flowers. The shrub grows wild in southern India,
Myanmar and Andamans; white flower trees bloom in August-September, whereas
yellow flower variety blooms in February-March; flowers have a sweet, perfumed
fruity odor.CV Almost all parts of the plant are medicinally useful. The fragrant
watery distillate (kewra water) extracted from male flowers is almost exclusively
used in medicine, and also to flavor sweet dishes in Indian subcontinent. It was
introduced to Yemen from India, where it is predominantly found alongside flowing
streams, and most commonly in high rainfall areas, and only male trees seem to
grow, and the fragrant flowers are used in perfumery [1]. Flowers wrapped in leaves
are sold in Yemen by the roadside and in the markets (Figs. 1 and 2).CLIII
Actions and Uses: According to Nighantas, the plant has bitter-sweet, light and
pungent properties and removes phlegmatic humors; Muslim physicians consider it
cardiacal, cephalic and aphrodisiacal. The wood ashes promote wound healing, and
the seeds strengthen heart and liver.XL Razi said it cures leprosy and smallpox.LXIX,XL
In Unani medicine, the fragrant distillate (kewra water) (temperament, hot 2° and dry
2°) or syrup made with it is described as cardiorefrigerant and cardiotonic, and is very
beneficial in epidemic diseases, such as small pox, measles, and typhoid fever; also
used for palpitation and anxiety (wahshat).LXXVII Syrup administered during early
Pandanus odorifer (Forssk.) Kuntze 1373

Fig. 1 Pandanus odorifer, Tree with Fruit, Northwest Coast of Borneo, Dick Culbert, Wikimedia-
Commons; 2.0 Generic CC BY 2.0, https://commons.wikimedia.org/wiki/File:Pandanus_odorifer_
(14637587503).jpg; https://creativecommons.org/licenses/by/2.0/deed.en

Fig. 2 Pandanus odorifer, Trees, Southern Bangka Island, Indonesia, Wibowo Djatmiko, Wiki-
mediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/
File:Pandanu_odori_111025-19693_bml.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

stages of small pox lessens the number and intensity of eruptions.LXXVII The kewra
water is also described as stimulant, diaphoretic and antispasmodic, and used in
the treatment of general debility, faintness, and giddiness;LXXXI,CV and the root
brayed (ground) in milk is used in cases of sterility and threatened abortion.LXXXI
1374 Pandanus odorifer (Forssk.) Kuntze

In Ayurveda, various parts of the plant such as leaves, root, flowers, and oils are also
used as anthelmintic, tonic, stomachic, digestive and in the treatment of jaundice and
various liver disorders [8], and stress related disorders [2]. In Hawaii, chewed flowers
(by the mother) are given to ten to sixty days old babies to relieve constipation, and
the roots are useful for mothers weakened due to large number of births, and for those
with chest pain.LXXVI In the Philippines, the leaves are cooked with rice to impart
them the smell of new rice, and also used to flavor ice cream and sherbets.CXVII The
fruits are consumed in Solomon Islands, Papua New Guinea, and throughout the atoll
island countries of the central and northern Pacific [3].
Phytoconstituents: It contains alkaloids, phenolic compounds, glycosides, lignans
and isoflavones, coumestrol, steroids, carbohydrates, proteins, amino acids, vitamins
and other nutrients. Pandanus fruits paste (100 g) provides 321 kcal, protein (2.2 g),
Ca (134 mg), P (108 mg), Fe (5.7 mg), thiamin (0.04 mg), vitamin C (5 mg), and
b-carotene (19–19,000 lg) [3]. Hydroalcohol leaf extract showed the presence of
alkaloids and flavonoids [7]; lignans and benzofurans have also been isolated from
the roots [4]. a-Terpineol, b-carotene, b-sitosterol, benzyl benzoate, germacrene-B,
pinoresinol, vitamin C, viridine, tangeterine, 5,8-hydroxy-7methoxyflavone, and
vanidine have been isolated from the root extract, and the hydrodistilled EO from the
inflorescences contains ether, terpene-4-ol, a-terpineol, 2-phenylethyl alcohol, benzyl
benzoate, viridine, and germacrene-B, with small amounts of benzyl salicylate, benzyl
acetate, and benzyl alcohol [3]. The volatile oil also contains aromatic compound,
2-acetyl-1-pyrollidine [5]. Six lignans: eudesmin, kobusin, pinoresinol, epipinor-
esinol, de-4′-O-methyleudesmin, and 3,4-bis(4-hydroxy-3-methoxy-benzyl)-tetra-
hydrofuran have been reported from the methanol root extract [3].
Pharmacology: Ethanol root extract significantly protected against CCl4- and
APAP-hepatotoxicity in rats [6, 8]. Hydroethanol leaf extract reversed stress-induced
physiological and biochemical changes, indicating a significant adaptogenic activity
[4], and also protected mice against experimental convulsions and death [2]. Methanol
leaf extract reduced spontaneous motor activity, motor coordination and prolonged
pentobarbital sodium-induced sleeping time in mice, indicative of a potential
CNS-depressant action [10]. Hydroalcohol leaf extract exhibited significant antimi-
crobial activity against S. aureus and B. subtilis [7]. Aqueous root and leaf extracts
show significant cytotoxic and antimitotic activities [9].
Human A/Es, Allergy and Toxicity: No known A/Es, allergy or toxicity.
Animal Toxicity: Hydroethanol leaf extract [2], and methanol leaf extract were
nontoxic to mice up to an oral dose of 2,000 mg/kg [10].
Commentary: The essence of the leaves is widely used as a food and medicine
flavoring agent, but not as much of an independent medicine. Any systematic
clinical studies could reveal its potential as a therapeutic drug, especially in pal-
pitations and cardiac weakness.
Pandanus odorifer (Forssk.) Kuntze 1375

References
1. Abdul Wali A, al-Khulaidi. Flora of Yemen. Sustainable Environmental
Management Program (YEM/97/100), Republic of Yemen; 2000. p. 13, 149.
2. Adkar PP, Jadhav PP, Ambavade SD, Shelke TT, Bhaskar VH. Protective
effect of leaf extract of Pandanus odoratissimus Linn. on experimental
model of epilepsy. Int J Nutr Pharmacol Neurol Dis. 2014;4:81–7.
3. Adkar PP, Bhaskar VH. Pandanus odoratissimus (Kewda): a review on
ethnopharmacology, phytochemistry, and nutritional aspects. Adv Pharma-
col Sci. 2014;2014:120895.
4. Adkar PP, Jadhav PP, Ambavade SD, Bhaskar VH, Shelke T. Adaptogenic
activity of lyophilized hydroethanol extract of Pandanus odoratissimus in
Swiss albino mice. Int Sch Res Notices. 2014;2014:429828.
5. Chilkwad SR, Manjunath KP, Akki KS, Savadi RV, Deshpande N. Pharma-
cognostic and phytochemical investigation of leaves of Pandanus odoratis-
simus Linn. f. Anc Sci Life. 2008;28:3–6.
6. Ilanchezhian R, Joseph R. Hepatoprotective and hepatocurative activity of
the traditional medicine ketaki (Pandanus odoratissimus Roxb.). Asian J
Trad Med. 2006;5:212–8.
7. Kumar D, Kumar S, Singh J, Sharma C, Aneja KR. Antimicrobial and
preliminary phytochemical screening of crude leaf extract of Pandanus
odoratissimus L. Pharmacologyonline. 2010;2:600–10.
8. Mishra G, Khosa RL, Singh P, Jha KK. Hepatoprotective potential of
ethanolic extract of Pandanus odoratissimus root against paracetamol-
induced hepatotoxicity in rats. J Pharm Bioallied Sci. 2015;7:45–8.
9. Raj GG, Varghese HS, Kotagiri S, et al. Anticancer studies of aqueous
extract of roots and leaves of Pandanus odoratissimus f. ferreus (Y. Kimura)
Hatus: an in vitro approach. J Tradit Complement Med. 2014;4:279–84.
10. Rajuh S, Subbaiah NV, Reddy KS, Das A, Murugan KB. Potential of
Pandanus odoratissimus as a CNS depressant in Swiss albino mice. Braz J
Pharm Sci. 2011;47:630–4.
Papaver somniferum L.
(Papaveraceae)

Abstract
The plant is commercially cultivated in many parts of the world, chiefly in India,
Afghanistan, China, Egypt, Asian part of Turkey, Iran, southeastern Europe,
Nepal and Myanmar. Opium poppy and opium have been used since time
immemorial. The milky exudate or latex was named opion by the ancient Greeks,
derived from opos meaning sap or juice, which later became opium as its modern
name. Opium is the dried latex, and poppy straw is the dried mature plant except
the seeds. Opium poppy extracts were used to dull the pain of surgery during
ancient times, and were also combined with other plants extracts with sedative
properties, the primitive form of anesthesia. Most of these sedative plants belong
to the botanical family, Solanaceae. The Romans also knew the anesthetic power
of Solanaceous plants was increased when they were combined with extracts
from opium poppy. In the 16th and 17th centuries Europe, opium preparations
were marketed as Laudanum and Dover’s powder that were widely used for pain
relief. Unani medicine physicians use opium to treat moderate to severe pain of
pleurisy, sciatica, and arthritis, chronic cold, cough due to nerve irritation,
ophthalmitis, and chronic dysentery; it is also useful in premature ejaculation,
bloody and bilious meningitis, melancholia and schizophrenia. The capsule and
seeds contain a large percentage of fixed oil, pale-golden in color, of agreeable
odor, dries easily, and was used as food or burning in lamps. Opium contains over
twenty different isoquinoline alkaloids which account for most deaths due to
poppies. More than 200 years ago, between 1803 and 1805, the pharmacolog-
ically active pure compound, morphine, was isolated by the German pharmacist,
Friedrich Sertürner, from seed pods of the poppy, and is believed to be the first
isolation of an active ingredient from a plant source. Poppy seeds significantly
inhibited B[a]P-induced squamous cell carcinomas in the stomachs of Swiss
mice. A liquid alcoholic extract, named Elixir Paregorico® is extensively used for
diarrheal diseases in Brazil.

© Springer Nature Switzerland AG 2020 1377

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_142
1378 Papaver somniferum L.

Keywords






Adormidera Afeem Ahiphenam Anfião Haşhaş Khashkhas Oeillette





Ofu-yung Ölmohn Opium poppy

Vernaculars: Urd.: Afeem, Afyun, Khashkhas (seeds); Hin.: Afeem (resin),

Khashkhas (seeds), Koknar; San.: Ahiphenam (resin), Chosa, Kasa bijam and
Kakasha (seeds), Postu-bijam (dried capsule); Ben.: Afeem, Poshto, Posto dana
(seeds), Posto-dheri; Mal.: Banga-pion, Karuppa, Kasha-kasha; Mar.: Aphim (resin),
Khashkhas (seeds), Koknar; Tam.: Abini, Abhini (resin), Casha-pal, Gasa-gasalu,
Kasakasa (seeds), Posthakkai (dried capsule); Tel.: Gasha-dashala-palu, Gasugasalu,
Kasa-kasa, Nallamanthu, Posta-katol; Ara.: Abu-un-naum, Afyun, Bazrul-khas,
Khashkhash aswad, Laban al-khashkhas; Bur.: Bhainzi, Bhinbin; Chi.: Ofu-yung,
Opien, Ying su; Cze.: Mák sety; Dan.: Birkes, Opiumvalmue (plant), Valmue frø
(seeds); Dut.: Blauwmaanzaad, Maankop, Maanzaad, Slaapbol; Eng.: Opium poppy,
Poppy seeds, White poppy; Fin.: Oopiumiunikko, Pioniunikko, Uniko; Fre.: Oeil-
lette, Pavot à opium, Pavot blanc, Pavot des jardins, Pavot somnifère; Ger.:
Gartenmohn, Mohn, Ölmohn, Opiummohn, Schlafmohn; Gre.: Aphioni; Hun.: Mák;
Ita.: Papavero bianco, Papavero da opio, Papavero domestico, Papavero sonnolento;
Jap.: Keshi, Popi; Kor.: Apyeon, Apyon, Popi, Yang gwi bi; Nep.: Aphim; Nor.:
Opiumvalmue, Valmue; Per.: Khashkhas (seeds), Shir-e-khashkhas (resin), Tiryak,
Tukhme-koonar (seeds); Pol.: Mak lekarski; Por.: Anfião, Dormideira, Papoulo;
Rus.: Mak opiinyi; Spa.: Adormidera, Amapola real; Swe.: Opievallmo, Pionvallmo,
Vallmo; Tur.: Haşhaş.
Description: The plant is commercially cultivated in many parts of the world,
chiefly in India, Afghanistan, China, Egypt, Asian part of Turkey, Iran, southeastern
Europe, Nepal and Myanmar.CV It is a strong-smelling, annual plant, 0.4–1-m tall,
with hollow and unbranched stems, and all parts of the plant are strongly glaucous.
Leaves oblong, base cordate; the inferior leaves nearly petiolate, grayish-green,
coarsely lobed and toothed; cauline leaves clasping the stem. Stems and leaves are
sparsely covered with coarse hairs; flowers are up to 120 mm in diameter, white,
pink, red or purple, solitary, pedunculate (blooming season April–May). Fruit is a
hairless, rounded capsule, 6–7 cm long, topped with 12–18 radiating stigmatic rays;
seeds are numerous and very small. All parts of the plant exude white latex when
wounded.LXXIX Each capsule has a very small, thick stalk at the bottom, with a
large radiating sessile stellate stigma at the top, which distinguishes them from
colocynth. Seeds are reniform, reticulated, whitish-grey or greyish-black, taste
sweet and oily. Black seed poppy (maw seed) has purple or red flowers, capsule
smaller and rounder, and black seeds; whereas white seed poppy has white flowers
and white seeds.LXXXI It was introduced in India by Arab and Persian physicians.
The poppy generally cultivated in India is P. somniferum var. album, with white
flowers and white seeds. When the plant is in full flower, and just before the time
for the fall of the petals, they are collected. A few days after removing the petals,
the capsules (while still green) are incised vertically from base to the summit, by
Papaver somniferum L. 1379

forked blades in the afternoon. The number of incisions required to complete the
exudation of all juice varies with the size of capsule, from 2 to 6 or even 8; and two
to three days are allowed to alternate. A milky juice (sap or latex) (opium) exudes
almost immediately after scarification; it varies in color from milky-white and
smoky-white through pale-pink to a very bright-pink, but rapidly begins to darken
due to oxidation. As the water it contains evaporates slowly and the outer portion of
the tear drying somewhat, it thickens a little and acquires a rose-red color, while the
inner portion is semifluid and of a pinkish tinge. Next morning at 6 a.m. or later if
there is a heavy dew, the opium is collected by scrapping off the cut surface with the
blunt edged iron scoop. The process of lancing the capsule is repeated after every
three days for 4–5 times or as long as the capsule provides significant yield of the
latex. The latex obtained at the first incision is richer in morphine contents than at
the latter incisions. The cloudy weather or East winds considerably reduce the yield
of latex [2, 3] (Figs. 1, 2 and 3).XL
Actions and Uses: Opium poppy and opium have been used since time immemorial.
The milky exudate or latex was named opion by the ancient Greeks, derived from
opos meaning sap or juice, which later became opium as its modern name. Opium is
the dried latex, and poppy straw is the dried mature plant except the seeds. Opium
poppy extracts were used to dull the pain of surgery during ancient times, and were
also combined with other plants extracts with sedative properties, the primitive form
of anesthesia. Most of these sedative plants belong to the botanical family,

Fig. 1 Papaver somniferum, Plant with Flower and Poppies, Dinkum, WikimediaCommons;
1.0 Universal CC0 1.0, https://commons.wikimedia.org/wiki/File:Coquelicots_-_Parc_floral_6.
JPG; https://creativecommons.org/publicdomain/zero/1.0/deed.en
1380 Papaver somniferum L.

Fig. 2 Papaver somniferum, Latex Exuding from the Capsule, KGM007, WikimediaCommons,
https://commons.wikimedia.org/wiki/File:Opium_pod_cut_to_demonstrate_fluid_extraction1.jpg

Fig. 3 Papaver somniferum, Ornamental Red Poppy Flower, Jolly Janner, WikimediaCommons,
https://commons.wikimedia.org/wiki/File:Poppy_from_above.JPG

Solanaceae. During Roman Empire, Greek physician, Dioscorides described how

wine extracted the active constituents of mandrake (Mandragora officinarium): ‘the
wine of the bark of the root was to be given to such as shall be cut or cauterized. They
do not apprehend the pain because they are overborne with dead sleep.’ The Romans
Papaver somniferum L. 1381

also knew the anesthetic power of Solanaceous plants was increased when they were
combined with extracts from opium poppy: ‘there is another, more efficacious way for
producing sleep. It is made from mandrake with opium seed and seed of henbane
bruised up with wine’ [7]. In the 16th and 17th centuries Europe, opium preparations
were marketed as Laudanum and Dover’s powder that were widely used for pain
relief [17]. Ibn al-BaitarLXIX mentioned that taking it in the amount of pea size
relieves all pains and chronic cough, induces sleep, but in higher dose causes coma
and even death. He described the best quality that is bitter, heavy, not solid like wax,
readily soluble in water, melts in sun light, and burns quickly over flame, and just
smelling it induces sleep. He described 7 g as the lethal dose for adult human. Opium
produces narcotic, analgesic, antispasmodic, aphrodisiac, astringent and miotic
effects. Unani medicine physicians use opium (temperament, cold 4° and dry 4°) to
treat moderate to severe pain of pleurisy, sciatica, and arthritis, chronic cold, cough
due to nerve irritation, ophthalmitis, and chronic dysentery;LXXVII it is also useful in
premature ejaculation, bloody and bilious meningitis, melancholia and schizophrenia
(Junoon Sehr).LXXVII Vaids of Ayurveda use it as a sedative, prescribing it for
headaches, diarrhea, dysentery and digestive troubles of children. Opium is also used
as household remedy for children during teething periods by mothers and grand-
mothers of India.CV Poppy seeds (temperament, cold 2° and moist 1°) are demulcent,
nutritive and mild astringent, while poppy capsules are somniferous, sedative,
narcotic, and astringent. White poppy seeds are used as an article of food, during
summer, in the Indian subcontinent. Opium first stimulates brain, heart and respira-
tion, then produces respiratory and generalized depression. Topically, opium relieves
pain and allays spasms, and as astringent, checks hemorrhages, lessens bodily
secretions and restrains tissue changes.CV It is also used in patients who suffer from
nervousness or anxiety [1]. In China, the dried, empty capsules from which the latex
has been extracted are used medicinally. Opium is described as antitussive,
antispasmodic, analgesic, astringent and narcotic, and is used in the treatment of
chronic enteritis, diarrhea, enterorrhagia, headache, toothache and asthma, and the
seeds are used as condiment in bread by the Ethiopians [12].
Phytoconstituents: The capsule and seeds contain a large percentage of fixed oil,
pale-golden in color, of agreeable odor, dries easily, and was used as food or burning
in lamps.XXI,LXXXI Opium contains over twenty different isoquinoline alkaloids
which account for most deaths due to poppies.CXXXV More than 200 years ago,
between 1803 and 1805, the pharmacologically active pure compound, morphine,
was isolated by the German pharmacist, Friedrich Sertürner, from seed pods of the
poppy, and is believed to be the first isolation of an active ingredient from a plant
source [19]. Despite the undesirable side effects, morphine continues to be one of the
most used drugs in clinical practice for the treatment of pain disorders [6, 9]; codeine
and papaverine are the other opium alkaloids used therapeutically. Crude opium and
fresh poppy latex contain large amounts of free amino acids (I) in addition to
polypeptides which liberate I on hydrolysis. Since the relative amount of I varies
for different geographical regions, the determination of polypeptides pattern serves
as a means for determining the origin of the sample [10]. A new opium alkaloid,
1382 Papaver somniferum L.

oripavine, was isolated from the dried capsules of a variety cultivated in Tasmania
[16], and a novel morphinan alkaloid, bismorphine B, in which two morphine units
are coupled through a biphenyl ether-bond was identified in the wounded capsules
[15], and 5′-O-demethylnarcotine was also reported from P. sominefrum [18]. Seeds
also contain significant amount of morphine and codeine. Three white poppy seed
samples were found to contain total morphine in the range of 58.4–62.2 lg/g seeds
and total codeine in the range of 28.4–54.1 lg/g seeds. Soaking seeds in water
removes 45.6% of free morphine and 48.4% of free codeine [13]. Flavonols
(kaempferol and quercetin) are also present in all flower organs at all stages of floral
development, but their contents and distribution markedly vary in different organs
and at different stages of flower development [5]. Poppy seed oil is used for culinary
and pharmaceutical purposes, as well as for making soaps, paints, and varnishes.
Predominant triglycerides components are composed of linoleic, oleic, and palmitic
acids, comprising approximately 70% of the oil [11].
Pharmacology: Poppy seeds significantly inhibited B[a]P-induced squamous cell
carcinomas in the stomachs of Swiss mice [4].
Clinical Studies: A liquid alcoholic extract, named Elixir Paregorico® is exten-
sively used for diarrheal diseases in Brazil. To allay concerns about any toxic
effects of the elixir, 28 middle-aged healthy males (n = 14) and female (n = 14)
volunteers were given four oral doses per day of the elixir (3 mL diluted in 30 mL
of water) for 10-days. Hematological and biochemical tests performed pre and
post-treatment on 5th and 10th day showed no statistical differences [8].
Mechanism of Action: Opium alkaloids (the opioids), chiefly morphine produces
analgesia by binding to opioid (l and d) receptors in the brain. The analgesic,
sedative, euphoria, physical dependence, and respiratory depressant effects of
morphine are mediated via l-receptors.
Human A/Es, Allergy and Toxicity: Pharmaceutical factory workers, extracting
morphine and other alkaloids from shells of P. somniferum have developed clinical
symptoms of sensitization and positive skin tests [14]. In toxic doses, labored
breathing and coma follows, with feeble and slow pulse, cold clammy perspiration,
and constricted (pinpoint) pupil, resulting in death.CV
Animal Toxicity: No animal toxicity studies are reported in the literature.
Antidote: Specific antidote for morphine poisoning is naloxone, but in Unani
medicine, malkangni (Celastrous paniculatus) has been mentioned as antidote for
opium overdose.LXXVII
Commentary: Opium is the nature’s gift to allay human suffering from pain, and it
has been serving this purpose for millennia. Semisynthetic and synthetic opioids
have the increased efficacy of the natural alkaloid (morphine) by several fold, but it
still remains an indispensable nature’s remedy.
Papaver somniferum L. 1383

References
1. Alonso Osorio MJ. States of nervousness. Useful medicinal plants. Rev
Enferm. 2004;27:8–12 (Spanish).
2. Annett HE. Factors influencing alkaloidal content and yield of latex in the
opium poppy (Papaver somniferum). Biochem J. 1920;14:618–36.
3. Annett HE. The enzymes of the latex of the Indian poppy (Papaver
Somniferum). Biochem J. 1922;16:765–9.
4. Aruna K, Sivaramakrishnan VM. Anticarcinogenic effects of some Indian
plant products. Food Chem Toxicol. 1992;30:953–6.
5. Beliaeva RG, Evdokimova LI. Variability of flavonol contents during floral
morphogenesis in Papaver somniferum L. Ontogenez. 2004;35:16–22.
6. Calixto JB, Scheidt C, Otuki M, Santos AR. Biological activity of plant
extracts: novel analgesic drugs. Expert Opin Emerg Drugs. 2001;6:261–79.
7. Carter AJ. Narcosis and nightshade. BMJ. 1996;313:1630–2.
8. de Moraes M, Bezerra M, Bezerra F, et al. Safety evaluation of Elixir
paregorico(R) in healthy volunteers: a phase I study. Hum Exp Toxicol. 2008;
27:751–6.
9. Duarte DF. Opium and opioids: a brief history. Rev Bras Anestesiol.
2005;55:135–46 (Portuguese).
10. Jabbar A, Brochmann-Hanssen E. Amino acids in opium. J Pharm Sci. 1961;
50:406–8.
11. Krist S, Stuebiger G, Unterweger H, et al. Analysis of volatile compounds
and triglycerides of seed oils extracted from different poppy varieties
(Papaver somniferum L.). J Agric Food Chem. 2005;53:8310–6.
12. Lemordant D. Contribution a l’ethnobotanique Ethiopienne. J Agric Trop
Bot Appl. 1971;18:1–35; 18:142–79.
13. Lo DS, Chua TH. Poppy seeds: implications of consumption. Med Sci Law.
1992;32:296–302.
14. Moneo I, Alday E, Ramos C, Curiel G. Occupational asthma caused by
Papaver somniferum. Allergol Immunopathol (Madr). 1993;21:145–8.
15. Morimoto S, Suemori K, Taura F, Shoyama Y. New dimeric morphine from
opium poppy (Papaver somuniferum) and its physiological function. J Nat
Prod. 2003;66:987–9.
16. Nielsen B, Röe J, Brochmann-Hanssen E. Oripavine—a new opium alkaloid.
Planta Med. 1983;48:205–6.
17. Pasero G, Marson P. A short history of antirheumatic therapy—V. analgesics.
Reumatismo. 2011;63:55–60 (Italian).
18. Répási J, Hosztafi S, Szabó Z. 5′-O-demethylnarcotine: a new alkaloid from
Papaver somniferum. Planta Med. 1993;59:477.
19. Wachtel-Galor S, Benzie IFF. Herbal medicine: an introduction to its history,
usage, regulation, current trends, and research needs. In: Benzie IFF, Wachtel-
Galor S, editors. Herbal medicine: biomolecular and clinical aspects, 2nd ed.
Boca Raton, FL: CRC Press; 2011.
Persicaria bistorta L.
(Polygonaceae)

(Syns.: Polygonum bistorta L.; P. lapidosum (Kitag) Kitag; P. plumosum Small;

Bistorta abbreveata Kom.; B. carnea (K. Koch) Kom.; B. ensigera (Juz.) Tzvelev;
B. officinalis Del.)

Abstract
A perennial plant, native to Europe and North and West Asia, Syria, but universal
in distribution. All parts of this plant are very astringent, and very beneficial in
bleeding piles, intestinal irritation, chronic diarrhea, vomiting, and curative of
hemoptysis and bleeding from other organs, such as hematuria. In Unani medicine
rhizomes/roots are considered astringent, constipating, styptic, stomach and
intestinal tonic, soothing bile and blood heat; and used in the treatment of chronic
bloody or nonbloody diarrhea, bloody dysentery, nausea, vomiting, hematuria,
and hemoptysis. The roots and leaves are used as food by Native Americans, and
leaves, young shoots or aerial parts are one of the main ingredients of a savory
pudding common to parts of North of England. Dried rhizomes are widely used in
TCM and are listed in the Chinese Pharmacopoeia (2005 edition), to treat
dysentery with bloody stools, diarrhea of acute gastroenteritis, hematemesis,
epistaxis, leucorrhea, cholera, scrofula, hemorrhoidal bleeding, oral ulcers, and
acute respiratory infection with cough, and venomous snake bites. Tannins,
flavonoids, phenolic acids and triterpenoids are the major chemical constituents of
the rhizomes. Rhizomes are rich in phenolic contents, such as chlorogenic acid,
and gallic acid. Both preventive and curative significant anti-inflammatory activity
of aqueous ethanol extract, highly significant in vitro XO inhibitory activity,
antibacterial, antioxidant, and antimutative activities of the rhizomes have been
reported.

Keywords






Adderswort Ancubar Anjbaar Bijband Bistorta Hozâr bandak Natterwurz





Nisomali Quan can Slangeurt

Vernaculars: Urd.: Anjbaar; Hin.: Ban-natia, Bijband, Kuwar, Machoti, Nisomali;

San.: Miromati, Nisomali; Ben.: Machutie; Ara.: Anjubar, Asár-râi; Chi.: Caoheche,
Quan can, Quanshen; Dan.: Almindeling slangeurt, Slangeurt; Dut.: Adderwortel;
© Springer Nature Switzerland AG 2020 1385
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_143
1386 Persicaria bistorta L.

Eng.: Adderswort, Bistorta root, Knot grass, Snake root; Fin.: Konnantatar; Fre.:
Andrelles, Bistorte, Couleuvrée, Feuillote, Langue de boeuf, Renouée bistorte, Ser-
pentaire; Ger.: Natternknöterich, Natterwurz, Schlangenknöterich, Wiesenknöterich;
Ita.: Bistorta, Poligono bistorta, Poligono dei pascoli, Serpentina; Jap.: Ibuki-tora-
no-o; Per.: Hozâr bandak; Pol.: Rdest wężownik; Por.: Bistorta, Colubrine, Ser-
pentária-vermelha; Spa.: Bistorta, Bistorta menor, Polígono bistorta; Swe.: Stor
ormrot; Tur.: Ancubar, Çiançik, Ҫimen eveleği, Kurd pençesi.
Description: A native to Europe and North and West Asia, Syria, but universal in
distribution. A perennial plant growing to a height of 80 cm with hairless leaves;
basal leaves are longish-oval with long winged stalks and rounded at the bases, upper
leaves are triangular, tapered and stalkless. Rhizomes are S-shaped, bistorted, 5 cm
long and flattened, upper side striate, and under surface marked with root scars.LXXXI
KabeeruddinLXXVII described the plant (Anjbaar) 180 cm tall, with thin reddish
leaves and red flowers. The deep roots/rhizomes are rough and blackish-red in color;
these roots/rhizomes or root bark are used in Unani medicine (Figs. 1, 2 and 3).
Actions and Uses: All parts of this plant are very astringent, and very beneficial in
bleeding piles, intestinal irritation, chronic diarrhea, vomiting, and curative of
hemoptysis and bleeding from other organs, such as hematuria.LXIX Avicenna in
Canon of Medicine recommended it for the treatment of abnormal uterine bleeding
[12]. In Unani medicine rhizomes/roots (temperament, cold 1° and dry 1°) are

Fig. 1 Persicaria bistorta, Large Stem, Hans Hillewaert, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Bistorta_officinalis.jpg; https:
//creativecommons.org/licenses/by-sa/3.0/deed.en
Persicaria bistorta L. 1387

Fig. 2 Persicaria bistorta, Foliage, Scotland, Roger Griffith, WikimediaCommons, https:

//commons.wikimedia.org/wiki/File:Bistort_at_Kilmaurs.JPG

Fig. 3 Persicaria bistorta, Seeds, Paul Henjum, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:PersicariaBistorta.jpg

considered astringent, constipating, styptic, stomach and intestinal tonic, soothing

bile and blood heat; and used in the treatment of chronic bloody or nonbloody
diarrhea, bloody dysentery, nausea, vomiting, hematuria, and hemoptysis; also
applied as poultice for sprains and strains, and as powder to stop bleeding from
wounds.LXXVII It is described as expectorant, diuretic, tonic, astringent, antiseptic
and antiperiodic by Nadkarni.CV The roots and leaves are used as food by Native
Americans,XXVIII,XCVIII and leaves, young shoots or aerial parts are one of the main
ingredients of a savory pudding common to parts of North of England [7]. Dried
rhizomes are widely used in TCM and are listed in the Chinese Pharmacopoeia
1388 Persicaria bistorta L.

(2005 edition) [15] to treat dysentery with bloody stools, diarrhea of acute gas-
troenteritis, hematemesis, epistaxis, leucorrhea, cholera, scrofula, hemorrhoidal
bleeding, oral ulcers, and acute respiratory infection with cough, and venomous
snake bites [9].
Phytoconstituents: Tannins, flavonoids, phenolic acids and triterpenoids are the
major chemical constituents of the rhizomes [9]. Rhizomes are rich in phenolic
contents, chlorogenic acid, gallic acid, and relatively lower amounts of p-hydro-
xybenzoic acid, hydroquinone, vanillic acid, syringic acid, 4-methyl catechol, syr-
ingol, catechol and pyrogallol, and anticancer fatty acids, myristic acid, palmitic acid
and linoleic acid [5]. A tannin-related compound, bistortaside A and quercetin-
3′-O-b-D-glucopyranoside were also reported from the rhizomes [10]. The plant also
contain aglycones of the flavonoids, taxifolin, luteolin, quercetin, quercetin-3-methyl
ether, isorhamnetin, kaempferol, and rhamnetin [14]. Aerial parts of the plant are also
a rich source of polyphenols and some of these have anti-inflammatory potential [7].
Chemical constituents of volatile fraction of aerial parts collected from western
Italian Alps varied quantitatively and qualitatively during vegetative, flowering, and
fruiting stages. Most abundant compounds identified were 3-methylbut-3-en-1-ol in
the vegetative stage, linalool in the flowering stage, and dodecanoic acid and its
methyl ester in the fruiting stage [1]. P. bistorta is often adulterated in China,
with Paris polyphylla due to their common popular name Caoheche in history,
and with Polygonum paleaceum due to their similar appearances. Three compounds,
24(E)-ethylidenecycloartanone, epifridelanol and b-sitosterolol, are found in both
P. bistorta and P. paleaceum but not in P. polyphylla [9].
Pharmacology: Both preventive and curative significant anti-inflammatory activ-
ity of aqueous ethanol extract [3, 4], highly significant in vitro XO inhibitory
activity [13], antibacterial [6, 8], antioxidant [2], and antimutative [11] activities of
the rhizomes have been reported. The extract exhibited strong inhibitory activity on
secretion of IL-8 from H. pylori-infected gastric epithelial cells [16].
Human A/Es, Allergy and Toxicity: KabeeruddinLXXVII mentioned that it should
be used with caution in individuals with cold temperament.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Its syrup is widely used in Unani medicine for various conditions,
but there are no systematic RCTs done on any of its clinical effects, and pharma-
cological studies reported in mainstream literature are also limited.

References
1. Cecotti R, Carpana E, Falchero L, Paoletti R, Tava A. Determination of the
volatile fraction of Polygonum bistorta L. at different growing stages and
evaluation of its antimicrobial activity against two major honeybee (Apis
mellifera) pathogens. Chem Biodivers. 2012;9:359–69.
Persicaria bistorta L. 1389

2. Chang X, Liu YX, Kang WY. Antioxidant activity of extracts from

Polygonum bistorta L. Fine Chem Interm. 2009;39:2.
3. Duwiejua M, Zeitlin IL, Gray AI, Waterman PG. Anti-inflammatory activity
of Polygonum bistorta, Quaiacum officinale and Hamamelis virginiana in
rats. J Pharm Pharmacol. 1994;46:286–90.
4. Duwiejua M, Zeitlin IL, Gray AI, Waterman PG. The anti-inflammatory
compounds of Polygonum bistorta: isolation and characterization. Planta
Med. 1999;65:371–4.
5. Intisar A, Zhang L, Luo H, et al. Anticancer constituents and cytotoxic
activity of methanol-water extract of Polygonum bistorta L. Afr J Tradit
Complement Altern Med. 2012;10:53–9.
6. Khalid A, Waseem A, Saadullah M, et al. Antibacterial activity analysis of
extracts of various plants against gram-positive and -negative bacteria. Afr J
Pharm Pharmacol. 2011;5:887–93.
7. Klimczak U, Woźniak M, Tomczyk M, Granica S. Chemical composition
of edible aerial parts of meadow bistort (Persicaria bistorta (L.) Samp.).
Food Chem. 2017;230:281–90.
8. Liu CQ, Wang XL, Zeng J. Preliminary study on antimicrobial activity of
Polygonum bistorta L. J Gannan Med Univ. 2006;26:489–90.
9. Liu XQ, Du LL, Li WW, Guan HF, Liu F. Simultaneous qualitative and
quantitative analysis of commercial bistorta rhizome and its differentiation
from closely related herbs using TLC and HPLC-DAD fingerprinting. Chem
Pharm Bull (Tokyo). 2008;56:75–8.
10. Liu XQ, Hua HM, Liu J, Chen FK, Wu LJ. A new tannin-related compound
from the rhizome of Polygonum bistorta L. J Asian Nat Prod Res. 2006;8:
299–302.
11. Miki N, A-Fu W, Takahiko S, Hisamitsu N, Hideaki K. Effects of Chinese
medicinal plant extracts on mutagenecity of Trp-P-1. J Nat Med. 1995;49:
329–31.
12. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal plants
used for the treatment of abnormal uterine bleeding by Avicenna. Arch
Gynecol Obstet. 2015;292:21–35.
13. Orbán-Gyapai O, Lajter I, Hohmann J, Jakab G, Vasas A. Xanthine oxidase
inhibitory activity of extracts prepared from Polygonaceae species. Phyto-
ther Res. 2015;29:459–65.
14. Smolarz HD. Comparative study on the free flavonoid aglycones in herbs of
different species of Polygonum L. Acta Pol Pharm. 2002;59:145–8.
15. The State Pharmacopoeia Commission of People’s Republic of China 2005.
Pharmacopoeia of the People’s Republic of China, vol. I. Beijing, China:
Chemical Industry Press; 2005. p. 202.
16. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and cytopro-
tective effects of selected Pakistani medicinal plants in Helicobacter pylori-
infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
Phyllanthus emblica L.
(Phyllanthaceae)

(Syns.: Emblica officinalis Gart.; E. arborea Raf.)

Abstract
The fruits are used medicinally in both fresh and dried forms, and also preserved
in syrup, in India. Ibn al-Baitar, referring to Avicenna, described it as one of the
most astringent drugs and thus a very useful cardiotonic, and to improve
memory. It is especially useful in diseases caused by black bile, quenches thirst,
is aphrodisiac, and antiemetic. In its fresh form, Hindu physicians consider it
refrigerant, diuretic and laxative; and the dried one as cooling, stomachic and
astringent. Muslim practitioners of Unani medicine also regard it as astringent,
refrigerant, cardiacal, and a purifier of body humours. It strengthens vital organs,
stomach, and eyes, and is especially useful to improve memory, eyesight,
relieves palpitation, and heart weakness. It is also used to treat stomach
‘weakness’ and diarrhea, and its use, both topically and systemically, helps
strengthen hairs and to maintain their shine and color. In Ayurveda, it is one of
the rasayana plants with adaptogenic property, and is used as a powerful
rejuvenator. Fresh fruit pulp and the pericarp of dried mature fruits are used in
raktapitta, amlapittaprameha, and dãha. It is one of the major constituent plants
of polyherbal memory and vitality-enhancing medicines marketed in India.
Seventeen countries in the world are reported to use various parts of P. emblica
in their medical treatment for hepatitis, cancer, tumors, regulation of stomach
function, as a traditional immunomodulator and a natural adaptogen. Aqueous
fruit extracts show the presence of tannins, saponins, flavonoids, terpenoids and
phenols. Gallic acid, ellagic acid, chebulinic acid, quercetin, chebulagic acid,
corilagin, ellagitannins, phenolic constituents, bisabolane-type sesquiterpenoid,
bisabolane sesquiterpenoid glycoside, phyllaemblic acid and glochicoccin D
have been isolated from the fruits. Aqueous extract significantly attenuated
behavioral, biochemical and molecular alterations, and in combination with
insulin also reversed neuropathic pain in diabetic rats; and significantly inhibited
rat lens and recombinant human aldose reductase, and tannoids fraction was 100
times more potent than the aqueous extract, comparable to or better than

© Springer Nature Switzerland AG 2020 1391

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_144
1392 Phyllanthus emblica L.

quercetin. Aqueous fruit extract also produced antidepressant-like effect in mice;

whereas the hydroalcohol extract showed memory enhancing, antioxidant, and
anti-AChE activity in scopolamine-induced cognitive impairment in mice.

Keywords





Amla Āmalaki Amblabaum Amlaj Amuleh Anvula Emblic myrobalan





Me rừng Mirobalano Yu gan zi

Vernaculars: Urd.: Amla; Hin.: Amla, Amlika, Anvula, Aonla; San.: Amalakam,
Āmalaki, Amritaphala, Amrtaphalã, Dhãtri, Dhatriphala, Śivam, Sriphalam,
Tisyaphalã, Vayasthã; Ben.: Amla, Amlaki, Amritaphala, Dhatri; Guj.: Amalak;
Mal.: Amalakam, Nelli, Nelli-kaya; Mar.: Anvala, Avala, Avalkathi; Tam.:
Amalaki, Amirta-palam, Attakoram, Nellikkai, Perunelli, Toppi, Toppu-nelli; Tel.:
Amalakama, Nelli-kaya, Usiri, Usirike-kaya; Ara.: Amlaj; Bur.: Mai kham,
Ziphiyu-si; Chi.: 余甘子, Yu gan zi; Eng.: Emblic myrobalan, Indian gooseberry;
Fre.: Phyllanthe emblic; Ger.: Amblabaum, Gebrauchlicher; Maly.: Melakka,
Pokok dukung anak, Pokok melaka; Nep.: Amalaa; Per.: Amelah, Amial, Amuleh;
Rus.: Fillantus emblika; Spa.: Mirobalano, Neli; Tha.: Kam huat, Kan tot,
Makhaam pom; Vie.: Chùm ruột núi, Mắc kham, Me mận, Me rừng.
Description: The fruits are used medicinally in both fresh and dried forms, and
also preserved in syrup, in India. Fresh Emblic myrobalans are globular, fleshy,
smooth, six-striated of a yellowish-green color, and sometimes as large as a walnut.
They contain an obovate, obtusely triangular, 3-celled nut, each cell of which
contains two triangular seeds. Taste of the pulp is acid, astringent, and somewhat
acrid. Dried fruit is the size of a cob nut (hazel nut) sub-hexagonal, wrinkled of a

Fig. 1 Phyllanthus emblica, Fruits on a Tree, L. Shyamal, WikimediaCommons; 2.5 Generic CC

BY 2.5, https://commons.wikimedia.org/wiki/File:Phyllanthus_officinalis.jpg; https://creativecommons.
org/licenses/by/2.5/deed.en
Phyllanthus emblica L. 1393

Fig. 2 Phyllanthus emblica, Ripe Fruits in Syrup, Prof. Akbar, Original

Fig. 3 Phyllanthus emblica, Dried Fruit Seeds, Prof. Akbar, Original

grey-black color if it has been collected when immature, but yellowish-brown when
mature. Mature fruit breaks up, upon pressure, into six parts, each of which consists
of a section of the pulp and nut, and contains one triangular brown seed.XL Best
quality amla shred were obtained when blanched with potassium metabisulphite
and dried in solar dryer with addition of 3% common salt. It provided ascorbic
acid content 298.3 mg/100 g, tannin 2.4%, acidity 2.6%, reducing sugar 3%,
non-reducing sugar 21% and total sugar 24% [89] (Figs. 1, 2 and 3).
1394 Phyllanthus emblica L.

Actions and Uses: Ibn al-BaitarLXIX referring to Avicenna, described it as one of

the most astringent drugs and thus a very useful cardiotonic, and to improve
memory. It is especially useful in diseases caused by black bile, quenches thirst, is
aphrodisiac, and antiemetic. In its fresh form, Hindu physicians consider it refrig-
erant, diuretic and laxative; and the dried one as cooling, stomachic and astringent.
Muslim practitioners of Unani medicine also regard it as astringent, refrigerant,
cardiacal, and a purifier of body humours.XL It strengthens vital organs, stomach,
and eyes, and is especially useful to improve memory, eyesight, relieves palpitation,
and heart ‘weakness.’ It is also used to treat stomach ‘weakness’ and diarrhea, and
its use, both topically and systemically, helps strengthen hairs and to maintain their
shine and color.LXXVII GhaniL described it as blood purifier, astringent, memory
and cardiac tonic, phlegm and black bile expectorant, that relieves palpitation. In
Ayurveda, it is one of the rasayana plants with adaptogenic property [99], and is
used as a powerful rejuvenator [118]. Adaptogens are defined as agents that afford
protection to human physiological systems against diverse stressors [74]. Fresh fruit
pulp and the pericarp of dried mature fruits are used in raktapitta, amlapit-
taprameha, and dãha.CXXXVI It is one of the major constituent plants of polyherbal
memory and vitality-enhancing medicines marketed in India; other plants being
Bacopa monnieri, Evolvulus alsinoides, Withania somnifera, Nardostychys jata-
mansi, and Acorus calamus [108]. NadkarniCV said it prevents vicious humours in
the stomach and intestine, and is used in chronic diarrhea and convalescence from
typhoid and other fevers. Tribal practitioners of the Marakh sect of the Garos
indigenous community of Bangladesh use it for the treatment of diabetes [92].
Fresh fruit is refrigerant, diuretic and laxative, and used in chronic constipation, and
dried fruit is cooling, stomachic and astringent.LXXXI Xia et al. [137] reported
that 17 countries in the world use various parts of P. emblica in their medical
treatment for hepatitis, cancer, tumors, regulation of stomach function, as a tradi-
tional immunomodulator and a natural adaptogen.
Phytoconstituents: Aqueous, methanol and ethyl acetate extracts test positive for
alkaloids and tannins [135]. Gallic acid, ellagic acid, chebulinic acid, quercetin,
chebulagic acid, 1-O-galloyl-b-D-glucose, 3,6-di-O-galloyl-D-glucose, corilagin,
3-ethylgallic acid (3-ethoxy-4,5-dihydroxybenzoic acid), isostrictiniin, 1,6-di-
O-galloyl-b-D-glucose [142], ellagitannins [144], phenolic constituents [145],
kaempferol-3-O-a-L-(6″-methyl)-rhamnopyranoside and kaempferol-3-O-a-L-
(6″-ethyl)-rhamnopyranoside [39], mucic acid 3-O-gallate [110], bisabolane-type
sesquiterpenoid [143], bisabolane sesquiterpenoid glycoside, phyllaemblicins
G1–G8, phyllaemblicin F, phyllaemblic acid and glochicoccin D [67] have been
isolated from the fruits. In addition, triacontanol, triacontanoic acid, b-amyrin
ketone, betulonic acid, daucosterol, lupeol acetate, b-amyrin-3-palmitate, betulinic
acid, ursolic acid, oleanolic acid, and rutin have been isolated [66]. Kumaran and
Karunakaran [63] identified gallic acid, methyl gallate, corilagin, furosin and ger-
aniin as the nitric oxide scavenging components. Aqueous fruit extracts (both
infusions and decoctions) show the presence of tannins, saponins, flavonoids, ter-
penoids and phenols [60]. Ascorbic acid contents of the Indian gooseberry fruit
Phyllanthus emblica L. 1395

range from 1,100 to 1,700 mg/100 g of fruit [23], and the fruit juice contains more
vitamin C (478.56 mg/100 ml) than apple, lime, pomegranate, Perlette grapes, and
Pusa Navrang grapes [47]. It also contains significant amounts of cobalt, chromium
and sodium [136].
Pharmacology: Aqueous extract significantly attenuated behavioral, biochemical
and molecular alterations, and in combination with insulin also reversed neuro-
pathic pain in diabetic rats [130]. Methanol extracts of fruits and leaves also sig-
nificantly reduced blood sugar in diabetic rats [76, 100], and exhibited antioxidant
activity [78]. Aqueous extract significantly inhibited rat lens and recombinant
human aldose reductase (AR) (the enzyme involved in cataract formation in dia-
betics), and tannoids fraction was 100 times more potent than the aqueous extract,
comparable to or better than quercetin [120, 121]; b-glucogallin has been identified
as the novel AR inhibitor [91]. Supplementation with fresh fruit homogenate, juice
or an emblicanin-A and -B enriched fraction of fresh juice in diet showed significant
antioxidant activity against oxidative stress in rat heart [17, 81, 84, 93, 128], and in
diabetic rats [95]. Fruit powder also showed in vitro antioxidant activity [111].
Hydroalcohol fruit extract demonstrated efficient antioxidant activity, that was
correlated to its phenolic and flavonoid contents [9, 22, 104, 107], and to the
presence of hydrolyzable tannins having ascorbic acid-like action [88]. Role of
ascorbic acid and the presence of emblicannins A and B, responsible for its
antioxidant activity has recently been questioned because their presence and
quantities do not justify the extent of the activity [69]. Hydroalcohol lyophilized
extract significantly lowered deoxycorticosterone acetate/high salt-induced hyper-
tension and HR, and the related cardiac and renal hypertrophy in rats [11]. Amla
supplementation to cholesterol-rich diet-fed animals significantly lowered serum
TC [73], and tissue cholesterol levels [8, 58, 125–127]. Fresh fruit juice lowered
serum cholesterol, TGs, phospholipid and LDL-C levels by 82%, 66%, 77% and
90%, respectively [70]. Flavonoids isolated from Amla exhibited highly potent
hypolipidemic and hypoglycemic effects, raised Hb in rats [4], and significantly
inhibited hepatic HMG Co-A reductase [5]. Ethyl acetate extract, a polyphenol rich
fraction of the fruit showed potent hypolipidemic and anti-LPO activities [56],
reduced iNOS and COX-2 expression levels, which are increased with aging, by
inhibiting NF-kappaB activation in aged rats [57, 140], and also attenuated
age-related oxidative stress-induced renal dysfunction [141].
Aqueous fruit extract produced antidepressant-like effect in mice [29]; whereas
the hydroalcohol extract showed memory enhancing, antioxidant, and anti-AChE
activity in scopolamine-induced cognitive impairment in mice [35]. Pretreatment of
rats with hydroalcohol extract also abolished PTZ- and kainic acid-induced seizures,
improved cognitive deficit and ameliorated oxidative stress [34, 36]. The extract
lowered brain LPO and elevated activities of antioxidant enzymes in alcohol-
induced oxidative stress in rats [96, 97]. Tannoid principles of fruits, emblicanin A,
emblicanin B, punigluconin and pedunculagin normalized stress-induced perturba-
tions in oxidative free radical scavenging enzymes in rat brain frontal cortex and
striatum, and reduced LPO [14], and exerted a prophylactic effect against
neuroleptic-induced tardive dyskinesia in rats, due to its antioxidant effects [12].
1396 Phyllanthus emblica L.

A number of in vitro studies reported cytotoxic, apoptotic, antimetastatic,

autophagy and antiproliferative effects of various extracts and active constituents on
diverse cancer cells [27, 50, 54, 64, 68, 71, 79, 86, 94, 139, 147]. Aqueous extract
significantly reduced tumor incidence, yield, and cumulative number of DMBA-
induced papillomas in mice [105], increased life span of tumor-bearing animals by
20% [50], and the methanol fruit extract restored antioxidant status to normal in
DMBA-induced buccal pouch carcinoma in hamsters [59]. It was first reported to
be active against Yoshida sarcoma [77]. Various extracts and active fractions
produced gastric ulcer protective effects in rats and a significant ulcer healing
effect with significant decrease in offensive factors like gastric acid and pepsin
and increase in mucin secretion, and significantly strengthening antioxidant status
[3, 10, 16, 19, 103]. Aqueous, standardized extract reversed effects of cisplatin on
gastric emptying, and strengthened defense mechanisms against free radical damage
during stress, that appeared to depend on the ability of target tissues to synthesize
PGs [99]. Fruit pulp extracts also protected mice against ionizing radiation-induced
changes, increased survival and decreased mortality [113], increased antioxidant
enzymes and GSH levels, and reduced LPO [41, 49, 114], and DNA damage in
animals [46]. Antioxidant property is also responsible for protection against con-
trast media-induced acute kidney injury in rats [122]. A standardized extract helped
protect skin from damaging effects of free radicals, nonradicals and transition
metal-induced oxidative stress [20]. Various fruit extracts inhibited in vitro and
in vivo LPO [42, 48, 61].
Aqueous fruit extract was most active against K. pneumoniae, while the methanol
extract was most active against E. coli [60], and dietary supplementation with Amla
protected against bacterial colonization of lungs in K. pneumoniae pneumonia in
mice [102]. Saeed and Tariq [101] reported aqueous infusion and decoction of fruit
showing potent activity against E. coli, K. pneumoniae, K. ozaenae, P. mirabilis,
P. aeruginosa, S. typhi, S. paratyphi A, S. paratyphi B and S. marcescens; whereas
Ahmad et al. [1] reported alcohol extract more active antibacterial than the aqueous
extract. Methanol fruit extract showed significant activity against S. aureus and
E. coli [135], and HIV reverse transcriptase; putranjivain A was identified as a potent
HIV reverse transcriptase inhibitory substance with IC50 of 3.9 µg/ml [31]. Aqueous
extract containing flavonoids, hydrolysable tannins, saponin and terpenes, also
exhibited significant in vitro and in vivo antiplasmodial activity [87]. A polyphenolic
compound, 1,2,4,6-tetra-O-galloyl-b-D-glucose, isolated from fruits inhibited HSV-1
and HSV-2 [138].
Both ethanol and aqueous fruit extracts cause significant reduction in brewer’s
yeast-induced hyperthermia in rats, and elicit pronounced analgesic response in mice
[85]. Flavonoid rich fruit extract also elicits significant analgesic activity in diabetic
neuropathic pain and attenuates diabetes-induced axonal degeneration in rats [62].
Phenolic compounds in high doses show significant anti-inflammatory activity in
rats [75]; pyrogallol was identified responsible for the anti-inflammatory effect [80].
Extracts of leaves have also shown anti-inflammatory activity [7, 44]. Amla extracts
exhibit both in vitro and in vivo immunomodulatory activity [43, 119], and protect
against CP nephrotoxicity [40]. Daily administration of ethanol fruit extract for
Phyllanthus emblica L. 1397

30-days in levothyroxin-induced hyperthyroid mice reduced T3 and T4 concentra-

tions by 64 and 70% respectively, as compared to propylthiouracil that decreased
levels by 59 and 40%, respectively [83]. Aqueous extract ameliorates spermatotoxic
effects of ochratoxin in mice, and reduces LPO in testes [18, 133, 134]. Fruit pulp
extracts protected from experimentally-induced acute pancreatitis [112, 129], and its
constituents [15] were protective against various hepatotoxic challenges [21, 26, 38,
42, 51, 65, 72, 82, 90, 98, 106, 109, 115, 117, 123, 124], and prevented and
ameliorated hepatocarcinogenesis in animals [48, 116].
Clinical Studies: Daily fresh Amla consumption for 4-weeks significantly lowered
TC in both normal and hypercholesterolemic Indian patients [45]. Supplementation
of a standardized extract to overweight/Class-1 obese (BMI: 25–35) Indian adults
for 12-weeks significantly lowered LDL-C and TC/HDL ratio, significantly
decreased circulatory hs-CRP, and significantly downregulated both ADP- and
collagen-induced platelet aggregation [55]. Intake of a purified, standardized, dried
extract of Amla, containing about 35% galloellagitannins and other hydrolysable
tannins, by 26 mildly hypercholesterolemic Indian volunteers for 6-months sig-
nificantly lowered TC, LDL-C, and VLDL-C, and TGs, reduced CRP and increased
HDL-C [6]. Similarly, significant reduction in TC and LDL-C and TGs, and
improvement in HDL-C was reported in normal and diabetic Pakistani volunteers
after 21-days treatment with Amla powder; additionally, the fasting and 2-h post-
prandial blood glucose levels were significantly decreased [2]. In a comparative
trial with simvastatin in hyperlipidemic Pakistani patients, both treatments signifi-
cantly improved lipid profile, but treatment with Amla had better BP lowering effect
[37], while in another double-blind RCT, comparison with atorvastatin showed that
both treatments significantly improved lipid profile and HbA1c levels, significantly
improved endothelial function and reduced biomarkers of oxidative stress and
systemic inflammation in Type-2 diabetic Indian patients [131]. Review of clinical
studies also reveal that polyherbal supplements containing E. officinalis are most
consistent in lowering FBG or HbA1c in diabetic patients [28]. Even in uremic
patients, supplementation with Amla extract reduced plasma oxidative marker, and
improved plasma antioxidant status without significantly affecting liver function,
renal function and diabetic index [23, 24]. Another proprietary extract significantly
decreased cold pressor stress test-induced changes on aortic wave reflections, such
as arterial stiffness and increase in subendocardial viability ratio in healthy Indian
volunteers [33]. Fruit extract also decreased platelet aggregation, and potentiated
antiaggregation effect of clopidogrel and aspirin, and increased bleeding and clot-
ting time in type-2 diabetic patients [32]. Aqueous fruit powder extract significantly
inhibited in vitro activities of hyaluronidase and collagenase type-2, and exhibited
significant long-term chondroprotective activity in cartilage explants from 50% of
the osteoarthritis patients tested [118].
Mechanism of Action: Antioxidant properties of low-molecular weight hydro-
lysable tannins present in the fruit are generally credited for the biological effects
[13]. The anticancer activity is considered to be principally mediated by polyphe-
nols, especially tannins and flavonoids [146]. Antidiabetic effects of the fruits and/or
1398 Phyllanthus emblica L.

some of its important constituents, including gallic acid, gallotanin, ellagic acid
and corilagin, are due to their antioxidant and free radical scavenging properties
[30, 52, 132], and insulin-sensitizing effect [53].
Human A/Es, Allergy and Toxicity Constipation and colicky pain are common
A/Es; honey and almond oil may help avoid the adverse effects.LXXVII Polyherbal
products on the market were found frequently contaminated with Aspergillus flavus,
that could cause serious toxicity [25].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This fruit in various forms is so widely trusted in Indian subcon-
tinent culture that common people would vouch for its beneficial effects, even when
they had only heard about them. It is extensively used both as a medicine and a
general tonic as syrup-preserved fruit, and in numerous polyherbal formulations. It
has shown significant blood sugar and lipid modifying and antioxidant effects, but
these effects have not been reproduced in patients of different ethnicities. Therefore,
large scale RCTs in diverse populations are needed to validate the effectiveness of
this amazing versatile nutritious fruit.

References
1. Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal
plants for their antimicrobial properties. J Ethnopharmacol. 1998;62:183–93.
2. Akhtar MS, Ramzan A, Ali A, Ahmad M. Effect of Amla fruit (Emblica
officinalis Gaertn.) on blood glucose and lipid profile of normal subjects
and type 2 diabetic patients. Int J Food Sci Nutr. 2011;62:609–16.
3. Al-Rehaily AJ, Al-Howiriny TA, Al-Sohaibani MO, Rafatullah S. Gas-
troprotective effects of ‘Amla’ Emblica officinalis on in vivo test models in
rats. Phytomedicine. 2002;9:515–22.
4. Anila L, Vijayalakshmi NR. Beneficial effects of flavonoids from Sesamum
indicum, Emblica officinalis and Momordica charantia. Phytother Res.
2000;14:592–5.
5. Anila L, Vijayalakshmi NR. Flavonoids from Emblica officinalis and
Mangifera indica—effectiveness for dyslipidemia. J Ethnopharmacol. 2002;
79:81–7.
6. Antony B, Benny M, Kaimal TN. A Pilot clinical study to evaluate the
effect of Emblica officinalis extract (Amlamax™) on markers of systemic
inflammation and dyslipidemia. Indian J Clin Biochem. 2008;23:378–81.
7. Asmawi MZ, Kankaanranta H, Moilanen E, Vapaatalo H. Anti-inflammatory
activities of Emblica officinalis Gaertn. leaf extracts. J Pharm Pharmacol.
1993;45:581–4.
8. Augusti KT, Arathy SL, Asha R, et al. A comparative study on the beneficial
effects of garlic (Allium sativum Linn), Amla (Emblica officinalis Gaertn.)
and onion (Allium cepa Linn) on the hyperlipidemia induced by butter fat
and beef fat in rats. Indian J Exp Biol. 2001;39:760–6.
Phyllanthus emblica L. 1399

9. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and antioxi-

dant activity of some food and medicinal plants. Int J Food Sci Nutr.
2005;56:287–91.
10. Bandyopadhyay SK, Pakrashi SC, Pakrashi A. The role of antioxidant
activity of Phyllanthus emblica fruits on prevention from indomethacin
induced gastric ulcer. J Ethnopharmacol. 2000;70:171–6.
11. Bhatia J, Tabassum F, Sharma AK, et al. Emblica officinalis exerts
antihypertensive effect in a rat model of DOCA-salt-induced hypertension:
role of (p) eNOS, NO and oxidative stress. Cardiovasc Toxicol. 2011;11:
272–9.
12. Bhattachary SK, Bhattacharya D, Muruganandam AV. Effect of Emblica
officinalis tannoids on a rat model of tardive dyskinesia. Indian J Exp Biol.
2000;38:945–7.
13. Bhattacharya A, Chatterjee A, Ghosal S, Bhattacharya SK. Antioxidant
activity of active tannoid principles of Emblica officinalis (Amla). Indian J
Exp Biol. 1999;37:676–80.
14. Bhattacharya A, Ghosal S, Bhattacharya SK. Antioxidant activity of tannoid
principles of Emblica officinalis (Amla) in chronic stress induced changes in
rat brain. Indian J Exp Biol. 2000;38:877–80.
15. Bhattacharya A, Kumar M, Ghosal S, Bhattacharya SK. Effect of bioactive
tannoid principles of Emblica officinalis on iron-induced hepatic toxicity in
rats. Phytomedicine. 2000;7:173–5.
16. Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK.
Healing properties of some Indian medicinal plants against indomethacin-
induced gastric ulceration of rats. J Clin Biochem Nutr. 2007;41:106–14.
17. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Effect of bioactive
tannoid principles of Emblica officinalis on ischemia-reperfusion-induced
oxidative stress in rat heart. Phytomedicine. 2002;9:171–4.
18. Chakraborty D, Verma R. Spermatotoxic effect of ochratoxin and its amelio-
ration by Emblica officinalis aqueous extract. Acta Pol Pharm. 2009;66:
689–95.
19. Chatterjee A, Chattopadhyay S, Bandyopadhyay SK. Biphasic effect of
Phyllanthus emblica L. extract on NSAID-induced ulcer: an antioxidative
trail weaved with immunomodulatory effect. Evid Based Complement
Alternat Med. 2011:146808.
20. Chaudhuri RK. Emblica cascading antioxidant: a novel natural skin care
ingredient. Skin Pharmacol Appl Skin Physiol. 2002;15:374–80.
21. Chen KH, Lin BR, Chien CT, Ho CH. Emblica officinalis Gaertn. atten-
tuates N-nitrosodiethylamine-induced apoptosis, autophagy, and inflam-
mation in rat livers. J Med Food. 2011;14:746–55.
22. Chen TS, Liou SY, Chang YL. Antioxidant evaluation of three adaptogen
extracts. Am J Chin Med. 2008;36:1209–17.
23. Chen TS, Liou SY, Chang YL. Supplementation of Emblica officinalis
(Amla) extract reduces oxidative stress in uremic patients. Am J Chin Med.
2009;37:19–25.
1400 Phyllanthus emblica L.

24. Chen TS, Liou SY, Wu HC, et al. Efficacy of epigallocatechin-3-gallate

and Amla (Emblica officinalis) extract for the treatment of diabetic-uremic
patients. J Med Food. 2011;14:718–23.
25. Choudhary GP. Biodeterioration in Emblica based medicinal products and
their aflatoxin contamination. Anc Sci Life. 2011;30:65–71.
26. Damodara Reddy V, Padmavathi P, Gopi S, et al. Protective effect of
Emblica officinalis against alcohol-induced hepatic injury by ameliorating
oxidative stress in rats. Indian J Clin Biochem. 2010;25:419–24.
27. De A, De A, Papasian C, et al. Emblica officinalis extract induces autophagy
and inhibits human ovarian cancer cell proliferation, angiogenesis, growth
of mouse xenograft tumors. PLoS ONE. 2013;8:e72748.
28. Deng R. A review of the hypoglycemic effects of five commonly used
herbal food supplements. Recent Pat Food Nutr Agric. 2012;4:50–60.
29. Dhingra D, Joshi P, Gupta A, Chhillar R. Possible involvement of mono-
aminergic neurotransmission in antidepressant-like activity of Emblica
officinalis fruits in mice. CNS Neurosci Ther. 2012;18:419–25.
30. D’souza JJ, D’souza PP, Fazal F, et al. Antidiabetic effects of the Indian
indigenous fruit Emblica officinalis Gaertn.: active constituents and modes
of action. Food Funct. 2014;5:635–44.
31. el-Mekkawy S, Meselhy MR, Kusumoto IT, et al. Inhibitory effects of
Egyptian folk medicines on human immunodeficiency virus (HIV) reverse
transcriptase. Chem Pharm Bull (Tokyo). 1995;43:641–8.
32. Fatima N, Pingali U, Muralidhar N. Study of pharmacodynamic interaction
of Phyllanthus emblica extract with clopidogrel and ecosprin in patients
with type II diabetes mellitus. Phytomedicine. 2014;21:579–85.
33. Fatima N, Pingali U, Pilli R. Evaluation of Phyllanthus emblica extract on
cold pressor induced cardiovascular changes in healthy human subjects.
Pharmacognosy Res. 2014;6:29–35.
34. Golechha M, Bhatia J, Arya DS. Hydroalcoholic extract of Emblica offici-
nalis Gaertn. affords protection against PTZ-induced seizures, oxidative stress
and cognitive impairment in rats. Indian J Exp Biol. 2010;48:474–8.
35. Golechha M, Bhatia J, Arya DS. Studies on effects of Emblica officinalis
(Amla) on oxidative stress and cholinergic function in scopolamine induced
amnesia in mice. J Environ Biol. 2012;33:95–100.
36. Golechha M, Bhatia J, Ojha S, Arya DS. Hydroalcoholic extract of
Emblica officinalis protects against kainic acid-induced status epilepticus
in rats: evidence for an antioxidant, anti-inflammatory, and neuroprotective
intervention. Pharm Biol. 2011;49:1128–36.
37. Gopa B, Bhatt J, Hemavathi KG. A comparative clinical study of
hypolipidemic efficacy of Amla (Emblica officinalis) with 3-hydroxy-
3-methylglutaryl-coenzyme-A reductase inhibitor simvastatin. Indian J
Pharmacol. 2012;44:238–42.
38. Gulati RK, Agarwal S, Agrawal SS. Hepatoprotective studies on Phyllan-
thus emblica Linn. and quercetin. Indian J Exp Biol. 1995;33:261–8.
Phyllanthus emblica L. 1401

39. Habib-ur-Rehman, Yasin KA, Choudhary MA, et al. Studies on the chemical
constituents of Phyllanthus emblica. Nat Prod Res. 2007;21:775–81.
40. Haque R, Bin-Hafeez B, Ahmad I, et al. Protective effects of Emblica
officinalis Gaertn. in cyclophosphamide-treated mice. Hum Exp Toxicol.
2001;20:643–50.
41. Hari Kumar KB, Sabu MC, Lima PS, Kuttan R. Modulation of haematopo-
etic system and antioxidant enzymes by Emblica officinalis Gaertn. and its
protective role against gamma-radiation induced damages in mice. J Radiat
Res (Tokyo). 2004;45:549–55.
42. Hiraganahalli BD, Chinampudur VC, Dethe S, et al. Hepatoprotective and
antioxidant activity of standardized herbal extracts. Pharmacogn Mag. 2012;
8:116–23.
43. Huabprasert S, Kasetsinsombat K, Kangsadalampai K, et al. The Phyl-
lanthus emblica L. infusion carries immunostimulatory activity in a mouse
model. J Med Assoc Thai. 2012;95 Suppl 2:S75–82.
44. Ihantola-Vormisto A, Summanen J, Kankaanranta H, et al. Anti-inflammatory
activity of extracts from leaves of Phyllanthus emblica. Planta Med. 1997;
63:518–24.
45. Jacob A, Pandey M, Kapoor S, Saroja R. Effect of the Indian gooseberry
(Amla) on serum cholesterol levels in men aged 35–55 years. Eur J Clin
Nutr. 1988;42:939–44.
46. Jagetia GC. Radioprotective potential of plants and herbs against the
effects of ionizing radiation. J Clin Biochem Nutr. 2007;40:74–81.
47. Jain SK, Khurdiya DS. Vitamin C enrichment of fruit juice based
ready-to-serve beverages through blending of Indian gooseberry (Emblica
officinalis Gaertn.) juice. Plant Foods Hum Nutr. 2004;59:63–6.
48. Jeena KJ, Joy KL, Kuttan R. Effect of Emblica officinalis, Phyllanthus
amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepa-
tocarcinogenesis. Cancer Lett. 1999;136:11–6.
49. Jindal A, Soyal D, Sharma A, Goyal PK. Protective effect of an extract
of Emblica officinalis against radiation-induced damage in mice. Integr
Cancer Ther. 2009;8:98–105.
50. Jose JK, Kuttan G, Kuttan R. Antitumour activity of Emblica officinalis.
J Ethnopharmacol. 2001;75:65–9.
51. Jose JK, Kuttan R. Hepatoprotective activity of Emblica officinalis and
Chyavanaprash. J Ethnopharmacol. 2000;72:135–40.
52. Kalekar SA, Munshi RP, Thatte UM. Do plants mediate their antidiabetic
effects through antioxidant and antiapoptotic actions? An in vitro assay of
3 Indian medicinal plants. BMC Complement Altern Med. 2013;13:257.
53. Kalekar SA, Munshi RP, Bhalerao SS, Thatte UM. Insulin sensitizing
effect of 3 Indian medicinal plants: an in vitro study. Indian J Pharmacol.
2013;45:30–3.
1402 Phyllanthus emblica L.

54. Khan MT, Lampronti I, Martello D, et al. Identification of pyrogallol as an

antiproliferative compound present in extracts from the medicinal plant
Emblica officinalis: effects on in vitro cell growth of human tumor cell
lines. Int J Oncol. 2002;21:187–92.
55. Khanna S, Das A, Spieldenner J, Rink C, Roy S. Supplementation of a
standardized extract from Phyllanthus emblica improves cardiovascular
risk factors and platelet aggregation in overweight/class-1 obese adults.
J Med Food. 2015;18:415–20.
56. Kim HJ, Yokozawa T, Kim HY, et al. Influence of Amla (Emblica
officinalis Gaertn.) on hypercholesterolemia and lipid peroxidation in
cholesterol-fed rats. J Nutr Sci Vitaminol (Tokyo). 2005;51:413–8.
57. Kim HY, Okubo T, Juneja LR, Yokozawa T. The protective role of Amla
(Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome
in a rat model. Br J Nutr. 2010;103:502–12.
58. Koshy SM, Bobby Z, Hariharan AP, Gopalakrishna SM. Amla (Emblica
officinalis) extract is effective in preventing high fructose diet-induced
insulin resistance and atherogenic dyslipidemic profile in ovariectomized
female albino rats. Menopause. 2012;19:1146–55.
59. Krishnaveni M, Mirunalini S. Chemopreventive efficacy of Phyllanthus
emblica L. (Amla) fruit extract on 7,12-dimethylbenz(a)anthracene induced
oral carcinogenesis—a dose-response study. Environ Toxicol Pharmacol.
2012;34:801–10.
60. Kumar A, Tantry BA, Rahiman S, Gupta U. Comparative study of antimi-
crobial activity and phytochemical analysis of methanolic and aqueous
extracts of the fruit of Emblica officinalis against pathogenic bacteria.
J Tradit Chin Med. 2011;31:246–50.
61. Kumar KCS, Müller K. Medicinal plants from Nepal; II. Evaluation as
inhibitors of lipid peroxidation in biological membranes. J Ethnopharma-
col. 1999;64:135–9.
62. Kumar NP, Annamalai AR, Thakur RS. Antinociceptive property of
Emblica officinalis Gaertn. (Amla) in high fat diet-fed/low dose streptozo-
tocin induced diabetic neuropathy in rats. Indian J Exp Biol. 2009;47:
737–42.
63. Kumaran A, Karunakaran RJ. Nitric oxide radical scavenging active compo-
nents from Phyllanthus emblica L. Plant Foods Hum Nutr. 2006;61:1–5.
64. Lambertini E, Piva R, Khan MT, et al. Effects of extracts from Bangladeshi
medicinal plants on in vitro proliferation of human breast cancer cell lines
and expression of estrogen receptor alpha gene. Int J Oncol. 2004;24:
419–23.
65. Lee CY, Peng WH, Cheng HY, et al. Hepatoprotective effect of Phyllanthus
in Taiwan on acute liver damage induced by carbon tetrachloride. Am J
Chin Med. 2006;34:471–82.
Phyllanthus emblica L. 1403

66. Li B, Huang GQ, Lu RM, Wei JH, Zhong ZG. Study on chemical
composition of Phyllanthus emblica. Zhong Yao Cai. 2015;38:290–3
(Chinese).
67. Lv JJ, Wang YF, Zhang JM, et al. Antihepatitis B virus activities and
absolute configurations of sesquiterpenoid glycosides from Phyllanthus
emblica. Org Biomol Chem. 2014;12:8764–74.
68. Mahata S, Pandey A, Shukla S, et al. Anticancer activity of Phyllanthus
emblica Linn. (Indian gooseberry): inhibition of transcription factor AP-1
and HPV gene expression in cervical cancer cells. Nutr Cancer. 2013;65
Suppl 1:88–97.
69. Majeed M, Bhat B, Jadhav AN, et al. Ascorbic acid and tannins from
Emblica officinalis Gaertn. fruits. A Revisit. J Agric Food Chem. 2009;
57:220–5.
70. Mathur R, Sharma A, Dixit VP, Varma M. Hypolipidaemic effect of fruit
juice of Emblica officinalis in cholesterol-fed rabbits. J Ethnopharmacol.
1996;50:61–8.
71. Menon LG, Kuttan R, Kuttan G. Effect of rasayanas in the inhibition of
lung metastasis induced by B16F-10 melanoma cells. J Exp Clin Cancer
Res. 1997;16:365–8.
72. Mir AI, Kumar B, Tasduq SA, et al. Reversal of hepatotoxin-induced
prefibrogenic events by Emblica officinalis—a histological study. Indian J
Exp Biol. 2007;45:626–9.
73. Mishra M, Pathak UN, Khan AB. Emblica officinalis Gaertn. and serum
cholesterol level in experimental rabbits. Br J Exp Pathol. 1981;62:526–8.
74. Muruganandam AV, Kumar V, Bhattacharya SK. Effect of polyherbal
formulation, EuMil, on chronic stress-induced homeostatic perturbations in
rats. Indian J Exp Biol. 2002;40:1151–60.
75. Muthuraman A, Sood S, Singla SK. The anti-inflammatory potential of
phenolic compounds from Emblica officinalis L. in rat. Inflammopharma-
cology. 2011;19:327–34.
76. Nain P, Saini V, Sharma S, Nain J. Antidiabetic and antioxidant potential
of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced
type-2 diabetes mellitus (T2DM) rats. J Ethnopharmacol. 2012;142:65–71.
77. Nakanishi K, Sasaki S, Kiang AK, et al. Phytochemical survey of Malaysian
plants preliminary chemical and pharmacological screening. Chem Pharm
Bull (Tokyo). 1965;13:882–90.
78. Nampoothiri SV, Prathapan A, Cherian OL, et al. In vitro antioxidant and
inhibitory potential of Terminalia bellerica and Emblica officinalis fruits
against LDL oxidation and key enzymes linked to type 2 diabetes. Food
Chem Toxicol. 2011;49:125–31.
79. Ngamkitidechakul C, Jaijoy K, Hansakul P, et al. Antitumour effects
of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition
of in vivo tumour promotion and in vitro invasion of human cancer cells.
Phytother Res. 2010;24:1405–13.
1404 Phyllanthus emblica L.

80. Nicolis E, Lampronti I, Dechecchi MC, et al. Pyrogallol, an active compound

from the medicinal plant Emblica officinalis, regulates expression of
proinflammatory genes in bronchial epithelial cells. Int Immunopharmacol.
2008;8:1672–80.
81. Ojha S, Golechha M, Kumari S, Arya DS. Protective effect of Emblica
officinalis (Amla) on isoproterenol-induced cardiotoxicity in rats. Toxicol
Ind Health. 2012;28:399–411.
82. Panchabhai TS, Ambarkhane SV, Joshi AS, et al. Protective effect of
Tinospora cordifolia, Phyllanthus emblica and their combination against
antitubercular drugs induced hepatic damage: an experimental study.
Phytother Res. 2008;22:646–50 (Erratum in: Phytother Res. 2008;22:1274).
83. Panda S, Kar A. Fruit extract of Emblica officinalis ameliorates hyperthy-
roidism and hepatic lipid peroxidation in mice. Pharmazie. 2003;58:753–5.
84. Patel SS, Goyal RK. Prevention of diabetes-induced myocardial dysfunc-
tion in rats using the juice of the Emblica officinalis fruit. Exp Clin Cardiol.
2011;16:87–91.
85. Perianayagam JB, Sharma SK, Joseph A, Christina AJ. Evaluation of
antipyretic and analgesic activity of Emblica officinalis Gaertn. J Ethnophar-
macol. 2004;95:83–5.
86. Pinmai K, Chunlaratthanabhorn S, Ngamkitidechakul C, et al. Synergistic
growth inhibitory effects of Phyllanthus emblica and Terminalia bellerica
extracts with conventional cytotoxic agents: doxorubicin and cisplatin
against human hepatocellular carcinoma and lung cancer cells. World J
Gastroenterol. 2008;14:1491–7.
87. Pinmai K, Hiriote W, Soonthornchareonnon N, et al. In vitro and in vivo
antiplasmodial activity and cytotoxicity of water extracts of Phyllanthus
emblica, Terminalia chebula, and Terminalia bellerica. J Med Assoc Thai.
2010;93 Suppl 7:S120–6.
88. Pozharitskaya ON, Ivanova SA, Shikov AN, Makarov VG. Separation and
evaluation of free radical-scavenging activity of phenol components of
Emblica officinalis extract by using an HPTLC-DPPH* method. J Sep Sci.
2007;30:1250–4.
89. Prajapati VK, Nema PK, Rathore SS. Effect of pretreatment and drying
methods on quality of value-added dried aonla (Emblica officinalis Gaertn.)
shreds. J Food Sci Technol. 2011;48:45–52.
90. Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C. The
protective effects of Phyllanthus emblica Linn. extract on ethanol induced
rat hepatic injury. J Ethnopharmacol. 2006;107:361–4.
91. Puppala M, Ponder J, Suryanarayana P, et al. The isolation and character-
ization of b-glucogallin as a novel aldose reductase inhibitor from Emblica
officinalis. PLoS ONE. 2012;7:e31399.
92. Rahmatullah M, Azam MN, Khatun Z, et al. Medicinal plants used for
treatment of diabetes by the Marakh sect of the Garo tribe living in
Mymensingh district, Bangladesh. Afr J Tradit Complement Altern Med.
2012;9:380–5.
Phyllanthus emblica L. 1405

93. Rajak S, Banerjee SK, Sood S, et al. Emblica officinalis causes myocardial
adaptation and protects against oxidative stress in ischemic-reperfusion
injury in rats. Phytother Res. 2004;18:54–60.
94. Rajeshkumar NV, Pillai MR, Kuttan R. Induction of apoptosis in mouse
and human carcinoma cell lines by Emblica officinalis polyphenols and
its effect on chemical carcinogenesis. J Exp Clin Cancer Res. 2003;22:
201–12.
95. Rao TP, Sakaguchi N, Juneja LR, et al. Amla (Emblica officinalis Gaertn.)
extracts reduce oxidative stress in streptozotocin-induced diabetic rats.
J Med Food. 2005;8:362–8.
96. Reddy VD, Padmavathi P, Kavitha G, et al. Emblica officinalis ameliorates
alcohol-induced brain mitochondrial dysfunction in rats. J Med Food.
2011;14:62–8.
97. Reddy VD, Padmavathi P, Paramahamsa M, Varadacharyulu NC. Ame-
lioration of alcohol-induced oxidative stress by Emblica officinalis (Amla)
in rats. Indian J Biochem Biophys. 2010;47:20–5.
98. Reddy VD, Padmavathi P, Varadacharyulu NCh. Emblica officinalis pro-
tects against alcohol-induced liver mitochondrial dysfunction in rats. J Med
Food. 2009;12:327–33.
99. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six
rasayana herbs used in Ayurvedic medicine. Phytother Res. 1999;13:275–91.
100. Sabu MC, Kuttan R. Antidiabetic activity of medicinal plants and its
relationship with their antioxidant property. J Ethnopharmacol. 2002;81:
155–60.
101. Saeed S, Tariq P. Antibacterial activities of Emblica officinalis and
Coriandrum sativum against Gram negative urinary pathogens. Pak J
Pharm Sci. 2007;20:32–5.
102. Saini A, Sharma S, Chhibber S. Protective efficacy of Emblica officinalis
against Klebsiella pneumoniae induced pneumonia in mice. Indian J Med
Res. 2008;128:188–93.
103. Sairam K, Rao ChV, Babu MD, et al. Antiulcerogenic effect of methanolic
extract of Emblica officinalis: an experimental study. J Ethnopharmacol.
2002;82:1–9.
104. Saito K, Kohno M, Yoshizaki F, Niwano Y. Extensive screening for edible
herbal extracts with potent scavenging activity against superoxide anions.
Plant Foods Hum Nutr. 2008;63:65–70.
105. Sancheti G, Jindal A, Kumari R, Goyal PK. Chemopreventive action of
Emblica officinalis on skin carcinogenesis in mice. Asian Pac J Cancer
Prev. 2005;6:197–201.
106. Sarkar R, Hazra B, Mandal N. Amelioration of iron overload-induced liver
toxicity by a potent antioxidant and iron chelator Emblica officinalis Gaertn.
Toxicol Ind Health. 2015;31:656–69.
107. Sarkar R, Mandal N. Hydroalcoholic extracts of Indian medicinal plants can
help in amelioration from oxidative stress through antioxidant properties.
J Complement Integr Med. 2012;9:Article 7.
1406 Phyllanthus emblica L.

108. Shah JS, Goyal RK. Usage trends for memory and vitality-enhancing
medicines: a pharmacoepidemiological study involving pharmacists of the
Gujarat region. Int J Ayurveda Res. 2010;1:138–43.
109. Sharma A, Sharma MK, Kumar M. Modulatory role of Emblica offi-
cinalis fruit extract against arsenic induced oxidative stress in Swiss albino
mice. Chem Biol Interact. 2009;180:20–30.
110. She G, Cheng R, Sha L, et al. A novel phenolic compound from Phyllanthus
emblica. Nat Prod Commun. 2013;8:461–2.
111. Shukla V, Vashistha M, Singh SN. Evaluation of antioxidant profile and
activity of amalaki (Emblica officinalis), spirulina and wheat grass. Indian J
Clin Biochem. 2009;24:70–5.
112. Sidhu S, Pandhi P, Malhotra S, et al. Beneficial effects of Emblica
officinalis in L-arginine-induced acute pancreatitis in rats. J Med Food.
2011;14:147–55.
113. Singh I, Sharma A, Nunia V, Goyal PK. Radioprotection of Swiss albino
mice by Emblica officinalis. Phytother Res. 2005;19:444–6.
114. Singh I, Soyal D, Goyal PK. Emblica officinalis (Linn.) fruit extract
provides protection against radiation-induced hematological and biochem-
ical alterations in mice. J Environ Pathol Toxicol Oncol. 2006;25:643–54.
115. Sultana S, Ahmad S, Khan N, Jahangir T. Effect of Emblica officinalis
(Gaertn.) on CCl4 induced hepatic toxicity and DNA synthesis in Wistar
rats. Indian J Exp Biol. 2005;43:430–6.
116. Sultana S, Ahmed S, Jahangir T. Emblica officinalis and hepatocarcino-
genesis: a chemopreventive study in Wistar rats. J Ethnopharmacol. 2008;
118:1–6.
117. Sultana S, Ahmed S, Sharma S, Jahangir T. Emblica officinalis reverses
thioacetamide-induced oxidative stress and early promotional events of
primary hepatocarcinogenesis. J Pharm Pharmacol. 2004;56:1573–9.
118. Sumantran VN, Kulkarni A, Chandwaskar R, et al. Chondroprotective
potential of fruit extracts of Phyllanthus emblica in osteoarthritis. Evid
Based Complement Alternat Med. 2008;5:329–35.
119. Suresh K, Vasudevan DM. Augmentation of murine natural killer cell and
antibody dependent cellular cytotoxicity activities by Phyllanthus emblica,
a new immunomodulator. J Ethnopharmacol. 1994;44:55–60.
120. Suryanarayana P, Kumar PA, Saraswat M, et al. Inhibition of aldose
reductase by tannoid principles of Emblica officinalis: implications for the
prevention of sugar cataract. Mol Vis. 2004;10:148–54.
121. Suryanarayana P, Saraswat M, Petrash JM, Reddy GB. Emblica officinalis
and its enriched tannoids delay streptozotocin-induced diabetic cataract in
rats. Mol Vis. 2007;13:1291–7.
122. Tasanarong A, Kongkham S, Itharat A. Antioxidant effect of Phyllanthus
emblica extract prevents contrast-induced acute kidney injury. BMC
Complement Altern Med. 2014;14:138.
Phyllanthus emblica L. 1407

123. Tasduq SA, Kaisar P, Gupta DK, et al. Protective effect of a 50%
hydroalcoholic fruit extract of Emblica officinalis against antituberculosis
drugs induced liver toxicity. Phytother Res. 2005;19:193–7.
124. Tasduq SA, Mondhe DM, Gupta DK, Baleshwar M, Johri RK. Reversal of
fibrogenic events in liver by Emblica officinalis (fruit), an Indian natural
drug. Biol Pharm Bull. 2005;28:1304–6.
125. Thakur CP, Mandal K. Effect of Emblica officinalis on cholesterol-induced
atherosclerosis in rabbits. Indian J Med Res Sect A—Infect Dis. 1984;79:
142–6.
126. Thakur CP, Thakur B, Singh S, et al. The ayurvedic medicines Haritaki,
Amala and Bahira reduce cholesterol-induced atherosclerosis in rabbits.
Int J Cardiol. 1988;21:167–75.
127. Thakur CP. Emblica officinalis reduces serum, aortic and hepatic choles-
terol in rabbits. Experientia. 1985;41:423–4.
128. Thirunavukkarasu M, Selvaraju V, Tapias L, et al. Protective effects
of Phyllanthus emblica against myocardial ischemia-reperfusion injury: the
role of PI3-kinase/glycogen synthase kinase 3b/b-catenin pathway. J Phys-
iol Biochem. 2015;71:623–33.
129. Thorat SP, Rege NN, Naik AS, et al. Emblica officinalis: a novel therapy
for acute pancreatitis—an experimental study. HPB Surg. 1995;9:25–30.
130. Tiwari V, Kuhad A, Chopra K. Emblica officinalis corrects functional,
biochemical and molecular deficits in experimental diabetic neuropathy by
targeting the oxidonitrosative stress mediated inflammatory cascade.
Phytother Res. 2011;25:1527–36.
131. Usharani P, Fatima N, Muralidhar N. Effects of Phyllanthus emblica extract
on endothelial dysfunction and biomarkers of oxidative stress in patients
with type 2 diabetes mellitus: a randomized, double-blind, controlled study.
Diabetes Metab Syndr Obes. 2013;6:275–84.
132. Vasant RA, Narasimhacharya AV. Amla as an antihyperglycemic and
hepatorenal protective agent in fluoride induced toxicity. J Pharm Bioallied
Sci. 2012;4:250–4.
133. Verma R, Chakraborty D. Alterations in DNA, RNA and protein contents
in liver and kidney of mice treated with ochratoxin and their amelioration
by Emblica officinalis aqueous extract. Acta Pol Pharm. 2008;65:3–9.
134. Verma R, Chakraborty D. Emblica officinalis aqueous extract ameliorates
ochratoxin-induced lipid peroxidation in the testis of mice. Acta Pol
Pharm. 2008;65:187–94.
135. Vijayalakshmi S, Arunkumar V, Anju D, et al. Comparative antimicrobial
activities of Emblica officinalis and Ocimum sanctum. Anc Sci Life. 2007;
27:1–6.
136. Waheed S, Fatima I. Instrumental neutron activation analysis of Emblica
officinalis, Terminalia belerica and Terminalia chebula for trace element
efficacy and safety. Appl Radiat Isot. 2013;77:139–44.
1408 Phyllanthus emblica L.

137. Xia Q, Xiao P, Wan L, Kong J. Ethnopharmacology of Phyllanthus

emblica L.]. Zhongguo Zhong Yao Za Zhi. 1997;22:515–8, 525, 574
(Chinese).
138. Xiang Y, Pei Y, Qu C, et al. In vitro antiherpes simplex virus activity of
1,2,4,6-tetra-O-galloyl-b-D-glucose from Phyllanthus emblica L. (Euphor-
biaceae). Phytother Res. 2011;25:975–82.
139. Yahayo W, Supabphol A, Supabphol R. Suppression of human fibrosar-
coma cell metastasis by Phyllanthus emblica extract in vitro. Asian Pac J
Cancer Prev. 2013;14:6863–7.
140. Yokozawa T, Kim HY, Kim HJ, et al. Amla (Emblica officinalis Gaertn.)
prevents dyslipidaemia and oxidative stress in the ageing process. Br J
Nutr. 2007;97:1187–95.
141. Yokozawa T, Kim HY, Kim HJ, et al. Amla (Emblica officinalis Gaertn.)
attenuates age-related renal dysfunction by oxidative stress. J Agric Food
Chem. 2007;55:7744–52.
142. Zhang LZ, Zhao WH, Guo YJ, et al. Studies on chemical constituents in
fruits of Tibetan medicine Phyllanthus emblica. Zhongguo Zhong Yao Za
Zhi. 2003;28:940–3 (Chinese).
143. Zhang Y, Zhao L, Guo X, et al. Chemical constituents from Phyllanthus
emblica and the cytoprotective effects on H2O2-induced PC12 cell injuries.
Arch Pharm Res. 2016;39:1202–11.
144. Zhang YJ, Abe T, Tanaka T, et al. Phyllanemblinins A-F, new ellagitannins
from Phyllanthus emblica. J Nat Prod. 2001;64:1527–32.
145. Zhang YJ, Tanaka T, Yang CR, Kouno I. New phenolic constituents from
the fruit juice of Phyllanthus emblica. Chem Pharm Bull (Tokyo).
2001;49:537–40.
146. Zhao T, Sun Q, Marques M, Witcher M. Anticancer properties of Phyl-
lanthus emblica (Indian Gooseberry). Oxid Med Cell Longev. 2015;2015:
950890.
147. Zhu X, Wang J, Ou Y, Han W, Li H. Polyphenol extract of Phyllanthus
emblica (PEEP) induces inhibition of cell proliferation and triggers apop-
tosis in cervical cancer cells. Eur J Med Res. 2013;18:46.
Picrorhiza kurroa Royle ex Benth.
(Plantaginaceae)

Abstract
An herbaceous suckering plant, that is found in the Himalayas (India, Nepal), and
China. It is called White Christmas Rose because the flowers appear in winter
during Christmas time. In Unani medicine, the rhizomes/root are considered
stomachic, carminative, anthelmintic, and laxative; purgative in high doses. It is
used to strengthen stomach function in cases of indigestion, in ascites due to
hepatic involvement, to kill and expel intestinal worms, and especially useful for
brain ailments. In small doses, it is a bitter, stomachic and laxative, and in large
doses, a cathartic, and used in the treatment of epilepsy, paralysis, as an emme-
nagogue, emetic, abortifacient, and antidote to dog bite. It is also used in chronic
dysentery, asthma, hepatic derangement, jaundice, and as a valuable antiperiodic
in low continued fevers. It is one of the most commonly used drugs in polyherbal
preparations clinically used in India for their potent antihepatotoxic activity in
various liver disorders. Hepatoprotective effects of P. kurroa are similar and
superior to the effect of Silybum marianum in the treatment of toxic hepatitis, fatty
liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis, due to its
antioxidative, antilipidperoxidative, antifibrotic, anti-inflammatory, immunomod-
ulating, and liver regenerating effects. Iridoids: pikuroside, picroside I, picroside
II, and 6-feruloyl catalpol, iridoid glycosides: 6-feruloylcatalpol, veronicoside and
minecoside, and two phenol glucosides, picein and androsin, cucurbitacine
glycosides, and apocynin have been isolated from the rhizomes. Aqueous extract
significantly reduced TC, LDL-C, and TGs of hyperlipemic mice. Hydroalcohol
extract, methanol extract, and picroliv are protective against various hepatotoxic
agents, and picroliv is also a potent choleretic and anticholestatic agent than
silymarin. Alcohol extract lowers blood glucose in basal conditions and after a
heavy glucose load in normal rats, and in diabetic rats; aqueous extract also
significantly reduces diabetic hyperglycemia and nephropathy, and a standardized

© Springer Nature Switzerland AG 2020 1409

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_145
1410 Picrorhiza kurroa Royle ex Benth.

aqueous extract significantly lowered blood glucose and the lipids (TC, LDL-C
and TGs). Ethanol rhizome extract enhanced healing rate of gastric ulcers in rats,
with significant elevation of antioxidant enzymes; and picroliv methanol and
aqueous extracts demonstrated significant free radical scavenging capacity.

Keywords





Asava Hellebore Katu-rohini Kharbaq-e-aswad Kharbaq-e-hindi Kutki siah

Vernaculars: Urd.: Kutki siah; Hin.: Katki, Kuru, Kutki, Pathanbed; San.:
Katuka, Katu-rohini, Krishna bhedi, Kutaki, Kutaki-dhauvan, Matsya-pitta, Mtsya-
vinna, Rohini, Vakragra; Ben.: Katki, Kutki, Tita; Mar.: Balakadu; Tam.:
Kadugu-rohini, Katuku-rogani; Tel.: Katuku-roni; Ara.: Asava, Kharbaq-e-aswad;
Eng.: Hellebore, White Christmas rose; Per.: Kharbaq-e-hindi.
Description: An herbaceous suckering plant with short stem and a thick root, is
found in the Himalayas (India, Nepal), and China. It is called White Christmas Rose
because the flowers appear in winter during Christmas time.LXXXI Leaves in rosettes
near the base of the stem, narrowing toward the petiole, oblong, crenelate-dentate,
5–10 cm long. Inflorescence a terminal spike, peduncle scapiform; flowers sessile,
purple, provided with lanceolate bracts. Fruit an acute capsule with 4 coriaceous
valves, 12 mm long. Root is available in pieces 3–5 cm long, 1 cm in diameter,
epidermis brownish-yellow, interior black; odor of the root is hay-like and tastes
bitter.LXXIX Available drug in India is a rhizome, broken into pieces from 2.5 to 5 cm
long, 3–4 mm in diameter, the lower portion of which is covered by a shriveled,
greyish-brown, corky bark, and marked by prominent scars, the remains of rootlets;
towards the upper end it becomes larger, and is thickly set with dark greyish-brown
scales, and terminates in a scaly leaf-bud or stem; it is black internally, no odor and a
very bitter taste.XL However, a monograph on P. kurroa described the plants as “a
small perennial herb from the Scrophulariaceae family, found in the Himalayan
region growing at elevations of 3,000–5,000 m. Picrorhiza kurroa has a long,
creeping rootstock that is bitter in taste, and grows in rock crevices and moist, sandy
soil. The leaves of the plant are flat, oval, and sharply serrated. Flowers, which
appear June through August, are white or pale-purple and borne on a tall spike;
manual harvesting of the plant takes place October through December [1].” In Unani
medicine, both P. kurroa and Helliborus niger (black Hellebore) are described as
Kali Kutki (black Kutki) and Gentiana Kurroo as Kutki or Safed Kutki (white Kutki).
However, Dymock et al.XL have disputed the description of black Hellebore as Kutki
and they quote Ainslie who said that the drug available in Indian bazaars was very
different in appearance from the black Hellebore available in European markets.
Later, Muslim writers and others confirmed kutki as being the rhizome of P. kurroa.
Therefore, description of kutki in some Unani books as Helliborus niger seems to be
incorrect. NadkarniCV mentioned that P. kurroa is very commonly used either as an
adulterant of or as substitute for Gentiana kurroo.
Picrorhiza kurroa Royle ex Benth. 1411

Actions and Uses: In Unani medicine, the rhizomes/root (temperament, hot 3° and
dry 3°; NadkarniCV mentioned the temperament as hot 1° and dry 2°) are considered
stomachic, carminative, anthelmintic, and laxative; purgative in high doses. It is used
to strengthen stomach function in cases of indigestion, in ascites due to hepatic
involvement, to kill and expel intestinal worms, and especially useful for brain
ailments.LXXVII In small doses, it is a bitter, stomachic and laxative, and in large
doses, a cathartic, and used in the treatment of epilepsy, paralysis, as an emmena-
gogue, emetic, abortifacient, and antidote to dog bite.CV It is also used in chronic
dysentery, asthma, hepatic derangement, jaundice, and as a valuable antiperiodic in
low continued fevers.LXXXI In Ayurveda, it is described as digestive, bitter, pungent,
dry, aperient, light and cold, and is recommended as a remedy for worms, asthma,
bile, phlegm, and fever. It is also a favorite remedy for bilious dyspepsia accompanied
by fever, and is given daily in decoction with liquorice, raisins and neem bark, 5 g of
each in 320 ml of water boiled down to one fourth.XL Rhizomes and roots are also
used in fevers, jaundice and various stomach ailments in children [53]. It is one of the
most commonly used drugs in polyherbal preparations clinically used in India for
their potent antihepatotoxic activity in various liver disorders [43, 60, 62]. Hepato-
protective effects of P. kurroa are similar and superior to the effect of Silybum
marianum in the treatment of toxic hepatitis, fatty liver, cirrhosis, ischemic injury,
radiation toxicity, and viral hepatitis, due to its antioxidative, antilipidperoxidative,
antifibrotic, anti-inflammatory, immunomodulating, and liver regenerating effects
[34]. KeysLXXIX described it as antipyretic and stomachic.
Phytoconstituents: Basu et al. [5, 6] first isolated and elucidated the structure of
the bitter glucoside, picroliv or Kutkin; which is an iridoid glycoside mixture
containing 60% picroside I and kutkoside in the ratio of 1:1.5 that is normally
obtained from 3 to 4 years old roots and rhizomes [62]. Iridoids: pikuroside, picroside
I, picroside II, and 6-feruloyl catalpol [24], iridoid glycosides: 6-feruloylcatalpol,
veronicoside and minecoside, and two phenol glucosides, picein and androsin [58],
cucurbitacine glycosides [59], and apocynin (4-hydroxy-3-methoxyacetophenone)
have been isolated from the rhizomes; apocynin is regarded as a specific inhibitor for
NADPH oxidase in cell and animal models [64]. Picrosides I and II accumulation is
directly correlated with altitude, and plants grown at lower altitude have reduced
picroside contents; the quantities of picrosides are highest in rhizomes, followed by
roots, inflorescence and leaves [29]. Picrorhiza acid, picrorhizoside A–C, (-)-shikimic
acid, gallic acid, ellagic acid, isocorilagin, 1-O-galloyl-b-D-glucose, 1-O,3-O,6-O-
trigalloyl-b-D-glucose, and 1-O,2-O,3-O,4-O,6-O-pentagalloyl-b-D-glucose have
been isolated from seeds. Ellagic acid and 1-O,2-O,3-O,4-O,6-O-pentagalloyl-b-D-
glucose inhibit COX-1 by 70 and 89%, respectively; and isocorilagin and 1-O,2-O,
3-O,4-O,6-O-pentagalloyl-b-D-glucose also inhibit COX-2 by 42 and 43%, respec-
tively [69]. Luteolin-5-O-glucopyranoside and picein were isolated from leaves [27].
Picroliv, the active principle, has picroside I, catalpol, kutkoside I, and kutkoside as
its major components [36].
1412 Picrorhiza kurroa Royle ex Benth.

Pharmacology: Powdered drug (100 mg/kg bw) suspended in gum acacia sig-
nificantly reduced carrageenan-induced paw edema in rats [28]. The extract also
significantly inhibited joint inflammation in formaldehyde and adjuvant-induced
arthritis in rats, and considerably reduced synovial expression of IL-1b, IL-6, TNF
receptor-1 and VEGF, and increased levels of GSH and activities of SOD and CAT
[30], and also significantly inhibited carrageenan-induced paw edema and cotton
pellet implantation-induced granuloma formation in rats [31]. Apocynin inhibits
in vitro formation of TXA2, and stimulates the release of PGE2 and PGF2a; and
potently inhibits AA-induced aggregation of bovine platelets [19]. Aqueous extract
significantly reduced TC, LDL-C, and TGs in high fat diet-induced hyperlipemic
mice [32]; whereas picroliv prevented hydrazine-induced hyperlipidemia, and
hepatic steatosis in rats [63]. Hydroalcohol extract [39, 55], methanol extract,XIX
and picroliv are protective against various hepatotoxic agents [8, 12–18, 45–48, 51,
57, 61, 66, 67] and picroliv is also a potent choleretic and anticholestatic agent than
silymarin [56]. Ethanol rhizome extract enhanced healing rate of indomethacin-
induced gastric ulcers in rats, with significant elevation of antioxidant enzymes
[3, 49], and picroliv ameliorated DSS-induced colitis in mice [68]. Methanol and
aqueous extracts possess a significant free radical scavenging capacity [42, 50], and
methanol extract protects against H2O2-induced DNA damage in human nonim-
mortalized fibroblasts [50]. Butanol and ethyl acetate leaf extracts showed greater
antioxidant activity than ethanol extract [27]. Ethanol extracts of rhizomes and
leaves potently stimulate, both cell-mediated and humoral immunity [2, 7, 21, 54].
Hydroalcohol extract and picroliv significantly inhibited NDEA-induced hepato-
carcinogenesis [23, 40], and 20-MCA-induced sarcoma tumor burden and death in
mice [26, 41]. Topical application of picroliv also reduced DMBA-induced papil-
lomas in mice [41]. Alcohol extract lowers blood glucose in basal conditions and
after a heavy glucose load in normal and diabetic rats [25]; aqueous extract also
significantly reduces diabetic hyperglycemia and nephropathy [33], and a stan-
dardized aqueous extract with 5% kutkin contents significantly lowered blood
glucose and the lipids (TC, LDL-C and TGs) [20]. Pretreatment of rats with ethanol
extract for 15-days significantly ameliorated isoproterenol-induced MI [37, 52].
Treatment of rats with picroliv at two doses (6 and 12 mg/kg, p.o.) during the
last 4-weeks of 24-weeks cadmium challenge, ameliorated Cd-induced early tes-
ticular damage [65], and significantly ameliorated hepatic and renal manifestations
of cadmium toxicity [67]. Cold and hot alcohol extracts inhibited growth of
P. falciparum by 100% and 90%, respectively [22], and methanol extract showed
moderate activity against MDR S. typhi [44]. Four-weeks pretreatment with pow-
dered roots rendered guinea pigs less sensitive to histamine, markedly enhanced the
bronchodilator effects of isoproterenol and epinephrine, and significantly reduced
severity and duration of allergic bronchospasm, and reduced histamine content of
lung tissue [35]. Androsin, a phenol glycoside was identified as the active com-
pound that prevented allergen and PAF-induced bronchial obstruction in guinea
pigs [9, 10]. Oral administration of picroliv also inhibited passive cutaneous ana-
phylaxis in mice (82%) and rats (50–85%) and protected mast cells degranulation
(60–80%) [4].
Picrorhiza kurroa Royle ex Benth. 1413

Clinical Studies: In a pilot double-blind, placebo-controlled study, administration

of root powder, 300 mg thrice daily for 14-weeks, to 72 Indian patients with COPD
and bronchial asthma yielded inconclusive results, because a large number of 50
patients defaulted [11]. Root powder (375 mg three times a day) given for 2-weeks
to patients with acute viral hepatitis improved LFTs, and reduced time required for
total serum bilirubin to drop to average value of 2.5 mg% from 75.9 days in
placebo group to 27.44 days in the treated group [61].
Mechanism of Action: Anti-inflammatory activity is mediated through suppres-
sion of macrophage-derived cytokines and other mediators, via suppression of NF-j
B signaling pathway [31]. A nonneural augmentation of b-adrenoceptor function or
consequent cellular events were also suggested responsible for its anti-inflammatory
effects [38].
Human A/Es, Allergy and Toxicity: Ten out of 52 patients (*20%) in the COPD
trial were reported to experience vomiting (4), cutaneous rash (1), anorexia (3),
diarrhea (2), itching (2) and giddiness (1) [11].
Animal Toxicity: Oral LD50 of ethanol extract in mice was reported to be 1,288
mg/kg (range 979–1,596 mg) [7].
Commentary: Although one RCT demonstrated its hepatoprotective effect vali-
dating pharmacological results in animals, more clinical studies are needed to
corroborate this effect. Also, the antiasthmatic effect should be evaluated in only
bronchial asthma patients not complicated with COPD. Its anti-inflammatory
activity is also worth to be tested in patients.

References
1. Anonymous. Picrorhiza kurroa. Monograph. Altern Med Rev. 2001;6:
319–21.
2. Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of
plant origin. I: Preliminary Screening. J. Ethnopharmacol. 1986;18:133–41.
3. Banerjee D, Maity B, Nag SK, et al. Healing potential of Picrorhiza kurroa
(Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration:
a mechanistic exploration. BMC Complement Altern Med. 2008;8:3.
4. Baruah CC, Gupta PP, Nath A, et al. Antiallergic and antianaphylactic
activity of picroliv—a standardised iridoid glycoside fraction of Picrorhiza
kurroa. Pharmacol Res. 1998;38:487–92.
5. Basu K, Dasgupta B, Ghosal S. Chemistry of kutkin, isolated from
Picrorhiza kurroa Royle ex Benth. Experientia. 1970;26:818–9.
6. Basu K, Dasgupta B, Ghosal S. Structure of kutkin, the bitter glucoside of
Picrorhiza kurroa Royle ex Benth. J Org Chem. 1970;35:3159–61.
7. Bellanti JA. Immunology II. Philadelphia, PA: W.B. Saunders Co.; 1978.
p. 225–42.
1414 Picrorhiza kurroa Royle ex Benth.

8. Dhuley JN. Effect of picroliv administration on hepatic microsomal mixed

function oxidases and glutathione-conjugating enzyme system in cholestatic
rats. Hindustan Antibiot Bull. 2005–2006;47–48:13–9.
9. Dorsch W, Stuppner H, Wagner H, et al. Antiasthmatic effects of Picrorhiza
kurroa: androsin prevents allergen- and PAF-induced bronchial obstruction
in guinea pigs. Int Arch Allergy Appl Immunol. 1991;95:128–33.
10. Dorsch W, Wagner H. New antiasthmatic drugs from traditional medicine?
Int Arch Aller Appl Immunol. 1991;94:262–5.
11. Doshi VB, Shetye VM, Mahashur AA, Kamat SR. Picrorrhiza kurroa in
bronchial asthma. J Postgrad Med. 1983;29:89–95.
12. Dwivedi Y, Rastogi R, Chander R, et al. Hepatoprotective activity of
picroliv against carbon tetrachloride-induced liver damage in rats. Indian J
Med Res. 1990;92:195–200.
13. Dwivedi Y, Rastogi R, Garg NK, Dhawan BN. Effects of picroliv, the active
principle of Picrorhiza kurroa, on biochemical changes in rat liver poisoned
by Amanita phalloides. Zhongguo Yao Li Xue Bao. 1992;13:197–200.
14. Dwivedi Y, Rastogi R, Garg NK, Dhawan BN. Perfusion with picroliv
reverses biochemical changes induced in livers of rats toxicated with
galactosamine or thioacetamide. Planta Med. 1993;59:418–20.
15. Dwivedi Y, Rastogi R, Garg NK, Dhawan BN. Picroliv and its components
kutkoside and picroside I protect liver against galactosamine-induced
damage in rats. Pharmacol Toxicol. 1992;71:383–7.
16. Dwivedi Y, Rastogi R, Mehrotra R, et al. Picroliv protects against aflatoxin
B1 acute hepatotoxicity in rats. Pharmacol Res. 1993;27:189–99.
17. Dwivedi Y, Rastogi R, Sharma SK, et al. Picroliv affords protection against
thioacetamide-induced hepatic damage in rats. Planta Med. 1991;57:25–8.
18. Dwivedi Y, Rastogi R, Sharma SK, et al. Picroliv protects against monocro-
taline-induced hepatic damage in rats. Pharmacol Res. 1991;23:399–407.
19. Engels F, Renirie BF, Hart BA, et al. Effects of apocynin, a drug isolated
from the roots of Picrorhiza kurroa, on arachidonic acid metabolism. FEBS
Lett. 1992;305:254–6.
20. Husain GM, Singh PN, Kumar V. Antidiabetic activity of standardized
extract of Picrorhiza kurroa in rat model of NIDDM. Drug Discov Ther.
2009;3:88–92.
21. Hussain A, Shadma W, Maksood A, Ansari SH. Protective effects of
Picrorhiza kurroa on cyclophosphamide-induced immunosuppression in
mice. Pharmacognosy Res. 2013;5:30–5.
22. Irshad S, Mannan A, Mirza B. Antimalarial activity of three Pakistani
medicinal plants. Pak J Pharm Sci. 2011;24:589–91.
23. Jeena KJ, Joy KL, Kuttan R. Effect of Emblica officinalis, Phyllanthus
amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepato-
carcinogenesis. Cancer Lett. 1999;136:11–6.
24. Jia Q, Hong MF, Minter D. Pikuroside: a novel iridoid from Picrorhiza
kurroa. J Nat Prod. 1999;62:901–3.
Picrorhiza kurroa Royle ex Benth. 1415

25. Joy KL, Kuttan R. Antidiabetic activity of Picrorrhiza kurroa extract.

J Ethnopharmacol. 1999;67:143–8.
26. Joy KL, Rajeshkumar NV, Kuttan G, Kuttan R. Effect of Picrorrhiza kurroa
extract on transplanted tumours and chemical carcinogenesis in mice.
J Ethnopharmacol. 2000;71:261–6.
27. Kant K, Walia M, Agnihotri VK, Pathania V, Singh B. Evaluation of
antioxidant activity of Picrorhiza kurroa (leaves) extracts. Indian J Pharm
Sci. 2013;75:324–9.
28. Kantibiswas T, Marjit B, Maity LN. Effect of Picrorhiza kurroa benth. In
acute inflammation. Anc Sci Life. 1996;16:11–4.
29. Katoch M, Fazli IS, Suri KA, et al. Effect of altitude on picroside content in
core collections of Picrorhiza kurrooa from the northwestern Himalayas.
J Nat Med. 2011;65:578–82.
30. Kumar R, Gupta YK, Singh S, Arunraja S. Picrorhiza kurroa inhibits
experimental arthritis through inhibition of proinflammatory cytokines,
angiogenesis and MMPs. Phytother Res. 2016;30:112–9.
31. Kumar R, Gupta YK, Singh S, Raj A. Anti-inflammatory effect of Picrorhiza
kurroa in experimental models of inflammation. Planta Med. 2016;82:
1403–9.
32. Lee HS, Yoo CB, Ku SK. Hypolipemic effect of water extracts of Picrorrhiza
kurroa in high fat diet treated mouse. Fitoterapia. 2006;77:579–84.
33. Lee HS, Ku SK. Effect of Picrorrhiza rhizoma extracts on early diabetic
nephropathy in streptozotocin-induced diabetic rats. J Med Food. 2008;11:
294–301.
34. Luper S. A review of plants used in the treatment of liver disease: part 1.
Altern Med Rev. 1998;3:410–21.
35. Mahajani SS, Kulkarni RD. Effect of disodium cromoglycate and Picrorhiza
kurroa root powder on sensitivity of guinea pigs to histamine and sympa-
thomimetic amines. Int Arch Allergy Appl Immunol. 1977;53:137–44.
36. Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN. In vitro
studies on the effect of certain natural products against hepatitis B virus.
Indian J Med Res Section A-Infectious Dis. 1990;92:133–8.
37. Nandave M, Ojha SK, Kumari S, et al. Cardioprotective effect of root extract
of Picrorhiza kurroa (Royle ex Benth.) against isoproterenol-induced
cardiotoxicity in rats. Indian J Exp Biol. 2013;51:694–701.
38. Pandey BL, Das PK. Immunopharmacological studies on Picrorhiza kurroa
Royle-ex-Benth. Part III: adrenergic mechanisms of anti-inflammatory
action. Indian J Physiol Pharmacol. 1988;32:120–5.
39. Rahman S, Sultana S. Protective effects of Picorrhiza kurroa extract against
2-acetylaminofluorene-induced hepatotoxicity in Wistar rats. J Environ
Pathol Toxicol Oncol. 2007;26:195–205.
40. Rajeshkumar NV, Kuttan R. Inhibition of N-nitrosodiethylamine-induced
hepatocarcinogenesis by Picroliv. J Exp Clin Cancer Res. 2000;19:459–65.
1416 Picrorhiza kurroa Royle ex Benth.

41. Rajeshkumar NV, Kuttan R. Protective effect of Picroliv, the active

constituent of Picrorhiza kurroa, against chemical carcinogenesis in mice.
Teratog Carcinog Mutagen. 2001;21:303–13.
42. Rajkumar V, Guha G, Kumar RA. Antioxidant and antineoplastic activities
of Picrorhiza kurroa extracts. Food Chem Toxicol. 2011;49:363–9.
43. Ram VJ. Herbal preparations as a source of hepatoprotective agents. Drug
News Perspect. 2001;14:353–63.
44. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
45. Rastogi R, Saksena S, Garg NK, et al. Picroliv protects against alcohol-
induced chronic hepatotoxicity in rats. Planta Med. 1996;62:283–5.
46. Rastogi R, Srivastava AK, Rastogi AK. Biochemical changes induced in
liver and serum of aflatoxin B1-treated male Wistar rats: preventive effect of
picroliv. Pharmacol Toxicol. 2001;88:53–8.
47. Rastogi R, Srivastava AK, Rastogi AK. Long term effect of aflatoxin B(1)
on lipid peroxidation in rat liver and kidney: effect of picroliv and silymarin.
Phytother Res. 2001;15:307–10.
48. Rastogi R, Srivastava AK, Srivastava M, Rastogi AK. Hepatocurative effect
of picroliv and silymarin against aflatoxin B1 induced hepatotoxicity in rats.
Planta Med. 2000;66:709–13.
49. Ray A, Chaudhuri SR, Majumdar B, Bandyopadhyay SK. Antioxidant
activity of ethanol extract of rhizome of Picrorhiza kurroa on indomethacin
induced gastric ulcer during healing. Indian J Clin Biochem. 2002;17:44–51.
50. Russo A, Izzo AA, Cardile V, et al. Indian medicinal plants as antiradicals
and DNA cleavage protectors. Phytomedicine. 2001;8:125–32.
51. Saraswat B, Visen PK, Patnaik GK, Dhawan BN. Ex vivo and in vivo
investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication
model in rats. J Ethnopharmacol. 1999;66:263–9.
52. Senthil Kumar SH, Anandan R, Devaki T, Santhosh Kumar M. Cardiopro-
tective effects of Picrorrhiza kurroa against isoproterenol-induced myocar-
dial stress in rats. Fitoterapia. 2001;72:402–5.
53. Shah NC. Herbal folk medicines in Northern India. J Ethnopharmacol.
1982;6:293–301.
54. Sharma ML, Rao CS, Duda PL. Immunostimulatory activity of Picrorhiza
kurroa leaf extract. J Ethnopharmacol. 1994;41:185–92.
55. Shetty SN, Mengi S, Vaidya R, Vaidya AD. A study of standardized
extracts of Picrorhiza kurroa Royle ex Benth. in experimental nonalcoholic
fatty liver disease. J Ayurveda Integr Med. 2010;1:203–10.
56. Shukla B, Visen PK, Patnaik GK, Dhawan BN. Choleretic effect of picroliv,
the hepatoprotective principle of Picrorhiza kurroa. Planta Med. 1991;57:
29–33.
57. Singh M, Tiwari V, Jain A, Ghoshal S. Protective activity of picroliv on
hepatic amoebiasis associated with carbon tetrachloride toxicity. Indian J
Med Res. 2005;121:676–82.
Picrorhiza kurroa Royle ex Benth. 1417

58. Stuppner H, Wagner H. Minor iridoid and phenol glycosides of Picrorhiza

kurrooa. Planta Med. 1989;55:467–9.
59. Stuppner H, Wagner H. New cucurbitacin glycosides from Picrorhiza
kurrooa. Planta Med. 1989;55:559–63.
60. Thyagarajan SP, Jayaram S, Gopalakrishnan V, et al. Herbal medicines for
liver diseases in India. J Gastroenterol Hepatol. 2002;17 Suppl 3:S370–6.
61. Vaidya AB, Antarkar DS, Doshi JC, et al. Picrorhiza kurroa (Kutaki) Royle
ex Benth. as a hepatoprotective agent—experimental & clinical studies.
J Postgrad Med. 1996;42:105–8.
62. Verma PC, Basu V, Gupta V, et al. Pharmacology and chemistry of a potent
hepatoprotective compound picroliv isolated from the roots and rhizomes
of Picrorhiza kurroa Royle ex Benth. (kutki). Curr Pharm Biotechnol. 2009;
10:641–9.
63. Vivekanandan P, Gobianand K, Priya S, et al. Protective effect of picroliv
against hydrazine-induced hyperlipidemia and hepatic steatosis in rats. Drug
Chem Toxicol. 2007;30:241–52.
64. Wang Q, Smith RE, Luchtefeld R, et al. Bioavailability of apocynin through
its conversion to glycoconjugate but not to diapocynin. Phytomedicine. 2008;
15:496–503.
65. Yadav N, Khandelwal S. Effect of picroliv on cadmium induced testicular
damage in rat. Food Chem Toxicol. 2008;46:494–501.
66. Yadav N, Khandelwal S. Effect of picroliv on cadmium-induced hepatic and
renal damage in the rat. Hum Exp Toxicol. 2006;25:581–91.
67. Yadav N, Khandelwal S. Therapeutic efficacy of picroliv in chronic
cadmium toxicity. Food Chem Toxicol. 2009;47:871–9.
68. Zhang DK, Yu JJ, Li YM, et al. A Picrorhiza kurroa derivative, picroliv,
attenuates the development of dextran-sulfate-sodium-induced colitis in
mice. Mediators Inflamm. 2012;2012:751629.
69. Zhang Y, DeWitt DL, Murugesan S, Nair MG. Novel lipid-peroxidation-
and cyclooxygenase-inhibitory tannins from Picrorhiza kurroa seeds. Chem
Biodivers. 2004;1:426–41.
Pimpinella anisum L.
(Apiaceae/Umbelliferae)

(Syn.: Anisum vulgare Gart.)

Abstract
An annual herb, a native of Egypt, but cultivated in Iran, India, Mediterranean
region, and Europe. Ibn al-Baitar, quoting Dioscorides, said that the fruits (seeds)
are diuretic, carminative, analgesic, anti-inflammatory, diaphoretic, galactagogue,
and aphrodisiac. According to Razi, it is useful in ascites and relieves flatulence
and borborygmus, and Avicenna called Anisun deobstruent for kidney, bladder,
liver and uterine obstructions, useful in chronic fevers and swelling of face and
feet. Ibn Jazlah described Anisun as fennel seeds, with a sweet taste, causes
constipation, and is used to prevent obstruction of liver, and as antidote against
poisons. Ibn Buţlān used it for cold stomach, against flatulence, and considered it
diuretic, to relieve constipation, to increase postpartum milk production, and to
improve eyesight. In Unani medicine, the fruits are included in diets of patients
suffering from paralysis, facial palsy and epilepsy. Anise water and oil are
topically applied to head in headache and to abdomen in flatulence and intestinal
colic. Anise was not known to Hindu physicians and was introduced in India by
Muslim physicians from Persia. In Iranian traditional medicine, the fruits are used
as carminative, aromatic, disinfectant, antimicrobial, galactagogue, antioxidant,
anticonvulsant, analgesic and muscle relaxant, and anise oil for treatment of
convulsions. In Cayenne and French Guiana, whole plant is used as carminative
and vermifuge, while the flowers and seeds decoctions are used for gas pain by
Guyana Patamona people. The plant is used for respiratory disorders in Upper
Egypt. In addition to anethol-glycol, creosol, anethol, acetaldehyde, isoamy-
lamine, umbelliferone, bergaptene, isopimpinellin, isobergaptene and sphondin,
anise seeds (fruit) contain protein, fat, carbohydrate, fiber, and minerals. The
flavonoids reported include, quercetin-3-glucoronide, rutin, luteolin 7-glucoside,
isoorientin, isovitexin, apigenin 7-glucoside, and a luteolin glycoside. Aqueous
and ethanol extracts significantly increased milk production in rats by 68 and 81%,
respectively. The weight gain by pups during the study period was correlated with

© Springer Nature Switzerland AG 2020 1419

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_146
1420 Pimpinella anisum L.

the milk production. Aqueous suspension of powdered seeds (fruit) exhibited

significant cytoprotective and antiulcer activities against gastric lesions. In a
double-blind RCT of patients with functional dyspepsia, symptoms and quality of
life were highly significantly improved after 12-weeks of treatment with anise
powder.

Keywords







Adis-manis Anacio Anijs Anise Anisoon Glikaniso Raziyanah Saunf




Shatava Vilayati saunf

Vernaculars: Urd.: Anisoon, Badyan, Saunf; Hin.: Choti saunf, Saunf, Vilayati
saunf; San.: Awak-pushpi, Karavasata-pushpha, Karavee, Madhurimisi, Shata-
pushpa, Shatava, Shetpushpa; Ben.: Mahoori, Mitha jira, Muhuri; Mal.: Adis-manis,
Jira-manis, Perinchirakam; Mar.: Somp; Tam.: Shombu; Tel.: Kuppi-chattu, Sompu;
Ara.: Anisun, Bazar-ul-razianaj rumi, Bazar-ul-razianaj shami, Kamoon-al-hilu,
Raziyanaj, Shamar; Dut.: Anijs; Eng.: Anise, Aniseed, Sweet cumin, Sweet fennel;
Fre.: Anis, Anis vert, Boucage; Ger.: Anis, Anis-biberrell; Gre.: Anison, Glikaniso,
Glykaniso; Ita.: Anacio, Anice verde, Anice vero; Per.: Badyan rumi, Raziyanah,
Raziyan-e-rumi, Zeera-e-rumi; Por.: Anis, Erva-doce; Spa.: Anis; Tur.: Anason.
Description: An annual herb, a native of Egypt, but cultivated in Iran, India,
Mediterranean region, and Europe. The size of the fruit varies quite a bit, if well
grown it should be about 5 mm long; the mericarps often adhere together with the
pedicel attached, forming an ovoid body crowned by a pair of styles. Each fruit has
ten ridges, and is covered with short hairs. The vittae which contain essential oil,
are very numerous, each mericarp containing about fifteen of them. Taste is
remarkably sweet and aromatic.XL Ibn al-BaitarLXIX quoting Dioscorides said that
fresh, larger, very aromatic and one shedding scales-like is the best (Figs. 1 and 2).
Actions and Uses: Ibn al-Baitar,LXIX quoting Dioscorides, said that the fruits (seeds)
are diuretic, carminative, analgesic, anti-inflammatory, diaphoretic, galactagogue,
and aphrodisiac. According to Razi, it is useful in ascites and relieves flatulence and
borborygmus, and Avicenna called Anisun deobstruent for kidney, bladder, liver and
uterine obstructions, useful in chronic fevers and swelling of face and feet. Ibn Jazlah
described Anisun as fennel seeds, with a sweet taste, causes constipation, and is used
to prevent obstruction of liver, and as antidote against poisons.LIII Ibn Buţlān used it
for cold stomach, against flatulence, and considered it diuretic, to relieve constipa-
tion, to increase postpartum milk production, and to improve eyesight.LIII In Unani
medicine, the fruits (temperament, hot 3° and dry 3° per Galen) are regarded as
carminative, analgesic, diuretic, diaphoretic, lactogenic, and improve facial com-
plexion; and included in diets of patients suffering from paralysis, facial palsy and
epilepsy.L Anise water and oil are topically applied to head in headache and to
abdomen in flatulence and intestinal colic.CV Anise was not known to Hindu
physicians and was introduced in India by Muslim physicians from Persia. The
volatile oil which is the active component is aromatic, slightly stimulant of heart and
Pimpinella anisum L. 1421

Fig. 1 Pimpinella anisum, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Koehler1887-PimpinellaAnisum.jpg

Fig. 2 Pimpinella anisum, Anise Fruits, Ben_pcc, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:AniseSeeds.jpg

digestive organs. It liquifies bronchial secretions, and hence used as expectorant, and
for infantile bronchial catarrh, after the acute stage has passed. Due to its carminative
and stomachic properties, it is used in flatulence, intestinal colic and in bowel
complaints, and is added as a corrective to allay griping of purgative medicines.
Externally, it is applied to joints in rheumatism.LXXXI It is also reported abortifacient,
1422 Pimpinella anisum L.

anodyne, antiseptic, aromatic, collyrium, fungicidal, pectoral, stimulant, tonic, and

sudorific; and used for asthma, bronchitis, cancer, cholera, cough, dropsy, dysmen-
orrhea, epilepsy, halitosis, indigestion, insomnia, lice, migraine, nausea, nephrosis,
neuralgia, scabies, and renal stones.XXXVIII In Iranian traditional medicine, the fruits
are used as carminative, aromatic, disinfectant, antimicrobial, galactagogue, antiox-
idant, anticonvulsant, analgesic and muscle relaxant [47], and anise oil for the
treatment of convulsions [25, 40]. In Cayenne and French Guiana, whole plant is used
as carminative and vermifuge, while the flowers and seeds decoctions are used for gas
pain by Guyana Patamona people.XXXIV The plant is used for respiratory disorders in
Upper Egypt [2]. Hot water extracts of seeds have been used in Lebanese folk
medicine for their diuretic, laxative, expectorant and antispasmodic effects, and their
ability to ease intestinal colic and flatulence [33]. In Palestine, about 34% university
students, especially females and medical college students use herbal drugs for
self-therapy, and aniseed is one of the most commonly used herbs [45]. Anise oil,
mixed with Sassafras oil is used against insects. Anethole, anisaldehyde, d-carvone
and myristicin, all have mild insecticidal properties, and the fungicidal oil is used in
oil-painting in China.XXXVIII It is also one of the commonly used herbs by the Carib
population of Guatemala [20]. Aniseed is reputed to facilitate birth, increase milk
secretion, promote menstruation, alleviate symptoms of male climacteric, and
increase libido [6]. P. anisum is approved for GI disorders use in Europe since Nov.
2005 by the HMPC of the European Medicines Agency.
Phytoconstituents: Anise seeds (fruits)(100 g) contain 337 calories, 17.6 g protein,
15.9 g fat, 50 g total carbohydrate, 14.6 g fiber, 7 g ash, 646 mg Ca, 440 mg P,
37 mg Fe, 170 mg Mg, 16 mg Na, 1,441 mg K and 5.3 mg Zn, in addition to
anethol-glycol, creosol, anethol, acetaldehyde, isoamylamine, umbelliferone, ber-
gaptene, isopimpinellin, isobergaptene and sphondin.XXXVIII The flavonoids reported
include, quercetin-3-glucoronide, rutin, luteolin 7-glucoside, isoorientin, isovitexin,
apigenin 7-glucoside, and a luteolin glycoside [34]. Fruits EO (yield 2–3.5%) con-
tains 90% anethole, also methyl chavicol, p-methoxyphenyl acetone and acetalde-
hyde.XLVII Several sesquiterpenes were identified in the oil [10]. Most important
compounds of EO of aniseeds are trans-anethole, c-himachalen, p-anisaldehyde,
methyl chavicol [47], cis-isoeugenol and linalool [43]. There are differences in the
composition of EO from different European countries; trans-anethole (76.9–93.7%)
is the major component, and c-himachalene (0.4–8.2%), trans-pseudoisoeugenyl
2-methylbutyrate (0.4–6.4%), p-anisaldehyde (tr—5.4%) and methyl chavicol
(0.5–2.3%) are the other principal compounds. Highest content of trans-anethole
(>90%) were found in samples from Greece, Hungary, Scotland, Lithuania, Italy,
and Germany; whereas oil from Estonia was rich in c-himachalene (8.2%) and
trans-pseudoisoeugenyl 2-methylbutyrate (6.4%). French sample of oil contained
highest amount of anisaldehyde (5.4%) compared to other samples (0-3.1%) [39].
Fitsiou et al. [14] also reported trans-anethole (88.1%) as the major component of EO
from Greece. Various glucosides and glycosides have also been isolated from fruits
[15, 23, 30]. Application of Zn fertilizer considerably increased the number of
detected EO components from 27 to 45, and considerably increased levels of phenolic
compounds, especially of chlorogenic acid [51].
Pimpinella anisum L. 1423

Pharmacology: Aqueous and ethanol extracts significantly increased milk pro-

duction in rats by 68 and 81%, respectively. The weight gain by pups during the
study period was correlated with the milk production [22]. Aqueous suspension of
powdered seeds exhibited significant cytoprotective and antiulcer activities against
gastric lesions, which was possibly PG-mediated and/or through its antisecretory
and antioxidative properties [4]. The plant also stimulated pancreatic lipase activity,
increasing it by 186.5% [3]. Ethanol seed extract protected rats against
gentamicin-nephrotoxicity [11], and exhibited strong antioxidant activity, not cor-
related with its flavonoid contents [38]. Essential oil obtained by SCCD extraction
exhibited higher antioxidant activity than steam distilled oil [52].
Aqueous seed (fruit) extract failed to demonstrate antianxiety effects in rats up to
an oral dose of 2 g/kg [16], but the aqueous and ethanol extracts were suggested to
possess fluoxetine-like antidepressant activity in mice [46]. Anise oil elevated
threshold of PTZ-induced clonic convulsions in mice and suppressed tonic con-
vulsions induced by both PTZ and MES [40], and was protective to rats against
aspartame-neurotoxicity [1]. The oil significantly enhanced glucose absorption
from rat jejunum and increased Na+-K+ ATPase activity in jejunal homogenate
without altering colonic Na+-K+ ATPase activity. However, administered to rats in
drinking water, it reduced urine volume and increased activity of renal Na+-K+
ATPase even at extremely low concentrations [33]. Both hydroethanol extract and
EO significantly reversed the increase in TC, LDL-C and TGs due to nonalcoholic
fatty liver disease in rats [7]. n-Hexane seed extract significantly protected against
CCl4-toxicity both to HepG2 cells and to rats, compared to ethanol extract and EO
[24]. Anethole and EO significantly stimulated regeneration of hepatic cells in rats.
Aqueous extract stimulated osteoblastic cell differentiation and exhibited antie-
strogenic effect on breast cancer cells without proliferative effects on cervical
adenocarcinoma cells [28].
Anise oil completely inhibited growth of A. flavus, A. ochraceus, A. parasiticus
and F. moniliforme fungi at < or = 500 ppm [50], and significantly inhibited HSV-2
[31]. Singh et al. [49] reported antibacterial activity of the oil against eight human
pathogenic bacteria, comparable to standard antibiotics. Anise EO could be used in
expectorants in combination with amoxicillin or ciprofloxacin for S. pneumoniae
infections without diminishing the antibiotics efficacy, as it showed positive inter-
action with them [21]. Methanol seed extract inhibited growth of 15 strains of
H. pylori with an MIC of 100 µg/ml [36], while Robles-Zepeda [41] reported 50%
MIC of methanol extract against H. pylori between 200 and 400 µg/ml. Anise
seeds fluid extract exhibited activity against C. albicans, C. parapsilosis, C. tropicalis,
C. pseudotropicalis and C. krusei, and no activity against C. glabrata, and a growth
promotion activity on Geotrichum spp. It also inhibited growth of dermatophytes,
T. rubrum, T. mentagrophytes, M. canis and M. gypseum. Anise EO exhibits
stronger antifungal activities against yeasts and dermatophytes [32]. p-Anisaldehyde
inhibited growth of 10 fluconazole-resistant and 5 fluconazole-sensitive Candida
strains, drastically reducing ergosterol content by 62% in sensitive and 66% in
resistant strains-that did not correlate well with MIC90 values [48]. Aqueous
decoction showed only 18% inhibition against 176 bacterial isolates from oral cavity
1424 Pimpinella anisum L.

of 200 individuals [12], while methanol extract and EO showed maximum

antibacterial activities against S. aureus, B. cereus and P. vulgaris; and EO was also
highly active against C. butyricum [26]. Combinations of EOs and methanol extracts
of Thymus vulgaris and P. anisum showed additive action against most tested
pathogens especially P. aeruginosa [5]. Methanol extract also enhanced inhibitory
effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid
against both the standard strain and the resistant strain of E. coli; it generally
enhanced activity against resistant strain [13]. Hydroalcohol seed extract was active
against S. mutans, L. rhamnosus, and A. viscosus [29]. Three antiviral and immunos-
timulating substances, isolated from hot water seed extract interfered with virus
adsorption to the host cell surface and directly inactivated viruses, and enhanced NO
production by inducing iNOS mRNA and protein expression [35].
Clinical Studies: In a double-blind RCT involving 107 Iranian patients with func-
tional dyspepsia, symptoms and quality of life were highly significantly improved
after 12-weeks of treatment with anise powder (3 g tid), compared to placebo [19]. In
an RCT of 72 postmenopausal Iranian women suffering from hot flashes, adminis-
tration of a capsule containing 330 mg P. anisum thrice daily reduced the frequency
and severity of hot flashes from 4.21% and 56.21% to 1.06% and 14.44%, respec-
tively, at the end of the fourth-week; the placebo treated group showed no significant
changes [37].
Mechanism of Action: Anise oil is reported to produce anticonvulsant effect
through GABA-ergic mechanism [42] or via inhibition of synaptic plasticity [27].
Bronchodilatory effect of EO, aqueous, and ethanol extracts is mediated through
antagonism of muscarinic receptors, and not due to antihistaminic, or b2-adrenergic
receptors stimulation [9]. Anethole has been considered to be the active estrogenic
agent, but studies suggest that the pharmacologically active agents are polymers of
anethole, such as dianethole and photoanethole [6]. The antiestrogenic effect of
aqueous extract on MCF-7 cells was inhibited in the presence of estradiol sug-
gesting an estrogen receptor-related mechanism and selective estrogen receptor
modulator (SERM)-like properties [28].
Human A/Es, Allergy and Toxicity: Aniseeds have caused cheilitis and stom-
atitis, and anethole can cause dermatitis (erythema, scaling and vesiculation).
Anethole used to flavor toothpastes is reported to produce contact sensitivity.
Aniseed allergens may cause occupational rhinoconjunctivitis and food allergy
[17], and reportedly produced repeated nocturnal tongue angioedema in a hyper-
sensitive Spanish patient after consumption of aniseed liqueur [18]. A severe case
of poisoning from anise oil was also reported from Denmark [8]. Simultaneous
hypersensitivity to celery, mugwort pollen, and spices of the Umbelliferae family
(aniseeds, cumin, tare, fennel, dill, coriander, and parsley) is known as the celery-
mugwort-spices syndrome [18].
Animal Toxicity: LD50 (i.p.) values of aqueous and ethanolic extracts in rats were
reported as 4,930 and 3,770 mg/kg, respectively, and the maximum nonlethal dose
was 2,200 mg/kg [22]. Anethole is a moderate acute toxin with an oral LD50 of
Pimpinella anisum L. 1425

2,090 mg/kg in rats. Rats fed a diet containing 0.25% anethole for 1-year showed
no ill-effects, while those receiving 1% for 15-weeks had microscopic alterations of
hepatocytes. Trans-anethole fed in diet to Sprague-Dawley rats at concentrations of
0, 0.25, 0.5 and 1% for 117–121 weeks, caused no excess mortality, but only a
transient retardation of body-weight gain [53].
Potential for Drug-Herb Interactions: Anise oil can have interactions with many
prescription drugs, as pretreatment with oil significantly increased analgesic effect
of codeine, enhanced midazolam-induced motor impairment, and augmented effect
of diazepam on motor activity. Antidepressant effects of imipramine and fluoxetine
were diminished by pretreatment with aniseed oil [43]. Five days pretreatment of
mice with EO (0.3 mg/kg/day) also significantly reduced peak plasma concentra-
tions of orally administered APAP and caffeine [44].
Commentary: Antispasmodic, antiflatulent and other benefits in functional gastric
disorders are proven in widespread traditional uses, the basis for its approval by the
HMPC of the European Medicines Agency for GI disorders, and also demonstrated
in Iranian patients. However, its other uses are either not systematically evaluated or
in a limited way, such as in hot flashes of postmenopausal women. Further clinical
studies may expand the horizon of its evidence-based uses.

References
1. Abdul-Hamid M, Gallaly SR. Ameliorative effect of Pimpinella anisum oil
on immunohistochemical and ultrastuctural changes of cerebellum of albino
rats induced by aspartame. Ultrastruct Pathol. 2014;38:224–36.
2. AbouZid SF, Mohamed AA. Survey on medicinal plants and spices used in
Beni-Sueif, Upper Egypt. J Ethnobiol Ethnomed. 2011;7:18.
3. Ado MA, Abas F, Mohammed AS, Ghazali HM. Anti- and pro-lipase activity
of selected medicinal, herbal and aquatic plants, and structure elucidation of
an antilipase compound. Molecules. 2013;18:14651–69.
4. Al Mofleh IA, Alhaider AA, Mossa JS, et al. Aqueous suspension of anise
Pimpinella anisum protects rats against chemically induced gastric ulcers.
World J Gastroenterol. 2007;13:1112–8.
5. Al-Bayati FA. Synergistic antibacterial activity between Thymus vulgaris
and Pimpinella anisum essential oils and methanol extracts. J Ethnophar-
macol. 2008;116:403–6.
6. Albert-Puleo M. Fennel and anise as estrogenic agents. J Ethnopharmacol.
1980;2:337–44.
7. Asadollahpoor A, Abdollahi M, Rahimi R. Pimpinella anisum L. fruit:
chemical composition and effect on rat model of nonalcoholic fatty liver
disease. J Res Med Sci. 2017;22:37.
8. Bang J, Mortensen OS, Ebbehøj N. Poisoning by anis oil. Ugeskr Laeger.
2008;170:461 (Danish).
1426 Pimpinella anisum L.

9. Boskabady MH, Ramazani-Assari M. Relaxant effect of Pimpinella anisum

on isolated guinea pig tracheal chains and its possible mechanism(s).
J Ethnopharmacol. 2001;74:83–8.
10. Burkhardt G, Reichling J, Martin R, Becker H. Terpene hydrocarbons in
Pimpinella anisum L. Pharmaceutisch Weekblad—Scientific Edition. 1986;8:
190–3.
11. Changizi-Ashtiyani S, Seddigh A, Najafi H, et al. Pimpinella anisum L.
ethanolic extract ameliorates the gentamicin- induced nephrotoxicity in rats.
Nephrology (Carlton). 2017;22:133–8.
12. Chaudhry NM, Tariq P. Bactericidal activity of black pepper, bay leaf,
aniseed and coriander against oral isolates. Pak J Pharm Sci. 2006;19:214–8.
13. Darwish RM, Aburjai TA. Effect of ethnomedicinal plants used in folklore
medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli.
BMC Complement Altern Med. 2010;10:9.
14. Fitsiou E, Mitropoulou G, Spyridopoulou K, et al. Phytochemical profile
and evaluation of the biological activities of essential oils derived from the
Greek aromatic plant species Ocimum basilicum, Mentha spicata, Pimpinella
anisum and Fortunella margarita. Molecules. 2016;21. pii: E1069.
15. Fujimatu E, Ishikawa T, Kitajima J. Aromatic compound glucosides, alkyl
glucoside and glucide from the fruit of anise. Phytochemistry. 2003;63:
609–16.
16. Gamberini MT, Rodrigues DS, Rodrigues D, Pontes VB. Effects of the
aqueous extract of Pimpinella anisum L. seeds on exploratory activity and
emotional behavior in rats using the open field and elevated plus maze tests.
J Ethnopharmacol. 2015;168:45–9.
17. García-González JJ, Bartolomé-Zavala B, Fernández-Meléndez S, et al.
Occupational rhinoconjunctivitis and food allergy because of aniseed
sensitization. Ann Allergy Asthma Immunol. 2002;88:518–22.
18. Gázquez García V, Gaig Jané P, Bartolomé Zavala B. Aniseed-induced
nocturnal tongue angioedema. J Investig Allergol Clin Immunol. 2007;17:
406–8.
19. Ghoshegir SA, Mazaheri M, Ghannadi A, et al. Pimpinella anisum in modi-
fying the quality of life in patients with functional dyspepsia: a double-blind
randomized clinical trial. J Res Med Sci. 2014;19:1118–23.
20. Giron LM, Freire V, Alonzo A, Caceres A. Ethnobotanical survey of the
medicinal flora used by the Caribs of Guatemala. J Ethnopharmacol. 1991;
34:173–87.
21. Gradinaru AC, Miron A, Trifan A, et al. Screening of antibacterial effects of
anise essential oil alone and in combination with conventional antibiotics
against Streptococcus pneumoniae clinical isolates. Rev Med Chir Soc Med
Nat Iasi. 2014;118:537–43.
22. Hosseinzadeh H, Tafaghodi M, Abedzadeh S, Taghiabadi E. Effect of aqueous
and ethanolic extracts of Pimpinella anisum L. seeds on milk production in
rats. J Acupunct Meridian Stud. 2014;7:211–6.
Pimpinella anisum L. 1427

23. Ishikawa T, Fujimatu E, Kitajima J. Water-soluble constituents of anise:

new glucosides of anethole glycol and its related compounds. Chem Pharm
Bull (Tokyo). 2002;50:1460–6.
24. Jamshidzadeh A, Heidari R, Razmjou M, et al. An in vivo and in vitro
investigation on hepatoprotective effects of Pimpinella anisum seed essen-
tial oil and extracts against carbon tetrachloride-induced toxicity. Iran J
Basic Med Sci. 2015;18:205–11.
25. Janahmadi M, Farajnia S, Vatanparast J, et al. The fruit essential oil of
Pimpinella anisum L. (Umblliferae) induces neuronal hyperexcitability in
snail partly through attenuation of after-hyperpolarization. J Ethnopharma-
col. 2008;120:360–5.
26. Kačániová M, Vukovič N, Horská E, et al. Antibacterial activity against
Clostridium genus and antiradical activity of the essential oils from different
origin. J Environ Sci Health B. 2014;49:505–12.
27. Karimzadeh F, Hosseini M, Mangeng D, et al. Anticonvulsant and neuro-
protective effects of Pimpinella anisum in rat brain. BMC Complement
Altern Med. 2012;12:76.
28. Kassi E, Papoutsi Z, Fokialakis N, et al. Greek plant extracts exhibit
selective estrogen receptor modulator (SERM)-like properties. J Agric Food
Chem. 2004;52:6956–61.
29. Kermanshah H, Kamangar SS, Arami S, et al. The effect of hydroalcoholic
extract of seven plants on cariogenic bacteria—an in vitro evaluation. Oral
Health Dent Manag. 2014;13:395–401.
30. Kitajima J, Ishikawa T, Fujimatu E, et al. Glycosides of 2-C-methyl-
D-erythritol from the fruits of anise, coriander and cumin. Phytochemistry.
2003;62:115–20.
31. Koch C, Reichling J, Schneele J, Schnitzler P. Inhibitory effect of essential
oils against herpes simplex virus type 2. Phytomedicine. 2008;15:71–8.
32. Kosalec I, Pepeljnjak S, Kustrak D. Antifungal activity of fluid extract and
essential oil from anise fruits (Pimpinella anisum L., Apiaceae). Acta Pharm.
2005;55:377–85.
33. Kreydiyyeh SI, Usta J, Knio K, et al. Aniseed oil increases glucose
absorption and reduces urine output in the rat. Life Sci. 2003;74:663–73.
34. Kunzemann J, Herrmann K. Isolation and identification of flavon(ol)-
O-glycosides in caraway (Carum carvi L.), fennel (Foeniculum vulgare
Mill.), anise (Pimpinella anisum L.), and coriander (Coriandrum sativum
L.), and of flavon-C-glycosides in anise. I. Phenolics of spices (author’s
transl). Z Lebensm Unters Forsch. 1977;164:194–200 (German).
35. Lee JB, Yamagishi C, Hayashi K, Hayashi T. Antiviral and immunostim-
ulating effects of lignin-carbohydrate-protein complexes from Pimpinella
anisum. Biosci Biotechnol Biochem. 2011;75:459–65.
36. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Heli-
cobacter pylori to botanical extracts used traditionally for the treatment of
gastrointestinal disorders. Phytother Res. 2005;19:988–91.
1428 Pimpinella anisum L.

37. Nahidi F, Kariman N, Simbar M, Mojab F. The study on the effects of

Pimpinella anisum on relief and recurrence of menopausal hot flashes. Iran J
Pharm Res. 2012;11:1079–85.
38. Nickavar B, Abolhasani FA. Screening of antioxidant properties of seven
umbelliferae fruits from Iran. Pak J Pharm Sci. 2009;22:30–5.
39. Orav A, Raal A, Arak E. Essential oil composition of Pimpinella anisum L.
fruits from various European countries. Nat Prod Res. 2008;22:227–32.
40. Pourgholami MH, Majzoob S, Javadi M, et al. The fruit essential oil of
Pimpinella anisum exerts anticonvulsant effects in mice. J Ethnopharmacol.
1999;66:211–5.
41. Robles-Zepeda RE, Velázquez-Contreras CA, Garibay-Escobar A, Gálvez-
Ruiz JC, Ruiz-Bustos E. Antimicrobial activity of Northwestern Mexican
plants against Helicobacter pylori. J Med Food. 2011;14:1280–3.
42. Sahraei H, Ghoshooni H, Hossein Salimi S, et al. The effects of fruit
essential oil of the Pimpinella anisum on acquisition and expression of
morphine induced conditioned place preference in mice. J Ethnopharmacol.
2002;80:43–7.
43. Samojlik I, Mijatović V, Petković S, et al. The influence of essential oil of
aniseed (Pimpinella anisum, L.) on drug effects on the central nervous
system. Fitoterapia. 2012;83:1466–73.
44. Samojlik I, Petković S, Stilinović N, et al. Pharmacokinetic herb-drug
interaction between essential oil of aniseed (Pimpinella anisum L.,
Apiaceae) and acetaminophen and caffeine: a potential risk for clinical
practice. Phytother Res. 2016;30:253–9.
45. Sawalha AF, Sweileh WM, Zyoud SH, Jabi SW. Self-therapy practices
among university students in Palestine: focus on herbal remedies. Comple-
ment Ther Med. 2008;16:343–9.
46. Shahamat Z, Abbasi-Maleki S, Mohammadi Motamed S. Evaluation of
antidepressant-like effects of aqueous and ethanolic extracts of Pimpinella
anisum fruit in mice. Avicenna J Phytomed. 2016;6:322–8.
47. Shojaii A, Abdollahi Fard M. Review of pharmacological properties and
chemical constituents of Pimpinella anisum. ISRN Pharm. 2012;2012:
510795.
48. Shreaz S, Bhatia R, Khan N, et al. Exposure of Candida to p-anisaldehyde
inhibits its growth and ergosterol biosynthesis. J Gen Appl Microbiol. 2011;
57:129–36.
49. Singh G, Kapoor IP, Pandey SK, et al. Studies on essential oils: part 10;
antibacterial activity of volatile oils of some spices. Phytother Res. 2002;
16:680–2.
50. Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants
on different mycotoxigenic fungi. Food Chem Toxicol. 2002;40:1669–75.
51. Tavallali V, Rahmati S, Bahmanzadegan A. Antioxidant activity, polyphe-
nolic contents and essential oil composition of Pimpinella anisum L. as
affected by zinc fertilizer. J Sci Food Agric. 2017;97:4883–9.
Pimpinella anisum L. 1429

52. Topal U, Sasaki M, Goto M, Otles S. Chemical compositions and

antioxidant properties of essential oils from nine species of Turkish plants
obtained by supercritical carbon dioxide extraction and steam distillation.
Int J Food Sci Nutr. 2008;59:619–34.
53. Truhaut R, Le Bourhis B, Attia M, et al. Chronic toxicity/carcinogenicity
study of trans-anethole in rats. Food Chem Toxicol. 1989;27:11–20.
Piper cubeba L.f.
(Piperaceae)

(Syn.: Cubeba officinalis Raf.)

Abstract
The woody vine is a native plant of India, Sri Lanka, and East Indies (south and
southeast Asia). Avicenna described it as a good deobstruent and useful as an
application to putrid sores and pustules in the mouth; good for voice, and hepatic
obstructions, and a valuable diuretic expelling gravel and stone from kidneys and
bladder. He also states that application of the saliva, after chewing it, increases
sexual orgasm. Europeans were not aware of its medicinal properties and used it
only as a spice. In Unani medicine, it is regarded deobstruent, resolvent, stom-
achic, carminative, emmenagogue, diuretic, strengthens teeth and gums, clears
voice, rubefacient, improves complexion, and expels out kidney stones; and used
in the treatment of liver and spleen obstructions, and syphilis. Singers and public
speakers suck on it to prevent hoarseness of voice. Dried seeds of unripe fruits
were used in chronic bronchitis, as urinary antiseptic and to promote healing of
mucous membranes. Major chemical constituents identified in fruit EO are
sabinene, eucalyptol, 4-terpineol, b-pinene, camphor, and d-3-carene. Powdered
fruits exhibited both preventive and curative effect on gentamicin-nephrotoxicity
in rats, and fruit extract produced potent anti-inflammatory activity in various
experimental models of inflammation, and ethanol extract also inhibited in vitro
activities of COX-1, COX-2 and 5-LOX, and exhibited antiandrogenic, and
antiestrogenic activities. Ethanol extract significantly ameliorated CCl4-hepato-
toxicity, and restored antioxidant enzymes activities. Cubebin, the most abundant
lignan in Piper cubeba reportedly promotes vasorelaxation via NO/cGMP path-
way in rat aorta, without the involvement of prostacyclin.

Keywords




Betre Cheng qie Cubèbe Dhumkimirch Habb el’arûs

Kababchini





Kebebiye Stielpfeffer Sugandha-muricha Tailed pepper

© Springer Nature Switzerland AG 2020 1431

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_147
1432 Piper cubeba L.f.

Vernaculars: Urd.: Dhumkimirch, Kababa, Kababchini; Hin.: Kababchini, Kan-

kol, Sitalachini; San.: Sugandha-muricha, Vidanga, Vilenga; Ben.: Kababchini,
Kankola, Shitalachini; Mal.: Lada-barekor, Val-mulaka; Mar.: Kababchini, Kan-
kola, Kombonkoos; Tam.: Valmilaku; Tel.: Chalava-mirialu, Toka-miriyalu; Ara.:
Habb el’arûs, Kabāba, Kabâbah; Chi.: Bi cheng qie, Cheng qie; Dut.: Cubebe,
Cubebepeper. Staartpeper; Eng.: Cubebs, Tailed pepper; Fre.: Cubèbe, Cubèche,
Embebe, Poivre de Java, Poivre à queue; Ger.: Jawanischer pfeffer, Kubebenpf-
effer, Kubebenpfefferstrauch, Schwanzpfeffer, Stielchenpfefferstrauch, Stielpfeffer;
Gre.: Karifiyun, Mahilyun; Hun.: Jávai bors, Kubéba bors; Ind.: Cabé jawa,
Kamukus, Temukus; Ita.: Cubebe, Pepe a coda; Jap.: Kubeba; Nep.: Kabaab
chiinii, Thulo pipla; Per.: Habb-el-arus, Kibabeh; Por.: Bétis, Betre, Betris,
Cubeba, Pimenta-de-rabo; Rus.: Dikij perets, Kubeba, Perets kubebe, Yavanskij
perets; Spa.: Cubeba; Swe.: Kubebapeppar; Tur.: Hind biberi, Kebebe, Kebebiye.
Description: A native plant of India, Sri Lanka, and East Indies (south and southeast
Asia). Leaves of this woody vine, becoming a tree, are alternate, elliptical or oval, tip
acute and base irregularly cordate. Flowers simple, minute, white, in catkin-like
spikes; no sepals or petals. The woody vine bears a small berry-like brownish to
grayish-black fruit; fruits occur as drupes, the upper portion globular, acute, pointed,
the lower portion tapering into a thecaphore. Dried unripe fruits are spherical,
wrinkled, grayish-brown to black in color, look similar to black pepper but are easily
distinguished from black pepper by the pedicel at their base; the stalk is formed from
the contraction of the base of the fruit itself. It has aromatic odor with strongly
pungent taste. Beneath the pericarp is a nut which contains the seed. As the fruit is
gathered when immature (the form used medicinally), the drug usually consists of
little else than pericarp (Figs. 1 and 2).LXXIX,XL
Actions and Uses: Avicenna described it as a good deobstruent and useful as an
application to putrid sores and pustules in the mouth; good for voice, and hepatic
obstructions, and a valuable diuretic expelling gravel and stone from kidneys and
bladder. Europeans were not aware of its medicinal properties and used it only as a
spice.XL In Unani medicine, it (temperament, hot 3° and dry 3°) is regarded
deobstruent, resolvent, stomachic, carminative, emmenagogue, diuretic, strengthens
teeth and gums, clears voice, rubefacient, improves complexion, and expels out
kidney stones; and used in the treatment of liver and spleen obstructions, and
syphilis.LXXVII Razi described it as a urinary tract purifier, and quoting Avicenna
says that women enjoy sex if after chewing cubeb, the saliva is applied to the penis
before sexual intercourse.LXIX Due to its diuretic and stimulant properties, it is used
in gonorrhea, in affections of the genitourinary tract and inflammation of urinary
passages, and chronic bronchial catarrh. Singers and public speakers suck on it to
prevent hoarseness of voice.LXXIX,LXXXI,CV Dried seeds of unripe fruits were used
in chronic bronchitis, as urinary antiseptic and to promote healing of mucous
membranes.XXIV,CXI,CXXXII
The Book of One Thousand and One Nights mentioned cubeb as the main
ingredient in making an aphrodisiac remedy for infertility:
Piper cubeba L.f. 1433

Fig. 1 Piper cubeba, Plant, Kembangraps, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Piper_cubeba_muda.jpg; https://creative-
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Piper cubeba, Fruits, Prof. Akbar, Original

1434 Piper cubeba L.f.

He took two ounces of Chinese cubebs, one ounce of fat extract of Ionian hemp, one ounce
of fresh cloves, one ounce of red cinnamon from Sarandib, ten drachms of white Malabar
cardamoms, five of Indian ginger, five of white pepper, five of pimento from the isles, one
ounce of the berries of Indian star-anise, and half an ounce of mountain thyme. Then he
mixed cunningly, after having pounded and sieved them; he added pure honey until the
whole became a thick paste; then he mingled five grains of musk and an ounce of pounded
fish roe with the rest. Finally, he added a little concentrated rose-water and put all in the
bowl. The mixture, called “seed-thickener”, was given to Shams-al-Din, a wealthy mer-
chant who had no child, with the instruction that he must eat the paste two hours before
having intercourse with his wife. According to the story, the merchant did get the child he
desired after following these instructions. Other Arab authors wrote that cubeb rendered the
breath fragrant, cured affections of the bladder, and that eating it “enhances the delight of
coitus”.
(My apology, and credit is due to the original author who quoted the above incidence, as I
have lost the reference).

Phytoconstituents: Seeds contain 10–18% volatile oil, which contains cubebin,

tetrahydrofuran and 1% cubebic acid,CXXXII 1,4 cineol, terpene and sesquiterpene
alcohols.XLVII Major chemical constituents identified in fruit EO are sabinene,
eucalyptol, 4-terpineol, b-pinene, camphor, and d-3-carene [12].
Pharmacology: Powdered fruits exhibited both preventive and curative effect on
gentamicin-nephrotoxicity in rats [2], and fruit extract produced potent anti-
inflammatory activity in various experimental models of inflammation [6], and
ethanol extract also inhibited in vitro activities of COX-1, COX-2 and 5-LOX, and
exhibited antiandrogenic, and antiestrogenic activities [19, 20]. Antioxidant com-
ponents of Piper species constitute a very efficient system in scavenging a wide
variety of ROS; and P. cubeb possesses significant catalase activity [1, 11].
Treatment of rats with fruit extract for 3-weeks significantly increased SOD and
CAT activities [5]. Ethanol extract significantly ameliorated CCl4-hepatotoxicity,
and restored antioxidant enzymes activities [3]. Methanol extract showed signifi-
cant cytotoxic activity against breast cancer cell lines [9]; and, Rajalekshmi et al.
[14] reported significant anticancer activity of (−)-cubebin, but its cytotoxicity to
human colon adenocarcinoma cells was at very high concentrations [13]. Ethanol
extract inhibited growth of S. salivarius, while (−)-cubebin was more active against
S. mitis and E. faecalis, and fungicidal against C. albicans [15]. Fruit EO was active
against S. mansoni [8], and aqueous fruit extract caused >/=90% in vitro inhibition
of HCV protease [10].
Mechanism of Action: Cubebin, the most abundant lignan in Piper cubeba
reportedly promotes vasorelaxation via NO/cGMP pathway in rat aorta, without the
involvement of prostacyclin [4].
Human A/Es, Allergy and Toxicity: In large doses, it irritates stomach, intestines,
uterus and the urinary passages.LXXIX,LXXXI,CV It also produces immunosuppres-
sive effect [7].
Piper cubeba L.f. 1435

Animal Toxicity: Ethanol extract, up to an oral dose of 1,000 mg/kg, caused no

mortality or significant behavioral changes in rats during 72 h observations [3].
CYP450 and Potential for Drug-Herb Interactions: Ethyl acetate-soluble frac-
tion of water extract potently inhibited in vitro CYP3A4 activity; methylene-
dioxyphenyl lignans, (−)-clusin, (−)-dihydroclusin, (−)-yatein, (−)-hinokinin, and
(−)-dihydrocubebin, have been identified as the active CYP3A4 inhibitors, with
(−)-clusin and (−)-dihydroclusin being the most potent [16–18].
Commentary: There have not been any clinical studies reported on this important
spice. Its nephroprotective and anti-inflammatory activities should be of interest.

References
1. Aboul-Enein HY, Kładna A, Kruk I. Radical scavenging ability of some
compounds isolated from Piper cubeba towards free radicals. Lumines-
cence. 2011;26:202–7.
2. Ahmad QZ, Jahan N, Ahmad G. Tajuddin: Nephroprotective effect of
Kababchini (Piper cubeba) in gentamycin-induced nephrotoxicity. Saudi J
Kidney Dis Transpl. 2012;23:773–81.
3. AlSaid M, Mothana R, Raish M, et al. Evaluation of the effectiveness
of Piper cubeba extract in the amelioration of CCl4-induced liver injuries
and oxidative damage in the rodent model. Biomed Res Int. 2015;2015:
359358.
4. Carvalho MT, Rezende KC, Evora PR, et al. The lignan (−)-cubebin inhibits
vascular contraction and induces relaxation via nitric oxide activation in
isolated rat aorta. Phytother Res. 2013;27:1784–9.
5. Choi EM, Hwang JK. Effect of some medicinal plants on plasma antioxidant
system and lipid levels in rats. Phytother Res. 2005;19:382–6.
6. Choi EM, Hwang JK. Investigations of anti-inflammatory and antinocicep-
tive activities of Piper cubeba, Physalis angulata and Rosa hybrida. J Ethno-
pharmacol. 2003;89:171–5.
7. Daoudi A, Aarab L, Abdel-Sattar E. Screening of immunomodulatory
activity of total and protein extracts of some Moroccan medicinal plants.
Toxicol Ind Health. 2013;29:245–53.
8. Esperandim VR, da Silva Ferreira D, Sousa Rezende KC, et al. In vitro
antiparasitic activity and chemical composition of the essential oil obtained
from the fruits of Piper cubeba. Planta Med. 2013;79:1653–5.
9. Graidist P, Martla M, Sukpondma Y. Cytotoxic activity of Piper cubeba
extract in breast cancer cell lines. Nutrients. 2015;7:2707–18.
10. Hussein G, Miyashiro H, Nakamura N, et al. Inhibitory effects of sudanese
medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res.
2000;14:510–6.
11. Karthikeyan J, Rani P. Enzymatic and nonenzymatic antioxidants in
selected Piper species. Indian J Exp Biol. 2003;41:135–40.
1436 Piper cubeba L.f.

12. Magalhães LG, de Souza JM, Wakabayashi KA, et al. In vitro efficacy of
the essential oil of Piper cubeba L. (Piperaceae) against Schistosoma
mansoni. Parasitol Res. 2012;110:1747–54.
13. Niwa AM, de Paula NA, Vesenick DC, et al. Evaluation of lignan (−)-
cubebin extracted from Piper cubeba on human colon adenocarcinoma cells
(HT29). J Toxicol Environ Health A. 2016;79:92–100.
14. Rajalekshmi DS, Kabeer FA, Madhusoodhanan AR, et al. Anticancer activity
studies of cubebin isolated from Piper cubeba and its synthetic derivatives.
Bioorg Med Chem Lett. 2016;26:1767–71.
15. Silva ML, Coímbra HS, Pereira AC, et al. Evaluation of Piper cubeba
extract, (−)-cubebin and its semisynthetic derivatives against oral pathogens.
Phytother Res. 2007;21:420–2.
16. Usia T, Watabe T, Kadota S, Tezuka Y. Metabolite-cytochrome P450
complex formation by methylenedioxyphenyl lignans of Piper cubeba:
mechanism-based inhibition. Life Sci. 2005;76:2381–91.
17. Usia T, Watabe T, Kadota S, Tezuka Y. Potent CYP3A4 inhibitory
constituents of Piper cubeba. J Nat Prod. 2005;68:64–8.
18. Usia T, Iwata H, Hiratsuka A, et al. CYP3A4 and CYP2D6 inhibitory
activities of Indonesian medicinal plants. Phytomedicine. 2006;13:67–73.
19. Yam J, Kreuter M, Drewe J. Piper cubeba targets multiple aspects of the
androgen-signalling pathway. A potential phytotherapy against prostate
cancer growth? Planta Med. 2008;74:33–8.
20. Yam J, Schaab A, Kreuter M, Drewe J. Piper cubeba demonstrates
antiestrogenic and anti-inflammatory properties. Planta Med. 2008;74:142–6.
Piper nigrum L.
(Piperaceae)

(Syn.: Piper aromaticum Lam.)

Abstract
A woody vine, native and cultivated in India, Sumatra, Java, Singapore, Penang,
Brazil, and West Indies. Theophrastus mentioned two types of pepper in the 4th
century B.C. and Dioscorides described white pepper, long pepper and black
pepper. It was described in the Nighantas as bitter, pungent, digestive, hot and dry,
and considered useful in intermittent fevers, hemorrhoids, dyspepsia, cough,
gonorrhea, and flatulence, and to promote secretion of bile. Externally black
pepper acts as detergent, absorbent, and irritant initially followed by analgesic
effect, and is used for this property in leucoderma and discolored skin spots, and
to relieve pain. It also grows hair when applied as a paste with onion and salt to
ringworm of the scalp. Chewing it causes copious salivation; internally it is
tonic for nerves, stomach and liver, digestant, appetizer, carminative, diuretic,
emmenagogue, aphrodisiac and mucolytic. Dioscorides said that using powdered
pepper with vinegar is useful in spleen inflammation, and Razi said that it relieves
sour eructations, thins blood and improves complexion. Regular use of black
pepper prevents intestinal colic, and keeps lungs clear of sticky phlegm. Twenty-
one alkamides, including piperine, piperettine, piperettyline and feruperine have
been isolated from the ethyl acetate extract; piperine is the main alkaloid present in
the fruits. Major components of the fruit EO are b-caryophyllene, limonene,
sabinene, b-pinene, 3-carene, and a-pinene. Cryogenic grinding of black pepper
preserves the main potent aroma constituents than hammer milling and results in
minimal damage to the color, flavor, and sensory attributes of the spice, but the
concentrations of the main aroma constituents are dramatically reduced after
storage at 4 °C for 6 months. Ethyl acetate or aqueous extracts markedly reduced
body weight, percent fat, and fat-free mass, hyperlipidemia and its constituent
physiological alterations in HFD-fed rats, and piperine in diet for 6-weeks
simulated the above effects in HFD-fed rats. The extract of P. nigrum is the most
effective cholesterol uptake inhibitor in vitro. Antioxidant components of Piper
species constitute a very efficient system in scavenging a wide variety of ROS.

© Springer Nature Switzerland AG 2020 1437

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_148
1438 Piper nigrum L.

Keywords


Black pepper Filfil-e-aswad Golmirch

Hu-chia
Kâli mirch
Kara biber




Maricham Peper Pfeffer Pimienta

Vernaculars: Urd.: Kâli mirch, Siah mirch; Hin.: Choca mirch, Golmirch, Kâli
mirch; San.: Hapusha, Krishnam, Maricha, Maricham, Ooshnam, Valliyam; Ben.:
Golmarich, Kâla morich, Vellajung; Guj.: Kaalaamirich, Kaalaamirii; Mal.:
Kurukulak, Kuru-milagu, Kuru-mulaka, Nallamulak; Mar.: Kaaliimirii, Kâli mirch;
Tam.: Milagu, Milaguvally; Tel.: Kodi miriyalu, Miryala-tige, Miriyalu, Savyamu;
Ara.: Filfil-e-aswad, Filfil-siah; Bur.: Nayukon, Nga youk kuan, Sa-yo-mai; Chi.:
Hei hu jiao, Hu-chia, Hu jiao; Dan.: Peber; Dut.: Peper, Schwartze pfeffer; Eng.:
Black pepper, Common pepper; Fin.: Pippuri; Fre.: Poivre, Poivre noir, Poivrier
cultivé; Ger.: Gemeiner pfefferstrauch, Grüner pfeffer, Pfeffer, Schwarzer pfeffer,
Weißer pfeffer; Gre.: Pipéri; Hun.: Bors; Ind.: Lada, Marica, Marica hitam; Ita.:
Pepe, Pianta del pepe; Jap.: Burakku peppaa, Koshou, Peppaa; Maly.: Ladahitam;
Nep.: Marich; Nor.: Pepper; Per.: Filfil-e-siah, Pilpil; Pol.: Pieprz; Por.: Pimenta,
Pimenta negra, Pimenteiro; Rus.: Perets bélyi, Perets chërnyi; Sin.: Gammiris,
Miris; Spa.: Pimienta, Pimentero; Swe.: Peppar; Tag.: Malisa, Pamintá; Tha.: Phrik
thai; Tur.: Kara biber, Siah biber; Vie.: Trieu.
Description: A woody vine (climber), native and cultivated in India, Sumatra,
Java, Singapore, Penang, Brazil, and West Indies. Theophrastus mentioned two
types of pepper in the 4th century B.C. and Dioscorides described white pepper,
long pepper and black pepper. Earliest travelers from the West to India found the
pepper vine in cultivation in coastal Malabar.XL It has aerial roots; stem ligneous at
the base, branches herbaceous; leaves 13–18 cm long by 5–14 cm wide, alternate,

Fig. 1 Piper nigrum, Plant with Unripe Fruits, J.M. Garg, WikimediaCommons; 3.0 Unported CC
BY 3.0, https://commons.wikimedia.org/wiki/File:Piper_nigrum_W_IMG_2444.jpg; https://creative
commons.org/licenses/by/3.0/deed.en
Piper nigrum L. 1439

Fig. 2 Piper nigrum, Fruits, Prof. Akbar, Original

petiolate, elliptical, acuminate, base cordate or rounded; fruit a spherical berry

without style, 3–4 mm in diameter; dried unripe wrinkled fruits are greyish to
black, with aromatic odor and sharp pungent taste (Figs. 1 and 2).LXXIX
Actions and Uses: It was described in the Nighantas as bitter, pungent, digestive, hot
and dry, and considered useful in intermittent fevers, hemorrhoids, dyspepsia, cough,
gonorrhea, and flatulence, and to promote secretion of bile.XL Externally black pepper
(temperament, hot 3° and dry 3°) acts as detergent, absorbent, and irritant initially
followed by analgesic effect, and is used for this property in leucoderma and dis-
colored skin spots, and to relieve pain. Chewing it causes copious salivation; inter-
nally it is tonic for nerves, stomach and liver, digestant, appetizer, carminative,
diuretic, emmenagogue, aphrodisiac and mucolytic.LXXVII Dioscorides said that
using powdered pepper with vinegar is useful in spleen inflammation, and Razi said
that it relieves sour eructations, thins blood and improves complexion. Regular use of
black pepper prevents intestinal colic, and keeps lungs clear of sticky phlegm.LXIX
Externally it is rubefacient and used as a counterirritant in alopecia and skin dis-
eases;LXXIX and grows hair when applied as a paste with onion and salt to ringworm of
the scalp.LXIX In medicinal doses, it stimulates the heart, the kidney, and mucous
membranes of the urinary and intestinal tracts, and is chiefly used in flatulence,
dyspepsia, and stomach atony,LXXXI,CV and as stomachic and carminative.LXXIX
It has also been effectively used in vertigo, paralytic and arthritic disorders.CXVII
Phytoconstituents: Twenty-one alkamides, including piperine, piperettine,
piperettyline and feruperine have been isolated from the ethyl acetate extract [20];
piperine is the main alkaloid present in the fruits [21]. Major components of the fruit
EO are b-caryophyllene, limonene, sabinene, b-pinene, 3-carene, and a-pinene [1].
However, b-pinene (34.4%), d-3-carene (19.7%), limonene (18.7%) and a-pinene
(10.4%) were reported as the major constituents of P. nigrum oil from Serbia [13].
1440 Piper nigrum L.

Cryogenic grinding of black pepper preserves the main potent aroma constituents
than hammer milling and results in minimal damage to the color, flavor, and sensory
attributes of the spice, but the concentrations of the main aroma constituents are
dramatically reduced after storage at 4 °C for 6 months [11].
Pharmacology: Oral administration of ethyl acetate or aqueous extracts markedly
reduced body weight, percent fat, and fat-free mass, hyperlipidemia and its con-
stituent physiological alterations in HFD-fed rats [15], and piperine in diet for
6-weeks simulated the above effects in HFD-fed rats [2]. The extract of P. nigrum is
the most effective cholesterol uptake inhibitor in vitro [4]. Methanol fruit extract
improved memory and exhibited anxiolytic and antidepressant effects in b-amyloid-
induced spatial memory impairment [6, 7]. Piperine, piperettyline, and piperettine
in vitro inhibited both AChE and BChE, while feruperine was the most potent
selective inhibitor of BChE [20]. Both ethanol extract and piperine exhibited sig-
nificant analgesic and anti-inflammatory activities in rats [19], and administration of
piperine to rats with collagen-induced arthritis decreased arthritis scoring and bone
histology, and significantly reduced levels of proinflammatory mediators (IL-1b,
TNF-a and PGE2) and increased level of IL-10 [21]. Antioxidant components of
Piper species constitute a very efficient system in scavenging a wide variety of
ROS; P. nigrum fruits possess significant GPx, G-6-PD, and CAT activities, and is
rich in vitamin E [8]. Hydroalcohol extract also showed strong in vitro aldose
reductase inhibitory activity [5].
Aqueous extract exhibited both in vitro and in vivo significant antimicrobial
activity against S. aureus and E. coli [12], and significantly enhanced growth of one
strain of probiotic bacteria (Lactobacillus reuteri) and inhibited growth of patho-
genic strains of E. coli [18]. Ethyl acetate, acetone and methanol extracts exhibited
various degrees of modest in vitro antibacterial activity against K. pneumonia,
P. aeroginosa, S. aureus, E. coil, C. xerosis, and S. faecalis [9]. Hexane and ethanol
extracts exhibited profound leishmanicidal activity against L. donovani promastig-
otes and amastigotes [3]; ethanol fruit extract also exhibited potential larvicidal
activity against female Aedes aegypti mosquito [16]. Piperine-free P. nigrum fruit
extract (PFPE) selectively inhibited growth of breast cancer cells than colorectal
cancer, lung cancer, and neuroblastoma cells, and in vivo the incidence of tumor-
bearing rats in PFPE-treated group was 10–20% in N-nitrosomethylurea-induced
mammary tumors, compared with the control groups [17]. Piperine also exhibited
cytotoxic activity against HeLa cell lines [14].
Clinical Studies: Black pepper (2 g in capsule form) used by young adults with
below average feelings of energy, and while wearing a nose clip to block olfactory
effects, did not induce consistent short-term improvements in sustained attention,
motivation to perform cognitive tasks, or feelings of mental energy and fatigue [10].
Mechanism of Action: Hritcu et al. [7] suggested that the improvement in
b-amyloid-induced spatial memory impairment in rats was due to attenuation of
oxidative stress in the rat hippocampus; whereas piperine, piperettine and
piperettyline have been reported to significantly inhibit in vitro AChE [20].
Piper nigrum L. 1441

Human A/Es, Allergy and Toxicity: In large doses, it may cause abdominal pain,
vomiting, irritation of bladder and urethra, and skin urticaria.LXXXI,CV
Animal Toxicity: In acute toxicity study, a single oral administration of PFPE at a
dose of 5,000 mg/kg body weight caused no mortality and morbidity in rats during
a 14-day observation period [17].
Commentary: There are no clinical studies, not even epidemiological studies,
reported on this most commonly used spice throughout the world since antiquity,
simply because it is generally used for its flavor and not for medicinal benefits
except in traditional polyherbal formulations. Nevertheless, a long-term low-dose or
high dose study might unravel some unexpected results.

References
1. Bagheri H, Abdul Manap MY, Solati Z. Antioxidant activity of Piper nigrum
L. essential oil extracted by supercritical CO2 extraction and hydrodistillation.
Talanta. 2014;121:220–8.
2. BrahmaNaidu P, Nemani H, Meriga B, et al. Mitigating efficacy of piperine
in the physiological derangements of high fat diet induced obesity in
Sprague Dawley rats. Chem Biol Interact. 2014;221:42–51.
3. Chouhan G, Islamuddin M, Want MY, et al. Leishmanicidal activity of
Piper nnigrum bioactive fractions is interceded via apoptosis in vitro and
substantiated by Th1 immunostimulatory potential in vivo. Front Microbiol.
2015;6:1368.
4. Duangjai A, Ingkaninan K, Limpeanchob N. Potential mechanisms of
hypocholesterolaemic effect of Thai spices/dietary extracts. Nat Prod Res.
2011;25:341–52.
5. Gupta S, Singh N, Jaggi AS. Evaluation of in vitro aldose reductase inhibitory
potential of alkaloidal fractions of Piper nigrum, Murraya koenigii, Arge-
mone mexicana, and Nelumbo nucifera. J Basic Clin Physiol Pharmacol.
2014;25:255–65.
6. Hritcu L, Noumedem JA, Cioanca O, et al. Anxiolytic and antidepressant
profile of the methanolic extract of Piper nigrum fruits in beta-amyloid
(1–42) rat model of Alzheimer’s disease. Behav Brain Funct. 2015;11:13.
7. Hritcu L, Noumedem JA, Cioanca O, et al. Methanolic extract of Piper nigrum
fruits improves memory impairment by decreasing brain oxidative stress in
amyloid beta (1-42) rat model of Alzheimer’s disease. Cell Mol Neurobiol.
2014;34:437–49.
8. Karthikeyan J, Rani P. Enzymatic and nonenzymatic antioxidants in selected
Piper species. Indian J Exp Biol. 2003;41:135–40.
9. Keskin D, Toroglu S. Studies on antimicrobial activities of solvent extracts
of different spices. J Environ Biol. 2011;32:251–6.
1442 Piper nigrum L.

10. Lindheimer JB, Loy BD, O’Connor PJ. Short-term effects of black pepper
(Piper nigrum) and rosemary (Rosmarinus officinalis and Rosmarinus erioca-
lyx) on sustained attention and on energy and fatigue mood states in young
adults with low energy. J Med Food. 2013;16:765–71.
11. Liu H, Zeng F, Wang Q, et al. The effect of cryogenic grinding and hammer
milling on the flavour quality of ground pepper (Piper nigrum L.). Food
Chem. 2013;141:3402–8.
12. Nassan MA, Mohamed EH. Immunopathological and antimicrobial effect of
black pepper, ginger and thyme extracts on experimental model of acute
hematogenous pyelonephritis in albino rats. Int J Immunopathol Pharmacol.
2014;27:531–41.
13. Nikolić MM, Jovanović KK, Marković TL, et al. Antimicrobial synergism
and cytotoxic properties of Citrus limon L., Piper nigrum L. and Melaleuca
alternifolia (Maiden and Betche) Cheel essential oils. J Pharm Pharma-
col. 2017;69:1606–14.
14. Paarakh PM, Sreeram DC, Shruthi SD, Ganapathy SP. In vitro cytotoxic
and in silico activity of piperine isolated from Piper nigrum fruits Linn.
Silico Pharmacol. 2015;3:9.
15. Parim B, Harishankar N, Balaji M, Pothana S, Sajjalaguddam RR. Effects
of Piper nigrum extracts: restorative perspectives of high-fat diet-induced
changes on lipid profile, body composition, and hormones in Sprague-Dawley
rats. Pharm Biol. 2015;53:1318–28.
16. Santiago VS, Alvero RG, Villaseñor IM. Aedes aegypti larvicide from the
ethanolic extract of Piper nigrum black peppercorns. Nat Prod Res. 2015;
29:441–3.
17. Sriwiriyajan S, Tedasen A, Lailerd N, et al. Anticancer and cancer prevention
effects of piperine-free Piper nigrum extract on N-nitrosomethylurea-induced
mammary tumorigenesis in rats. Cancer Prev Res (Phila). 2016;9:74–82.
18. Sutherland J, Miles M, Hedderley D, et al. In vitro effects of food extracts on
selected probiotic and pathogenic bacteria. Int J Food Sci Nutr. 2009;60:
717–27.
19. Tasleem F, Azhar I, Ali SN, Perveen S, Mahmood ZA. Analgesic and
anti-inflammatory activities of Piper nigrum L. Asian Pac J Trop Med.
2014;7S1:S461–8.
20. Tu Y, Zhong Y, Du H, et al. Anticholinesterases and antioxidant alkamides
from Piper nigrum fruits. Nat Prod Res. 2016;30:1945–9.
21. Umar S, Golam Sarwar AH, Umar K, et al. Piperine ameliorates oxidative
stress, inflammation and histological outcome in collagen induced arthritis.
Cell Immunol. 2013;284:51–9.
Pistacia lentiscus L.
(Anacardiaceae)

(Syns.: Lentiscus vulgaris Fourr.; Terebinthus lentiscus (L.) Moench)

Abstract
A small tree, native to Mediterranean region countries. Mastic gum (oleogum
resin) is mentioned in the works of Herodotus, Dioscorides and Galen, and
several Roman, Byzantine, Arab and European authors have extensively referred
to mastic’s healing properties. It has been used for more than 2500 years in
traditional Greek and other medicines around the world for treating diseases
such as gastralgia and peptic ulcers. P lentiscus var. chia grows exclusively on
the island of Chios, Greece, and has reportedly been used for a variety of gastric
ailments in the Mediterranean and Middle Eastern countries for at least
3000 years. Some estimate its use in various parts of the world for as long as
5000 years. The resin is still used extensively in Greece as an aphrodisiac, and as
a constituent of herbal drugs or functional foods. Ancient Egyptians used it as
incense and for embalming. It has also been used as a preservative and breath
sweetener. Avicenna mentioned it in Canon of Medicine for the treatment of
abnormal uterine bleeding, and as a hepatoprotective, usually as part of com-
pound drugs. It was considered detergent, astringent and restorative by Arab
physicians. In Jordanian folk medicine, aqueous extract is used for the treatment
of jaundice. In North African traditional medicine, mastic oil is used externally
to treat sore throats, burns and wounds, and internally for respiratory disorders,
and in Tunisian folk medicine, the fixed (edible) oil is also used as an antiseptic,
and for cancer treatment. Mastic is one of the most commonly cited drugs
(25 times) in The Chilandar Medical Codex, the best preserved medieval Serbian
manuscript on European medical science from the 12th to 15th centuries. It is
also one of the four plants of the Jerusalem Balsam formula that possesses
anti-inflammatory, antioxidative, and antiseptic properties. Chios mastic gum
and its EO consist of nearly 70 constituents. Thirty-six triterpenes, and arabino-
galactan proteins were identified in Pistacia lentiscus var. chia resin. In a
double-blind RCT, mastic powder in a dose of 350 mg thrice daily for three-
weeks significantly improved symptoms in Greek patients suffering from func-
tional dyspepsia.
© Springer Nature Switzerland AG 2020 1443
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_149
1444 Pistacia lentiscus L.

Keywords






Alfostigueiro Almástiga Ju-shiang Kinnah Lentisc Lentischio Mastagi





Mastixpistazie Rumi mastaki Sakız ağacı

Vernaculars: Urd.: Mastagi; Hin.: Kundar rumi, Rumi mastaki; Ben.: Rumi
mastaki, Rumi-mastungi; Mar.: Rumi mastaki; Tam.: Irumi-malait-taki; Tel.:
Rumaroha ramu; Ara.: Kinnak, Kiya, Mastaki, Uluk-baghdame; Chi.: Ju-shiang;
Dan.: Mastikstræ, Mastixbusk; Dut.: Mastikboom; Eng.: Gum mastiche, Lentisc;
Fre.: Arbre au mastic, Lentisque, Lentisque d’Espagne, Pistachier lentisque,
Restringe; Ger.: Mastixbaum, Mastixpistazie, Mastixpistazienstrauch, Mastrix-
strauch; Hun.: Masztix, Örökzöld pistácia; Ita.: Lentischio, Lentisco, Sondro,
Stinco; Per.: Kinnah, Kinnoli, Kundari, Sakir-rumi; Por.: Alfostigueiro, Alme-
cegueira, Almessigeira, Almestigueiro, Aroeira, Árvore-do-mástique, Darmacho,
Daro, Daroeira, Lentisco, Lentisco-verdadeiro, Moita-do-dro; Spa.: Almástiga,
Entina, Lentisco, Mata dentisca; Tur.: Sakız ağacı.
Description: A small tree, native to Mediterranean region countries, 1–3 m tall
with tortuous branches and persistent peripinnate leaves; flowers in spiciform
clusters. A pale-yellow or greenish-yellow, globular, elongate or pear-shaped,
concrete resinous exudation of the tree, called Mastic, is used medicinally. Mastic is

Fig. 1 Pistacia lentiscus, Shrub, Rafaelji, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Pistacia_lentiscus_sp.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Pistacia lentiscus L. 1445

smooth, shiny and transparent with slightly balsamic odor and pungent taste.LXXIX
True mastic obtained from stem by incision occurs as small, oval, smooth,
yellowish-white tears, brittle, shiny and transparent, being usually covered with its
own dust, resembling gum resin, friable, of a vitreous fracture, odor agreeable and
flavor weak and balsamic, softening in the mouth and becoming ductile when
chewed (Figs. 1, 2 and 3).LXXXI
Actions and Uses: Mastic gum (oleogum resin) is mentioned in the works of
Herodotus, Dioscorides and Galen, and several Roman, Byzantine, Arab and
European authors have extensively referred to mastic’s healing properties. It has
been used for more than 2500 years in traditional Greek and other medicines
around the world for treating diseases such as gastralgia and peptic ulcers [51].
P lentiscus var. chia grows exclusively on the island of Chios, Greece, and has
reportedly been used for a variety of gastric ailments in the Mediterranean and
Middle Eastern countries for at least 3000 years [13]. Some estimate its use in
various parts of the world for as long as 5000 years [9]. The resin is still used
extensively in Greece as an aphrodisiac [57], and as a constituent of herbal drugs or
functional foods [30]. Ancient Egyptians used it as incense and for embalming [48].
It has also been used as a preservative and breath sweetener [12]. Avicenna men-
tioned it in Canon of Medicine for the treatment of abnormal uterine bleeding [45],
and as a hepatoprotective, usually as part of compound drugs [58]. It was con-
sidered detergent, astringent and restorative by Arab physicians.XL In Jordanian

Fig. 2 Pistacia lentiscus, Foliage and Flowers, Sakız ağacı, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Pistacia_lentiscus.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
1446 Pistacia lentiscus L.

Fig. 3 Pistacia lentiscus (Mastic), Resin, Slashme, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Mastic.jpg; https://creativecommons.
org/licenses/by-sa/3.0/deed.en

folk medicine, aqueous extract is used for the treatment of jaundice [23]. In North
African traditional medicine, mastic oil is used externally to treat sore throats, burns
and wounds, and internally for respiratory disorders [16, 26], and in Tunisian folk
medicine, the fixed (edible) oil is also used as an antiseptic [40], and for cancer
treatment [43]. Mastic is one of the most commonly cited drugs (25 times) in The
Chilandar Medical Codex, the best preserved medieval Serbian manuscript on
European medical science from the 12th to 15th centuries [24]. It is also one of the
four plants of the Jerusalem Balsam formula that possesses anti-inflammatory,
antioxidative, and antiseptic properties [46]. Unani physicians in India regard it
(temperament, hot 2° and dry 2°) carminative, digestive, stomach and liver tonic,
diuretic, emmenagogue, mucolytic, anti-inflammatory, detergent, styptic, secretions
absorbent and antiseptic, and use it in the treatment of digestive weakness, dys-
pepsia, flatulence, diarrhea, and inflammations; rubbing teeth with its powder cleans
them.LXXVII It preserves teeth and sweetens breadth when used as tooth-paste.CV
It is a mild stimulant and diuretic, and used in catarrh of respiratory and urinary
passages; as an aphrodisiac it is combined with Salep and given in genital debil-
ity;LXXXI,CV also used as analgesic and sedative in gastralgia, cardiodynia, mastitis,
peptic ulcers, boils, carbuncles; and as antitussive and expectorant.LXXIX In TCM,
the resin is regarded analgesic, sedative, antitussive and expectorant.LXVI
Phytoconstituents: Chios mastic gum and its EO consist of nearly 70 constituents
[14]. Thirty-six triterpenes [5], and arabinogalactan proteins [27] were identified in
Pistacia lentiscus var. chia resin. Flavonol glycosides (myricetin, quercetin gly-
cosides and catechin), gallic acid and galloyl derivatives of both glucose and quinic
acid, and anthocyanins (delphinidin 3-O-glucoside and cyanidin 3-O-glucoside)
were isolated from the leaves [55]; myricetin is the major flavonoid [61]. Essential
oil from aerial parts contains a total of 45 compounds accounting for 97.5–98.4% of
Pistacia lentiscus L. 1447

the total EO; major compounds are a-pinene (14.8–22.6%), b-myrcene (1–19.4%),
p-cymene (1.6–16.2%), and terpinen-4-ol (14.2–28.3%) [8]. Magiatis et al. [35]
reported a-pinene, myrcene, trans-caryophyllene and germacrene D as the major
constituents of EOs of P. lentiscus var. chia gum, leaves and twigs, while a-pinene,
b-pinene, b-myrcene, limonene, and b-caryophyllene were found in mastic oil and
resin by Koutsoudaki et al. [29]. a-Pinene, b-pinene, limonene, terpinen-4-ol and
a-terpineol were the major components of EOs of leaves and resin from Turkey
[19], and the leaves EO from Morocco had germanicol, thunbergol, himachalene,
trans-squalene, terpinyl propionate, 3,3-dimenthol and cadina-1.4-diene as the main
constituents [44]. Fruits fixed oils from Tunisia were reported to contain three major
fatty acids: oleic, palmitic and linoleic acids; oleic acid being the main fatty acid
presenting >50% of the total fatty acid contents [41, 47]. Major sterol in seed oil
was identified as b-sitosterol, making up more than 54% of the total sterols, and
cycloartenol (11%) and 24-methylene-cycloartenol (5%) being the other two main
sterols [42].
Pharmacology: Mastic gum protects against gastrointestinal disorders and bacte-
rial infections, and possesses hepatoprotective, cardioprotective, anti-inflammatory,
antiatherogenic, antioxidant and anticancer properties [21]. It is an efficacious
remedy for the treatment of IBD in traditional Iranian medicine; supplementation
with the resin delays the onset and progression of the disease and prevents weight
loss in animal models of colitis, and inhibits production of proinflammatory sub-
stances such as NO and PGE2 [54]. Oral administration of mastic powder ame-
liorated TNBSA-induced colitis in rats, and decreased all inflammatory cytokines
after 3-days of treatment [22]; the resin downregulated IL-8 and NF-jB p65 [49].
Ripe fruits oil also provided protection against intestinal inflammation in TNBSA-
induced colitis in rats [47]. Mastic also significantly reduced gastric mucosal
damage induced by various noxious stimuli, and significantly decreased free gastric
acid in rats [3]. Mastic gum killed 50% of clinical isolates of H. pylori at a con-
centration of 125 µg/ml and 90% at a concentration of 500 µg/ml [38], and
administration of total mastic extract without the polymer (the insoluble portion) to
H. pylori-infected mice for 3-months reduced H. pylori colonization by about
30-fold, but without attenuation in the associated chronic inflammatory infiltration
and chronic gastritis; the most active pure compound was identified as isomasti-
cadienolic acid [50].
Mastic reduced airway hyperresponsiveness, significantly inhibited eosinophilia
and production of inflammatory cytokines, IL-5 and IL-13 in ovalbumin-induced
asthma in mice [52]. High dose of mastic (800 mg/kg i.p.) produced 100% inhi-
bition of carrageenan-induced inflammation [37]. Topical application of the EO
also exhibited significant anti-inflammatory effect [39]. Mastic shows antioxidant
activity by inhibiting activity of purified protein kinase C that attenuates cellular
production of superoxide and H2O2 [60]. Total mastic extract without polymer
significantly lowered TC, and reduced the infarct size in normal rabbits, and also
demonstrated significant antiatherogenic and hypolipidemic activities in hyperc-
holesterolemic rabbits [4], and the fatty oil significantly decreased TC, TGs, LDL-C
1448 Pistacia lentiscus L.

and the LDL-C/HDL-C ratio of hyperlipidemic rabbits [18]. Mastic extract was
very effective in suppressing iron-induced LPO in rat liver homogenate [31], and
mastic oil mitigated arsenic-induced oxidative damage in rat [26]. Anthocyanins
produced the highest radical scavenging effects [33]. Acute treatment with mastic
EO also protected rat cerebral cortex from I/R injury, and decreased brain levels of
COX-2 [53]. Ethanol and hexane extracts of mastic resin inhibited proliferation and
induced death of human colon cancer cells [7]; the hexane extract also inhibited
tumor growth in mice of a xenografted human colon cancer [13]. Mastic oil exerted
antiproliferative and proapoptotic effect on human leukemia cells and inhibited
VEGF release from mouse melanoma [34] and Lewis lung carcinoma cells, and
significantly inhibited tumor growth [36]. Both aqueous infusion and boiled extract
have shown marked antihepatotoxic activity against CCl4-hepatotoxicity in rats; the
infusion being more effective [23]. Topical application of virgin fatty oil to burn
wounds in rabbits significantly accelerated wound healing with significantly higher
wound contraction, compared to Vaseline [17].
Aqueous mastic plant extract completely inhibited growth of dermatophyte
M. canis, and to a lesser extent of T. mentagrophytes and T. violaceum [2]. Mastic-
containing chewing gum exhibited significant in vitro and in vivo antibacterial
activity against S. mutans [1], and mastic selectively inhibited growth of P. gingivalis
and P. melaninogenica [56]. Mastic resin oil inhibited growth of T. vaginalis
trophozoites, with an MIC of 15 mg/ml after 24 h, and 5 mg/ml after 96 h incubation
[20]. Terpinenol and a-terpineol, two major components of EO, completely inhibited
mycelian growth of A. flavus [8]. Trace components, verbenone, a-terpineol and
linalool, reportedly contribute significantly to the antibacterial activity of mastic oil.
The sensitivity of E. coli, S. aureus, and B. subtilis to these compounds varies,
suggesting synergistic antibacterial activity of various components of mastic oil [29].
Essential oil of the leaves shows strong activity against K. pneumoniae [44] and
mastic fruit fixed (edible) oil from Tunisia and its phenolic fraction significantly
inhibited growth of S. aureus and A. niger [40].
Clinical Studies: In a double-blind RCT, mastic powder in a dose of 350 mg
thrice daily for three-weeks significantly improved symptoms in Greek patients
suffering from functional dyspepsia [11]. Arabinogalactan proteins (AGP) extracted
from gum also inhibited neutrophil activation in the presence of H. pylori neu-
trophil activating protein (HP-NAP) both in vitro and in H. pylori positive patients
who consumed it for two-months. HP-NAP is responsible for H. pylori-associated
pathologies of gastric mucosa [28]. A high dose of 5 g powder daily for 18-months
lowered serum TC, LDL-C, TC/HDL ratio, Lp(a), apoA-1, apoB, SGOT, SGPT and
gamma-GT levels; and a daily low dose for 12-months also lowered blood glucose
levels in Greek male subjects [59].
Mechanism of Action: Mastic inhibits production of proinflammatory substances,
such as NO and PGE2 by LPS-activated mouse macrophage-like RAW264.7 cells,
by inhibiting the expression of iNOS and COX-2 [63]. Mastic gum constituents,
triterpenoids, appear to be mainly responsible for its anticancer potential [21].
Pistacia lentiscus L. 1449

Human A/Es, Allergy and Toxicity: Acute generalized exanthematous pustulosis

due to ingestion of P. lenticus EO has been reported in Tunisian patients [62].
Pollens of various species of Pistacia are allergenic and are cause for allergy in
many atopic patients [10, 25].
Animal Toxicity: Mastic was nontoxic to mice up to a dose of 3,000 mg/kg (i.p.)
body weight [37]. In the subacute toxicity study, P. lentiscus fruits fatty oil did not
produce any mortality or significant physiological changes in treated rabbits [15], or
mice [6]. However, topical application of oil caused a reversible irritant contact
dermatitis [15]. Long-term administration of aqueous dried leaves extract to healthy
rats induced hepatic fibrosis and inflammatory response, mild cholestasis and
depletion of GSH [32].
CYP450 and Potential for Drug-Herb Interactions: Treatment of mice with
Mastic oil for 5-days specifically inhibited activities and expression of CYP450s,
CYP2E1, CYP3A4, CYP1A1 and CYP1A2 in different tissues [6].
Commentary: Scientific research has justified the beneficial action of mastic in
gastric diseases, especially functional dyspepsia; also, its activity against H. pylori
may help in cases of gastric ulcers. However, comprehensive systematic clinical
studies to test anti-inflammatory, antioxidant and antibacterial activities are lacking,
and would validate some of the uses of this ancient drug.

References
1. Aksoy A, Duran N, Koksal F. In vitro and in vivo antimicrobial effects of
mastic chewing gum against Streptococcus mutans and mutans streptococci.
Arch Oral Biol. 2006;51:476–81.
2. Ali-Shtayeh MS, Abu Ghdeib SI. Antifungal activity of plant extracts
against dermatophytes. Mycoses. 1999;42:665–72.
3. Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude
drug obtained from Pistacia lentiscus for gastric and duodenal antiulcer
activity. J Ethnopharmacol. 1986;15:271–8.
4. Andreadou I, Mitakou S, Paraschos S, et al. “Pistacia lentiscus L.” reduces
the infarct size in normal fed anesthetized rabbits and possess antiathero-
matic and hypolipidemic activity in cholesterol fed rabbits. Phytomedicine.
2010;23:1220–6.
5. Assimopoulou AN, Papageorgiou VP. GC-MS analysis of penta- and tetra-
cyclic triterpenes from resins of Pistacia species. Part I. Pistacia lentiscus var.
Chia. Biomed Chromatogr. 205;19:285–311.
6. Attoub S, Karam SM, Nemmar A, et al. Short-term effects of oral adminis-
tration of Pistacia lentiscus oil on tissue-specific toxicity and drug
metabolizing enzymes in mice. Cell Physiol Biochem. 2014;33:1400–10.
1450 Pistacia lentiscus L.

7. Balan KV, Prince J, Han Z, et al. Antiproliferative activity and induction of

apoptosis in human colon cancer cells treated in vitro with constituents of a
product derived from Pistacia lentiscus L. var. chia. Phytomedicine. 2007;
14:263–72.
8. Barra A, Coroneo V, Dessi S, et al. Characterization of the volatile
constituents in the essential oil of Pistacia lentiscus L. from different origins
and its antifungal and antioxidant activity. J Agric Food Chem. 2007;55:
7093–8.
9. Bozorgi M, Memariani Z, Mobli M, et al. Five Pistacia species (P. vera,
P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): a review of their
traditional uses, phytochemistry, and pharmacology. ScientificWorldJour-
nal. 2013:219815.
10. Cvitanović S, Marusić M. Hypersensitivity to pollen allergens on the
Adriatic coast. J Investig Allergol Clin Immunol. 1994;4:96–100.
11. Dabos KJ, Sfika E, Vlatta LJ, et al. Is Chios mastic gum effective in the
treatment of functional dyspepsia? A prospective randomised double-blind
placebo-controlled trial. J Ethnopharmacol. 2010;127:205–9.
12. derMarderosian A, Beutler JA. The review of natural products. 6th ed.
Missouri: Wolters Kluwer Health; 2010.
13. Dimas K, Hatziantoniou S, Wyche JH, Pantazis P. A mastic gum extract
induces suppression of growth of human colorectal tumor xenografts in
immunodeficient mice. In Vivo. 2009;23:63–8.
14. Dimas KS, Pantazis P, Ramanujam R. Review: Chios mastic gum: a plant-
produced resin exhibiting numerous diverse pharmaceutical and biomedical
properties. In Vivo. 2012;26:777–85.
15. Djerrou Z, Djaalab H, Riachi F, et al. Irritantcy potential and subacute
dermal toxicity study of Pistacia lentiscus fatty oil as a topical traditional
remedy. Afr J Tradit Complement Altern Med. 2013;10:480–9.
16. Djerrou Z, Hamdi-Pacha Y, Belkhiri AM, et al. Evaluation of Pistacia
lentiscus fatty oil effects on glycemic index, liver functions and kidney
functions of New Zealand rabbits. Afr J Tradit Complement Altern Med.
2011;8(5 Suppl):214–9.
17. Djerrou Z, Maameri Z, Hamdi-Pacha Y, et al. Effect of virgin fatty oil of
Pistacia lentiscus on experimental burn wound’s healing in rabbits. Afr J
Tradit Complement Altern Med. 2010;7:258–63.
18. Djerrou Z. Antihypercholesterolemic effect of Pistacia lentiscus fatty oil in
egg yolk-fed rabbits: a comparative study with simvastatin. Chin J Nat Med.
2014;12:561–6.
19. Duru ME, Cakir A, Kordali S, et al. Chemical composition and antifungal
properties of essential oils of three Pistacia species. Fitoterapia. 2003;74:
170–6.
20. Ezz Eldin HM, Badawy AF. In vitro anti-Trichomonas vaginalis activity of
Pistacia lentiscus mastic and Ocimum basilicum essential oil. J Parasit Dis.
2015;39:465–73.
Pistacia lentiscus L. 1451

21. Giaginis C, Theocharis S. Current evidence on the anticancer potential of

Chios mastic gum. Nutr Cancer. 2011;63:1174–84.
22. Gioxari A, Kaliora AC, Papalois A, et al. Pistacia lentiscus resin regulates
intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced
colitis. J Med Food. 2011;14:1403–11.
23. Janakat S, Al-Merie H. Evaluation of hepatoprotective effect of Pistacia
lentiscus, Phillyrea latifolia and Nicotiana glauca. J Ethnopharmacol. 2002;
83:135–8.
24. Jarić S, Mitrović M, Djurdjević L, et al. Phytotherapy in medieval Serbian
medicine according to the pharmacological manuscripts of the Chilandar
Medical Codex (15–16th centuries). J Ethnopharmacol. 2011;137:601–19.
25. Keynan N, Tamir R, Waisel Y, et al. Allergenicity of the pollen of Pistacia.
Allergy. 1997;52:323–30.
26. Klibet F, Boumendjel A, Khiari M, et al. Oxidative stress-related liver
dysfunction by sodium arsenite: alleviation by Pistacia lentiscus oil. Pharm
Biol. 2016;54:354–63.
27. Kottakis F, Lamari F, Matragkou Ch, et al. Arabinogalactan proteins from
Pistacia lentiscus var. Chia: isolation, characterization and biological func-
tion. Amino Acids. 2008;34:413–20.
28. Kottakis F, Kouzi-Koliakou K, Pendas S, et al. Effects of mastic gum Pistacia
lentiscus var. Chia on innate cellular immune effectors. Eur J Gastroenterol
Hepatol. 2009;21:143–9.
29. Koutsoudaki C, Krsek M, Rodger A. Chemical composition and antibac-
terial activity of the essential oil and the gum of Pistacia lentiscus var. Chia.
J Agric Food Chem. 2005;53:7681–5.
30. Lemonakis N, Magiatis P, Kostomitsopoulos N, et al. Oral administration of
chios mastic gum or extracts in mice: quantification of triterpenic acids by
liquid chromatography-tandem mass spectrometry. Planta Med. 2011;77:
1916–23.
31. Ljubuncic P, Azaizeh H, Portnaya I, et al. Antioxidant activity and cytotoxi-
city of eight plants used in traditional Arab medicine in Israel. J Ethnophar-
macol. 2005;99:43–7.
32. Ljubuncic P, Song H, Cogan U, et al. The effects of aqueous extracts
prepared from the leaves of Pistacia lentiscus in experimental liver disease.
J Ethnopharmacol. 2005;100:198–204.
33. Longo L, Platini F, Scardino A, et al. Autophagy inhibition enhances antho-
cyanin-induced apoptosis in hepatocellular carcinoma. Mol Cancer Ther.
2008;7:2476–85.
34. Loutrari H, Magkouta S, Pyriochou A, et al. Mastic oil from Pistacia
lentiscus var. chia inhibits growth and survival of human K562 leukemia
cells and attenuates angiogenesis. Nutr Cancer. 2006;55:86–93.
35. Magiatis P, Melliou E, Skaltsounis AL, et al. Chemical composition and
antimicrobial activity of the essential oils of Pistacia lentiscus var. Chia.
Planta Med. 1999;65:749–52.
1452 Pistacia lentiscus L.

36. Magkouta S, Stathopoulos GT, Psallidas I, et al. Protective effects of mastic

oil from Pistacia lentiscus variation Chia against experimental growth of
Lewis lung carcinoma. Nutr Cancer. 2009;61:640–8.
37. Mahmoudi M, Ebrahimzadeh MA, Nabavi SF, et al. Anti-inflammatory and
antioxidant activities of gum mastic. Eur Rev Med Pharmacol Sci. 2010;14:
765–9.
38. Marone P, Bono L, Leone E, et al. Bactericidal activity of Pistacia lentiscus
mastic gum against Helicobacter pylori. J Chemother. 2001;13:611–4.
39. Maxia A, Sanna C, Frau MA, et al. Anti-inflammatory activity of Pistacia
lentiscus essential oil: involvement of IL-6 and TNF-alpha. Nat Prod
Commun. 2011;6:1543–4.
40. Mezni F, Aouadhi C, Khouja ML, Khaldi A, Maaroufi A. In vitro antimi-
crobial activity of Pistacia lentiscus L. edible oil and phenolic extract. Nat
Prod Res. 2015;29:565–70.
41. Mezni F, Khouja ML, Gregoire S, et al. Effect of growing area on
tocopherols, carotenoids and fatty acid composition of Pistacia lentis-
cus edible oil. Nat Prod Res. 2014;28:1225–30.
42. Mezni F, Labidi A, Khouja ML, et al. Diversity of sterol composition in
Tunisian Pistacia lentiscus seed oil. Chem Biodivers. 2016;13:544–8.
43. Mezni F, Shili S, Ben Ali N, et al. Evaluation of Pistacia lentiscus seed oil
and phenolic compounds for in vitro antiproliferative effects against BHK21
cells. Pharm Biol. 2016;54:747–51.
44. Mharti FZ, Lyoussi B, Abdellaoui A. Antibacterial activity of the essential
oils of Pistacia lentiscus used in Moroccan folkloric medicine. Nat Prod
Commun. 2011;6:1505–6.
45. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal
plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
46. Moussaieff A, Fride E, Amar Z, et al. The Jerusalem Balsam: from the
Franciscan Monastery in the old city of Jerusalem to Martindale 33.
J Ethnopharmacol. 2005;101:16–26.
47. Naouar MS, Mekki LZ, Charfi L, Boubaker J, Filali A. Preventive and
curative effect of Pistacia lentiscus oil in experimental colitis. Biomed
Pharmacother. 2016;83:577–83.
48. Nicholson TM, Gradl M, Welte B, et al. Enlightening the past: analytical
proof for the use of Pistacia exudates in ancient Egyptian embalming resins.
J Sep Sci. 2011;34:3364–71.
49. Papalois A, Gioxari A, Kaliora AC, et al. Chios mastic fractions in experi-
mental colitis: implication of the nuclear factor jB pathway in cultured HT29
cells. J Med Food. 2012;15:974–83.
50. Paraschos S, Magiatis P, Mitakou S, et al. In vitro and in vivo activities of
Chios mastic gum extracts and constituents against Helicobacter pylori.
Antimicrob Agents Chemother. 2007;51:551–9.
51. Paraschos S, Mitakou S, Skaltsounis AL. Chios gum mastic: a review of its
biological activities. Curr Med Chem. 2012;19:2292–302.
Pistacia lentiscus L. 1453

52. Qiao J, Li A, Jin X, Wang J. Mastic alleviates allergic inflammation in

asthmatic model mice by inhibiting recruitment of eosinophils. Am J Respir
Cell Mol Biol. 2011;45:95–100.
53. Quartu M, Serra MP, Boi M, et al. Effect of acute administration of Pista-
cia lentiscus L. essential oil on rat cerebral cortex following transient
bilateral common carotid artery occlusion. Lipids Health Dis. 2012;11:8.
54. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J Gas-
troenterol. 2010;16:4504–14.
55. Romani A, Pinelli P, Galardi C, et al. Identification and quantification of gal-
loyl derivatives, flavonoid glycosides and anthocyanins in leaves of Pistacia
lentiscus L. Phytochem Anal. 2002;13:79–86.
56. Sakagami H, Kishino K, Kobayashi M, et al. Selective antibacterial and
apoptosis-modulating activities of mastic. In Vivo. 2009;23:215–23.
57. Sawidis T, Yurukova L, Askitis T. Chios mastic, a natural supplement for
zinc to enhance male sexuality and prostate function. Pharm Biol. 2010;48:
48–54.
58. Shamsi-Baghbanan H, Sharifian A, Esmaeili S, Minaei B. Hepatoprotective
herbs, Avicenna viewpoint. Iran Red Crescent Med J. 2014;16:e12313.
59. Triantafyllou A, Chaviaras N, Sergentanis TN, et al. Chios mastic gum modu-
lates serum biochemical parameters in a human population. J Ethnophar-
macol. 2007;111:43–9.
60. Triantafyllou A, Bikineyeva A, Dikalova A, et al. Anti-inflammatory activity
of Chios mastic gum is associated with inhibition of TNF-alpha induced
oxidative stress. Nutr J. 2011;10:64.
61. Vaya J, Mahmood S. Flavonoid content in leaf extracts of the fig (Ficus
carica L.), carob (Ceratonia siliqua L.) and pistachio (Pistacia lentiscus L.).
Biofactors. 2006;28:169–75.
62. Zaraa I, Ben Taazayet S, Trojjet S, et al. Acute generalized exanthematous
pustulosis induced by the essential oil of Pistacia lentiscus. Clin Exp
Dermatol. 2012;37:361–3.
63. Zhou L, Satoh K, Takahashi K, et al. Reevaluation of anti-inflammatory
activity of mastic using activated macrophages. In Vivo. 2009;23:583–9.
Plantago major L.
(Plantaginaceae)

Abstract
A perennial herb, native to Europe, Asia, India (temperate regions), and Persia,
but with pantropic distribution. Dioscorides described two varieties of Plantago,
the greater and the lesser, and stated that the first is the best and most generally
used. The plants were known to the Romans as Plantago and were considered
to be very effective in arresting the fluxes known by the Greeks as “rheumatismi”
or “griping pains in the bowels.” Galen described leaves and roots as astringent
and febrifuge, and beneficial for intestinal inflammation, intestinal ulcers, piles
and as a styptic. In Unani medicine, green leaves and seeds are considered astrin-
gent, styptic and analgesic, and used to treat nosebleed, bloody piles, excessive
menstrual bleeding, and hemoptysis. Seeds are demulcent and their cold infusion
is used in urinary disorders, dysentery and in arresting fluxes and griping pain
in the bowels. In Iranian traditional medicine, it has been used for the treatment of
IBD. Biologically active constituents include alkaloids, flavonoids, iridoid
glycosides, terpenoids, polysaccharides, lipids, caffeic acid derivatives, and some
organic acids. Seeds contain fixed oil, planterolic acid, plantasan, proteins,
succinic acid, adenine, choline, catalpol, and fatty acids (palmitic acid, stearic
acid, arachidic acid, linolenic acid and lenoleic acid). Hydroalcohol leaf extract to
citric acid-induced asthmatic rats for four-weeks restored lung histopathology to
near normal. Methanol extracts of leaves and seeds produced significant analgesic
effect against various noxious stimuli in mice. Methanol seed extract also exhib-
ited significant anti-inflammatory activity against carrageenan-induced edema and
hepatoprotective activity against CCl4-hepatotoxicity in rats. A rapid favorable
effect of P. major treatment on subjective complaints and objective findings was
reported in Bulgarian patients with chronic bronchitis, with or without spastic
character and with light or moderately severe deviations in ventilation indices.

© Springer Nature Switzerland AG 2020 1455

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_150
1456 Plantago major L.

Keywords




Antén Asvagola Bartang Breitwegerich Cheqiancao

Lahuriya




Lisaanul hamal Petacciola Ripple seed Sinirotu

Vernaculars: Urd.: Bartang; Hin.: Baratunga, Lahuriya, Luhuriya; San.: Asvagola;

Ben.: Plyānṭagō pradhāna; Mar.: Plāṇṭō mōṭhē; Tam.: Ishappukol vitai; Ara.:
Lisaanul hamal; Chi.: Ch’e-ch’ien, Cheqiancao, Chu erh-to; Dut.: Getande weeg-
bree, Grote weegbree, Weversblad; Eng.: Broad leaf plantain, Cart-track, Greater
plantain, Hog’s ear, Rat’s-tail-plantain, Ribwort, Ripple seed, Way bread; Fre.:
Grand plantain, Plantain commun, Plantain à grandes feuilles, Plantain majeur; Ger.:
Breitwegerich, Großer wegerich; Ita.: Petacciola, Piantaggine maggiore; Jap.:
Onioobako, Seiyooobako; Per.: Barhang, Bartang, Tukhme-bartang (seeds); Por.:
Erva-de-orelha (Br.), Tanchagem, Tanchagem-maior, Transagem; Spa.: Anchu,
Antén, Cancerina, Diantén, Ilantén de hojas anchas, Ilantén mayor, Lantén, Lengua
de carnero, Toraja cimarrona (Mexico), Vestigo del hombre blanco; Tag.: Lanting;
Tha.: Mo noi, Phak kat nam, Ya en yuet; Tur.: Sinirotu.
Description: A perennial herb, native to Europe, Asia, India (temperate regions),
and Persia, but with pantropic distribution; 10–15 cm tall, without aerial stems;
leaves occur in a rosette near the ground and are oblong or oblong-ovate, 5–10 cm

Fig. 1 Plantago major, Leaves and Seed Spikes, Rasbak, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Grote_weegbree_bloeiwijze_
Plantago_major_subsp._major.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Plantago major L. 1457

long usually 5-nerved, borne on petioles often as long as the leaf blade; the margins
are entire or toothed. Flowers are usually crowded on erect, slender spikes 6–12 cm
long.CXVII Seeds are minute, oblong, or irregularly angled, of a darkish-brown
color, and marked with slightly elevated longitudinal ridges; taste insipid and
mucilaginous, like ispaghol (Figs. 1 and 2).XL
Actions and Uses: Dioscorides described two varieties of Plantago, the greater and
the lesser, and stated that the first is the best and most generally used. The plants
were known to the Romans as Plantago and were considered to be very effective in
arresting the fluxes known by the Greeks as “rheumatismi” or “griping pains in the
bowels.” Galen described leaves and roots as astringent and febrifuge,XL and ben-
eficial for intestinal inflammation, intestinal ulcers, piles and as a styptic.LXIX In
Unani medicine, green leaves and seeds (temperament, cold 2° and dry 2°) are
considered astringent, styptic and analgesic, and used to treat nosebleed, bloody
piles, excessive menstrual bleeding, and hemoptysis.LXXVII Seeds are demulcent and
their cold infusion is used in urinary disorders, dysentery and in arresting fluxes and
griping pain in the bowels.LXXXI,CV In Iranian traditional medicine, it has been used
for the treatment of IBD [34]. Leaves are reported to possess anti-inflammatory,
antimicrobial, antitumor and wound healing properties [16], and used for stom-
achache in Ethiopia [24], and seed decoction is diuretic, increases excretion of urea,
uric acid and sodium chloride.LXXIX In China, a herb called Cheqiancao is derived
from Plantago asiatica, P. major and P. depressa, and the plantago seeds are called
Cheqianzi. Both the plant and the seeds are sweetish in taste and have a cold
property. Their actions include improvement or restoration of vision by curing

Fig. 2 Plantago major, Developing Fruits, Frank Vincentz, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Plantago_major_05_ies.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
1458 Plantago major L.

hepatic hyperactivity; diuresis in strangury; antitussis, and mucolysis. In the book of

Yao Xing Lun (Properties of Chinese Materia Medica), Cheqiancao is described as a
cure for hematuria, tonic for the visceral organs, and a remedy for poor vision and for
urinary disturbances (due to urolithiasis, dysfunction of the urinary bladder, chy-
luria, overfatigue, and hematuria). According to the Shen Nong Ben Cao Jing
(Herbal of the Divine Plowman), Cheqianzi is recommended for ‘disorders of vital
energy, pain, diuresis and rheumatism.’XVIII It has also been used in the treatment of
infections, inflammation and cancer in the traditional medicine of Taiwan [7], and is
popularly used in Mexican traditional medicine to treat tumors, infections and as a
blood purifier [43]. In Brazilian traditional medicine, the plant is known as Trans-
agem, Tanchagem or Erva-de-orelha and is used for wound healing [41], the leaves
and seeds are used as antiseptic, anti-inflammatory and antibacterial [19], and
infrequently used in the treatment of cutaneous leishmaniasis due to Leishmania
braziliensis by rural population of a cocoa-producing coastal area of Bahia state of
Brazil [12]. It is one of the most frequently used folk medicine for inflammation by
the population of the Atlantic Coast of Colombia [15]. In Japan, a water extract of
seeds (var. asiatica) is given for whooping cough and the seeds have a great repu-
tation as a remedy for dysentery and diarrhea, and as pectoral and demulcent. The
plant is used in folklore medicine for asthma treatment in Indonesia [22], and is
known in Iran for its therapeutic benefits in respiratory and gastrointestinal diseases
[11]. Former President Laurel (of Japan) was prescribed water decoction of the plant
when he suffered from asthma in October, 1943. He was given half a glass for
gargles and one half of a glass to drink three times daily.CXVII Leaves were official in
the Argentine, Danish, French, Mexican, Spanish and Venezuelan Pharmacopoeia;
and the seeds in Danish and Spanish Pharmacopoeias.XV
Phytoconstituents: Biologically active constituents include alkaloids, flavonoids,
iridoid glycosides, terpenoids, polysaccharides, lipids, caffeic acid derivatives, and
some organic acids [17, 25, 31, 37]. The plant also contains large amount of potas-
sium salts; the leaves, roots and inflorescences contain glucoside, aucubin, as well as
enzymes, invertin and emulsin.CXVII Methanol leaf extract showed presence of
unsaturated sterols, triterpenes, tannins, flavonoids and carbohydrates and/or gly-
cosides as the major constituents [1], and luteolin-7-O-glucoside, apigenin-7-O-
glucoside, luteolin, apigenin, rutin, and quercetin were the identified flavonoids [4].
Whole plant contains plantagin, aucubin, ursolic acid, b-sitosterol, n-hentriacontane,
and plantaglucide, which is composed of methyl D-galacturonate, D-galactose,
L-arabinose, and L-rhamnose; and seeds contain 16.7–22.1% of fixed oil; planterolic
acid, plantasan (composed of xylose, arabinose, galacturonic acid, and rhamnose),
proteins, succinic acid, adenine, choline, catalpol, and fatty acids: palmitic acid,
stearic acid, arachidic acid, linolenic acid and lenoleic acid.XVIII
Pharmacology: Chang and ButXVIII referred to some Chinese experiments on
dogs, rabbits and humans that showed the plant and seeds could increase excretion
of water, urea, uric acid, and sodium chloride. However, absence of specific drug
dosage, water intake and strict control over studies made the results less reliable.
Recent studies showed no obvious diuretic action in rats, rabbits, and healthy
Plantago major L. 1459

subjects after oral administration of the seed decoction on urine output or the
sodium excretion [9]. Whole plant hydroalcohol extract significantly ameliorated
cisplatin-nephrotoxicity in rats [32], and the ethanol extract significantly inhibited
the size of in vitro calcium oxalate crystals formation [3].
Hydroalcohol leaf extract (i.p.) to citric acid-induced asthmatic rats for
four-weeks restored lung histopathology to near normal [11]. Methanol extracts of
leaves and seeds produced significant analgesic effect against various noxious
stimuli in mice [1]. Freeze-dried extract inhibited carrageenan-induced inflammation
in rats [39], and methanol leaf extract showed 26% in vitro anti-inflammatory
activity, compared to 21 and 12% by the ethanol and aqueous extracts, respectively,
and significantly reduced proinflammatory cytokine levels in APAP-induced liver
injury in rats [21]. Methanol seed extract also exhibited significant anti-inflammatory
activity against carrageenan-induced edema and hepatoprotective activity against
CCl4-hepatotoxicity in rats [42]. Methanol leaf extract produced a significant
antidiarrheal effect on castor oil-induced diarrhea in rats, and inhibited motility of
isolated rabbit duodenum after an initial transient stimulation [2]. The polyholozidic
fraction extracted from leaves and seeds is a significant gastroprotective, and at
higher doses a laxative [20]. Immunomodulating property of leaf extracts and iso-
lated compounds has also been reported [8, 16, 43]. Endotoxin-free methanol leaf
extract increased NO and TNF-a production by rat peritoneal macrophages, and
potentiated ConA-induced lymphoproliferation [16]. Hot-water leaf extract exhib-
ited dual immunomodulatory effects, enhancing lymphocyte proliferation and
secretion of IFN-c at low concentrations, but inhibiting the same at higher con-
centrations [8]. Antioxidant activity of various extracts has been reported [4, 5,
27, 29]. An unidentified compound isolated from methanol leaf extract is also
reported to in vitro inhibit ACE [28]. Topical application of the hydroalcohol extract
ointment improved wound healing in rats [41]. Ethanol- and water-based leaf
extracts also stimulated wound healing in porcine skin, with ethanol-based extract
showing a somewhat stronger effect [44].
Hydroalcohol leaf extract demonstrated weak antibacterial activity against
S. aureus, and moderate anticandidal activity against C. krusei and C. tropicalis [19].
A soluble pectin polysaccharide isolated from leaves protected mice against
S. pneumoniae infection through stimulation of innate, but not the adaptive immune
system [18]. Aqueous extract possesses weak antiherpes virus activity; however, pure
compounds caffeic acid exhibited strongest activity against HSV-1, HSV-2 and
ADV-3, and chlorogenic acid showed strongest anti-ADV-11 activity [6]. Antigia-
rdiasis activity was reported with 76% in vitro inhibition of G. duodenalis tropho-
zoites viability that was comparable to 79% by tinidazol [33]. Ethanol infusion of
husk was inactive against primary plaque colonizers and periodontal pathogens [38].
Methanol leaf extract showed cytotoxicity against human hepatocellular carcinoma
cell line, HepG2 [36] and inhibited Ehrlich ascites tumors in mice [30]. A polyphe-
nolic complex from the plant inhibited endogenic synthesis of carcinogenic NDMA,
reduced toxic damage to the liver and decreased tumor yield from 87.5 to 33.3% [23].
Luteolin-7-O-b-glucoside was identified as the major flavonoid responsible for
cytotoxic activity [13]. Water extract (infusion) significantly enhanced tone of
isolated rabbit and guinea pig uterine horns [40].
1460 Plantago major L.

Clinical Studies: In Bulgaria, twenty-five patients with chronic bronchitis, with or

without spastic character and with light or moderately severe deviations in venti-
lation indices, were treated with a P. major preparation for 25 to 30 days. A rapid
favorable effect on subjective complaints and objective findings was reported in
80% patients. The preparation was well tolerated without any toxic effects on
gastrointestinal tract, liver, kidneys or hemopoiesis [26].
Mechanism of Action: Ursolic acid is a triterpenoid isolated from the plant that
selectively and significantly inhibits COX-2 enzyme, and may contribute to its
anti-inflammatory effect [35].
Human A/Es, Allergy and Toxicity: Acute irritant contact dermatitis in Turkish
individuals has been reported [10].
Animal Toxicity: Mice treated with aqueous leaf extract in a dose of 2,000 mg/kg
five days a week for 40-days produced no significant signs of toxicity or change in
corporal weight; the extract caused no significant eye irritation on instillation into
rabbit’s eyes [14]. Single oral doses of methanol extracts of leaves and seeds were
nonlethal and nontoxic up to doses of 2,000 mg/kg body weight in mice [1].
Commentary: A plant with a rich history of use in GI disorders has not yet been
clinically evaluated in an objective systematic manner. Its clinical effects on res-
piratory system, especially bronchitis and bronchial asthma would be interesting.

References
1. Atta AH, Abo EL-Sooud K. The antinociceptive effect of some Egyptian
medicinal plant extracts. J Ethnopharmacol. 2004;95:235–8.
2. Atta AH, Mouneir SM. Evaluation of some medicinal plant extracts for
antidiarrhoeal activity. Phytother Res. 2005;19:481–5.
3. Aziz SA, See TL, Khuay LY, et al. In vitro effects of Plantago major extract
on urolithiasis. Malays J Med Sci. 2005;12:22–6.
4. Beara IN, Lesjak MM, Jovin ED, et al. Plantain (Plantago L.) species as novel
sources of flavonoid antioxidants. J Agric Food Chem. 2009;57:9268–73.
5. Bol’shakova IV, Lozovskaia EL, Sapezhinskiĭ II. Antioxidant properties of
plant extracts. Biofizika. 1998;43:186–8 (Russian).
6. Chiang LC, Chiang W, Chang MY, et al. Antiviral activity of Plantago major
extracts and related compounds in vitro. Antiviral Res. 2002;55:53–62.
7. Chiang LC, Chiang W, Chang MY, Lin CC. In vitro cytotoxic, antiviral and
immunomodulatory effects of Plantago major and Plantago asiatica. Am J
Chin Med. 2003;31:225–34.
8. Chiang LC, Ng LT, Chiang W, et al. Immunomodulatory activities of
flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic
compounds of Plantago species. Planta Med. 2003;69:600–4.
Plantago major L. 1461

9. Doan DD, Nguyen NH, Doan HK, et al. Studies on the individual and
combined diuretic effects of four Vietnamese traditional herbal remedies
(Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus).
J Ethnopharmacol. 1992;36:225–31.
10. Erdem T, Caferoğlu Sakat S, Ismail Engin R, et al. Acute irritant contact
dermatitis caused by Plantago major. Contact Dermatitis. 2009;60:237–9.
11. Farokhi F, Khaneshi F. Histophatologic changes of lung in asthmatic male
rats treated with hydroalcoholic extract of Plantago major and theo-
phylline. Avicenna J Phytomed. 2013;3:143–51.
12. França F, Lago EL, Marsden PD. Plants used in the treatment of leishmanial
ulcers due to Leishmania (Viannia) braziliensis in an endemic area of Bahia.
Brazil. Rev Soc Bras Med Trop. 1996;29:229–32.
13. Gálvez M, Martín-Cordero C, López-Lázaro M, et al. Cytotoxic effect of
Plantago spp. on cancer cell lines. J Ethnopharmacol. 2003;88:125–30.
14. García González M, Coto Morales T, Soto Rodríguez GA, Pazos L.
Subchronic toxicity and test of eye irritability of leaf aqueous extract from
Plantago major (plantaginaceae). Rev Biol Trop. 2003;51:635–8 (Spanish).
15. Gómez-Estrada H, Díaz-Castillo F, Franco-Ospina L, et al. Folk medicine
in the northern coast of Colombia: an overview. J Ethnobiol Ethnomed.
2011;7:27.
16. Gomez-Flores R, Calderon CL, Scheibel LW, et al. Immunoenhancing
properties of Plantago major leaf extract. Phytother Res. 2000;14:617–22.
17. Grigorescu E, Stanescu U, Basceanu V, Aur MM. Phytochemical and micro-
biological control of some plant species used in folk medicine. II. Plantago
lanceolata L., Plantago media L., Plantago major L. Revista Medico-
Chirurgicala a Societatii de Medici Si Naturalisti Din Iasi. 1973;77:835–41
(Rumanian).
18. Hetland G, Samuelsen AB, Løvik M, et al. Protective effect of Plantago
major L. pectin polysaccharide against systemic Streptococcus pneumoniae
infection in mice. Scand J Immunol. 2000;52:348–55.
19. Holetz FB, Pessini GL, Sanches NR, et al. Screening of some plants used in
the Brazilian folk medicine for the treatment of infectious diseases. Mem
Inst Oswaldo Cruz. 2002;97:1027–31.
20. Hriscu A, Stanescu U, Ionescu A, Verbuta A. A pharmacodynamic
investigation of the effect of polyholozidic substances extracted from
Plantago sp. on the digestive tract. Revista Medico-Chirurgicala a Societatii
de Medici Si Naturalisti Din Iasi. 1990;94:165–70 (Rumanian).
21. Hussan F, Mansor AS, Hassan SN, et al. Anti-Inflammatory property of
Plantago major leaf extract reduces the inflammatory reaction in experi-
mental acetaminophen-induced liver injury. Evid Based Complement
Alternat Med. 2015;2015:347861.
22. Ikawati Z, Wahyuono S, Maeyama K. Screening of several Indonesian
medicinal plants for their inhibitory effect on histamine release from RBL-
2H3 cells. J Ethnopharmacol. 2001;75:249–56.
1462 Plantago major L.

23. Karpilovskaia ED, Gorban’ GP, Pliss MB, Zakharenko LN, Gulich MP.
Inhibiting effect of the polyphenolic complex from Plantago major
(plantastine) on the carcinogenic effect of endogenously synthesized
nitrosodimethylamine. Farmakol Toksikol. 1989;52:64–7 (Russian).
24. Lemordant D. Contribution a l’ethnobotanique Ethiopienne. J Agric Trop
Bot Appl. 1971;18(1–3):1-35; 18(4–6):142–79.
25. Maksiutina NP. Polyphenol compounds of Plantago major L. leaves.
Farmatsevtichnii Zhurnal. 1972;27:59–63 (Ukranian).
26. Matev M, Angelova I, Koichev A, Leseva M, Stefanov G. Clinical trial of a
Plantago major preparation in the treatment of chronic bronchitis. Vutreshni
Bolesti. 1982;21:133–7 (Bulgarian).
27. Mello JC, Guimarães NS, Gonzalez MV, et al. Hydroxyl scavenging activity
accounts for differential antioxidant protection of Plantago major against
oxidative toxicity in isolated rat liver mitochondria. J Pharm Pharmacol.
2012;64:1177–87.
28. Nhiem NX, Tai BH, Van Kiem P, et al. Inhibitory activity of Plantago
major L. on angiotensin I-converting enzyme. Arch Pharm Res. 2011;34:
419–23.
29. Oto G, Ekin S, Ozdemir H, et al. Plantago major protective effects on
antioxidant status after administration of 7,12-dimethylbenz(a)anthracene in
rats. Asian Pac J Cancer Prev. 2011;12:531–5.
30. Ozaslan M, Didem Karagöz I, Kalender ME, et al. In vivo antitumoral effect
of Plantago major L. extract on Balb/C mouse with Ehrlich ascites tumor.
Am J Chin Med. 2007;35:841–51.
31. Pailer M, Haschke-Hofmeister E. Contents from Plantago major. Planta
Med. 1969;17:139–45 (German).
32. Parhizgar S, Hosseinian S, Hadjzadeh MA, et al. Renoprotective effect of
Plantago major against nephrotoxicity and oxidative stress induced by
cisplatin. Iran J Kidney Dis. 2016;10:182–8.
33. Ponce-Macotela M, Navarro-Alegría I, Martínez-Gordillo MN, Alvarez-
Chacón R. In vitro effect against Giardia of 14 plant extracts. Rev Invest
Clin. 1994;46:343–7 (Spanish).
34. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J Gas-
troenterol. 2010;16:4504–14.
35. Ringbom T, Segura L, Noreen Y, et al. Ursolic acid from Plantago major, a
selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthe-
sis. J Nat Prod. 1998;61:1212–5.
36. Ruffa MJ, Ferraro G, Wagner ML, et al. Cytotoxic effect of argentine medicinal
plant extracts on human hepatocellular carcinoma cell line. J Ethnopharmacol.
2002;79:335–9.
37. Samuelsen AB. The traditional uses, chemical constituents and biological
activities of Plantago major L. A review. J Ethnopharmacol. 2000;71:1–21.
Plantago major L. 1463

38. Sharma H, Yunus GY, Mohapatra AK, et al. Antimicrobial efficacy of three
medicinal plants Glycyrrhiza glabra, Ficus religiosa, and Plantago major
on inhibiting primary plaque colonizers and periodontal pathogens: an in vitro
study. Indian J Dent Res. 2016;27:200–4.
39. Shipochliev T, Dimitrov A, Aleksandrova E. Anti-inflammatory action of a
group of plant extracts. Vet Med Nauki. 1981;18:87–94 (Bulgarian).
40. Shipochliev T. Uterotonic action of extracts from a group of medicinal
plants. Vet Med Naoki (Bulgaria). 1981;18:94–8.
41. Thomé RG, dos Santos HB, dos Santos FV, et al. Evaluation of healing
wound and genotoxicity potentials from extracts hydroalcoholic of Plan-
tago major and Siparuna guianensis. Exp Biol Med (Maywood). 2012;237:
1379–86.
42. Türel I, Ozbek H, Erten R, et al. Hepatoprotective and anti-inflammatory
activities of Plantago major L. Indian J Pharmacol. 2009;41:120–4.
43. Velasco-Lezama R, Tapia-Aguilar R, Román-Ramos R, et al. Effect of
Plantago major on cell proliferation in vitro. J Ethnopharmacol. 2006;103:
36–42.
44. Zubair M, Nybom H, Lindholm C, Brandner JM, Rumpunen K. Promotion
of wound healing by Plantago major L. leaf extracts—ex-vivo experiments
confirm experiences from traditional medicine. Nat Prod Res. 2016;30:622–4.
Plantago ovata Forssk.
(Plantaginaceae)

(Syn.: P. ispaghula Roxb. ex Fleming)

Abstract
The plant is native to Canary Islands, Mediterranean regions of southern Europe
and West Africa, and cultivated in northern and western India and in Pakistan. In
India, seeds are considered cooling and demulcent, and useful in inflammatory
and bilious derangements of digestive organs. Roasted seeds have an astringent
effect and are useful in irritation of bowel of children, and in dysentery. Crushed
seeds made into poultice with vinegar and oil are applied to rheumatic and gouty
swellings. Powdered seeds are injurious, therefore, internally seeds are only used
as whole. Seeds are also used in gastric catarrh, gonorrhea, urethritis and kidney
afflictions due to their emollient and diuretic properties. In modern allopathic
medicine, psyllium is described as a bulk-forming laxative that is high in both
fiber and mucilage, and a potent agent in lowering plasma cholesterol. Psyllium-
containing laxatives are used by 4 million Americans daily, and as dietary
supplements for the management of hypercholesterolemia, and for the preven-
tion of colon cancer. Consumption of P. ovata was found inversely correlated
with mortality from colorectal cancer in Spanish population. It is on the
inventory for constipation in Europe since Mar. 2005 by the HMPC of the
European Medicines Agency. In Serbia, it is used in the treatment of
constipation, fecal incontinence, hemorrhoids, ulcerative colitis, hyperlipidemia,
and diabetes mellitus. Mucilage constitutes over 30% of the whole seed. The
husk yields a colloidal mucilage consisting mainly of xylose, arabinose and
galacturonic acid; also present are rhamnose and galactose. It is reported to have
immunomodulatory, antioxidant, anti-inflammatory and wound healing activi-
ties, and decreases levels of NO and LTB4. A fiber-supplemented diet (5%
seeds) for 13-weeks to transgenic rats ameliorated development of colonic
inflammation, with a decrease in proinflammatory mediators, such as NO, LTB4,
and TNF-a, and a significantly higher production of short-chain fatty acids,
butyrate and propionate in intestinal contents. In an open label, multicenter RCT,

© Springer Nature Switzerland AG 2020 1465

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_151
1466 Plantago ovata Forssk.

treatment of Spanish patients with ulcerative colitis in remission, with seeds for
12-months maintained remission in 14 out of 35 patients, compared to 13 out of
37 patients treated with mesalamine.

Keywords




Bazre-qatuna Blonde psyllium Cáscara de ispágula Flohsamen Isabghol







Ispaghul Jirun Isparzah Spogel Yuan bao che qian

Vernaculars: Urd.: Isabghol, Ispghol; Hin.: Isbaghol, Ispaghul, Issufgul, Jirun;

San.: Ispaghul, Snigdhajeera; Ben.: Eshopghol, Isabgul; Guj.: Isafaghol; Mal.:
Karkalasaringi; Mar.: Esabgol; Tam.: Ishappukol-virai; Tel.: Isapagala-vittulu;
Ara.: Luqmatulnaajah, Bazre-qatuna; Chi.: 圆苞车前, Yuan bao che qian, Che
qian cao (dried mature seeds); Eng.: Blonde psyllium, Ispaghula, Spogel seeds,
Indian plantago; Fre.: Graines de psyllium, Graines d’ispaghul; Ger.: Flohsamen,
Indische flohsamen, Spogel, Spogelwegerich; Ita.: Bazerequatuna, Cuticola del
seme, Guscio del seme, Ispaghul, Psillo; Per.: Esfarzah, Isparzah, Shikam-daridah
Banghust; Spa.: Arta de agua, Cáscara de ispágula, Hierba pulguera, Ispágula,
Llantén de perro; Tha.: Thian klet hoi.
Description: The plant is native to Canary Islands, Mediterranean regions of
southern Europe and West Africa, and cultivated in northern and western India and
in Pakistan. It is a stemless or short-stemmed annual herb; leaves in a rosette or
alternate, clasping the stem, strap-like, recurved, 7.5–25 cm long, narrow, 6–
12.5 mm in width, tapering to a point and covered with fine hairs. Seeds are ovate,
elliptical, boat-shaped, translucent, pinkish pale-brown in color and about 3 mm
long. On both their convex and concave surfaces, seeds have ridges which are
peculiar in character. Each seed is encased in a thin, white, translucent membrane
(“husk”) which is odorless and tasteless [31] (Figs. 1 and 2).
Actions and Uses: In India, seeds are considered cooling and demulcent, and
useful in inflammatory and bilious derangements of digestive organs. Roasted seeds
have an astringent effect and are useful in irritation of bowel of children, and in
dysentery. Crushed seeds made into poultice with vinegar and oil are applied to
rheumatic and gouty swellings. Powdered seeds are injurious, therefore, internally
seeds are only used as whole.XL Seeds are also used in gastric catarrh, gonorrhea,
urethritis and kidney afflictions due to their emollient and diuretic properties.LXXVII,
LXXXI,CV
Husked seeds are dark-red and hard; both husk and seeds (temperament,
cold 2° and moist 2°) are used medicinally in Unani system of medicine,LXXVII and
used effectively as a remedy for IBD in traditional Iranian medicine [29]. Seeds
soaked in water at night are very beneficial in bacillary dysentery (Zaheer kazib)
and hemorrhoides.1 In modern allopathic medicine, psyllium is described as a
bulk-forming laxative that is high in both fiber and mucilage [41], and a potent
agent in lowering plasma cholesterol [32]. Psyllium-containing laxatives are used

1
Tayyab M: Personal Communication.
Plantago ovata Forssk. 1467

Fig. 1 Plantago ovata, Plant, Stan Shebs, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Plantago_ovata_form.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Plantago ovata, Seeds, Prof. Akbar, Original

1468 Plantago ovata Forssk.

by four million Americans daily, and as dietary supplements for the management of
hypercholesterolemia, and for the prevention of colon cancer [11]. Consumption of
P. ovata was found inversely correlated with mortality from colorectal cancer in
Spanish population [22]. It is on the inventory for constipation in Europe since Mar.
2005 by the HMPC of the European Medicines Agency. In Serbia, it is used in the
treatment of constipation, fecal incontinence, hemorrhoids, ulcerative colitis,
hyperlipidemia, and diabetes mellitus [3]. The mucilage also serves as a stabilizer in
ice cream, as an ingredient in chocolates and in the formation of pharmaceutical
tablets and cosmetics.CLII
Phytoconstituents: Mucilage constitutes over 30% of the whole seed. The husk
yields a colloidal mucilage consisting mainly of xylose, arabinose and galacturonic
acid; also present are rhamnose and galactose.
Pharmacology: It is reported to have immunomodulatory, antioxidant, anti-
inflammatory and wound healing activities, and decreases levels of NO and LTB4
[29]. Alcohol seed extract showed cholinergic activity.IV A fiber-supplemented diet
(5% seeds) for 13-weeks to transgenic rats ameliorated development of colonic
inflammation, with a decrease in proinflammatory mediators, such as NO, LTB4,
and TNF-a, and a significantly higher production of short-chain fatty acids, butyrate
and propionate in intestinal contents [30]. Husk-supplementation of diet signifi-
cantly reduced body weight, TNF-a, hyperlipidemia, hyperinsulinemia and
hyperleptinemia in obese Zucker rats and reduced adiponectin secretion by adipose
tissue [12, 13]; significantly lowered blood glucose and cholesterol in mildly dia-
betic rabbits, increased insulin secretion, and also decreased TC, LDL-C, athero-
genic index, and HbA1c in healthy rabbits [5]. In rats, supplementation of a
fiber-free elemental diet with 100 or 200 g seeds/kg for 4-weeks increased fecal
fresh weight, fecal dry weight and fecal water contents; the husk was more effective
at high concentration only, and more pronounced in small intestine [21]. Dietary
fiber also protected rats from TNBSA-induced colitis by significant reduction in
colonic myeloperoxidase activity and restoration of colonic GSH levels, and lower
TNF-a levels and NO synthase activity [31].
Clinical Studies: In an open label, multicenter RCT, treatment of Spanish patients
with ulcerative colitis in remission, with seeds for 12-months maintained remission in
14 out of 35 patients, compared to 13 out of 37 patients treated with mesalamine [9].
In a double-blind study comprising 20 patients with chronic constipation, of which 10
had associated IBS, at a University Hospital in Valencia, Spain, all patients treated
with P. ovata had significant improvement in frequency of stools and decrease in
transit time, compared to only one in the placebo group [38]. However, 149 patients
with chronic constipation (84% women) treated with P. ovata seeds (15–30 g/day)
for at least 6-weeks at two gastroenterology departments in Munich, Germany,
reported no response in 80% of patients with slow transit and 63% of patients with a
disorder of defecation, whereas 85% of patients without a pathological condition
improved or became symptom-free. Therefore, slow GI transit and/or a disorder of
defecation may explain sometimes a poor outcome of dietary fiber therapy in patients
Plantago ovata Forssk. 1469

with chronic constipation [40]. Healthy individuals taking normal diet and lop-
eramide in a dose sufficient to double the individual colonic transit time, were given
Agiocur® (30 g) as a fiber product containing 20 g P. ovata seeds/husks, which did
not influence loperamide-prolonged colonic transit; however, the stool weight was
increased significantly [6]. Bleeding on contact decreased from 5 out of 22 Spanish
patients before treatment to none after treatment with a commercially available
preparation of P. ovata in patients with bleeding internal hemorrhoids; no difference
occurred in the control group [28]. Serbian patients treated with 3.26 g P. ovata
(Laxomucil®) twice daily for twenty days, after hemorrhoidectomy, significantly
shortened postoperative length of hospital stay, and pain after stool was significantly
more tolerable [18, 19].
Psyllium supplementation to obese children and adolescents with carbohydrate
and lipid metabolism abnormalities, produced changes in postprandial glucose
(–12.2 to –20.2%) in type-2 DM patients; LDL-C (2.78 to −22.8%), TGs (8.49 to
−19.54%) and HDL-C (−4.16 to 3.05%), in hypercholesterolemic children [26]. In
a double-blind placebo-controlled study, diet supplemented with 5.1 g psyllium
husk fiber half an hour before breakfast and dinner in patients with type-2 diabetes
in combination with antidiabetic drugs for 8-weeks improved tolerance to met-
formin, with significant reduction in FBG and HbA1c, and significant increase in
HDL-C [41]. Even in patients with CVD (MI or stable angina) and an LDL-C </
=3.35 mmol/L, consumption of 10.5 g husk or seeds/d decreased plasma triacyl-
glycerol (6.7%), and the ratio of Apo B 100 to Apo A-I (4.7%), and increased apo
A-I (4.3%); intake of husk increased HDL-C by 6.7% and decreased ratio of
TC/HDL-C and LDL/HDL-C by 10.6% [35]. In another multicenter, double-blind,
parallel RCT of mild to moderately hypercholesterolemic patients of primary care
clinics in Spain, France and Holland, addition of husk (14 g/d) in diet for 8-weeks,
reduced plasma LDL-C by 6%, TC by 6%, TGs by 21.6%, Apo B-100 by 6.7%,
oxidized LDL by 6.82 U/L, insulin by 4.68 pmol/L and systolic BP by 4.0 mm Hg
[36]. Administration of P. ovata preparation (20 g granules with 200 ml water),
placebo (20 g granules with 200 ml water), or water (200 ml) 3 h premeal and
immediately premeal to normal, healthy subjects in a randomized order, signifi-
cantly lowered total fat intake and increased feeling of fullness in treated subjects
[39]. In a paired case-control study of patients diagnosed with colon cancer, reg-
istered at the Cancer Data Exchange Systems of the Community of Madrid, con-
sumption of P. ovata was associated with a reduced risk of colon cancer in
constipated patients [17].
A cervical dilator, Isaptent, prepared from granulated P. ovata seed husk achieved
satisfactory dilatation in 94% of the 750 Indian patients by a single tent [20].
Mechanism of Action: Psyllium seed husk (Ispaghula) is a source of soluble
dietary fiber that is indigestible but may be fermented in the intestines by
butyrate-producing bacteria into butyrate which is the pharmacologically active
short-chain fatty acid [9]. It absorbs water (hygroscopic) and expands to provide
increased bulk and moisture content to the stool; the increased bulk encourages
normal peristalsis and bowel motility [3]. Ispaghula was found more resistant to
1470 Plantago ovata Forssk.

fermentation than previously reported in healthy human volunteers who ingested a

low fiber-controlled diet plus 18 g/day of ispaghula for 15-days and its bulking
effect largely resulting from intact material [24]. Hannan et al. [16] suggested that
hot-water husk extract improves glucose tolerance in normal, type-1 and type-2
diabetic rats via inhibition of intestinal glucose absorption and enhancement of
motility. P. ovata decreases serum cholesterol, mainly LDL-C, through enhancing
cholesterol elimination as fecal bile acids resulting in a significant increase in serum
cholesterol precursors [25].
Human A/Es, Allergy and Toxicity: Ingestion of unsoaked psyllium seeds may
cause gastrointestinal irritation, inflammation, constipation and mechanical
obstruction [33].LXXII,CXI Psyllium and seeds of P. ovata are reported as occupa-
tional respiratory allergen in healthcare and pharmaceutical workers [1, 2, 23, 27,
34]. Patients have developed allergic reactions to psyllium even after using it for a
long time [11], and severe anaphylactic reactions have occurred after ingestion of
psyllium laxative [37]. Allergens in psyllium are protein in nature and derived from
the inner seed endospore and embryo rather than from the husk itself [11]. The U.S.
FDA issued a warning that over-the-counter laxatives containing bulk-forming
psyllium ingredients, psyllium seed, psyllium seed husks, P. ovata husks, and
Plantago seed are not generally recognized as safe and effective (GRASE), and any
granules swallowed dry prior to drinking liquid, chewed, partially chewed, or
unchewed, and then swallowed with liquid or sprinkled over food, may cause
esophageal obstruction; this rule did not apply to psyllium laxatives in nongranular
dosage forms, such as powders, tablets, or wafers [10].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Potential for Drug-Herb Interactions: Concurrent oral administration of P. ovata
seeds or P. ovata seed cuticles (husk) with ethinylestradiol (EE) decreases the
extent of EE absorption between 29 and 35%, without affecting the rate of
absorption in rabbits [8]; whereas, repeated use of the husk improves bioavailability
of levodopa [4, 7, 14, 15].
Commentary: There are credible clinical studies establishing its effectiveness in
constipation and dyslipidemia. However, there aren’t sufficient systematic
long-term clinical studies to validate the claim of an inverse relationship between
intake of P. ovata and colorectal cancer.

References
1. Alemán AM, Quirce S, Bombín C, Sastre J. Asthma related to inhalation of
Plantago ovata. Med Clin (Barc). 2001;116:20–2 (Spanish).
2. Bernedo N, García M, Gastaminza G, et al. Allergy to laxative compound
(Plantago ovata seed) among healthcare professionals. J Investig Allergol
Clin Immunol. 2008;18:181–9.
Plantago ovata Forssk. 1471

3. Ceranić M, Kecmanović D, Pavlov M, et al. Plantago ovata. Acta Chir

Iugosl. 2006;53:9–11 (Review, Serbian).
4. Diez MJ, Garcia JJ, Prieto C, et al. The hydrosoluble fiber Plantago ovata
husk improves levodopa (with carbidopa) bioavailability after repeated
administration. J Neurol Sci. 2008;271:15–20.
5. Díez R, García JJ, Diez MJ, et al. Hypoglycemic and hypolipidemic
potential of a high fiber diet in healthy versus diabetic rabbits. Biomed Res
Int. 2013;2013:960568.
6. Ewe K, Ueberschaer B, Press AG. Influence of senna, fibre, and
fibre + senna on colonic transit in loperamide-induced constipation. Phar-
macology. 1993;47 Suppl 1:242–8.
7. Fernandez N, Carriedo D, Sierra M, et al. Hydrosoluble fiber (Plantago ovata
husk) and levodopa II: experimental study of the pharmacokinetic interaction
in the presence of carbidopa. Eur Neuropsychopharmacol. 2005;15:505–9.
8. Fernández N, Diez MJ, Terán MT, et al. Influence of two commercial fibers
in the pharmacokinetics of ethinylestradiol in rabbits. J Pharmacol Exp
Ther. 1998;286:870–4.
9. Fernández-Bañares F, Hinojosa J, Sánchez-Lombraña JL, et al. Randomized
clinical trial of Plantago ovata seeds (dietary fiber) as compared with
mesalamine in maintaining remission in ulcerative colitis. Spanish Group
for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU). Am J
Gastroenterol. 1999;94:427–33.
10. Food and Drug Administration (FDA), HHS. Laxative drug products for
over-the-counter human use; psyllium ingredients in granular dosage forms.
Final rule. Fed Regist. 2007;72:14669–74.
11. Freeman GL. Psyllium hypersensitivity. Ann Allergy. 1994;73:490–2.
12. Galisteo M, Sánchez M, Vera R, et al. A diet supplemented with husks of
Plantago ovata reduces the development of endothelial dysfunction,
hypertension, and obesity by affecting adiponectin and TNF-alpha in obese
Zucker rats. J Nutr. 2005;135:2399–404.
13. Galisteo M, Morón R, Rivera L, et al. Plantago ovata husks-supplemented
diet ameliorates metabolic alterations in obese Zucker rats through
activation of AMP-activated protein kinase. Comparative study with other
dietary fibers. Clin Nutr. 2010;29:261–7.
14. Garcia JJ, Fernandez N, Carriedo D, et al. Hydrosoluble fiber (Plantago
ovata husk) and levodopa I: experimental study of the pharmacokinetic
interaction. Eur Neuropsychopharmacol. 2005;15:497–503.
15. García JJ, Fernández N, Calle AP, et al. Effects of Plantago ovata husk on
levodopa (with carbidopa) bioavailability in rabbits with autonomic
gastrointestinal disorders. Drug Metab Dispos. 2009;37:1434–42.
16. Hannan JM, Ali L, Khaleque J, et al. Aqueous extracts of husks of Plantago
ovata reduce hyperglycaemia in type 1 and type 2 diabetes by inhibition of
intestinal glucose absorption. Br J Nutr. 2006;96:131–7.
1472 Plantago ovata Forssk.

17. Juarranz M, Calle-Purón ME, González-Navarro A, et al. Physical exercise,

use of Plantago ovata and aspirin, and reduced risk of colon cancer. Eur J
Cancer Prev. 2002;11:465–72.
18. Kecmanović D, Pavlov M, Ceranić M, et al. Plantago ovata (Laxomucil)
after hemorrhoidectomy. Acta Chir Iugosl. 2004;51:121–3 (Serbian).
19. Kecmanovic DM, Pavlov MJ, Ceranic MS, et al. Bulk agent Plantago ovata
after Milligan-Morgan hemorrhoidectomy with Ligasure. Phytother Res.
2006;20:655–8.
20. Khanna NM, Sarin JP, Nandi RC, et al. Isaptent—a new cervical dilator.
Contraception. 1980;21:29–40.
21. Leng-Peschlow E. Plantago ovata seeds as dietary fibre supplement:
physiological and metabolic effects in rats. Br J Nutr. 1991;66:331–49.
22. López JC, Villanueva R, Martínez-Hernández D, et al. Plantago ovata
consumption and colorectal mortality in Spain, 1995–2000. J Epidemiol.
2009;19:206–11.
23. Machado L, Zetterstrom O, Fagerberg E. Occupational allergy in nurses to a
bulk laxative. Allergy. 1979;34:51–5.
24. Marteau P, Flourié B, Cherbut C, et al. Digestibility and bulking effect of
ispaghula husks in healthy humans. Gut. 1994;35:1747–52.
25. Miettinen TA, Tarpila S. Serum lipids and cholesterol metabolism during guar
gum, Plantago ovata and high fibre treatments. Clin Chim Acta. 1989;183:
253–62.
26. Moreno LA, Tresaco B, Bueno G, et al. Psyllium fibre and the metabolic
control of obese children and adolescents. J Physiol Biochem. 2003;59:
235–42 (Review).
27. Muñoz X, Culebras M, Cruz MJ, Morell F. Occupational asthma related to
aescin inhalation. Ann Allergy Asthma Immunol. 2006;96:494–6.
28. Perez-Miranda M, Gomez-Cedenilla A, León-Colombo T, et al. Effect of
fiber supplements on internal bleeding hemorrhoids. Hepatogastroenterol-
ogy. 1996;43:1504–7.
29. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J Gas-
troenterol. 2010;16:4504–14.
30. Rodríguez-Cabezas ME, Gálvez J, Camuesco D, et al. Intestinal anti-
inflammatory activity of dietary fiber (Plantago ovata seeds) in HLA-B27
transgenic rats. Clin Nutr. 2003;22:463–71.
31. Rodríguez-Cabezas ME, Gálvez J, Lorente MD, et al. Dietary fiber downreg-
ulates colonic tumor necrosis factor alpha and nitric oxide production in
trinitrobenzenesulfonic acid-induced colitic rats. J Nutr. 2002;132:3263–71.
32. Romero AL, West KL, Zern T, Fernandez ML. The seeds from Plantago
ovata lower plasma lipids by altering hepatic and bile acid metabolism in
guinea pigs. J Nutr. 2002;132:1194–8.
Plantago ovata Forssk. 1473

33. Salguero Molpeceres O, Seijas Ruiz-Coello MC, Hernández Núñez J, et al.

Esophageal obstruction caused by dietary fiber from Plantago ovata, a
complication preventable by adequate information. Gastroenterol Hepatol.
2003;26:248–50 (Review, Spanish).
34. Singh AB, Kumar P. Common environmental allergens causing respiratory
allergy in India. Indian J Pediatr. 2002;69:245–50 (Review).
35. Solà R, Godàs G, Ribalta J, et al. Effects of soluble fiber (Plantago ovata
husk) on plasma lipids, lipoproteins, and apolipoproteins in men with
ischemic heart disease. Am J Clin Nutr. 2007;85:1157–63.
36. Solà R, Bruckert E, Valls RM, et al. Soluble fibre (Plantago ovata husk)
reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides,
insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic
patients: a randomised trial. Atherosclerosis. 2010;211:630–7.
37. Suhonen R, Kantola I, Bjorksten F. Anaphylactic shock due to ingestion of
psyllium laxative (Plantago ovata seeds). Allergy (Denmark). 1983;38:363–5.
38. Tomás-Ridocci M, Añón R, Mínguez M, et al. The efficacy of Plantago
ovata as a regulator of intestinal transit. A double-blind study compared to
placebo. Rev Esp Enferm Dig. 1992;82:17–22 (Spanish).
39. Turnbull WH, Thomas HG. The effect of a Plantago ovata seed containing
preparation on appetite variables, nutrient and energy intake. Int J Obes
Relat Metab Disord. 1995;19:338–42.
40. Voderholzer WA, Schatke W, Mühldorfer BE, et al. Clinical response to
dietary fiber treatment of chronic constipation. Am J Gastroenterol. 1997;
92:95–8.
41. Ziai SA, Larijani B, Akhoondzadeh S, et al. Psyllium decreased serum
glucose and glycosylated hemoglobin significantly in diabetic outpatients.
J Ethnopharmacol. 2005;102:202–7.
Plumbago zeylanica L.
(Plumbaginaceae)

(Syn.: P. viscosa Blanco)

Abstract
It is a herbaceous plant with glabrous, climbing, prostrate, or erect stems, that
grows in the tropical climates of India and Australia. The root is powerfully
poisonous and its internal use is attended with great risk. It increases digestive
function and promotes appetite, stimulates nervous system in small doses, and in
higher doses causes paralysis, leading to death. It causes abortion if used
internally, but most commonly employed as local irritant to os uteri. In
Ayurveda, roots are used to treat skin diseases, diarrhea, plague and leprosy, and
Hindu physicians describe the plant as digestive, light, astringent, hot and
appetizing, and use it for the treatment of dyspepsia, piles, leprosy, anasarca,
worms, cough, phlegm, flatulence and biliousness. Muslim physicians in India
described it as caustic, vesicant, abortifacient, an expellant of phlegmatic
humours, and considered it useful in rheumatism and splenic and digestive
disorders. Shitraj of Muslim physicians is regarded to be any species of
Plumbago, and not necessarily the species zeylanica; however, P. rosea is more
powerful and more vesicant. Root and its constituents are also credited with
antiatherogenic, cardiotonic, hepatoprotective and neuroprotective properties,
and as a GIT flora normalizer. In the Philippines, pounded roots are used for
blistering, and their decoction is used as antiscabies remedy, and the Ethiopians
also use the root to treat skin disorders and a number of other diseases. Roots are
reported to contain alkaloids, flavonoids, coumarins, terpenoids, quinones,
phenols, tannins, steroids and sugars. Both aqueous and alcohol root extracts,
and plumbagin exhibit significant antioxidant potentials, and pretreatment of
mice with alcoholic root extract protected against CP-genotoxicity and oxidative
stress, and cisplatin-nephrotoxicity. Root paste made in water and applied
topically exhibited anti-inflammatory activity.

© Springer Nature Switzerland AG 2020 1475

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_152
1476 Plumbago zeylanica L.

Keywords




Agni-shikha Ceylonische Chitrak Chitra-mul
Dentelaire de ceylon




Shitarah Shitraj hindi White leadwort

Vernaculars: Urd.: Shitraj hindi; Hin.: Chita, Chiti, Chitra, Chitrak; San.:
Agni-shikha, Chitraka, Dahana, Druna; Ben.: Chita, Chitra-mul, Chitruk; Mal.:
Tumba-Kodivali, Vellakotuveri; Mar.: Chitraka, Chitra-mul; Tam.: Chitramulum,
Chittira, Codiveli; Tel.: Agnimatha, Chitra, Chitra-mulam; Ara.: Miswak arrai,
Shitaraj; Eng.: Ceylon leadwort, White leadwort; Fre.: Dentelaire de Ceylon; Ger.:
Bleiwurz, Ceylonische; Per.: Shatraj, Shitarah.
Description: It is a herbaceous plant with glabrous, climbing, prostrate, or erect
stems, that grows in the tropical climates of India and Australia. Leaves are peti-
olate or sessile and have ovate, lance-elliptic, or spatulate to oblanceolate blades,
that measure 5–9 cm long and 2.5–4 cm wide. Roots are 6–50 mm in diameter,
seldom branched; when dry, the external surface of the bark is of a dark
reddish-brown color, somewhat shriveled, and marked here and there by small
warty projections. Internally, it is brown and striated, the fracture is short; the taste
acrid and biting. A section of fresh bark when magnified shows numerous bundles
of bright yellow stone cells forming an irregular zone towards the inner part of the
middle layer of the bark. The cells of parenchyma are large and contain much starch
(Fig. 1).XL
Actions and Uses: The root is powerfully poisonous and its internal use is attended
with great risk. It increases digestive function and promotes appetite, stimulates
nervous system in small doses, and in higher doses causes paralysis, leading to
death. It causes abortion if used internally, but most commonly employed as local
irritant to os uteri.CV In Ayurveda, roots are used to treat skin diseases, diarrhea,
plague and leprosy [20], and Hindu physicians describe the plant as digestive, light,
astringent, hot and appetizing, and use it for the treatment of dyspepsia, piles,
leprosy, anasarca, worms, cough, phlegm, flatulence and biliousness. A powder
composed of equal parts of Plumbago root, seeds of Holarrhena antidysenterica,
roots of Sessampelos pereira, or Picrorrhiza kurroa and Aconitum heterophyllum,
Chebulic myrobalans, in a dose of 3.89 g is a favorite prescription for flatulence.
Muslim physicians in India described it as caustic, vesicant, abortifacient, an
expellant of phlegmatic humours, and considered it useful in rheumatism and
splenic and digestive disorders [35].CXVII,CL Shitraj of Muslim physicians is
regarded to be any species of Plumbago, and not necessarily the species zeylanica;
however, P. rosea is more powerful and more vesicant.XL In Unani medicine, root
(temperament, hot 3° and dry 3°) is considered nerve stimulant, refrigerant,
aphrodisiac (stimulatory), and externally detergent and irritant, and used in skin
diseases such as leucoderma, and discolored skin spots (bahaq).1 A paste made
with milk, vinegar or salt and water is applied in leprosy and other obstinate skin

1
Tayyab M: Personal Communication.
Plumbago zeylanica L. 1477

Fig. 1 Plumbago zeylanica, Flowers and Leaves, Bernard Loison, WikimediaCommons; Share-
Alike 2.5 Generic CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Plumbago_
zeylanica1MTFL.jpg; https://creativecommons.org/licenses/by-sa/2.5/deed.en

diseases and allowed to remain until a blister was formed; in case of rheumatism it
was removed after 15–20 min.XL The root as alterative and gastric stimulant is used
in the treatment of chronic diarrhea, dyspepsia and general anasarca. Externally, a
paste is used as a stimulant application to rheumatic joints, paralytic limbs, leprosy,
and to abscesses to promote suppuration.LXXXI Root and its constituents are also
credited with antiatherogenic, cardiotonic, hepatoprotective and neuroprotective
properties [48], and Iyengar and Pendse [19] described it as a GIT flora normalizer.
Various extracts of P. zeylanica have been used in China and other Asian countries
as folk medicine for the treatment of cancer, rheumatoid arthritis and dysmenorrhea
[30]. Folkloric use by the people of Assam in India is to achieve permanent birth
control [49], and the Ethiopian also use the root to treat skin disorders and a number
of other diseases [14, 15, 47]. In the Philippines, pounded roots are used for
blistering, and their decoction is used as antiscabies remedy.CXVII
Phytoconstituents: Roots are reported to contain alkaloids, flavonoids, terpenoids,
quinones, phenols, tannins, steroids and sugars [33]. Coumarins (seselin, suberosin,
xanthoxyletin, xanthyletin and 5-methoxyseselin), naphthaquinones (plumbagin,
chitranone, isoshinanolone, maritinone, and elliptinone), and plumbagic acid glu-
cosides (3′-O-b-glucopyranosyl plumbagic acid and 3′-O-b-glucopyranosyl plum-
bagic acid methylester) [25], and a prenyloxynaphthoquinone, 2-methyl-5-(3′-
methyl-but-2′-enyloxy)-[1,4]naphthoquinone, showing strong antileishmanial activity
have been isolated from the roots [26]. Plumbagin is the active principle that demon-
strated uterine stimulant activity [9, 21]. Ethanol root extract is reported to contain
significant amounts of L-DOPA, and shows anti-Parkinson activity in rats [34]. From
the aerial parts eleven guanidine alkaloids, plumbagines A–G and plumbagosides
A–D, have been isolated [10].
1478 Plumbago zeylanica L.

Pharmacology: Both aqueous and alcohol root extracts, and plumbagin exhibit
significant antioxidant potentials [48], and pretreatment of mice with alcoholic root
extract protected against CP-genotoxicity and oxidative stress [44], and
cisplatin-nephrotoxicity [33]. The root extract and plumbagin significantly reduced
platelet aggregation in rats on day 15th and 31st of oral administration, without
affecting platelet count [50]. Plumbagin highly significantly reduced serum TC and
LDL-C in hyperlipidemic rabbits, significantly elevated HDL-C, and prevented
accumulation of cholesterol and TGs in liver and aorta [40]. Ethanol root extract
reportedly caused hyperglycemia, due to impaired delivery to and utilization of
glucose by the peripheral tissue in rats [28]. Ethanol root extract also enhanced
spontaneous ambulatory activity in rats without inducing stereotypic behavior, and
elevated levels of DA and HVA in striatum [6], and hydroalcohol extract protected
against haloperidol-induced catalepsy in rats [18].
Root paste made in water and applied topically exhibited anti-inflammatory
activity [22]. Acetone leaf extract also significantly reduced inflammation in rats,
and both the acetone and petroleum ether extracts produced significant analgesic
effect; plumbagin was identified as the active constituent in acetone extract [41].
Ethanol root extract exhibits strong antibacterial activity [2], significantly inhibiting
growth of MRSA and ESbetaL-producing enteric bacteria [4], antiplasmodial
activity against P. falciparum [42], and exhibits synergistic interaction with one or
more antibiotics, tetracycline, chloramphenicol, ciprofloxacin, cefuroxime and cef-
tidizime [3]. Ethyl acetate fraction of ethanol extract is also active against E. coli and
Shigella species [1]. Ethanol, ethyl acetate and acetone extracts and plumbagin were
strongly active against H. pylori [51–53]; and plumbagin prevented development of
antibiotic resistance in antibiotic sensitive strains of E. coli and S. aureus [12], and
exhibited significant synergism with INH against four atypical mycobacteria,
namely, M. intracellulare, M. smegmatis, M. xenopei and M. chelonei [27]. Methanol
(80%) root extract also inhibits growth of coxsackievirus B3 [14] and while
methanol leaf extract strongly inhibited growth of S. aureus and F. oxysporum,
methanol stem extract was active against P. aeruginosa and P. expansum [43].
Ahmad et al. [2] reported the alcohol extract to be more active antibacterial than the
aqueous extract.
Administration of ethanol root extract to male rats for 60-days caused arrest of
spermatogenesis [32]. Plumbagin-free alcohol root extract reversibly decreased
serum levels of progesterone, FSH and LH, and increased serum prolactin con-
centration [37]. Acetone and ethanol leaf extracts interrupted estrous cycle of
female rats, causing a temporary reversible inhibition of ovulation [13]. However,
Saksena et al. [36] had reported no inhibition of implantation in rats administered
petroleum ether, ether and water root extracts on days 1–7 of pregnancy. Ethanol
stem extract also dose-dependently inhibits systemic anaphylactic shock induced by
compound 48/80 in mice, and reduces homologous passive cutaneous anaphylaxis
and skin reactions induced by histamine or serotonin in rats [11].
Plumbagin suppresses activation of NF-kappaB in tumor cells, and inhibits ConA-
induced T cell proliferation and a decrease in the levels of IL-2, IL-4, IL-6 and IFN-c
cytokines [7]. Plumbagin also induces tumor regression in 3′MeDAB-induced
Plumbago zeylanica L. 1479

hepatoma and restores to near normal levels of hexokinase, phosphoglucoisomerase,

and aldolase increased in hepatoma bearing Wistar male rats [29]; inhibits in vitro
TNF-a and other carcinogens and inflammatory stimuli-induced NF-kappaB activa-
tion [38]; inhibits cell invasion and selectively induces apoptosis in human prostate
cancer cells [5, 16, 17, 31], human gastric cancer cells [24], and human pancreatic
cancer cells [8]. Plumbagin significantly reduces blood glucose, restores all
biochemical parameters to near normal, increases hexokinase activity and
significantly decreases activities of G-6-P and fructose-1,6-bisphosphatase in diabetic
rats [46].
Mechanism of Action: Generation of ROS is a critical mediator of plumbagin-
induced apoptosis in cancer cells [54, 55]. Antibacterial activity against E. coli
involves disruption of membrane potential, inner membrane permeabilization, and
leakage of cellular contents [39]. Anti-inflammatory activity of plumbagin is sug-
gested to be mediated via inhibition of NF-kappaB activation [7]. Plumbagin
enhanced GLUT4 mRNA and protein expression in diabetic rats [46].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Oral LD50s of petroleum ether, acetone and hydroalcohol
extracts are reported to be 93.45, 928.4, and 928.4 mg/kg, respectively, which were
correlated to the contents of plumbagin of the extract [23]. However, single oral
dose of 150 mg/kg, and repeated daily dose of 25 mg/kg of plumbagin for 28-days
were reported nonlethal and nontoxic to rats [45].
CYP450 and Potential for Drug-Herb Interactions: Plumbagin did not modu-
late in vitro mRNA expression of CYP1A2 and CYP3A11 in mouse liver micro-
somes [45].
Commentary: There are no clinical studies reported on this plant in the main-
stream English literature, despite historical uses and significant pharmacological
effects in animals.

References
1. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal
plants against ESbetaL-producing multidrug-resistant enteric bacteria.
Microbiol Res. 2007;162:264–75.
2. Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal
plants for their antimicrobial properties. J Ethnopharmacol. 1998;62:183–93.
3. Aqil F, Ahmad I, Owais M. Evaluation of antimethicillin-resistant Staphy-
lococcus aureus (MRSA) activity and synergy of some bioactive plant
extracts. Biotechnol J. 2006;1:1093–102.
4. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian
medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
1480 Plumbago zeylanica L.

5. Aziz MH, Dreckschmidt NE, Verma AK. Plumbagin, a medicinal

plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion
of hormone-refractory prostate cancer. Cancer Res. 2008;68:9024–32.
6. Bopaiah CP, Pradhan N. Central nervous system stimulatory action from the
root extract of Plumbago zeylanica in rats. Phytother Res. 2001;15:153–6.
7. Checker R, Sharma D, Sandur SK, et al. Anti-inflammatory effects of
plumbagin are mediated by inhibition of NF-kappaB activation in lympho-
cytes. Int Immunopharmacol. 2009;9:949–58.
8. Chen CA, Chang HH, Kao CY, et al. Plumbagin, isolated from Plumbago
zeylanica, induces cell death through apoptosis in human pancreatic cancer
cells. Pancreatology. 2009;9:797–809.
9. Cho D. Jap J Obstet Gynecol. 1933;16:254; through Biol. Abst. 1936;10:
15945.
10. Cong HJ, Zhang SW, Shen Y, et al. Guanidine alkaloids from Plumbago
zeylanica. J Nat Prod. 2013;76:1351–7.
11. Dai Y, Hou LF, Chan YP, et al. Inhibition of immediate allergic reactions by
ethanol extract from Plumbago zeylanica stems. Biol Pharm Bull. 2004;27:
429–32.
12. Durga R, Sridhar P, Polasa H. Effects of plumbagin on antibiotic resistance in
bacteria. Indian J Med Res Section A-Infectious Diseases. 1990;91:18–20.
13. Edwin S, Joshi SB, Jain DC. Antifertility activity of leaves of Plumbago
zeylanica Linn. in female albino rats. Eur J Contracept Reprod Health Care.
2009;14:233–9.
14. Gebre-Mariam T, Neubert R, Schmidt PC, et al. Antiviral activities of some
Ethiopian medicinal plants used for the treatment of dermatological disorders.
J Ethnopharmacol. 2006;104:182–7.
15. Giday M, Teklehaymanot T, Animut A, Mekonnen Y. Medicinal plants of
the Shinasha, Agew-awi and Amhara peoples in northwest Ethiopia.
J Ethnopharmacol. 2007;110:516–25.
16. Hafeez BB, Jamal MS, Fischer JW, et al. Plumbagin, a plant derived natural
agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via
targeting EGFR, Stat3 and NF-jB signaling pathways. Int J Cancer. 2012;
131:2175–86.
17. Hafeez BB, Zhong W, Fischer JW, et al. Plumbagin, a medicinal plant
(Plumbago zeylanica)-derived 1,4-naphthoquinone, inhibits growth and
metastasis of human prostate cancer PC-3 M-luciferase cells in an
orthotopic xenograft mouse model. Mol Oncol. 2013;7:428–39.
18. Ittiyavirah SP, Ruby R. Effect of hydroalcoholic root extract of Plumbago
zeylanica l alone and its combination with aqueous leaf extract of Camellia
sinensis on haloperidol induced Parkinsonism in wistar rats. Ann Neurosci.
2014;21:47–50.
19. Iyengar MA, Pendse GS. Plumbago zeylanica L. (Chitrak): a gastrointesti-
nal flora normaliser. Planta Med. 1966;14:337–51.
Plumbago zeylanica L. 1481

20. Jetty A, Subhakar C, Rajagopal D, et al. Antimicrobial activities of neo- and

1-epineoisoshinanolones from Plumbago zeylanica roots. Pharm Biol. 2010;
48:1007–11.
21. Ku K. Jap J Med Sci, IV Pharmacol. 1932;6:259; through Biol. Abst. 1934;
8:3494.
22. Kumar D, Ganguly K, Hegde HV, et al. Activity of Plumbago zeylanica Linn.
root and Holoptelea integrifolia Roxb. bark pastes in acute and chronic paw
inflammation in Wistar rat. J Ayurveda Integr Med. 2014;5:33–7.
23. Kumar D, Patil PA, Roy S, et al. Comparative toxicity profiles of Plumbago
zeylanica L. root petroleum ether, acetone and hydroalcoholic extracts in
Wistar rats. Ayu. 2015;36:329–34.
24. Li J, Shen L, Lu FR, et al. Plumbagin inhibits cell growth and potentiates
apoptosis in human gastric cancer cells in vitro through the NF-jB signaling
pathway. Acta Pharmacol Sin. 2012;33:242–9.
25. Lin LC, Yang LL, Chou CJ. Cytotoxic naphthoquinones and plumbagic acid
glucosides from Plumbago zeylanica. Phytochemistry. 2003;62:619–22.
26. Mishra BB, Gour JK, Kishore N, et al. An antileishmanial prenyloxynaph-
thoquinone from roots of Plumbago zeylanica. Nat Prod Res. 2013;27:480–5.
27. Mossa JS, El-Feraly FS, Muhammad I. Antimycobacterial constituents from
Juniperus procera, Ferula communis and Plumbago zeylanica and their
in vitro synergistic activity with isonicotinic acid hydrazide. Phytother Res.
2004;18:934–7.
28. Olagunju JA, Jobi AA, Oyedapo OO. An investigation into the biochemical
basis of the observed hyperglycaemia in rats treated with ethanol root
extract of Plumbago zeylanica. Phytother Res. 1999;13:346–8.
29. Parimala R, Sachdanandam P. Effect of Plumbagin on some glucose
metabolising enzymes studied in rats in experimental hepatoma. Mol Cell
Biochem. 1993;125:59–63.
30. Poosarla A, Rao DN, Athota RR, Sunkara VG. Modulation of T cell
proliferation and cytokine response by plumbagin, extracted from Plumbago
zeylanica in collagen induced arthritis. BMC Complement Altern Med.
2011;11:114.
31. Powolny AA, Singh SV. Plumbagin-induced apoptosis in human prostate
cancer cells is associated with modulation of cellular redox status and
generation of reactive oxygen species. Pharm Res. 2008;25:2171–80.
32. Purohit A, Vyas SK, Vyas KB. Contraceptive efficacy of Plumbago
zeylanica root extract (50% EtOH) in male albino rats with special emphasis
on testicular cell population dynamics. Anc Sci Life. 2008;27:31–5.
33. Rajakrishnan R, Lekshmi R, Benil PB, et al. Phytochemical evaluation of
roots of Plumbago zeylanica L. and assessment of its potential as a
nephroprotective agent. Saudi J Biol Sci. 2017;24:760–6.
34. Ramya KB, Thaakur S. Herbs containing L-Dopa: an update. Anc Sci Life.
2007;27:50–5.
35. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
1482 Plumbago zeylanica L.

36. Saksena SK, Garg SK, Chaudhury RR. Indian J Med Res. 1970;58:253.
37. Sandeep G, Dheeraj A, Sharma NK, et al. Effect of plumbagin free alcohol
extract of Plumbago zeylanica Linn. root on reproductive system of female
Wistar rats. Asian Pac J Trop Med. 2011;4:978–84.
38. Sandur SK, Ichikawa H, Sethi G, et al. Plumbagin (5-hydroxy-2-methyl-
1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-
regulated gene products through modulation of p65 and IkappaBalpha
kinase activation, leading to potentiation of apoptosis induced by cytokine
and chemotherapeutic agents. J Biol Chem. 2006;281:17023–33.
39. Saritha K, Rajesh A, Manjulatha K, Setty OH, Yenugu S. Mechanism of
antibacterial action of the alcoholic extracts of Hemidesmus indicus (L.) R.
Br. ex Schult, Leucas aspera (Wild.), Plumbago zeylanica L., and Tridax
procumbens (L.) R. Br. ex Schult. Front Microbiol. 2015;6:577.
40. Sharma I, Gusain D, Dixit VP. Hypolipidaemic and antiatherosclerotic
effects of plumbagin in rabbits. Indian J Physiol Pharmacol. 1991;35:10–4.
41. Sheeja E, Joshi SB, Jain DC. Bioassay-guided isolation of anti-inflammatory
and antinociceptive compound from Plumbago zeylanica leaf. Pharm Biol.
2010;48:381–7.
42. Simonsen HT, Nordskjold JB, Smitt UW, et al. In vitro screening of Indian
medicinal plants for antiplasmodial activity. J Ethnopharmacol. 2001;74:
195–204.
43. Singh MK, Pandey A, Sawarkar H, et al. Methanolic extract of Plumbago
zeylanica—a remarkable antibacterial agent against many human and
agricultural pathogens. J Pharmacopuncture. 2017;20:18–22.
44. Sivakumar V, Niranjali Devaraj S. Protective effect of Plumbago zeylanica
against cyclophosphamide-induced genotoxicity and oxidative stress in
Swiss albino mice. Drug Chem Toxicol. 2006;29:279–88.
45. Sumsakul W, Plengsuriyakarn T, Na-Bangchang K. Pharmacokinetics,
toxicity, and cytochrome P450 modulatory activity of plumbagin. BMC
Pharmacol Toxicol. 2016;17:50.
46. Sunil C, Duraipandiyan V, Agastian P, Ignacimuthu S. Antidiabetic effect of
plumbagin isolated from Plumbago zeylanica L. root and its effect on
GLUT4 translocation in streptozotocin-induced diabetic rats. Food Chem
Toxicol. 2012;50:4356–63.
47. Teshome K, Gebre-Mariam T, Asres K, et al. Toxicity studies on dermal
application of plant extract of Plumbago zeylanica used in Ethiopian
traditional medicine. J Ethnopharmacol. 2008;117:236–48.
48. Tilak JC, Adhikari S, Devasagayam TP. Antioxidant properties of Plumbago
zeylanica, an Indian medicinal plant and its active ingredient, plumbagin.
Redox Rep. 2004;9:219–27.
49. Tiwari KC, Majumder R, Bhattacharjee S. Folklore information from Assam
for family planning and birth control. Int J Crude Drug Res. 1982;20:
133–7.
Plumbago zeylanica L. 1483

50. Vijayakumar R, Senthilvelan M, Ravindran R, Devi RS. Plumbago zeylanica

action on blood coagulation profile with and without blood volume reduction.
Vascul Pharmacol. 2006;45:86–90.
51. Wang YC, Huang TL. Screening of anti-Helicobacter pylori herbs deriving
from Taiwanese folk medicinal plants. FEMS Immunol Med Microbiol.
2005;43:295–300.
52. Wang YC, Huang TL. Anti-Helicobacter pylori activity of Plumbago
zeylanica L. FEMS Immunol Med Microbiol. 2005;43:407–12.
53. Wang YC, Huang TL. High-performance liquid chromatography for
quantification of plumbagin, an anti-Helicobacter pylori compound of
Plumbago zeylanica L. J Chromatogr A. 2005;1094:99–104.
54. Xu KH, Lu DP. Plumbagin induces ROS-mediated apoptosis in human
promyelocytic leukemia cells in vivo. Leuk Res. 2010;34:658–65.
55. Xu TP, Shen H, Liu LX, Shu YQ. Plumbagin from Plumbago zeylanica L
induces apoptosis in human nonsmall cell lung cancer cell lines through
NF-jB inactivation. Asian Pac J Cancer Prev. 2013;14:2325–31.
Polygonum aviculare L.
(Polygonaceae)

(Syn.: Polygonum heterophyllum Lindm.nom.illeg.)

Abstract
An annual glabrous herb, that is widespread in temperate countries. The herb is
distributed on the Mediterranean coastal regions of Egypt and used in folkloric
medicine. It is the Polygonos of Pliny, and the male vulnerary and astringent herb
of Dioscorides. It was used by the ancients to arrest bleeding, and the seeds were
considered laxative and diuretic, and used for defluxions. Roots have been used in
Algeria as febrifuge, and as an excellent remedy for chronic diarrhea and urinary
bladder stones. Seeds are regarded to improve quality of semen, and used to treat
nocturnal emissions and premature ejaculation. Roots are diuretic, expectorant,
tonic, astringent, and antiperiodic; used in malarial fevers, chronic diarrhea,
pulmonary affections, and lithiasis. In Chinese medicine, leaves and stems are
regarded diuretic, anthelmintic and antidiarrheal, and externally used as emollient
and astringent for hemorrhoids, pruritus, and chancroid, and in traditional Korean
medicine it is used to treat obesity and symptoms associated with hypertension.
The plant is used in Swedish traditional medicine to treat inflammatory diseases
and/or wounds, and also used in Polish traditional medicine. The plant wildly
grown on the Mediterranean coastal regions of Egypt showed the presence of
tannins, saponins, flavonoids, alkaloids and sesquiterpenes. Myricetin, kaemp-
ferol, isorhamnetin and kaempferide glucuronides, taxifolin, luteolin, quercetin,
quercetin-3-methyl ether, kaempferol, and the anthraquinones: emodin and
physcion, were identified as the major phytoconstituents in the whole herb from
Poland. Quercetin and kaempferol, and a compound named, avicularin, were
reported from the Chinese herb, while quercitrin hydrate, caffeic acid, and rutin
were reported in the Korean herb. Aqueous extract significantly prevented
ethylene glycol and ammonium chloride-induced kidney stones in rats. The
extract and its active constituents, quercitrin hydrate, caffeic acid and rutin,
accelerated wound healing in mice.

© Springer Nature Switzerland AG 2020 1485

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_153
1486 Polygonum aviculare L.

Keywords
Bai jie cao
Bijband
Çoban deghinghi
Kesri
Knotgrass
Miromati

Sanguinaria
Trampört
Vejpileurt
Vogelknöterich

Vernaculars: Urd.: Beejband1; Hin.: Bijband, Kesri, Kuwar, Machoti, Nisomali;

San.: Miromati; Ben.: Meto ghas (whole plant); Ara.: Anjubar, Aśar-râi, Assâ er
râ’î, Batbát, Shabat el ghûl, Turnah; Chi.: Bai jie cao, Bian zhu, Bian zhu liao, Fen
jie cao, Pian xu; Dan.: Vejpileurt; Dut.: Varkensgras; Eng.: Birdweed, Knotgrass,
Knotweed, Lowgrass; Fin.: Pihatatar; Fre.: Centinode, Herbe à cochon, Renouee
des oiseaux, Traînasse; Ger.: Vogelknöterich; Ita.: Bistorte aviculare, Bistorta
centinodio, Centinodia, Correggiola, Poligono degli uccelli; Jap.: Michi yanagi;
Nor.: Tungras; Per.: Hozâr bandâk; Spa.: Corregüela de los aminos, Lengua de
pajaro, Sanguinaria; Swe.: Trampört; Tur.: Çoban deghinghi; Vie.: Rau đắng.
Description: An annual glabrous herb, that is widespread in temperate countries,
10–40 cm high, sometimes erect, sometimes diffuse or decumbent, with branching
stems; leaves silvery white, alternate, briefly petiolate, lanceolate or elliptical,
obtuse, with short-stalks;LXXIX flowers, variegated with white, crimson and
green.XL The root is very tough, fibrous, and somewhat woody; seeds are black
with shining luster are acutely triangular (Fig. 1).LXXXI
Actions and Uses: It is the Polygonos of Pliny, and the male vulnerary and
astringent herb of Dioscorides. It was used by the ancients to arrest bleeding, and
the seeds were considered laxative and diuretic, and used for defluxions. Roots have
been used in Algeria as febrifuge, and as an excellent remedy for chronic diarrhea
and urinary bladder stones.XL The herb is distributed on the Mediterranean coastal
regions of Egypt and used in folkloric medicine [12]. Seeds (temperament, cold 1°
and dry 1°) are regarded to improve quality of semen, and used to treat nocturnal
emissions and premature ejaculation.LXXVII Roots are diuretic, expectorant, tonic,
astringent, and antiperiodic; used in malarial fevers, chronic diarrhea, pulmonary
affections, and lithiasis.LXXXI In Chinese medicine, leaves and stems are regarded
diuretic, anthelmintic and antidiarrheal, and externally used as emollient and
astringent for hemorrhoids, pruritus, and chancroid,LXXIX and in traditional Korean
medicine it is used to treat obesity and symptoms associated with hypertension [8].
The plant is used in Swedish traditional medicine to treat inflammatory diseases
and/or wounds [18], and also used in Polish traditional medicine [15]. In southern
region of Vietnam, it is used in soups and hot pot.
Phytoconstituents: The plant wildly grown on the Mediterranean coastal regions of
Egypt showed the presence of tannins, saponins, flavonoids, alkaloids and sesquiter-
penes [12]. Myricetin, kaempferol, isorhamnetin and kaempferide glucuronides [6],
taxifolin, luteolin, quercetin, quercetin-3-methyl ether [15], and the anthraquinones
(emodin and physcion) [1] were identified as the major phytoconstituents in the whole

1
Persicaria bistorta is also known as Bijband in Urdu and Hindi languages.
Polygonum aviculare L. 1487

Fig. 1 Polygonum aviculare, Plant, Dalgial, WikimediaCommons; ShareAlike Unported 3.0 CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Polygonum_aviculare_4.JPG; https://creative
commons.org/licenses/by-sa/3.0/deed.en

herb from Poland. Quercetin and kaempferol [2], and a compound named, avicularin,
were reported from the Chinese herb [19, 21], while Seo et al. [14] reported quercitrin
hydrate, caffeic acid, and rutin present in the Korean herb.
Pharmacology: Aqueous extract significantly prevented ethylene glycol and
ammonium chloride-induced kidney stones in rats [13]. Ethanol extract supple-
mentation to high-fat diet-fed obese mice for 45-days, reduced body weight, adipose
tissue weight, serum TGs, leptin, and MDA concentrations [17], and the extract
administration for twelve-weeks to ApoE knock-out mice fed Western diet also
decreased atherosclerotic plaque, decreased body weight gain and lowered serum
lipid levels and blood pressure [8]. Hexane and n-butanol extracts are also reported
to exhibit significant endothelium-dependent vasorelaxant activity in isolated rat
aorta that also disappeared after pretreatment with L-NAME [20]. Methanol extract
treatment of rats significantly improved morphological characteristics and bio-
chemical profile of bile duct ligation and scission-induced liver fibrosis [11], and the
herb produced a strong recovery effect (98%) on APAP-induced damage of human
embryonic kidney cells [16]. Methanol extract also induced cytotoxicity in MCF-7
cell line via apoptosis [7]. Aqueous extract inhibited in vitro PG biosynthesis and
1488 Polygonum aviculare L.

PAF-induced exocytosis [18]. The extract and its active constituents, quercitrin
hydrate, caffeic acid and rutin, accelerated wound healing in mice [14]. Aqueous,
chloroform and ethanol stem extracts showed significant and better antibacterial
activity against S. aureus, S. pyogenes, B. subtilis, P. mirabilis, E.coli, P. aeruginosa,
S. typhi, S. paratyphi, S. flexneri, and antifungal activity against A. flavus,
A. fumigates, and A. niger, than leaves extracts [12]. Ethanol extract also exhibits
significant in vitro antioxidant activity [3, 9], and protects against EMF-induced
changes in morphology and motility of sperm in mice [10]. Acetylated kaempferol
and isorhamnetin glucuronides significantly inhibited in vitro ROS production as
well as elastase release from human neutrophils [5].
Clinical Studies: Two weeks use of Mexican Sanguinaria extract in an oral rinse,
significantly decreased gingivitis, but caused a significant increase in dental plaque
formation [4].
Mechanism of Action: Vasorelaxant activity is mediated via generation of NO
[20], and the anticancer activity involves apoptosis [7]. Its antioxidant activity may
also play a role in some of its effects.
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: In Unani medicine, seeds are used to improve semen quality and
treat premature ejaculation; roots are also used for various ailments. However, all
pharmacological studies published in journals listed on PubMed, have been done on
aerial parts, an aspect usually overlooked when a plant is chosen for screening.
Nevertheless, there are no clinical studies on any of its claimed clinical uses in
traditional medicines.

References
1. Avula B, Joshi VC, Wang YH, Khan IA. Simultaneous identification and
quantification of anthraquinones, polydatin, and resveratrol in Polygonum
multiflorum, various Polygonum species, and dietary supplements by liquid
chromatography and microscopic study of Polygonum species. J AOAC Int.
2007;90:1532–8.
2. Chen J, Shi Y. Determination of quercetin and kaempferol in Polygonum
aviculare by HPLC. Zhongguo Zhong Yao Za Zhi. 2009;34:423–7 (Chinese).
3. Gan RY, Kuang L, Xu XR, et al. Screening of natural antioxidants from
traditional Chinese medicinal plants associated with treatment of rheumatic
disease. Molecules. 2010;15:5988–97.
4. González Begné M, Yslas N, Reyes E, et al. Clinical effect of a Mexican
sanguinaria extract (Polygonum aviculare L.) on gingivitis. J Ethnopharma-
col. 2001;74:45–51.
Polygonum aviculare L. 1489

5. Granica S, Czerwińska ME, Zyżyńska-Granica B, Kiss AK. Antioxidant

and anti-inflammatory flavonol glucuronides from Polygonum aviculare L.
Fitoterapia. 2013;91:180–8.
6. Granica S, Piwowarski JP, Popławska M, et al. Novel insight into qualitative
standardization of Polygoni avicularis herba (Ph. Eur.). J Pharm Biomed
Anal. 2013;72:216–22.
7. Habibi RM, Mohammadi RA, Delazar A, et al. Effects of Polygonum
aviculare herbal extract on proliferation and apoptotic gene expression of
MCF-7. Daru. 2011;19:326–31.
8. Haeng Park S, Sung YY, Jin Nho K, Kyoung Kim H. Antiatherosclerotic
effects of Polygonum aviculare L. ethanol extract in ApoE knock-out mice
fed a Western diet mediated via the MAPK pathway. J Ethnopharmacol.
2014;151:1109–115.
9. Hsu CY. Antioxidant activity of extract from Polygonum aviculare L. Biol
Res. 2006;39:281–8.
10. Milan PB, Nejad DM, Ghanbari AA, et al. Effects of Polygonum aviculare
herbal extract on sperm parameters after EMF exposure in mouse. Pak J Biol
Sci. 2011;14:720–4.
11. Nan JX, Park EJ, Kim HJ, Ko G, Sohn DH. Antifibrotic effects of the
methanol extract of Polygonum aviculare in fibrotic rats induced by bile
duct ligation and scission. Biol Pharm Bull. 2000;23:240–3.
12. Salama HM, Marraiki N. Antimicrobial activity and phytochemical analyses
of Polygonum aviculare L. (Polygonaceae), naturally growing in Egypt.
Saudi J Biol Sci. 2010;17:57–63.
13. Saremi J, Kargar Jahromi H, Pourahmadi M. Effect of Polygonum aviculare
L. on nephrolithiasis induced by ethylene glycol and ammonium chloride in
rats. Urol J. 2018;15:79–82.
14. Seo SH, Lee SH, Cha PH, et al. Polygonum aviculare L. and its active
compounds, quercitrin hydrate, caffeic acid, and rutin, activate the Wnt/
b-catenin pathway and induce cutaneous wound healing. Phytother Res.
2016;30:848–54.
15. Smolarz HD. Comparative study on the free flavonoid aglycones in herbs of
different species of Polygonum L. Acta Pol Pharm. 2002;59:145–8.
16. Sohn SH, Lee EY, Lee JH, et al. Screening of herbal medicines for recovery
of acetaminophen-induced nephrotoxicity. Environ Toxicol Pharmacol.
2009;27:225–30.
17. Sung YY, Yoon T, Yang WK, et al. The antiobesity effect of Polygonum
aviculare L. ethanol extract in high-fat diet-induced obese mice. Evid Based
Complement Alternat Med. 2013;2013:626397.
18. Tunón H, Olavsdotter C, Bohlin L. Evaluation of anti-inflammatory activity
of some Swedish medicinal plants. Inhibition of prostaglandin biosynthesis
and PAF-induced exocytosis. J Ethnopharmacol. 1995;48:61–76.
1490 Polygonum aviculare L.

19. Xu LX, Liu AR. Determination of avicularin in Polygonum aviculare L.

Yao Xue Xue Bao. 1983;18:700–4 (Article in Chinese).
20. Yin MH, Kang DG, Choi DH, Kwon TO, Lee HS. Screening of
vasorelaxant activity of some medicinal plants used in Oriental medicines.
J Ethnopharmacol. 2005;99:113–7.
21. Zhang XQ, Xu LS. Determination of avicularin in Polygonum aviculare L.
by square wave polarography. Proc Chin Acad Med Sci Peking Union Med
Coll. 1989;4:193–5.
Portulaca oleracea L.
(Portulacaceae)

Abstract
An annual prostrate or spreading herb, found in India, China, Malaysia, North
Africa, Europe, North America, and wastelands. A nutritious vegetable, rich in
polyunsaturated essential fatty acids, a-linolenic acid and linoleic acid, and a rich
source of K, Mg, and Ca, and a vegetable source of omega-3 fatty acid,
a-tocopherol, ascorbic acid, a good source of a- and c-linolenic acids, and
selenium. It is extensively used as a vegetable, a potherb in many areas of Europe,
in Mediterranean and tropical Asian countries, and added in soups and salads.
Total phenolic contents and antioxidant activity are significantly higher in stems
than in leaves or flowers. Dioscorides described it as “andrachne” in De Materia
Medica and as a remedy for headaches, inflammation of the eyes and other
organs, burning of the stomach, erysipelas, disorders of bladder, numbness of
teeth, excessive sexual desire, burning fevers, dysentery, hemorrhoids, worms,
eruptions of blood, and bites; while Al-Kindi considered it good for pustules on
lips, as a remedy for spitting blood, cough and sore throat. Ibn-Jazlah said eating
it with vinegar is beneficial for bilious conditions, and employed it to eliminate
excessive yellow bile, reduce swellings, as a remedy for stomach and liver, and
for fever. It is also used for wound healing in diabetic conditions, and is one of the
most commonly used plant for medicinal purposes in Eastern Anatolia region of
Turkey. Arabian and Persian writers described it as detergent and astringent, and
recommend the leaves and seeds in many diseases of the kidneys, bladder and
lungs, which are supposed to be caused by hot or bilious humours. Diverse
pharmacologically active compounds, such as flavonoids, alkaloids, polysaccha-
rides, fatty acids, terpenoids, sterols, proteins, vitamins and minerals have been
isolated from the plant. Pharmacological activities such as neuroprotective,
antimicrobial, antidiabetic, antioxidant, anti-inflammatory, antiulcerogenic, and
anticancer have been reported. Aqueous extract exhibited moderate diuretic

© Springer Nature Switzerland AG 2020 1491

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_154
1492 Portulaca oleracea L.

activity in rats, and prevented in vitro TNF-a-induced vascular inflammatory

process and markedly blocked TNF-a-induced intracellular ROS production.
A significant decrease was reported in TC, LDL-C, and TG after one-month
treatment with powdered seeds of obese adolescents with dyslipidemia.

Keywords
Baq’lah
Baqlatul-humqa
Beldroaga
Khurfah
Lonika
Mǎ chǐ xiàn

Portulak
Postelein
Purslane
Semizotu

Vernaculars: Urd.: Khurfah, Rajla; Hin.: Khurfa, Kulfa, Lonia; San.: Ghol, Kulfa,
Loni, Lonika, Lunia, Oopadyki; Ben.: Bara-lonia, Buro luccia, Lonia; Mal.: Kar-
ichira; Mar.: Bhuigholi; Tam.: Karil kilaj, Parukire, Parpukire, Passelie keeray; Tel.:
Bodda-aveli-kura, Gangabayalakura, Peddapavila kura; Ara.: Baqlah, Baqlatul-
humqa, Birbain, Farfag, Farfan, Najlah, Rijlah; Bur.: Mya-byit, Myet-htauk; Chi.:
马齿苋, Ma-ch’ih hsien, Mǎ chǐ xiàn, Lao-shu erh; Dan.: Haveportulak; Dut.:
Postelein, Postelijn, Wilde postelein; Eng.: Little hogweed, Pigweed, Purslane; Fin.:
Portulakka, Vihannesportulakka; Fre.: Porcelaine, Porchailles, Pourpier, Pourpier
commun, Pourpier maraîcher, Pourpier potager; Ger.: Portulak; Gre.: Adrajne
agria, Antrakla, Glystrida; Haw.: Ihi-ai, Lumaha’I; Ind.: Gelang, Krokot; Ita.:
Porcellana, Portulaca comune; Jap.: Hana-suberi-hiyu, Pôchuraka, Suberi-hiyu;
Nor.: Portulakk; Per.: Baq’lah, Kholza, Kurfah, Turuk; Por.: Baldroaga, Beldroega-
comum, Bredo-fémea; Spa.: Beldroaga, Berdolaga, Loraca, Verdolaga, Verdolaga
común, Verdolaga porquera; Swe.: Portlak, Portulak, Trädgårdsportlak; Tag.:
Golasiman, Kolasiman, Makabling, Olasiman, Sahikan, Ulisiman; Tha.: Phak bia
yai; Tur.: Semizotu.
Description: An annual prostrate or spreading, succulent, branched, smooth herb
with reddish flashy stem, 10–30 cm long; found in India, China, Malaysia, North
Africa, Europe, North America, and wastelands. Leaves are clustered at stem joints
and ends, are fleshy, flat, oblong-obovate, 1–2.5 cm in length, with obtuse apex and
wedge-shaped base. Flowers, up to 6 mm wide, are yellow, stalkless, axillary and
terminal few-flowered heads; the plant blooms all year round. There are five yellow
petals which are about as long as the sepals and are notched at the tip. The flowers
(June–September) open singly at the center of the leaf cluster for only a few hours
on sunny mornings. Seeds are formed in a tiny pod, which opens when the seeds are
mature (Figs. 1, 2 and 3).CXVII
Actions and Uses: A nutritious vegetable, rich in polyunsaturated essential fatty
acids, a-linolenic acid and linoleic acid [56], and a rich source of K, Mg, and Ca, and
a vegetable source of omega-3 fatty acid [60], a-tocopherol, ascorbic acid, a good
source of a- and c-linolenic acids [78], and selenium [85]. It is extensively used as a
vegetable, a potherb in many areas of Europe, in Mediterranean and tropical Asian
countries, and added in soups and salads [95]. Total phenolic contents and antiox-
idant activity are significantly higher in stems than in leaves or flowers, so the stems
should not be discarded to fully benefit from its consumption [71].
Portulaca oleracea L. 1493

Fig. 1 Portulaca oleracea, Plant with Flowers, Isidre blanc, WikimediaCommons; ShareAlike
4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:PORTULACA_
OLERACEA_-_EMPALOUS_-_IB-518_(Verdolaga).JPG; https://creativecommons.org/licenses/
by-sa/4.0/deed.en

Fig. 2 Portulaca oleracea, Greek Salad with Purslane, Lemur12, WikimediaCommons; Share-
Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Glistrida_Greek_
salad.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Dioscorides described it as “andrachne” in De Materia Medica and as a remedy

for headaches, inflammation of the eyes and other organs, burning of the stomach,
erysipelas, disorders of bladder, numbness of teeth, excessive sexual desire, burning
fevers, dysentery, hemorrhoids, worms, eruptions of blood, and bites [28]; while
Al-Kindi considered it good for pustules on lips, as a remedy for spitting blood,
cough and sore throat.LIII Avicenna mentioned it in Canon of Medicine for the
1494 Portulaca oleracea L.

Fig. 3 Portulaca oleracea, Seed Pods, Closed and Open, 6th Happiness, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:6H-diGangi-
Purslane-Seed-Pods.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

treatment of abnormal uterine bleeding [49], while Ibn-Jazlah said eating it with
vinegar is beneficial for bilious conditions, and employed it to eliminate excessive
yellow bile, reduce swellings, as a remedy for stomach and liver, and for fever.LIII
Externally, the leaves (temperament, cold 3° and moist 2°) exert cooling and
analgesic effect; the same effects are exerted on intestines with added constipation.
Internally it is used in bilious and bloody fevers, dysuria, tuberculosis, bilious
diarrhea, and liver, stomach and uterine heat.LXXVII It is also used for wound
healing in diabetic conditions [36], and is one of the most commonly used plants for
medicinal purposes in Eastern Anatolia region of Turkey [11]. Arabian and Persian
writers described it as detergent and astringent, and recommend the leaves and
seeds in many diseases of the kidneys, bladder and lungs, which are supposed to be
caused by hot or bilious humours. They also praised its external application in
burns, scalds and various forms of skin diseases.XL It is diuretic, styptic, lithotriptic,
and is useful in dysuria, cough, diabetes, and intestinal worms.L Therapeutic ben-
efits for respiratory diseases are indicated in ancient Iranian medical books [46], and
is used in Iranian folk medicine for abnormal uterine bleeding [70]. In Indian
traditional systems of medicine, the plant is reputed as vulnerary, antiscorbutic,
refrigerant and diuretic.LXXXIV,CV Leaves are bitter, diuretic, demulcent, refrigerant
and alterative, and are used in scanty and high-colored urine, cystitis, albuminuria
and chronic bronchitis. Bruised leaves are used as cooling application in erysipelas,
burns, scalds and other inflamed and swollen parts.LXXXI Seeds are considered
anthelmintic and used as vermifuge, also prescribed for dysentery and mucous
diarrhea,LXXXIV,CV and the powdered seeds are used in hemoptysis.LXXXI Fresh
bruised leaves are applied to the temples to allay excessive heat and pain.CV In the
Philippines, leaves and tops are used as antihemorrhagic, to heal burns and in the
Portulaca oleracea L. 1495

treatment of skin diseases (topically) and internally as a diuretic.LVI While the seed
decoction was considered an emollient and an excellent diuretic,XXXIII it has also
been used to treat bacillary dysentery for thousands of years in China [41], is
nicknamed “longevity vegetable [80],” or “a vegetable for long life [92] .” Even in
North America, the plant was considered a cooling diuretic.CL In Colombia, the
plant is used as an emollient and applied to tumors and callosities; and topically
used for swellings, bruises and whitlows in West Africa [10]. In rural Dominica, the
plant is effectively used to treat intestinal worms [62], and in Trinidad and Tobago,
it is used to treat hypercholesterolemia [37]. In Hawaiian Islands, it is used in
combination with other plant constituents for the treatment of extreme weakness of
vital organs.LXXVI Fresh roots may be chewed or pounded and soaked in water for
snakebite treatment in East Africa.LXXXV Leaves are used as antiphlogistic and
bactericide in bacillary dysentery, diarrhea, hemorrhoids and enterorrhagia.LXXIX
Phytoconstituents: Diverse pharmacologically active compounds, such as flavo-
noids, alkaloids, polysaccharides, fatty acids, terpenoids, sterols, proteins, vitamins
and minerals have been isolated from the plant [95]. It contains high levels of
antioxidant compounds and mineral concentrations, higher than typical edible veg-
etables [1]. Mineral contents of various parts at various stages of growth and from
different parts of the world vary. Calcium and magnesium contents increase and the
phosphorus content decrease as the plant matures from 15 days to 30 days old [34].
Concentrations of K, Fe and Zn [77], and soluble dietary fiber contents also increase
significantly from tender to mature stage [61]. Leaves and roots have the highest
Fe content and significantly higher Mn content, and total P content in leaves are
significantly higher than in stems and roots, and vary significantly among growth
stages [50]. Potassium contents are the highest among the micro- and macrominerals
present, followed by N, Na, Ca, Mg, P, Fe, Zn, and Mn [2]. Fresh purslane leaves
from Washington were reported to contain about 300–400 mg of a-linolenic acid,
12.2 mg of a-tocopherol, 26.6 mg of ascorbic acid, 1.9 mg of b-carotene, and
14.8 mg of glutathione per 100 g [72], whereas in Australian purslane, b-carotene
content ranged from 22 to 30 mg/g of fresh leaves [44]. Alkaloids, oleracone [48],
oleraceins A–E [35, 76, 83, 84, 88, 89], oleracimine, oleracimine A, oleracone A and
B [43], oleraisoindole [29], oleraciamide A and B [42], oleraciamide C [86], olera-
ciamide D [93], homoisoflavonoids named, portulacanones A–D [87], antibacterial
compounds (portulaceramide A and portulacerebroside B–D) [41], indoline amide
glucosides [30], phenylpropanoid acids and amides [35], hesperidin and caffeic acid
[89], clerodene diterpene, portulene, lupeol, b-sitosterol, and daucosterol [20],
b-sitosterol-glucoside, N,N′-dicyclohexylurea, and allantoin [65], hydroxydihy-
drobovolide, catechol, uracil, 4-aminophenol, vanillic acid and 3-hydroxypyridine
[86], b-carboline [43], 7′-ethoxy-trans-feruloyltyramine, N-trans-feruloyltyramine,
N-trans-feruloyl-3-methoxytyramine, N-trans-p-coumaroyltyramine, ferulic acid
methyl ester, aurantiamide [29], indole-3-aldehyde, portulacatone, N-trans-feruloyl-
octopamine, and N-trans-feruloyl-3′-O-methyldopamine [93] from aerial parts have
been reported. Noradrenaline and dopamine have also been isolated from different
parts (stem, leaves, and seeds) [22, 91].
1496 Portulaca oleracea L.

Pharmacology: Pharmacological activities such as neuroprotective, antimicrobial,

antidiabetic, antioxidant, anti-inflammatory, antiulcerogenic, and anticancer have
been reported [4, 23, 31, 95]. Aqueous extract exhibited moderate diuretic activity
in rats [24], and prevented in vitro TNF-a-induced vascular inflammatory process
and markedly blocked TNF-a-induced intracellular ROS production [38]. A novel
alkaloid, oleracone, produced anti-inflammatory effects by effecting NO production
and proinflammatory cytokines [48]. Ethanol extract of aerial parts of P. oleracea
subsp. sativa exhibited significant anti-inflammatory and analgesic effects through
intraperitoneal and topical routes but not via oral administration [13]. Pretreat-
ment of mice with ethanol extract markedly reduced levels of proinflammatory
cytokines, transvascular leakage and oxidative stress due to hypobaric hypoxia, and
inhibited upregulation of NF-kB in mouse lung [92], and protected rats against
methylmercury-induced neurotoxicity by increasing antioxidant activities of CAT,
SOD, GPx, and level of GSH [75]. Pretreatment of rats with diet supplemented with
alcohol extract ameliorated LPS-induced memory deficit, possibly due to inhibition
of TNF-a and anti-inflammatory activity [52]. Aqueous extract protected against
D-galactose neurotoxicity [27], and both aqueous and ethanol extracts protected
against hypoxia-induced nerve damage [15, 81, 82]. While, aqueous extract offered
better protection than ethanol extract against 6-OHDA neurotoxicity [47], ethanol
extract significantly decreased neurological deficit, infarct size, brain edema, and
decreased serum cytokines (TNF-a, IL-1b, INF-c, IL-6) in rats with I/R-induced
brain damage [94]. Betacyanins isolated from P. oleracea protected against
D-galactose-neurotoxicity and cognition deficit in mice [79].
Aqueous extract treatment of diabetic rats for 4-weeks significantly reduced
HbA1c, serum glucose, TNF-a and IL-6, and significantly increased C peptide and
insulin [63], and treatment of diabetic mice for 10-weeks markedly lowered blood
glucose, and plasma creatinine level of rats with diabetic nephropathy through
inhibition of renal fibrosis and inflammation [39], markedly lowered SBP, LDL-C
and TGs, and significantly increased HDL-C and insulin levels [40], lowered MDA,
IL-6, and TNF-a, and improved GSH, and TAS levels in diabetic rats [67]. Aqueous
extract lowered serum TC and TGs levels, and improved reverse cholesterol trans-
port in hypercholesterolemic rats [96], and aqueous-ethanol extract exhibited very
strong in vitro inhibitory effect on pancreatic lipase that did not show any rela-
tionship with total phenolic contents [16]. Extract of fresh leaves compared to dried
leaves show stronger blood glucose lowering effect in diabetic mice, and improve-
ment in oral GTT, and enhanced insulin secretion and antioxidative activities [23].
Petroleum ether fraction of alcoholic seed extract showed the most significant
hypolipidemic effect in diabetic rats, which was attributed to the presence of phy-
tosterols, fatty acid and amide compounds [51]. A water-soluble polysaccharide
isolated from the plant significantly reduced FBG, elevated fasting serum insulin,
improved GTT and ISI, significantly reduced TNF-a and IL-6 levels and MDA and
SOD activities in the liver of diabetic rats [7]. Purslane leaves in diet protect against
vitamin A deficiency-induced oxidative stress in rats [6]. Aqueous and ethanol
extracts are cytoprotective against free radical initiator-induced hemolytic damages
[33]; however, only aqueous extract markedly alleviated high-fat diet-induced
Portulaca oleracea L. 1497

oxidative injury in mice by enhancing blood and liver antioxidant enzymes activi-
ties [14], and significantly inhibited oxidative DNA damage of human lymphocytes
[8]. Total phenolic contents and antioxidant activity are significantly higher in stems
than in leaves or flowers [71], and methanol extract contains higher total phenolic
and flavonoid contents, and show the highest antioxidant activity [26]. Purslane
polysaccharides also show significant superoxide scavenging activity [90]. Both
aqueous and ethanol extracts were protective against experimental gastric ulcers
in mice and reduced gastric acid secretion [32]. Hepatoprotective effects of aqueous
extract against cisplatin-hepatotoxicity [74], in combination with lycopene against
CCl4-[5], and ethanol extract against CCl4-[19, 69], APAP-induced [45], and in bile
duct ligation liver damage [3] have been reported.
A crude ethyl acetate extract showed marked antifungal activity against der-
matophytes of the genera Trichophyton [53], and ethanol extract was markedly
active against C. albicans, S. aureus, P. aeruginosa, E. coli, MDR A. baumannii
and K. pneumoniae [73]. A pectic polysaccharide isolated from the plant showed
anti-HSV-2 activity, preventing virus penetration into host cells [18], and linoleic
and oleic acids isolated from the plant acted synergistically with erythromycin
against MRSA strains [12]. A polysaccharide from the plant significantly inhibited
growth of transplantable Sarcoma 180 and potentiated animals’ immune responses
[68], and the seed oil was cytotoxic to human liver and lung cancer cell lines [4].
Topical application of fresh homogenized crude aerial parts on excision wound
surface accelerated wound healing [64]. Aqueous extract of leaves and stems
relaxed isolated smooth muscles, produced a negative inotropic and chronotropic
effects on isolated rabbit atria and a pressor response on BP; the effects were
blocked by phentolamine [58]. Aqueous extract also showed in vitro [54, 55], and
in vivo skeletal muscle relaxing effects, comparable to chlordiazepoxide, diazepam
and dantrolene sodium [57, 59]; the neuromuscular blocking activity was credited
to its high potassium contents [25]. Aqueous-ethanol extract stimulated b2-adre-
noceptors of isolated tracheal smooth muscle [9].
Clinical Studies: In a triple-blind RCT, 37 young obese Iranian adolescents
(12–18 years old of both sexes) with documented dyslipidemia were treated with
500 mg of powdered seeds twice daily, and a matching number of controls with
placebo. A significant decrease in TC, LDL-C, and TGs resulted after one month of
treatment [66]. A dose of 5 g seeds powder twice daily to 15 type-2 diabetic Iranian
patients significantly lowered their serum levels of TGs, TC, LDL-C, liver
enzymes, fasting and postprandial blood glucose and insulin, and caused a sig-
nificant increase in HDL-C, comparable to 15 patients treated with 1,500 mg
metformin a day [21]. Seed consumption (2.5 g at lunch and 5 g at dinner) along
with aerobic exercise by Iranian women with type-2 DM for 16-weeks, significantly
reduced blood glucose, LDL-C, TGs, creatinine, urea, and uric acid, and signifi-
cantly increased HDL-C [17]. In a pilot clinical study of 10 premenopausal Iranian
women with abnormal uterine bleeding (menorrhagia, metrorrhagia, polymenorrhea
and intermenstrual bleeding) unresponsive to standard treatment, 5 g of purslane
1498 Portulaca oleracea L.

seeds powder was orally given with a glass of water every 4 h for 3 days, starting
48 h after the onset of menstruation. Eight (80%) patients had their duration and
volume of bleeding reduced and their patterns of periods normalized [70]. In
asthmatic patients, decoction of the plant produced a potent but relatively
short-lived bronchodilatory effect [46].
Mechanism of Action: Presence of dopamine precursor, the antioxidant activity
[47], and anti-inflammatory activity [94] are credited for its neuroprotective effects.
The antioxidant activity, decrease in TNF-a and IL-6, and significant insulinotropic
effect may contribute to its antidiabetic activity [63].
Human A/Es, Allergy and Toxicity: It is considered harmful for spleen and the
eyesight.LXXVII
Animal Toxicity: LD50 (i.p.) of aqueous leaves extract in mice was reported to be
1,040 mg/kg; whereas 1,000 mg/kg i.p. was lethal to 80% mice [59].
Commentary: Reported significant effects of its seeds in diabetic and dyslipidemic
patients are encouraging but need further validation in patients of various ethnici-
ties. Also, claims of seeds’ effectiveness in abnormal uterine bleeding is an area for
further investigation in clinical trials. The plant holds promise for several clinical
applications and should be explored.

References
1. Aberoumand A. Preliminary assessment of nutritional value of plant-based
diets in relation to human nutrients. Int J Food Sci Nutr. 2009;60 Suppl 4:
155–62.
2. Alam MA, Juraimi AS, Rafii MY, et al. Evaluation of antioxidant
compounds, antioxidant activities, and mineral composition of 13 collected
purslane (Portulaca oleracea L.) accessions. Biomed Res Int. 2014;2014:
296063.
3. Ali SI, Said MM, Hassan EK. Prophylactic and curative effects of purslane
on bile duct ligation-induced hepatic fibrosis in albino rats. Ann Hepatol.
2011;10:340–6.
4. Al-Sheddi ES, Farshori NN, Al-Oqail MM, et al. Portulaca oleracea seed
oil exerts cytotoxic effects on human liver cancer (HepG2) and human lung
cancer (A-549) cell lines. Asian Pac J Cancer Prev. 2015;16:3383–7.
5. Anusha M, Venkateswarlu M, Prabhakaran V, et al. Hepatoprotective activity
of aqueous extract of Portulaca oleracea in combination with lycopene in
rats. Indian J Pharmacol. 2011;43:563–7.
6. Arruda SF, Siqueira EM, Souza EM. Malanga (Xanthosoma sagittifolium)
and purslane (Portulaca oleracea) leaves reduce oxidative stress in vitamin
A-deficient rats. Ann Nutr Metab. 2004;48:288–95.
Portulaca oleracea L. 1499

7. Bai Y, Zang X, Ma J, Xu G. Antidiabetic effect of Portulaca oleracea L.

polysaccharide and its mechanism in diabetic rats. Int J Mol Sci. 2016;17.
8. Behravan J, Mosafa F, Soudmand N, et al. Protective effects of aqueous and
ethanolic extracts of Portulaca oleracea L. aerial parts on H2O2-induced
DNA damage in lymphocytes by comet assay. J Acupunct Meridian Stud.
2011;4:193–7.
9. Boskabady MH, Hashemzehi M, Khazdair MR, Askari VR. Hydroethanolic
extract of Portulaca oleracea affects beta-adrenoceptors of guinea pig
tracheal smooth muscle. Iran J Pharm Res. 2016;15:867–74.
10. Caius JF. Medicinal and poisonous plants of India: Flacourtiads, Pittospo-
rads, Milkworta, Seahealths, Purslanes. Tamaricks. J Bombay Nat Hist Soc.
1939;41:123–42.
11. Cakilcioglu U, Turkoglu I. An ethnobotanical survey of medicinal plants in
Sivrice (Elazığ-Turkey). J Ethnopharmacol. 2010;132:165–75.
12. Chan BC, Han XQ, Lui SL, et al. Combating against methicillin-resistant
Staphylococcus aureus—two fatty acids from Purslane (Portulaca oleracea
L.) exhibit synergistic effects with erythromycin. J Pharm Pharmacol. 2015;
67:107–16.
13. Chan K, Islam MW, Kamil M, et al. The analgesic and anti-inflammatory
effects of Portulaca oleracea L. subsp. sativa (Haw.) Celak. J Ethnophar-
macol. 2000;73:445–51.
14. Chen B, Zhou H, Zhao W, et al. Effects of aqueous extract of Portulaca
oleracea L. on oxidative stress and liver, spleen leptin, PARa and FAS mRNA
expression in high-fat diet induced mice. Mol Biol Rep. 2012;39:7981–8.
15. Chen CJ, Wang WY, Wang XL, et al. Antihypoxic activity of the ethanol
extract from Portulaca oleracea in mice. J Ethnopharmacol. 2009;124:
246–50.
16. Conforti F, Perri V, Menichini F, et al. Wild Mediterranean dietary plants as
inhibitors of pancreatic lipase. Phytother Res. 2012;26:600–4.
17. Dehghan F, Soori R, Gholami K, et al. Purslane (Portulaca oleracea) seed
consumption and aerobic training improves biomarkers associated with
atherosclerosis in women with type 2 diabetes (T2D). Sci Rep. 2016;6:37819.
18. Dong CX, Hayashi K, Lee JB, Hayashi T. Characterization of structures and
antiviral effects of polysaccharides from Portulaca oleracea L. Chem Pharm
Bull (Tokyo). 2010;58:507–10.
19. Eidi A, Mortazavi P, Moghadam JZ, Mardani PM. Hepatoprotective effects
of Portulaca oleracea extract against CCl4-induced damage in rats. Pharm
Biol. 2015;53:1042–51.
20. Elkhayat ES, Ibrahim SR, Aziz MA. Portulene, a new diterpene from
Portulaca oleracea L. J Asian Nat Prod Res. 2008;10:1039–43.
21. El-Sayed MI. Effects of Portulaca oleracea L. seeds in treatment of type-2
diabetes mellitus patients as adjunctive and alternative therapy. J Ethnophar-
macol. 2011;137:643–51.
22. Feng PC, Haynes LJ, Magnus KE. High concentration of (-)-noradrenaline
in Portulaca oleracea L. Nature. (Lond.) 1961;191:1108.
1500 Portulaca oleracea L.

23. Gu JF, Zheng ZY, Yuan JR, et al. Comparison on hypoglycemic and
antioxidant activities of the fresh and dried Portulaca oleracea L. in
insulin-resistant HepG2 cells and streptozotocin-induced C57BL/6 J dia-
betic mice. J Ethnopharmacol. 2015;161:214–23.
24. Gujral ML, Saxena PN, Mishra SS. An experimental study of the compar-
ative activity of indigenous diuretics. J Indian Med Assoc. 1955;25:49.
25. Habtemariam S, Harvey AL, Waterman PG. The muscle relaxant properties
of Portulaca oleracea are associated with high concentrations of potassium
ions. J Ethnopharmacol. 1993;40:195–200.
26. Handique JG, Boruah MP, Kalita D. Antioxidant activities and total
phenolic and flavonoid contents in three indigenous medicinal vegetables of
northeast India. Nat Prod Commun. 2012;7:1021–3.
27. Hongxing Z, Nancai Y, Guofu H, et al. Neuroprotective effects of purslane
herb aquenous extracts against D-galactose induced neurotoxicity. Chem
Biol Interact. 2007;170:145–52.
28. Iranshahy M, Javadi B, Iranshahi M, et al. A review of traditional uses,
phytochemistry and pharmacology of Portulaca oleracea L. J Ethnophar-
macol. 2017;205:158–72.
29. Jiang M, Zhang W, Yang X, et al. An isoindole alkaloid from Portulaca
oleracea L. Nat Prod Res. 2018;32:2431–6.
30. Jiao ZZ, Yue S, Sun HX, et al. Indoline amide glucosides from Portulaca
oleracea: isolation, structure, and DPPH radical scavenging activity. J Nat
Prod. 2015;78:2588–97.
31. Jiménez Misas CA, Rojas Hernandez NM, López Abraham AM. Biological
evaluation of Cuban plants. V. Rev Cubana Med Trop. 1979;31:37–43
(Spanish).
32. Karimi G, Hosseinzadeh H, Ettehad N. Evaluation of the gastric antiulcero-
genic effects of Portulaca oleracea L. extracts in mice. Phytother Res.
2004;18:484–7.
33. Karimi G, Aghasizadeh M, Razavi M, Taghiabadi E. Protective effects of
aqueous and ethanolic extracts of Nigella sativa L. and Portulaca oleracea
L. on free radical induced hemolysis of RBCs. Daru. 2011;19:295–300.
34. Khader V, Rama S. Effect of maturity on macromineral content of selected
leafy vegetables. Asia Pac J Clin Nutr. 2003;12:45–9.
35. Kokubun T, Kite GC, Veitch NC, Simmonds MS. Amides and an alkaloid
from Portulaca oleracea. Nat Prod Commun. 2012;7:1047–50.
36. Laitiff AA, Teoh SL, Das S. Wound healing in diabetes mellitus: traditional
treatment modalities. Clin Ter. 2010;161:359–64.
37. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary
problems and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2:45.
38. Lee AS, Kim JS, Lee YJ, et al. Anti-TNF-a activity of Portulaca oleracea
in vascular endothelial cells. Int J Mol Sci. 2012;13:5628–44.
39. Lee AS, Lee YJ, Lee SM, et al. An aqueous extract of Portulaca oleracea
ameliorates diabetic nephropathy through suppression of renal fibrosis and
inflammation in diabetic db/db mice. Am J Chin Med. 2012;40:495–510.
Portulaca oleracea L. 1501

40. Lee AS, Lee YJ, Lee SM, et al. Portulaca oleracea ameliorates diabetic
vascular inflammation and endothelial dysfunction in db/db mice. Evid
Based Complement Alternat Med. 2012;2012:741824.
41. Lei X, Li J, Liu B, Zhang N, Liu H. Separation and identification of four
new compounds with antibacterial activity from Portulaca oleracea L.
Molecules. 2015;20:16375–87.
42. Li C, Ying Z, Gao M, et al. Two new similar alkaloids from Portulaca
oleracea L. Nat Prod Res. 2017;31:1792–8.
43. Li CY, Meng YH, Ying ZM, et al. Three novel alkaloids from Portulaca
oleracea l. and their anti-inflammatory effects. J Agric Food Chem. 2016;
64:5837–44.
44. Liu L, Howe P, Zhou YF, et al. Fatty acids and beta-carotene in Australian
purslane (Portulaca oleracea) varieties. J Chromatogr A. 2000;893:207–13.
45. Liu XF, Zheng CG, Shi HG, et al. Ethanol extract from Portulaca oleracea
L. attenuated acetaminophen-induced mice liver injury. Am J Transl Res.
2015;7:309–18.
46. Malek F, Boskabady MH, Borushaki MT, Tohidi M. Bronchodilatory effect
of Portulaca oleracea in airways of asthmatic patients. J Ethnopharmacol.
2004;93:57–62.
47. Martins WB, Rodrigues SA, Silva HK, et al. Neuroprotective effect of
Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of
dopaminergic neurons. An Acad Bras Cienc. 2016;88:1439–50.
48. Meng Y, Ying Z, Xiang Z, et al. The anti-inflammation and pharmacoki-
netics of a novel alkaloid from Portulaca oleracea L. J Pharm Pharmacol.
2016;68:397–405.
49. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal
plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
50. Mohamed AI, Hussein AS. Chemical composition of purslane (Portulaca
oleracea). Plant Foods Hum Nutr. 1994;45:1–9.
51. Nazeam JA, El-Hefnawy HM, Omran G, Singab AN. Chemical profile and
antihyperlipidemic effect of Portulaca oleracea L. seeds in streptozotocin-
induced diabetic rats. Nat Prod Res. 20:1–5.
52. Noorbakhshnia M, Karimi-Zandi L. Portulaca oleracea L. prevents
lipopolysaccharide-induced passive avoidance learning and memory and
TNF-a impairments in hippocampus of rat. Physiol Behav. 2017;169:69–73.
53. Oh KB, Chang IM, Hwang KJ, Mar W. Detection of antifungal activity in
Portulaca oleracea by a single-cell bioassay system. Phytother Res. 2000;
14:329–32.
54. Okwuasaba F, Ejike C, Parry O. Comparison of the skeletal muscle relaxant
properties of Portulaca oleracea extracts with dantrolene sodium and
methoxyverapamil. J Ethnopharmacol. 1987;20:85–106.
55. Okwuasaba F, Ejike C, Parry O. Skeletal muscle relaxant properties of the
aqueous extract of Portulaca oleracea. J Ethnopharmacol. 1986;17:139–60.
1502 Portulaca oleracea L.

56. Palaniswamy UR, McAvoy RJ, Bible BB. Stage of harvest and polyunsat-
urated essential fatty acid concentrations in purslane (Portulaca oleraceae)
leaves. J Agric Food Chem. 2001;49:3490–3.
57. Parry O, Marks JA, Okwuasaba FK. The skeletal muscle relaxant action of
Portulaca oleracea: role of potassium ions. J Ethnopharmacol. 1993;40:
187–94.
58. Parry O, Okwuasaba F, Ejike C. Effect of an aqueous extract of Portulaca
oleracea leaves on smooth muscle and rat blood pressure. J Ethnopharmacol.
1988;22:33–44.
59. Parry O, Okwuasaba FK, Ejike C. Skeletal muscle relaxant action of an
aqueous extract of Portulaca oleracea in the rat. J Ethnopharmacol. 1987;19:
247–53.
60. Petropoulos SA, Karkanis A, Fernandes Â, et al. Chemical composition and
yield of six genotypes of common purslane (Portulaca oleracea L.): an
alternative source of omega-3 fatty acids. Plant Foods Hum Nutr. 2015;70:
420–6.
61. Punna R, Rao Paruchuri U. Effect of maturity and processing on total,
insoluble and soluble dietary fiber contents of Indian green leafy vegetables.
Int J Food Sci Nutr. 2004;55:561–7.
62. Quinlan MB, Quinlan RJ, Nolan JM. Ethnophysiology and herbal treatments
of intestinal worms in Dominica, West Indies. J Ethnopharmacol. 2002;80:
75–83.
63. Ramadan BK, Schaalan MF, Tolba AM. Hypoglycemic and pancreatic
protective effects of Portulaca oleracea extract in alloxan induced diabetic
rats. BMC Complement Altern Med. 2017;17:37.
64. Rashed AN, Afifi FU, Disi AM. Simple evaluation of the wound healing
activity of a crude extract of Portulaca oleracea L. (growing in Jordan) in
Mus musculus JVI-1. J Ethnopharmacol. 2003;88:131–6.
65. Rasheed AN, Afifi FU, Shaedah M, Taha MO. Investigation of the active
constituents of Portulaca oleraceae L. (Portulacaceae) growing in Jordan.
Pak J Pharm Sci. 2004;17:37–45.
66. Sabzghabaee AM, Kelishadi R, Jelokhanian H, et al. Clinical effects of
Portulaca oleracea seeds on dyslipidemia in obese adolescents: a triple-
blinded randomized controlled trial. Med Arch. 2014;68:195–9.
67. Samarghandian S, Borji A, Farkhondeh T. Attenuation of oxidative stress
and inflammation by Portulaca oleracea in streptozotocin-induced diabetic
rats. J Evid Based Complementary Altern Med. 2017;22:562–6.
68. Shen H, Tang G, Zeng G, et al. Purification and characterization of an
antitumor polysaccharide from Portulaca oleracea L. Carbohydr Polym.
2013;93:395–400.
69. Shi H, Liu X, Tang G, et al. Ethanol extract of Portulaca Oleracea L.
reduced the carbon tetrachloride induced liver injury in mice involving
enhancement of NF-jB activity. Am J Transl Res. 2014;6:746–55.
Portulaca oleracea L. 1503

70. Shobeiri SF, Sharei S, Heidari A, Kianbakht S. Portulaca oleracea L. in the

treatment of patients with abnormal uterine bleeding: a Pilot clinical trial.
Phytother Res. 2009;23:1411–4.
71. Silva R, Carvalho IS. In vitro antioxidant activity, phenolic compounds and
protective effect against DNA damage provided by leaves, stems and flowers
of Portulaca oleracea (Purslane). Nat Prod Commun. 2014;9:45–50.
72. Simopoulos AP, Norman HA, Gillaspy JE, Duke JA. Common purslane: a
source of omega-3 fatty acids and antioxidants. J Am Coll Nutr. 1992;11:
374–82.
73. Soliman SSM, Semreen MH, El-Keblawy AA, et al. Assessment of herbal
drugs for promising anti-Candida activity. BMC Complement Altern Med.
2017;17:257.
74. Sudhakar D, Krishna Kishore R, Parthasarathy PR. Portulaca oleracea L.
extract ameliorates the cisplatin-induced toxicity in chick embryonic liver.
Indian J Biochem Biophys. 2010;47:185–9.
75. Sumathi T, Christinal J. Neuroprotective effect of Portulaca oleraceae
ethanolic extract ameliorates methylmercury induced cognitive dysfunction
and oxidative stress in cerebellum and cortex of rat brain. Biol Trace Elem
Res. 2016;172:155–65.
76. Tian JL, Liang X, Gao PY, et al. Two new alkaloids from Portulaca oleracea
and their cytotoxic activities. J Asian Nat Prod Res. 2014;16:259–64.
77. Uddin MK, Juraimi AS, Ali ME, Ismail MR. Evaluation of antioxidant
properties and mineral composition of purslane (Portulaca oleracea L.) at
different growth stages. Int J Mol Sci. 2012;13:10257–67.
78. Uddin MK, Juraimi AS, Hossain MS, et al. Purslane weed (Portulaca
oleracea): a prospective plant source of nutrition, omega-3 fatty acid, and
antioxidant attributes. ScientificWorld J. 2014;2014:951019.
79. Wang CQ, Yang GQ. Betacyanins from Portulaca oleracea L. ameliorate
cognition deficits and attenuate oxidative damage induced by D-galactose in
the brains of senescent mice. Phytomedicine. 2010;17:527–32.
80. Wang P, Sun H, Liu D, et al. Protective effect of a phenolic extract containing
indoline amides from Portulaca oleracea against cognitive impairment in
senescent mice induced by large dose of D-galactose/NaNO2. J Ethnophar-
macol. 2017;203:252–9.
81. Wang W, Gu L, Dong L, et al. Protective effect of Portulaca oleracea
extracts on hypoxic nerve tissue and its mechanism. Asia Pac J Clin Nutr.
2007;16 Suppl 1:227–33.
82. Wanyin W, Liwei D, Lin J, et al. Ethanol extract of Portulaca oleracea L.
protects against hypoxia-induced neuro damage through modulating
endogenous erythropoietin expression. J Nutr Biochem. 2012;23:385–91.
83. Xiang L, Xing D, Wang W, et al. Alkaloids from Portulaca oleracea L.
Phytochemistry. 2005;66:2595–601.
1504 Portulaca oleracea L.

84. Xing J, Yang Z, Lv B, Xiang L. Rapid screening for cyclodopa and

diketopiperazine alkaloids in crude extracts of Portulaca oleracea L. using
liquid chromatography/tandem mass spectrometry. Rapid Commun Mass
Spectrom. 2008;22:1415–22.
85. Xu H, Xu HE. Analysis of trace elements in Chinese therapeutic foods and
herbs. Am J Chin Med. 2009;37:625–38.
86. Xu L, Ying Z, Wei W, et al. A novel alkaloid from Portulaca oleracea L.
Nat Prod Res. 2017;31:902–8.
87. Yan J, Sun LR, Zhou ZY, et al. Homoisoflavonoids from the medicinal
plant Portulaca oleracea. Phytochemistry. 2012;80:37–41.
88. Yang Z, Liu C, Xiang L, Zheng Y. Phenolic alkaloids as a new class of
antioxidants in Portulaca oleracea. Phytother Res. 2009;23:1032–5.
89. Yang ZJ, Zheng YN, Xiang L. Study on chemical constituents of Portulaca
oleracea. Zhong Yao Cai. 2007;30:1248–50 (Chinese).
90. YouGuo C, ZongJi S, XiaoPing C. Evaluation of free radicals scavenging
and immunity-modulatory activities of Purslane polysaccharides. Int J Biol
Macromol. 2009;45:448–52.
91. Yue ME, Jiang TF, Shi YP. Simultaneous determination of noradrenaline
and dopamine in Portulaca oleracea L. by capillary zone electrophoresis.
J Sep Sci. 2005;28:360–4.
92. Yue T, Xiaosa W, Ruirui Q, et al. The effects of Portulaca oleracea on
hypoxia-induced pulmonary edema in mice. High Alt Med Biol. 2015;16:
43–51.
93. Zhao C, Ying Z, Tao X, et al. A new lactam alkaloid from Portulaca
oleracea L. and its cytotoxity. Nat Prod Res. 2018;32:1548–53.
94. Zheng C, Liu C, Wang W, et al. Ethanol extracts from Portulaca oleracea L.
attenuated ischemia/reperfusion induced rat neural injury through inhibi-
tion of HMGB1 induced inflammation. Am J Transl Res. 2016;8:5016–24.
95. Zhou YX, Xin HL, Rahman K, et al. Portulaca oleracea L.: a review of
phytochemistry and pharmacological effects. Biomed Res Int. 2015;2015:
925631.
96. Zidan Y, Bouderbala S, Djellouli F, Lacaille-Dubois MA, Bouchenak M.
Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves
lecithin: cholesterol acyltransferase activity in rats fed enriched-cholesterol
diet. Phytomedicine. 2014;21:1504–8.
Quercus infectoria G. Olivier
(Fagaceae)

(Syns.: Q. boissieri Reut.; Q. carpinea Kotschy ex A.DC; Q. grosseserrata Kotschy

ex Wenz.; Q. puberula O. Schwarz; Q. thirkeana K.Koch)

Abstract
It is a native of Greece, Iran, Syria, Turkey, southwest Asia, and southern
Europe. Greeks and Romans used galls for their astringent properties, and they
were introduced into India via the Persian Gulf countries. Hindu physicians
classified them into black and white, but did not differentiate in their properties.
Whereas, Muslim physicians considered dark-colored unperforated ones as the
best. Tannic and gallic acids in the galls coagulate albumin, and it is therefore a
useful application in skin conditions deprived of epidermis, such as intertrigo,
impetigo and eczema. Galen recommended its use as a styptic after roasting over
coals and soaked in wine, and Dioscorides said it darkens hair black when used
soaked in vinegar, and Avicenna vouches cure for eczema when galls ground in
vinegar are applied to it. Galls powder is used in diarrhea, gleet, long-standing
gonorrhea, leucorrhea and other vaginal discharges. Being astringent and
antibacterial, its powder is externally used to control excessive sweating, bad
odor and for wound healing. In Malay traditional medicine, galls are commonly
used to treat wound infections after childbirth, and due to their astringent
properties, they help in the tightening of the vaginal epithelium in the postnatal
period. Galls contain large amount of tannins (50–70%), gallic acid, syringic
acid, ellagic acid, sitosterol, amentoflavone, hexamethyl ether, isocryptomerin,
methyl betulate, methyloleanate and hexagalloyl glucose. They have demon-
strated analgesic, anti-inflammatory, anticancer, a-glucosidase inhibitory,
antidyslipidemic, CNS depressant, antioxidant, ACE inhibitory, and antivenom
activities.

Keywords






Afas Aleppoek Chêne d’alep Gall-eiche Majuphal Mayika Mazı meşesi





Mazu Oak galls Roble tintoreto

© Springer Nature Switzerland AG 2020 1505

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_155
1506 Quercus infectoria G. Olivier

Vernaculars: Urd.: Mazoo; Hin.: Majuphal, Maphal, Mazu; San.: Majauhu,

Majuphal, Mayika, Mayin; Ben.: Majuphal, Maphal; Mal.: Maja-kanee; Mar.:
Maiphala, Maja; Tam.: Machakai, Mashik-kay; Tel.: Mashi-kaya; Ara.: Afas,
Ajees; Bur.: Pinza-kani-si, Pyintagar-ne-thi; Cze.: Dub hálkový; Eng.: Aleppo oak,
Asian holly-oak, Cyprus oak, Oak galls, The Dyer’s oak; Fre.: Chêne à galles,
Chêne d’Alep, Chêne du Kurdistan; Ger.: Gall-eiche, Gallapfel-eiche, Kurdistan-
eiche; Ita.: Quercia alle galle; Maly.: Manja-kani; Per.: Mazu, Mazun; Spa.:
Encina de la agalla, Roble de Aleppo, Roble tintoreto; Swe.: Aleppoek; Tur.:
Mazı meşesi.
Description: It is a native of Greece, Iran, Syria, Turkey, southwest Asia, and
southern Europe. The galls are globose, 1.4–2.3 cm long and 1–1.5 cm in diameter,
greyish-brown to brownish-black with smooth surface punctuated by numerous
horny protuberances, making it rough to touch, and with unpleasant odor [30]. Two
kinds of Oak galls, Mazouj and Ghalghaf, are available in Iran that are formed by
two different gall-wasp species, i.e., Cynips gallae tinctoriae and Andricus quer-
custozae, respectively [22]. Galls from Xinjiang Uyghur Autonomous Region are
produced as a result of infections of trees or shrubs by the Cynips gallae tinctoriae
wasp [15], or attack by the insect Adleria gallac-tinctoriae Oliv. Dioscorides
described fresh and tender unperforated galls as the best, but very astringent
(Figs. 1 and 2).LXIX
Actions and Uses: Greeks and Romans used galls for their astringent properties,
and they were introduced into India via the Persian Gulf countries. Hindu physicians
classified them into black and white, but used both in the same prescription, meaning
did not differentiate for their properties. Whereas, Muslim physicians considered

Fig. 1 Quercus infectoria, Illustration Leaves and Galls, George Ripley and Charles A. Dana,
The American Cyclopaedia, WikimediaCommons, https://commons.wikimedia.org/wiki/File:Quercus_
infectoria.jpg
Quercus infectoria G. Olivier 1507

Fig. 2 Quercus infectoria, Autumn Foliage, Veyis Polat, WikimediaCommons; 2.0 Generic CC BY
2.0, https://commons.wikimedia.org/wiki/File:Quercus_boissieri_Izmir.jpg; https://creativecommons.
org/licenses/by/2.0/deed.en

dark-colored unperforated ones as the best. Tannic and gallic acids in the galls
coagulate albumin, and it is therefore a useful application in skin conditions deprived
of epidermis, such as intertrigo, impetigo and eczema.XL Galen recommended its use
as a styptic after roasting over coals and soaked in wine, and Dioscorides said it
darkens hair black when used soaked in vinegar, and Avicenna vouches cure for
eczema when galls ground in vinegar are applied to it.LXIX Galls powder is used in
diarrhea, gleet, long-standing gonorrhea, leucorrhea and other vaginal discharges.CV
Being astringent and antibacterial, its powder is externally used to control excessive
sweating, bad odor and for wound healing. Also, used to rub on gums to stop
bleeding and to strengthen them, and used as gargles for sore-throat, pharyngitis and
to treat halitosis. Internally, galls are used for intestinal ulcers, chronic diarrhea and
leucorrhea. The decoction is also used as enema for bloody diarrhea.LXXVII GhaniL
says that it cures all types of chronic diarrhea. Galls are astringent and tonic, constrict
muscular tissues in small blood vessels’ wall to stop hemorrhage and reduce local
inflammation.LXXXI Gall extract is used in traditional Uyghur medicine as an
astringent, a moisture eliminator, an anti-inflammatory agent (to treat erysipelas),
antiseptic and antidiarrheal agent in the treatment of intestinal dysmotility, dysen-
tery, functional enteritis, hemorrhagic sores, alopecia areata, dental caries, peri-
odontitis, halitosis, pharyngolaryngitis and tympanitis, and as an enema in ulcerative
colitis [15]. In Malay traditional medicine, galls are commonly used to treat wound
infections after childbirth, and due to their astringent properties, they help in the
tightening of the vaginal epithelium in the postnatal period. In India, they are also
used in the treatment of toothache and gingivitis [2, 3], and as gargle for relaxed
throat.LXXXI
Phytoconstituents: Galls show positive reaction to the presence of phenols, flavo-
noids, steroids, triterpenes, tannins, saponins and alkaloids [30]. They contain large
amount of tannins (50–70%), gallic acid, syringic acid, ellagic acid, sitosterol,
1508 Quercus infectoria G. Olivier

amentoflavone, hexamethyl ether, isocryptomerin, methyl betulate, methyloleanate

and hexagalloyl glucose; five main components include gallic acid, m-digallic acid,
methyl gallate, 1,2,3,6-tetra-O-galloyl-b-D-glucose and 1,2,3,4,6-penta-O-galloyl-b-
D-glucose [15]. Syringic acid was credited for its CNS depressant activity [9].

Pharmacology: Galls possess analgesic [8, 10], anti-inflammatory [18, 19], anti-
cancer [40], a-glucosidase inhibitory [13], CNS depressant [9], antioxidant [18, 19],
antidyslipidemic [11, 17], ACE inhibitory [29], and antivenom activities [20, 23].
Galls exhibit antimicrobial activities against S. aureus [21, 32], MRSA [3, 5–7, 34],
E. coli [33], streptomycin-resistant E. coli [36], oral pathogenic bacteria, Gram-
positive (S. mutans and S. salivarius) and two Gram-negative bacteria (P. gingivalis
and F. nucleatum) [2, 14], S. aureus, L. acidophilus and S. sanguis [32], P. aeruginosa,
E. faecalis, K. oxytocoa, K. pneumoniae and P. mirabilis [25], Shiga toxigenic
E. coli [31, 37], verocytotoxin-producing enterohemorrhagic E. coli [35, 38],
intestinal protozoan parasite, B. hominis [28], E. histolytica [27], larvicidal [26], and
HCV [12]. Galls water extract demonstrated in vitro anti-inflammatory and antioxi-
dant activities and protection against CCl4-hepatotoxicity [24]. Both aqueous and
ethanol extracts showed substantial inhibitory effects against methicillin resistant
coagulase negative Staphylococcus and MRSA, but no inhibition of ESbetaL
K. pneumoniae and E. coli isolates [39]. Ethanol extract possesses high bacteriostatic
and bactericidal activities against enterohemorrhagic strains of E. coli, including
E. coli O157:H7 with MICs of 0.12–0.98 mg/ml and MBCs of 1.95–3.91 mg/ml
[38]. While methanol and aqueous extracts exhibited significant anti-Candida activity
against C. albicans, C. krusei, C. glabrata, C. parapsilosis and C. tropicalis [1];
methanol, ethanol, and acetone extracts also showed strong inhibitory effects on
S. mutans [22].
Oral administration of ethanol extract significantly inhibited carrageenan, his-
tamine, serotonin and PGE2-induced paw edema, while topical application inhibited
PMA-induced ear inflammation. It also inhibited iNOS in macrophages, without
affecting the catalytic activity of the enzyme [19]. Topical application of an ethanol
extract formulation enhanced wound healing in diabetic rats [4]. An acetone-treated
methanol extract showed analgesic activity and significantly lowered blood glucose
levels in rabbits. Another chloroform-methanol extract subfraction exhibited CNS
depressant activity and potentiated barbiturate sleeping time without affecting the
onset of loss of righting reflex [8].
Clinical Studies: An herbal toothpaste containing Q. infectoria, along with other
herbs, significantly improved plaque index, bleeding on probing from gums and the
presence of anaerobic bacteria in mouths of patients with gingivitis, after treatment
of 12-weeks [16].
Human A/Es, Allergy and Toxicity: Tannic acid from galls used in burn therapy
and in rectal enemas as an astringent and styptic in cases of anal fissures and
hemorrhoids, and to stop diarrhea and dysentery, was absorbed and caused severe
liver necrosis.CXI Adversely affects chest and throat.LXXVII
Quercus infectoria G. Olivier 1509

Animal Toxicity: Aqueous gall extract was nontoxic to mice up to a dose of

10,000 mg/kg body weight in acute toxicity study, and up to 2,000 mg/kg dose in
Wistar rats for 180-days [15].
Commentary: There are no clinical studies on galls except in a polyherbal
toothpaste. Most reported pharmacological studies have shown broad-spectrum
antimicrobial activity of various exracts. The antimicrobial and astringent properties
are clinically attractive areas for further research on nutgalls.

References
1. Baharuddin NS, Abdullah H, Abdul Wahab WN. Anti-Candida activity of
Quercus infectoria gall extracts against Candida species. J Pharm Bioallied
Sci. 2015;7:15–20.
2. Basri DF, Tan LS, Shafiei Z, et al. In vitro antibacterial activity of galls of
Quercus infectoria Olivier against oral pathogens. Evid Based Complement
Alternat Med. 2012;2012:632796.
3. Basri DF, Khairon R. Pharmacodynamic interaction of Quercus infectoria
galls extract in combination with vancomycin against MRSA using microdi-
lution checkerboard and time-kill assay. Evid Based Complement Alternat
Med. 2012;2012:493156.
4. Chokpaisarn J, Chusri S, Amnuaikit T, Udomuksorn W, Voravuthikunchai
SP. Potential wound healing activity of Quercus infectoria formulation in
diabetic rats. Peer J. 2017;5:e3608.
5. Chusri S, Voravuthikunchai SP. Damage of staphylococcal cytoplasmic
membrane by Quercus infectoria G. Olivier and its components. Lett Appl
Microbiol. 2011;52:565–72.
6. Chusri S, Voravuthikunchai SP. Detailed studies on Quercus infectoria
Olivier (nutgalls) as an alternative treatment for methicillin-resistant Staphy-
lococcus aureus infections. J Appl Microbiol. 2009;106:89–96.
7. Chusri S, Voravuthikunchai SP. Quercus infectoria: a candidate for the
control of methicillin-resistant Staphylococcus aureus infections. Phytother
Res. 2008;22:560–2.
8. Dar MS, Ikram M, Fakouhi T. Pharmacology of Quercus infectoria. J Pharm
Sci. 1976;65:1791–4.
9. Dar MS, Ikram M. Studies on Quercus infectoria; isolation of syringic acid
and determination of its central depressive activity. Planta Med. 1979;35:
156–61.
10. Fan SH, Ali NA, Basri DF. Evaluation of analgesic activity of the methanol
extract from the galls of Quercus infectoria (Olivier) in rats. Evid Based
Complement Alternat Med. 2014;2014:976764.
11. Gholamhoseinian A, Shahouzehi B, Joukar S, et al. Effect of Quercus
infectoria and Rosa damascena on lipid profile and atherosclerotic plaque
formation in rabbit model of hyperlipidemia. Pak J Biol Sci. 2012;15:27–33.
1510 Quercus infectoria G. Olivier

12. Hussein G, Miyashiro H, Nakamura N, et al. Inhibitory effects of Sudanese

medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res.
2000;14:510–6.
13. Hwang JK, Kong TW, Baek NI, et al. Alpha-Glycosidase inhibitory activity
of hexagalloylglucose from the galls of Quercus infectoria. Planta Med.
2000;66:273–4.
14. Hwang JK, Shim JS, Chung JY. Anticariogenic activity of some tropical
medicinal plants against Streptococcus mutans. Fitoterapia. 2004;75:596–8.
15. Iminjan M, Amat N, Li XH, et al. Investigation into the toxicity of
traditional Uyghur medicine Quercus infectoria galls water extract. PLoS
One. 2014;9:e90756.
16. Jayashankar S, Panagoda GJ, Amaratunga EA, et al. A randomised double-
blind placebo-controlled study on the effects of a herbal toothpaste on gin-
gival bleeding, oral hygiene and microbial variables. Ceylon Med J. 2011;56:
5–9.
17. Joukar S, Askarzadeh M, Shahouzehi B, et al. Assessment of safety and ther-
apeutic efficacy of Rosa damascena L. and Quercus infectoria on cardio-
vascular performance of normal and hyperlipidemic rabbits: physiologically
based approach. J Toxicol. 2013;2013:769143.
18. Kaur G, Athar M, Alam MS. Quercus infectoria galls possess antioxidant
activity and abrogates oxidative stress-induced functional alterations in
murine macrophages. Chem Biol Interact. 2008;171:272–82.
19. Kaur G, Hamid H, Ali A, et al. Anti-inflammatory evaluation of alcoholic
extract of galls of Quercus infectoria. J Ethnopharmacol. 2004;90:285–92.
20. Leanpolchareanchai J, Pithayanukul P, Bavovada R. Antinecrosis potential
of polyphenols against snake venoms. Immunopharmacol Immunotoxicol.
2009;31:556–62.
21. Mekseepralard C, Kamkaen N, Wilkinson JM. Antimicrobial and antiox-
idant activities of traditional Thai herbal remedies for aphthous ulcers.
Phytother Res. 2010;24:1514–9.
22. Mohammadi-Sichani M, Karbasizadeh V, Dokhaharani SC. Evaluation of
biofilm removal activity of Quercus infectoria galls against Streptococcus
mutans. Dent Res J (Isfahan). 2016;13:46–51.
23. Pithayanukul P, Ruenraroengsak P, Bavovada R, et al. Inhibition of Naja
kaouthia venom activities by plant polyphenols. J Ethnopharmacol. 2005;
97:527–33.
24. Pithayanukul P, Nithitanakool S, Bavovada R. Hepatoprotective potential of
extracts from seeds of Areca catechu and nutgalls of Quercus infectoria.
Molecules. 2009;14:4987–5000.
25. Priya PS, Sasikumar JM, Gowsigan G. Antibacterial activity of methanol
extract of Ruta chalapensis (L.), Quercus infectoria (Oliver) and Canthium
parviflorum (Lam.). Anc Sci Life. 2009;29:28–31.
26. Redwane A, Lazrek HB, Bouallam S, et al. Larvicidal activity of extracts
from Quercus lusitania var. infectoria galls (Oliv.). J Ethnopharmacol.
2002;79:261–3.
Quercus infectoria G. Olivier 1511

27. Sawangjaroen N, Sawangjaroen K, Poonpanang P. Effects of Piper longum

fruit, Piper sarmentosum root and Quercus infectoria nut gall on caecal
amoebiasis in mice. J Ethnopharmacol. 2004;91:357–60.
28. Sawangjaroen N, Sawangjaroen K. The effects of extracts from anti-
diarrheic Thai medicinal plants on the in vitro growth of the intestinal
protozoa parasite: Blastocystis hominis. J Ethnopharmacol. 2005;98:67–72.
29. Sharifi N, Souri E, Ziai SA, et al. Discovery of new angiotensin converting
enzyme (ACE) inhibitors from medicinal plants to treat hypertension using
an in vitro assay. Daru. 2013;21:74.
30. Shrestha S, Kaushik VS, Eshwarappa RS, et al. Pharmacognostic studies
of insect gall of Quercus infectoria Olivier (Fagaceae). Asian Pac J Trop
Biomed. 2014;4:35–9.
31. Suwalak S, Voravuthikunchai SP. Morphological and ultrastructural changes
in the cell structure of enterohaemorrhagic Escherichia coli O157:H7
following treatment with Quercus infectoria nut galls. J Electron Microsc
(Tokyo). 2009;58:315–20.
32. Vermani A. Navneet, Prabhat: screening of Quercus infectoria gall extracts
as antibacterial agents against dental pathogens. Indian J Dent Res. 2009;20:
337–9.
33. Voravuthikunchai S, Lortheeranuwat A, Jeeju W, et al. Effective medicinal
plants against enterohaemorrhagic Escherichia coli O157:H7. J Ethnophar-
macol. 2004;94:49–54.
34. Voravuthikunchai SP, Kitpipit L. Activity of medicinal plant extracts
against hospital isolates of methicillin-resistant Staphylococcus aureus. Clin
Microbiol Infect. 2005;11:510–2.
35. Voravuthikunchai SP, Suwalak S. Antibacterial activities of semipurified
fractions of Quercus infectoria against enterohemorrhagic Escherichia coli
O157:H7 and its verocytotoxin production. J Food Prot. 2008;71:1223–7.
36. Voravuthikunchai SP, Suwalak S, Mitranan W. Ellagitannin from Quercus
infectoria eradicates intestinal colonization and prevents renal injuries in
mice infected with Escherichia coli O157:H7. J Med Microbiol. 2012;61:
1366–72.
37. Voravuthikunchai SP, Suwalak S. Changes in cell surface properties of
shiga toxigenic Escherichia coli by Quercus infectoria G. Olivier. J Food
Prot. 2009;72:1699–704.
38. Vorayuthikunchai SP, Limsuwan S. Medicinal plant extracts as anti-
Escherichia coli O157:H7 agents and their effects on bacterial cell aggre-
gation. J Food Prot. 2006;69:2336–41.
39. Wan Nor Amilah WA. Masrah M, Hasmah A, Noor Izani NJ. In vitro
antibacterial activity of Quercus infectoria gall extracts against multidrug
resistant bacteria. Trop Biomed. 2014;31:680–8.
40. Yarani R, Mansouri K, Mohammadi-Motlagh HR, et al. In vitro inhibition
of angiogenesis by hydroalcoholic extract of oak (Quercus infectoria) acorn
shell via suppressing VEGF, MMP-2, and MMP-9 secretion. Pharm Biol.
2013;51:361–8.
Rauvolfia serpentina (L.) Benth. ex Kurz
(Apocynaceae)

(Syns.: Ophioxylon album Gaertn.; O. obversum Miq.; O. salutiferum Salisb.;

O. serpentinum L.; O. trifoliatum Gaertn.; Rauvolfia obversa (Miq.) Baill.; R. trifoliata
(Gaertn.) Baill.)

Abstract
The plant is native to India, Bangladesh, Sri Lanka, Burma, Thailand, Malaya, the
Andaman Islands, the Philippines and Indonesia. In India, the root has been used
for the treatment of snake and scorpion bites, insect stings, nervous disorders,
mania and epilepsy for thousands of years. It is also used as a vermifuge and for
the treatment of colic, diarrhea, dysentery, cholera, dysmenorrhea, fever, and to
facilitate childbirth. Javanese call it Pulipandak and use it as anthelmintic. In
Unani medicine, the root is regarded analgesic and antihypertensive, and used for
mania, insomnias and neuropsychotic behavior. It is said to lose its effectiveness
on boiling and is only used as powder. In China, R. verticillata is used as Luofumu
but R. serpentina has also been introduced in the country. It is described to have
cold property, latent-heat-clearing, antipyretic, detumescent, reduces pathogenic
heat in the liver and is used to treat fever in common cold, pharyngolaryngitis,
headache and vertigo in hypertension, acute abdominal pain, vomiting, urticaria,
scabies, mania, and for snake and scorpion bites. In the northern part of Thailand,
the plant has traditionally been used for the treatment of diabetes mellitus and
other diseases by the Thai-Lanna people. Its alkaloid, ajmaline possesses potent
antiarrhythmic effects, and reserpine was widely used clinically as antihyperten-
sive agent, but its use declined over the years due to its sedative and extrapyra-
midal effects. The root bark is primarily rich in alkaloids, which constitute
40–56% of the whole root alkaloid contents and contains 90% of the total
alkaloids present in the plant. The fibrous roots are more active than the interior of
the main taproot. Total alkaloid contents vary with the location, season and other
factors, and range from 1.49–2.38%. There are wo main classes of alkaloids; the
reserpine group or tertiary indoles, and the ajmaline group or tertiary indoline
alkaoids. Aqueous extract caused significant reduction in FBG of normoglycemic
and alloxan-diabetic mice. Methanol root extract also improved body weight,
glucose and insulin levels, insulin/glucose ratio, glycosylated and total Hb, and
significantly decreased levels of TC, TGs, LDL-C, and VLDL-C of diabetic mice.

© Springer Nature Switzerland AG 2020 1513

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_156
1514 Rauvolfia serpentina (L.) Benth. ex Kurz

Keywords





Arbre aux serpents Asrol Chhota chaand Chandrika Luofumu Sarpagandha






Schlangenwurzel Segno serpentine Serpentine root Shégēn mù

Vernaculars: Urd.: Asrol; Hin.: Chandrabagha, Chhota chaand; San.: Chandrika,

Sarpagandha; Ben.: Chandra; Mal.: Chivanna-avilpori, Suvapavalforiyan; Mar.:
Harkai, Harkaya, Harki; Tam.: Chivan-melpodi, Covannamilapori, Sarpaganthi;
Tel.: Patala-gandhi; Chi.: 蛇根木, Luofumu, Shégēn mù, Yìndù shémù; Eng.:
Rauwolfia root, Serpentine root; Fre.: Arbre aux serpents; Ger.: Schlangen-
holzbaum, Schlangenwurzel; Ita.: Segno serpentine; Jav.: Pulipandak.
Description: The plant is native to India, Bangladesh, Sri Lanka, Burma, Thailand,
Malaya, the Andaman Islands, the Philippines and Indonesia. It grows in moist
deciduous forests from sea level to 4,000 feet, often associated with bamboo plants
[40]. It is an erect subshrub, 15–45 cm high, and seldom as high as 90 cm. Leaves
are 7.5–20 cm long, deciduous, elliptic-lanceolate or obovate, pointed, green on the
upper surface, pale-green on the underside and borne in whorls of 3 or 4. Flowers
are numerous, in terminal or axillary, long-stalked clusters; are tubular, five-lobed,
1–3 cm long, the lobes white, the tube pink; calyx is yellowish at first; at the onset
of fruit-setting, the calyces, pedicels and flowering stalk become bright-red. Fruits,
usually in pairs united for half their length; obliquely ovoid, 7.5 mm long,
purple-black and glossy when ripe, scantily fleshy, with a hard stone containing 1 or
2 seeds. The stem, when broken, exudes a pale, sticky sap. Root is nearly vertical,
tapering taproot becoming as much as 15 cm thick at the crown and up to 50 cm
long, occasionally branched or tortuous, and developing several smaller, fibrous
side roots; grayish-yellow externally, pale-yellow within; acrid in odor when fresh,
odorless when dried; very bitter [11, 16, 40].IV Dymock et al.XL described the root
as crooked, tapering from about 13 mm in diameter downwards; bark soft, corky,
marked by longitudinal fissures, light brown in color; wood brittle, showing rings
and medullary rays visible to naked eyes; taste very bitter, odor of the fresh root
acrid (Figs. 1 and 2).
Actions and Uses: In India, the root has been used for the treatment of snake and
scorpion bites, insect stings, nervous disorders, mania and epilepsy for thousands of
years. It is also used as a vermifuge and for the treatment of colic, diarrhea,
dysentery, cholera, dysmenorrhea, fever, and to facilitate childbirth.XXI,LXXXI
Javanese call it Pulipandak and use it as anthelmintic.XL In Unani medicine, the
root (temperament, cold 2° and dry 3°) is regarded analgesic and antihypertensive,
and used for mania, insomnias and neuropsychotic behavior (Hejaan). It is used
only as powder and loses its effectiveness on boiling.1 NadkarniCV described root as
bitter tonic and sedative, and its decoction is used to increase uterine contractions
and promote expulsion of the fetus. In China, R. verticillata is used as Luofumu

1
Tayyab M: Personal Communication.
Rauvolfia serpentina (L.) Benth. ex Kurz 1515

Fig. 1 Rauvolfia serpentina, Plant, Aashish Bhatnagar, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Rauwolfia_serpentina_at_talkatora_gardens_delhi.jpg

Fig. 2 Rauvolfia serpentina, Flowers, Fruits and Leaves, Forestowlet, WikimediaCommons;

ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Rauvolfia_
serpentina_11.JPG; https://creativecommons.org/licenses/by-sa/4.0/deed.en
1516 Rauvolfia serpentina (L.) Benth. ex Kurz

but R. serpentina has also been introduced in the country. It is described to have
cold property, latent-heat-clearing, antipyretic, detumescent, reduces pathogenic
heat in the liver and is used to treat fever in common cold, pharyngolaryngitis,
headache and vertigo in hypertension, acute abdominal pain, vomiting, urticaria,
scabies, mania, and for snake and scorpion bites.XVIII In the northern part of
Thailand, the plant has traditionally been used for the treatment of diabetes mellitus
and other diseases by the Thai-Lanna people [31]. Its alkaloid, ajmaline possesses
potent antiarrhythmic effects [38], and reserpine was widely used clinically as
antihypertensive agent, but its use declined over the years due to its sedative and
extrapyramidal effects [35].
Phytoconstituents: The root bark is primarily rich in alkaloids, which constitute
40–56% of the whole root alkaloid contents and contains 90% of the total alkaloids
present in the plant. The fibrous roots are more active than the interior of the main
taproot [11, 16]. Total alkaloid contents vary with the location, season and other
factors, and range from 1.49–2.38% [8]. There are wo main classes of alkaloids; the
reserpine group or tertiary indoles, and the ajmaline group or tertiary indoline
alkaoids [7]. Main alkaloids are ajmaline (rauwolfine), ajmalicine (d-yohimbine),
ajmalinine, isoajmaline, neoajmaline, yohimbine, alloyohimbine, g-yohimbine,
isoyohimbine, alkaloids A, C and F, deserpidine, methyl reserpate, papaverine,
corynanthine, raunatine, rauwolfinine, rauwolscine, reserpine, reserpiline, rescin-
namine, reserpinine, sarpagine, serpinine, reserpoxidine, serpine, serpentine, ser-
pentinine, thebaine, chandrine, and unnamed alkaloids I and II [7, 13, 14, 26, 34,
41, 43–45, 53, 54], ajmalimine, tetraphyllicine, rescinnamine N(b)-methylajmaline,
raubasine, N(b)-methylisoajmaline, 3-hydroxysarpagine, yohimbinic acid, and
isorauhimbinic acid [10, 22, 47]. The 2 indole-type hypotensive alkaloids, rau-
galline and ajmaline were found identical [49]. An iridoid glucoside, 7-epiloganin,
and a new sucrose derivative (6′-O-(3,4,5-trimethoxybenzoyl) glomeratose A) have
also been isolated from the roots [22]. The globulin proteins of the seeds contained
asparagine, serine, threonine, alanine, methionine, phenylalanine and leucine [36].
Pharmacology: Aqueous extract caused significant reduction in FBG of normo-
glycemic and alloxan-diabetic mice [31]. Methanol root extract also improved body
weight, glucose and insulin levels, insulin/glucose ratio, glycosylated and total Hb,
and significantly decreased levels of TC, TGs, LDL-C, and VLDL-C of diabetic
mice [5]. Methanol leaf extract exhibits significant antidiarrheal activity in castor
oil-induced diarrhea in mice [12]. Reserpine was an effective protection against
radiation: mice subcutaneously injected with serpasil (reserpine 4 mg/kg) and
exposed to X-rays totaling as much as 955r, 24 h later had a better survival rate
[32]. Raubasine (ajmalicine) significantly reduced ex vivo platelet aggregation in
patients at risk due to complications of atherosclerosis [37].
Clinical Studies: Rauwolfia serpentina, an ancient Indian folk remedy, was
introduced to the world by Dr. Rustom Jal Vakil in 1949 through his work on
reserpine as the modern pharmacotherapy of hypertension [15, 21, 24]. Treatment
with combination of a diuretic and R. serpentine reduced DBP an average of 10 mm
Rauvolfia serpentina (L.) Benth. ex Kurz 1517

Hg (systolic equals 16 mm Hg) with no change in the placebo group over a period
of 7–10 years. Although major end points of death, MI, and stroke were nearly
equally divided between treatment and placebo groups; complications such as left
ventricular hypertrophy, radiogrpahic cardiomegaly, and retinopathy were reduced
by 55% by the drug [48]. A Cochrane Database Systematic Review (2009) of
clinical trials concluded a statistically significant SBP reduction in patients taking
reserpine was achieved with a dose of 0.5 mg/day or greater, compared to placebo,
and roughly to the same degree as other first-line antihypertensive drugs [46].
Rauwolfia preparations were still at the top of antihypertensive medications in
1980s Germany, despite the fact that b-blockers were being promoted as the first
choice for hypertension treatment [28]. Reserpine was used as tranquilizer and for
the treatment of mild hypertension and anxiety,CXI showed usefulness for menstrual
tension and menopausal disturbances [33], and also contributed as an important
clinical tool in the treatment of schizophrenia [18, 29].
Mechanism of Action: Reserpine depletes 5-HT and catecholamines in the brain
by irreversibly blocking vesicular monoamine transporter (VMAT) [20], and affects
concentrations of ACh, GABA, glycogen, nucleic acids, ADH and substance P. It
suppresses respiration, stimulates peristalsis and miosis, relaxes nictitating mem-
branes and affects temperature regulation; it also promotes and acidifies gastric
secretions and sometimes stimulates prothrombin activity.
Dose: Powdered root is used in a dose of 100 mg twice daily as a tranquilizer. In
chronic cases higher doses, 50–300 mg daily may be used. Maximum effect is
evidenced after a period of one to three weeks and lasts for a month after cessation of
medication. Reserpine, on the contrary, is given orally in doses of 0.05–0.75 mg
daily. Higher doses are used only for neuropsychotic patients under hospital care.CXI
Human A/Es, Allergy and Toxicity: R. serpentina causes increase in prolactin
secretion and galactorrhea by depleting stores of hypothalamic prolactin inhibitory
factor, i.e. dopamine [9], and an increase in the risk of breast cancer in women on
rauwolfia was suggested [1, 2, 6, 17], which was later disputed [3, 4, 25, 27, 30, 39].
Doubts about a possible correlation between the use of reserpine and rauwolfia drugs
as antihypertensive agents and breast cancer incidence were dispelled experimentally
when they showed no genotoxic, mutagenic and recombinogenic effects [19, 50, 51].
Crude drug is hypnotic and purgative, and may cause impotence in males. However,
reserpine causes too many adverse effects; even in small doses it may cause gastritis,
aggravation and perforation of gastric ulcers and hemorrhage [52]. Other reactions
include dizziness, nasal congestion, respiratory difficulty, skin irritation, joint and
muscular pain, frequent bowel movements, and weight gain [33]. In higher doses,
reserpine may induce edema, cardiac depression, pseudoparkinsonism, insomnia,
nightmares, despondency and suicidal tendency. In toxic doses, unconsciousness and
death results from respiratory paralysis.XXI Therefore, it should not be used in
patients with bronchitis, asthma or gastric ulcers [23]. Reserpine required higher
doses through IM route than oral route for hypertension treatment. CNS disturbances
were the most common unwanted effects, followed by GIT disturbances. Adverse
effects were more common in patients receiving higher doses through IM route [42].
1518 Rauvolfia serpentina (L.) Benth. ex Kurz

Animal Toxicity: No animal toxicity studies on the plant are reported in the
literature.
Commentary: This plant is mainly recognized for its alkaloids, especially the
reserpine. Since reserpine has been replaced as antihypertensive by many other
more effective drugs with lesser adverse effects, the plant has been relegated to
history and neglected for further investigations, despite being used in Indian
medicine for thousands of years. It deserves a fresher look and more pharmaco-
logical and clinical studies.

References
1. Anonymous. Editorial: Rauwolfia and breast cancer. Br Med J. 1974;4:121–2.
2. Armstrong B, Stevens N, Doll R. Retrospective study of the association
between use of rauwolfia derivatives and breast cancer in English women.
Lancet. 1974;2:672–5.
3. Armstrong B. Recent trends in breast-cancer incidence and mortality in
relation to changes in possible risk factors. Int J Cancer. 1976;17:204–11.
4. Aromaa A, Hakama M, Hakulinen T, et al. Breast cancer and use of rauwolfia
and other antihypertensive agents in hypertensive patients: a nationwide
case-control study in Finland. Int J Cancer. 1976;18:727–38.
5. Azmi MB, Qureshi SA. Methanolic root extract of Rauwolfia serpentina
Benth improves the glycemic, antiatherogenic, and cardioprotective indices
in alloxan-induced diabetic mice. Adv Pharmacol Sci. 2012;2012:376429.
6. Boston Collaborative Drug Surveillance Programme (BCDSP). Lancet. 1974;
2:669.
7. Chatterjee A, Ray AB. Recent developments in the chemistry of indole
alkaloids from Rauvolfia serpentina Benth. J Sci Indus Res. 1962;21A:
515–27.
8. Cornett GBR. Rauvolfia serpentina. World Crops. 1965;17:33–7.
9. Dickey RP, Stone SC. Drugs that affect the breast and lactation. Clin Obstet
Gynecol. 1975;18:95–111 (Review).
10. Duncan RJ, Nash CB. Electropharmacology of the rauwolfia alkaloids,
ajmaline tetraphyllicine, and serpentine on the canine heart. Arch Int
Pharmacodyn Ther. 1973;206:181–90.
11. Dutta PK, Chopra IC, Kapoor LD. Cultivation of Rauvolfia serpentina in
India. Econ Bot. 1963;17:243–51.
12. Ezeigbo I, Ezeja M, Madubuike K, et al. Antidiarrhoeal activity of leaf
methanolic extract of Rauwolfia serpentina. Asian Pac J Trop Biomed. 2012;
2:430–2.
13. Feuell AJ. The genus Rauwolfia; some aspects of its botany, chemistry, and
medicinal uses. Col Pl Anim Prod. 1955;5:33.
14. Fleming TS. Rauwolfia serpentina and its alkaloids. Mo Med. 1954;51:754–5.
15. Goenka AH. Rustom Jal Vakil and the saga of Rauwolfia serpentina. J Med
Biogr. 2007;15:195–200.
Rauvolfia serpentina (L.) Benth. ex Kurz 1519

16. Gupta R. Raise Rauvolfia for export. Indian Farming. 1972;21:9–12.

17. Heinonen OP, Shapiro S, Tuominen L, Turunen MI. Reserpine use in relation
to breast cancer. Lancet. 1974;2:675–7.
18. Heinrich K. Psychopharmacology since 1952. Fortschr Neurol Psychiatr.
1994;62:31–9 (Article in German).
19. Henriques JA, Moreno PR, Von Poser GL, et al. Genotoxic effect of
alkaloids. Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:71–4.
20. Henry JP, Scherman D. Radioligands of the vesicular monoamine trans-
porter and their use as markers of monoamine storage vesicles. Biochem
Pharmacol. 1989;38:2395–404.
21. Isharwal S, Gupta S. Rustom Jal Vakil: his contributions to cardiology. Tex
Heart Inst J. 2006;33:161–70.
22. Itoh A, Kumashiro T, Yamaguchi M, et al. Indole alkaloids and other
constituents of Rauwolfia serpentina. J Nat Prod. 2005;68:848–52.
23. Jain SK. Medicinal plants. New Delhi: National Book Trust; 1968. p. 176.
24. Jerie P. Milestones of cardiovascular therapy. IV. Reserpine. Cas Lek Cesk.
2007;146:573–7 (Review, Czech).
25. Kewitz H, Jesdinsky HJ, Schröter PM, Lindtner E. Reserpine and breast
cancer in women in Germany. Eur J Clin Pharmacol. 1977;11:79–83.
26. Kleinsorge H, Wittig HH. Alkaloids from Rauwolfia serpentina used
therapeutically in hypertension. Medizinische. 1954;33–34:1086–9.
27. Lilienfeld AM, Chang L, Thomas DB, Levin ML. Rauwolfia derivatives
and breast cancer. Johns Hopkins Med J. 1976;139:41–50.
28. Lohmann D, Görlt H, Rühle H. Changing of therapeutic habits in the drug
therapy of high blood pressure. Z Gesamte Inn Med. 1980;35(Suppl):
109–11 (German).
29. López-Muñoz F, Bhatara VS, Alamo C, Cuenca E. Historical approach to
reserpine discovery and its introduction in psychiatry. Actas Esp Psiquiatr.
2004;32:387–95 (Spanish).
30. Mack TM, Henderson BE, Gerkins VR, et al. Reserpine and breast cancer in
a retirement community. N Engl J Med. 1975;292:1366–71.
31. Manosroi J, Moses ZZ, Manosroi W, Manosroi A. Hypoglycemic activity of
Thai medicinal plants selected from the Thai/Lanna Medicinal Recipe
Database MANOSROI II. J Ethnopharmacol. 2011;138:92–8.
32. Melching HJ, Langendorff M. Naturwissenschaften. 1957;44:377.
33. Miner RW (editor). Reserpine (Serpasil) and other alkaloids of Rauwolfia
serpentina: chemistry, pharmacology and clinical applications. Ann NY Acad
Sci. 1954;59:140.
34. Mukherji D, Robinson R, Schlittler E. Chemistry of ajmaline, rauwolfine of
Van Itallie and Steenhauer. Experientia. 1949;5:215–7.
35. Nammi S, Boini KM, Koppula S, Sreemantula S. Reserpine-induced central
effects: pharmacological evidence for the lack of central effects of reserpine
methiodide. Can J Physiol Pharmacol. 2005;83:509–15.
36. Nath Yoginder, Rao PR. Amino acid composition of the proteins of the
seeds of Rauwolfia serpentina. Indian J Pharm. 1962;24:187.
1520 Rauvolfia serpentina (L.) Benth. ex Kurz

37. Neuman J, de Engel AM, Neuman MP. Pilot study of the effect of raubasine
on platelet biological activity. Arzneimittelforschung. 1986;36:1394–8.
38. Obayashi K, Nagasawa K, Mandel WJ, et al. Cardiovascular effects of
ajmaline. Am Heart J. 1976;92:487–96.
39. O’Fallon WM, Labarthe DR, Kurland LT. Rauwolfia derivatives and breast
cancer. A case/control study in Olmsted County, Minnesota. Lancet. 1975;2:
292–6.
40. Paa NF, Blando JG, Milan FD. Rauwolfia serpentina (Benth.) and its intro-
duction in the Philippines. Phil Geog J. 1968;12:12–5.
41. Pakrashi SC, Achari B. Rauwolfia alkaloids in retrospect. J Sci Indus Res.
1968;27:58–69.
42. Pfeifer HJ, Greenblatt DK, Koch-Wester J. Clinical toxicity of reserpine in
hospitalized patients: a report from the Boston Collaborative Drug
Surveillance Program. Am J Med Sci. 1976;271:269–76.
43. Phillips DD, Chadha MS. The alkaloids of Rauwolfia serpentina Benth.
J Am Pharm Assoc. 1955;44:553–67.
44. Rakshit B. Chandrine. Another alkaloid from R. serpentina. Indian Pharma-
cist. 1954;9:226–7.
45. Schlittler E, Macphillamy HB, Dorfman L, et al. Chemistry of Rauwolfia
alkaloids, including reserpine. Ann N Y Acad Sci. 1954;59:1–7.
46. Shamon SD, Perez MI. Blood pressure lowering efficacy of reserpine for
primary hypertension. Cochrane Database Syst Rev. 2009;4:CD007655.
47. Siddiqui S, Ahmad SS, Haider SI. A New Alkaloid ajmalimine from the
roots of Rauwolfia serpentina. Planta Med. 1987;53:288–9.
48. Smith WM. Treatment of mild hypertension: results of a ten-year interven-
tion trial. Circ Res. 1977;40(5 Suppl 1):198–205.
49. Taylor WI, Potier P. Men JLe. Ajmaline, an alkaloid from Rauwolfia
serpentina. Ann Pharm Franc. 1963;21:321–3.
50. Tsutsui T, Taguchi S, Hasegawa K, et al. Reserpine-induced cell transfor-
mation without detectable genetic effects in Syrian hamster embryo cells in
culture. Carcinogenesis. 1994;15:11–4.
51. von Poser G, Andrade HH, da Silva KV, et al. Genotoxic, mutagenic and
recombinogenic effects of rauwolfia alkaloids. Mutat Res. 1990;232:37–43.
52. Weiss Y, Merceron RE, Sobel A, et al. Comparison of the antihypertensive
effects of alpha-methyldopa, clonidine, guanethidine and reserpine. I. Clin-
ical study. J Pharmacol Clin. 1973;1:24–29. BA 57:68252.
53. Willaman JJ, Schubert BG. Alkaloid-bearing plants and their contained
alkaloids. Technical Bulletin 1234. USDA, ARS, Washington, DC; 1961.
p. 287.
54. Willaman JJ, Hui-lin Li. Alkaloid bearing plants and their contained
alkaloids 1957–1968. Lloydia. 1970;33(Suppl):1–286.
Rheum emodi Wall. ex Meisn
(Polygonaceae)

(Syn.: Rheum australe D. Don)

Abstract
The plant is native to China and western Himalayas of India. It has large (Ta)
leaves and a yellow color (Huang), hence named Ta-Huang in Chinese. In The
Herbal by Shen Nung, it is described as an inferior (toxic) drug, used as a
stomachic and purgative for internal heat, constipation, abdominal ache, mania,
edema, amenorrhea and jaundice. In India, root of Rheum emodi is described as
Revandchini or rhubarb; a bitter stomachic in low doses and a purgative in high
doses. It is reported to have been cultivated for over 5000 years by rural and
tribal people of Kashmir for its medicinal properties, and used for the treatment
of cancer. In Unani medicine, the best revandchini is described as the one that is
large, heavy, horseshoe-shaped, dark red, strongly aromatic, and tastes astringent
and bitter. It is purgative of all humours, and is diuretic and emmenagogue. In
cases of dysmenorrhea coupled with irregular blood flow, finely ground
revandchini with sugar (Misri) is started two days before the start of menses and
continued for 3 or more days for complete relief. The root is emmenagogue, and
is used as a substitute for R. officinale. In Western medicine, rhubarb was mainly
employed as a purgative, but not in constipation or any affection in which a
continuous aperient action was necessary. It is eliminated by the skin, kidneys
and in milk, staining urine, sweat and milk. Rhubarb can cause purgation even if
it is applied as a poultice to abraded skin or as a dusting powder on ulcers. The
plant mainly contains 1,8-dihydroxyanthraquinones, such as rhein, aloe emodin,
emodin, chrysophanol and physcion with diverse pharmacological and thera-
peutic effects. It is reported to possess protective effects in many inflammatory
diseases and oxidative stress-related injuries. Methanol rhizome extract contains
higher polyphenolic contents than the aqueous extract, and shows higher
antioxidant potential. Various extracts of the rhizome exhibit hepatoprotective
effect against CCl4-hepatotoxicity in rats. In a single-blind, randomized trial,
R. emodi powder twice daily, two days before the expected date, and continued
for the first three days of menstruation significantly decreased menstrual pain of
primary dysmenorrhea, comparable to mefenamic acid three times daily.
© Springer Nature Switzerland AG 2020 1521
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_157
1522 Rheum emodi Wall. ex Meisn

Keywords





Amplaparni Dahuang Emodi-rhabarber Indian rhubarb Revand-e-hindi





Revandchini Rhubarb de perse Riwas Ta-huang Variyattu

Vernaculars: Urd.: Revand-e-hindi, Revandchini; Hin.: Revandchini; San.:

Amplaparni, Amlavetasa, Revatchini; Ben.: Bangla revanchini, Rheuchini; Mal.:
Amalvetas; Mar.: Ladakirevanda chini, Raevaachini, Reval-chinni; Tam.: Nattu-
manjat-chinak, Reval sinni, Variyattu; Tel.: Nattu-ireval-chinni, Naattu raevalchini;
Ara.: Rewand; Chi.: 藏边大黄, Dahuang, Huang-hang, Ta-Huang, Zang bian da
huang; Eng.: Himalayan rhubarb, Indian rhubarb; Fre.: Rhubarb de perse; Ger.:
Emodi-rhabarber, Himalaya-rhabarber; Jap.: Reumu emodi; Nep.: Padamchaal; Per.:
Rewand, Riwas, Tursak; Rus.: Reven emodi.
Description: The plant is native to China and western Himalayas of India. It has
large (Ta) leaves and a yellow color (Huang), hence named Ta-Huang in Chi-
nese.LXVI Commercial rhubarb known as “Turkish,” “Russian,” “Chinese,” and
“East Indian” is attributed to R. officinale and R. palmatum. Root of the Indian
variety is darker, not excoriated, coarser and untrimmed, and inferior in aroma than
the commercial Chinese variety; the powder is also dull brownish-yellow instead of
bright yellow.CV
Actions and Uses: In India, root of Rheum emodi is described as Revandchini or
rhubarb; a bitter stomachic in low doses and a purgative in high doses.LXXIX It is
reported to have been cultivated for over 5000 years by rural and tribal people of
Kashmir for its medicinal properties, and used for the treatment of cancer [10]. In
Unani medicine, GhaniL mentioned that the best revandchini (temperament, hot 2°
and dry 1°) is the one that is large, heavy, horseshoe-shaped, dark red, strongly
aromatic, and tastes astringent and bitter. It is purgative of all humours, and is
diuretic and emmenagogue. He writes that in cases of dysmenorrhea coupled with
irregular blood flow, finely ground revandchini with sugar (Misri) should be started
two days before the start of menses and continued for 3 or more days for complete
relief. The root is emmenagogue, and is used as a substitute for R. officinale [15].
KabeeruddinLXXVII says external application of rhubarb is detergent, irritant,
resolvent and analgesic; whereas internally, it is phlegm-expectorant, diuretic,
emmenagogue, and in small doses, gastric, intestinal and liver tonic. Ground in
vinegar, it is externally used as poultice for treatment of freckles, eczema, and
inflammations. Internally, it is used to relieve flatulence, and to treat stomach and
intestinal weakness, jaundice, ascites, inflammation of liver and spleen, cough,
asthma and bleeding; also used to relieve renal and urinary bladder pain.LXXVII In
Western medicine, rhubarb was mainly employed as a purgative, but not in con-
stipation or any affection in which a continuous aperient action was necessary.CV
Khory and KatrakLXXXI described it as aperient, and in small doses as gastric tonic
and intestinal astringent; and in large doses a cathartic, producing copious yellow
stools with gripping as an aftereffect. They also mention that it is eliminated by the
skin, kidneys and in milk, staining urine, sweat and milk. Rhubarb can cause
Rheum emodi Wall. ex Meisn 1523

purgation even if it is applied as a poultice to abraded skin or as a dusting powder

on ulcers. In The Herbal by Shen Nung, it is described as an inferior (toxic) drug,
used as a stomachic and purgative for internal heat, constipation, abdominal ache,
mania, edema, amenorrhea and jaundice.LXVI
Phytoconstituents: The plant mainly contains 1,8-dihydroxyanthraquinones, such
as rhein, aloe emodin, emodin, chrysophanol and physcion with diverse pharma-
cological and therapeutic effects [3]. Revandchinone-1–4 [4], a sulfated emodin
glucoside, emodin 8-O-b-D-glucopyranosyl-6-O-sulfate, two rare auronols, carpusin
and maesopsin [9], glucopyranosylchrysophanol, three anthrone C-glucosides, 10-
hydroxycascaroside C and D, and 10R-chrysaloin 1-O-b-D-glucopyranoside, cas-
caroside C, cascaroside D and cassialoin [8], emodin glycoside and chrysophanol
glycoside [16, 21] have been isolated from the rhizomes. Stilbenes are the major
constituents of unofficial rhubarb (R. emodi) in China [24]. Mineral elements
concentration in roots are reported to be in the order of K > Ca > Fe > Mn >
Na > Zn > Co > Li > Cu [17]. Major phenolic compounds in the roots responsible
for the antioxidant activity are eugenol, gallic acid, quercetin, rutin, epicatechin,
desoxyrhapontigenin, rhapontigenin and mesopsin [18].
Pharmacology: It is reported to possess protective effects in many inflammatory
diseases and oxidative stress-related injuries. Methanol rhizome extract contains
higher polyphenolic contents than the aqueous extract, and shows higher antioxi-
dant potential [12]. The most abundant stilbenoid, piceatannol-4′-O-b-D-glucopyr-
anoside and its aglycon, piceatannol possess significant antioxidant activity [5].
Water-soluble fraction of alcohol extract protects kidneys from cadmium chloride,
mercuric chloride, potassium dichromate and gentamicin-induced nephrotoxicity in
rats, possibly through antioxidant action of the tannins present in the fraction [2].
Various extracts of the rhizome also exhibit hepatoprotective effect against CCl4-
hepatotoxicity in rats [6]. Ethanol extract shows significant activity against triton-
WR-1339-induced dyslipidemia, whereas emodin significantly lowered lipids in
high-fat diet-fed rats [11]. Rhein, aloe emodin, emodin, chrysophanol and physcion
exhibit good antihyperglycemic activity with aloe emodin exhibiting the maximum
blood glucose lowering effect, but only emodin potently inhibited intestinal a-gluco-
sidase (AG) [3]. Methanol extract displays mild yeast and mammalian intestinal AG
inhibitory activity, and the active compounds, chrysophanol-8-O-b-D-glucopyrano-
side, desoxyrhaponticin and torachrysone-8-O-b-D-glucopyranoside exhibit potent to
moderate mammalian AG inhibitory activity [20]. Ethanol and benzene extracts
inhibit resistant clinical isolates of H pylori at very low concentrations [7], and rhein,
physcion, aloe-emodin and chrysophanol exhibit antifungal activity against C. albi-
cans, C. neoformans, T. mentagrophytes and A. fumigates [1]. Methanol and aqueous
extracts induce apoptosis in human breast carcinoma, hepatocellular carcinoma and
prostate cancer cell lines [13]. Cold and hot ethyl acetate rhizome extracts show
significant antioxidant activity and cancer-specific cytotoxicity towards human breast
cancer cells, and induce significant apoptosis in estrogen receptor (ER)-negative cells,
compared to ER-positive cells [10]. R. emodi is also reported to be anti-inflammatory/
antipyretic and adaptogenic.CXXXXVII
1524 Rheum emodi Wall. ex Meisn

Clinical Studies: In a single-blind, randomized trial, administration of R. emodi

powder twice daily, two days before the expected date of menstruation, and con-
tinued for the first three days of menstruation significantly decreased menstrual pain
of primary dysmenorrhea, comparable to mefenamic acid three times a day on the
same protocol [14].
Mechanism of Action: Anthraquinones and flavanols, such as rhein, emodin,
catechin, and epicatechin, act synergistically to produce therapeutic effect in renal
interstitial fibrosis, through regulation of abnormal accumulation of extracellular
matrix, controlling the release of inflammatory factors and maintaining balance of
coagulation and fibrinolysis [22].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Aqueous extract produced no significant changes in body weight,
food consumption, hematology, biochemistry, relative organ weight and histopatho-
logy of Sprague Dawley rats in acute and subchronic administration of oral doses of up
to 4,000 mg/kg for 90-days [23].
CYP450 and Potential for Drug-Herb Interactions: Emodin inhibits CYP1A1,
CYP1A2, and CYP2B1 [19], but studies about the effects of whole rhubarb on
CYP450s are lacking.
Commentary: Rhubarb is an important drug with dual spectrum of action in low
and high doses. Except one clinical study in dysmenorrhea that validated one of its
historical uses, no other studies have been conducted to explore other clinical uses.

References
1. Agarwal SK, Singh SS, Verma S, Kumar S. Antifungal activity of anthraquinone
derivatives from Rheum emodi. J Ethnopharmacol. 2000;72:43–6.
2. Alam MM, Javed K, Jafri MA. Effect of Rheum emodi (Revand Hindi) on
renal functions in rats. J Ethnopharmacol. 2005;96:121–5.
3. Arvindekar A, More T, Payghan PV, et al. Evaluation of antidiabetic and
alpha glucosidase inhibitory action of anthraquinones from Rheum emodi.
Food Funct. 2015;6:2693–700.
4. Babu KS, Srinivas PV, Praveen B, et al. Antimicrobial constituents from the
rhizomes of Rheum emodi. Phytochemistry. 2003;62:203–7.
5. Chai YY, Wang F, Li YL, et al. Antioxidant activities of stilbenoids from
Rheum emodi Wall. Evid Based Complement Alternat Med. 2012;2012:
603678.
6. Ibrahim M, Khaja MN, Aara A, et al. Hepatoprotective activity of Sapindus
mukorossi and Rheum emodi extracts: in vitro and in vivo studies. World J
Gastroenterol. 2008;14:2566–71.
Rheum emodi Wall. ex Meisn 1525

7. Ibrahim M, Khan AA, Tiwari SK, et al. Antimicrobial activity of Sapindus

mukorossi and Rheum emodi extracts against H. pylori: in vitro and in vivo
studies. World J Gastroenterol. 2006;12:7136–42.
8. Krenn L, Pradhan R, Presser A, et al. Anthrone C-glucosides from Rheum
emodi. Chem Pharm Bull (Tokyo). 2004;52:391–3.
9. Krenn L, Presser A, Pradhan R, et al. Sulfemodin 8-O-beta-D-glucoside, a
new sulfated anthraquinone glycoside, and antioxidant phenolic compounds
from Rheum emodi. J Nat Prod. 2003;66:1107–9.
10. Kumar DR, George VC, Suresh PK, Kumar RA. Cancer-specific chemo-
prevention and antimetastatic potentials of Rheum emodi rhizome ethyl
acetate extracts and identification of active principles through HPLC and
GC-MS analysis. Pak J Pharm Sci. 2015;28:83–93.
11. Mishra SK, Tiwari S, Shrivastava A, et al. Antidyslipidemic effect and antiox-
idant activity of anthraquinone derivatives from Rheum emodi rhizomes in
dyslipidemic rats. J Nat Med. 2014;68:363–71.
12. Rajkumar V, Guha G, Ashok Kumar R. Antioxidant and anticancer
potentials of Rheum emodi rhizome extracts. Evid Based Complement
Alternat Med. 2011;2011:697986.
13. Rajkumar V, Guha G, Kumar RA. Apoptosis induction in MDA-MB-435S,
Hep3B and PC-3 cell lines by Rheum emodi rhizome extracts. Asian Pac J
Cancer Prev. 2011;12:1197–200.
14. Rehman H, Begum W, Anjum F, Tabasum H, Zahid S. Effect of rhubarb
(Rheum emodi) in primary dysmenorrhoea: a single-blind randomized
controlled trial. J Complement Integr Med. 2015;12:61–9.
15. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
16. Singh NP, Gupta AP, Sinha AK, Ahuja PS. High-performance thin layer
chromatography method for quantitative determination of four major anthra-
quinone derivatives in Rheum emodi. J Chromatogr A. 2005;1077:202–6.
17. Singh P, Negi JS, Rawat MS, Nee Pant GJ. Quantification of mineral
elements of Rheum emodi Wall. (Polygonaceae). Biol Trace Elem Res.
2010;138:293–9.
18. Singh PP. Ambika, Chauhan SM. Activity-guided isolation of antioxidants
from the roots of Rheum emodi. Nat Prod Res. 2013;27:946–9.
19. Sridhar J, Liu J, Foroozesh M, Klein Stevens CL. Inhibition of cytochrome
p450 enzymes by quinones and anthraquinones. Chem Res Toxicol. 2012;25:
357–65.
20. Suresh Babu K, Tiwari AK, Srinivas PV, et al. Yeast and mammalian alpha-
glucosidase inhibitory constituents from Himalayan rhubarb Rheum emodi
Wall. ex Meisson. Bioorg Med Chem Lett. 2004;14:3841–5.
21. Verma SC, Singh NP, Sinha AK. Determination and locational variations in the
quantity of hydroxyanthraquinones and their glycosides in rhizomes of Rheum
emodi using high-performance liquid chromatography. J Chromatogr A. 2005;
1097:59–65.
1526 Rheum emodi Wall. ex Meisn

22. Xiang Z, Sun H, Cai X, Chen D, Zheng X. The study on the material basis
and the mechanism for antirenal interstitial fibrosis efficacy of rhubarb
through integration of metabonomics and network pharmacology. Mol
BioSyst. 2015;11:1067–78.
23. Ye BG, Feng Y, Wang S. Scientific evaluation of the acute toxicity and
13-week subchronic toxicity of Rheum emodi rhizome extracts in Sprague
Dawley rats. Food Chem Toxicol. 2014;66:278–85.
24. Ye M, Han J, Chen H, et al. Analysis of phenolic compounds in rhubarbs
using liquid chromatography coupled with electrospray ionization mass
spectrometry. J Am Soc Mass Spectrom. 2007;18:82–91.
Rheum officinale Baill.; R. palmatum L.
(Polygonaceae)

Abstract
A perennial suffruticose herb from western China and Tibet. Rha is derived from
the Indo-European protolanguage sreu, which means river or to flow. Rha
barbarum was transformed to rhubarb in English and to Rhabarber in German.
Medicinal rhubarbs come from R. palmatum (the shape of its leaves palm-shaped),
R. tanguticum from Tangut (China), and R. officinale and R. coreanum. Chinese
rhubarb is described as the best (hence the Indian name), which is of a saffron
color, tastes bitter and astringent, gritty when chewed, has a fractured surface and
is friable. Chinese were acquainted with this herb long before all modern
civilizations, as it is mentioned in the Chinese Herbal called Pen-king, which is
attributed to the Emperor Shen Nung, the father of Chinese agriculture and
medicine, who reigned about 2700 B.C. In China the root and rhizomes of
R. palmatum, R. tanguticum, or R. officinale, are the official rhubarb and all are
known as Dahuangand, and are described to have cold property and a bitter taste.
Dioscorides mentioned that it was brought from beyond the Bosphorus, and Pliny
described a root termed Rhacoma, which when pounded yielded a color like that
of wine, but inclining to saffron, and was brought from beyond Pontus. Various
authors have described three kinds of rhubarb; Chinese, Persian and Indian; the
Chinese being the best. It is purgative of all humours, and is diuretic and
emmenagogue. Ground in vinegar, it is externally used as poultice for treatment of
freckles, eczema, and inflammations. Internally, it is used to relieve flatulence,
and to treat stomach and intestinal weakness, jaundice, ascites, inflammation of
liver and spleen, cough, asthma and bleeding; also used to relieve renal and
urinary bladder pain. R. officinale is approved for constipation in Europe
since Nov. 2005 by the HMPC of the European Medicines Agency. Chemical

Rheum officinale and R. palmatum are two separate species but used interchangeably; they share
Indian vernaculars with R. emodi.

© Springer Nature Switzerland AG 2020 1527

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_158
1528 Rheum officinale Baill.; R. palmatum L.

constituents of rhubarb include many 1,8-dihydroxyanthracene derivatives

including chrysophanol, emodin, rhein, erythroeretin, rhabarberon; also, rheotan-
nic acid, methylchrysophanic acid, catechin, gallic acid, and calcium oxalate.
A Cochrane Database Systemic review of clinical trials found R. officinale
treatment of patients with CKD to have a positive effect on serum creatinine and
BUN, compared to those with no treatment.

Keywords




Amlavetasa Chinese rhubarb Da huang Læge-rabarber Revandchini







Rewand makhzani Rhabarber Rubaabu Ruibarbo de la china Turkse rabarber

Vernacular: Urd.: Revandchini; Hin.: Revandchini; San.: Amlaparni, Amlavetasa,

Revatchini; Ben.: Bangla Revanchini, Rheuchini; Mar.: Reval-chinni; Tam.:
Nattu-manjat-chinak; Tel.: Nattu, Reval-chinni; Ara.: Rewand makhzani; Chi.:
大黄, Da huang, Huang-hang, Ta-huang, Yào yòng dà huáng; Cze.: Reveň lékařská;
Dan.: Læge-rabarber; Dut.: Turkse rabarber; Eng.: Chinese rhubarb, Rhubarb; Fre.:
Rhubarbe médicinale; Ger.: Chinesischer rhabarber, Gebräuchlicher Kanton-
rhabarber, Rhabarber, Südchinesischer rhabarber; Gre.: Rion to farmakeftiko;
Hun.: Orvosi rebarbara; Jap.: Rubaabu, Rubarubu; Per.: Rewand, Riwas; Pol.:
Rabarbar lekarski, Rzewień lekarski; Por.: Ruibarbo, Ruibarbo-da-China; Rus.:
Reven aptečnyj, Reven kitajskij, Reven moskovskij; Spa.: Ruibarbo de la China.
Description: A perennial suffruticose herb from western China and Tibet, stems
1–2.5 m high; leaves alternate, petiolate, oval, orbiculate, 30–90 cm in diameter,
lobes 3–7, palmately veined, irregularly incised. Floral stalks 1.5 m high, thick,
erect, pubescent. Inflorescence a dense, spiciform cluster; flowers greenish. Rhi-
zomes are used medicinally, which are available as long, transverse or oblique
pieces of the peeled roots, texture fibrous and resinous, yellowish to reddish-brown
in color, surface smooth and longitudinally wrinkled. The taste is bitter and
astringent, and the odor aromatic.LXXIX According to Uchibayashi [33], Rha is
derived from the Indo-European protolanguage sreu, which means river or to flow.
Rha barbarum was transformed to rhubarb in English and to Rhabarber in German.
Medicinal rhubarbs come from R. palmatum (the shape of its leaves palm-shaped),
R. tanguticum from Tangut (China), and R. officinale and R. coreanum. The plant
has large (Ta) leaves and a yellow color (Huang), hence named Ta-Huang in
Chinese.LXVI Chinese rhubarb is described as the best (hence the Hindi name),
which is of a saffron color, tastes bitter and astringent, gritty when chewed, has a
fractured surface and is friable (Figs. 1 and 2).LXXXI
Actions and Uses: Chinese were acquainted with this herb long before all modern
civilizations, as it is mentioned in the Chinese Herbal called Pen-king, which is
attributed to the Emperor Shen Nung, the father of Chinese agriculture and medi-
cine, who reigned about 2700 B.C. A review of the original research reports pub-
lished in Chinese medical journals over a 10-years period from 2000 to 2009
revealed that R. officinalis was a constituent of 7 out of 87 (8%) reports [3].
Rheum officinale Baill.; R. palmatum L. 1529

Fig. 1 Rheum officinale, Plant, Kurt Stüber, WikimediaCommons; ShareAlike 3.0 Unported CC
BY-SA-3.0, https://commons.wikimedia.org/wiki/File:Rheum_officinale1.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

Dioscorides mentioned that it was brought from beyond the Bosphorus, and Pliny
described a root termed Rhacoma, which when pounded yielded a color like that of
wine, but inclining to saffron, and was brought from beyond Pontus. Various
authors have described three kinds of rhubarb; Chinese, Persian and Indian; the
Chinese being the best. The plant of Persian rhubarb grows in the cold snowy
mountains, and the root of this plant is rhubarb, which is called Ribas-i-Mu’ammiri
in Persian, because one Mu’ammir was the first to discover this plant.XL In India,
root of Rheum emodi is described as Revandchini or rhubarb; a bitter stomachic in
low doses and a purgative in high doses.LXXIX In Unani medicine, rhizomes derived
from both R. emodi and R. officinalis are known as Revandchini. GhaniL mentioned
that the best revandchini (temperament, hot 2° and dry 1°) is the one that is large,
heavy, horse shoe-shaped, dark red, strongly aromatic, and tastes astringent and
bitter. It is purgative of all humours, and is diuretic and emmenagogue. Ground in
vinegar, it is externally used as poultice for treatment of freckles, eczema, and
inflammations. Internally, it is used to relieve flatulence, and to treat stomach and
intestinal weakness, jaundice, ascites, inflammation of liver and spleen, cough,
asthma and bleeding; also used to relieve renal and urinary bladder pain.LXXVII
Dried rhizomes and roots are antidiarrheal in small doses and purgative in large
doses.XXIV,CXI,CXVIII,CXXXII,CXXXXI,CLIV R. officinale is approved for constipation in
Europe since Nov. 2005 by the HMPC of the European Medicines Agency.
In China the root and rhizomes of R. palmatum, R. tanguticum, or R. officinale, are
1530 Rheum officinale Baill.; R. palmatum L.

Fig. 2 Rheum palmatum, Plant with Flowers, Nancy, WikimediaCommons; 2.0 Generic CC BY
2.0, https://commons.wikimedia.org/wiki/File:Rhubarb_Flower.jpg; https://creativecommons.org/
licenses/by/2.0/deed.en

the official rhubarb and all are known as Dahuangand, and are described to have
cold property and a bitter taste. Unofficial rhubarb species are R. franzenbachii,
R. hotaoense, and R. emodi [44]. Dahuangand is sthenic-heat-purgative, laxative,
stasis-deobstruent, anti-inflammatory and detoxicant, and used for constipation due
to sthenic heat, abdominal pain due to indigestion, jaundice due to damp heat,
amenorrhea due to blood stasis, in carbuncles, fruncles, scalds and burns.XVIII
Rhubarb is widely used as antipyretic and anti-inflammatory agent [14], for wound
healing [31], for the treatment of neonatal jaundice in TCM [8, 13], and to treat
chronic renal failure in China and Japan [37]. In The Herbal by Shen Nung, it is
described as an inferior (toxic) drug, used as a stomachic and purgative for internal
heat, constipation, abdominal ache, mania, edema, amenorrhea and jaundice.LXVI
Cooked and wine processed raw rhizomes of R. officinale are one of the
processed rhubarbs clinically used in TCM to prepare antidiabetic formulas and
remove pathogenic heat or toxin from the body [10]. Emodin possesses a wide
spectrum of pharmacological properties, including anticancer, hepatoprotective,
anti-inflammatory, antioxidant and antimicrobial activities, but it could also cause
hepatotoxicity, nephrotoxicity and reproductive toxicity, particularly in high doses
and with long-term use [5]. Emodin use as a nutritional supplement has been
identified as beneficial for the treatment and/or prevention of type-2 diabetes [17].
Rheum officinale Baill.; R. palmatum L. 1531

Phytoconstituents: Chemical constituents of rhubarb include many 1,8-

dihydroxyanthracene derivatives including chrysophanol, emodin, rhein, ery-
throeretin, rhabarberon; also, rheotannic acid, methylchrysophanic acid, catechin,
gallic acid, and calcium oxalate.CXXXII,CXXXXI It contains large amounts of anthra-
quinones as the active compounds, 3.4 mg of emodin, 2.1 mg of chrysophanol and
1.8 mg of rhein in 10 g of dry matter [28]. Anthraquinones, mainly emodin,
chrysophanol, rhein and physcion and phenolic acids, are more abundant in branch
root than in tap roots [9]. Rhein is reportedly the main anthraquinone derivative
absorbable into systemic circulation after oral administration in rats [37]. Chro-
matographic fingerprints of rhubarb samples from different producing areas in China
are dissimilar; generally, the rhubarb samples produced in Famous-region contained
more anthraquinones, providing chemical rationality on the traditional use of rhubarb
from the Famous region. Rhubarb is categorized into two types, chrysophanol-type
and rhein-type, based on the proportion of the two constituents in the total anthra-
quinones after acid hydrohysis. Rhubarb samples of rhein-type are mostly produced
in Famous-regions of China, such as Qinghai, Xizang, West Sichuan and Gansu.
The rhein type is superior to chrysophanol type in many pharmacological effects and
pharmacokinetic properties, and is considered of high-quality [36]. Sennosides, rhein,
anthraquinones, stilbenes, naphthalenes, glucose gallates, and catechins were iden-
tified in official rhubarbs. Sennoside A, considered to be the major purgative com-
ponent of rhubarb was found only in R. officinale. Sennoside A is transformed into an
active metabolite, rheinanthrone by intestinal bacteria, and Sennoside A in rhubarb
shows significantly accelerated metabolic activity when rhein 8-O-b-D-glucopyr-
anoside or rhein was concomitantly given with sennoside A than sennoside A
administered alone [30]. Predominant anthraquinone glycosides in R. officinale are
rhein 8-O-glucoside and emodin 1-O-glucoside, whereas rhein 1-O-glucoside and
emodin 8-O-glucoside are the major anthraquinone glycosides of R. palmatum and
R. tanguticum [44]. All anthranoids are present in oxidized form in summer months,
i.e. the anthraquinone, and in the reduced form, the anthrone in winter months.
Mean total anthranoid content in freeze-dried plant material were found to be 3.17%
[34]. Eight out of the ten nonanthraquinones isolated from rhizomes were identified as
rheosmine, daucosterol, d-catechin, 6-cinnamoylisolindleyin, resveratrol-4′-O-b-D-
(6″-O-galloyl)-glucopyranoside, (-)-epicatechin-3-O-gallate, gallic acid, and D-
sorbitol [19]. Tannins and gallic acid are the predominant antioxidant phenolic
constituents in roots [2]. Aloe-emodin-O-glucosides, emodin-O-glucosides, chryso-
phanol-O-glucosides, physcion-O-glucosides, rhein and the corresponding aglycones
are biotransformed by rat intestinal bacteria [27].
Pharmacology: Pharmacological studies conducted on rhubarb in China did use
root and rhizomes of R. palmatum, R. tanguticum, or R. officinale, as they are all
known as Dahuangand. Total anthraquinones extract obviously showed stronger
purgative activity than the ethanol extract, whereas total tannins extract produced
antidiarrheal activity in mice, confirming the bidirectional activities of rhubarb [24].
Rhubarb treatment is reportedly beneficial in diabetic nephropathy [42], and chronic
renal failure in rats [37, 51], and rhein is a potent inhibitor of renal interstitial
fibrosis [12]. In a comparative study of rhein and simvastatin in mice with diabetic
1532 Rheum officinale Baill.; R. palmatum L.

nephropathy, rhein reduced urinary albumin excretion after 8-weeks, whereas

simvastatin reduced after 12-weeks of treatment. However, both equally reduced
TC, TGs, LDL-C and ApoE levels [11]. Very high (unlikely) dose (40 g/kg) of
rhubarb exhibited a significant protective effect on CCl4-hepatotoxicity in rats, but
this hepatoprotective effect turns into toxicity with further increase in dose and
frequency [40]. Moderate twice daily dosing of rhubarb was more beneficial in
experimental jaundice in rats than high dose once daily or a lower dose thrice daily
[21]. Free rhubarb anthraquinone derivatives distribution in normal animals is
higher than in pathological models of liver injury, with little cumulative toxicity of
rhubarb [6]. Rhein is beneficial and preventive of experimental fatty [26], and
cholestatic liver injury in animals [52]. Emodin significantly decreases intracellular
accumulation of triglycerides in adipocytes through AMPK activation, and reduces
body weight gain and plasma lipid levels of high-fat diet-fed rats [32]. However,
another study reported that rhein, but not emodin, reduced fat weight, lowered
serum TC, LDL-C, and FBG levels in diet-induced obesity, and inhibited PPARc
transactivity and expression of its target genes [50].
Rhubarb possesses significant antibacterial activity against B. fragilis, a major
anaerobic microorganism of human intestinal flora; rhein was identified as the
active substance [4]. Hot glycerin and ethanol rhubarb extracts inactivate HSV-1
[14, 29, 38] and aloe emodin also inactivated HSV-1 and HSV-2, VZV, Pseu-
dorabies virus, and Influenza virus [29]. Although antimicrobial activity of rhein-
type rhubarb against S. aureus was stronger than that of chrysophanol-type rhubarb,
it was not positively correlated to the contents of rhein [49]. Emodin and rhein show
synergistic effect with ampicillin and oxacillin against strains of MRSA [16, 18].
Chrysophanol-8-O-glucoside shows most potent inhibitory effect on collagen- and
thrombin-induced platelet aggregation, and significantly prolongs bleeding time in
treated mice [25], whereas rhein protects endothelial cells against H2O2-oxidative
injury [53]. R. officinale shows significant antioxidant activity that correlates with
the presence of total phenolics and flavonoid contents [48]. A combination of
R. officinale and Astragalus membranaceus is one of the eight traditional Chinese
herbal pairs that shows significantly larger scavenging capacity than would be
expected from the theoretical sum of respective constituent herbs [43]. Acetone
rhizomes extract possesses strong tyrosinase inhibitory activity. Two compounds
identified as 3,4′,5-trihydroxystilbene-4′-O-b-D-(2″-O-galloyl) glucopyranoside
and 3,4′,5-trihydroxystilbene-4′-O-b-D-(6″-O-galloyl) glucopyranoside, also com-
petitively inhibited tyrosinase and melanin biosynthesis [15]. Emodin significantly
improves healing and markedly increases tissue regeneration and hydroxyproline
content of experimental wounds in rats [31]. R. officinale also shows tendency to
prevent pathological changes in experimental acute necrotizing pancreatitis [41],
probably by inhibiting activation of MAPKs and expression of inflammatory
mediators [7].
Clinical Studies: A Cochrane Database Systemic review of clinical trials found
R. officinale treatment of patients with CKD to have a positive effect on serum
creatinine and BUN, compared to those with no treatment [35]. A total of 968
participants with acute ischemic stroke, included in 12 RCTs, had significant
Rheum officinale Baill.; R. palmatum L. 1533

improvement in clinical efficacy rate when treated with rhubarb root or

rhizome-based Chinese prescriptions [20]. Patients with severe burns, treated with
10 g rhubarb by nasal feeding, had their bowel sound restored within 24 h and
better tolerated enteral nutrition, the number of patients with abdominal distension
decreased, and had earlier and more bowel movements with soft feces, compared to
control group patients [22]. Treatment of gastric and duodenal ulcer patients with
alcoholic extract tablets of rhubarb showed more than 90% effective rate, and the
stool occult blood test became negative within 57 h [54]. A meta-analysis of
clinical trial shows that adjuvant treatment with crude rhubarb in patients with
systemic inflammation reaction syndrome/sepsis produces additional benefits
to standard treatment, due probably to its anti-inflammation and anticoagulant/
antiaggregant properties [47].
Mechanism of Action: Anthraquinones and flavanols, such as rhein, emodin,
catechin, and epicatechin, are the main active components of rhubarb, that act
synergistically to produce therapeutic effect in renal interstitial fibrosis, through
regulation of abnormal accumulation of extracellular matrix, controlling release of
inflammatory factors and maintaining the balance of coagulation and fibrinolysis
[39]. Rhubarb protects intestinal mucosal barrier through increasing secretion of
gastrointestinal hormones and by restoring gastrointestinal motility [22].
Human A/Es, Allergy and Toxicity: Acute secondary oxalate nephropathy
occurred in a patient with type-1 diabetes due to excessive ingestion of rhubarb [1].
Animal Toxicity: Administration of rhubarb to normal rats for 3-weeks, caused no
death and no nephrotoxicity but minor hepatotoxicity [37]. Mice orally adminis-
tered emodin (50 mg/kg daily) for 5-days caused testicular toxicity, including
hypospermatogenesis, eosinophilic change and apoptosis of germ cell [23].
CYP450 and Potential for Drug-Herb Interactions: Rhei Rhizoma extract sig-
nificantly suppressed CYP3A-mediated 6b-hydroxylation of testosterone in hepatic
microsomes, and may cause pharmacokinetic herb-drug interactions as it is used
orally at 0.5–1 g dose or 1–3 g daily doses in Japanese and Chinese clinical practice
[45]. Methanol extract showed highly significant in vitro CYP1A1 inhibitory
activity [28]. Cooked rhubarb induces CYP3A1 activity, while wine processed
rhubarb induces CYP1A2 activity, and both processed rhubarbs inhibit CYP2C6
activity and induce CYP2E1 activity and reduce absorption and bioavailability, and
increase clearance of saxagliptin, an oral antidiabetic drug [10]. R. palmatum
ingestion is also reported to reduce systemic bioavailability of cyclosporin through
activation of p-glycoprotein and CYP3A in rats [46].
Commentary: Clinical trials have shown its effectiveness in renal insufficiency or
chronic kidney disease, duodenal ulcers, restoring intestinal motility in burn
patients, and systemic inflammation reaction syndrome. However, these benefits
need to be validated with more extensive blinded RCTs, and more exploratory
clinical uses. Its effects on CYP450 isozymes under various conditions of use and
other potential interactions also require further scrutiny.
1534 Rheum officinale Baill.; R. palmatum L.

References
1. Albersmeyer M, Hilge R, Schröttle A, et al. Acute kidney injury after
ingestion of rhubarb: secondary oxalate nephropathy in a patient with type 1
diabetes. BMC Nephrol. 2012;13:141.
2. Cai Y, Sun M, Xing J, Corke H. Antioxidant phenolic constituents in roots of
Rheum officinale and Rubia cordifolia: structure-radical scavenging activity
relationships. J Agric Food Chem. 2004;52:7884–90.
3. Collins RA. A ten-year audit of traditional Chinese medicine and other
natural product research published in the Chinese Medical Journal (2000–
2009). Chin Med J (England). 2011;124:1401–8.
4. Cyong J, Matsumoto T, Arakawa K, et al. Anti-Bacteroides fragilis
substance from rhubarb. J Ethnopharmacol. 1987;19:279–83.
5. Dong X, Fu J, Yin X, et al. Emodin: a review of its pharmacology, toxicity
and pharmacokinetics. Phytother Res. 2016;30:1207–18.
6. Fang F, Wang JB, Zhao YL, et al. A comparative study on the tissue
distributions of rhubarb anthraquinones in normal and CCl4-injured rats
orally administered rhubarb extract. J Ethnopharmacol. 2011;137:1492–7.
7. Feng Z, Fei J, Wenjian X, et al. Rhubarb attenuates the severity of acute
necrotizing pancreatitis by inhibiting MAPKs in rats. Immunotherapy.
2012;4:1817–21.
8. Fok TF. Neonatal jaundice—traditional Chinese medicine approach. J Peri-
natol. 2001;21 Suppl 1: S98–S100; discussion S104–7.
9. Fu SZ, Wang TT, Gao WY, Li X. Comparision of contents of anthraquinones
and phenolic acids compounds in different processed products from Rheum
officinale by principal component analysis. Zhongguo Zhong Yao Za Zhi.
2014;39:833–7 (Chinese).
10. Gao J, Shi Z, Zhu S, et al. Influences of processed rhubarbs on the activities
of four CYP isozymes and the metabolism of saxagliptin in rats based on
probe cocktail and pharmacokinetics approaches. J Ethnopharmacol. 2013;
145:566–72.
11. Gao Q, Qin WS, Jia ZH, et al. Rhein improves renal lesion and ameliorates
dyslipidemia in db/db mice with diabetic nephropathy. Planta Med. 2010;
76:27–33.
12. He D, Lee L, Yang J, Wang X. Preventive effects and mechanisms of rhein
on renal interstitial fibrosis in obstructive nephropathy. Biol Pharm Bull.
2011;34:1219–26.
13. Ho NK. Traditional Chinese medicine and treatment of neonatal jaundice.
Singapore Med J. 1996;37:645–51 (Review).
14. Hsiang CY, Hsieh CL, Wu SL, et al. Inhibitory effect of antipyretic and
anti-inflammatory herbs on herpes simplex virus replication. Am J Chin
Med. 2001;29:459–67.
15. Iida K, Hase K, Shimomura K, et al. Potent inhibitors of tyrosinase activity
and melanin biosynthesis from Rheum officinale. Planta Med. 1995;61:425–8.
Rheum officinale Baill.; R. palmatum L. 1535

16. Joung DK, Joung H, Yang DW, et al. Synergistic effect of rhein in combi-
nation with ampicillin or oxacillin against methicillin-resistant Staphylo-
coccus aureus. Exp Ther Med. 2012;3:608–12.
17. Lee T, Dugoua JJ. Nutritional supplements and their effect on glucose
control. Curr Diab Rep. 2011;11:142–8.
18. Lee YS, Kang OH, Choi JG, et al. Synergistic effect of emodin in combi-
nation with ampicillin or oxacillin against methicillin-resistant Staphylo-
coccus aureus. Pharm Biol. 2010;48:1285–90.
19. Li JL, Wang AQ, Wu ZZ. Studies on nonanthraquinones in Rheum
officinale Baill. Zhongguo Zhong Yao Za Zhi. 2000;25:612–4 (Chinese).
20. Lu L, Li HQ, Fu DL, Zheng GQ, Fan JP. Rhubarb root and rhizome-based
Chinese herbal prescriptions for acute ischemic stroke: a systematic review
and meta-analysis. Complement Ther Med. 2014;22:1060–70.
21. Lv J, Fu S, Guo J, et al. Primary research on daily administration times of
rhubarb used to treat experimental jaundice in rats. Zhongguo Zhong Yao
Za Zhi. 2011;36:3506–10 (Article in Chinese).
22. Meng YB, Lei J, Hao ZM, Cao RL. Influence of rhubarb on gastrointestinal
motility and intestinal mucosal barrier in patients with severe burn.
Zhonghua Shao Shang Za Zhi. 2011;27:337–40 (Chinese).
23. Oshida K, Hirakata M, Maeda A, et al. Toxicological effect of emodin in
mouse testicular gene expression profile. J Appl Toxicol. 2011;31:790–800.
24. Qin Y, Wang JB, Kong WJ, et al. The diarrhoeogenic and antidiarrhoeal
bidirectional effects of rhubarb and its potential mechanism. J Ethnophar-
macol. 2011;133:1096–102.
25. Seo EJ, Ngoc TM, Lee SM, et al. Chrysophanol-8-O-glucoside, an
anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant
activities. J Pharmacol Sci. 2012;118:245–54.
26. Sheng X, Wang M, Lu M, et al. Rhein ameliorates fatty liver disease through
negative energy balance, hepatic lipogenic regulation, and immunomodu-
lation in diet-induced obese mice. Am J Physiol Endocrinol Metab. 2011;
300:E886–93.
27. Song R, Xu L, Xu F, et al. Metabolic analysis of rhubarb extract by rat
intestinal bacteria using liquid chromatography-tandem mass spectrometry.
Biomed Chromatogr. 2011;25:417–26.
28. Sun M, Sakakibara H, Ashida H, et al. Cytochrome P4501A1-inhibitory
action of antimutagenic anthraquinones in medicinal plants and the structure-
activity relationship. Biosci Biotechnol Biochem. 2000;64:1373–8.
29. Sydiskis RJ, Owen DG, Lohr JL, et al. Inactivation of enveloped viruses by
anthraquinones extracted from plants. Antimicrob Agents Chemother.
1991;35:2463–6.
30. Takayama K, Tsutsumi H, Ishizu T, Okamura N. The influence of rhein
8-O-b-D-glucopyranoside on the purgative action of sennoside A from
rhubarb in mice. Biol Pharm Bull. 2012;35:2204–8.
1536 Rheum officinale Baill.; R. palmatum L.

31. Tang T, Yin L, Yang J, Shan G. Emodin, an anthraquinone derivative from

Rheum officinale Baill., enhances cutaneous wound healing in rats. Eur J
Pharmacol. 2007;567:177–85.
32. Tzeng TF, Lu HJ, Liou SS, et al. Emodin protects against high-fat diet-
induced obesity via regulation of AMP-activated protein kinase pathways in
white adipose tissue. Planta Med. 2012;78:943–50.
33. Uchibayashi M. Rhubarb in the East and the West. Yakushigaku Zasshi.
2001;36:171–4 (Japanese).
34. Verhaeren EH, Dreessen M, Lemli J. Studies in the field of drugs containing
anthracene derivatives. Planta Med. 1982;45:15–9.
35. Wang H, Song H, Yue J, et al. Rheum officinale (a traditional Chinese
medicine) for chronic kidney disease. Cochrane Database Syst Rev. 2012;7:
CD008000.
36. Wang J, Zhang X, Xiao X, et al. Rationality of commercial specification of
rhubarb based on chemical analysis. Zhongguo Zhong Yao Za Zhi. 2010;
35:470–6 (Chinese).
37. Wang J, Zhao Y, Xiao X, et al. Assessment of the renal protection and
hepatotoxicity of rhubarb extract in rats. J Ethnopharmacol. 2009;124:18–25.
38. Wang Z, Wang G, Xu H, Wang P. Antiherpes virus action of ethanol-extract
from the root and rhizome of Rheum officinale Baill. Zhongguo Zhong Yao
Za Zhi. 1996;21:364–6, 384 (Chinese).
39. Xiang Z, Sun H, Cai X, Chen D, Zheng X. The study on the material basis
and the mechanism for antirenal interstitial fibrosis efficacy of rhubarb
through integration of metabonomics and network pharmacology. Mol
BioSyst. 2015;11:1067–78.
40. Xing XY, Zhao YL, Kong WJ, et al. Investigation of the “dose-time-
response” relationships of rhubarb on carbon tetrachloride-induced liver
injury in rats. J Ethnopharmacol. 2011;135:575–81.
41. Yang CY, Shen L, Xie ZG, et al. Experimental studies of therapeutic effect
of Rheum officinale on acute pancreatitis. Zhong Yao Cai. 2011;34:84–8
(Chinese).
42. Yang JW, Li LS. Effects of Rheum on renal hypertrophy and hyperfiltration
of experimental diabetes in rat. Zhongguo Zhong Xi Yi Jie He Za Zhi.
1993;13:286–8, 261–2 (Chinese).
43. Yang WJ, Li DP, Li JK, et al. Synergistic antioxidant activities of eight
traditional Chinese herb pairs. Biol Pharm Bull. 2009;32:1021–6.
44. Ye M, Han J, Chen H, et al. Analysis of phenolic compounds in rhubarbs
using liquid chromatography coupled with electrospray ionization mass
spectrometry. J Am Soc Mass Spectrom. 2007;18:82–91.
45. Yokooji T, Kida M, Mori M, et al. Interaction of Rhei Rhizoma extract with
cytochrome P450 3A and efflux transporters in rats. Pharmazie. 2010;65:
367–74.
46. Yu CP, Lin HJ, Lin SP, et al. Rhubarb decreased the systemic exposure of
cyclosporine, a probe substrate of P-glycoprotein and CYP3A. Xenobiotica.
2016;46:677–82.
Rheum officinale Baill.; R. palmatum L. 1537

47. Zhang L, Chen J, Jiang D, Zhang P. Adjuvant treatment with crude rhubarb
for patients with systemic inflammation reaction syndrome/sepsis: a
meta-analysis of randomized controlled trials. J Crit Care. 2015;30:282–9.
48. Zhang L, Ravipati AS, Koyyalamudi SR, et al. Antioxidant and anti-inflam-
matory activities of selected medicinal plants containing phenolic and
flavonoid compounds. J Agric Food Chem. 2011;59:12361–7.
49. Zhang XR, Wang JB, Xiao XH, et al. Antimicrobial activity and chemical
differences between the two chemotypes of rhubarbs. Yao Xue Xue Bao.
2010;45:1144–8 (Chinese).
50. Zhang Y, Fan S, Hu N, et al. Rhein reduces fat weight in db/db mouse and
prevents diet-induced obesity in C57Bl/6 mouse through the inhibition of
PPARc signaling. PPAR Res. 2012;2012:374936.
51. Zhang ZH, Vaziri ND, Wei F, et al. An integrated lipidomics and
metabolomics reveal nephroprotective effect and biochemical mechanism of
Rheum officinale in chronic renal failure. Sci Rep. 2016;6:22151.
52. Zhao YL, Wang JB, Zhou GD, et al. Investigations of free anthraquinones
from rhubarb against alpha-Naphthylisothiocyanate-induced cholestatic
liver injury in rats. Basic Clin Pharmacol Toxicol. 2009;104:463–9.
53. Zhong XF, Huang GD, Luo T, et al. Protective effect of rhein against oxidative
stress-related endothelial cell injury. Mol Med Rep. 2012;5:1261–6.
54. Zhou H, Jiao D. 312 cases of gastric and duodenal ulcer bleeding treated
with 3 kinds of alcoholic extract rhubarb tablets. Zhong Xi Yi Jie He Za Zhi.
1990;10:150–1, 131–2 (Chinese).
Ricinus communis L.
(Euphorbiaceae)

Abstract
This perennial bush or shrub is indigenous to India, East Africa, southeastern
Mediterranean Basin and other tropical regions. Hindu physicians used this plant
medicinally from an early period, and the Arab and Persian physicians learnt
about it through them. Muslim physicians described two varieties of the plant,
red and white; the red is said to be most active. Both the root and oil are
described as purgative and useful in costiveness, flatulence, rheumatism, fever
and inflammatory affections. Seeds freed from husks and germs, and boiled in
milk and water form a decoction which is used in rheumatism; most compound
medicines used in rheumatic and neuralgic affections contain the root. Leaves are
applied to breasts to stop secretion of milk, and boiled with the root in goat’s
milk are used as local application in ophthalmia. The oil is considered resolvent
and purgative of cold humours, and is prescribed in palsy, asthma, colds, colic,
flatulence, rheumatism, dropsy and amenorrhea. A poultice of crushed seeds is
used to reduce gouty and rheumatic swellings, and inflammation of breasts of
women during lactation. Externally, seeds are beneficial in paralysis and colic,
and resolve all forms of hard inflammations; leaves application with or without
any oil is very beneficial in gouty or arthritic inflammations. In Hawaii, leaves
are put around the head in case of a child with high fever; leaves draw heat from
the body and cause sweating to lower body temperature. Zulus also apply a paste
of the root for toothache, apply leaves to head for headache and as poultice for
boils, the rootbark as purgative and for skin diseases and burns, and an infusion
of leaves for stomachache. In South Africa, it has been utilized to treat
inflammatory diseases including wounds, sores, and boils, and for the treatment
of sores in the Bapedi culture of Limpopo Province. Leaf extract shows presence
of alkaloids, coumarins, flavonoids, and phenols; predominant alkaloid is
ricinine. The phytotoxin, ricin, is a very toxic protein, and is very effective
against transplantable animal tumors, such as mouse EAC, ascitic hepatoma,
cervical cancer, sarcoma and leukemia.

© Springer Nature Switzerland AG 2020 1539

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_159
1540 Ricinus communis L.

Keywords







Arandi Bafureira Baid anjeer Bì má shǔ Castor Eranda Fico d’inferno




Hintyağı Rizinus Simsim-el-hindi

Vernaculars: Urd.: Arand, Baid anjeer; Hin.: Arandi; San.: Eranda, Gandharva
hasthah, Panchangulam, Ruvu, Ruvuka, Uruvuka; Ben.: Bherenda, Sadabherenda,
Verenda; Guj.: Divelli, Divelligo, Tirki; Mal.: Avanakku, Chittamanakku, Eran-
dam; Mar.: Erandi; Tam.: Aamanakku, Amanakkam-chedi, Chittmani, Vilakken-
nai; Tel.: Amidamu, Amudapu-chettu, Chittamin drak, Eramudapu, Erandthailam;
Ara.: Dhun-ul-kerwa, Jaar, Kharoo, Simsim-el-hindi; Bur.: Kesu, Kesusi, Kyekesu;
Chi.: Bì má shǔ, Bimazi, Hung p’i, P’i-ma, Psuna, Ta ma-tzu; Dan.: Rizinus; Dut.:
Wonderboom; Eng.: Castor, Castor beans; Fin.: Risiini; Fre.: Févé castor, Ricin,
Ricin commun; Ger.: Cemeiner wunderbaum, Palma christi, Rizinus, Wunderbaum,
Wunderstrauch; Haw.: Koli keokeo, Koli ulaula; Ita.: Fico d’inferno, Palma christi,
Ricino; Jap.: Casutaa biin, Hima, Rikinusu, Rishin, Tôgoma; Maly.: Miniakjarah;
Nep.: Aderi, Andel, Anderii; Per.: Baid-i-anjir, Khirwa, Khora, Kinnatu; Por.:
Bafureira, Carrapateiro, Catapúcia, Erva-dos-carrapatos, Figueira-do-inferno,
Mamona, Mamoneiro, Catapúcia-maior (Br.), Mamoeiro (Br.); Rus.: Kastorka,
Kleshchevina, Kotoroi kastorka, Ritsin; Sin.: Eudaru, Telendary; Spa.: Alcherva,
Árbol del demonio, Bafureura, Catapucia mayor, Cherva, Higuera del demonio,
Higuera del infierno, Higuera infernal, Higuera loca, Higuereta, Higuerillo,
Mamona, Mosquitera, Palma de cristo, Palmacristi, Querva, Rejalgar, Ricino, Rizno,
Tártago, Tártago de Venezuela; Swe.: Ricin; Tag.: Lansina, Lingang-sina,
Tangan-tangan; Tha.: Lahung, Mahong; Tur.: Hintyağı.
Description: This erect, branched, smooth, somewhat woody perennial bush or
shrub is 1–4 m high, that is indigenous to India, East Africa, southeastern Mediter-
ranean Basin and other tropical regions. New breeds using a range of cultivars can
greatly vary the appearance and growth of this plant, growing it up to a height of 12 m.
Vegetative parts and inflorescences are generally green or purplish. Glossy leaves are
smooth, alternate, palmately divided, long-stalked and 15–45 cm long. In some
varieties they start off dark reddish-purple or bronze when young, gradually changing
to a dark-green, sometimes with a reddish tinge as they mature. Male flowers are
yellowish-green, about 1 cm in diameter; the capsules (fruits) are ovoid, 1–1.5 cm
long, green or purplish, and covered with soft spine-like processes, containing large,
oval, shiny, bean-like, and highly poisonous seeds with variable brownish mottling.
The seeds are the source of commercially used castor oil (Figs. 1, 2 and 3).CXVII
Actions and Uses: Hindu physicians used this plant medicinally from an early
period, and the Arab and Persian physicians learnt about it through them. Both the
root and oil are described as purgative and useful in costiveness, flatulence,
rheumatism, fever and inflammatory affections. Seeds freed from husks and germs,
and boiled in milk and water form a decoction which is used in rheumatism; a
decoction of the root with carbonate of potash is also prescribed; most compound
medicines used in rheumatic and neuralgic affections contain the root. Leaves are
Ricinus communis L. 1541

Fig. 1 Ricinus communis, Plant, Alvesgaspar, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Ricinus_March_2010-1.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

applied to breasts to stop secretion of milk, and boiled with the root in goat’s milk
are used as local application in ophthalmia. Muslim physicians described two
varieties of the plant, red and white; the red is said to be most active. The oil is
considered resolvent and purgative of cold humours, and is prescribed in palsy,
asthma, colds, colic, flatulence, rheumatism, dropsy and amenorrhea. A poultice of
crushed seeds is used to reduce gouty and rheumatic swellings, and inflammation of
breasts of women during lactation.XL Externally, seeds are beneficial in paralysis
and colic, and resolve all forms of hard inflammations; leaves application with or
without any oil is very beneficial in gouty or arthritic inflammations.LXIX It is used
in the Dharwad district of Karnataka in southern India for the treatment of aphthae
[18]. Leaves are also used for hemorrhoids, and seeds as laxative, for wound
dressing, rheumatism and mental illnesses [26]. Leaves, seed and seed oil are all
emmenagogue [43], and leaves have been used in traditional medicines of Africa,
India and the Americas as emmenagogue [49].CL Unani physicians described seeds
(temperament, hot 2° and dry 2°) as analgesic, anti-inflammatory, detergent,
purgative, emmenagogue, anthelmintic, and antidote for poison; and used for
phlegmatic diseases, such as paralysis, palsy, tremors, dyspnea, rheumatism and
ascites.LXXVII Seeds are the source of 50–55% of castor oil.LXXIX Seed oil is a
nonirritant purgative; however, when it reaches duodenum it is decomposed by
pancreatic juice into recinoleic acid which irritates bowels, stimulates intestinal
1542 Ricinus communis L.

Fig. 2 Ricinus communis, Developing Seed Capsules, Martina Nolte, WikimediaCommons;

ShareAlike 3.0 DE CC BY-SA 3.0 DE, https://commons.wikimedia.org/wiki/File:Ricinus_
communis_DSC_0022.JPG; https://creativecommons.org/licenses/by-sa/3.0/de/legalcode

Fig. 3 Ricinus communis, Seeds, Schnobby, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Seeds_of_Ricinus_communis.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en
Ricinus communis L. 1543

glands and muscles to cause purgation.LXXXI,CV Ricin was also considered to be a

safe cathartic without any accompanied intestinal colic,LII and was used as an
adjunct after the administration of anthelmintic, santonin, that also reduced
absorption of santonin. It is one of the preferred plants to treat epilepsy patients by
the nomadic Gujjar community of the sub-Himalayan region of Uttarakhand, India
[47]. In the Philippines, fresh leaves have been used externally for headache, and
cooked with milk, in poultices for certain types of ulcers; the seeds are regarded as
purgative and antirheumatic.LVI
In Hawaii, leaves are put around the head in case of a child with high fever;
leaves draw heat from the body and cause sweating to lower body tempera-
ture.LXXVI Zulus also apply a paste of the root for toothache, apply leaves to head
for headache and as poultice for boils, the rootbark as purgative and for skin
diseases and burns, and an infusion of leaves for stomachache [5].CL In South
Africa, it has traditionally been utilized to treat inflammatory diseases including
wounds, sores, and boils [34] and for the treatment of sores in the Bapedi culture of
Limpopo Province by the traditional primary healthcare sector [46]. In East Africa,
roots are chewed in cases of infection by “Guinea worm” (Drancuculus medinensis)
and continuous treatment has been known to kill the worms. A decoction from
boiled roots is drunk to stimulate appetite, for abdominal trouble, or mixed with
another plant for the treatment of venereal diseases. Stems and leaves are pounded
and juice drunk for the treatment of ulcers, stomachache and diarrhea. Fresh young
leaves are tied on wounds to accelerate healing. Seeds are crushed with clean stone
and then mixed with water. The mixture is then taken for opening the bowels, as a
cure for afterbirth bleeding, and as a remedy for abdominal trouble. Pure oil
extracted from seeds is put in an aching ear. The flowers are ground together with
Commiphora africana leaves and a certain red soil called nondo (Meru), and the
mixture smeared on the skin to make it smooth.LXXXV In Chinese Medicine, seeds
are known as Bimazi and are described as sweet and pungent in taste, with a “mild”
property, and toxic. They are regarded detumescent, detoxicant, and purgative; and
are used for the treatment of carbuncle, furuncle, lymph node tuberculosis, laryn-
gitis, scabies, tinea, edema, abdominal distension and for constipation.XVIII The
Encyclopedia of Chinese Materia Medica [21] also mentions the use of the root to
treat epilepsy, tetanus, and bronchitis in children. Traditional Chinese processing
method lowers the toxicity of castor seeds but maintains their antitumor effect
against pulmonary carcinoma in mice [6].
Phytoconstituents: Ethyl acetate leaf extract showed the presence of alkaloids,
coumarins, flavonoids, and phenols [41]. Kang et al. [23] reported isolation of two
alkaloids, ricinine and N-demethylricinine and six flavonol glycosides: kaempferol-
3-O-b-D-xylopyranoside, kaempferol-3-O-b-D-glucopyranoside, quercetin-3-O-b-D-
xylopyranoside, quercetin-3-O-b-D-glucopyranoside, kaempferol-3-O-b-rutinoside
and quercetin-3-O-b-rutinoside; predominant alkaloid is ricinine (0.55%). Seven
terpenoids and three sterols, ficusic acid, phytol, callyspinol, lupeol, 30-norlupan-
3b-ol-20-one, lup-20(29)-en-3b,15a-diol, and acetylaleuritolic acid, stigmast4-en-
1544 Ricinus communis L.

3-one, stigmast-4-en-6b-ol-3-one, and stigmast4-en-3,6-dione have been isolated

from the aerial parts [27]. Seeds contain 40–50% of ricinic oil composed of
ricinoleic acid, isoricinoleic acid, oleic acid, linolenic acid and stearic acid. They
also contain R. communis hemagglutinin, ricinine, trace amounts of cytochrome C,
lipase and other enzymes. The phytotoxin, ricin, is a very toxic protein, while the
hemagglutinin is nontoxic.
Pharmacology: Methanol root extract exhibits significant anti-inflammatory and
free radical scavenging activities, which could be due to the presence of flavonoids,
alkaloids and tannins [19], and ethanol (50%) extract significantly lowers FBG,
both in normal and type-1 diabetic animals, and positively influences total lipid
profile and liver and kidney functions [48]. Ethanol extract of root bark also
exhibits antihistamine and anti-inflammatory properties [31]. High dose of pericarp
of castor bean extract shows typical CNS stimulant effects in mice, with exoph-
thalmos, tremors and clonic seizures and death within a few minutes. However, at
lower doses, the extract improves memory consolidation and shows some
neuroleptic-like properties, such as decrease in exploratory behavior and catalepsy
[11]. Ricinine, the neutral alkaloid, induces seizures in mice at doses higher than
20 mg/kg that are not inhibited by phenobarbital, phenytoin, or ethosuximide [12].
Both methanol and aqueous extracts of fermented seeds show marked antibacterial
activity against K. pneumoniae, E. coli, P. vulgaris, and S. aureus [22]. Castor bean
extract (i.p.) in rabbits on days 5–9 of pregnancy, markedly decreased maternal
body weight gain and caused death of all fetuses [44], and also exhibited
anti-implantation and abortifacient effects in female guinea pigs, and prolonged the
estrus cycle and dioestrus phase [33]. Ethanol extract drastically reduced epididy-
mal sperm counts, and altered motility and morphology of sperms in rats [45].
Methanol seed extract also decreased weight of reproductive organs, sperm func-
tions and serum levels of testosterone in treated rats [39].
Ricin is very effective against transplantable animal tumors, such as mouse EAC,
ascitic hepatoma, cervical cancer, sarcoma and leukemia. A complete inhibition of
growth of EAC cells and prolonged survival of mice was observed with i.p. injec-
tion of 7.5 ug/kg on the first and third days after tumor inoculation [29, 30]. Ricin at
concentrations of 0.002–0.3 ug/ml inhibited growth of various cell lines of lym-
phoma, myeloma, and myeloid leukemia [40], and also inhibited growth of normal
cells [2, 28]. Ricin is not readily hydrolyzed in the body and remains active for a
relatively long period, but once hydrolyzed it is quickly eliminated. Within 5 h of
an i.p. or i.v. injection in mice, ricin is concentrated in various tissues and organs,
the highest concentration being in the spleen, followed by the kidneys, heart, liver
and thymus. After that the levels decline rapidly and disappear from the liver in
10–12 h and from other organs and tissues in 10–30 h; the urine being the chief
excretion route [13].
Clinical Studies: Castor oil has been the traditional method of initiating labor in
midwifery practice. In Brooklyn Hospital of New York, pregnant women at
40–42-weeks of pregnancy who received 60 ml of castor oil had an increased
Ricinus communis L. 1545

likelihood of initiation of labor within 24-h and a vaginal delivery than those
women who received no treatment [15]. Seeds (RICOM-1013-J), administered as a
single oral dose of 2.3–2.5 g once per 12-months protected against pregnancy in 50
Nigerian women volunteers for a period of one year. The side effects were mild and
included headache, nausea, vomiting, weight gain, loss of appetite, hypertension
and dysmenorrhea [7, 20]. Chang and ButXVIII mentioned that in Jiangsu College of
New Medicine in China, three cases of facial paralysis were treated with crushed
kernel, applied from the mandibular joint to the corner of the mouth once daily.
They were reportedly cured in 10 days. They also use creams or ointments con-
taining 3–5% ricin and 3% dimethylsulfoxide to treat cervical cancer. The
cream/ointment is applied locally once daily, 5–6 times a week for a period of
1–2 months, resulting in some improvement.
Mechanism of Action: Castor oil is an intestinal irritant, and by itself possesses no
cathartic activity. Saponification of the oil in duodenum by lipase yields sodium
ricinate and glycerin. Sodium ricinate irritates small intestine causing reflexive
peristalsis and augmentation of propulsive movements of intestinal contents towards
the colon.LII Anticarcinogenic effect of ricin on various cancer cells is characterized
by strong inhibition of protein synthesis, moderate inhibition of DNA synthesis, and
slight inhibition of RNA synthesis [28, 36]. Ricin also strongly inhibits cell-free
protein synthesis of the lysate of rabbit reticulocytes, indicating a strong inhibition of
eukaryotic ribosomal protein synthesis and not affecting carbohydrate metabolism or
amino acid uptake by cancer cells [36, 37].
Dose: Castor oil (children 4 ml; adults 5–20 ml) is given in the morning on an
empty stomach.
Human A/Es, Allergy and Toxicity: Allergic reactions resulting in rhinitis and/or
asthma due to castor bean dust have been reported [4, 8, 24]. A young mother who
used castor beans orally as a contraceptive for eight-weeks after conception,
delivered a baby with moderate growth retardation, convulsions, craniofacial dys-
morphia, absence deformity of limbs and vertebral segmentation defect, and was
dubbed as “Ricin syndrome” [9]. Castor oil is a relatively safe purgative but is
contraindicated in menstruating or pregnant women, because it may cause mild
congestion of pelvic organs. Whole plant (but not the seed oil) is poisonous. Seeds
are extremely poisonous due to the presence of the phytotoxin, ricin, which is
amongst the most toxic substances known. Ingestion of seeds, intentional or
unintentional, is potently toxic to humans [10, 25], and ricin is the main protein
component of seeds that is exquisitely toxic to mammalian cells [32]. Possible
allergenic reactions of great severity have occurred with a single seed. A burning
sensation in mouth and throat is followed, some hours or more later, by signs of
gastroenteritis, diarrhea, abdominal pain and weakness of body and pulse. The
digestive tract shows hemorrhages and liver and kidneys damage. Chewing castor
beans as a laxative has proved fatal. Heating can inactivate the poison.CXXXV As
few as two seeds can prove serious or even fatal. Death due to injudicious oral
ingestion of about 20 seeds in adults and 2–7 seeds in children have been reported.
1546 Ricinus communis L.

However, the extent of morbidity and mortality due to castor bean ingestion has
lately been questioned, as these poisonings are not associated with serious mor-
bidity, mortality, or delayed symptoms [1, 17, 38, 42, 50, 52]. Ingestion of seeds
may cause violent gastroenteritis with nausea, headache, persistent vomiting,
abdominal colic, thirst, and great debility; severe intoxication causes small, rapid
pulse, cold sweat, icterus, and convulsions; low mortality is due to destruction of
the poison in the GIT.LXXIX Pure ricin, however, is amongst the most toxic com-
pounds, and the lethal dose by injection is about 0.0001 mg/kg (i.e. 7 ug for an
adult of 70 kg). By oral administration ricin is several hundred times less tox-
ic.LXXXIII Ricinin 160 mg or ricin 7 mg is lethal in adults. Toxicity of ricin is
reported to be 22 times greater than that of hydrogen cyanide; 1 g of it is sufficient
to kill 3,600 persons [2]. Ricin is also highly antigenic and administration of ricin
through different routes in man and various mammals induced allergic reactions and
produced antibodies. Farmers cultivating the plant were found to have ricin anti-
bodies in their blood. These stable antibodies can increase level of nonspecific
antibodies in their blood [2]. These antibodies may explain the attenuation of
specific deleterious effects of ricin on protein synthesis and suppression of pyro-
genic reaction [3].
Animal Toxicity: Poisonous effects have been recorded when seeds and leaves are
eaten by horses, goats, pigs and poultry. The plant causes nephrotoxicity in large
domestic animals [35]. Ricin intoxication increases coagulation time due to inter-
ference with glycolysis and decreased prothrombin and thrombokinase. RBC and
WBC counts, blood glucose and urea levels are increased; whereas blood con-
centration of Mg++ ion was decreased and the level of Ca++ ions was increased,
changing the ratio of Ca++ to Mg++ from 2:1 to 7.75:1 [2].
LD50 (i.v.) of ricin in mice is reported between 6 and 12 ug/kg [16]; through i.
p. route in 6–8 weeks old C57B1/6 mice was reported 75 ng per 18 g mouse [14],
and in rats by i.v. route was between 50 and 150 ug/kg [51]. However, higher
values have also been reported, which could be due to variations in its purity [15].
Mice, after the i.p. or i.v. injections of the lethal dose of ricin, died within from 10 h
to a few days. Onset of toxicity is relatively long and generally started with
unsteady gait after 12-h and lying sideways after 24-h. Later, animals developed
dyspnea, opisthotonus, diarrhea, convulsions and other central disturbances, fol-
lowed by death due to respiratory paralysis within 30-min after the onset of first
convulsion [2]. In acute and subacute toxicity studies, functional and morphological
changes involved most organs and tissues, but chiefly confined to liver, small
intestine and endocrine glands in rats, mice, guinea pigs and rabbits. In liver, main
damage is to the endoplasmic reticulum and mitochondrial changes in hepatocytes
leading to hepatic degeneration and necrosis. Hemorrhagic necrosis and regressive
degeneration were evident in hypothalamic cells, adrenal glands, pituitary, thymus,
testicles, ovary, pancreas, and lymph tissues [2, 51].
Ricinus communis L. 1547

Commentary: This plant is generally known for the extreme toxicity of ricin.
However, the plant and the seed oil have been used for centuries for different
ailments. Ironically, sometimes the very toxic plants hide some useful remedies in
them. A fresh look at the plant is needed and ancient methods of detoxification may
be required to explore more therapeutic uses.

References
1. Aplin PJ, Eliseo T. Ingestion of castor oil plant seeds. Med J Aust. 1997;
167:260–1.
2. Balint GA. Ricin: the toxic protein of castor oil seeds. Toxicol. 1974;
2:77–102.
3. Balint GA, et al. Chem. Abstr. 1975;82:84364a.
4. Baur X, Chen Z, Hürter T. Asthma and rhinoconjunctivitis caused by castor
bean dust. Pneumologie. 1998;52:539–40 (German).
5. Caius JF. Medicinal and poisonous plants of India. Waterlilies, Poppywrots,
Fumitorius. J Bombay Nat Hist Soc. 1938;40:513–27.
6. Chen BX, Ding YS, Chen LG. Experimental study on the processed drug of
castor seeds in the therapy of pulmonary carcinoma. Zhongguo Zhong Yao
Za Zhi. 1994;19:726–7 (Chinese).
7. Das SC, Isichei CO, Okwuasaba FK, et al. Chemical, pathological and
toxicological studies of the effects of RICOM-1013-J of Ricinus communis
var minor on women volunteers and rodents. Phytother Res. 2000;14:15–9.
8. Davison AG, Britton MG, Forrester JA, et al. Asthma in merchant seamen
and laboratory workers caused by allergy to castor beans: analysis of
allergens. Clin Allergy. 1983;13:553–61.
9. El Mauhoub M, Khalifa MM, Jaswal OB, Garrah MS. “Ricin syndrome”.
A possible new teratogenic syndrome associated with ingestion of castor oil
seed in early pregnancy: a case report. Ann Trop Paediatrics. 1983;3:57–61.
10. Fernando R, Fernando DN. Poisoning with plants and mushrooms in Sri Lanka:
a retrospective hospital based study. Vet Hum Toxicol. 1990;32:579–81.
11. Ferraz AC, Angelucci ME, Da Costa ML, et al. Pharmacological evaluation
of ricinine, a central nervous system stimulant isolated from Ricinus
communis. Pharmacol Biochem Behav. 1999;63:367–75.
12. Ferraz AC, Pereira LF, Ribeiro RL, et al. Ricinine-elicited seizures. A novel
chemical model of convulsive seizures. Pharmacol Biochem Behav. 2000;65:
577–83.
13. Fodstad O, Olsnes S, Pihl A. Toxicity, distribution and elimination of the
cancerostatic lectins abrin and ricin after parenteral injection into mice. Br J
Cancer. 1976;34:418–25.
14. Fu T, Burbage C, Tagge EP, et al. Ricin toxin contains three lectin sites which
contribute to its in vivo toxicity. Int J Immunopharmacol. 1996;18:685–92.
15. Garry D, Figueroa R, Guillaume J, Cucco V. Use of castor oil in pregnancies at
term. Altern Ther Health Med. 2000;6:77–9.
1548 Ricinus communis L.

16. Gürtler LG, Horstmann HJ. Subunits of toxin and agglutinin of Ricinus
communis. Biochim Biophys Acta. 1973;295:582–94.
17. Hamouda C, Amamou M, Thabet H, et al. Plant poisonings from herbal
medication admitted to a Tunisian toxicologic intensive care unit, 1983–
1998. Vet Hum Toxicol. 2000;42:137–41.
18. Hebbar SS, Harsha VH, Shripathi V, Hegde GR. Ethnomedicine of
Dharwad district in Karnataka, India—plants used in oral health care.
J Ethnopharmacol. 2004;94:261–6.
19. Ilavarasan R, Mallika M, Venkataraman S. Anti-inflammatory and free
radical scavenging activity of Ricinus communis root extract. J Ethnophar-
macol. 2006;103:478–80.
20. Isichei CO, Das SC, Ogunkeye OO, et al. Preliminary clinical investigation
of the contraceptive efficacy and chemical pathological effects of RICOM-
1013-J of Ricinus communis var minor on women volunteers. Phytother
Res. 2000;14:40–2.
21. Jiangsu College of New Medicine. Encyclopedia of Chinese Materia
Medica. vol. 2. Shanghai People’s Publishing House; 1975. p. 2446.
22. Jombo GT, Enenebeaku MN. Antibacterial profile of fermented seed
extracts of Ricinus communis: findings from a preliminary analysis. Niger J
Physiol Sci. 2008;23:55–9.
23. Kang SS, Cordell GA, Soejarto DD, Fong HS. Alkaloids and flavonoids
from Ricinus communis. J Nat Prod. 1985;48:155–6.
24. Kemeny DM, Frankland AW, Fahkri ZI, Trull AK. Allergy to castor bean in
the Sudan: measurement of serum IgE and specific IgE antibodies. Clin
Allergy. 1981;11:463–71.
25. Kinamore PA, Jaeger RW, de Castro FJ. Abrus and ricinus ingestion:
management of three cases. Clin Toxicol. 1980;17:401–5.
26. Lemordant D. Contribution a l’ethnobotanique Ethiopienne. J Agric Trop
Bot Appl. 1971;18:1–35; 18:142–79.
27. Li SH, Deng Q, Zhu L, et al. Terpenoids and sterols from Ricinus
communis and their activities against diabetes. Zhongguo Zhong Yao Za
Zhi. 2014;39:448–52 (Chinese).
28. Lin JY, Liu K, Chen CC, Tung TC. Effect of crystalline ricin on the
biosynthesis of protein, RNA, and DNA in experimental tumor cells. Cancer
Res. 1971;31:921–4.
29. Lin JY, Chang YC, Huang LY, Tung TC. The cytotoxic effects of abrin and
ricin on Ehrlich ascites tumor cells. Toxicon. 1973;11:379–81.
30. Lin JY, Tserng KY, Chen CC, Lin LT, Tung TC. Abrin and ricin: new
antitumour substances. Nature. 1970;227:292–3.
31. Lomash V, Parihar SK, Jain NK, Katiyar AK. Effect of Solanum nigrum
and Ricinus communis extracts on histamine and carrageenan-induced
inflammation in the chicken skin. Cell Mol Biol. 2010;(Noisy-le-grand) 56
Suppl:OL1239–51.
32. Lord JM, Roberts LM, Robertus JD. Ricin: structure, mode of action, and
some current applications. FASEB J. 1994;8:201–8 (Review).
Ricinus communis L. 1549

33. Makonnen E, Zerihun L, Assefa G, Rostom AA. Antifertility activity of Ricinus

communis seed in female guinea pigs. East Afr Med J. 1999;76:335–7.
34. Nemudzivhadi V, Masoko P. In vitro assessment of cytotoxicity, antiox-
idant, and anti-inflammatory activities of Ricinus communis (Euphor-
biaceae) leaf extracts. Evid Based Complement Alternat Med. 2014;2014:
625961.
35. Oladosu LA, Case AA. Large animal hepatotoxic and nephrotoxic plants.
Vet Hum Toxicol. 1979;21:363–5.
36. Olsnes S, Refsnes K, Pihl A. Mechanism of action of the toxic lectins abrin
and ricin. Nature. 1974;249:627–31.
37. Olsnes S, Sandvig K, Refsnes K, Pihl A. Rates of different steps involved in
the inhibition of protein synthesis by the toxic lectins abrin and ricin. J Biol
Chem. 1976;251:3985–92.
38. Palatnick W, Tenenbein M. Hepatotoxicity from castor bean ingestion in a
child. J Toxicol Clin Toxicol. 2000;38:67–9.
39. Raji Y, Oloyo AK, Morakinyo AO. Effect of methanol extract of Ricinus
communis seed on reproduction of male rats. Asian J Androl. 2006;8:115–21.
40. Ralph P, Nakoinz I. Inhibitory effects of lectins and lymphocyte mitogens
on murine lymphomas and myelomas. J Natl Cancer Inst. 1973;51:883–90.
41. Rampadarath S, Puchooa D, Ranghoo-Sanmukhiya VM. A comparison of
polyphenolic content, antioxidant activity and insecticidal properties of
Jatropha species and wild Ricinus communis L. found in Mauritius. Asian
Pac J Trop Med. Sep 2014;7S1:S384–90.
42. Rauber A, Heard J. Castor bean toxicity re-examined: a new perspective.
Vet Hum Toxicol. 1985;27:498–502.
43. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
44. Salhab AS, Shomaf MS, Gharaibeh MN, Amer NA. Effects of castor bean
extract and ricin A-chain on ovulation and implantation in rabbits. Contra-
ception. 1999;59:395–9.
45. Sandhyakumary K, Bobby RG, Indira M. Antifertility effects of Ricinus
communis (Linn) on rats. Phytother Res. 2003;17:508–11.
46. Semenya S, Potgieter M, Tshisikhawe M, Shava S, Maroyi A. Medicinal
utilization of exotic plants by Bapedi traditional healers to treat human
ailments in Limpopo province, South Africa. J Ethnopharmacol. 2012;144:
646–55.
47. Sharma J, Gairola S, Gaur RD, Painuli RM, Siddiqi TO. Ethnomedicinal plants
used for treating epilepsy by indigenous communities of sub-Himalayan region
of Uttarakhand, India. J Ethnopharmacol. 2013;150:353–70.
48. Shokeen P, Anand P, Murali YK, Tandon V. Antidiabetic activity of 50%
ethanolic extract of Ricinus communis and its purified fractions. Food Chem
Toxicol. 2008;46:3458–66.
49. Sussman LK. Herbal medicine on Mauritius. J Ethnopharmacol. 1980;2:
259–78.
1550 Ricinus communis L.

50. Thornton SL, Darracq M, Lo J, Cantrell FL. Castor bean seed ingestions: a
statewide poison control system’s experience. Clin Toxicol (Phila). 2014;
52:265–8.
51. Waller GR, Ebner KE, Scroggs RA, et al. Studies on the toxic action of
ricin. Proc Soc Exp Biol Med. 1966;121:685–91.
52. Wedin GP, Neal JS, Everson GW, Krenzelok EP. Castor bean poisoning.
Am J Emerg Med. 1986;4:259–61.
Rubia cordifolia L.
(Rubiaceae)

(Syns.: R. manjith Roxb. ex Flem.; R. javana DC; Dioscorea verticillata Lam.;

Galium cordifolium (L.) Kuntze)

Abstract
A creeping or climbing perennial herb, indigenous to India, China, Malaysia,
Japan, Africa, and tropical Australia. In China, it is widely distributed in most
regions, especially the provinces of Shaanxi, Henan, Anhui, Hebei, Shandong,
Hubei, Jiangsu, and Zhejiang. In Unani medicine, the dark-red roots are
considered deobstruent of liver and spleen, emmenagogue and diuretic; but mostly
used as a diuretic and emmenagogue. Excessive use of it as a diuretic may lead to
hematuria. Root infusion has also been used in women after childbirth to increase
flow of lochia. In Ayurveda, it has been used as a coloring agent for medicated oils,
used for external applications on inflammed parts, ulcers, and fractures. A paste
made of the root with honey is applied to skin to clear brown spots, freckles and
other discolorations of skin, and used to promote wound healing. In Chinese
medicine, the root is known as Qiancaogen and Chien-tsao, bitter with cold
property, that removes pathogenic heat from blood, and exerts hemostatic, stasis-
eliminative, and channel-deobstruent actions, and chiefly used as a hemostatic
agent to treat hematemasis, epistaxis, metrorrhagia, wounds, injuries and strains,
and prescribed to treat psoriasis. It is an important herbal drug in TCM for curing
syndromes caused by blood heat, as it cools blood, eliminates stasis, stop bleeding
and unblocks meridians, and is still listed in Chinese Pharmacopeia, and approved
by the Ministry of Health as dietary supplement. In Korean traditional medicine,
roots are used for the treatment of cough, bladder and kidney stones, joint
inflammation, uterine hemorrhage and uteritis. In Uganda, traditional healers use
the plant to treat cases of tuberculosis. In the Philippines, the root decoction is used
for urinary tract disorders. Over one hundred phytoconstituents have been isolated
from it. Root contains ruberythric acid, a number of anthraquinones, naphtho-
quinones, bicyclic hexapeptides, gallic acid and tannins. Ethanol root extract
reduced blood sugar in diabetic animals, prevented cold stress-induced gastric
ulcers, antagonized scopolamine-induced learning and memory impairment, and
increased brain GABA levels and decreased brain DA and plasma corticosterone
levels.
© Springer Nature Switzerland AG 2020 1551
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_160
1552 Rubia cordifolia L.

Keywords


Chien-tsao Farberwurzel Fuwwah

Garance de l’inde
Indian madder




Majith Manjishta Ruiva-da-Sibéria
Runas
Urooqussabagh

Vernaculars: Urd.: Fuwwah; Hin.: Majith, Manjith; San.: Chitravalli, Gandari,

Manjista, Manjishta, Manjistha; Ben.: Manjistha, Munjeet; Mal.: Manjetti, Poont;
Mar.: Manjestha; Tam.: Manditta, Manjitti, Shevelli; Tel.: Mandastic, Manjishta,
Manjishtatige, Tamravalli; Ara.: Fuvvah, Urooqussabagh; Chi.: 茜草, Chien-tsao,
Hsi ts-ao, Qian cao, Qiancaogen, Hong teng zi cao; Eng.: Aromatic madder,
Common madder, Indian madder, Red madder; Fre.: Garance de l’Inde; Ger.:
Farberwurzel, Ostindischer krapp, Tibetischer färberkrapp; Jap.: Indo akane; Nep.:
Mangito; Per.: Runas; Por.: Ruiva-da-Sibéria; Tag.: Mankit.
Description: Indigenous to India, China, Malaysia, Japan, Africa, and tropical
Australia. In China, it is widely distributed in most regions, especially the provinces
of Shaanxi, Henan, Anhui, Hebei, Shandong, Hubei, Jiangsu, and Zhejiang [48].
It is a slender, branched, creeping or climbing perennial herb growing up to a height
of 4 m (some mentioned the height to be 1.5 m), that has numerous small prickles
on tetragonal stems. Leaves are stalked, 4–7 in a whorl around the stem, ovate,
5–10 cm long and 2–3 cm wide, pointed tipped, heart-shaped at the base, rough
above, veins beneath, and especially on the margins. Flowers are minute, on short,
smooth stalks, white or yellow (during August–September). Fruit is rounded, 6 to
8 mm long, shining and purplish-black.LXXIX,CXVII Roots could be up to a meter
long and are known for its red pigment, which was commercially exploited since
antiquity for dyeing textiles. Generally, the root and rhizome are collected for
medicinal use in spring or autumn in the third or fourth year of growth [48] (Fig. 1).

Fig. 1 Rubia cordifolia, Plant, Vinayaraj, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Rubia_cordifolia.jpg; https://creativecommons.
org/licenses/by-sa/3.0/deed.en
Rubia cordifolia L. 1553

Actions and Uses: In Unani medicine, the dark-red roots (temperament, hot 2° and
dry 2°) are considered deobstruent of liver and spleen, emmenagogue and diuretic;
but mostly used as a diuretic and emmenagogue. Excessive use of it as a diuretic may
lead to hematuria;LXIX,LXXVII also useful for nervous diseases, such as paralysis and
facial palsy, bloody diarrhea and jaundice.L Root infusion has also been used in
women after childbirth to increase flow of lochia.LXXXIV NadkarniCV described its
uses in dropsy, paralysis, jaundice, amenorrhea and visceral obstructions. In Ayur-
veda, it has been used as a coloring agent for medicated oils, and used for external
applications on inflamed parts, ulcers, and fractures. A paste made of the root with
honey is applied to skin to clear brown spots, freckles and other discolorations of
skin,XL and used to promote wound healing [8]. Emmenagogue, hemostatic in
hemorrhoidal hemorrhage, and used in jaundice and rheumatism.LXXIX In Chinese
medicine, the root is known as Qiancaogen and Chien-tsao, bitter with cold prop-
erty,LXVI that removes pathogenic heat from blood, and exerts hemostatic, stasis-
eliminative, and channel-deobstruent actions, and chiefly used as a hemostatic agent
to treat hematemesis, epistaxis, metrorrhagia, wounds, injuries and strains [54],XVIII
and prescribed to treat psoriasis [62]. It is an important herbal drug in TCM for
curing syndromes caused by blood heat, as it cools blood, eliminates stasis, stops
bleeding and unblocks meridians, and is still listed in Chinese Pharmacopeia, and
approved by the Ministry of Health as dietary supplement [48]. Aerial parts are
known for their antidiarrheal property and their aqueous extract is widely used to
treat diarrhea in many parts of China [18, 54]. In Korean traditional medicine, roots
are used for the treatment of cough, bladder and kidney stones, joint inflammation,
uterine hemorrhage and uteritis [53]. In Uganda, traditional healers use the plant to
treat cases of tuberculosis [9]. In the Philippines, the root decoction is used for
urinary tract disorders.CXVII
Phytoconstituents: Over one hundred phytoconstituents have been isolated from it
[48]. Root contains ruberythric acid,LXXIX a number of anthraquinones, naphtho-
quinones [1, 15, 16, 20, 23, 26, 34, 44, 56, 63, 64, 66], bicyclic hexapeptides
[19, 32, 33, 38, 55], gallic acid and tannins [10]. Alizarin, munjistin, purpurin,
rubiadin, tectoquinone and xanthopurpurin are common anthraquinones; mollugin
is representative of naphthoquinones. Triterpenoids isolated from roots/rhizomes
include ursolic acid, oleanolic acid, rubiprasin A–C, rubiarbonol A and B, rubi-
coumaric acid and rubifolic acid [48]. Hydroxyanthraquinones are the predominant
antioxidant compounds of the root [10]; rubiadin, isolated from the roots, has also
shown antioxidant activity [58].
Pharmacology: Ethanol root extract reduced blood sugar in alloxan diabetic ani-
mals, prevented cold stress-induced gastric ulcers, antagonized scopolamine-
induced learning and memory impairment, and increased brain GABA levels and
decreased brain DA and plasma corticosterone levels [40]. Triterpene isolated from
roots inhibit seizures induced by MES, electrical kindling, PTZ, and lithium-
pilocarpine [28]. It offers in vitro neuroprotection by attenuating oxidative
stress-mediated cell injury during oxygen-glucose deficiency [46]. Root and rhi-
zome extracts significantly protect animals against reserpine-induced orofacial
1554 Rubia cordifolia L.

dyskinesia [41]. Both crude extract [11, 21, 27] and the isolated compounds [17]
from roots have shown anti-inflammatory, and in vitro antioxidant activities [6, 39,
58–60]. Ethanol extract also provides significant protection against radiation
induced LPO, hemopoietic injury and genotoxicity [61]. Mollugin is a potent
neuroprotective against glutamate-induced neurotoxicity and anti-inflammatory
[22]. Mollugin also attenuates LPS-induced expression of NO, iNOS, IL-1b and
IL-6, but augments expression of TNF-a in LPS-stimulated macrophages [67] and
significantly inhibits TNF-a-induced inflammatory responses in HT-29 human
colon epithelial cells [31]. Aqueous, chloroform and methanol extracts of the roots
were significantly active against B. subtilis and S. aureus; whereas methanol extract
also inhibited Gram-negative P. aeruginosa [5], and was potentially active against
HIV [47]. A commercially available aqueous extract reportedly showed mild
thrombolytic activity [43], and a partially purified fraction of whole plant inhibited
PAF-induced but not thrombin-induced platelet aggregation [57].
Hydroalcohol root extract protected against ethylene glycol-induced urolithiasis in
rats [13], and significantly decreased cisplatin-nephrotoxicity in mice by improving
antioxidant status, and considerably reduced serum creatinine, urea levels, and LPO
in kidney and liver tissues [24]; also, significantly protected against lead nitrate-
induced immune response impairment and kidney oxidative damage in mice [36].
Anthraquinone glycosides from root also prevented recurrence of experimental cal-
cium urinary stones [7]. Chloroform fraction of methanol root extract was signifi-
cantly gastroprotective against aspirin- and pylorus-ligated gastric ulcers, decreased
gastric acid secretion and increased PG synthesis [12], and hydroalcohol extract
reduced intensity of indomethacin-induced enterocolitis in rats [42]. Aqueous extract
of aerial parts delayed onset of semisolid feces, reduced evacuation index in senna
leaf-induced diarrhea in mice, and inhibited propulsive movement in castor oil-
induced intestinal transit [18]. Rubiadin potently protected against CCl4-hepato-
toxicity in rats [45]. The root extract also prevents peanut-induced anaphylaxis in
experimental animals [37]. Aqueous and methanol crude root extracts [2, 50, 52],
ethanol extract [62], and isolated constituents [3, 4, 14, 25, 29, 65] exhibited potent
cytotoxicity and antiproliferative effects inducing apoptosis in various cancer cell
lines, and in NDEA-induced hepatocellular carcinoma [51]. Ethyl acetate fraction of
ethanol extract also inhibited keratinocyte proliferation and promoted in vivo ker-
atinocyte differentiation [35]. Ethanol (90%) root extract exhibited an insignificant
33% anti-implantation activity in rats [49].
Human A/Es, Allergy and Toxicity: No reported A/Es or allergies.
Animal Toxicity: There are no published reports on its animal toxicity studies.
CYP450 and Potential for Drug-Herb Interactions: Mollugin has shown strong
in vitro inhibitory activity of CYP1A2 [30].
Commentary: There are no clinical studies reported in the English journals listed
on PubMed. Its anti-inflammatory, anticancer, nephroprotective and neuroprotective
effects observed in pharmacological studies may be subjected to further exploration.
Rubia cordifolia L. 1555

References
1. Abdullah ST, Ali A, Hamid H, et al. Two new anthraquinones from the
roots of Rubia cordifolia Linn. Pharmazie. 2003;58:216–7.
2. Adwankar MK, Chitnis MP, Khandalekar DD, Bhadsavale CG. Anticancer
activity of the extracts of Rubia cordifolia Linn. (NSC b668893). Indian J
Exp Biol. 1980;18:102.
3. Adwankar MK, Chitnis MP. Effect of RC-18, a new anticancer principle
isolated from Rubia cordifolia, Linn. on cell cycle of P388 tumour system.
Biomed Pharmacother. 1982;36:104–5.
4. Adwankar MK, Chitnis MP. In vivo anticancer activity of RC-18: a plant
isolate from Rubia cordifolia, Linn. against a spectrum of experimental
tumour models. Chemotherapy. 1982;28:291–3.
5. Basu S, Ghosh A, Hazra B. Evaluation of the antibacterial activity of Venti-
lago madraspatana Gaertn., Rubia cordifolia Linn. and Lantana camara
Linn.: isolation of emodin and physcion as active antibacterial agents.
Phytother Res. 2005;19:888–94.
6. Basu S, Hazra B. Evaluation of nitric oxide scavenging activity, in vitro and
ex vivo, of selected medicinal plants traditionally used in inflammatory
diseases. Phytother Res. 2006;20:896–900.
7. Berg W, Hesse A, Hensel K, et al. Influence of anthraquinones on the
formation of urinary calculi in experimental animals (author’s transl).
Urologe A. 1976;15:188–91 (German).
8. Biswas TK, Mukherjee B. Plant medicines of Indian origin for wound
healing activity: a review. Int J Low Extrem Wounds. 2003;2:25–39.
9. Bunalema L, Obakiro S, Tabuti JR, Waako P. Knowledge on plants used
traditionally in the treatment of tuberculosis in Uganda. J Ethnopharmacol.
2014;151:999–1004.
10. Cai Y, Sun M, Xing J, Corke H. Antioxidant phenolic constituents in roots
of Rheum officinale and Rubia cordifolia: structure-radical scavenging
activity relationships. J Agric Food Chem. 2004;52:7884–90.
11. Chen CL, Zhang DD. Anti-inflammatory effects of 81 chinese herb extracts
and their correlation with the characteristics of traditional chinese medicine.
Evid Based Complement Alternat Med. 2014;2014:985176.
12. Deoda RS, Kumar D, Bhujbal SS. Gastroprotective effect of Rubia cordi-
folia Linn. on aspirin plus pylorus-ligated ulcer. Evid Based Complement
Alternat Med. 2011;2011:541624.
13. Divakar K, Pawar AT, Chandrasekhar SB, et al. Protective effect of the
hydroalcoholic extract of Rubia cordifolia roots against ethylene glycol
induced urolithiasis in rats. Food Chem Toxicol. 2010;48:1013–8.
14. Do MT, Hwang YP, Kim HG, et al. Mollugin inhibits proliferation and
induces apoptosis by suppressing fatty acid synthase in HER2-overexpressing
cancer cells. J Cell Physiol. 2013;228:1087–97.
15. Dosseh C, Tessier AM, Delaveau P. New quinones in Rubia cordifolia L.
roots, III. Planta Med. 1981;43:360–6 (German).
1556 Rubia cordifolia L.

16. Dosseh C, Tessier AM, Delaveau P. Rubia cordifolia roots. II: New
quinones. Planta Med. 1981;43:141–7 (German).
17. Ghosh S, Das Sarma M, Patra A, Hazra B. Anti-inflammatory and anticancer
compounds isolated from Ventilago madraspatana Gaertn., Rubia cordifolia
Linn. and Lantana camara Linn. J Pharm Pharmacol. 2010;62:1158–66.
18. Gong XP, Sun YY, Chen W, et al. Antidiarrheal and anti-inflammatory
activities of aqueous extract of the aerial part of Rubia cordifolia. BMC
Complement Altern Med. 2017;17:20.
19. Hitotsuyanagi Y, Odagiri M, Kato S, et al. Isolation, structure determina-
tion, and synthesis of allo-RA-V and neo-RA-V, RA-series bicyclic
peptides from Rubia cordifolia L. Chemistry. 2012;18:2839–46.
20. Itokawa H, Ibraheim ZZ, Qiao YF, Takeya K. Anthraquinones, naphtho-
hydroquinones and naphthohydroquinone dimers from Rubia cordifolia and
their cytotoxic activity. Chem Pharm Bull (Tokyo). 1993;41:1869–72.
21. Jain A, Basal E. Inhibition of Propionibacterium acnes-induced mediators
of inflammation by Indian herbs. Phytomedicine. 2003;10:34–8.
22. Jeong GS, Lee DS, Kim DC, et al. Neuroprotective and anti-inflammatory
effects of mollugin via upregulation of heme oxygenase-1 in mouse
hippocampal and microglial cells. Eur J Pharmacol. 2011;654:226–34.
23. Jeong SY, Zhao BT, Lee CS, et al. Constituents with DNA topoisomerases I
and II inhibitory activity and cytotoxicity from the roots of Rubia cordifolia.
Planta Med. 2012;78:177–81.
24. Joy J, Nair CK. Amelioration of cisplatin induced nephrotoxicity in Swiss
albino mice by Rubia cordifolia extract. J Cancer Res Ther. 2008;4:111–5.
25. Jun do Y, Han CR, Choi MS, et al. Effect of mollugin on apoptosis and
adipogenesis of 3T3-L1 preadipocytes. Phytother Res. 2011;25:724–31.
26. Kang W, Zhang L, Song Y. Alpha-glucosidase inhibitors from Rubia
cordifolia. Zhongguo Zhong Yao Za Zhi. 2009;34:1104–7 (Chinese).
27. Kasture SB, Kasture VS, Chopde CT. Anti-inflammatory activity of Rubia
cordifolia roots. J Nat Remedies. 2001;1:111–5.
28. Kasture VS, Deshmukh VK, Chopde CT. Anticonvulsant and behavioral
actions of triterpene isolated from Rubia cordifolia Linn. Indian J Exp Biol.
2000;38:675–80.
29. Kato T, Suzumura Y, Takamoto S, Ota K. Antitumor activity and toxicity in
mice of RA-700, a cyclic hexapeptide. Anticancer Res. 1987;7:329–34.
30. Kim H, Choi HK, Jeong TC, et al. Selective inhibitory effects of mollugin on
CYP1A2 in human liver microsomes. Food Chem Toxicol. 2013;51:33–7.
31. Kim KJ, Lee JS, Kwak MK, et al. Anti-inflammatory action of mollugin and
its synthetic derivatives in HT-29 human colonic epithelial cells is mediated
through inhibition of NF-kappaB activation. Eur J Pharmacol. 2009;622:
52–7.
32. Lee JE, Hitotsuyanagi Y, Fukaya H, et al. New cytotoxic bicyclic hexapep-
tides, RA-XXIII and RA-XXIV, from Rubia cordifolia L. Chem Pharm Bull
(Tokyo). 2008;56:730–3.
Rubia cordifolia L. 1557

33. Lee JE, Hitotsuyanagi Y, Kim IH, et al. A novel bicyclic hexapeptide,
RA-XVIII, from Rubia cordifolia: structure, semisynthesis, and cytotoxi-
city. Bioorg Med Chem Lett. 2008;18:808–11.
34. Li X, Liu Z, Chen Y, et al. Rubiacordone A: a new anthraquinone glycoside
from the roots of Rubia cordifolia. Molecules. 2009;14:566–72.
35. Lin ZX, Jiao BW, Che CT, et al. Ethyl acetate fraction of the root of Rubia
cordifolia L. inhibits keratinocyte proliferation in vitro and promotes kerati-
nocyte differentiation in vivo: potential application for psoriasis treatment.
Phytother Res. 2010;24:1056–64.
36. Lodi S, Sharma V, Kansal L. The protective effect of Rubia cordifolia against
lead nitrate-induced immune response impairment and kidney oxidative
damage. Indian J Pharmacol. 2011;43:441–4.
37. López-Expósito I, Castillo A, Yang N, et al. Chinese herbal extracts of
Rubia cordifolia and Dianthus superbus suppress IgE production and
prevent peanut-induced anaphylaxis. Chin Med. 2011;6:35.
38. Morita H, Yamamiya T, Takeya K, Itokawa H. New antitumor bicyclic
hexapeptides, RA-XI, -XII, -XIII and -XIV from Rubia cordifolia. Chem
Pharm Bull (Tokyo). 1992;40:1352–4.
39. Pandey S, Sharma M, Chaturvedi P, Tripathi YB. Protective effect of Rubia
cordifolia on lipid peroxide formation in isolated rat liver homogenate.
Indian J Exp Biol. 1994;32:180–3.
40. Patil RA, Jagdale SC, Kasture SB. Antihyperglycemic, antistress and
nootropic activity of roots of Rubia cordifolia Linn. Indian J Exp Biol. 2006;
44:987–92.
41. Patil RA, Kasture SB. Protective effect of Rubia cordifolia on reserpine-
induced orofacial dyskinesia. Nat Prod Res. 2012;26:2159–61.
42. Pawar AT, Anap RM, Ghodasara JV, Kuchekar BS. Protective effect of
hydroalcoholic root extract of Rubia cordifolia in indomethacin-induced
enterocolitis in rats. Indian J Pharm Sci. 2011;73:250–3.
43. Prasad S, Kashyap RS, Deopujari JY, et al. Effect of Fagonia arabica
(Dhamasa) on in vitro thrombolysis. BMC Complement Altern Med. 2007;
7:36.
44. Qiao YF, Wang SX, Wu LJ, et al. Studies on antibacterial constituents
from the roots of Rubia cordifolia L. Yao Xue Xue Bao. 1990;25:834–9
(Chinese).
45. Rao GM, Rao CV, Pushpangadan P, Shirwaikar A. Hepatoprotective effects
of rubiadin, a major constituent of Rubia cordifolia Linn. J Ethnopharmacol.
2006;103:484–90.
46. Rawal AK, Muddeshwar MG, Biswas SK. Rubia cordifolia, Fagonia
cretica Linn and Tinospora cordifolia exert neuroprotection by modulating
the antioxidant system in rat hippocampal slices subjected to oxygen
glucose deprivation. BMC Complement Altern Med. 2004;4:11.
47. Sabde S, Bodiwala HS, Karmase A, et al. Anti-HIV activity of Indian
medicinal plants. J Nat Med. 2011;65:662–9.
1558 Rubia cordifolia L.

48. Shan M, Yu S, Yan H, et al. A review of the botany, phytochemistry,

pharmacology and toxicology of rubiae radix et rhizoma. Molecules.
2016;21. pii: E1747.
49. Sharma BB, Varshney MD, Gupta DN, Prakash AO. Antifertility screening
of plants. Part I. Effect of ten indigenous plants on early pregnancy in albino
rats. Int J Crude Drug Res. 1983;24:183–7.
50. Shilpa PN, Sivaramakrishnan V, Niranjali Devaraj S. Induction of apoptosis
by methanolic extract of Rubia cordifolia Linn in HEp-2 cell line is mediated
by reactive oxygen species. Asian Pac J Cancer Prev. 2012;13:2753–8.
51. Shilpa PN, Venkatabalasubramanian S, Devaraj SN. Ameliorative effect of
methanol extract of Rubia cordifolia in N-nitrosodiethylamine-induced
hepatocellular carcinoma. Pharm Biol. 2012;50:376–83.
52. Shoemaker M, Hamilton B, Dairkee SH, et al. In vitro anticancer activity of
twelve Chinese medicinal herbs. Phytother Res. 2005;19:649–51.
53. Son JK, Jung SJ, Jung JH, et al. Anticancer constituents from the roots of
Rubia cordifolia L. Chem Pharm Bull (Tokyo). 2008;56:213–6.
54. Sun Y, Gong X, Tan JY, et al. In vitro antiviral activity of Rubia cordifo-
lia aerial part extract against rotavirus. Front Pharmacol. 2016;7:308.
55. Takeya K, Yamamiya T, Morita H, Itokawa H. Two antitumour bicyclic
hexapeptides from Rubia cordifolia. Phytochemistry. 1993;33:613–5.
56. Tessier AM, Delaveau P, Champion B. New Anthraquinones in Rubia
cordifolia Roots. Planta Med. 1981;41:337–43 (German).
57. Tripathi YB, Pandey S, Shukla SD. Antiplatelet activating factor property of
Rubia cordifolia Linn. Indian J Exp Biol. 1993;31:533–5.
58. Tripathi YB, Sharma M, Manickam M. Rubiadin, a new antioxidant from
Rubia cordifolia. Indian J Biochem Biophys. 1997;34:302–6.
59. Tripathi YB, Sharma M. Comparison of the antioxidant action of the alcoholic
extract of Rubia cordifolia with rubiadin. Indian J Biochem Biophys. 1998;
35:313–6.
60. Tripathi YB, Sharma M. The interaction of Rubia cordifolia with iron redox
status: a mechanistic aspect in free radical reactions. Phytomedicine. 1999;
6:51–7.
61. Tripathi YB, Singh AV. Role of Rubia cordifolia Linn. in radiation protec-
tion. Indian J Exp Biol. 2007;45:620–5.
62. Tse WP, Che CT, Liu K, Lin ZX. Evaluation of the antiproliferative
properties of selected psoriasis-treating Chinese medicines on cultured
HaCaT cells. J Ethnopharmacol. 2006;108:133–41.
63. Vidal-Tessier AM, Delaveau P, Champion B. New anthraquinones of the
roots of Rubia cordifolia L. Ann Pharm Fr. 1987;45:261–7 (French).
64. Vidal-Tessier AM, Delaveau P, Champion B. New quinones from the roots
of Rubia cordifolia L. Ann Pharm Fr. 1986;44:117–22 (French).
65. Wakita Ki, Minami M, Venkateswarlu A, et al. Antitumor bicyclic hexapep-
tide RA-VII modulates cyclin D1 protein level. Anticancer Drugs. 2001;12:
433–9.
Rubia cordifolia L. 1559

66. Wang SX, Hua HM, Wu LJ, et al. Studies on anthraquinones from the roots
of Rubia cordifolia L. Yao Xue Xue Bao. 1992;27:743–7 (Chinese).
67. Zhu ZG, Jin H, Yu PJ, et al. Mollugin inhibits the inflammatory response in
lipopolysaccharide-stimulated RAW264.7 macrophages by blocking the
Janus kinase-signal transducers and activators of transcription signaling
pathway. Biol Pharm Bull. 2013;36:399–406.
Rumex vesicarius L.
(Polygonaceae)

(Syns.: R. roseus Desf.; Acetosa vesicaria (L.) Á. Löve)

Abstract
It is a glabrous herb, that grows as a weed along roadsides but is also extensively
cultivated, and is used as a leafy vegetable in many parts of south India, Egypt and
Saudi Arabia. Leaves juice is said to allay pain of toothache, and by its astringent
properties to check nausea, promote appetite, and allay morbid craving for
unwholesome substances. It is also considered very cooling and of use in heat of
stomach, and externally as an epithem to allay pain, especially that caused by bites
or stings of reptiles and insects. Roasted seeds are prescribed in dysentery, and as
antidote to scorpion stings. In Unani medicine, roots are used for diarrhea,
leucorrhea, jaundice, and menorrhagia; whereas seeds are used to relieve
palpitations, jaundice, dysuria, inflammation and ulcers of the stomach, intestines,
and ulcerative colitis. Aerial parts showed the presence of cardiac glycosides,
flavonoids, tannins, sterols and/or triterpenes and anthraquinones. Thirteen
phenolic compounds, ascorbic acid, a-tocopherol, and b-carotene have been
isolated from the leaves. All plant parts are rich in flavonoids, especially high
contents of quercetin. Chukkah leaves are also high in phosphorus, magnesium
and iron contents, in addition to lutein and b-carotene, the amount of which is
increased after cooking. Ethanol extracts of roots, leaves, and fruits, and methanol
extract of whole plant exhibited marked hepatoprotective activity against
CCl4-hepatotoxicity in rats, comparable to silymarin, that is attributed to their
antioxidant potential, membrane stabilizing effect, and antifibrogenic activities.
Methanol extract of aerial parts is also reported effective in NDEA-induced
hepatocellular carcinoma in rats. Ethanol and chloroform extracts of aerial parts
produced sedation, accompanied by slowing of respiration, and ataxia in ethanol
extract treated group. Ethanol extract also significantly reduced BP of normoten-
sive anesthetized rabbit, that was attenuated by pretreatment with atropine.

© Springer Nature Switzerland AG 2020 1561

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_161
1562 Rumex vesicarius L.

Keywords




Agreta Amilo bethe Amlavetasa Bladder dock
Chukkah
Chukrika




Colagria Humeez Lolika Turshah

Vernaculars: Urd.: Chukkah, Tukhme hummaz; Hin.: Chukkah, Chukra, Chuk-

rika, Lolika, Shatavedhi; San.: Amlavetasa, Chukra, Chukram, Shuta-vedhi-chukra;
Ben.: Bun palung, Chukkah; Mar.: Amlavetasa; Tam.: Cukkan kirai, Shakkan
kirai, Sukh-gukire; Tel.: Chukka kura, Kuraku, Shukku; Ara.: Hamed, Hommad,
Humaz, Humbaaz, Humeez; Eng.: Bladder dock, Ruby dock; Nep.: Amilo bethe,
Bhote palungo; Per.: Turshah; Spa.: Agreta, Agria, Colagria.
Description: It is a glabrous herb, branching from the base that grows as a weed
along roadsides but is also extensively cultivated, and is used as a leafy vegetable in
many parts of south India, Egypt and Saudi Arabia [16]. Leaves are lanceolate,
smooth, margins wavy, curled, acute, subcordate at the base; fruits reddish-brown,
having a 3-fringed leaf-like expansions each with a glandular body; seeds dark
brown, triangular and polished, often confounded with Bijband (which is believed
to derive from a species of Rumex as both belong to Polygonaceae family). Root is
embedded deep into the ground, fusiform, yellow, fleshy and highly wrinkled;
externally of a rusty-brown color, internally whitish; bark thick with a short frac-
ture; odor peculiar, taste bitter and astringent (Fig. 1).LXXXI
Actions and Uses: Leaves juice is said to allay pain of toothache, and by its
astringent properties to check nausea, promote appetite, and allay morbid craving
for unwholesome substances. It is also considered very cooling and of use in heat of
stomach, and externally as an epithem to allay pain, especially that caused by bites
or stings of reptiles and insects. Roasted seeds are prescribed in dysentery, and as

Fig. 1 Rumex vesicarius, Flowering Plant, Patrice78500, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Rumex_vesicarius_
Montana_Bermeja.JPG; https://creativecommons.org/licenses/by-sa/4.0/deed.en
Rumex vesicarius L. 1563

antidote to scorpion stings.XL,CV The plant is traditionally used as aperient, diuretic

and cooling agent, and fresh fruits are eaten against Jaundice, hepatic conditions,
constipation and indigestion [20]. In Unani medicine, aerial parts are used for the
treatment of bilious diarrhea, nausea and vomiting, thirst and to soothe bilious
excess of liver and jaundice, and as analgesic and antidote for scorpion bite. Roots
are used for diarrhea, leucorrhea, jaundice, and menorrhagia; whereas seeds
(temperament, cold 1° and dry 2°) are used to relieve palpitations (Khafqan),
jaundice, dysuria, inflammation and ulcers of the stomach, intestines, and ulcerative
colitis.L,LXXVII The plant is available in south Hijaz areas of Saudi Arabia and is
used as stomachic and diuretic by folk medicine practitioners [10].
Phytoconstituents: Phytochemical analyses of aerial parts showed the presence of
cardiac glycosides, flavonoids, tannins, sterols and/or triterpenes and anthraqui-
nones. Thirteen phenolic compounds, 8-C-glucosylapigenin, 8-C-glucosylluteolin,
6-C-hexosylquercetin, 3-O-rutinosylquercetin, 7-O-rhamnohexosyldiosmetin, 7-O-
rhamnoacetylhexosyldiosmetin, epicatechin, catechin, ferulohexoside, 6-C-gluco-
sylnaringenin, epicatechin gallate, 6-C-glucosylcatechin, and epigallocatechin
gallate, and ascorbic acid, a-tocopherol, and b-carotene [5], and flavonoids and
tannins [2] have been isolated from the leaves. El-Bakry [4] reported that roots
contain the highest total phenolics at the early vegetative state, followed by leaves
and stems; whereas all plant parts are rich in flavonoids, especially high contents of
quercetin. Chukkah leaves are also high in phosphorus, magnesium and iron con-
tents [14], in addition to lutein and b-carotene, the amount of which is increased
after cooking [3, 7]. Methanol seed extract yielded a new aliphatic ester, a steroidal
diglucoside, two bioflavonoids and stigmasterol [17]. Rai and Thakar [12] isolated
two anthraquinones from roots, identified as emodin and crysophanol. Protein
extract of the plant showed presence of cystine, glutamic acid, proline, histidine and
phenylalanine [19]. Since it is used as a vegetable in the Indian subcontinent, it has
also been widely analyzed for its nutrient constituents [9, 11, 13, 15, 18].
Pharmacology: Ethanol extracts of roots, leaves, and fruits [5], and methanol
extract of whole plant exhibited marked hepatoprotective activity against CCl4-
hepatotoxicity in rats, comparable to silymarin, that is attributed to their antioxidant
potential, membrane stabilizing effect, and antifibrogenic activities [6, 20]. Methanol
extract of aerial parts is also reported effective in NDEA-induced hepatocellular
carcinoma in rats [16]. Hydroalcohol extract and its various fractions and methanol
extract of aerial parts exhibit significant antioxidant activity [2, 8]. Methanol extract
showed maximum antioxidant activity and had the highest total phenolic, total
flavonoids and total proanthocyanidin contents [8]. Ethanolic extract inhibited
growth of P. vulgaris and B. subtilis, and extraction of seeds in sodium phosphate
citrate buffer and sodium acetate buffer showed antibacterial activity against
P. vulgaris, E. coli and S. aureus [1]. Ethanol and chloroform extracts of aerial parts
produced sedation, accompanied by slowing of respiration, and ataxia in ethanol
extract treated group. Ethanol extract caused significant spasmogenic effect on
1564 Rumex vesicarius L.

isolated guinea pig ileum, that was antagonized by atropine. Both extracts produced
negative inotropic and chronotropic effects on isolated rabbit heart; and the BP of
normotensive anesthetized rabbit was significantly reduced by the ethanolic extract,
that was attenuated by pretreatment with atropine.
Human A/Es, Allergy and Toxicity: It reduces male libido.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: This plant is mainly used as a vegetable in certain regions of India
due to its high nutrient contents and cooling property. It has limited pharmaco-
logical screening and there are no published reports on any clinical trials.

References
1. Al Akeel R, Al-Sheikh Y, Mateen A, et al. Evaluation of antibacterial
activity of crude protein extracts from seeds of six different medical plants
against standard bacterial strains. Saudi J Biol Sci. 2014;21:147–51.
2. Beddou F, Bekhechi C, Ksouri R, Chabane Sari D, Atik Bekkara F. Poten-
tial assessment of Rumex vesicarius L. as a source of natural antioxidants and
bioactive compounds. J Food Sci Technol. 2015;52:3549–60.
3. Bélanger J, Balakrishna M, Latha P, et al. Contribution of selected wild and
cultivated leafy vegetables from South India to lutein and beta-carotene
intake. Asia Pac J Clin Nutr. 2010;19:417–24.
4. El-Bakry AA, Mostafa HAM, Alam EA. Antioxidant activity of R. vesicarius
at the vegetative stage of growth. Asian J Pharm Clin Res. 2012;5:111–7.
5. El-Hawary SA, Sokkar NM, Ali ZY, Yehia MM. A profile of bioactive
compounds of Rumex vesicarius L. J Food Sci. 2011;76:C1195–202.
6. Ganaie MA, Khan TH, Siddiqui NA, Ansari MN. Ameliorative effect of
methanol extract of Rumex vesicarius on CCl4-induced liver damage in
Wistar albino rats. Pharm Biol. 2015;53:1163–7.
7. Karkal M, Navalkar BS. The phosphorus fractions in some edible plant
leaves grown in Bombay and its suburbs. J Univ Bombay (Section B).
1961–62;30:7.
8. Khan TH, Ganaie MA, Siddiqui NA, Alam A, Ansari MN. Antioxidant poten-
tial of Rumex vesicarius L.: in vitro approach. Asian Pac J Trop Biomed.
2014;4:538–44.
9. Malek RB, Ahmad K. Analysis of some foods of East Pakistan. Pak J Biol
Agr Sci. 1966;9:25.
10. Migahid AM. Flora of Saudi Arabia, Riyadh University Press, Riyadh,
Saudi Arabia, 2nd ed., 1978, p. 196.
11. Nageswara Rao C. True vitamin A value of some vegetables. J Nutr Diet.
1967;4:10.
12. Rai J, Thakar KA. Chemical investigation of Rumex vesicarius. Indian J
Chem. 1970;8:1046.
Rumex vesicarius L. 1565

13. Rao SB, Tulpule PG. Vitamin B6 content of some Indian foods and regional
diets and effect of cooking on the vitamin content. Indian J Nutr Diet.
1981;18:9.
14. Reddy NS, Bhatt G. Contents of minerals in green leafy vegetables
cultivated in soil fortified with different chemical fertilizers. Plant Foods
Hum Nutr. 2001;56:1–6.
15. Sengupta SR, Pal B. Composition of edible wild greens. J Sci Food Agr.
1970;21:215.
16. Shahat AA, Alsaid MS, Kotob SE, Ahmed HH. Significance of Rumex
vesicarius as anticancer remedy against hepatocellular carcinoma: a proposal-
based on experimental animal studies. Asian Pac J Cancer Prev. 2015;16:
4303–10.
17. Siddiqui AW, Ali M, Naquvi KJ, Husain SS. New aliphatic ester,
b-sitosterol diglucoside and vesicaria biflavones from the seeds of Rumex
vesicarius L. Acta Pol Pharm. 2015;72:965–71.
18. Singh PP. Oxalic acid content of Indian foods. Qual Plant Mater Veg. 1973;
22:335.
19. Tiwari KP, Rathore YKS. Amino acid contents in Rumex vesicarius.
Vijnana Parishad Anusandhan Patrika. 1977;20:65.
20. Tukappa NKA, Londonkar RL, Nayaka HB, Kumar CBS. Cytotoxicity and
hepatoprotective attributes of methanolic extract of Rumex vesicarius L.
Biol Res. 2015;48:19.
Ruta graveolens L.
(Rutaceae)

(Syn.: R. hortensis Mill.)

Abstract
Native to the Mediterranean region but distributed throughout the world and
cultivated as medicinal and ornamental herb. The herb was held in high esteem
by the Greeks and Romans. Aristotle mentioned that the weasel rubs itself
against this plant before fighting with serpents. Hippocrates considered it
resolvent and diuretic, while Pliny called it one of the best medicinal herbs. Rue
has been called the “Herb of Grace” because its bitterness makes it the symbol of
repentance. Among the Muslims it is highly revered, for it was blessed by the
grateful Prophet after it had cured him of an illness. In superstitious practices of
the time, the plant was hung round the neck as a charm against vertigo and
epilepsy; it was considered emblematic of good luck, and a protection against
sorcery, an herb dear to women. Dioscorides described rue injurious to pregnant
women, as it was regarded antaphrodisiac and to cause abortion in pregnant
women. Arab physicians regarded it attenuant, vesicant and stimulant, and used
it to increase mental powers, to act as a tonic and digestive, and to increase
urinary and menstrual excretions. Old European physicians considered it
antispasmodic, emmenagogue, and stimulant, and prescribed it in hysteria and
flatulent colic. In Taiwan its decoction is used for cardioprotection, and to treat
various rheumatological and skin diseases in Spain. Traditionally it is used by
the Jordanian population for its diuretic, antispasmodic, sedative and analgesic
effects, and externally as an antirheumatic, and was used in medieval Persian
medicine as a male contraceptive. It has frequently been used with success to
procure abortion, starting with pain in the back bearing down, and frequent
micturition, followed by pains and abortion about ten days after starting
administration of the herb. Roots yielded coumarin derivative, naphthoherniarin,
furanoacridone and dihydrofuroacridone alkaloids. Aerial parts contain simple
coumarins, furanocoumarins, dihydrofuranocoumarins, quinoline and quinolone

© Springer Nature Switzerland AG 2020 1567

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_162
1568 Ruta graveolens L.

alkaloids, phenolic compounds, glycosides, and ketones. Potential anticoncep-

tion activity of powdered root, aerial parts and the aqueous extract of aerial parts
was reported in rats. Reduced spermatogenesis in rats was also reported of
ethanol extract after 20-days treatment.

Keywords


Arrudão Garden rue Raute

Rue fétide
Sadapaha
Satap
Somalata



Suddab Wijnruit Zafri

Vernaculars: Urd.: Suddab; Hin.: Satab, Sudab; San.: Sadapaha, Somalata; Ben.:
Ispand, Tatli; Mal.: Aruta, Somarayen; Mar.: Sudab; Tam.: Arvada; Tel.: Arudu,
Sadapa, Sadapaka; Ara.: Zafri; Dut.: Wijnruit; Eng.: Garden rue, Herb of Grace;
Fre.: Herbe de Grâce, Péganium, Rue fétide, Rue malodorante, Rue odorante; Ger.:
Gartenraute, Raute, Starkriechende raute, Weinkraut, Weinraute; Ita.: Riccola,
Richetta, Ruta, Ruta comune; Per.: Satap, Suddab; Por.: Arruda-comum,
Arruda-das-boticas, Arruda-dos-jardins, Arrudão, Erva-das-bruxas; Spa.: Ruda
común, Ruda hortense, Ruda mayor, Ruda medicinal, Ruda vera, Ruta.
Description: Native to the Mediterranean region but distributed throughout the
world and cultivated as medicinal and ornamental herb. It has flat, grey-green
leaves and small greenish-yellow flowers; its most noticeable characteristics are its
pungent smell and bitter taste. Due to common vernacular names in regional lan-
guages, its identity is confused with Euphorbia dracunculoides. R. graveolens also
shares pharmacognostic characters with R. chalepensis. However, it can be differ-
entiated from R. chalepensis by its nonfringed petals and blunted apices of fruit
lobes; whereas petals are fringed or ciliated and apices of the fruit lobes are sharp
and projected in R. chalepensis [26] (Figs. 1 and 2).

Fig. 1 Ruta graveolens, Flowers, Kurt Stüber, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Ruta_graveolens3.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Ruta graveolens L. 1569

Fig. 2 Ruta graveolens, Foliage, Raffi Kojian, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Gardenology.org-IMG_2800_rbgs11jan.
jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Actions and Uses: The herb was held in high esteem by the Greeks and Romans.
Aristotle mentioned that the weasel rubs itself against this plant before fighting with
serpents. Hippocrates considered it resolvent and diuretic, while Pliny called it one
of the best medicinal herbs. Rue has been called the “Herb of Grace” because its
bitterness makes it the symbol of repentance. Among the Muslims it is highly
revered, for it was blessed by the grateful Prophet Mohammad (Peace Be Upon
Him) after it had cured him of an illness. In superstitious practices of the time, the
plant was hung round the neck as a charm against vertigo and epilepsy; it was
considered emblematic of good luck, and a protection against sorcery, an herb dear
to women. Dioscorides described rue injurious to pregnant women, as it was
regarded antaphrodisiac and to cause abortion in pregnant women. Arab physicians
regarded it attenuant, vesicant and stimulant, and used it to increase mental powers,
to act as a tonic and digestive, and to increase urinary and menstrual excretions. Old
European physicians considered it antispasmodic, emmenagogue, and stimulant,
and prescribed it in hysteria and flatulent colic.XL It has frequently been used with
success to procure abortion, starting with pain in the back bearing down, and
frequent micturition, followed by pains and abortion about ten days after starting
administration of the herb. Sometimes, it produces painful vomiting, always great
prostration, confusion of mind, cloudy vision, feebleness and slowness of pulse,
coldness of the extremities and twitching of the limbs.XL In Unani medicine, it
(temperament, hot 3° and dry 3°) is described as appetizer, carminative, antiflatu-
lent, deobstruent, diuretic, emmenagogue, abortifacient, and beneficial for brain and
nervous afflictions, such as paralysis, tremors, arthritis and gout. Its oil is coun-
terirritant, and is beneficial for laxity and coldness of kidneys and bladder, backache
and fever with shivering; also, for tremors and deafness.L,LXIX,LXXVII Leaves
1570 Ruta graveolens L.

decoction is very beneficial in chronic amebiasis.1 Traditionally it is used by the

Jordanian population for its diuretic, antispasmodic, sedative and analgesic effects,
and externally as an antirheumatic [29], and was used in medieval Persian medicine
as a male contraceptive [52]. NadkarniCV described it as stimulant, expectorant,
antispasmodic and anthelmintic in children, and in large doses, a narcotic poison;
and being useful in some kinds of hysteria and flatulent colic. In Taiwan its
decoction is used for cardioprotection [55], and to treat various rheumatological and
skin diseases in Spain [4]. KeysLXXIX described it as antispasmodic, carminative
and emmenagogue and a very potent herb that needs to be taken quite sparingly, it
cures many mental disorders. It improves condition of the veins and arteries and
will cure cramps. To relieve sciatica and many forms of rheumatism, a teaspoonful
of leaves infused in 500 ml of water is sufficient. Take a desertspoonful nightly
before retiring to bed, but suspend the treatment if the herb upsets the stomach (as
occasionally happens). Rue’s active principle, rutin, is frequently used in natur-
opathy, and is a respected tonic for nerves, the glands and the arteries; it also
reduces high BP.XXVI In the United States, however, individuals of Spanish and
Mexican descent in New Mexico State most commonly use rue as emmenagogue
and abortifacient, but with more probability of toxic side effects when used as an
abortifacient [9]. The plant is used in Danish folk medicine for improvement of
memory and cognition [1]. Rue is considered a national herb of Lithuania, and is
the most frequently referred herb in Lithuanian folk songs, as an attribute of young
girls, associated with virginity and maidenhood. It was common in traditional
Lithuanian weddings for only virgins to wear a rue (ruta) at their wedding, a symbol
to show their purity. Likewise, rue is prominent in the Ukrainian folklore songs and
culture. It is one of the most commonly used plants to induce abortion in Uruguay
[8], and Brazil [11], and used for fertility regulation in Peru [21]. In South Africa it
is used to treat toothache, earache, rheumatism and fever [33]. In Trinidad and
Tobago, it is used for childbirth, female infertility, and other reproductive issues
[32]. In Bredasdorp/Elim region of the southern Overberg in western Cape Province
of South Africa, it is one of the two most common traditionally used plants for
various ailments [57], and one of the most frequently used antiparasitic plants by
Shepherds and farmers in central Italy [20]. The roots were once used in Germany
to induce illegal abortions [60].
Phytoconstituents: This plant was extensively studied for phytoconstituents in the
1960s, especially in Germany. Roots yielded coumarin derivative, naphthoherniarin
[50], furanoacridone alkaloid, isogravacridonchlorine [41], and dihydrofuroacridone
alkaloid, gravacridondiol acetate [42]. Aerial parts contain simple coumarins
(pinnarin and rutacultin), furanocoumarins (bergapten, isopimpinelin, xanhotoxin,
7-hydroxycoumarin, 4-hydroxycoumarin, 7-methoxycoumarin, psoralen, and 5- and
8-methoxypsoralen), dihydrofuranocoumarins (chalepin, rutamarin), quinoline and
quinolone alkaloids (skimmianine), phenolic compounds, such as flavonoids (rutin,
rutamarin), glycosides (3′,6-disinapoylsucrose, cnidioside A, picraquassioside A,

1
Tayyab M: Personal Communication.
Ruta graveolens L. 1571

3′-sinapoyl-6-feruloylsucrose, methylcnidioside A, and methylpicraquassioside A),

and ketones [6, 22, 34, 39, 40, 53]. Essential oil of aerial parts (yield 0.74% on dry
weight basis) contains thirty-eight components with undecan-2-one (46.8%) and
nonan-2-one (18.8%) as the predominant ketones [10]. Seed oil contains lauric,
myristic, palmitic, stearic, oleic, linolic, linolenic, arachinic and begenic acids [30].
Other constituents reported in essential oil are rutin, flavonol, bergapten, xantho-
toxin, and psoralen [38].LXXIX
Pharmacology: Potential anticonception activity of powdered root, aerial parts
and the aqueous extract of aerial parts was reported in rats [16]. Aqueous extract
also interfered with preimplantation development and embryo transport [21].
A limited anti-implantation activity and inhibition of pregnancy in 50–60% of rats
was reported [43]. However, lyophilized hydroalcohol extract of aerial parts did not
cause preimplantation embryonic loss or resorptions, but caused fetal death [11].
Chalepensin was identified as the active antifertility component in chloroform
extract [31]. Aqueous extract administration to male rats for 60-days significantly
decreased weight of reproductive organs, sperm motility and density in cauda
epididymis, spermatogenesis, and suppressed sexual and aggressive behavior [29].
Reduced spermatogenesis in rats was also reported of ethanol extract after 20-days
treatment [52]. Addition of lyophilized aqueous extract to fresh semen immediately
immobilized sperms [23]; coumarins were suspected of causing the immobilizing
effect [24]. However, while hexane and ethanol fractions of aqueous extract sig-
nificantly impaired sperm vitality, coumarins were inactive. Xanthotoxin was the
only coumarin that significantly reduced sperm motility [36]. Skimmianine showed
uterine stimulant activity [37]. Oral administration of ether extract to growing rats
for 3-weeks increased body weight, total food intake and protein efficiency ratio [3].
Methanol leaf extract exhibited analgesic, antipyretic and anti-inflammatory
activities [33], and decreased levels of TC, LDL-C, atherogenic index, increased
HDL-C, and improved activities of antioxidant enzymes in hypercholesterolemic
rats [47]. The alkaloidal fraction possesses higher anti-inflammatory activity than
the polyphenol fraction and diclofenec [48], and significantly lowered TC and
LDL-C, increased HDL-C, and reduced oxidative stress of hypercholesterolemic
rabbits [46]. Skimmianine, the quinoline alkaloid, decreased mRNA of TNF-a and
IL-6, and significantly reduced PGE2 and NO, and activities of COX-2 and 5-LOX
in carrageenan-induced edema in rats [49]. Ethanol extract of flowering tops, in an
oral dose of 100 mg/kg, produced 29% inhibition of carrageenan-induced inflam-
mation in rats [35]. This activity was attributed to the presence of rutin derivatives
[59]. Ethanol extract also exerted antinociceptive effect in mice [5], and methanol
extract was effective as anti-inflammatory, and improved antioxidant status in
adjuvant-induced arthritis in rats [45]. The extract also strongly inhibited secretion
of IL-8 from H. pylori-infected gastric epithelial cells [61].
Aqueous extract impairs cell network formation without affecting cell viability;
however, the major constituent, rutin, failed to reproduce this effect [20]. Methanol
extract was cytotoxic to Dalton’s lymphoma ascites, Ehrlich ascites carcinoma and
L929 cells in culture, decreased solid tumors development and increased lifespan of
1572 Ruta graveolens L.

tumor bearing animals [44], and was also cytotoxic to colon, breast and prostate
cancer cells lines [14]. Ethanol extract significantly reduced DMBA-induced skin
tumor burden of mice, without any acute or chronic toxicity, and caused death of
skin melanoma cells through induction of apoptosis [19]. Hydroalcohol extract
protected rats against indomethacin-, and pylorus-ligation-induced gastric ulcers
[56]. However, hydroalcohol, aqueous and methanol extracts failed to inhibit
in vitro growth of E. fecalis [51]. Aqueous extract lowered BP of normotensive rats
and produced positive chronotropic and inotropic effects on isolated right atria, and
relaxed KCl preconstricted rat tail artery strips, probably by a direct effect on
vascular smooth muscle [7]. Both methanol extract and its alkaloid fraction
increased atrioventricular conduction time and functional refractory period of iso-
lated rat heart [28]. Hydroalcohol extract antagonized potassium chloride- and
carbachol-induced contractions of rat tracheal rings [2].
Clinical Studies: A homeopathic preparation of Ruta graveolens 9c transiently
improved quality of life in patients with locally-advanced solid tumors or metastases
with no significant change in anxiety/depression or effect on tumor progression [15].
Another pilot study with homeopathic preparation of Ruta graveolens 5CH signif-
icantly decreased frequency, intensity and number of sites of aromatase inhibitor
associated joint pain and/or stiffness in twenty women with early, hormone-receptor
positive breast cancer, after three months of treatment [27].
Mechanism of Action: Aqueous extract inhibits ERK1/2 phosphorylation, which
is crucial in cell network formation, preventing ERK1/2 activation and, in turn,
downregulating VEGF [18].
Human A/Es, Allergy and Toxicity: Since it contains photosensitizing furo-
coumarins (psoralens) that are photoactive chemicals, contact of skin to R. grave-
olens may produce phytophotodermatitis [4, 12, 13, 17, 25, 54]. Systemic toxicity
due to ingestion of decoction resulting in bradycardia, acute renal failure with
hyperkalemia and coagulopathy, requiring hemodialysis was also reported in a
78 years old Taiwanese patient who used it for the treatment of palpitations and
heart protection [55]. Use of the plant to induce abortion has caused multiple organ
systems failure and death in Uruguay [8].
Animal Toxicity: Oral LD50 of methanol extract in mice is reported to be greater
than 4,000 mg/kg [33].
CYP450 and Potential for Drug-Herb Interactions: Seven days treatment of
mice with aqueous extract of the aerial parts induced hepatic CYP1A and CYP2B
activities and protein levels [58], thus, it is likely to increase metabolism of those
drugs that are metabolized by CYP1A and CYP2B, if a similar induction occurs in
humans.
Ruta graveolens L. 1573

Commentary: Despite having a long historical human medicinal use, there are no
experimental clinical data available except the two brief reports of homeopathic
formulations.

References
1. Adsersen A, Gauguin B, Gudiksen L, Jäger AK. Screening of plants used in
Danish folk medicine to treat memory dysfunction for acetylcholinesterase
inhibitory activity. J Ethnopharmacol. 2006;104:418–22.
2. Águila L, Ruedlinger J, Mansilla K, et al. Relaxant effects of a hydroal-
coholic extract of Ruta graveolens on isolated rat tracheal rings. Biol Res.
2015;48:28.
3. Al-Okbi SY, El-Sayed EM, Ammar NM, et al. Effect of Ruta graveolens L.
and Euphorbia peplus L. anti-inflammatory extracts on nutritional status of
rats and the safety of their use. Indian J Exp Biol. 2002;40:45–8.
4. Arias-Santiago SA, Fernández-Pugnaire MA, Almazán-Fernández FM, et al.
Phytophotodermatitis due to Ruta graveolens prescribed for fibromyalgia.
Rheumatology (Oxford). 2009;48:1401.
5. Atta AH, Alkofahi A. Antinociceptive and anti-inflammatory effects of
some Jordanian medicinal plant extracts. J Ethnopharmacol. 1998;60:117–
24.
6. Chen CC, Huang YL, Huang FI, et al. Water-soluble glycosides from Ruta
graveolens. J Nat Prod. 2001;64:990–2.
7. Chiu KW, Fung AY. The cardiovascular effects of green beans (Phaseolus
aureus), common rue (Ruta graveolens), and kelp (Laminaria japonica) in
rats. Gen Pharmacol. 1997;29:859–62.
8. Ciganda C, Laborde A. Herbal infusions used for induced abortion.
J Toxicol Clin Toxicol. 2003;41:235–9.
9. Conway GA, Slocumb JC. Plants used as abortifacients and emmenagogues
by Spanish New Mexicans. J Ethnopharmacology. 1979;1:241–61.
10. De Feo V, De Simone F, Senatore F. Potential allelochemicals from the
essential oil of Ruta graveolens. Phytochemistry. 2002;61:573–8.
11. de Freitas TG, Augusto PM, Montanari T. Effect of Ruta graveolens L. on
pregnant mice. Contraception. 2005;71:74–7.
12. Dubakiene R, Kupriene M. Scientific problems of photosensitivity.
Medicina (Kaunas). 2006;42:619–24 (Review).
13. Eickhorst K, DeLeo V, Csaposs J. Rue the herb: Ruta graveolens—
associated phytophototoxicity. Dermatitis. 2007;18:52–5.
14. Fadlalla K, Watson A, Yehualaeshet T, et al. Ruta graveolens extract
induces DNA damage pathways and blocks Akt activation to inhibit cancer
cell proliferation and survival. Anticancer Res. 2011;31:233–41.
15. Freyer G, You B, Villet S, et al. Open-label uncontrolled pilot study to
evaluate complementary therapy with Ruta graveolens 9c in patients with
advanced cancer. Homeopathy. 2014;103:232–8.
1574 Ruta graveolens L.

16. Gandhi M, Lal R, Sankaranarayanan A, Sharma PL. Postcoital antifertility

action of Ruta graveolens in female rats and hamsters. J Ethnopharmacol.
1991;34:49–59.
17. Gawkrodger DJ, Savin JA. Phytophotodermatitis due to common rue (Ruta
graveolens). Contact Derm. 1983;9:224.
18. Gentile MT, Russo R, Pastorino O, et al. Ruta graveolens water extract
inhibits cell-cell network formation in human umbilical endothelial cells via
MEK-ERK1/2 pathway. Exp Cell Res. 2018;364:50–8.
19. Ghosh S, Sikdar S, Mukherjee A, Khuda-Bukhsh AR. Evaluation of chemo-
preventive potentials of ethanolic extract of Ruta graveolens against A375
skin melanoma cells in vitro and induced skin cancer in mice in vivo. J Integr
Med. 2015;13:34–44.
20. Guarrera PM. Traditional antihelmintic, antiparasitic and repellent uses of
plants in Central Italy. J Ethnopharmacol. 1999;68:183–92.
21. Gutiérrez-Pajares JL, Zúñiga L, Pino J. Ruta graveolens aqueous extract
retards mouse preimplantation embryo development. Reprod Toxicol. 2003;
17:667–72.
22. Hale AL, Meepagala KM, Oliva A, et al. Phytotoxins from the leaves of
Ruta graveolens. J Agric Food Chem. 2004;52:3345–9.
23. Harat ZN, Sadeghi MR, Sadeghipour HR, et al. Immobilization effect of
Ruta graveolens L. on human sperm: a new hope for male contraception.
J Ethnopharmacol. 2008;115:36–41.
24. Harat ZN, Lakpour N, Sadeghipoor HR, et al. Immobilising effect of Ruta
graveolens L. on human spermatozoa: coumarin compounds are involved.
Andrologia. 2015;47:1183–9.
25. Heskel NS, Amon RB, Storrs FJ, White CR Jr. Phytophotodermatitis due to
Ruta graveolens. Contact Dermatitis. 1983;9:278–80.
26. Kannan R, Babu UV. Identity and pharmacognosy of Ruta graveolens Linn.
Anc Sci Life. 2012;32:16–9.
27. Karp JC, Sanchez C, Guilbert P, et al. Treatment with Ruta graveolens 5CH
and Rhus toxicodendron 9CH may reduce joint pain and stiffness linked to
aromatase inhibitors in women with early breast cancer: results of a pilot
observational study. Homeopathy. 2016;105:299–308.
28. Khori V, Nayebpour M, Semnani S, et al. Prolongation of AV nodal refrac-
toriness by Ruta graveolens in isolated rat hearts. Potential role as an antiar-
rhythmic agent. Saudi Med J. 2008;29:357–63.
29. Khouri NA, El-Akawi Z. Antiandrogenic activity of Ruta graveolens L in
male albino rats with emphasis on sexual and aggressive behavior. Neuro
Endocrinol Lett. 2005;26:823–9.
30. Kikalishvili BIu, Zurabishvili DZ, Turabelidze DG, Shanidze LA, Niko-
laĭshvili MN. The fatty acid composition of Ruta graveolens seed oil and its
byological activity. Georgian Med News. 2013;224:82–4 (Russian).
31. Kong YC, Lau CP, Wat KH, et al. Antifertility principle of Ruta graveolens.
Planta Med. 1989;55:176–8.
Ruta graveolens L. 1575

32. Lans C. Ethnomedicines used in Trinidad and Tobago for reproductive

problems. J Ethnobiol Ethnomed. 2007;3:13.
33. Loonat F, Amabeoku GJ. Antinociceptive, anti-inflammatory and antipyretic
activities of the leaf methanol extract of Ruta graveolens L. (Rutaceae) in
mice and rats. Afr J Tradit Complement Altern Med. 2014;11:173–81.
34. Mancuso G, Borgonovo G, Scaglioni L, Bassoli A. Phytochemicals from
Ruta graveolens activate TAS2R bitter taste receptors and TRP channels
involved in gustation and nociception. Molecules. 2015;20:18907–22.
35. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal
plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
36. Naghibi Harat Z, Lakpour N, Sadeghipoor HR, et al. Immobilising effect
of Ruta graveolens L. on human spermatozoa: coumarin compounds are
involved. Andrologia, 2015;47:1183–9.
37. Nieschulz O, Schneider G. Pharmacological findings on alkaloids from Ruta
graveolens L. Naturwissenschaften. 1965;52:394–5 (German).
38. Novak I, Buzas G, Minker E, et al. Active constituents of Ruta graveolens.
Pharmazie. 1965;20:738.
39. Oliva A, Meepagala KM, Wedge DE, et al. Natural fungicides from Ruta
graveolens L. leaves, including a new quinolone alkaloid. J Agric Food
Chem. 2003;51:890–6.
40. Orlita A, Sidwa-Gorycka M, Paszkiewicz M, et al. Application of chitin and
chitosan as elicitors of coumarins and fluoroquinolone alkaloids in Ruta
graveolens L. (common rue). Biotechnol Appl Biochem. 2008;51:91–6.
41. Paulini H, Popp R, Schimmer O, et al. Isogravacridonchlorine: a potent and
direct acting frameshift mutagen from the roots of Ruta graveolens. Planta
Med. 1991;57:59–61.
42. Paulini H, Waibel R, Kiefer J, Schimmer O. Gravacridondiol acetate, a new
dihydrofuroacridone alkaloid from Ruta graveolens. Planta Med. 1991;57:
82–3.
43. Prakash AO, Saxena V, Shukla S, et al. Anti-implantation activity of some
indigenous plants in rats. Acta Europaea Fertilitatis. 1985;16:441–8.
44. Preethi KC, Kuttan G, Kuttan R. Antitumour activity of Ruta graveolens
extract. Asian Pac J Cancer Prev. 2006;7:439–43.
45. Ratheesh M, Shyni GL, Helen A. Methanolic extract of Ruta graveolens L.
inhibits inflammation and oxidative stress in adjuvant induced model of
arthritis in rats. Inflammopharmacology. 2009;17:100–5.
46. Ratheesh M, Helen A. Oral administration of alkaloid fraction from Ruta
graveolens inhibits oxidative stress and inflammation in hypercholes-
terolemic rabbits. Pharm Biol. 2013;51:1552–8.
47. Ratheesh M, Shyni GL, Sindhu G, Helen A. Inhibitory effect of Ruta
graveolens L. on oxidative damage, inflammation and aortic pathology in
hypercholesteromic rats. Exp Toxicol Pathol. 2011;63:285–90.
48. Ratheesh M, Shyni GL, Sindhu G, Helen A. Protective effects of isolated
polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and
chronic models of inflammation. Inflammation. 2010;33:18–24.
1576 Ruta graveolens L.

49. Ratheesh M, Sindhu G, Helen A. Anti-inflammatory effect of quinoline

alkaloid skimmianine isolated from Ruta graveolens L. Inflamm Res. 2013;
62:367–76.
50. Rózsa Z, Mester I, Reisch J, Szendrei K. Naphthoherniarin: an unusual
coumarin derivative from Ruta graveolens1. Planta Med. 1989;55:68–9.
51. Saeidinia A, Keihanian F, Delavar SF, et al. Lack of antibacterial activity
of Ruta graveolens extracts against Enterococcus fecalis. Pak J Pharm Sci.
2016;29(4 Suppl):1371–4.
52. Sailani MR, Moeini H. Effect of Ruta graveolens and Cannabis sativa
alcoholic extract on spermatogenesis in the adult Wistar male rats. Indian J
Urol. 2007;23:257–60.
53. Salib JY, El-Toumy SA, Hassan EM, et al. New quinoline alkaloid
from Ruta graveolens aerial parts and evaluation of the antifertility activity.
Nat Prod Res. 2014;28:1335–42.
54. Schempp CM, Schöpf E, Simon JC. Bullous phototoxic contact dermatitis
caused by Ruta graveolens L. (garden rue), Rutaceae. Case report and
review of literature. Hautarzt 1999;50:432–34 (German).
55. Seak CJ, Lin CC. Ruta graveolens intoxication. Clin Toxicol (Phila).
2007;45:173–5.
56. Tarique M, Siddiqui HH, Khushtar M, Rahman MA. Protective effect of
hydroalcoholic extract of Ruta graveolens Linn. leaves on indomethacin
and pylorus ligation-induced gastric ulcer in rats. J Ayurveda Integr Med.
2016;7:38–43.
57. Thring TS, Weitz FM. Medicinal plant use in the Bredasdorp/Elim region of
the Southern Overberg in the Western Cape Province of South Africa.
J Ethnopharmacol. 2006;103:261–75.
58. Ueng YF, Chen CC, Huang YL, et al. Effects of aqueous extract of Ruta
graveolens and its ingredients on cytochrome P450, uridine diphosphate
(UDP)-glucuronosyltransferase, and reduced nicotinamide adenine dinu-
cleotide (phosphate) (NAD(P)H)-quinone oxidoreductase in mice. J Food
Drug Anal. 2015;23:516–28.
59. Van Cauwenberge H, Franchimont P. Anti-inflammatory activity of Z 6000
(trihydroxyethylrutoside) in rats. Arch Int Pharmacodyn Ther. 1977;170:74.
60. Wehr K. Criminal abortion using ruta roots (Ruta graveolens L.). Beitr
Gerichtl Med. 1974;32:126–31 (German, Eng. Abstr).
61. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and
cytoprotective effects of selected Pakistani medicinal plants in Helicobacter
pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:403–10.
Salix caprea L.
(Salicaceae)

(Syns.: S. coaetanea Flod.; S. lanata Vill.; S. sphacelata Sm.; S. tomentosa Ser.)

Abstract
A species of willow, commonly known as Goat Willow, is native to Europe and
Asia. In Italy, it is grown as an ornamental plant. In China and Persia, the tree was
considered a symbol of immortality. Ancient Greek and Roman writers were
aware of the plant as Herodotus mentioned it, and Theophrastus mentioned two
kinds, and Dioscorides described its astringent properties; the ancients considered
it to be very cooling, and to cause sterility in women. Following Dioscorides,
Avicenna mentioned it under the name khiláf, but separately mentioned the use of
flowers under the name of Behramaj. Muslim physicians mention about the juice
or gum which Haji Zein stated exudes from the leaves. Persian settlers in India
introduced flowers (Bidmishk) and the distilled water (Ma-el- khiláf). Raughan-i-
bid is an oil prepared by boiling two parts of distilled water (Ma-el- khiláf, Arq
Bedmushk) with one of sesamum oil until the water has all evaporated; it is a
favorite remedy for cough. Decoction of the bark is astringent. Unani physicians
use only distilled water (Arq Bedmushk) for medicinal purpose. In Italy its
bud extracts have lately been used for the treatment of oxidative stress related
disorders. Phenolic extractives, vanillic acid, 3-p-coumaryl alcohol, coniferyl
alcohol, sinapylaldehyde, dihydrokaempferol, catechin, naringenin, gallocate-
chin, dihydromyrcetin and taxifolin were isolated from stemwood and knots.
Nineteen constituents were identified in the aromatic hydrodistillate of flowers;
hexahydrofarnesylacetone, 2-butyl-octanol, and 2-hexyl-1-octanol being the
major components. Ethanol flower extract exhibits significant antioxidant and
hepatoprotective properties, and is an effective chemopreventive agent against
phorbol ester-induced tumor promotion. Bud extracts nonselectively block
voltage-gated Ca2+ channels, known to be potentiated during oxidative stress, and
markedly decrease Ca2+-dependent catecholamines secretion in chromaffin cells.
Hydrodistillate of flowers exhibited significant antioxidant and anti-inflammatory
effects.

© Springer Nature Switzerland AG 2020 1577

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_163
1578 Salix caprea L.

Keywords






Abhrapuspa Baid Bedmushk Boswilg Goat willow Huáng huā liǔ Keçi





söğüdü Ṣafṣāf al miʿzā Sauce cabruno Solweide

Vernaculars: Urd.: Bedmushk, Gurba baid; Hin.: Baid, Bedmushk, Laila safeda
bhainsa; San.: Abhrapuspa, Namraka, Vaanira, Vañjula, Vaanjulaa, Vitika; Ben.:
Pani-jurna; Mar.: Bedmusk; Ara.: Ma el khilaf, Khilaf-ul-balakhi, Ṣafṣāf al miʿzā;
Chi.: 黄花柳, Huáng huā liǔ; Cze.: Vrba jíva; Dan.: Selje-pil; Dut.: Boswilg,
Waterwilg; Eng.: Goat’s sallow, Goat willow, Pussy willow; Fre.: Bonnade,
Boursault, Civette, Gévrine, Marsaule, Marsault, Osier cendré, Petit marceau, Saule
cendré, Saule des chèvres, Saule gris, Saule male, Saule marsault, Vorde; Ger.:
Palmweide, Sahle, Salweide, Solweide; Gre.: Gidoïtiá; Hun.: Kecskefűz; Ita.:
Salcio caprino, Salcio delle capre, Salica, Salicone; Jap.: Bakko yanagi, Ezo no
bakko yanagi, Yama neko yanagi; Nor.: Selje; Per.: Behramaj and Bidmishk
(flowers), Bid-i-balkhi, Khiláf, Mushk e baid; Pol.: Wierzba iwa; Por.: Salce
blanco, Salcie capreasca, Salgueiro-cabuxo, Sauce cabruna, Sauce cabruno, Zar-
gatillo; Rus.: Bredina, Iva koz’ja, Rakita; Spa.: Salce cabruno, Sauce cabruno,
Zargatillo; Swe.: Sälg; Tag.: Libás, Malatiki, Tiáun; Tur.: Keçi söğüdü, Sorgun.
Description: Native to Europe and Asia, is a species of willow, commonly known
as Goat Willow. In Italy, it is grown as an ornamental plant [3]. A deciduous
shrub or small tree, reaching a height of 8–10 m, rarely to 13 m; leaves long,
pointed, entire, 3–12 cm long and 2–8 cm wide, broader than most other willows.
Flowers are soft silky, and silvery 3–7 cm long. Catkins, a flower cluster, are bright
yellow, fragrant, produced in early spring before new leaves appear; male and
female catkins are on different plants. Male catkins mature yellow, while the female
catkins mature pale-green. Fruits are white small capsule 5–10 mm long, contain-
ing numerous minute seeds (about 0.2 mm) embedded in fine, cottony hairs. Bark
purplish-brown externally, tough, fibrous, and white internally (Fig. 1).XL,LXXXI
Actions and Uses: In China and Persia, the tree was considered a symbol of
immortality. Ancient Greek and Roman writers were aware of the plant as Herodotus
mentioned it, and Theophrastus mentioned two kinds, and Dioscorides described its
astringent properties; the ancients considered it to be very cooling, and to cause
sterility in women.XL Following Dioscorides, Avicenna mentioned it under the name
khiláf, but separately mentioned the use of flowers under the name of Behramaj.
Muslim physicians mention about the juice or gum which Haji Zein stated exudes
from the leaves. Persian settlers in India introduced flowers (Bidmishk) and the
distilled water (Ma-el- khiláf, Arq Bedmushk). Raughan-i-bid is an oil prepared by
boiling two parts of distilled water (Ma-el- khiláf, Arq Bedmushk) with one of
sesamum oil until the water has all evaporated; it is a favorite remedy for cough.XL
Unani physicians of India consider it (temperament, leaves: cold 1° and dry 1°;
flowers: cold 1° and moist 2°) cardiorefrigerant, cardiotonic, brain tonic, beneficial
for all forms of palpitations (Khafqan), analgesic for headache, cooling, diuretic,
laxative, aphrodisiac for hot temperament individuals, and antipyretic;LXXVII tonic
Salix caprea L. 1579

Fig. 1 Salix caprea, Male Catkins, Kurt Stüber, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Salix_caprea8.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en

and febrifuge, used in ague and during convalescence from malarial fever and
cachexia.LXXXI Decoction of the bark is astringent.CV Unani physicians use only
distilled water (Arq Bedmushk) for medicinal purpose.LXXVII In Italy its bud extracts
have lately been used for the treatment of oxidative stress related disorders [3].
Phytoconstituents: Phenolic extractives, vanillic acid, 3-p-coumaryl alcohol, con-
iferyl alcohol, sinapylaldehyde, dihydrokaempferol, catechin, naringenin, gallocat-
echin, dihydromyrcetin and taxifolin were isolated from stemwood and knots [4].
Tantry et al. [6] reported isolation of a triterpene, 1a,3b,25-trihydroxy-9(11)-
ene-16-one-9,10-seco-9,19-cyclolanostane and fatty alcohols. Nineteen constituents
representing (99.2%) were identified in the aromatic hydrodistillate of flowers
(Arq Bedmushk); hexahydrofarnesylacetone (38.3%), 2-butyl-octanol (24.0%), and
2-hexyl-1-octanol (8.6%) being the major components [1].
Pharmacology: Ethanol flower extract contains large amounts of polyphenols and
exhibits significant antioxidant and hepatoprotective properties [2], and is an
effective chemopreventive agent against phorbol ester-induced tumor promotion
[5]. Bud extracts also nonselectively block voltage-gated Ca2+ channels, known to
be potentiated during oxidative stress, and markedly decrease Ca2+-dependent
catecholamines secretion in chromaffin cells [3]. Hydrodistillate of flowers also
exhibited significant antioxidant and anti-inflammatory effects [1].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
1580 Salix caprea L.

Commentary: The hydrodistillate of flowers is commonly used in Unani medicine

as an adjunct to enhance effectiveness of other drugs, especially for heart problems.
However, there are no systematic objective experimental cilical data available about
its effectiveness. It has also not been subjected sufficiently for pharmacological
screening. A drug that has been used for thousands of years deserves a better scrutiny.

References
1. Ahmed A, Akbar S, Shah WA. Chemical composition and pharmacological
potential of aromatic water from Salix caprea inflorescence. Chin J Integr
Med. 2017. https://doi.org/10.1007/s11655-017-2781-5 (Epub ahead of print).
2. Alam MS, Kaur G, Jabbar Z, Javed K, Athar M. Evaluation of antioxidant
activity of Salix caprea flowers. Phytother Res. 2006;20:479–83.
3. Calorio C, Donno D, Franchino C, Carabelli V, Marcantoni A. Bud extracts
from Salix caprea L. inhibit voltage gated calcium channels and catecholami-
nes secretion in mouse chromaffin cells. Phytomedicine. 2017;36:168–75.
4. Pohjamo SP, Hemming JE, Willför SM, Reunanen MH, Holmbom BR.
Phenolic extractives in Salix caprea wood and knots. Phytochemistry. 2003;
63:165–9.
5. Sultana S, Saleem M. Salix caprea inhibits skin carcinogenesis in murine
skin: inhibition of oxidative stress, ornithine decarboxylase activity and DNA
synthesis. J Ethnopharmacol. 2004;91:267–76.
6. Tantry MA, Shah S, Dar MY, et al. 9,10-seco-9,19-cyclolanostane triterpene
from Salix caprea L. (goat willow). Nat Prod Res. 2013;27:171–5.
Salvia officinalis L./Salvia haematodes Wall.
(Lamiaceae/Labiatae)

(Syns.: S. chromatica Hoffmanns.; S. clusii Vilm.; S. cretica L.; S. crispa Ten.)

Abstract
The plant is a native of Mediterranean region, but naturalized in India and many
other countries. Both Salvia haematodes and S. officinalis have been described by
various authors interchangeably, as they appear similar in their actions profile.
S. officinalis is described to have stimulant, tonic, antiemetic, carminative and
astringent properties; and used in fevers, dyspepsia, flatulence, and to check
sweating and colliquative sweats of phthisis. Whereas, S. haematodes is tonic,
astringent and aphrodisiac, and is one of the ingredients in compound decoctions
and aphrodisiac confections; and is mainly used for seminal debility, chlorosis,
anemia and amenorrhea. Its name is derived from Latin, meaning ‘to heal.’ In
Mediterranean countries, S. officinalis is used as a spice and in food industry, and
as a traditional medicine to treat several infectious diseases. In southern Brazil it
is used as a food condiment, and as tea-beverage for the treatment of several
disorders. It is one of the plants used by Jordanian patients for self-treatment of
diabetes, based on friends’ recommendations, and is credited with memory
improving properties in old European Medical Herbals. While it has been used as
a general tonic and to treat sweating and menopausal hot flushes, and associated
menopausal symptoms in traditional Swiss medicine, traditional medical uses of
aqueous infusion of dried leaves (sage tea) in Austria include symptomatic
treatment of mild dyspeptic complaints, inflammations in the mouth and the
throat, and relief of excessive sweating and minor skin inflammations. Major
phytoconstituents in aerial parts of S. officinalis are phenolic glycosides, phenolic

Salvia haematodes Wall. is a synonym of Salvia pratensis subsp. haematodes (L.) Arcang.
However, Nadkarni (1954)CV has described S. haematodes as Lal Bahmana or Behman surkh. All
descriptions here are for S. officinalis, unless stated otherwise.

© Springer Nature Switzerland AG 2020 1581

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_164
1582 Salvia officinalis L./Salvia haematodes Wall.

diterpenes, terpenoids, immunomodulatory polysaccharides, flavones, and arabino-

galactan. Sage tea in place of drinking water for 14-days lowered FBG in normal
mice but did not affect glucose clearance in response to i.p. glucose tolerance test.
In a parallel group, placebo-controlled trial of patients with mild to moderate
Alzheimer’s disease, S. officinalis extract in a dose of 60 drops/day for 4-months,
produced a significant improvement in cognitive functions compared to placebo.
In a multicenter clinical trial, treatment of menopausal Swiss women with
once-daily tablet of fresh sage leaves, completely decreased intensity and
frequency of hot flashes after 8-weeks.

Keywords
Behman surkh

Chá-da-grécia

Danshen Echte salie
Garden sage






Gartensalbei Herbe sacrée Lal behaman Madreselva Salva-brava

Vernaculars: Urd.: Behman surkh; Hin.: Lala bahamana, Salbia; Ben.: Lal beha-
man; Mar.: Lala bahamana; Tam.: Sefa-kas; Ara.: Behman ahmar; Chi.: Danshen,
Sā ěr wéi yà; Dut.: Echte salie; Eng.: Blood-veined sage, Common sage, Dalmatian
sage, Garden sage; Fre.: Grande sauge, Herbe sacrée, Sauge commune, Sauge
officinale, Thé de France, Thé de la Grèce, Thé sacré; Ger.: Echter salbei, Garten-
salbei, Salbei; Gre.: Alisfakia, Faskomilo; Ita.: Salvia domestica, Salvia officinale;
Per.: Bahman-e-surkh; Por.: Chá-da-éuropa, Chá-da-frança, Chá-da-grécia, Erva-
sacra, Grande-salva, Salva-brava, Salva-das-boticas, Salva-de-catalunha, Salva-mansa,
Salva-menor, Salva-rubra, Salvetta; Spa.: Celima, Hierba del mudo, Madreselva,
Mermasangre, Salima fina, Salvia blanca, Salvia de moncayo, Salvia fina, Salvia
hortense menor, Té indigena, Verdecillo.
Description: The plant is a native of Mediterranean region, but naturalized in India
and many other countries. A tuberous root, consisting of a central portion of about
5 cm in diameter, from which spring 5 or 6 tapering tubers from 3 to 5 cm long, and
from 1.25 to 2.5 cm in diameter at the base. At the top of the central tuber is a scaly
crown about 2.5 cm in diameter. External surface of the root is of a reddish-brown
color, scabrous and marked by numerous circular and longitudinal wrinkles. Inter-
nally, there is a dull red woody central portion, surrounded by a thick, yellowish-white
horny layer, which near the crown becomes spongy. Commercially available root is
sliced and with the central woody part removed (Figs. 1, 2, 3 and 4).XL
Actions and Uses: Both Salvia haematodes and S. officinalis have been described
by various authors interchangeably, as they appear similar in their actions profile.
However, Khory and KatrakLXXXI described them separately as Blood-veined sage
and Garden sage, respectively. S. officinalis is described to have stimulant, tonic,
antiemetic, carminative and astringent properties; and used in fevers, dyspepsia,
flatulence, and to check sweating and colliquative sweats of phthisis. Whereas, red
bahman (S. haematodes) is tonic, astringent and aphrodisiac, and is one of the
Salvia officinalis L./Salvia haematodes Wall. 1583

Fig. 1 Salvia officinalis, Sage Illustration, Walther Otto Müller (1833–1887), Köhler’s Medizinal-
Pflanzen, WikimediaCommons, https://commons.wikimedia.org/wiki/File:Salvia_officinalis_-_K%
C3%B6hler%E2%80%93s_Medizinal-Pflanzen-126.jpg

Fig. 2 Salvia officinalis, Leaves, Jonathunder, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Growing_leaves_of_garden_sage_(Salvia_officinalis).jpg
1584 Salvia officinalis L./Salvia haematodes Wall.

Fig. 3 Salvia officinalis, Sage Flowers, Kurt Stüber, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Salvia_officinalis0.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 4 Salvia officinalis, Dried Sage Leaves as sold in the U.S., Prof. Akbar, Original
Salvia officinalis L./Salvia haematodes Wall. 1585

ingredients in compound decoctions and aphrodisiac confections; and is mainly used

for seminal debility, chlorosis, anemia and amenorrhea.LXXXI Its name is derived
from Latin, meaning ‘to heal.’ In Unani medicine, the rhizomes of S. haematodes
(temperament, hot 3° and dry 2°) are cardiac-refrigerant, cooling, carminative,
lithotriptic, very aphrodisiac, increase semen production, fattening, and beneficial for
gout.L,LXXVII Powdered root alone or with other drugs is used as aphrodisiac and to
increase semen production.LXXVII In Urdu translated version of Ibn al-Baitar’s book
Al-Jame-al-Mufradat al-Advia wal Aghzia it is described under the Greek name
Al-Asfafis and Arabic name Lisan al-Ibl with properties that do not match the
description by other authors.LXIX In Mediterranean countries, it is used as a spice and
in food industry, and as a traditional medicine to treat several infectious diseases [13].
In southern Brazil it is used as a food condiment, and as tea-beverage for the treat-
ment of several disorders [34]. It is one of the plants used by Jordanian patients for
self-treatment of diabetes, based on friends’ recommendations [83], and is credited
with memory improving properties in old European reference books (Medical Her-
bals) [46, 86, 87]. While it has been used as a general tonic and to treat sweating and
menopausal hot flushes, and associated menopausal symptoms in traditional Swiss
medicine [12], traditional medical uses of aqueous infusion of dried leaves (sage tea)
in Austria include symptomatic treatment of mild dyspeptic complaints, inflamma-
tions in the mouth and the throat, and relief of excessive sweating and minor skin
inflammations [114]. Drinking or gargling with sage infusion is thought to soothe
sore-throat, tonsillitis, and inflamed red gums [27]. In central Italy, decoction of
leaves drunk after meals is used to soothe headache [60]. S. officinale is approved for
GI disorders use in Europe since Mar. 2009 by the HMPC of the European Medicines
Agency [30].
Salvia miltiorrhiza Bge. or Chinese sage is known as Danshen in China. It is
bitter in taste with a slightly cold property, and is nontoxic. It is blood stimulant,
stasis deobstruent, sedative, tranquilizing, anticarbuncular and analgesic, and is
recommended for the treatment of coronary and cerebrovascular diseases, angina
pectoris, palpitation, irregular menstruation, amenorrhea, dysmenorrhea, injuries
due to impact, fractures, contusions and strains, insomnia, carbuncle and furuncles
[45],XVIII hepatitis, hepatocirrhosis, and chronic renal failure [45].
Phytoconstituents: Major phytoconstituents in aerial parts are phenolic glycosides
[68, 115, 116], phenolic diterpenes (carnosic acid, carnosol, epirosmanol, rosmanol,
12-methoxycarnosic acid, sageone, and carnosaldehyde) [32], terpenoids [75],
immunomodulatory polysaccharides [15, 16], flavones [49], and arabinogalactan
[17]. From methanol extract of aerial parts phenolic diterpenes—sageone, 12-methyl-
carnosol, 7b-methoxyrosmanol, 7a-methoxyrosmanol, isorosmanol, carnosol, and
epirosmanol were isolated [101]. Aerial parts of sage collected during the month of
May are richest in total flavonoids, show the best antioxidant and highest antimi-
crobial activity [35]. Antioxidant activity of sage extracts is dependent on the solvent
used for extraction [57]; highest concentration of phenolic compounds is found in
1586 Salvia officinalis L./Salvia haematodes Wall.

aqueous decoction, followed by methanol/water extract and aqueous infusion [69].

Diterpenes: carnosic acid, carnosol and rosmanol, and the hydroxycinnamic acid and
caffeic acid were identified as the antioxidant components of aqueous infusion [71];
whereas, carnosol, rosmanol, epirosmanol, isorosmanol, galdosol, and carnosic acid
were reported remarkably strong antioxidant components [74]. Antioxidant potential
of sage tea are highly dependent on the presence of rosmarinic acid [118], and
commercially available products show extensive variation, up to 20-fold differences
for rosmarinic acid [114]. Diterpene quinones: royleanone, horminone, and
7-O-acetylhorminone were identified in the petroleum ether extract of roots from
Slovakia [70].
Sage EO is used in food industry and in pharmaceutical products [5, 10, 25, 99].
There have been numerous reports showing variations in the composition of EO
that may have significant implications. Essential oils from stems and leaves contain
50 compounds with a-thujone being the major compound, about 40 of those
compounds are also present in EO from flowers of sage from Portugal [102],
whereas in EOs obtained from sage growing in various European countries, prin-
cipal components were 1,8-cineole, camphor, a-thujone, b-thujone, borneol, and
viridiflorol [91], and from Italy main components were a-thujone, camphor, bor-
neol, c-muurolene and sclareol [99]. Essential oils of 25 populations of sage from
nine Balkan countries showed a total of 80 compounds: b-pinene, 1,8-cineole,
cis-thujone, trans-thujone, camphor, borneol, trans-caryophyllene, a-humulene,
viridiflorol, and manool, being 42.60–85.70% of total components [23]. Essential
oil of sage growing in Tunisia showed 57 compounds with a-thujone, viridiflorol,
1,8-cineole, camphor, manool, b-caryophyllene, a-humulene and b-thujone being
the major components [10], and EO extracted from aerial parts of a cultivated sage
in Tunisia revealed 68 constituents, with major constituents being 1,8-cineole
(33.27%), b-thujone (18.40%), a-thujone (13.45%), and borneol (7.39%); the oil
exhibited higher antibacterial activity against C. albicans [40]. Another study on
Tunisian EO reported 49 components, with camphor (25.14%), a-thujone
(18.83%), 1,8-cineole (14.14%), viridiflorol (7.98%), b-thujone (4.46%) and
b-caryophyllene (3.30%) as the major constituents [53]. Essential oils obtained
from fresh and dried sage cultivated in Romania reportedly showed only 12
compounds, with a-thujone being the major compound, followed by camphor and
viridiflorol [81]. Essential oil obtained from samples, growing wild in Atlas
Mountains region of Ourika in Morocco, by hydrodistillation (HD) and microwave
distillation (MW) differed. Thirty-six compounds accounted for 97.32% of the total
oil composition of MW-extracted oil, while 33 compounds were detected in HD oil
representing 98.67%. Major components included trans-thujone (14.10 and
29.84%), 1,8-cineole (5.10 and 16.82%), camphor (4.99 and 9.14%), viridiflorol
(16.42 and 9.92%), b-caryophyllene (19.83 and 5.20%) and a-humulene (13.54 and
4.02%) [13]. Major constituents of EOs from four S. officinalis cultivated in Murcia
Province of Spain were a-thujone (22.8–41.7%), camphor (10.7–19.8%),
1,8-cineole (4.7–15.6%), and b-thujone (6.1–15.6%). The EOs inhibited growth of
Salvia officinalis L./Salvia haematodes Wall. 1587

E. coli, S. aureus, and C. albicans [22]. Five major chemotypes based on volatile
constituents (EOs) from sage grown in Mexico, commercial oils from California
and Albania have been identified; the most common being a-thujone > camphor >
1,8-cineole chemotype, a-humulene-rich chemotype, a b-thujone-rich chemotype,
a 1,8-cineole/camphor chemotype, and a sclareol/a-thujone chemotype. Major
constituents of all three samples included a-thujone (17.2–27.4%), 1,8-cineole
(11.9–26.9%), and camphor (12.8–21.4%) [21].
Pharmacology: Sage tea in place of drinking water for 14-days lowered FBG in
normal mice but did not affect glucose clearance in response to i.p. glucose toler-
ance test [62]. Aqueous-ethanol extract significantly reduced blood glucose of
fasting normal mice after i.p. injection, and significantly diminished hyperglycemia
in mildly diabetic mice [3]. Intraperitoneal injection of EO, however, did not
change serum glucose in normal or diabetic rats, but methanol extract significantly
decreased serum glucose in diabetic rats without effecting insulin release from
pancreas but not in healthy rats [29]. Methanol leaf extract decreased blood glucose,
and plasma insulin, improved insulin-sensitivity, comparable to rosiglitazone, and
increased plasma levels of anti-inflammatory cytokines IL-2, IL-4 and IL-10 in
diet-induced obese mice [11]. Methanol leaf extract also significantly inhibited
increase in serum TG in olive oil-loaded mice and in vitro inhibited pancreatic
lipase. Carnosic acid was identified as the active constituent for triglyceride-
lowering activity and reducing weight gain [77].
Ethanol extract potentiated memory retention in rats and interacted with mus-
carinic and nicotinic cholinergic systems involved in memory retention process
[28]. Ethanolic tincture as well as n-hexane, chloroform, and aqueous-ethanol
subextracts show no in vitro selective 5-HT reuptake or AChE inhibition activity.
The EO from Turkey, though, very highly inhibited in vitro activities of AChE and
BChE; single components of the oil were not as active as the oil [82]; however,
7a-methoxyrosmanol and isorosmanol were reported to inhibit AChE activity by
>50% [101], and 1,8-cineole was reported to be the most potent single AChE
inhibitor [104]. Hydroalcohol extract may also decrease morphine-induced toler-
ance and dependence [39]. Among herbs, sage exhibits one of the strongest
antioxidant activities [103]. Ethanol extract of S. haematodes roots enhanced
anabolic activity, testicular function and sexual behavioral performance in rats [6].
An extract reportedly showed anti-inflammatory activity against LPS-induced
inflammatory response in rats, and increased activities of antioxidant enzymes [58].
High amounts of phenolic diterpenes in sage leaves, such as carnosol and carnosic
acid display in vitro antioxidant and anti-inflammatory effects [96]. n-Hexane and
chloroform leaf extracts also exhibit anti-inflammatory activity on topical application
[7]. Borneol, the active component of EO, fed to ICR mice for 5-days before induction
of TNBSA-colitis significantly suppressed proinflammatory cytokines mRNA
expression [48]. The volatile compounds are more effective anti-inflammatory than
rosmarinic acid, 1,8-cineole, borneol, and camphor, and a-/b-thujone chiefly con-
tributed to the anti-inflammatory activity of sage infusion in human gingival fibrob-
lasts [27]. Hydroalcohol extract protected against ethanol- and acetic acid-induced
1588 Salvia officinalis L./Salvia haematodes Wall.

gastric lesions in rats, and inhibited H+, K+-ATPase activity; carnosol was identified
as a possible active constituent [72]. Aqueous-alcohol extract (i.v.) caused moderate
but prolonged fall in BP of cats, and inhibited to various degrees ACh-, histamine-,
5-HT- and BaCl2-induced isolated smooth-muscle contractions [112]. Sage EO did
not show any immunomodulatory activity in mice [18].
Decoction (1:1) of the herb showed inhibitory effects against S. aureus, E. coli,
P. vulgaris, Sh. flexneri and S. typhi,XVIII and the aqueous extract inhibited some tinea
fungi to various degree and inhibited growth of V. cholera [66]. Ethanol extract
demonstrated antibacterial activity against B. cereus, due to the presence of methyl
carnosate [20]. Acetone and ethyl acetate extracts act synergistically with amoxicillin,
while ethyl acetate extract also showed synergism with chloramphenicol, against
clinical isolates of S. aureus, B. subtilis, E. cloacae, K. pneumoniae, and P. mirabilis,
and decreased MIC values of antibiotics by 2- to 10-fold [110], a crude extract also
reduced MIC of aminoglycosides in vancomycin-resistant enterococci; the diter-
penoids, carnosol and carnosic acid, were synergistic with gentamicin [42]. Aqueous
extract showed high antiviral activity against HSV-1, HSV-2 and acyclovir-resistant
strain of HSV-1 [78], strongly inhibited HIV-1 replication [36], and a 20% ethanol
extract of a garden variety of sage was highly virucidal against HSV-1 and HSV-2
[105]. Essential oil from aerial parts demonstrated significant antibacterial activity
against S. mutans and A. viscosus [51], strains of C. albicans [109], against most
bacteria involved in food poisoning [67, 98, 108], A. ochraceus [8], enteric infections:
C. jejuni and H. pylori [24], E. coli, S. typhi, S. enteritidis, and Sh. sonei [14], and
against urinary pathogens: 100% efficiency against Klebsiella and Enterobacter
species, 96% against E. coli, 83% against P. mirabilis, and 75% against M. morganii
[85]. The EO also inhibited biofilm forming ability of clinical isolates of P. aerugi-
nosa [111].
Pretreatment of rats with EO protects against azathioprine-hepatotoxicity [4],
and the EO was not toxic to freshly isolated rat hepatocytes at concentrations below
200 nl/ml, but damaged cells at 2,000 nl/ml, and did not protect against t-BHP
toxicity [63]. Aqueous sage extract rendered rats’ hepatocytes resistant against
oxidative stress [43], significantly improved antioxidant enzymes [1, 19], protected
against oxidative damage to cells [41, 65, 95], LPO in isolated rat brain and liver
[79], and stimulated DNA repair [94]. Water infusion of sage (tea) to mice and rats
in drinking water for 14-days did not affect food consumption or body weight, but
caused a significant increase of liver GST activity (24%) in rats [61]; and signifi-
cantly increased CCl4-induced liver injury in mice, which was identified, due in
part, to increase in CYP2E1 activity, which is responsible for the bioactivation of
CCl4 [64]. Sage tea drinking exhibited a preventive effect on AOM-induced col-
orectal cancer, as it prevented initiation phases of colon carcinogenesis [84].
Aqueous extract of aerial parts also induced apoptosis in human colon carcinoma-
derived cell lines [117]. Ethanol extracts of leaves and roots were more toxic to
HepG2 cells than to normal human liver cells [47]. Ethanol extract of aerial parts
exhibited in vitro and ex vivo antiangiogenic activity [52], and the EO was cytotoxic
to squamous human cell carcinoma cell line of oral cavity [107].
Salvia officinalis L./Salvia haematodes Wall. 1589

Clinical Studies: In a parallel group, placebo-controlled trial of Iranian patients

with mild to moderate Alzheimer’s disease, S. officinalis extract in a dose of 60
drops/day for 4-months, produced a significant improvement in cognitive functions
compared to placebo [2]. Optimal significant enhancement of secondary cognitive
performance at 333 mg dose was observed in a double-blind, balanced, five-period
crossover RCT of healthy older Australian adults (>65 years of age), given single
doses (167, 333, 666 and 1,332 mg) of a standardized extract of S. officinalis [106].
Even sage EO aroma treatment significantly improved quality of memory and mood
in U.K. patients [76]. In a double-blind, placebo-controlled, crossover study, 30
healthy individuals from U.K. on three separate days, 7-days apart, received dif-
ferent treatment in counterbalanced order (placebo, 300, 600 mg dried sage leaf);
on each day mood was assessed pre-dose and at 1 and 4 h post-dose. This single
dose treatment improved mood and cognitive performance, reducing anxiety and
increasing alertness, compared to placebo [50].
A nonrandomized crossover pilot study of six healthy Portuguese female vol-
unteers (aged 40–50 years), showed no effects on plasma glucose after four-weeks
of sage tea treatment, but lowered plasma TC and LDL-C and increased plasma
HDL-C during and two-weeks after treatment [100]. Blood TC, LDL-C and
VLDL-C, TGs were also lowered, and HDL-C increased in 67 Iranian hyperlipi-
demic patients taking sage leaf extract (500 mg every 8 h for 2-months) in a
double-blind RCT [54], and lowered FBG, HbA1c, TC, TG and LDL-C, and
increased HDL-C of hyperlipidemic type-2 diabetic patients after 3-months of leaf
extract treatment [55], and addition of the extract to glyburide, metformin and
atorvastatin treatment of dyslipidemic type-2 DM Iranian patients further improved
glycemic control and lipid profile [56].
In a multicenter clinical trial, treatment of 71 menopausal Swiss women suf-
fering from hot flashes with once-daily tablet of fresh sage leaves for 8-weeks,
significantly decreased intensity and frequency of hot flashes within 4-weeks and
100% within 8-weeks [12]. A 150 mg of sage extract taken orally three-times daily
also significantly diminished hot flashes in prostate cancer Belgian patients treated
with androgen deprivation therapy [113]. In an Italian clinical trial called ‘SOPHY’
(Study on pH and Hygiene), use of S. officinalis extract for personal hygiene by
adolescents showed a positive clinical effect by reducing vaginal pH, improvement
of symptoms and quality of sexual activity [37]. In a randomized, double-blind,
parallel group phase II/III study of 286 German patients with acute viral pharyn-
gitis, treatment with a 15% spray containing S. officinalis fluid extract for 3-days
significantly reduced throat pain intensity score [44].
Mechanism(s) of Action: Sage leaves have PPARc agonistic, pancreatic lipase
and lipid absorption inhibitory, antioxidant, LPO inhibitory and anti-inflammatory
effects [54]. Phenolic diterpenes, carnosic acid and carnosol potently inhibit human
5-LOX, activate PPARc, and inhibit formation of proinflammatory leukotrienes
from human PMNL [89]. Cognitive decline and dementia associated with natural
aging involve downregulation of cholinergic system, and its amelioration by
S. officinalis extracts and EO are due to inhibition of AChE [88]. Anti-inflammatory
1590 Salvia officinalis L./Salvia haematodes Wall.

and antinociceptive effects of hydroalcohol, aqueous and butanol leaf extracts are
suggested to involve opioid mechanism [80, 90, 97], and carnosol and ursolic
acid/oleanolic acid appear to contribute to anti-inflammatory and anticarcinogenic
properties, possibly through a modulatory influence on TRPA1-receptors [9, 97].
Luteolin-7-O-glucoside is the putative estrogenic flavonoid involved in anti-hot-
flash effect [93]. Neurotoxic and behavior-modulating effects are attributed to
potentially toxic thujones, GABAA receptor-antagonizing monoterpenoid present in
EOs. However, constituents other than thujones have also been implicated in tox-
icity, antimicrobial effect or CNS activity of the EOs [92].
Human A/Es, Allergy and Toxicity: In a minority of patients, the herb caused
dryness of mouth, dizziness, lassitude, numbness and distending sensation of hands,
shortness of breath, tightness of chest, mild irritability, precordial pain, tachycardia,
N/V, and GIT disturbances. These symptoms usually subsided or disappeared spon-
taneously without interrupting the treatment [33]. Allergic contact dermatitis due to
sage extract has been reported [73], and unintentional exposure of newborn and
children to EO resulted in generalized tonic-clonic seizures [38, 59]. HMPC of the
European Medicines Agency warns that consumption of EO as single ingredient
involves high risk of exceeding maximum recommended daily intake of thujone
and the resulting neurotoxicity [31].
Animal Toxicity: Oral LD50 for hydroalcohol leaf extract in mice was reported to
be 44,760 mg/kg [97], and LD50 (i.p.) of methanol leaf extract was 4,000 mg/kg
[29]. Administration of EO in diet to female mice for two-weeks before mating
negatively affected preimplantation distribution of embryos [26].
CYP450 and Potential for Drug-Herb Interactions: Replacement of drinking
water with sage tea caused an increase in CYP2E1 protein [64].
Commentary: Sage tea is widely used in European countries for various benefits.
In addition to anecdotal accounts, clinical trials have shown significant improve-
ment in cognitive functions, lipid profile and menopausal hot-flashes in women, but
inconsistent results on blood glucose. Nevertheless, more RCTs are needed to
validate systematic use of sage for therapeutic purposes. Variations in chemical
constituents and due to different chemotypes of S. officinalis, it is prudent that all
pharmacological and clinical studies must report the chemical constituents of the
material used.

References
1. Aherne SA, Kerry JP, O’Brien NM. Effects of plant extracts on antioxidant
status and oxidant-induced stress in Caco-2 cells. Br J Nutr. 2007;97:321–8.
2. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Salvia officinalis
extract in the treatment of patients with mild to moderate Alzheimer’s
disease: a double blind, randomized and placebo-controlled trial. J Clin
Pharm Ther. 2003;28:53–9.
Salvia officinalis L./Salvia haematodes Wall. 1591

3. Alarcon-Aguilar FJ, Roman-Ramos R, Flores-Saenz JL, Aguirre-Garcia F.

Investigation on the hypoglycaemic effects of extracts of four Mexican
medicinal plants in normal and alloxan-diabetic mice. Phytother Res. 2002;
16:383–6.
4. Amin A, Hamza AA. Hepatoprotective effects of Hibiscus, Rosmarinus and
Salvia on azathioprine-induced toxicity in rats. Life Sci. 2005;77:266–78.
5. Baj T, Ludwiczuk A, Sieniawska E, et al. GC-MS analysis of essential oils
from Salvia officinalis L.: comparison of extraction methods of the volatile
components. Acta Pol Pharm. 2013;70:35–40.
6. Bansode FW, Rajendran SM, Singh RK. Dose-dependent effects of ethanol
extract of Salvia haematodes Wall. roots on reproductive function and
copulatory behaviour in male rats. Andrologia. 2015;47:266–75.
7. Baricevic D, Sosa S, Della Loggia R, et al. Topical anti-inflammatory
activity of Salvia officinalis L. leaves: the relevance of ursolic acid.
J Ethnopharmacol. 2001;75:125–32.
8. Basílico MZ, Basílico JC. Inhibitory effects of some spice essential oils on
Aspergillus ochraceus NRRL 3174 growth and ochratoxin A production.
Lett Appl Microbiol. 1999;29:238–41.
9. Bauer J, Kuehnl S, Rollinger JM, et al. Carnosol and carnosic acids from
Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1. J Phar-
macol Exp Ther. 2012;342:169–76.
10. Ben Farhat M, Jordán MJ, Chaouech-Hamada R, et al. Variations in
essential oil, phenolic compounds, and antioxidant activity of Tunisian
cultivated Salvia officinalis L. J Agric Food Chem. 2009;57:10349–56.
11. Ben Khedher MR, Hammami M, Arch JRS, et al. Preventive effects of Salvia
officinalis leaf extract on insulin resistance and inflammation in a model of
high fat diet-induced obesity in mice that responds to rosiglitazone. PeerJ.
2018;6:e4166.
12. Bommer S, Klein P, Suter A. First time proof of sage’s tolerability and efficacy
in menopausal women with hot flushes. Adv Ther. 2011;28:490–500.
13. Bouajaj S, Benyamna A, Bouamama H, et al. Antibacterial, allelopathic
and antioxidant activities of essential oil of Salvia officinalis L. growing
wild in the Atlas Mountains of Morocco. Nat Prod Res. 2013;27:1673–6.
14. Bozin B, Mimica-Dukic N, Samojlik I, Jovin E. Antimicrobial and antioxi-
dant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia
officinalis L., Lamiaceae) essential oils. J Agric Food Chem. 2007;55:
7879–85.
15. Capek P, Hríbalová V, Svandová E, et al. Characterization of immunomod-
ulatory polysaccharides from Salvia officinalis L. Int J Biol Macromol.
2003;33:113–9.
16. Capek P, Hríbalová V. Water-soluble polysaccharides from Salvia officinalis L.
possessing immunomodulatory activity. Phytochemistry 2004;65:1983–92.
1592 Salvia officinalis L./Salvia haematodes Wall.

17. Capek P. An arabinogalactan containing 3-O-methyl-D-galactose residues

isolated from the aerial parts of Salvia officinalis L. Carbohydr Res.
2008;343:1390–3.
18. Carrasco FR, Schmidt G, Romero AL, et al. Immunomodulatory activity of
Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum
L. essential oils: evidence for humor- and cell-mediated responses. J Pharm
Pharmacol. 2009;61:961–7.
19. Celik I, Isik I. Determination of chemopreventive role of Foeniculum
vulgare and Salvia officinalis infusion on trichloroacetic acid-induced
increased serum marker enzymes lipid peroxidation and antioxidative
defense systems in rats. Nat Prod Res. 2008;22:66–75.
20. Climati E, Mastrogiovanni F, Valeri M, et al. Methyl carnosate, an
antibacterial diterpene isolated from Salvia officinalis leaves. Nat Prod
Commun. 2013;8:429–30.
21. Craft JD, Satyal P, Setzer WN. The chemotaxonomy of common sage
(Salvia officinalis) based on the volatile constituents. Medicines (Basel).
2017;4. pii: E47.
22. Cutillas AB, Carrasco A, Martinez-Gutierrez R, Tomas V, Tudela J. Salvia
officinalis L. Essential oils from Spain: determination of composition,
antioxidant capacity, antienzymatic, and antimicrobial bioactivities. Chem
Biodivers. 2017;14.
23. Cvetkovikj I, Stefkov G, Karapandzova M, Kulevanova S, Satović Z. Essen-
tial oils and chemical diversity of southeast European populations of Salvia
officinalis L. Chem Biodivers. 2015;12:1025–39.
24. Cwikla C, Schmidt K, Matthias A, et al. Investigations into the antibac-
terial activities of phytotherapeutics against Helicobacter pylori and Campy-
lobacter jejuni. Phytother Res. 2010;24:649–56.
25. Daniela T. Salvia officinalis L. I. Botanic characteristics, composition, use
and cultivation. Cesk Farm 1993;42:111–6 (Slovak).
26. Domaracký M, Rehák P, Juhás S, Koppel J. Effects of selected plant
essential oils on the growth and development of mouse preimplantation
embryos in vivo. Physiol Res. 2007;56:97–104.
27. Ehrnhöfer-Ressler MM, Fricke K, Pignitter M, et al. Identification of
1,8-cineole, borneol, camphor, and thujone as anti-inflammatory compounds
in a Salvia officinalis L. infusion using human gingival fibroblasts. J Agric
Food Chem. 2013;61:3451–9.
28. Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L. (sage) leaves on
memory retention and its interaction with the cholinergic system in rats.
Nutrition. 2006;22:321–6.
29. Eidi M, Eidi A, Zamanizadeh H. Effect of Salvia officinalis L. leaves on
serum glucose and insulin in healthy and streptozotocin-induced diabetic
rats. J Ethnopharmacol. 2005;100:310–3.
30. European Medicines Agency, EMA/HMPC/41843/2009, London, 12 Novem-
ber 2009.
Salvia officinalis L./Salvia haematodes Wall. 1593

31. European Medicines Agency. Evaluation of medicines for human use.

EMEA/HMPC/ 331653/2008, London, 14 January 2009.
32. Fischedick JT, Standiford M, Johnson DA, Johnson JA. Structure activity
relationship of phenolic diterpenes from Salvia officinalis as activators of
the nuclear factor E2-related factor 2 pathway. Bioorg Med Chem. 2013;21:
2618–22.
33. Gao XS et al. Chinese Trad Herbal Drugs Commun 1980;(4):33.
34. Garcia CS, Menti C, Lambert AP, et al. Pharmacological perspectives from
Brazilian Salvia officinalis (Lamiaceae): antioxidant, and antitumor in
mammalian cells. An Acad Bras Cienc. 2016;88:281–92.
35. Generalić I, Skroza D, Surjak J, et al. Seasonal variations of phenolic
compounds and biological properties in sage (Salvia officinalis L.). Chem
Biodivers. 2012;9:441–57.
36. Geuenich S, Goffinet C, Venzke S, et al. Aqueous extracts from peppermint,
sage and lemon balm leaves display potent anti-HIV-1 activity by increasing
the virion density. Retrovirology. 2008;20:27.
37. Guaschino S, Benvenuti C. SOPHY Study Group: SOPHY project: an
observational study of vaginal pH, lifestyle and correct intimate hygiene in
women of different ages and in different physiopathological conditions.
Part II. Minerva Ginecol. 2008;60:353–62.
38. Halicioglu O, Astarcioglu G, Yaprak I, Aydinlioglu H. Toxicity of Salvia
officinalis in a newborn and a child: an alarming report. Pediatr Neurol.
2011;45:259–60.
39. Hasanein P, Teimuri Far M, Emamjomeh A. Salvia officinalis L. attenuates
morphine analgesic tolerance and dependence in rats: possible analgesic
and sedative mechanisms. Am J Drug Alcohol Abuse. 2015;41:405–13.
40. Hayouni el A, Chraief I, Abedrabba M, et al. Tunisian Salvia officinalis L.
and Schinus molle L. essential oils: their chemical compositions and their
preservative effects against Salmonella inoculated in minced beef meat.
Int J Food Microbiol. 2008;125:242–51.
41. Hohmann J, Zupkó I, Rédei D, et al. Protective effects of the aerial parts of
Salvia officinalis, Melissa Officinalis and Lavandula angustifolia and their
constituents against enzyme-dependent and enzyme-independent lipid
peroxidation. Planta Med. 1999;65:576–8.
42. Horiuchi K, Shiota S, Kuroda T, et al. Potentiation of antimicrobial activity
of aminoglycosides by carnosol from Salvia officinalis. Biol Pharm Bull.
2007;30:287–90.
43. Horváthová E, Srančíková A, Regendová-Sedláčková E, et al. Enriching the
drinking water of rats with extracts of Salvia officinalis and Thymus vulgaris
increases their resistance to oxidative stress. Mutagenesis. 2016;31:51–9.
44. Hubbert M, Sievers H, Lehnfeld R, Kehrl W. Efficacy and tolerability of a
spray with Salvia officinalis in the treatment of acute pharyngitis—a
randomised, double-blind, placebo-controlled study with adaptive design
and interim analysis. Eur J Med Res. 2006;11:20–6.
1594 Salvia officinalis L./Salvia haematodes Wall.

45. Imanshahidi M, Hosseinzadeh H. The pharmacological effects of Salvia

species on the central nervous system. Phytother Res. 2006;20:427–37
(Review).
46. Iuvone T, De Filippis D, Esposito G, et al. The spice sage and its active
ingredient rosmarinic acid protect PC12 cells from amyloid-beta peptide-
induced neurotoxicity. J Pharmacol Exp Ther. 2006;317:1143–9.
47. Jiang Y, Zhang L, Rupasinghe HP. Antiproliferative effects of extracts
from Salvia officinalis L. and Saliva miltiorrhiza Bunge on hepatocellular
carcinoma cells. Biomed Pharmacother. 2017;85:57–67.
48. Juhás S, Cikos S, Czikková S, et al. Effects of borneol and thymoquinone
on TNBS-induced colitis in mice. Folia Biol (Praha). 2008;54:1–7.
49. Kavvadias D, Monschein V, Sand P, et al. Constituents of sage (Salvia
officinalis) with in vitro affinity to human brain benzodiazepine receptor.
Planta Med. 2003;69:113–7.
50. Kennedy DO, Pace S, Haskell C, et al. Effects of cholinesterase inhibiting
sage (Salvia officinalis) on mood, anxiety and performance on a psycho-
logical stressor battery. Neuropsychopharmacology. 2006;31:845–52.
51. Kermanshah H, Kamangar SS, Arami S, et al. The effect of hydroalcoholic
extract of seven plants on cariogenic bacteria—an in vitro evaluation. Oral
Health Dent Manag. 2014;13:395–401.
52. Keshavarz M, Mostafaie A, Mansouri K, et al. In vitro and ex vivo
antiangiogenic activity of Salvia officinalis. Phytother Res. 2010;24:1526–31.
53. Khedher MRB, Khedher SB, Chaieb I, Tounsi S, Hammami M. Chemical
composition and biological activities of Salvia officinalis essential oil from
Tunisia. EXCLI J. 2017;16:160–73.
54. Kianbakht S, Abasi B, Perham M, Hashem Dabaghian F. Antihyperlipi-
demic effects of Salvia officinalis L. leaf extract in patients with hyper-
lipidemia: a randomized double-blind placebo-controlled clinical trial.
Phytother Res 2011;25:1849–53.
55. Kianbakht S, Dabaghian FH. Improved glycemic control and lipid profile
in hyperlipidemic type 2 diabetic patients consuming Salvia officinalis L.
leaf extract: a randomized placebo controlled clinical trial. Complement
Ther Med 2013;21:441–6.
56. Kianbakht S, Nabati F, Abasi B. Salvia officinalis (Sage) leaf extract as
add-on to statin therapy in hypercholesterolemic type 2 diabetic patients: a
randomized clinical trial. Int J Mol Cell Med. 2016;5:141–8.
57. Kintzios S, Papageorgiou K, Yiakoumettis I, et al. Evaluation of the
antioxidants activities of four Slovene medicinal plant species by traditional
and novel biosensory assays. J Pharm Biomed Anal. 2010;53:773–6.
58. Kolac UK, Ustuner MC, Tekin N, et al. The anti-inflammatory and antioxi-
dant effects of Salvia officinalis on lipopolysaccharide-induced inflamma-
tion in rats. J Med Food. 2017;20:1193–200.
Salvia officinalis L./Salvia haematodes Wall. 1595

59. Lachenmeier DW, Walch SG. Epileptic seizures caused by accidental

ingestion of sage (Salvia officinalis L.) oil in children: a rare, exceptional
case or a threat to public health? Pediatr Neurol. 2012;46:201.
60. Leporatti ML, Posocco E, Pavesi A. Some new therapeutic uses of several
medicinal plants in the province of Terni (Umbria, Central Italy).
J Ethnopharmacol. 1985;14:65–8.
61. Lima CF, Andrade PB, Seabra RM, et al. The drinking of a Salvia
officinalis infusion improves liver antioxidant status in mice and rats.
J Ethnopharmacol. 2005;97:383–9.
62. Lima CF, Azevedo MF, Araujo R, et al. Metformin-like effect of Salvia
officinalis (common sage): is it useful in diabetes prevention? Br J Nutr.
2006;96:326–33.
63. Lima CF, Carvalho F, Fernandes E, et al. Evaluation of toxic/protective
effects of the essential oil of Salvia officinalis on freshly isolated rat
hepatocytes. Toxicol In Vitro. 2004;18:457–65.
64. Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Drinking of Salvia
officinalis tea increases CCl(4)-induced hepatotoxicity in mice. Food Chem
Toxicol. 2007;45:456–64.
65. Lima CF, Valentao PC, Andrade PB, et al. Water and methanolic extracts
of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative
damage. Chem Biol Interact. 2007;167:107–15.
66. Liu SS. Abstracts of Research Literature on Chinese Traditional Drugs
(1820–1961). Science Press; 1975. p. 113.
67. Lixandru BE, Drăcea NO, Dragomirescu CC, et al. Antimicrobial activity
of plant essential oils against bacterial and fungal species involved in food
poisoning and/or food decay. Roum Arch Microbiol Immunol. 2010;69:
224–30.
68. Lu Y, Foo LY. Flavonoid and phenolic glycosides from Salvia officinalis.
Phytochemistry. 2000;55:263–7.
69. Martins N, Barros L, Santos-Buelga C, et al. Evaluation of bioactive
properties and phenolic compounds in different extracts prepared from
Salvia officinalis L. Food Chem. 2015;170:378–85.
70. Masterová I, Misíková E, Sirotková L, et al. Royleanones in the roots of
Salvia officinalis L. of domestic provenance and their antimicrobial activity.
Ceska Slov Farm 1996;45:242–5 (Slovak).
71. Matsingou TC, Petrakis N, Kapsokefalou M, Salifoglou A. Antioxidant
activity of organic extracts from aqueous infusions of sage. J Agric Food
Chem. 2003;51:6696–701.
72. Mayer B, Baggio CH, Freitas CS, et al. Gastroprotective constituents of
Salvia officinalis L. Fitoterapia. 2009;80:421–6.
73. Mayer E, Gescheidt-Shoshany H, Weltfriend S. Allergic contact dermatitis
caused by Salvia officinalis extract. Contact Dermatitis. 2011;64:237–8.
1596 Salvia officinalis L./Salvia haematodes Wall.

74. Miura K, Kikuzaki H, Nakatani N. Antioxidant activity of chemical

components from sage (Salvia officinalis L.) and thyme (Thymus vulgaris
L.) measured by the oil stability index method. J Agric Food Chem.
2002;50:1845–51.
75. Miura K, Kikuzaki H, Nakatani N. Apianane terpenoids from Salvia
officinalis. Phytochemistry. 2001;58:1171–5.
76. Moss L, Rouse M, Wesnes KA, Moss M. Differential effects of the aromas of
Salvia species on memory and mood. Hum Psychopharmacol. 2010;25:388–96.
77. Ninomiya K, Matsuda H, Shimoda H, et al. Carnosic acid, a new class of
lipid absorption inhibitor from sage. Bioorg Med Chem Lett. 2004;14:
1943–6.
78. Nolkemper S, Reichling J, Stintzing FC, et al. Antiviral effect of aqueous
extracts from species of the Lamiaceae family against Herpes simplex virus
type 1 and type 2 in vitro. Planta Med. 2006;72:1378–82.
79. Oboh G, Henle T. Antioxidant and inhibitory effects of aqueous extracts of
Salvia officinalis leaves on prooxidant-induced lipid peroxidation in brain
and liver in vitro. J Med Food. 2009;12:77–84.
80. Oniga I, Pârvu AE, Toiu A, Benedec D. Effects of Salvia officinalis L.
extract on experimental acute inflammation. Rev Med Chir Soc Med Nat
Iasi 2007;111:290–4.
81. Oniga I, Oprean R, Toiu A, Benedec D. Chemical composition of the
essential oil of Salvia officinalis L. from Romania. Rev Med Chir Soc Med
Nat Iasi. 2010;114:593–5.
82. Orhan I, Kartal M, Kan Y, Sener B. Activity of essential oils and
individual components against acetyl- and butyrylcholinesterase. Z Natur-
forsch. 2008;63:547–53.
83. Otoom SA, Al-Safi SA, Kerem ZK, Alkofahi A. The use of medicinal
herbs by diabetic Jordanian patients. J Herb Pharmacother. 2006;6:31–41.
84. Pedro DF, Ramos AA, Lima CF, Baltazar F, Pereira-Wilson C. Colon
cancer chemoprevention by sage tea drinking: decreased DNA damage and
cell proliferation. Phytother Res. 2016;30:298–305.
85. Pereira RS, Sumita TC, Furlan MR, et al. Antibacterial activity of essential
oils on microorganisms isolated from urinary tract infection. Rev Saude
Publica. 2004;38:326–8 (Portuguese).
86. Perry EK, Pickering AT, Wang WW, et al. Medicinal plants and Alzheimer’s
disease: integrating ethnobotanical and contemporary scientific evidence.
J Altern Complement Med. 1998;4:419–28 (Review).
87. Perry EK, Pickering AT, Wang WW, et al. Medicinal plants and
Alzheimer’s disease: from ethnobotany to phytotherapy. J Pharm Phar-
macol. 1999;51:527–34.
88. Perry N, Court G, Bidet N, Court J, Perry E. European herbs with cholinergic
activities: potential in dementia therapy. Int J Geriatric Psychiatr. 1996;11:
1063–9.
Salvia officinalis L./Salvia haematodes Wall. 1597

89. Poeckel D, Greiner C, Verhoff M, et al. Carnosic acid and carnosol

potently inhibit human 5-lipoxygenase and suppress proinflammatory
responses of stimulated human polymorphonuclear leukocytes. Biochem
Pharmacol. 2008;76:91–7.
90. Qnais EY, Abu-Dieyeh M, Abdulla FA, Abdalla SS. The antinociceptive
and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol
extracts. Pharm Biol. 2010;48:1149–56.
91. Raal A, Orav A, Arak E. Composition of the essential oil of Salvia officinalis
L. from various European countries. Nat Prod Res. 2007;21:406–11.
92. Radulović NS, Genčić MS, Stojanović NM, et al. Toxic essential oils. Part V:
behaviour modulating and toxic properties of thujones and thujone-containing
essential oils of Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis
L. and Tanacetum vulgare L. Food Chem Toxicol. 2017;105:355–69.
93. Rahte S, Evans R, Eugster PJ, et al. Salvia officinalis for hot flushes:
towards determination of mechanism of activity and active principles.
Planta Med. 2013;79:753–60.
94. Ramos AA, Azqueta A, Pereira-Wilson C, Collins AR. Polyphenolic
compounds from Salvia species protect cellular DNA from oxidation and
stimulate DNA repair in cultured human cells. J Agric Food Chem. 2010;
58:7465–71.
95. Ramos AA, Pedro D, Collins AR, Pereira-Wilson C. Protection by Salvia
extracts against oxidative and alkylation damage to DNA in human HCT15
and CO115 cells. J Toxicol Environ Health A. 2012;75:765–75.
96. Reuter J, Jocher A, Hornstein S, et al. Sage extract rich in phenolic diterpenes
inhibits ultraviolet-induced erythema in vivo. Planta Med. 2007;73:1190–1.
97. Rodrigues MR, Kanazawa LK, das Neves TL, et al. Antinociceptive and
anti-inflammatory potential of extract and isolated compounds from the
leaves of Salvia officinalis in mice. J Ethnopharmacol. 2012;139:519–26.
98. Rota C, Carramiñana JJ, Burillo J, Herrera A. In vitro antimicrobial
activity of essential oils from aromatic plants against selected foodborne
pathogens. J Food Prot. 2004;67:1252–6.
99. Russo A, Formisano C, Rigano D, et al. Chemical composition and anticancer
activity of essential oils of Mediterranean sage (Salvia officinalis L.) grown in
different environmental conditions. Food Chem Toxicol 2013;55:42–7.
100. Sá CM, Ramos AA, Azevedo MF, et al. Sage tea drinking improves lipid
profile and antioxidant defences in humans. Int J Mol Sci. 2009;10:3937–50.
101. Sallam A, Mira A, Ashour A, Shimizu K. Acetylcholine esterase inhibitors
and melanin synthesis inhibitors from Salvia officinalis. Phytomedicine.
2016;23:1005–11.
102. Santos-Gomes PC, Fernandes-Ferreira M. Organ- and season-dependent
variation in the essential oil composition of Salvia officinalis L. cultivated
at two different sites. J Agric Food Chem. 2001;49:2908–16.
1598 Salvia officinalis L./Salvia haematodes Wall.

103. Santos-Gomes PC, Seabra RM, Andrade PB, Fernandes-Ferreira M.

Phenolic antioxidant compounds produced by in vitro shoots of sage (Salvia
officinalis L.). Plant Sci. 2002;162:981–7.
104. Savelev S, Okello E, Perry NSL, Wilkins RM, Perry EK. Synergistic and
antagonistic interactions of anticholinesterase terpenoids in Salvia lavan-
dulaefolia essential oil. Pharmacol Biochem Behav. 2003;75:661–8.
105. Schnitzler P, Nolkemper S, Stintzing FC, Reichling J. Comparative in vitro
study on the antiherpetic effect of phytochemically characterized aqueous
and ethanolic extracts of Salvia officinalis grown at two different locations.
Phytomedicine. 2008;15:62–70.
106. Scholey AB, Tildesley NT, Ballard CG, et al. An extract of Salvia (sage)
with anticholinesterase properties improves memory and attention in
healthy older volunteers. Psychopharmacology. 2008;198:127–39.
107. Sertel S, Eichhorn T, Plinkert PK, Efferth T. Anticancer activity of Salvia
officinalis essential oil against HNSCC cell line (UMSCC1). HNO. 2011;
59:1203–8 (German).
108. Soković M, Glamočlija J, Marin PD, et al. Antibacterial effects of the
essential oils of commonly consumed medicinal herbs using an in vitro
model. Molecules. 2010;15:7532–46.
109. Sookto T, Srithavaj T, Thaweboon S, et al. In vitro effects of Salvia officinalis L.
essential oil on Candida albicans. Asian Pac J Trop Biomed. 2013;3:376–80.
110. Stefanović OD, Stanojević DD, Comić LR. Synergistic antibacterial
activity of Salvia officinalis and Cichorium intybus extracts and antibiotics.
Acta Pol Pharm. 2012;69:457–63.
111. Stojanović-Radić Z, Pejcić M, Stojanović N, Sharifi-Rad J, Stanković N.
Potential of Ocimum basilicum L. and Salvia officinalis L. essential oils
against biofilms of P. aeruginosa clinical isolates. Cell Mol Biol (Noisy-
le-grand). 2016;62:27–33.
112. Todorov S, Philianos S, Petkov V, et al. Experimental pharmacological
study of three species from genus Salvia. Acta Physiol Pharmacol Bulg.
1984;10:13–20.
113. Vandecasteele K, Ost P, Oosterlinck W, et al. Evaluation of the efficacy and
safety of Salvia officinalis in controlling hot flashes in prostate cancer
patients treated with androgen deprivation. Phytother Res. 2012;26:208–13.
114. Walch SG, Tinzoh LN, Zimmermann BF, et al. Antioxidant capacity and
polyphenolic composition as quality indicators for aqueous infusions of
Salvia officinalis L. (sage tea). Front Pharmacol. 2011;2:79.
115. Wang M, Kikuzaki H, Zhu N, et al. Isolation and structural elucidation of
two new glycosides from sage (Salvia officinalis L.). J Agric Food Chem
2000;48:235–8.
Salvia officinalis L./Salvia haematodes Wall. 1599

116. Wang M, Shao Y, Li J, et al. Antioxidative phenolic glycosides from sage

(Salvia officinalis). J Nat Prod. 1999;62:454–6.
117. Xavier CP, Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Salvia
fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and
inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK
pathway. Nutr Cancer. 2009;61:564–71.
118. Zheng W, Wang SY. Antioxidant activity and phenolic compounds in
selected herbs. J Agric Food Chem. 2001;49:5165–70.
Santalum album L.
(Santalaceae)

Abstract
A small tropical evergreen tree, native to India, Sri Lanka, China, Indonesia,
Malaysia, the Philippines, and Australia. The tree also extensively grows in the
mountains of Hawaiian Islands, and resembles orange tree. It has been used
in India for over two thousand years for its wood and oil in religious practices
and in traditional medicines. Sanskrit writers described two kinds of Chandana:
the darker heartwood, called Pitachandana or yellow Chandan, and the lighter
wood, Srikhanda or white sandal. It is referred to in the epic Hindu poems of
Ramayana and Mahabharata; and is one of the trees of Buddhist paradise, and
the chariot of the sun is made of its wood bound with gold. Unani physicians
regard it sedative, cardiorefrigerant and cardiotonic, antiseptic, blood purifier, and
to strengthen stomach and intestines. It is used for heart weakness, palpitation,
hematuria, dysuria, gonorrhea, chronic tubercular cough, and kidney ulcers.
Externally, it is cooling, irritant and analgesic, and is used as paste for hot
inflammations and headache due to heat. Oil is antiseptic and analgesic for
urinary and pulmonary tracts, and expectorant, and used for the treatment of relief
of irritation and infection of gonorrhea, and for chronic cough with putrid sputum.
Sandalwood essential oil is usually prepared by steam distillation from chips and
billets cut from the heartwood, and used in the food industry as a flavor
ingredient, in perfumes, cosmetics, and sacred unguents. It is one of a number of
popular EOs currently in use as aromatherapy agents to relieve anxiety, stress,
and depression. The tree is rich in terpenoids, saponin, phenolics and tannins.
Phytochemical studies showed the presence of sesquiterpenes, including a and
b-santalol, sesquiterpenoids, geraniol, (+)-a-nuciferol, (+)-citronellol, and lig-
nans from the heartwood; and flavonoids from the leaves. Cold-water extract of
sandalwood and oil show highly significant antibacterial activity. Oral treatment
of diabetic rats with petroleum ether extract twice daily for 60-days, reduced
blood glucose, TC, LDL-C and TGs, and increased HDL-C.

© Springer Nature Switzerland AG 2020 1601

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_165
1602 Santalum album L.

Keywords





Árbol del sándalo Árvore do sandal Chandanam Iliahi Indian sandalwood






Safed chandan Safed sandal Sandelhout Santal blanc Tan-shiang

Vernaculars: Urd.: Sandal safed; Hin.: Safed chandan, Safed chondana, Safed
sandal; San.: Bhadra shree sandanam, Chandanam, Gandashrah, Sandalam, Srig-
andha, Srikhanda, Sweet chandan; Ben.: Chandon, Pitchandan, Sâdâchondan; Mal.:
Chandana-mutti, Chandena-maram; Mar.: Chandana, Gandhâ-che-khor; Tam.:
Chandanam, Sandanamaram, Sandanak kattai, Santhanam, Shandanak; Tel.:
Gandhapu-chekka; Ara.: Sandal abyad; Chi.: 自檀香, Tan-shiang, Tan xiang mu;
Dan.: Sandeltræ; Dut.: Sandelboom, Sandelhout; Eng.: Indian sandalwood, White
sandalwood, White saunders; Fre.: Arbre à baumes, Bois de santal, Santal blanc;
Ger.: Weißer sandelbaum, Weißer sandelholzbaum; Haw.: Iliahi; Ind.: Cendana;
Ita.: Sandalo bianco, Sandalo citrino, Sandalo mysore; Jap.: Byakudan,
Sandaru-uddo; Maly.: Miniak chandana; Per.: Sandal-e-supéd; Por.: Árvore do
sandal, Sândalo, Sândalo-branco; Rus.: Sandaloboe derevo; Spa.: Árbol del sándalo,
Sándalo blanco.
Description: A small tropical evergreen tree, native to India, Sri Lanka, China,
Indonesia, Malaysia, the Philippines, and Australia. The tree also extensively grows
in the mountains of Hawaiian Islands, and resembles orange tree, having smooth
bark, fragrant wood, and fragrant leaves similar to orange tree leaves.LXXVI It
attains a height of between 4 and 9 m; leaves thin, opposite, petiolate, entire,
oblong, acuminate, coriaceous, glabrous surface shiny and bright green, with a
glaucous pale reverse side; fruits after three years, and viable seeds after five years.
The tree is usually upright to sprawling, and may intertwine with other species. It
may live up to one hundred years of age. The wood, fibrous texture, light-yellow to
dark reddish-brown, aromatic with slightly sweet and pungent taste is used
medicinally. Only the heartwood is valuable, the sapwood and branches are not
used (Figs. 1, 2 and 3).XL
Actions and Uses: It has been used in India for over two thousand years for its
wood and oil in religious practices and in traditional medicines. Sanskrit writers
described two kinds of Chandana: the darker heartwood, called Pitachandana or
yellow Chandan, and the lighter wood, Srikhanda or white sandal. It is referred to
in the epic Hindu poems of Ramayana and Mahabharata; and is one of the trees of
Buddhist paradise, and the chariot of the sun is made of its wood bound with
gold.XL The author of Makhzan-e-Advia described it as cardiacal, tonic, astringent,
alexipharmic, antaphrodisiac, used against venereal diseases, a resolvent of
inflammatory swellings, and recommends an emulsion in bilious fever, on account
of its cooling and protective influence over heart, brain and stomach. In southern
India sandalwood given with milk is regarded as a valuable remedy in gonorrhea.XL
Unani physicians regard it (temperament, wood: cold 3° and dry 2°; oil: cold 2° and
moist 2°) sedative, cardiorefrigerant and cardiotonic, antiseptic, blood-purifier, and
to strengthen stomach and intestines. It is used for heart weakness, palpitation,
Santalum album L. 1603

Fig. 1 Santalum album, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Santalum_album_-_K%C3%B6hler%
E2%80%93s_Medizinal-Pflanzen-128.jpg

Fig. 2 Santalum album, Young Sapling, L. Shyamal, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:SantalumAlbumSapling.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
1604 Santalum album L.

Fig. 3 Santalum album, Flowers, J.M. Garg, WikimediaCommons; ShareAlike 4.0 Interna-
tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Santalum_album_(Chandan)_in_
Hyderabad,_AP_W2_IMG_0023.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

hematuria, dysuria, gonorrhea, chronic tubercular cough, and kidney ulcers. Exter-
nally, it is cooling, irritant and analgesic, and is used as paste for hot inflammations
and headache due to heat.LXXVII Oil is antiseptic and analgesic for urinary and
pulmonary tracts, and expectorant, and used for the relief of irritation and infection
of gonorrhea, and for chronic cough with putrid sputum.LXXVII The wood is bitter,
cooling, sedative, astringent and disinfectant of mucous membranes of the geni-
tourinary and bronchial tracts; the oil is astringent, diuretic, expectorant and
stimulant. The oil is used internally with cardamom and bamboo manna in gon-
orrhea, bronchitis, cystitis, pyelitis and chronic diarrhea.LXXXI,CV In TCM, wood is
regarded aromatic stomachic, carminative, and analgesic, and used for the treatment
of nervous gastralgia.LXVI Sandalwood is used by the tribal communities of Ladakh
region in India for the treatment of kidney and urinary disorders [2], and is a cancer
preventive and therapeutic agent in Chinese medicine [6]. Sandalwood oil, emul-
sion or paste of sandalwood have been used in India for the treatment of inflam-
matory and eruptive skin diseases [7]. Sandalwood is also traditionally used in India
for its antihyperlipidemic and diuretic activities [17], as a sedative in traditional
Japanese Oriental medicine [26], and in Japanese scent sachets [8]. Sandalwood
essential oil is usually prepared by steam distillation from chips and billets cut from
the heartwood, and used in the food industry as a flavor ingredient, in perfumes,
cosmetics, and sacred unguents [16]. It is one of a number of popular EOs currently
in use as aromatherapy agents to relieve anxiety, stress, and depression [29], and in
Santalum album L. 1605

the treatment of common colds, bronchitis, skin disorders, heart ailments, general
weakness, fever, UTI, inflammation of the mouth and pharynx, and liver and
gallbladder disorders [23]. On the Hawaiian Islands, the leaves and bark decoctions
are used as head wash to kill head lice and remove dandruff, to cleanse chronic
sores; and internally for both male and female sexual weakness (contrary to its
description as antaphrodisiac).LXXVI
Phytoconstituents: The tree is rich in terpenoids, saponin, phenolics and tannins
[24]. Phytochemical studies have demonstrated the presence of sesquiterpenes,
including a and b-santalol [22, 25], sesquiterpenoids (bisabolane-type and
santalane-type) [15], geraniol, (+)-a-nuciferol, (+)-citronellol, and lignans [21] from
the heartwood; and flavonoids (vicenin-2, vitexin, isovitexin, orientin, isoorientin,
chrysin-8-C-b-D-glucopyranoside, chrysin-6-C-b-D-glucopyranoside, and isorham-
netin) from the leaves [30]. Sandal contains several amino acids and amines, which
are not seen in other plants, including cis-4-hydroxy-l-proline in free form in leaves,
flowers and seeds, and trans-4-hydroxy-l-proline in bound form. It also contains
sym. homospermidine which has not yet been detected in any other plants [18].
A hydroxyproline-containing protein was isolated from soluble fraction of sandal
leaves; the principal amino acids were glutamic acid, aspartic acid, glycine, alanine,
arginine, lysine, proline and hydroxyproline, which together comprised 60% of the
total [20]. The wood contains a volatile oil comprising of a- and b-santalol, iso-
valeric aldehyde, santene, santenone, teresantol, santalone and santalene.LXXIX
Over 100 constituents have been identified in sandalwood oil, with a-santalol being
the major constituent [5]; majority of commercial oils contain approximately
50–70% santalols [11]. a-Santalol possesses a variety of therapeutic properties,
including anti-inflammatory, antioxidant, antiviral and antibacterial activities [28].
The pericarps volatile oil by hydrodistillation and n-hexane extraction are colorless
and yellow in color, respectively. They contain a total of 66 volatile components;
the most prominent being palmitic and oleic acids, representing about 40–70% of
the total oil, and the fragrant constituents include a- and b-santalol, cedrol, esters,
aldehydes, phytosterols, and squalene [31].
Pharmacology: Cold-water extract of sandalwood shows highly significant
antibacterial activity against P. vulgaris, B. subtilis, E. coli and P. aeruginosa;
whereas hot-water extract was significantly active only against P. aeruginosa and
P. vulgaris [14]. Sandalwood oil is highly effective against S. aureus, S. typhi-
murium, E. Coli and K. aerogenes, with an MIC of 0.078 to 5 lg/ml [24]. San-
dalwood oil inhibited replication of HSV-1 more than HSV-2, but was not virucidal
or cytotoxic at tested concentrations [4]. (Z)-a-Santalol and (Z)-b-santalol exhibited
strong activity against a clarithromycin-resistant strain of H. pylori [25]. Applica-
tion of sandalwood oil significantly decreased incidence, multiplicity, and ornithine
decarboxylase activity of DMBA-initiated and TPA-promoted skin papillomas in
mice [7]. cis-b-Santalol and b-santaldiol induce apoptotic cell death in HL-60 cells
[22]. Sandalwood oil suppressed in vitro viability of both human bladder cancer
cells and immortalized normal human bladder urothelial cells [6]. Oral feeding to
mice with 5 and 15 microliters sandalwood oil daily for 10 and 20-days exhibited
1606 Santalum album L.

increase in GST activity and acid soluble sulphydryl levels in liver, which was
suggested to be a possible mechanism of chemopreventive action of sandalwood oil
on carcinogenesis [3].
Oral treatment of diabetic rats with petroleum ether extract at a dose of 10 µg/kg
body weight twice daily for 60-days, reduced blood glucose by 140 mg/dl, TC,
LDL-C and TGs levels by 22, 31 and 44%, respectively, and increased HDL-C by
46% compared to 70 mg/dl decrease by metformin in blood glucose level [17]. The
oil shows significant sedative effect and a synergistic stronger effect with a mixture
of galangal, patchouli, spikenard, and borneol oils than for any of the single oils in
mice [8]. a- and b-Santalols are the major active constituents contributing to the
sedative effect of sandalwood preparations. They also significantly increase levels
of HVA, DOPAC and/or 5-HIAA in the brain of mice, similar to chlorpromazine
[26]. Methanol extract of sandalwood showed significant antidiarrheal activity
against castor oil-induced diarrhea, inhibited neostigmine induced small intestinal
hyperfunction (the gastric emptying and motility) in mice [9]. Sandalwood extract
also shows modest in vitro NO scavenging effect [12], but a highly significant
antiradical efficiency [13].
Clinical Studies: a-Santalol caused significant subjective relaxing/sedative effect,
and sandalwood oil provoked physiological deactivation, but behavioral activation
in healthy Thai volunteers after transdermal absorption [10]. In a pilot study of 34
UK patients under palliative care, aromatherapy massage with 1% sandalwood oil
was also reported effective in reducing anxiety, but the trial was inconclusive due to
small number of patients [19].
Mechanism of Action: Spasmolytic effect is probably mediated through inhibition
of muscarinic receptors, 5-HT receptors and calcium influx [9]. The oil induces
nonselective cell death via DNA damage and cell cycle arrest [6].
Human A/Es, Allergy and Toxicity: Occasional cases of irritation or allergic
reactions to sandalwood oil have been reported in humans, but in laboratory animals,
sandalwood oil and its major constituent show low acute oral and dermal toxicity [5].
However, in a clinical study, patients with fragrance allergy showed high frequency
of positive responses to sandalwood oil [1], and also contact allergy [27].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Sandalwood oil is claimed to reduce anxiety and commercially
promoted, but clinical evidence has been limited and inconclusive. Sandalwood is
also credited in traditional medicines with other clinical benefits, which remain to
be formally uninvestigated clinically.
Santalum album L. 1607

References
1. An S, Lee AY, Lee CH, et al. Fragrance contact dermatitis in Korea: a joint
study. Cont Derm. 2005;53:320–3.
2. Ballabh B, Chaurasia OP, Ahmed Z, Singh SB. Traditional medicinal plants of
cold desert Ladakh—used against kidney and urinary disorders. J Ethnophar-
macol. 2008;118:331–9.
3. Banerjee S, Ecavade A, Rao AR. Modulatory influence of sandalwood oil
on mouse hepatic glutathione S-transferase activity and acid soluble sul-
phydryl level. Cancer Lett. 1993;68:105–9.
4. Benencia F, Courrèges MC. Antiviral activity of sandalwood oil against
herpes simplex viruses-1 and -2. Phytomedicine. 1999;6:119–23.
5. Burdock GA, Carabin IG. Safety assessment of sandalwood oil (San-
talum album L.). Food Chem Toxicol. 2008;46:421–32.
6. Dozmorov MG, Yang Q, Wu W, et al. Differential effects of selective
frankincense (Ru Xiang) essential oil versus nonselective sandalwood (Tan
Xiang) essential oil on cultured bladder cancer cells: a microarray and
bioinformatics study. Chin Med. 2014;9:18.
7. Dwivedi C, Abu-Ghazaleh A. Chemopreventive effects of sandalwood oil
on skin papillomas in mice. Eur J Cancer Prev. 1997;6:399–401.
8. Fujiwara Y, Ito M. Synergistic effect of fragrant herbs in Japanese scent
sachets. Planta Med. 2015;81:193–9.
9. Guo H, Zhang J, Gao W, Qu Z, Liu C. Antidiarrhoeal activity of methanol
extract of Santalum album L. in mice and gastrointestinal effect on the
contraction of isolated jejunum in rats. J Ethnopharmacol. 2014;154:704–10.
10. Hongratanaworakit T, Heuberger E, Buchbauer G. Evaluation of the effects
of East Indian sandalwood oil and alpha-santalol on humans after transder-
mal absorption. Planta Med. 2004;70:3–7.
11. Howes MJ, Simmonds MS, Kite GC. Evaluation of the quality of sandalwood
essential oils by gas chromatography–mass spectrometry. J Chromatogr A.
2004;1028:307–12.
12. Jagetia GC, Baliga MS. The evaluation of nitric oxide scavenging activity of
certain Indian medicinal plants in vitro: a preliminary study. J Med Food.
2004;7:343–8.
13. Kamal R, Yadav S, Mathur M, Katariya P. Antiradical efficiency of 20
selected medicinal plants. Nat Prod Res. 2012;26:1054–62.
14. Khan UA, Rahman H, Niaz Z, et al. Antibacterial activity of some medicinal
plants against selected human pathogenic bacteria. Eur J Microbiol Immunol
(Bp). 2013;3:272–4.
15. Kim TH, Ito H, Hatano T, et al. Bisabolane- and santalane-type sesquiter-
penoids from Santalum album of Indian origin. J Nat Prod. 2005;68:1805–8.
16. Kim TH, Ito H, Hayashi K, et al. Aromatic constituents from the heartwood
of Santalum album L. Chem Pharm Bull (Tokyo). 2005;53:641–4.
1608 Santalum album L.

17. Kulkarni CR, Joglekar MM, Patil SB, Arvindekar AU. Antihyperglycemic
and antihyperlipidemic effect of Santalum album in streptozotocin induced
diabetic rats. Pharm Biol. 2012;50:360–5.
18. Kuttan R, Panikkar B, Binitha PP. Amino acids in sandal (Santalum album L.)
with special reference to cis-4-hydroxy-l-proline and sym. homospermidine.
Springerplus. 2015;4:546.
19. Kyle G. Evaluating the effectiveness of aromatherapy in reducing levels of
anxiety in palliative care patients: results of a pilot study. Complement Ther
Clin Pract. 2006;12:148–55.
20. Mani UV, Radhakrishnan AN. Isolation and characterization of a hydroxy-
proline-containing protein from soluble extracts of the leaves of sandal
(Santalum album L.). Biochem J. 1974;141:147–53.
21. Matsuo Y, Mimaki Y. Lignans from Santalum album and their cytotoxic
activities. Chem Pharm Bull (Tokyo). 2010;58:587–90.
22. Matsuo Y, Sakagami H, Mimaki Y. A rare type of sesquiterpene and
b-santalol derivatives from Santalum album and their cytotoxic activities.
Chem Pharm Bull (Tokyo). 2014;62:1192–9.
23. Misra BB, Dey S. Biological activities of East Indian sandalwood tree,
Santalum album. PeerJ PrePrints 2013;1:e96v1.
24. Misra BB, Dey S. Comparative phytochemical analysis and antibacterial
efficacy of in vitro and in vivo extracts from East Indian sandalwood tree
(Santalum album L.). Lett Appl Microbiol. 2012;55:476–86.
25. Ochi T, Shibata H, Higuti T, et al. Anti-Helicobacter pylori compounds
from Santalum album. J Nat Prod. 2005;68:819–24.
26. Okugawa H, Ueda R, Matsumoto K, Kawanishi K, Kato A. Effect of
a-santalol and b-santalol from sandalwood on the central nervous system in
mice. Phytomedicine. 1995;2:119–26.
27. Sabroe RA, Holden CR, Gawkrodger DJ. Contact allergy to essential oils
cannot always be predicted from allergy to fragrance markers in the baseline
series. Contact Dermatitis. 2016;74:236–41.
28. Santha S, Dwivedi C. Anticancer effects of sandalwood (Santalum album).
Anticancer Res. 2015;35:3137–45.
29. Setzer WN. Essential oils and anxiolytic aromatherapy. Nat Prod Commun.
2009;4:1305–16.
30. Yan C, Lin L, Liu H, et al. Study of flavonoids from leaves of Santalum al-
bum. Zhongguo Zhong Yao Za Zhi. 2011;36:3130–3 (Chinese).
31. Zhang XH, da Silva JA, Jia YX, Zhao JT, Ma GH. Chemical composition of
volatile oils from the pericarps of Indian sandalwood (Santalum album) by
different extraction methods. Nat Prod Commun. 2012;7:93–6.
Saussurea lappa (Falc.) Lipsch.
(Asteraceae/Compositae)

(Syns.: S. costus (Decne.) Sch.Bip.; Aplotaxis lappa Decne.; Aucklandia costus Falc;
A. lappa Decne.; Theodorea costus Kuntze)

Abstract
A perennial herb, distributed across Himalayan region of India. Costus root was
known to the Greeks and Arabs, and was introduced to Europe by Arab
physicians, and was called Arabian Costus. Dioscorides said: “The best is that
which is fresh, light-colored, compact and of firm texture, dry, not worm-eaten,
devoid of an acrid smell, and which tastes hot and biting.” Arabian writers
described costus as “a wood brought from India, a well-known drug of sweet
odor with which women and infants are fumigated; it is diuretic, beneficial to
liver in a high degree, and for the colic, and for worms, and quartan fever as a
beverage; and for rheum, and defluxions, and pestilence, when the patient is
fumigated therewith; and for leprous-like disorder called Bahq, and the
discoloration of the face called Kalaf, when applied as a liniment; and it
confines bowels, expels wind, strengthen the stomach and heart, occasions
pleasurable sensations, is an ingredient in many sorts of perfumes, and is the best
of perfumes in odor when one fumigates therewith.” In Atharvaveda, it holds the
position next to Soma (a divine plant) in curing several diseases, and in
Ayurveda, its roots are used for fevers, skin diseases, and headache. Other
authors described its uses in asthma, inflammatory diseases, ulcer and stomach
problems, and also as incense. Some writers have identified two kinds of costus;
Qust-e-talkh (bitter) and Qust-e-shirin (sweet); which have been suggested as
being the older and younger roots, respectively. Saussurea lappa was introduced
in China from India, and is now cultivated in southwest China. In Chinese
medicine, it is described as a superior drug in The Herbal by Shen Nung and is
regarded as an aromatic stomachic, vermifuge, and fragrant; and used for
asthma, distension and pain in the chest and abdomen, indigestion, vomiting,
diarrhea, tenesmus, and quieting of premature uterine contractions during
pregnancy, and is also described as a sedative. Most pharmacologically active
substances present in roots are sesquiterpenes and sesquiterpene lactones; other
compounds include glycosides, anthraquinones, chlorogenic acid, b-costic acid,
daucosterol, b-sitosterol, and saussureamines A to E.
© Springer Nature Switzerland AG 2020 1609
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_166
1610 Saussurea lappa (Falc.) Lipsch.

Keywords




Arabian costus Costus elegant Jazar-ul-bahr Koosht-i-shirin Kushtha






Kut Mu-shiang Practige kostwurz Pushkaramula Qust shirin

Vernaculars: Urd.: Kuth, Qust shirin; Hin.: Kushta patchuk, Kust, Kut, Kutha,
Pokharmul; San.: Kashmirja, Kashtam, Kushta, Kushtam, Kushtha, Pushkaramula,
Puskara, Takmanashana, Utpalam; Ben.: Koshta, Kust, Kut, Pachak; Mal.: Sep-
pudday; Mar.: Kushta; Tam.: Chagal koshtam, Goshtam, Gostan, Jathi koshtam,
Koshtam, Kottam; Tel.: Chengulva, Goshtamu, Kashm koot, Kostu, Kustam; Ara.:
Auklandia, Jazar-ul-bahr, Qust; Chi.: Mu-shiang, Yunmuxiang; Eng.: Arabian
costus, Kut root; Fre.: Costus elegant; Ger.: Indische kostuswurzel, Practige
kostwurz; Per.: Koosht-i-shirin.
Description: A sturdy perennial herb, distributed across Himalayan region of
India. Stem simple 2 m high, with triangular basal leaves, terminal lobe attaining
length of 30 cm; petiole winged; cauline leaves shortly petiolate or sessile, auric-
ulate, lyrate, 15–30 cm long. Floral heads axillary or terminal, grouped 2–3, nearly
lobular, sessile, 3–4 cm in diameter; bracts numerous, oval, lanceolate, acuminate,
stiff, purple, pubescent when young, glabrous at maturity. Fruit an oblong achene,
glabrous, compressed, with pappus consisting of hairs in several rows. Root frag-
ments 4 cm long and 1 cm in diameter, light-brown externally and white inside, are
used medicinally as stomachic (Fig. 1).LXXIX
Actions and Uses: Costus root was known to the Greeks and Arabs, and was
introduced to Europe by Arab physicians, and was called Arabian Costus.
Dioscorides said: “The best is that which is fresh, light-colored, compact and of firm
texture, dry, not worm-eaten, devoid of an acrid smell, and which tastes hot and
biting.” Arabian writers described costus as “a wood brought from India, a
well-known drug of sweet odor with which women and infants are fumigated; it is
diuretic, beneficial to liver in a high degree, and for the colic, and for worms, and
quartan fever as a beverage; and for rheum, and defluxions, and pestilence, when
the patient is fumigated therewith; and for leprous-like disorder called Bahq, and
the discoloration of the face called Kalaf, when applied as a liniment; and it con-
fines bowels, expels wind, strengthen the stomach and heart, occasions pleasurable
sensations, is an ingredient in many sorts of perfumes, and is the best of perfumes in
odor when one fumigates therewith.”XL Dioscorides and Galen described it as a
diuretic, emmenagogue, and recommended taking costus with honey and wine to
stimulate sexual desire, is counterirritant, rubefacient, and useful in blunt muscle
injuries and rupture. Razi recommended costus oil for paresthesia and tremors.LXIX
In Atharvaveda, it holds the position next to Soma (a divine plant) in curing several
diseases, and in Ayurveda, its roots are used for fevers, skin diseases, and headache
[32]. Other authors described its uses in asthma, inflammatory diseases, ulcer and
stomach problems [31], and also as incense [37]. Some writers have identified two
kinds of costus; Qust-e-talkh (bitter) and Qust-e-shirin (sweet); which have been
suggested as being the older and younger roots, respectively. KabeeruddinLXXVII
Saussurea lappa (Falc.) Lipsch. 1611

Fig. 1 Saussurea lappa, Plant, Dinesh Valke, WikimediaCommons; ShareAlike 2.0 Generic CC
BY-SA 2.0, https://commons.wikimedia.org/wiki/File:Saussurea_%C2%BF_costus_%3F_(78395
95576).jpg; https://creativecommons.org/licenses/by-sa/2.0/deed.en

described Qust-e-shirin as being yellowish-white, light in weight and fragrant;

whereas, Qust-e-talkh is thicker, blackish outside and yellowish inside, and is often
referred to as Qust-e-hindi. Externally, it is considered styptic, anti-inflammatory
and astringent, and internally as nervine and cardiac tonic, expectorant, stomachic,
carminative, anthelmintic, diuretic, emmenagogue, and aphrodisiac. In earlier times
in India, it was extensively smoked as stimulant, and in powder form or as
astringent stimulant ointment applied to severe ulcerations, for worms in wounds,
and for toothache; and also used for rheumatism. It was also universally used by
shawl merchants of Kashmir as a protector from attacks of moths and vermin.XL
GhaniL described bitter variety as carminative, anti-inflammatory, analgesic and
beneficial in gout; and mentions the sweet variety stronger in functions than the
bitter one; it is a nervine tonic, aphrodisiac, carminative, stomachic, abortifacient,
anthelmintic, diuretic, emmenagogue, deobstruent, peripheral vasodilator and
beneficial in paralysis, facial palsy, spasms, tremors and ascites. Tayyab1 mentioned
bitter variety as poisonous and used only externally. He recommended the oil from
the bitter variety for massage in cases of poliomyelitis. Powdered root and alcoholic
extract are expectorant, and beneficial in bronchial asthma, especially the vagotonic
type.CV Khory and KatrakLXXXI called it stimulant and alterative, and used in the
treatment of cough, asthma, cholera and dyspepsia, chronic skin diseases and
rheumatism. Externally, it is used as astringent on ulcers, and as a paste made in
rose-water applied to swollen hands and feet, and to abdomen in obesity, and to
sprains and contusions.

1
Tayyab M: Personal Communication.
1612 Saussurea lappa (Falc.) Lipsch.

Saussurea lappa was introduced in China from India, and is now cultivated in
southwest China [45]. Saussurea genus plants are used in both traditional Chinese
and Tibetan folk medicines, as they effectively relieve internal heat or fever, har-
monize menstruation, invigorate blood circulation, stop bleeding, alleviate pain,
increase energy, and cure rheumatic arthritis [43]. It is acrid and bitter, with warm
property and known as Yunmuxiang, is ‘Qi’ (vital energy)-stimulant, spleen-
invigorating and digestant. Arab physicians use it to treat rheumatism, persistent
hiccups, and intestinal parasites.XVIII In Chinese medicine, it is described as a
superior drug in The Herbal by Shen Nung and is regarded as an aromatic stom-
achic, vermifuge, and fragrant; and used for asthma, distension and pain in the chest
and abdomen, indigestion, vomiting, diarrhea, tenesmus, and quieting of premature
uterine contractions during pregnancy,LXVI and is also described as a sedative.LXV
Phytoconstituents: Most pharmacologically active substances present in roots are
sesquiterpenes and sesquiterpene lactones, such as costunolide, a-cyclocostunolide,
b-cyclocostunolide, dihydrocostunolide, dehydrocostus lactone, mokko lactone,
cynaropicrin, dehydrocostuslactone, lappadilactone, santamarine, 4a-hydroxy-4b-
methyldihydrocostol, 10a-hydroxylartemisinic acid, and trans-syingin [6, 8, 9, 11,
34, 42, 45, 46, 48, 50]. Other compounds reported from the roots are glyco-
sides [26, 33], anthraquinones (chrysophanol, emodin, aloe-emodin-8-O-b-D-
glucopyranoside), chlorogenic acid, magnolialide, b-costic acid, reynosin, arbus-
culin A [26], 5,7-dihydroxy-2-methylchromone, p-hydroxybenzaldehyde, 3,5-
dimethoxy-4-hydroxybenzaldehyde, 3,5-dimethoxy-4-hydroxyacetophenone, ethyl
2-pyrrolidinone-5(s)-carboxylate, 5-hydroxymethylfuraldehyde, palmitic acid, suc-
cinic acid, glucose, daucosterol, b-sitosterol [11, 49], and saussureamines A to E
[47]. Volatile constituents of the roots cultivated in Uttarakhand Himalayas of India
included aldehydes, ketones (dehydrocostus lactone), and alcohols (elemol, c-costol,
vulgarol B, valerenol, and terpinen-4-ol) [13]. Lappadilactone, dehydrocostuslac-
tone, and costunolide are the most potent cytotoxic to human cancer cell lines [38].
Roots are also reported to contain the alkaloid saussurine, and an essential oil
comprising of costulactone, costol, costene, camphene, and phellandrene.LXXIX
Pharmacology: Ethanol root extract exhibited significant anti-inflammatory effect
[12, 39], reduced serum levels of CRP, TNF-a, IL-1b, and IL-6, and improved
immune and antioxidant responses to inflammation [39]. Sesquiterpene lactone
fraction exhibited potent anti-inflammatory activity [10], and cynaropicrin and
dehydrocostus lactone strongly inhibited TNF-a release from LPS-stimulated mur-
ine macrophages [6]. Costunolide and dehydrocostuslactone also inhibit LPS-
induced NO production and NF-kB and IL-1b activation [16, 18, 19, 24, 25, 29, 36,
51], and inhibit killing activity of cytotoxic T lymphocytes [40]. Roots possess
significant antioxidant activity [4, 30], that has been attributed to the presence of
chlorogenic acid [30]. Aqueous-methanol extract exhibits protective effects against
D-galactosamine and LPS-hepatotoxicity in mice [44].
Saussurea lappa (Falc.) Lipsch. 1613

Methanol extract elicited significant positive inotropic effect, a negative chron-

otropic effect and increased coronary flow in isolated rabbit heart [2], while the
aqueous extract significantly protected against isoproterenol myocardial injury in
rats [35]. The rhizome extract is also reported to potentiate effect of barbiturate [3].
Ethanol extract significantly inhibited growth of clinical isolates of MRSA,
P. aeruginosa, E. coli, K. pneumoniae, ESbetaL, A. baumannii [14], standard and
clinical strains of H. pylori [27], and 100% growth inhibition of T. cruzi [28]. It
induces growth inhibition and apoptosis of human gastric cancer cells [22, 23], and
its sesquiterpene constituent, cynaropicrin potently inhibited proliferation of
leukocyte cancer cell lines [7]; whereas dehydrocostus lactone inhibited cell growth
and induced apoptosis in androgen-independent prostate cancer cells [20, 21], and
hepatocellular carcinoma cells [15].
Clinical Studies: Four-months treatment of a small number of Indian IHD patients
with aqueous extract resulted in moderate symptoms improvement in more than
50% patients, very significant reduction in serum cholesterol and TGs, and a
synergistic response with a calcium channel blocker [41]. A single dose of pow-
dered root and equivalent amount of its methanol extract to children with nema-
todes infection significantly reduced percentage in the fecal eggs per gram similar to
pyrantel pamoate [1].
Mechanism of Action: Costunolide is a novel angiogenesis inhibitor, and selec-
tively inhibits VEGF-induced proliferation and chemotaxis of HUVEC [17]; whereas,
cynaropicrin produced its cytotoxic effect by inducing apoptosis and cell cycle arrest
at G1/S phase [7].
Human A/Es, Allergy and Toxicity: Costus oil, used in perfumery, and its
sesquiterpene lactones, costunolide and dehydrocostuslactone, have commonly
caused allergic contact dermatitis [5].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It is an important drug in Unani and Ayurveda, but no significant
clinical trials have been conducted to validate any of its activities, except anecdotal
accounts.

References
1. Akhtar MS, Riffat S. Field trial of Saussurea lappa roots against nematodes
and Nigella sativa seeds against cestodes in children. J Pakistan Med Assoc.
1991;41:185–7.
2. Akhtar MS, Bashir S, Malik MN, Manzoor R. Cardiotonic activity of
methanolic extract of Saussurea lappa Linn roots. Pak J Pharm Sci. 2013;
26:1197–201.
3. Aswal BS, Bhakuni DS, Goel AK, et al. Screening of Indian plants for
biological activity: Part X. Indian J Exp Biol. 1984;22:312–32.
1614 Saussurea lappa (Falc.) Lipsch.

4. Chang KM, Choi SI, Kim GH. Antioxidant activity of Saussurea lappa C.
B. Clarke roots. Prev Nutr Food Sci. 2012;17:306–9.
5. Cheminat A, Stampf JL, Benezra C, et al. Allergic contact dermatitis to
costus: removal of haptens with polymers. Acta Derm Venereol. 1981;61:
525–9.
6. Cho JY, Baik KU, Jung JH, Park MH. In vitro anti-inflammatory effects of
cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Phar-
macol. 2000;398:399–407.
7. Cho JY, Kim AR, Jung JH, et al. Cytotoxic and proapoptotic activities of
cynaropicrin, a sesquiterpene lactone, on the viability of leukocyte cancer
cell lines. Eur J Pharmacol. 2004;492:85–94.
8. Choi HG, Lee DS, Li B, et al. Santamarin, a sesquiterpene lactone isolated
from Saussurea lappa, represses LPS-induced inflammatory responses via
expression of heme oxygenase-1 in murine macrophage cells. Int Immunophar-
macol. 2012;13:271–9.
9. Choi JY, Na M, Hyun Hwang I, et al. Isolation of betulinic acid, its methyl
ester and guaiane sesquiterpenoids with protein tyrosine phosphatase 1B
inhibitory activity from the roots of Saussurea lappa C.B. Clarke. Molecules.
2009;14:266–72.
10. Damre AA, Damre AS, Saraf MN. Evaluation of sesquiterpene lactone
fraction of Saussurea lappa on transudative, exudative and proliferative
phases of inflammation. Phytother Res. 2003;17:722–5.
11. Duan JA, Hou P, Tang Y, et al. A new sesquiterpene and other constituents
from Saussurea lappa root. Nat Prod Commun. 2010;5:1531–4.
12. Gokhale AB, Damre AS, Kulkami KR, Saraf MN. Preliminary evaluation of
anti-inflammatory and antiarthritic activity of S. lappa, A. speciosa and A.
aspera. Phytomedicine. 2002;9:433–7.
13. Gwari G, Bhandari U, Andola HC, Lohani H, Chauhan N. Volatile con-
stituents of Saussurea costus roots cultivated in Uttarakhand Himalayas.
India. Pharmacognosy Res. 2013;5:179–82.
14. Hasson SS, Al-Balushi MS, Alharthy K, et al. Evaluation of antiresistant
activity of Auklandia (Saussurea lappa) root against some human patho-
gens. Asian Pac J Trop Biomed. 2013;3:557–62.
15. Hsu YL, Wu LY, Kuo PL. Dehydrocostuslactone, a medicinal plant-derived
sesquiterpene lactone, induces apoptosis coupled to endoplasmic reticulum
stress in liver cancer cells. J Pharmacol Exp Ther. 2009;329:808–19.
16. Jeong GS, Pae HO, Jeong SO, et al. The alpha-methylene-gamma-butyrolactone
moiety in dehydrocostus lactone is responsible for cytoprotective heme
oxygenase-1 expression through activation of the nuclear factor E2-related
factor 2 in HepG2 cells. Eur J Pharmacol. 2007;565:37–44.
17. Jeong SJ, Itokawa T, Shibuya M, et al. Costunolide, a sesquiterpene lactone
from Saussurea lappa, inhibits the VEGFR KDR/Flk-1 signaling pathway.
Cancer Lett. 2002;187:129–33.
Saussurea lappa (Falc.) Lipsch. 1615

18. Jin M, Lee HJ, Ryu JH, Chung KS. Inhibition of LPS-induced NO
production and NF-kappaB activation by a sesquiterpene from Saussurea
lappa. Arch Pharm Res. 2000;23:54–8.
19. Kang JS, Yoon YD, Lee KH, et al. Costunolide inhibits interleukin-1beta
expression by downregulation of AP-1 and MAPK activity in LPS-stimulated
RAW 264.7 cells. Biochem Biophys Res Commun. 2004;313:171–7.
20. Kim EJ, Lim SS, Park SY, et al. Apoptosis of DU145 human prostate cancer
cells induced by dehydrocostus lactone isolated from the root of Saussurea
lappa. Food Chem Toxicol. 2008;46:3651–8.
21. Kim EJ, Hong JE, Lim SS, et al. The hexane extract of Saussurea lappa and
its active principle, dehydrocostus lactone, inhibit prostate cancer cell
migration. J Med Food. 2012;15:24–32.
22. Ko SG, Kim HP, Jin DH, et al. Saussurea lappa induces G2-growth arrest
and apoptosis in AGS gastric cancer cells. Cancer Lett. 2005;220:11–9.
23. Ko SG, Koh SH, Jun CY, et al. Induction of apoptosis by Saussurea lappa
and Pharbitis nil on AGS gastric cancer cells. Biol Pharm Bull. 2004;27:
1604–10.
24. Lee GI, Ha JY, Min KR, et al. Inhibitory effects of oriental herbal medicines
on IL-8 induction in lipopolysaccharide-activated rat macrophages. Planta
Med. 1995;61:26–30.
25. Lee HJ, Kim NY, Jang MK, et al. A sesquiterpene, dehydrocostus lactone,
inhibits the expression of inducible nitric oxide synthase and TNF-alpha in
LPS-activated macrophages. Planta Med. 1999;65:104–8.
26. Li S, An TY, Li J, et al. PTP1B inhibitors from Saussrurea lappa. J Asian
Nat Prod Res. 2006;8:281–6.
27. Li Y, Xu C, Zhang Q, Liu JY, Tan RX. In vitro anti-Helicobacter pylori
action of 30 Chinese herbal medicines used to treat ulcer diseases.
J Ethnopharmacol. 2005;98:329–33.
28. Lirussi D, Li J, Prieto JM, et al. Inhibition of Trypanosoma cruzi by plant
extracts used in Chinese medicine. Fitoterapia. 2004;75:718–23.
29. Matsuda H, Toguchida I, Ninomiya K, et al. Effects of sesquiterpenes
and amino acid-sesquiterpene conjugates from the roots of Saussurea lappa on
inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-
activated macrophages. Bioorg Med Chem. 2003;11:709–15.
30. Pandey MM, Govindarajan R, Rawat AK, Pushpangadan P. Free radical
scavenging potential of Saussarea costus. Acta Pharm. 2005;55:297–304.
31. Pandey MM, Rastogi S, Rawat AK. Saussurea costus: botanical, chemical
and pharmacological review of an ayurvedic medicinal plant. J Ethnophar-
macol. 2007;110:379–90 (Review).
32. Prasad PV, Subhaktha PK. Medicohistorical review of drug Kustha. Bull
Indian Inst Hist Med Hyderabad. 2002;32:79–92.
33. Rao KS, Babu GV, Ramnareddy YV. Acylated flavone glycosides from the
roots of Saussurea lappa and their antifungal activity. Molecules. 2007;
12:328–44.
1616 Saussurea lappa (Falc.) Lipsch.

34. Robinson A, Kumar TV, Sreedhar E, et al. A new sesquiterpene lactone

from the roots of Saussurea lappa: structure-anticancer activity study.
Bioorg Med Chem Lett. 2008;18:4015–7.
35. Saleem TS, Lokanath N, Prasanthi A, et al. Aqueous extract of Saus-
surea lappa root ameliorate oxidative myocardial injury induced by
isoproterenol in rats. J Adv Pharm Technol Res. 2013;4:94–100.
36. Sarwar A, Enbergs H. Effects of Saussurea lappa roots extract in ethanol on
leukocyte phagocytic activity, lymphocyte proliferation and interferon-
gamma (IFN-gamma). Pak J Pharm Sci. 2007;20:175–9.
37. Shah NC. Herbal folk medicines in Northern India. J Ethnopharmacol.
1982;6:293–301.
38. Sun CM, Syu WJ, Don MJ, et al. Cytotoxic sesquiterpene lactones from the
root of Saussurea lappa. J Nat Prod. 2003;66:1175–80.
39. Tag HM, Khaled HE, Ismail HA, El-Shenawy NS. Evaluation of anti-inflam-
matory potential of the ethanolic extract of the Saussurea lappa root (costus)
on adjuvant-induced monoarthritis in rats. J Basic Clin Physiol Pharmacol.
2016;27:71–8.
40. Taniguchi M, Kataoka T, Suzuki H, et al. Costunolide and dehydrocostus
lactone as inhibitors of killing function of cytotoxic T lymphocytes. Biosci
Biotechnol Biochem. 1995;59:2064–7.
41. Upadhyay OP, Ojha JK, Bajpai HS, Hathwal AK. Study of kustha
(Saussurea lappa, Clarke) in ischaemic heart disease. Anc Sci Life. 1993;
13:11–8.
42. Wang F, Xie ZH, Gao Y, et al. Sulfonated guaianolides from Saussurea
lappa. Chem Pharm Bull (Tokyo). 2008;56:864–5.
43. Wang YF, Ni ZY, Dong M, et al. Secondary metabolites of plants from the
genus Saussurea: chemistry and biological activity. Chem Biodivers. 2010;
7:2623–59.
44. Yaeesh S, Jamal Q, Shah AJ, Gilani AH. Antihepatotoxic activity of Saus-
surea lappa extract on D-galactosamine and lipopolysaccharide-induced
hepatitis in mice. Phytother Res. 2010;24 Suppl 2:S229–32. (Erratum in:
Phytother Res. 2010;24 Suppl 2:S233–4).
45. Yin HQ, Fu HW, Hua HM, et al. Two new sesquiterpene lactones with the
sulfonic acid group from Saussurea lappa. Chem Pharm Bull (Tokyo).
2005;53:841–2.
46. Yin HQ, Hua HM, Fu HW, et al. A new sesquiterpene lactone with sulfonic
acid group from Saussurea lappa. J Asian Nat Prod Res. 2007;9:579–82.
47. Yoshikawa M, Hatakeyama S, Inoue Y, Yamahara J. Saussureamines A, B,
C, D, and E, new antiulcer principles from Chinese Saussureae Radix. Chem
Pharmaceu Bull. 1993;41:214–6.
48. Zhang T, Ma L, Wu F, Chen R. Chemical constituents from a portion of
ethanolic extract of Saussurea lappa roots. Zhongguo Zhong Yao Za Zhi.
2012;37:1232–6 (Chinese).
Saussurea lappa (Falc.) Lipsch. 1617

49. Zhang T, Wang H, Du G, Chen R. Study on chemical constituents from

roots of Saussurea lappa. Zhongguo Zhong Yao Za Zhi. 2009;34:1223–4
(Chinese).
50. Zhang T, Yang Y, Du G, Chen R. Study on chemical constituents from the
roots of Saussurea lappa. Zhongguo Zhong Yao Za Zhi 2011;36:1620–2
(Chinese).
51. Zhao F, Xu H, He EQ, et al. Inhibitory effects of sesquiterpenes from
Saussurea lappa on the overproduction of nitric oxide and TNF-alpha release
in LPS-activated macrophages. J Asian Nat Prod Res. 2008;10:1045–53.
Semecarpus anacardium L.
(Anacardiaceae)

(Syns.: S. latifolia Pers.; Anacardium latifolium Lam.; A. officinarum Gaertn.;

A. orientale auct. ex Steud.)

Abstract
A small tree native to Himalayan and subtropical parts of India. Muslim
physicians order the juice to be always mixed with oil, butter or some oily seed
when used for internal administration; and consider it useful in all kinds of skin
diseases, palsy, epilepsy, and other affections of the nervous system. It is
regarded by the Hindus as acrid, heating, stimulant, digestive, nervine and
escharotic, and is used in dyspepsia, piles, skin diseases and nervous debility. It
is prepared for internal use in Ayurveda by boiling with cow dung and washed
with cold water. In Unani medicine, it is used as aphrodisiac, nerve tonic and
stimulant to improve intellect and memory, and to dye hair. Avicenna said its
juice is sweet and harmless; whereas, Ibn al-Baitar described the blackish red
juice as very poisonous and very hot, which if taken alone may result in
bodyaches, stimulation, hallucinations, leucoderma, leprosy, female infertility,
and sometimes instant death. It should never be used without detoxification and
in young men and those of hot temperament. Phytochemical analyses of the nut
show the presence of biflavonoids, phenolic compounds, bhilawanols, minerals,
vitamins and amino acids. Fruit and nut extracts show various activities like
antiatherogenic, antioxidant, anti-inflammatory, antimicrobial, antireproductive,
hypoglycemic, anticarcinogenic, CNS stimulant, and hair growth promoting.
Ethanol extract of dried nuts significantly reduced blood glucose of normal rats
and diabetic rats, and restored altered activities of enzymes involved in
carbohydrate metabolism and energy production. The nut milk extract signif-
icantly reversed alterations in bone turnover in arthritic animals by modulating
calcium and phosphorus levels, and activities of acid phosphatase and alkaline
phosphatase enzymes. Nut milk extract also decreased TC, LDL-C, VLDL-C,
TGs, phospholipids and FFA, and increased HDL-C levels of diabetic, and
hypercholesterolemic rats.

© Springer Nature Switzerland AG 2020 1619

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_167
1620 Semecarpus anacardium L.

Keywords




Anacardio orientale Anakardien-herznuß Bhallataka Bhilawan Biladur







Habb-al-fahm Ligas Malakkanoot Marking nut Ostindisk elefantlus

Vernaculars: Urd.: Bhilawan; Hin.: Bhela, Bhilawa (Bhilāvā); San.: Agnimukhi,

Arushkara, Bhallataka, Bhallatamu; Ben.: Bhalava, Bhela, Bhelatuki; Guj.: Bhilamu;
Mal.: Alakkucēru, Cēru, Chermara, Kanpura cherun-kuru, Themburi; Mar.: Bhil-
ama, Bibba, Bibnava; Tam.: Erimugi, Seragkottai, Shayrang, Shenkottai, Sher-
ankottai; Tel.: Bhallatamu-jodi, Jeedi ginja, Jeedivittulu, Jidi-chettu; Ara.: Baladar
(nut), Habb-al-fahm, Habb-al-qalb, Hatul-phahama; Dan.: Ostindisk elefantlus; Dut.:
Malakkanoot, Oostindische acajounoot, Oost-indische olifantsluis; Eng.: Marany
nut, Marking nut, Oriental cashew nut, Phobi nut-tree, Varnishtree; Fre.: Anacarde
d’orient, Noix à marquer, Noix des marais; Ger.: Anakardien-herznuß, Ostindischer
merkfruchtbaum, Ostindischer tintenbaum; Gre.: Semekarpos anakardion; Ita.:
Anacardio orientale; Jap.: Anakarudiumu orientaare; Nep.: Bhalaayo, Kaag bha-
laayo; Per.: Balazar, Behdur, Biladur; Por.: Anacárdio oriental; Rus.: Semekarpus
anakardii; Spa.: Anacardio oriental; Tag.: Kaming, Ligas.
Description: A small tree native to Himalayan and subtropical parts of India,
reaching a height of 12 m; leaves are somewhat crowded at the ends of the bran-
ches, lanceolate-obovate to oblong-obovate, 10–25 cm long, hairy, whitish beneath,
rounded or somewhat pointed at the tip, and usually pointed at the base. Flowers are
whitish, glomerate, 2–2.5 mm long and are borne on panicles which are usually
longer than the leaves. Fruit, borne in clusters, resemble in shape the cashew but is
much smaller.CXVII Arabs described the marking nut resembling the heart of an
animal, the torus representing the auricles, and the fruit the ventricles; in dry
commercial form the torus is seldom present, and the fruit is of the size and shape of
a broad bean, black in color, and quite hard and dry externally, but upon breaking
the outer skin with a knife, the central cellular portion of the pericarp is full of a
brown oily acrid juice; inside the pericarp is a thin shell conforming to it, and
containing a large flat kernel, which has no acrid properties (Figs. 1 and 2).XL
Actions and Uses: Muslim physicians order the juice (temperament, hot 4° and
dry 4°) to be always mixed with oil, butter or some oily seed when used for internal
administration; and consider it useful in all kinds of skin diseases, palsy, epilepsy,
and other affections of the nervous system. Marking nut is regarded by the Hindus
as acrid, heating, stimulant, digestive, nervine and escharotic, and is used in dys-
pepsia, piles, skin diseases and nervous debility. It is prepared for internal use in
Ayurveda by boiling with cow dung and washed with cold water.XL In Unani
medicine, it is used as aphrodisiac, nerve tonic and stimulant to improve intellect
and memory, and to dye hair.L Avicenna said its juice is sweet and harmless;
whereas, Ibn al-BaitarLXIX described the blackish red juice as very poisonous and
very hot, which if taken alone may result in bodyaches, stimulation, hallucinations,
leucoderma, leprosy, female infertility, and sometimes instant death. It should never
be used without detoxification and in young men and those of hot temperament.
Semecarpus anacardium L. 1621

Fig. 1 Semecarpus anacardium, Illustration, William Roxburgh, WikimediaCommons, https://

commons.wikimedia.org/wiki/File:Semecarpus_anacardium.jpg

Fig. 2 Semecarpus anacardium, Dried Fruit (Nut), H. Zell, WikimediaCommons; ShareAlike

Unported 3.0 CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Semecarpus_anacardium_
02.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en
1622 Semecarpus anacardium L.

It is, however, beneficial for all phlegmatic brain diseases, such as paralysis, palsy,
nerve looseness, loss and weakness of memory; daily use of 2 g is said to improve
memory. NadkarniCV described the juice of the pericarp and the oil as powerful
escharotics, locally caustic and vesicant; and the oil as a powerful antiseptic and
cholagogue. Black thick juice is used as a local stimulant for the relief of rheumatic
pains, leprous affections, inflammation of bones and joints, bruises and sprains.
When applied to the skin it causes intense pain and swelling, causes deep bluish
colored vesicles and intractable sore. The oil obtained from it, mixed with butter or
oil is used as stimulant, narcotic, digestive, alterative and nervine tonic, and given
in dyspepsia, worms, nervous debility, asthma and epilepsy.LXXXI In Ayurveda, it is
used for rejuvenation, rheumatoid arthritis, fever, neurological disorders [41], nadi
dourbalya, apasmara, gridhrasi, amavata, and shvasa [20]. Fruit of Bhallataka is
used either as a single drug or as an ingredient in many compound Ayurvedic
formulations. A variety of nut extract preparations are effective against many dis-
eases, viz. arthritis, tumors, infections, and are nontoxic even at a high dose of
2,000 mg/kg [25]. In the Philippines, the plant is generally regarded as poisonous
and severe cases of poisoning have occurred; the oil of the pericarp is sometimes
used as a caustic or escharotic, and in the treatment of indolent ulcers.LVI
Phytoconstituents: Phytochemical analyses of the nut show the presence of bifla-
vonoids, phenolic compounds, bhilawanols, minerals, vitamins and amino acids [25,
34]. Major constituents of the tarry oil are anacardic acid and bhilawanol, a mixture of
3-n-pentadec(en)yl catechols. Bhilawanol A and B are known as urushiols; anacardic
acid is also closely related to urushiol [19]. A biflavonoid compound tetrahydroa-
mentoflavone possesses potent XO [4], and COX-1 inhibitory activities [33], and two
flavonoids 3,4,2′,4′-tetrahydroxychalcone (butein) and 7,3′,4′-trihydroxyflavone
exhibit marked COX-1 and moderate COX-2 inhibitory activity [33]. A phenolic
glucoside, anacardoside, was also reported from the seeds [8].
Pharmacology: Fruit and nut extracts show various activities like antiatherogenic,
antioxidant, anti-inflammatory, antimicrobial, antireproductive, hypoglycemic,
anticarcinogenic, CNS stimulant, and hair growth promoting [34]. Chloroform nut
extract significantly reduced acute carrageenan-induced paw edema in rats and was
also active against secondary lesions of adjuvant-induced arthritis [26, 31]. Lyso-
somal enzyme activity and protein-bound carbohydrate component levels were
significantly normalized after oral administration of milk extract in olive oil to rats
with adjuvant-induced arthritis [44, 45], and reduced LPO and modulated cellular
antioxidant defense system [28, 29, 46]. The nut milk extract significantly reversed
alterations in bone turnover in arthritic animals by modulating calcium and phos-
phorus levels, and activities of acid phosphatase and alkaline phosphatase enzymes,
and decreasing levels and expression of TNFa [27], and significantly reduced NO
and myeloperoxidase levels. It also elicited strong analgesic and antipyretic effect in
yeast-induced hyperemia in rats [30]. However, Singh et al. [38] reported that the
extract inhibits spontaneous and LPS induced production of proinflammatory
cytokines IL-1b and IL-12p40, suppressed LPS activated NO production in mouse
macrophages, but had no effect on TNF-a and IL-6 production. Petroleum ether,
Semecarpus anacardium L. 1623

chloroform and methanol extracts of the stem bark also exhibit significant analgesic
activity, with methanol extract being more efficacious [18].
Ethanol extract of dried nuts significantly reduced blood glucose of normal rats
and STZ-diabetic rats [5], and restored altered activities of enzymes involved in
carbohydrate metabolism and energy production [6]. Nut milk extract also caused a
significant increase in plasma insulin, HOMA-b, and activities of glycolytic
enzymes, and decreased HOMA-IR of diabetic rats [14], and decreased HbA1c in
high-fat diet diabetic rats [15, 16]. Nut milk extract decreased production of reactive
oxygen and nitrogen species, and reversed changes in mitochondrial membrane
potential and the influx of calcium into mitochondria of STZ-[11], and alloxan-
diabetic rats [17]. Nut milk extract also decreased TC, LDL-C, VLDL-C, TGs,
phospholipids and FFA, and increased HDL-C levels of STZ-diabetic [10], and
hypercholesterolemic rats [47], and significantly increased mRNA expression of
PPAR c [13]. Ethanol bark extract lowered blood glucose, TC, LDL-C and TGs of
alloxan-diabetic rats [3]. Nut shell extract also significantly reduced serum TC and
LDL-C, and prevented accumulation of cholesterol/triglycerides in liver, heart
muscle and aorta and regressed aortic plaques in cholesterol-fed rabbits [35]. Nut
shell alcoholic extract significantly protected against ferrous sulfate-induced LPO,
without showing hydroxyl and superoxide anion scavenging property [42].
A fraction of the extract significantly reduced serum cholesterol in rats fed with
atherogenic diet and increased serum HDL-C, and inhibited LPS induced NO
production in rat macrophages [41]. Nut extract was also protective against lead
acetate-induced hepatotoxicity [1]. Alcohol extract of dry nuts is reported to show
antifungal activity against A. fumigatus and C. albicans [37]; whereas petroleum
ether and chloroform extracts were active against Indian earthworm (Pheritima
posthuma), comparable to albendazole and piperazine citrate [22]. Methanol extract
(20% ointment) of stem bark increased epithelialization of incision wounds with a
high rate of wound contraction, and significantly increased the tensile strength [19].
Hot methanol nut extract exhibited antitumor activity against lymphocytic
leukemia in mice and increased their median survival time [9]. Treatment with nut
milk reversed enzyme markers of aflatoxin B1-induced hepatocarcinogenicity in
rats to near normal control values [23], increased levels of nonenzymic antioxidants
[24], and reduced levels of proangiogenic factors in DMBA-induced mammary
tumor-bearing rats [32]. Nut milk extract in leukemia-bearing mice cleared leu-
kemic cells from bone marrow and internal organs [40]. Nut oil was cytotoxic to
leukemic cells but not to normal human lymphocytes [7]. Ethanol nut extract also
displayed strong cytotoxic effect on COLO 320 tumor cells [39]. Aqueous extract
increased activities of antioxidant enzymes, such as CAT, SOD and GST in
lymphoma-transplanted mice [43]. Fifty percent ethanol extract of fruit to male
albino rats for 60-days resulted in spermatogenic arrest, and the sperm motility and
density were significantly reduced [36].
Mechanism of Action: AChE inhibitory activity of methanol and aqueous extracts
(methanol extract being more active) may contribute to memory-enhancing effect
[48]. Two catechol alkenyls were identified as the AChE inhibitors [2].
1624 Semecarpus anacardium L.

Human A/Es, Allergy and Toxicity: Tarry oil (urushiol) present in fruit pericarp
induces contact dermatitis causing allergic rashes and blisters; topical application of
pounded leaves of Azadirachta indica reduces itching and burning sensations [20].
An 18-year-old man developed skin lesions and anuria following exposure to the
sap; renal biopsy showed diffuse cortical necrosis, the mechanism of which is
unknown [21].
Animal Toxicity: Oral LD50s of successively extracted petroleum ether, chloro-
form and methanol extracts of stem bark are reported to be 700 mg/kg for petro-
leum ether and chloroform extracts in mice, and 500 mg/kg for methanol extract in
Wistar rats [23, 24]. LD50 of chloroform soluble fraction of nut in rats was also
reported as 230 mg/kg body weight or 1,380 mg/m2 when expressed for body
surface area [12]. Oral administration of ethanol bark extracts to rats for 14-days
was nonlethal and nontoxic up to a dose of 400 mg/kg [3].
Commentary: This potentially toxic drug is valued in both Unani and Ayurveda,
but used cautiously. Despite its significant anti-inflammatory, lipids modifying,
antidiabetic and anticancer activities in pharmacological screenings, there are no
clinical studies to validate these effects in humans.

References
1. Abirami N, Raju VS, Rajathi K. Effect of Semecarpus anacardium against
lead induced toxicity in rats. Anc Sci Life. 2007;27:24–7.
2. Adhami HR, Linder T, Kaehlig H, et al. Catechol alkenyls from Semecarpus
anacardium: acetylcholinesterase inhibition and binding mode predictions.
J Ethnopharmacol. 2012;139:142–8.
3. Ali MA, Wahed MI, Khatune NA, et al. Antidiabetic and antioxidant
activities of ethanolic extract of Semecarpus anacardium (Linn.) bark. BMC
Complement Altern Med. 2015;15:138.
4. Arimboor R, Rangan M, Aravind SG, Arumughan C. Tetrahydroamento-
flavone (THA) from Semecarpus anacardium as a potent inhibitor of xan-
thine oxidase. J Ethnopharmacol. 2011;133:1117–20.
5. Arul B, Kothai R, Christina AJ. Hypoglycemic and antihyperglycemic effect
of Semecarpus anacardium Linn. in normal and streptozotocin-induced
diabetic rats. Methods Find Exp Clin Pharmacol. 2004;26:759–62.
6. Aseervatham J, Palanivelu S, Panchanadham S. Semecarpus anacardium
(Bhallataka) alters the glucose metabolism and energy production in diabetic
rats. Evid Based Complement Alternat Med. 2011;2011. pii:142978.
7. Chakraborty S, Roy M, Taraphdar AK, Bhattacharya RK. Cytotoxic effect
of root extract of Tiliacora racemosa and oil of Semecarpus anacardium nut
in human tumour cells. Phytother Res. 2004;18:595–600.
8. Gil RR, Lin LZ, Cordell GA, et al. Anacardoside from the seeds of Semecarpus
anacardium. Phytochemistry. 1995;39:405–7.
Semecarpus anacardium L. 1625

9. Indap MA, Ambaye RY, Gokhale SV. Antitumour and pharmacological

effects of the oil from Semecarpus anacardium Linn. f. Indian J Physiol
Pharmacol. 1983;27:83–91.
10. Jaya A, Shanthi P, Sachdanandam P. Hypolipidemic activity of Semecarpus
anacardium in streptozotocin induced diabetic rats. Endocrine. 2010;38:
11–7.
11. Jaya A, Shanthi P, Sachdanandam P. Modulation of oxidative/nitrosative
stress and mitochondrial protective effect of Semecarpus anacardium in
diabetic rats. J Pharm Pharmacol. 2010;62:507–13.
12. Kesava Rao KV, Gothoskar SV, Chitnis MP, Ranadive KJ. Toxicological
study of Semecarpus anacardium nut extract. Indian J Physiol Pharmacol.
1979;23:115–20.
13. Khan HB, Vinayagam KS, Moorthy BT, et al. Anti-inflammatory and
antihyperlipidemic effect of Semecarpus anacardium in a high fat diet:
STZ-induced Type 2 diabetic rat model. Inflammopharmacology. 2013;21:
37–46.
14. Khan HB, Vinayagam KS, Palanivelu S, Panchanadham S. Ameliorating
effect of Semecarpus anacardium Linn. nut milk extract on altered glucose
metabolism in high fat diet STZ induced type 2 diabetic rats. Asian Pac J
Trop Med. 2012;5:956–61.
15. Khan HB, Vinayagam KS, Renny CM, et al. Potential antidiabetic effect of
the Semecarpus anacardium in a type 2 diabetic rat model. Inflammophar-
macology. 2013;21:47–53.
16. Khan HB, Vinayagam KS, Sekar A, et al. Antidiabetic and antioxidant
effect of Semecarpus anacardium Linn. nut milk extract in a high-fat diet
STZ-induced type 2 diabetic rat model. J Diet Suppl. 2012;9:19–33.
17. Kothai R, Arul B, Kumar KS, Christina AJ. Hypoglycemic and antiper-
glycemic effects of Semecarpus anacardium Linn. in normal and alloxan-
induced diabetic rats. J Herb Pharmacother. 2005;5:49–56.
18. Lingaraju GM, Hoskeri HJ, Krishna V, Babu PS. Analgesic activity and
acute toxicity study of Semecarpus anacardium stem bark extracts using
mice. Pharmacognosy Res. 2011;3:57–61.
19. Lingaraju GM, Krishna V, Joy Hoskeri H, et al. Wound healing promoting
activity of stem bark extract of Semecarpus anacardium using rats. Nat Prod
Res. 2012;26:2344–7.
20. Llanchezhian R, Joseph CR, Rabinarayan A. Urushiol-induced contact
dermatitis caused during Shodhana (purificatory measures) of Bhallataka
(Semecarpus anacardium Linn.) fruit. Ayu. 2012;33:270–3.
21. Matthai TP, Date A. Renal cortical necrosis following exposure to sap of the
marking-nut tree (Semecarpus anacardium). Am J Trop Med Hyg. 1979;
28:773–4.
22. Pal D, Mohapatra TK, Das A. Evaluation of anthelmintic activity of nuts of
Semecarpus anacardium. Anc Sci Life. 2008;27:41–4.
1626 Semecarpus anacardium L.

23. Premalatha B, Muthulakshmi V, Sachdanandam P. Anticancer potency of

the milk extract of Semecarpus anacardium Linn. nuts against aflatoxin B1
mediated hepatocellular carcinoma bearing Wistar rats with reference to
tumour marker enzymes. Phytother Res. 1999;13:183–7.
24. Premalatha B, Sachdanandam P. Semecarpus anacardium L. nut extract
administration induces the in vivo antioxidant defence system in aflatoxin
B1 mediated hepatocellular carcinoma. J Ethnopharmacol. 1999;66:131–9.
25. Premalatha B. Semecarpus anacardium Linn. nuts—a boon in alternative
medicine. Indian J Exp Biol. 2000;38:1177–82 (Review).
26. Ramprasath VR, Shanthi P, Sachdanandam P. Anti-inflammatory effect of
Semecarpus anacardium Linn. nut extract in acute and chronic inflamma-
tory conditions. Biol Pharm Bull. 2004;27:2028–31.
27. Ramprasath VR, Shanthi P, Sachdanandam P. Curative effect of Semecarpus
anacardium Linn. nut milk extract against adjuvant arthritis—with special
reference to bone metabolism. Chem Biol Interact. 2006;160:183–92.
28. Ramprasath VR, Shanthi P, Sachdanandam P. Effect of Semecarpus
anacardium Linn. nut milk extract on rat neutrophil functions in adjuvant
arthritis. Cell Biochem Funct. 2006;24:333–40.
29. Ramprasath VR, Shanthi P, Sachdanandam P. Evaluation of antioxidant
effect of Semecarpus anacardium Linn. nut extract on the components of
immune system in adjuvant arthritis. Vascul Pharmacol. 2005;42:179–86.
30. Ramprasath VR, Shanthi P, Sachdanandam P. Immunomodulatory and anti-
inflammatory effects of Semecarpus anacardium Linn. nut milk extract in
experimental inflammatory conditions. Biol Pharm Bull. 2006;29:693–700.
31. Saraf MN, Ghooi RB, Patwardhan BK. Studies on the mechanism of action
of Semecarpus anacardium in rheumatoid arthritis. J Ethnopharmacol. 1989;
25:159–64.
32. Sathish S, Shanthi P, Sachdanandam P. Mitigation of DMBA-induced
mammary carcinoma in experimental rats by antiangiogenic property of
Kalpaamruthaa. J Diet Suppl. 2011;8:144–57.
33. Selvam C, Jachak SM. A cyclooxygenase (COX) inhibitory biflavonoid
from the seeds of Semecarpus anacardium. J Ethnopharmacol. 2004;95:
209–12.
34. Semalty M, Semalty A, Badola A, et al. Semecarpus anacardium Linn.: a
review. Pharmacogn Rev. 2010;4:88–94.
35. Sharma A, Mathur R, Dixit VP. Hypocholesterolemic activity of nut shell
extract of Semecarpus anacardium (Bhilawa) in cholesterol fed rabbits.
Indian J Exp Biol. 1995;33:444–8.
36. Sharma A, Verma PK, Dixit VP. Effect of Semecarpus anacardium fruits on
reproductive function of male albino rats. Asian J Androl. 2003;5:121–4.
37. Sharma K, Shukla SD, Mehta P, Bhatnagar M. Fungistatic activity of
Semecarpus anacardium Linn. f nut extract. Indian J Exp Biol. 2002;40:
314–8.
Semecarpus anacardium L. 1627

38. Singh D, Aggarwal A, Mathias A, Naik S. Immunomodulatory activity of

Semecarpus anacardium extract in mononuclear cells of normal individuals
and rheumatoid arthritis patients. J Ethnopharmacol. 2006;108:398–406.
39. Smit HF, Woerdenbag HJ, Singh RH, et al. Ayurvedic herbal drugs with
possible cytostatic activity. J Ethnopharmacol. 1995;47:75–84 (Review).
40. Sugapriya D, Shanthi P, Sachdanandam P. Restoration of energy metabolism
in leukemic mice treated by a Siddha drug—Semecarpus anacardium Linn.
nut milk extract. Chem Biol Interact. 2008;173:43–58.
41. Tripathi YB, Pandey RS. Semecarpus anacardium L, nuts inhibit lipopoly-
saccharide induced NO production in rat macrophages along with its
hypolipidemic property. Indian J Exp Biol. 2004;42:432–6.
42. Tripathi YB, Singh AV. Effect of Semecarpus anacardium nuts on lipid
peroxidation. Indian J Exp Biol. 2001;39:798–801.
43. Verma N, Vinayak M. Semecarpus anacardium nut extract promotes the
antioxidant defence system and inhibits anaerobic metabolism during
development of lymphoma. Biosci Rep. 2009;29:151–64.
44. Vijayalakshmi T, Muthulakshmi V, Sachdanandam P. Effect of milk extract
of Semecarpus anacardium nuts on glycohydrolases and lysosomal stability
in adjuvant arthritis in rats. J Ethnopharmacol. 1997;58:1–8.
45. Vijayalakshmi T, Muthulakshmi V, Sachdanandam P. Effect of the milk
extract of Semecarpus anacardium nut on adjuvant arthritis—a dose-
dependent study in Wistar albino rats. Gen Pharmacol. 1996;27:1223–6.
46. Vijayalakshmi T, Muthulakshmi V, Sachdanandam P. Salubrious effect of
Semecarpus anacardium against lipid peroxidative changes in adjuvant
arthritis studied in rats. Mol Cell Biochem. 1997;175:65–9.
47. Vinayagam KS, Khan HB, Keerthiga G, et al. Hypolipidemic effect of
Semecarpus anacardium in high cholesterol fed hypercholesterolemic rats.
Chin J Integr Med. 2012 (Epub ahead of print).
48. Vinutha B, Prashanth D, Salma K, et al. Screening of selected Indian
medicinal plants for acetylcholinesterase inhibitory activity. J Ethnophar-
macol. 2007;109:359–63.
Senna alexandrina Mill.
(Fabaceae/Leguminosae)

(Syns.: Cassia acutifolia Del.; C. senna L.; C. alexandriana (Garsault) Thell.; S. acutifolia
(Del.) Batka)

Abstract
An annual subshrub, that is a native to and abundant in the northern and central
Sudan and Sinai, and is cultivated along the Upper Nile and to some extent in
northwestern and southern India. In Ayurveda, dried leaves are used in vibandha
and udararoga. In Africa, dried, pulverized leaves are applied to wounds and
burns. An infusion of the tops (leaves, flowers and pods together) is taken as a
purge to allay fever. In Unani medicine, it is regarded as laxative, purgative
of phlegm, yellow and black-bile, deobstruent, blood purifier, anthelmintic,
spasmodic and emetic, and used in the treatment of periodic fevers, phlegmatic
arthritis, sciatica, gout, and bronchial asthma. In Iran, leaves are mixed with
rose-petals and tamarind pulp for purgative dosages. It is used as a laxative and
cathartic, generally combined with aromatics and stimulants to modify its griping
effects; also used for ascites and dyspepsia. Purgative qualities of senna are due
largely to anthraquinone derivatives. C. senna is approved for constipation in
Europe since May 2005 by the HMPC of the European Medicines Agency.
Pods contain sennosides, anthraquinones, aloe-emodin, cathartic acid, cathartin,
kaempferol, catharkaempferol, chrysophanic acid, rhein, isorhamnetin, emodin,
kaempferin, mucilage, phaeoretin, sennacrol, and sennapicrin. Senna leaves
contain free anthraquinones and their O- and C-glycosides and free sugars. Newly
sprouted leaves after the rain are high in sennosides which decline as the leaves
mature. Laxative potency of senna was found to be reasonably uniform in mice
with a variation of 25% of the mean, and repeated administration of the doses
over many weeks did not cause any tolerance. Sennatin, a preparation containing
20 mg of purified sennosides, reduced colonic transit time by more than half and
abolished loperamide-prolonged colonic transit in healthy volunteers.

Keywords





Aleksandriansenna Fan xie ye Hindi sana Markandikã Ostrolistnaja kassija






Sanãmaki Sana makki Sanaya Senna Tinnevelly senna

© Springer Nature Switzerland AG 2020 1629

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_168
1630 Senna alexandrina Mill.

Vernaculars: Urd.: Senna; Hin.: Bhuikhakhasa, Hindi sana, Hindisanakapat,

Sanay, Sanaya, Sana ka patt; San.: Kalyãni, Markandikã, Sanãmaki, Svarnapatri;
Ben.: Sannamakki, Shonpat, Sonamukhi, Sonpat, Sonapata, Svarnmukhi; Mal.:
Adapatiyan, Chinnukki, Connamukhi, Nilavaka, Sunnamukhi, Sunnamukkiyila;
Mar.: Bhuitarvada, Mulkacha, Shonamakhi, Sonamahi, Sonamukhi; Tam.: Avarai,
Kathunilavirai, Nattunelavarai, Nelavagai, Nilagirai, Nilapponnai, Nila vakai,
Sooratnilla avarai; Tel.: Neelaponna, Neelatangeedu, Sunamukhi; Ara.: Ishriq,
Sana makki, Sinna; Chi.: Fan xie ye; Eng.: Aden senna, Alexandrian senna,
Bombay senna, Indian senna, Lotus senna, Nubian senna, Tinnevelly senna; Fin.:
Aleksandriansenna, Intiansenna; Rus.: Ostrolistnaja kassija.
Description: It is an annual, semiherbaceous subshrub up to 1 m high, with pale,
somewhat zigzag branches, and is a native to and abundant in the northern and
central Sudan [3] and Sinai,CXVI and is cultivated along the Upper Nile [1] and to
some extent in northwestern and southern India.XXI Leaves are alternate, compound,
with 3–7 pairs of leaflets, shorter and narrower than those of C. angustifolia, being
3.2–4 cm long and 0.5–1 cm wide; elliptic to lanceolate, acute at the tip, glaucous,
with more hairs present on the underside than those of C. angustifolia.CXXXXI
Flowers are bright-yellow, and seedpods are greenish-brown, 3.75–6.4 cm long,
1.9–2.5 cm wide, flat, elliptic-oblong, tending to be more curved than the pods of
C. angustifolia [21]. Ralph Bienfang [8] described the length-breadth ratio of the
leaf, fruit and seeds; and palisade ratio of different cassia species as identifying
parameter were described by George [24] (Figs. 1 and 2).
Actions and Uses: In Ayurveda, dried leaves are used in vibandha and udararoga.LX
In Africa, dried, pulverized leaves are applied to wounds and burns. An infusion of
the tops (leaves, flowers and pods together) is taken as a purge to allay fever.XXX In

Fig. 1 Senna alexandrina, Plant, Lalithamba, WikimediaCommons; 2.0 Generic CC BY 2.0,

https://commons.wikimedia.org/wiki/File:Senna_alexandrina_Mill.-Cassia_angustifolia_L._(Senna_
Plant).jpg; https://creativecommons.org/licenses/by/2.0/deed.en
Senna alexandrina Mill. 1631

Fig. 2 Senna alexandrina, Senna Leaves as sold in the U.S., Prof. Akbar, Original

Unani medicine, it (temperament, hot 1° and dry 1°; by some hot 2° and dry 2°) is
regarded as laxative, purgative of phlegm, yellow and black-bile, deobstruent, blood
purifier, anthelmintic, spasmodic and emetic, and used in the treatment of periodic
fevers, phlegmatic arthritis, sciatica, gout, and bronchial asthma.LXXVII In Iran, leaves
are mixed with rose-petals and tamarind pulp for purgative dosages.LXIV It is used as a
laxative and cathartic, generally combined with aromatics and stimulants to modify its
griping effects; also used for ascites and dyspepsia. Purgative qualities of senna are
due largely to anthraquinone derivatives.C Various authors have reviewed pharma-
cognostical, phytochemical, commercial, cultural and medicinal aspects of the plant
[26, 32, 37, 51]. C. senna is approved for constipation in Europe since May 2005 by
the HMPC of the European Medicines Agency.
Phytoconstituents: Pods contain 2.5–4.5% sennosides, aloe-emodin, anthraqui-
nones, cathartic acid, cathartin, kaempferol, catharkaempferol, chrysophanic acid,
rhein, isorhamnetin, emodin, kaempferin, mucilage, phaeoretin, sennacrol, and
sennapicrin. Senna leaves contain free anthraquinones (aloe-emodin, chrysophanol,
rhein etc.) and their O- and C-glycosides and free sugars (fructose, glucose, pinitol,
sucrose).CXXXXI Various investigators described isolation of anthraquinones from
the extracts by different extraction and precipitation techniques [10, 30, 34, 43, 49],
and presence of anthraquinone glycosides has been reported by various authors
[6, 12, 19, 20, 35, 47, 48]. Seeds do not contain anthraquinones, and sennosides
decline with the onset of flowering. Newly sprouted leaves after the rain are high in
sennosides which decline as the leaves mature. An optical isomer of sennoside
A—called sennoside A1, was isolated from senna pods [12]. Amino acids [13]
and lipids [44] from the seeds have been reported. Investigators have found no
1632 Senna alexandrina Mill.

significant differences in the chemical constituents of Cassia senna and Cassia

angustifolia [21]. An improved method to obtain volatile oil from Cassia was
described by Rosebrook et al. [50]. Amino acid analysis of Cassia seeds has been
reported by Yoneda and Inoue [57], and metal contents in the decoction of the plant
have been assessed by Suzuki et al. [53].
Pharmacology: Laxative potency of senna was found to be reasonably uniform in
mice with a variation of 25% of the mean [27, 28], and repeated administration of
the doses over many weeks did not cause any tolerance [56]. Intravenous and
intraperitoneal injection of senna infusion produced negligible cathartic response
compared to the same dose after oral administration [29]. Senna extract causes
diarrhea after oral administration within 1 to 6 h and enhances GI motility in mice,
but intramuscular and hypodermic injection do not have cathartic effect [55]. Pure
sennosides act predominantly on large intestine motility after their degradation by
colonic microorganisms [22]. Ca-sennoside B has no or only minimum effects on
intestinal absorption in rats. Large doses reduce net sodium, chloride and water
absorption predominantly in the colon and ileum; the jejunum is unaffected [36].
However, ethanol and chloroform extracts produce no effect on isolated rabbit
duodenum. Sennosides A and B also produced no effect on isolated guinea pig
colon; both yield rhein on hydrolysis which produces contractions of the colon. It
was, therefore, inferred that anthraquinone glycosides must undergo hydrolysis
before they could exert a purgative action [54].
Youssef [58] observed prevention of bacterial growth by adding cassia extract in
culture media of growing fungi and yeast. Both ethanol and chloroform extracts
showed antimicrobial activity against S. aureus and B. subtilis in a minimum
concentration of 1 mg/ml for both organisms [54]. Preparations of this herbal drug
may decompose under high temperatures causing oxidative decomposition of the
sennosides to rhein 8-O-glucoside, and rhein 8-O-glucoside being hydrolyzed to
rhein by enzymatic processes [25]. However, rhein retains not only laxative
property but also possesses antimicrobial activity against MRSA and synergy or
partial synergy with antibiotics like oxacillin and ampicillin against MRSA [31].
Ethanol extract of commercial Senokot® tablets is nonmutagenic and rather inhibits
mutagenicity of promutagens [2].
Clinical Studies: Sennatin, a preparation containing 20 mg of purified sennosides,
reduced colonic transit time by more than half and abolished loperamide-prolonged
colonic transit in healthy volunteers [17]. In comparative clinical studies, Agiolax®,
a combination of fiber and senna pod significantly improved daily bowel frequency,
stool consistency and ease of evacuation in elderly patients with chronic consti-
pation, better than lactulose [33, 45]. A liquid form of a standardized extract of
senna-pods produced a better and more reliable cleansing of bowel prior to X-ray
examination than the standard regimen [52]. Bader et al. [5] proposed to use sen-
noside B as UV sunscreens because of their consistent UV screening properties.
Senna alexandrina Mill. 1633

Mechanism of action: Purgative action of senna depends on the amount of

hydroxyanthraquinone existing in the plant [4, 11] but the effect is not due to the
presence of sennoside A and B only [18], rather a synergistic action of different
components [46], because senna extracts are more potent laxatives than the pure
active principles [38]. Oral senna-pod extract reverses net absorption of water,
sodium and chloride to net secretion, and increases potassium secretion and stim-
ulates output of PGE2 into the colonic lumen [7]. The purgative action of senna has
been attributed, in part, to the release of histamine in the gut [16]. After oral
administration, sennoside is degraded only in the lower parts of GIT, releasing its
active metabolite rhein anthrone [14]. Oral ingestion of senna glucoside results in the
appearance of unsplit glucoside and conjugated emodin in urine within 12 h [23].
Human A/Es, Allergy and Toxicity: Senna use may cause gripping. A case control
analysis of German patients diagnosed with colorectal carcinoma, adenomatous
polyps, and matched controls, concluded that the long-term use of anthranoid lax-
atives were not associated with an increased significant risk of developing colorectal
adenoma or carcinoma [42].
Animal Toxicity: Anthranoids, present in senna posed no genotoxic risk in mice
[39], and chronic use of senna laxatives in a daily dose of up to 300 mg/kg for
two-years did not predispose to colon cancer [9, 40, 41]. No significant effect on
nutrition, normal growth curve and normal life span of male and female mice was
observed after feeding 0.5% senna in diet for 400-days [29]. Daily administration of
washed senna powder, virtually free from anthracene derivatives, at 50-fold the
human laxative dose for 11-weeks caused no light- or electron-microscopically
detectable lesions of the intestinal mucosa of mice. No tolerance was observed in
female mice and the slight tolerance in males was immediately overcome by feeding
a 1% senna diet [15]. However, LD50 values calculated after intravenous admin-
istration indicated that acute toxicity decreases as the purity of the drug increases.
Commentary: Senna is a safe and effective laxative, and is widely used throughout
the world. However, its use has been confined to only as a laxative, whereas other
ascribed clinical uses in traditional medicines have been completely ignored that
might be investigated.

References
1. Abrol BK, Kapoor LD, Jamwal KS. Cultivation of Tinnevelly senna in
Jammu Province. J Sci Indust Res. 1955;14A:432–3.
2. al-Dakan AA, al-Tuffail M, Hannan MA. Cassia senna inhibits mutagenic
activities of benzo[a]-pyrene, aflatoxin B1, shamma and methyl methane-
sulfonate. Pharmacol Toxicol. 1995;77:288–92.
3. Andrews FW. The flowering plants of the Sudan, vols. I–III. Arbroath,
Scotland: T. Buncle & Co., Ltd; 1950;1952; 1956, p. 237, 485, 579.
1634 Senna alexandrina Mill.

4. Auterhoff H. Anthraquinone. III. The pharmacological action of anthraqui-

none derivatives. Arzneimittel-Forsch. 1953;3:23–5.
5. Bader S, Carinelli L, Cozzi R, Cozzoli O. Natural hydroxyanthracenic
polyglycosides as sunscreens. Cosmet Toilet. 1981;96:67–74.
6. Baja MF, Delaveau P. Preliminary study on the extraction of anthracene
derivatives from infusion preparations. Plant Med Phytother. 1981;15:240–4.
7. Beubler E, Kollar G. Stimulation of PGE2 synthesis and water and
electrolyte secretion by senna anthraquinones is inhibited by indomethacin.
J Pharm Pharmacol. 1985;37:248–51.
8. Bienfang Ralph. Preliminary report on the length-breadth ratio as a possible
description for the leaf, fruit and seed drugs. Bull Natl Formulary Comm.
1938;7:68–75.
9. Borrelli F, Capasso R, Aviello G, et al. Senna and the formation of aberrant
crypt foci and tumors in rats treated with azoxymethane. Phytomedicine.
2005;12:501–5.
10. Brendel WD, Berger L. Quantitative determination in senna leaves and
fruits and their preparations. III. Statistical evaluation of the results. Planta
Med. 1974;26:124–7.
11. Caravaggi A, Manfredi A. Laxative action of active principles extracted
from some commonly used plants. Boll Chim Farm. 1937;76:117–23.
12. Christ B, Pöppinghaus T, Wirtz-Peitz F. Isolation and structural definition
of a new sennoside from Cassia senna L. (author’s transl). Arzneimit-
telforschung. 1978;28:225–31 (German).
13. Dale T, Court WE. Amino acids of cassia seeds. Quart J Crude Drug Res.
1981;19:25–9.
14. de Witte P. Metabolism and pharmacokinetics of anthranoids. Pharmacol-
ogy. 1993;47 Suppl 1:86–97 (Review).
15. Dufour P, Gendre P, Meurier JM, Canells J. Tolerance of mouse intestinal
mucosa to prolonged ingestion of senna powder. Ann Pharm Fr. 1983;41:
571–8.
16. Erspamer E, Paolini A. Histamine a positive conditioner of the purgative
action of some drastic agents. Experientia. 1946;2:455–8.
17. Ewe K, Ueberschaer B, Press AG. Influence of senna, fibre, and fibre +
senna on colonic transit in loperamide-induced constipation. Pharmacology.
1993;47 Suppl 1:242–8.
18. Fairbairn JW, Saleh MRI. Vegetable purgatives containing anthracene
derivatives. V. A third active glycoside of senna. J Pharm Pharmacol. 1951;3:
918–25.
19. Fairbairn JW, Shrestha AB. Aloe-eodin glycosides of senna leaf. J Pharm
Pharmacol. 1966;18:467–70.
20. Fairbairn JW, Shrestha AB. The distribution of anthraquinone glycosides in
Cassia senna L. Phytochemistry. 1967;6:1203–7.
Senna alexandrina Mill. 1635

21. Fairbairn JW, Shrestha AB. The taxonomic validity of Cassia acutifolia and
Cassia angustifolia. Lloydia. 1967;30:67–72.
22. Garcia-Villar R, Leng-Peschlow E, Ruckebusch Y. Effect of anthraquinone
derivatives on canine and rat intestinal motility. J Pharm Pharmacol. 1980;
32:323–9.
23. Gebhardt H. The Fate of senna in the organism. Arch Exptl Pathol Pharmakol.
1936;182:521–6.
24. George E. Senna leaflets. Their palisade ratio values and ranges. Pharm J.
1943;151:52.
25. Goppel M, Franz G. Stability control of senna leaves and senna extracts.
Planta Med. 2004;70:432–6.
26. Gritsanapan W. Anthraquinone compounds of Cassia species growing in
Thailand. Varasarn Paesachasarthara. 1983;10:90–6.
27. Grote IW, Woods M. Laxative action in mice of Tinnevelley and Alaxandria
senna, and of several botanically related plants. J Am Pharm Assoc Sci Ed.
1944;33:266–70.
28. Grote IW, Woods M. The laxative activity in mice of the various parts of the
senna plant. J Am Pharm Assoc. 1951;40:52–3.
29. Hazleton LW, Talbert KD. Factors influenceing the cathartic activity of
senna in mice. J Am Pharm Assoc. 1945;34:260–4.
30. Hietala P. Recovery of laxative compounds from senna drugs. Ger Offen DE
3,200, 131 (Cl. CO7H15), 14 Jul, 1983.
31. Joung DK, Joung H, Yang DW, et al. Synergistic effect of rhein in
combination with ampicillin or oxacillin against methicillin-resistant
Staphylococcus aureus. Exp Ther Med. 2012;3:608–12.
32. Kapur BM, Atal CK. Cultivation and utilization of senna in India. Cultiv
Util Med Aromat Plants. 1977;124–31.
33. Kinnunen O, Winblad I, Koistinen P, Salokannel J. Safety and efficacy of a
bulk laxative containing senna versus lactulose in the treatment of chronic
constipation in geriatric patients. Pharmacology. 1993;47 Suppl 1:253–5.
34. Lemli J, Cuveele J. Study on anthraquinone drugs. XXXI. Transformation of
anthrone glycosides by drying of the leaves of Cassia Senna and Rhamnus
frangula. Planta Med. 1978;34:311–8.
35. Lemli J, Toppet S, Cuveele J, Janssen G. Naphthalene glycosides in Cassia
senna and Cassia angustifolia. Studies in the field of drugs containing
anthracene derivatives. XXXII. Planta Med. 1981;43:11–7.
36. Leng-Peschlow E. Inhibition of intestinal water and electrolyte absorption
by senna derivatives in rats. J Pharm Pharmacol. 1980;32:330–5.
37. Marini D. Plant extracts and their analytical assay. Note II. Senna and
Cascara extracts. Rass Chim. 1982;34:187–93.
38. Marvola M, Koponen A, Hiltunen R, Hieltala P. The effect of raw material
purity on the acute toxicity and laxative effect of sennosides. J Pharm
Pharmacol. 1981;33:108–9.
1636 Senna alexandrina Mill.

39. Mengs U, Grimminger W, Krumbiegel G, et al. No clastogenic activity of a

senna extract in the mouse micronucleus assay. Mutat Res. 1999;444:421–6.
40. Mitchell JM, Mengs U, McPherson S, et al. An oral carcinogenicity and
toxicity study of senna (Tinnevelly senna fruits) in the rat. Arch Toxicol.
2006;80:34–44.
41. Morales MA, Hernández D, Bustamante S, Bachiller I, Rojas A. Is senna
laxative use associated to cathartic colon, genotoxicity, or carcinogenicity? J
Toxicol. 2009;2009:287247.
42. Nusko G, Schneider B, Schneider I, Wittekind C, Hahn EG. Anthranoid
laxative use is not a risk factor for colorectal neoplasia: results of a
prospective case control study. Gut. 2000;46:651–5.
43. Oshio H, Naruse Y, Tsukui M. Quantitative analysis of the purgative
components of rhubarb and senna. Chem Pharm Bull. 1978;26:2458–64.
44. Osman F, Fiad S. Lipids of two Cassia species and Datura stramonium
seeds. Nahrung. 1976;20:483–7.
45. Passmore AP, Davies KW, Flanagan PG, et al. A comparison of Agiolax
and lactulose in elderly patients with chronic constipation. Pharmacology.
1993;47 Suppl 1:249–52.
46. Ploss E. Synergism and potassium substitution as preferences in vegetable
laxatives. Dtsch Apoth. 1975;28:336–8.
47. Rai PO, Turner TD, Greensmith SL. Anthracene derivatives in tissue culture
of Cassia senna. J Pharm Pharmacol. 1974;26:722–6.
48. Rai PP, Abdullahi NI. Occurrence of anthraquinones in Cassia species.
Niger J Pharm. 1978;9:160–5.
49. Romanova AS, Kalashnikova GK, Tareeva NY, et al. Method for the
quantitative determination of anthracene derivatives in senna leaves and
fruits. Khim-Farm Zh. 1982;16:330–4.
50. Rosebrook DD, Bolze CC, Barney JE II. An improved method for
determining steam-volatile oil in cassia. J Assoc Offic Anal Chem. 1968;51:
644–50.
51. Selvaraj Y, Chander MS. Senna—its chemistry, distribution and pharma-
ceutical value. J Indian Inst Sci. 1978;60:179–96.
52. Sitiris G. A new laxative, X-preparation: to be used as a bowel evacuant
prior to X-ray examination. Tidsskr Nor Laegeforen. 1970;90:1477–8.
53. Suzuki A, Morimoti I, Okitsu T. Elution of metals from crude drugs.
Shoyakugaku Zasshi. 1982;36:190–5.
54. Valette G. Effects of the glycosides of senna (Sennosides A and B) and their
hydrolysis products on isolated intestine. Compt Rend Soc Biol. 1949;143:
74–6.
55. Wang X, Zhong YX, Lan M, et al. Screening and identification of proteins
mediating senna-induced gastrointestinal motility enhancement in mouse
colon. World J Gastroenterol. 2002;8:162–7.
Senna alexandrina Mill. 1637

56. Woods M, Grote IW. The repeated administration of Tinnevelly and

Alexandria senna to mice. J Am Pharm Assoc. 1951;40:198–202.
57. Yoneda K, Inou, A. Seed biology of medicinal plants. VIII. Amino acid
analysis of Cassiae seeds. Shoyakugaku Zasshi. 1978;32:165–7.
58. Youssef KA. Preventing the growth of bacteria in culture media for growing
fungi and yeasts. Ger Offen 2, 740, 013 (Cl.C12B3/6), 8 Mar 1979.
Senna occidentalis (L.) Link
(Fabaceae/Leguminosae)

(Syns.: Cassia caroliniana; C. falcata L.; C. foetida Pers.; C. occidentalis (L.) Rose;
C. torosa Cav.; Ditrimexa occidentalis (L.) Britton & Rose)

Abstract
An annual or perennial half-woody herb or shrub found in India. Muslim
physicians in India called it alexipharmic, useful in the expulsion of corrupt
humours and to relieve cough, especially whooping cough. Seeds are pounded
and heated with 10 ml of woman’s or cow’s milk, strained and given once a day
as a cure for convulsions in children. Whole plant is purgative, alterative, and
expectorant, and used in the treatment of skin diseases, such as ringworm,
scabies, pityriasis, and psoriasis. Bark of the root or whole root and seeds are
useful in snake and scorpion poisons and dropsy. Roasted and ground seeds have
been used as a substitute for coffee; medicinal properties are destroyed during
roasting process. In Ayurveda, all parts of the plant are regarded to possess similar
properties, such as purgative, tonic, febrifuge, expectorant and diuretic, and
therapeutically used in kasa, hikka, svasa, kustha, sidhma, jvara, sotha and
vicarcika. Native Americans also used infusion of the root as antidote against
various poisons, and a decoction of the whole plant to treat hysteria. In Brazil’s
rainforests and tropical regions, it is used as laxative, analgesic, antipyretic,
diuretic, hepatoprotective, and vermifuge, for snakebite, fungal infections and as
a potent abortifacient, and thus its use is not recommended during pregnancy.
A poultice of leaves to cheek is used for toothache in the Dutch Indies and for
headache in Malaya, and to combat irritation and eczema and other skin diseases.
It is claimed that any type of severe stomachache can be treated using this herb.
Aqueous leaf extract is used for the treatment of hypertension and associated
cardiovascular diseases in African traditional medicine, and in the Lubumbashi
region of Democratic Republic of Congo, the plant is used for the treatment of
diabetes. In Hawaii, it is mainly used to treat skin diseases, such as ringworm, and
white blotches of the skin. Chemical constituents present in roots, seeds and aerial
parts include achrosin, aloe-emodin, emodin, anthraquinones, anthrones, api-
genin, aurantiobtusin, campesterol, cassiollin, chrysoobtusin, chrysophanic acid,
chrysarobin, chrysophanol, chrysoeriol, polysaccharides and galactomannan.

© Springer Nature Switzerland AG 2020 1639

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_169
1640 Senna occidentalis (L.) Link

Keywords



Achuporoto Cassie puante Coffee senna Habu-sô

Kasondi
Kasonji





Seesabaan Stinkkassie Tararucu Wang jiang nan

Vernaculars: Urd.: Kasondhi; Kasonji; Hin.: Badikasondi, Chakunda, Gajarsag,

Kasonda, Kasondi, Sari-kasondi; San.: Arimarda, Karkaśa, Kãsaghna, Kãsamarda;
Ben.: Kalakasunda, Kalkashunda, Kasonda; Mal.: Natramtakara, Natrum-takara,
Ponnaviram; Mar.: Kasoda, Rankasvinda, Rantakala; Tam.: Nattamtakarai, Nat-
tutakarai, Paeravirai, Pera-verai, Ponnavirai, Ponthagarai; Tel.: Kasinda, Paidi-
tangedu, Peddakasinda, Tagara-chettu; Ara.: Seesabaan; Chi.: Wang jiang nan,
Wang jiang nan jue ming; Eng.: Coffee senna, Coffeeweed, Negro coffee, Rubbish
cassia, Stinking weed, Styptic weed; Fre.: Cassie puante; Ger.: Stinkkassie;
Haw.: Au-ko-i, Mikipalaga, Pi hohong; Jap.: Habu-sô; Por.: Fedegoso-verdadeiro,
Folha-de-page, Lava-pratos, Tararucu (Br.); Spa.: Achuporoto, Aya-poroto, Brusca
chuquichique, Café cimarrón, Café de Bonpland, Caffecillo, Caña-fista, Frijolillo
negro, Friquillo, Hierba hedionda brusca, Manjeiroba, Pico de pájaro, Pigue pájaro,
Rematilla, Taperiba; Tag.: Balatong-aso, Kabal-kabalan, Katangan-aso, Tambalisa,
Tigniman.
Description: An annual or perennial half-woody herb or shrub, 0.8–1.5 m high;
leaves are pinnate and about 20 cm long. Leaflets are rank-smelling, occur in 5
pairs, are oblong-lanceolate, 4–9 cm long, somewhat pointed at the base and taper
gradually to a fine, pointed tip. Flowers are yellow, 2 cm long, and are borne on
axillary and terminal recemes. Pods are 10 cm long, 9 mm wide, and thickened,
and contain about 40 seeds (Figs. 1, 2, and 3).CXVII
Actions and Uses: Muslim physicians in India called it alexipharmic, useful in the
expulsion of corrupt humours and to relieve cough, especially whooping cough.
Seeds (250–750 mg) are pounded and heated with 10 ml of woman’s or cow’s
milk, strained and given once a day as a cure for convulsions in children. Whole
plant is purgative, alterative, and expectorant, and used in the treatment of skin
diseases, such as ringworm, scabies, pityriasis, and psoriasis.LXXXI Unani physi-
cians consider it (temperament, hot 2° and dry 3°) diuretic, laxative, diaphoretic,
blood purifier,1 anti-inflammatory, digestive, and antidote for animal and mineral
poisons, and the leaves decoction is used for dropsy, liver ailments, cough, allergy,
asthma, arthritis and as vermifuge. Bark of the root or whole root and seeds are
useful in snake and scorpion poisons and dropsy.LXXVII Roasted and ground seeds
have been used as a substitute for coffee; medicinal properties are destroyed during
roasting process.CV Hindu physicians regard it as expectorant, depurative and
alterative, and the root with black pepper is used as a remedy for snakebite.XL In
Ayurveda, all parts of the plant are regarded to possess similar properties, such as
purgative, tonic, febrifuge, expectorant and diuretic, and therapeutically used in

1
Tayyab M: Personal Communication.
Senna occidentalis (L.) Link 1641

Fig. 1 Senna occidentalis, Plant, J.M. Garg, WikimediaCommons; ShareAlike 4.0 International
CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Cassia_occidentalis_in_Anantgiri,_AP_
W2_IMG_8828.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

Fig. 2 Senna occidentalis, Seed Pods, Jeevan Jose, © 2009 Jee & Rani Nature Photography,
WikimediaCommons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.
org/wiki/File:Coffee_Senna_2.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
1642 Senna occidentalis (L.) Link

Fig. 3 Senna occidentalis, Flower, Jeevan Jose, © 2009 Jee & Rani Nature Photography, Wiki-
mediaCommons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/
wiki/File:Senna_occidentalis.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

kasa, hikka, svasa, kustha, sidhma, jvara, sotha and vicarcika.LX Native Americans
also used infusion of the root as antidote against various poisons, and a decoction of
the whole plant to treat hysteria.XL
In Brazil’s rainforests and tropical regions, it is used as laxative, analgesic,
antipyretic, diuretic, hepatoprotective, and vermifuge [37], for snakebite, fungal
infections and as a potent abortifacient, and thus its use is not recommended during
pregnancy [3]. Leaves are used as febrifuge in Ethiopia [22] and for leucorrhea and
jaw pain, while the Gambians use the root as antipyretic, and the seeds are used as
coffee substitute in Indonesia. In tropical America, it is also used as coffee substitute
for chronic dysentery [16]. It is hypoglycemic; seeds are used as tonic and diuretic
[8], also reported antibacterial,CXXVI and the leaves and stems are uterine stimulant.
In the Philippines, seeds are used as antipyretic,LVI and a home remedy as tonic,
diuretic, stomachic, febrifuge, and in the treatment of dropsy, rheumatism, and
venereal diseases. A bark infusion is also reportedly used as a remedy for diabetes.
A poultice of leaves to cheek is used for toothache in the Dutch Indies and for
headache in Malaya, and to combat irritation and eczema and other skin dis-
eases.CXVII It is claimed that any type of severe stomachache can be treated using
this herb. The roots are dug out, washed and ground; to ground roots some cold
water is added, stirred and small particles are allowed to settle at the bottom. A clear
solution, very bitter and powerful is then given to the patient in very small quan-
tities, about one teaspoonful every 4 h. This dose is repeated for a couple of days
until the patient feels better. The roots are boiled and the liquid is drunk for swollen
testicles. Leaves are boiled in water and the steam is used as a vapor bath for fever,
or just rubbed directly on the body for fever. Leaves are also used for snakebites
and for kidney troubles. The Zaramo use roots for a disease caused by the
Kinyamkera spirit in East Africa.LXXXV Aqueous leaf extract is used for the
Senna occidentalis (L.) Link 1643

treatment of hypertension and associated cardiovascular diseases in African tradi-

tional medicine [9], and in the Lubumbashi region of Democratic Republic of
Congo, the plant is used for the treatment of diabetes [1]. In Hawaii, it is mainly
used to treat skin diseases, such as ringworm, and white blotches of the skin. As a
bath for certain skin diseases, the whole plant is pounded with water, then four
heated stones are sunk into it to cook it; this ‘cooked water’ is used to wash and
bathed afflicted skin parts.LXXVI
Phytoconstituents: Aerial parts are rich in flavonoids, alkaloids, lignin, tannins, and
phenols; with good nutritional value, such as high energy value, crude fibers, and
vitamin levels, and rich in minerals, especially Fe, Ca, K, Mn, Mg, Zn, Cu, Na, P,
and S [24]. Chemical constituents present in roots, seeds and aerial parts include
achrosin, aloe-emodin, emodin, anthraquinones, anthrones, apigenin, aurantiobtusin,
campesterol, cassiollin, chrysoobtusin, chrysophanic acid, chrysarobin, chryso-
phanol, chrysoeriol, polysaccharides and galactomannan [12, 13, 19–21, 43, 44, 50].
N-methylmorpholine [18], two sesquiterpenes [51], and a norsesquiterpene [34]
have been isolated from the seeds. From whole plant two cycloartane triterpenoids
and related saponins, cycloccidentalisides were reported [23]. Leaves volatile oil
mainly contains (E)-phytol acetate, hexahydrofarnesyl acetone and (E)-geranyl
acetone [29]. Organic extraction with methanol, ethanol, chloroform, ethyl acetate
and benzene does not remove toxin from seeds but an aqueous extraction with
25 mM sodium bicarbonate removes myodegenerative toxin from the seeds [14].
Pharmacology: Supplementation of the plant in diet to STZ-diabetic mice for
nine-days did not significantly affect hyperphagia and polydipsia [41]. However,
ethanol and aqueous extracts of whole plant significantly reduced FBG in both
normal and alloxan-diabetic rats [48, 49], and the aqueous extract significantly
(32%) lowered blood glucose of normoglycemic guinea pigs, compared to 55% fall
by glibenclamide (6 mg/kg) [1]. Both extracts also positively affected TC and TGs
and regenerated b-cells of diabetic rats [48, 49]. Four-weeks treatment with aqueous
leaf extract significantly ameliorated elevation of TC, LDL-C, and VLDL-C, and
formation of aortic atherosclerotic plaques in hypercholesterolemic rats [9]. Aqu-
eous leaf extract was most effective against free radicals, and the antioxidant
activity was correlated to the presence of phenolic compounds [4].
Leaf powder showed anti-inflammatory activity against carrageenan-induced
paw edema, and suppressed transudative, exudative and proliferative components
of cotton pellet granuloma; and reduced PLA2 activity and LPx content of gran-
uloma [36]. Similar anti-inflammatory effect was reported of whole plant ethanol
extract in mice, with significant antioxidant activity and inhibition of mast cells
degranulation [38]. Methanol leaf extract has been suggested to possess myelo-
protective activity against CP-induced bone marrow suppression [27]. Ethyl acetate
root extract also inhibited production of TNF-a, IL-1b and NO in LPS stimulated
macrophages [33]. Aqueous extracts of leaves and bark were active against
pathogenic fungi A. flavus, T. rubrum, E. floccosum, M. gypseum and T. menta-
grophytes [6, 7]. Incubation of T. brucei brucei with ethanol leaf extract completely
1644 Senna occidentalis (L.) Link

eliminated their motility 10-min postincubation and significantly ameliorated

severity of T. brucei brucei-infected rats and decreased severity of hepatomegaly,
spleenomegaly, and anemia [17].
Mechanism of Action: Anthrone and anthraquinone glycosides from roasted seeds
produce oxytocic and abortive effect by causing irritation and inflammation of
pelvic organs [2].
Human A/Es, Allergy and Toxicity: Cases of hepatomyoencephalopathy syn-
drome in children have occurred annually as outbreaks in the state of Uttar Pradesh
of India for several years, resulting in death or severe illness. In majority of cases a
history of eating C. occidentalis beans was positive, establishing a causal link with
the disease [28, 32, 45, 46].
Animal Toxicity: Ingestion of large amounts by grazing animals has caused
serious toxicity and death. Toxicity in large animals, rodents and chicken is mainly
manifested on skeletal muscles, liver, kidney and heart. However, toxicity and its
symptoms seem to be species-specific and dose-related [15, 26, 30, 31, 35, 47].
Contamination of feed grain with C. occidentalis seeds caused toxicity and death of
pigs, and caused rapid weight loss and severe debility in chicken. Histological
findings showed skeletal and cardiac degenerative myopathy [10]. Experimental
toxicity in horses [25], goats [39, 40] and domestic chickens [11] fed with ground
seeds, has been reported. Feeding of 4% ground seeds in diet of rabbits caused
death in the third week. Heart and liver were mainly affected with myocardial
necrosis and centrolobular degeneration [42]. A dose-dependent fiber degeneration
of skeletal and cardiac muscles was observed in Wistar rats fed with ground seeds
for two-weeks [5]. Oral hydroalcohol extract of leaf and stem was nontoxic up to a
dose of 5,000 mg/kg to male and female Wistar rats, and administration up to a
dose of 2,500 mg/kg daily for 30-days did not affect body weight, food or water
consumption, hematological or biochemical profile or caused any pathological
changes in organs [37]. The extract administered during organogenesis period of
pregnancy to female Wistar rats did not significantly affect fetuses, placentae and
ovaries weights, and number of implantations, but dead fetuses were found in rats
treated with 250 and 500 mg/kg doses [3]. Feeding seeds to Wistar rats in diet (0.5,
1 and 2% w/w) for 28-days caused significant increases in serum transaminases,
ALP and LDH along with histopathological lesions in hepatic tissue; increased
serum creatinine and CPK suggested muscular damage [32].
Commentary: Aerial parts are used in traditional medicines of many countries for
various ailments, especially for skin conditions, and are also suggested to be rich in
minerals and nutritious. Ingestion of seeds has resulted in outbreaks of severe
toxicity in children in India, but no efforts have been made to determine the
mechanism of action. Also, there are no published reports on clinical studies on any
parts of the plant, especially the widespread use of its aerial parts in skin diseases.
Senna occidentalis (L.) Link 1645

References
1. Amuri B, Maseho M, Simbi L, et al. Hypoglycemic and antihyperglycemic
activities of nine medicinal herbs used as antidiabetic in the region of
Lubumbashi (DR Congo). Phytother Res. 2017;31:1029–33.
2. Anton R, Duquenois P. Contribution to the chemical study of Cassia
occidentalis L. Ann Pharm Fran (France). 1968;26:673–80.
3. Aragão TP, Lyra MM, Silva MG, et al. Toxicological reproductive study of
Cassia occidentalis L. in female Wistar rats. J Ethnopharmacol. 2009;123:
163–6.
4. Arya V, Yadav S, Kumar S, Yadav JP. Antioxidant activity of organic and
aqueous leaf extracts of Cassia occidentalis L. in relation to their phenolic
content. Nat Prod Res. 2011;25:1473–9.
5. Barbosa-Ferreira M, Dagli ML, Maiorka PC, Górniak SL. Subacute
intoxication by Senna occidentalis seeds in rats. Food Chem Toxicol.
2005;43:497–503.
6. Caceres A, Lopez B, Juarez X, et al. Plants used in Guatemala for the
treatment of dermatophytic infections. 2. Evaluation of antifungal activity of
seven American plants. J Ethnopharmacol. 1993;40:207–13.
7. Caceres A, Lopez BR, Giron MA, Logemann H. Plants used in Guatemala
for the treatment of dermatophytic infections. 1. Screening for antimycotic
activity of 44 plant extracts. J Ethnopharmacol. 1991;31:263–76.
8. Farnsworth NR, Segelman AB. Hypoglycemic Plants. Tile Till. 1971;57:
52–5.
9. Fidèle N, Joseph B, Emmanuel T, Théophile D. Hypolipidemic, antioxidant
and antiatherosclerogenic effect of aqueous extract leaves of Cassia occi-
dentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats.
BMC Complement Altern Med. 2017;17:76.
10. Flory W, Spainhour CB Jr, Colvin B, Herbert CD. The toxicologic
investigation of a feed grain contaminated with seeds of the plant species
Cassia. J Vet Diag Invest. 1992;4:65–9.
11. Graziano MJ, Flory W, Seger CL, Hebert CD. Effects of a Cassia
occidentalis extract in the domestic chicken (Gallus domesticus). Am J Vet
Res. 1983;44:1238–44.
12. Gupta DS, Mukherjee S. Seed polysaccharide of Cassia occidentalis Linn.
Indian J Chem. 1973;11:1134–7.
13. Gupta DS, Mukherjee S. Structure of galactomannan from Cassia occiden-
talis seeds: isolation & structure elucidation of oligosaccharides. Indian J
Chem. 1975;13:1152–4.
14. Hebert CD, Flory W, Seger C, Blanchard RE. Preliminary isolation of a
myodegenerative toxic principle from Cassia occidentalis. Am J Vet Res.
1983;44:1370–4.
15. Henson JB, Dollahite JW. Toxic myodegeneration in calves produced by
experimental Cassia occidentalis intoxication. Am J Vet Res. 1966;27:947–9.
1646 Senna occidentalis (L.) Link

16. Hirschhorn HH. Constructing a phytotherapeutic concordance based upon

tropical American and Indonesian examples. J Ethnopharmacol. 1983;7:
157–67.
17. Ibrahim MA, Aliyu AB, Sallau AB, et al. Senna occidentalis leaf extract
possesses antitrypanosomal activity and ameliorates the trypanosome-
induced anemia and organ damage. Pharmacognosy Res. 2010;2:175–80.
18. Kim HL, Camp BJ, Grigsby RD. Isolation of N-methylmorpholine from the
seeds of Cassia occidentalis L. (coffee senna). J Agr Food Chem. 1971;19:
198–9.
19. Lal J, Gupta PC. Anthraquinone glycoside from the seeds of Cassia
occidentalis Linn. Experientia. 1973;29:141–2.
20. Lal J, Gupta PC. Physcion and phytosterol from the roots of Cassia
occidentalis. Phytochemistry. 1973;12:1186.
21. Lal J, Gupta PC. Two new anthraquinones from the seeds of Cassia
occidentalis Linn. Experientia. 1974;30:850–1.
22. Lemordant D. Contribution a l’ethnobotanique Ethiopienne. J Agric Trop
Bot Appl. 1971;18:1–35; 18:142–9.
23. Li SF, Di YT, Luo RH, et al. Cycloartane triterpenoids from Cassia
occidentalis. Planta Med. 2012;78:821–7.
24. Manikandaselvi S, Vadivel V, Brindha P. Studies on physicochemical and
nutritional properties of aerial parts of Cassia occidentalis L. J Food Drug
Anal. 2016;24:508–15.
25. Martin BW, Terry MK, Bridges CH, Bailey EM Jr. Toxicity of Cassia
occidentalis in the horse. Vet Hum Toxicol. 1981;23:416–7.
26. Mercer HD, Neal FC, Himes JA, Edds GT. Cassia occidentalis toxicosis in
cattle. J Am Vet Med Assoc. 1967;151:735–41.
27. Neboh EE, Ufelle SA. Myeloprotective activity of crude methanolic leaf
extract of Cassia occidentalis in cyclophosphamide-induced bone marrow
suppression in Wistar rats. Adv Biomed Res. 2015;4:5.
28. Nirupam N, Sharma R, Chhapola V, Kanwal SK, Kumar V. Hepatomy-
oencephalopathy due to Cassia occidentalis poisoning. Indian J Pediatr.
2013;80:1063–4.
29. Ogunwande IA, Avoseh NO, Flamini G, et al. Essential oils from the leaves
of six medicinal plants of Nigeria. Nat Prod Commun. 2013;8:243–8.
30. O’Hara PJ, Pierce KR, Read WK. Degenerative myopathy associated with
ingestion of Cassia occidentalis L.: clinical and pathologic features of the
experimentally induced disease. Am J Vet Res. 1969;30:2173–80.
31. O’Hara PJ, Pierce KR. A toxic cardiomyopathy caused by Cassia occiden-
talis. I. Morphologic studies in poisoned rabbits. Vet Pathol. 1974;11:97–109.
32. Panigrahi G, Tiwari S, Ansari KM, et al. Association between children
death and consumption of Cassia occidentalis seeds: clinical and experi-
mental investigations. Food Chem Toxicol. 2014;67:236–48.
Senna occidentalis (L.) Link 1647

33. Patel NK, Pulipaka S, Dubey SP, Bhutani KK. Proinflammatory cytokines
and nitric oxide inhibitory constituents from Cassia occidentalis roots. Nat
Prod Commun. 2014;9:661–4.
34. Qin RX, Zuo Q, Huang XH, et al. A new norsesquiterpene from Cassia
occidentalis and its bioactivity. Zhongguo Zhong Yao Za Zhi. 2016;41:4389–
92 (Article in Chinese).
35. Rogers RJ, Gibson J, Reichmann KG. The toxicity of Cassia occidentalis
for cattle. Austral Vet J. 1979;55:408–12.
36. Sadique J, Chandra T, Thenmozhi V, Elango V. Biochemical modes of
action of Cassia occidentalis and Cardiospermum halicacabum in inflam-
mation. J Ethnopharmacol. 1987;19:201–12.
37. Silva MG, Aragão TP, Vasconcelos CF, et al. Acute and subacute toxicity
of Cassia occidentalis L. stem and leaf in Wistar rats. J Ethnopharmacol.
2011;136:341–6.
38. Sreejith G, Latha PG, Shine VJ, et al. Antiallergic, anti-inflammatory and
antilipid peroxidant effects of Cassia occidentalis Linn. Indian J Exp Biol.
2010;48:494–8.
39. Suliman HB, Shommein AM. Toxic effect of the roasted and unroasted
beans of Cassia occidentalis in goats. Vet Hum Toxicol. 1986;28:6–11.
40. Suliman HB, Wasfi IA, Adam SE. The toxicity of Cassia occidentalis to
goats. Vet Hum Toxicol. 1982;24:326–30.
41. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Evaluation of traditional
plant treatments for diabetes: studies in streptozotocin diabetic mice. Acta
Diabet Lat. 1989;26:51–5.
42. Tasaka AC, Weg R, Calore EE, et al. Toxicity testing of Senna occidentalis
seed in rabbits. Vet Res Commun. 2000;24:573–82.
43. Tiwari RD, Singh J. Anthraquinone pigments from the leaves of Cassia
occidentalis. Planta Med. 1977;32:375–7.
44. Tiwari RD, Singh J. Flavonoids from the leaves of Cassia occidentalis.
Phytochem. 1977;16:1107–8.
45. Vashishtha VM, Kumar A, John TJ, Nayak NC. Cassia occidentalis
poisoning as the probable cause of hepatomyoencephalopathy in children in
western Uttar Pradesh. Indian J Med Res. 2007;125:756–62.
46. Vashishtha VM, Kumar A, John TJ, Nayak NC. Cassia occidentalis
poisoning causes fatal coma in children in western Uttar Pradesh. Indian
Pediatr. 2007;44:522–5.
47. Vashishtha VM, John TJ, Kumar A. Clinical and pathological features of
acute toxicity due to Cassia occidentalis in vertebrates. Indian J Med Res.
2009;130:23–30.
48. Verma L, Khatri A, Kaushik B, Patil UK, Pawar RS. Antidiabetic activity of
Cassia occidentalis (Linn.) in normal and alloxan-induced diabetic rats.
Indian J Pharmacol. 2010;42:224–8.
1648 Senna occidentalis (L.) Link

49. Verma L, Singour PK, Chaurasiya PK, et al. Effect of ethanolic extract of
Cassia occidentalis Linn. for the management of alloxan-induced diabetic
rats. Pharmacognosy Res. 2010;2:132–7.
50. Yadav JP, Arya V, Yadav S, et al. Cassia occidentalis L.: a review on its
ethnobotany, phytochemical and pharmacological profile. Fitoterapia. 2010;
81:223–30.
51. Yang Y, Wang YD, Xing HH, et al. A new sesquiterpene from seeds of
Cassia occidentalis and its cytotoxicity. Zhongguo Zhong Yao Za Zhi.
2016;41:3256–9 (Chinese).
Senna tora (L.) Roxb.
(Fabaceae/Leguminosae)

(Syns.: Cassia tora L.; C. borneensis Miq.; C. gallinaria Collad.; C. numilis Collad.;
Emelista tora Britton & Rose)

Abstract
A native of southern China, India, Iran, Indochina, Japan, the Philippines, and
Java. Muslim writers described seeds and leaves to have solvent properties in
those forms of skin diseases accompanied with induration, such as leprosy,
keloid and psoriasis. Seeds ground with sour buttermilk are used to ease
irritation of itchy eruptions, and the root, rubbed on a stone with lime juice is one
of the best remedies for ringworm. In Unani medicine, seeds and leaves are
described as purgative, blood purifier, good for piles, and to expel phlegm and
black-bile; and useful as a paste for skin diseases, such as leprosy, vitiligo, bahq,
and kalaf, and cold diseases, such as paralysis and arthritis. In India, it is also
used in oral healthcare to treat plaque and caries, and prescribed for various eye
and liver disorders. Decoction of the whole plant is used as vermifuge and
purgative in the Philippines. In Chinese medicine, it is considered a superior
drug and has been recorded in The Herbal by Shen Nung. Dried ripe seeds are
used for headache with fever, eye disorders, ophthalmia with swelling and pain,
glaucoma, and dry stools. Seeds are also used as laxative and tonic, and as a
popular health tea drink. Commercial products include both unroasted and
roasted samples, and the laxative effect is higher in unroasted compared with the
roasted seeds. Roasted seeds are favored for their flavor, and popularly used as
tea in Korea. Seeds contain antihepatotoxic naphthopyrone glycosides, cassi-
aside and rubrofusarin-6-b-gentiobioside. Roasting of seeds decreases the
contents of antihepatotoxic constituents. Anthraquinones, chrysophanol, emodin
and rhein contents in the extract decreased with increased roasting temperature;
the decrease in antigenotoxic potency of roasted seeds was related to reduction
in their anthraquinones contents. Water extract of roasted seeds reversed B[a]
P-induced DNA damage in human hepatoma cell line HepG2, which was less
effective than produced by unroasted seeds. Methanol seed extract exhibits
anticancer effects, induces apoptosis and exerts antimetastatic effects. It shows
anti-inflammatory activity and significantly downregulates expression of genes

© Springer Nature Switzerland AG 2020 1649

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_170
1650 Senna tora (L.) Roxb.

associated with inflammation. Ethanol seed extract significantly reduced blood

glucose, TC, TGs, phospholipids, and FFAs of diabetic rats.

Keywords




Aines-saratin Cassie sauvage Chakavat Chakramarda Gemüsekassie






Jue-ming-zi Kulkul-sanji Matapasto Panwad Sickle senna

Vernaculars: Urd.: Panwad; Hin.: Chakaunda, Chakavat, Chakunda, Chakvad,

Panevar, Panwar, Pavaad, Pavaar; San.: Ayudham, Chakramarda (to destroy
ringworm), Dadamardana, Dadrughna, Kharjugna, Mesalocana, Prabhoonata,
Prabhunatha, Prapunada, Taga, Uranaksha; Ben.: Chakondia, Chakunda, Chavuka,
Panevar, Takola; Mal.: Chakramandarakam, Takaraa; Mar.: Takla, Tankala,
Tankli, Tarota; Tam.: Tagarai, Takaruni, Tarotah, Thagarai-verai (seeds), Ushit-
tagarai; Tel.: Senavu, Tagarisha-chettu, Tagiris, Tagirisa cinnakasinda, Tantepu-
chettu, Tantiyamu, Tellakasinda, Vindu; Ara.: Aines-saratin (Crab’s eye), Kul-kul,
Saboyah, Sanji; Bur.: Dan-kilayiwai; Chi.: Chueh-ming-tzu, Jue-ming-zi; Eng.:
Foetid cassia, Sickle senna, Stinking cassia; Fre.: Cassie sauvage, Herbe pistache;
Ger.: Gemüsekassie; Ita.: Cassia selvatica; Jap.: Ebisugusa; Per.: Kulkul-
sanji; Por.: Fedegoso-branco, Matapasto-liso; Spa.: Caña fistula, Chilinchil,
Frijolilla, Guanina, Mamuri, Matapasto; Tag.: Katandá, Katandang-áso, Monggo-
monggohan.
Description: A native of southern China, India, Iran, Indochina, Japan, the
Philippines, and Java. An erect, stout, smooth, rank-smelling, half-woody annual
herb 30–90 cm high; leaves 8–12 cm long and pinnately compound; leaflets 6,
obovate to oblong-obovate, obtuse, base attenuate, 2–5 cm long. Leaves have
glands on the main rachis between the leaflets. Flowers are crowded in pairs, in the
axils of the upper leaves, and about 1.5 cm across. Pods (fruits) are slender, up to
15 cm long and 3–4 mm thick; and the seeds are flattened in the same direction as
the pod.CXVII Fruits in October, each pod contains about 25, oblong, rounded at the
base, 5 mm long and 2 mm in diameter, brown, smooth and glossy seeds. Taste is
mucilaginous and somewhat bitter.LXXIX Muslim authors described leaves being in
three pairs, the uppermost pair being largest and longest, and the leaves generally
close at night time.XL It grows on dry soil throughout tropical parts of India
(Fig. 1).CV
Actions and Uses: Muslim writers described seeds and leaves to have solvent
properties in those forms of skin diseases accompanied with induration, such as
leprosy, keloid and psoriasis. Seeds ground with sour buttermilk are used to ease
irritation of itchy eruptions, and the root, rubbed on a stone with lime juice is one of
the best remedies for ringworm.XL,LXXXI,CV,CXXII In Unani medicine, seeds and
leaves (temperament, hot 2° and dry 2°) are described as purgative, blood purifier,
good for piles, and to expel phlegm and black-bile; and useful as a paste for skin
diseases, such as leprosy, vitiligo, bahq, and kalaf, and cold diseases, such as
paralysis and arthritis.LXXVII GhaniL mentioned it as anti-inflammatory, desiccant,
Senna tora (L.) Roxb. 1651

Fig. 1 Senna tora, Plant, Dinesh Valke, WikimediaCommons; Share Alike 2.0 Generic CC BY-
SA 2.0, https://commons.wikimedia.org/wiki/File:Senna_tora_(1250292137).jpg; https://creative
commons.org/licenses/by-sa/2.0/deed.en

refrigerant, anthelmintic, astringent and digestive, and used for the treatment of skin
diseases. In Ayurveda, dried seeds are used in kaphav ãtajanya vikara, kustha,
vrana, dadru, paksãghãta, vibandha, gulma, krmi, pãmã, kandu, śvãsa and kãsa;LX
and the leaves and seeds are used in the treatment of leprosy, ringworm, flatulence,
colic, dyspepsia, constipation, cough, bronchitis and cardiac disorders [24]. In
India, it is also used in oral healthcare to treat plaque and caries [11], and prescribed
for various eye and liver disorders.LXXIX Decoction of the whole plant is used as
vermifuge and purgative in the Philippines.LVI,CXVII In Chinese medicine, it is
considered a superior drug and has been recorded in The Herbal by Shen Nung.
Dried ripe seeds are used for headache with fever, eye disorders, ophthalmia with
swelling and pain, glaucoma, and dry stools.LXVI Seeds are also used as laxative
and tonic, and as a popular health drink (tea). Commercial products include both
unroasted and roasted samples, and the laxative effect is higher in unroasted
compared with the roasted seeds [38]. Roasted seeds are favored for their flavor,
and popularly used as tea in Korea. It is also prescribed in oriental herbal medicine
to treat night blindness, hypertension, hypercholesterolemia, and constipation [16].II
In Senegal, the plant is traditionally used to treat infectious diseases [20].
Phytoconstituents: Seeds contain antihepatotoxic naphthopyrone glycosides,
cassiaside and rubrofusarin-6-b-gentiobioside [34]. Roasting of seeds decreases the
contents of antihepatotoxic constituents [37]. Anthraquinones, chrysophanol,
emodin and rhein contents in the extract decreased with increased roasting tem-
perature; the decrease in antigenotoxic potency of roasted seeds was related to
reduction in their anthraquinones contents [36]. The plant does not contain alka-
loids and unbound anthraquinones, but contains glycosides, flavonoids and bound
anthraquinones [28]. Anthraquinones present in seeds are aurantioobtusin,
chrysoobtusin, obtusin, chrysoobtusin-2-O-b-D-glucoside, physcion, chrysophanol,
1652 Senna tora (L.) Roxb.

emodin, obtusifolin, and obtusifolin-2-O-b-D-glucoside [14]. Seeds also contain

phenolic triglucosides: torachrysone 8-O-[b-D-glucopyranosyl(1– > 3)-O-b-D-glu-
copyranosyl(1– > 6)-O-b-D-glucopyranoside] and toralactone 9-O-[b-D-glucopyr-
anosyl-(1– > 3)-O-b-D-glucopyranosyl-(1– > 6)-O-b-D-glucopyranoside] [9], rubro-
fusarin [15], alaternin, glucoobtusifolin, cassiaside, glucoaurantioobtusin, cassi-
toroside, toralactone gentiobioside, chrysophanol triglucoside, questin and
2-hydroxyemodin 1-methylether [13], obtusifolin-2-glucoside, chrysoobtusin-6-
glucoside, and norrubrofusarin-6-glucoside [26]. Other constituents include rhein,
hydroxyanthraquinone derivatives, chrysophanic acid, and the major antifungal
compound chrysophanic acid-9-anthrone [1]. Seeds also contain water-soluble
polysaccharides, arabinoglucan and pectic polysaccharides that possess inhibitory
effects on the activities of a-amylase and pancreatic lipase and increase protease
activity. These water-soluble polysaccharides possess the ability to bind bile acids and
reduce the amount of cholesterol absorbed from the intestines [12]. The leaves contain
aloe-emodin [23].
Pharmacology: Water extract of roasted seeds reversed B[a]P-induced DNA
damage in human hepatoma cell line HepG2, which was less effective than pro-
duced by unroasted seeds [35]. Methanol seed extract exhibits in vitro anticancer
effects, induces apoptosis and exerts in vivo antimetastatic effects. It shows
anti-inflammatory activity and significantly downregulates expression of genes
associated with inflammation, including NF-jB, iNOS and COX-2 [38] and exhibits
antimutagenic activity against aflatoxin B1 in the S. typhimurium assay [7]. A high
dose of seeds fed to mice significantly increased levels of TNF-a and IL-1b cytokines
compared with those that were treated with lower doses [4]. Aqueous and methanol
seed extracts show hypotensive effects in anesthetized rats, which was significantly
reduced in vagotomized rats [17, 18]. Methanol extracts of raw and roasted
seeds exhibited significant ACE inhibitory properties; only the anthraquinone
glycoside fraction of the extracts demonstrated marked ACE inhibitory activity [13].
Ononitol monohydrate, structurally similar to glycoside, isolated from leaves
showed higher hepatoprotective activity than silymarin, against CCl4-hepatotoxicity
in rats [8]. Ethanol seed extract and its ether-soluble and water-soluble fractions
decreased serum levels of TC, LDL-C and TGs and increased HDL-C level in
triton-induced hyperlipidemic rats [2, 27], and ethanol seed extract also decreased
excessive hepatic lipid accumulation in high-fat diet-fed rats, and improved
HFD-induced hepatic histological lesions [33], and significantly reduced blood
glucose, TC, TGs, phospholipids, FFAs, and LPx of STZ-diabetic rats [19]. Soluble
fiber from seeds also lowered serum TC and increased HDL-C, significantly
reduced liver TC and TG levels, and increased fecal bile acid and lipid excretion in
high-cholesterol diet-fed rats [6]. Fractions of methanol seed extract have also
shown antidiabetic effects in STZ-diabetic rats [21, 22, 25].
Methanol leaf extract increased smooth muscles contractions of guinea pig ileum
and rabbit jejunum that were reversibly blocked by atropine [5]. Leaf extract
induces marked concentration dependent inhibition of proliferation, reduces DNA
content and apoptosis in HeLa cells [29]. Chrysophanic acid-9-anthrone possesses
Senna tora (L.) Roxb. 1653

antifungal activity against T. mentagrophytes, T. rubrum, M. canis, M. gypseum and

G. candidum [1]. Phenolic compounds from seeds, torachrysone, toralactone,
aloe-emodin, rhein and emodin showed significant antibacterial effects on four
strains of MRSA but did not show significant activity against P. aeruginosa and
E. coli [10]. Oral administration of ethyl acetate fraction of leaves significantly
decreased the onset and maturation of selenite-induced cataract in rat pups [31];
chrysophanol, emodin, kaemferol, quercetin, stigmasterol and isoquercetin were
identified in the extract [32]. Topical application of an oil/water base cream containing
crude methanol leaf extract showed potent antipsoriatic activity in ultraviolet-
B-induced psoriasis in rat [30].
Mechanism of Action: The hypotensive effect could possibly involve vagal reflex
[17, 18], but the role of medullary reticular formation was also suggested in
decreasing the vasomotor tone [3]. Methanol extracts of raw and roasted seeds also
exhibit significant ACE inhibitory effect [13].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: LD50 values of methanol leaf extract in mice are more than
2,000 mg/kg orally and intraperitoneally [5].
Commentary: There are only anecdotal accounts and traditional uses of the plant,
and no clinical data available to validate those claims.

References
1. Acharya TK, Chatterjee IB. Isolation of chrysophanic acid-9-anthrone, the
major antifungal principle of Cassia tora. Lloydia. 1975;38:218–20.
2. Awasthi VK, Mahdi F, Chander R, et al. Hypolipidemic activity of
Cassia tora seeds in hyperlipidemic rats. Indian J Clin Biochem. 2015;30:
78–83.
3. Chan SH, Koo A, Li KM. The involvement of medullary reticular formation
in the hypotensive effect of extracts from the seeds of Cassia tora. Am J
Chin Med. 1976;4:383–9.
4. Chen S, Li G, Zhu K, et al. Antitumor activities of Juemingzi (Cassia
tora L.) on Balb/c sarcoma 180-injected mice. Oncol Lett. 2014;7:250–4.
5. Chidume FC, Kwanashie HO, Adekeye JO, et al. Antinociceptive and
smooth muscle contracting activities of the methanolic extract of Cassia
tora leaf. J Ethnopharmacol. 2002;81:205–9.
6. Cho IJ, Lee C, Ha TY. Hypolipidemic effect of soluble fiber isolated from
seeds of Cassia tora Linn. in rats fed a high-cholesterol diet. J Agric Food
Chem. 2007;55:1592–6.
7. Choi JS, Lee HJ, Park KY, et al. In vitro antimutagenic effects of
anthraquinone aglycones and naphthopyrone glycosides from Cassia tora.
Planta Med. 1997;63:11–4.
1654 Senna tora (L.) Roxb.

8. Dhanasekaran M, Ignacimuthu S, Agastian P. Potential hepatoprotective

activity of ononitol monohydrate isolated from Cassia tora L. on carbon
tetrachloride induced hepatotoxicity in Wistar rats. Phytomedicine. 2009;16:
891–5.
9. El-Halawany AM, Chung MH, Nakamura N, et al. Estrogenic and anti-
estrogenic activities of Cassia tora phenolic constituents. Chem Pharm Bull
(Tokyo). 2007;55:1476–82.
10. Hatano T, Uebayashi H, Ito H, et al. Phenolic constituents of Cassia seeds and
antibacterial effect of some naphthalenes and anthraquinones on methicillin-
resistant Staphylococcus aureus. Chem Pharm Bull (Tokyo). 1999;47:1121–7.
11. Hebbar SS, Harsha VH, Shripathi V, Hegde GR. Ethnomedicine of Dharwad
district in Karnataka, India—plants used in oral health care. J Ethnophar-
macol. 2004;94:261–6.
12. Huang YL, Chow CJ, Tsai YH. Composition, characteristics, and in-vitro
physiological effects of the water-soluble polysaccharides from Cassia seed.
Food Chem. 2012;134:1967–72.
13. Hyun SK, Lee H, Kang SS, Chung HY, Choi JS. Inhibitory activities
of Cassia tora and its anthraquinone constituents on angiotensin-converting
enzyme. Phytother Res. 2009;23:178–84.
14. Jang DS, Lee GY, Kim YS, et al. Anthraquinones from the seeds of Cassia
tora with inhibitory activity on protein glycation and aldose reductase. Biol
Pharm Bull. 2007;30:2207–10.
15. Kaneda M, Morishita E, Shibata S. Chemical studies on the oriental plant
drugs. XXI. The constituents of Cassia tora L. 2. A glycoside of rubro-
fusarin. Chem. Pharmaceut. Bull. 1969;17:458–61.
16. Kim JM, Kim HT, Hwang SM. Instant tea preparation from Cassia
tora seeds. Korean J Food Sci Tech. 1990;22:241–7.
17. Koo A, Chan WS, Li KM. A possible reflex mechanism of hypotensive
action of extract from Cassia tora seeds. Am J Chin Med. 1976;4:249–55.
18. Koo A, Wang JC, Li KM. Extraction of hypotensive principles from seeds
of Cassia tora. Am J Chin Med. 1976;4:245–8.
19. Kumar V, Singh R, Mahdi F, Mahdi AA, Singh RK. Experimental validation
of antidiabetic and antioxidant potential of Cassia tora (L.): an indigenous
medicinal plant. Indian J Clin Biochem. 2017;32:323–8.
20. Le Grand A. Antiinfective phytotherapies of the tree-savannah, Senegal
(occidental Africa). III: A review of phytochemical substances and the
antimicrobial activity of 43 species. J Ethnopharmacol. 1989;25:315–38
(Review in French).
21. Lim SJ, Han HK. Hypoglycemic effect of fractions of Cassia tora extract in
streptozotocin-induced diabetic Rats. J Korean Soc Food Sci Nutr. 1997;
13:23–9.
22. Lim SJ, Kim SY, Lee JW. The effects of Korean wild vegetables on blood
glucose levels and liver muscle metabolism of streptozotocin-induced
diabetic rats. Korean J Nutr. 1995;28:585–94.
Senna tora (L.) Roxb. 1655

23. Maity TK, Mandal SC, Bhakta T, et al. Metabolism of 1,8-dihydroxy

3-hydroxymethyl anthraquinone (aloe-emodin) isolated from the leaves of
Cassia tora in albino rats. Phytother Res. 2001;15:459–60.
24. Mazumder A, Lahkar V, Sahay J, et al. Pharmacognostical studies on the
leaves of Cassia tora Linn. (Fam. Caesalpiniaceae). Anc Sci Life. 2005;
25:74–8.
25. Nam J, Choi H. Effect of butanol fraction from Cassia tora L. seeds on
glycemic control and insulin secretion in diabetic rats. Nutr Res Pract. 2008;
2:240–6.
26. Park YB, Kim SB. Isolation and identification of antitumor promoters from
the seeds of Cassia tora. J Microbiol Biotechnol. 2011;21:1043–8.
27. Patil UK, Saraf S, Dixit VK. Hypolipidemic activity of seeds of Cassia tora
Linn. J Ethnopharmacol. 2004;90:249–52.
28. Rasul N, Saleem B, Nawaz R. Preliminary phytochemical screening of four
common plants of family Caesalpiniaceae. Pak J Pharm Sci. 1989;2:55–7.
29. Rejiya CS, Cibin TR, Abraham A. Leaves of Cassia tora as a novel cancer
therapeutic—an in vitro study. Toxicol In Vitro. 2009;23:1034–8.
30. Singhal M, Kansara N. Cassia tora Linn cream inhibits ultraviolet-B-
induced psoriasis in rats. ISRN Dermatol. 2012;2012:346510.
31. Sreelakshmi V, Abraham A. Anthraquinones and flavonoids of Cassia tora
leaves ameliorate sodium selenite induced cataractogenesis in neonatal rats.
Food Funct. 2016;7:1087–95.
32. Sreelakshmi V, Abraham A. Polyphenols of Cassia tora leaves prevents
lenticular apoptosis and modulates cataract pathology in Sprague-Dawley
rat pups. Biomed Pharmacother. 2016;81:371–8.
33. Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. Cassia tora (Leguminosae)
seed extract alleviates high-fat diet-induced nonalcoholic fatty liver. Food
Chem Toxicol. 2013;51:194–201.
34. Wong SM, Wong MM, Seligmann O, Wagner H. New antihepatotoxic
naphthopyrone glycosides from the seeds of Cassia tora. Planta Med. 1989;
55:276–80.
35. Wu CH, Hsieh CL, Song TY, Yen GC. Inhibitory effects of Cassia tora L.
on benzo[a]pyrene-mediated DNA damage toward HepG2 cells. J Agric
Food Chem. 2001;49:2579–86.
36. Wu CH, Yen GC. Antigenotoxic properties of Cassia tea (Cassia tora L.):
mechanism of action and the influence of roasting process. Life Sci. 2004;
76:85–101.
37. Zhang Q, Zhou Z, Yin J, et al. Influence of temperature on the chemical
constituents and pharmacological effects of semen Cassiae. Zhongguo
Zhong Yao Za Zhi. 1996;21:663–5, 703 (Chinese).
38. Zhao X, Wang Q, Qian Y, Pang L. Cassia tora L. (Jue-ming-zi) has anticancer
activity in TCA8113 cells in vitro and exerts antimetastatic effects in vivo. Oncol
Lett. 2013;5:1036–42.
Sida cordifolia L.
(Malvaceae)

(Syns.: S. conferta Link; S. herbacea Cav.; S. maculata Cav.; S. micans Cav.;

S. rotundifolia Lam.)

Abstract
An erect perennial subshrub that is native to India, but pantropic in distribution. In
Ayurveda, roots are regarded as cooling, astringent, stomachic, tonic and aromatic
bitters and having antipyretic, demulcent and diuretic properties. In nervous
afflictions, such as hemiplegia, facial paralysis, and headache, root is used either
by itself or with asafetida and rock salt. The roots are also used as cardiac
stimulant (tonic) and for the treatment of asthma. Roots infusion is used in
nervous (insanity, facial palsy) and urinary diseases, bleeding piles, strangury and
hematuria, gonorrhea, cystitis, leucorrhea, chronic dysentery, and asthma. Roots
of Sida species are also known in Indian traditional medicines for their antitumor,
anti-HIV, and hepatoprotective properties. Seeds mixed with other ingredients are
used to relieve muscular pain, and crushed leaves and root juice are used to
promote wound healing. The plant is also reportedly used for the management of
neurodegenerative diseases such as Parkinson’s, Alzheimer’s, loss of memory,
degeneration of nerves and other neuronal disorders by Ayurvedic practitioners.
Muslim physicians in India consider the drug aphrodisiac. In the Philippines,
leaves decoction is considered emollient and diuretic. Seeds are considered
aphrodisiac, and also used for gonorrhea, cystitis, colic and tenesmus. In East
Africa, roots are pounded, and mixed with fat are rubbed-in as a cure for lumbago.
Bark is chewed to stimulate menstruation, and the plant is used as abortifacient. In
Burkina Faso (West Africa), leaf decoction is traditionally used in the treatment
of coughs, rheumatic and abdominal pain, diarrhea, fever and to prevent
miscarriage (the opposite to what it is reportedly used in East Africa), for
abdominal infections and associated diseases. Predominant of the reported 142
chemical constituents isolated from this genus are alkaloids, flavonoids and
ecdysteroids. Ethanol extract of roots of S. cordifolia shows the presence of
reducing sugar, alkaloids, steroids and saponins. From this genus, Sida cordifolia
reportedly possesses the highest total phenolic content, total flavonoid content

© Springer Nature Switzerland AG 2020 1657

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_171
1658 Sida cordifolia L.

and the highest antioxidant activity. Hydroalcohol extract of leaves showed CNS
depressant activity in mice, and ethanol root extract demonstrated significant
antistress and adaptogenic activities.

Keywords




Baryal Batyalaka Country mallow Hulba-e-barri Llima

Ke dong





Khurainti Malva-branca Maruba kingojika Shanbalide-barri

Vernaculars: Urd.: Kharenti, Khurainti; Hin.: Bariara, Baryal, Khareti, Kungyi;

San.: Bala, Batyalaka (seeds), Beejband, Bijband; Ben.: Bala, Barela, Barjala,
Bonmethi, Chuka, Hamaz, Koreta, Svet-barela; Guj.: Jangli methi; Mal.: Cheru,
Kurumthotti, Paruva, Velluram; Mar.: Chikana-pata, Karaiti, Tukati, Tupkaria;
Tam.: Chitaamuttie, Malai-tangi, Mayir-manikham, Paniyar-tutti; Tel.: Chirubenda,
Chitimutti, Mailmanikkam, Mayir-manikham, Muttuva, Tutturabenda; Ara.:
Al-khabbaza, Hulba-e-barri; Chi.: Ke dong; Eng.: Country mallow, Flannel weed,
Heart-leaf sida, Indian Ephedra; Ger.: Herzformblättrige samtmalve; Haw.: Ilima;
Jap.: Maruba kingojika; Nep.: Balu; Per.: Shanbalide-barri; Por.: Malva-branca or
Malva-branca sedosa (Br.); Rus.: Bala, Sida serdtselistnaia; Spa.: Escoba negra,
Escobilla, llima, Malva de playa; Tag.: Gulipas; Tha.: Ya khat bai pom.
Description: Native to India, but pantropic in distribution. An erect perennial
subshrub (weed), or half-woody shrub that reaches up to one meter in height and is
covered with soft white felt-like velvety hairs, hence it is called “flannel weed.”
Leaves are hairy, ovate and 3.5–7.5 cm long and 2.5–6.0 cm wide, with blunt tips
and heart-shaped base, and toothed margins. Stems are yellow-green, hairy, long,
and slender. Flowers are yellow, sometimes with a darker orange center, with a
hairy 5-lobed calyx and 5-lobed corolla, borne in the axils of leaves, and often
crowded on younger branches, forming leafy racemes. Roots of different species of
Sida are 6 mm in diameter at the stock, woody, and fibrous. Bark is of a yellowish-
brown color, unless the leaves are attached, they cannot be distinguished with any
certainty (Figs. 1 and 2).XL
Actions and Uses: In Ayurveda, roots are regarded as cooling, astringent, stom-
achic, tonic and aromatic bitters and having antipyretic, demulcent and diuretic
properties. In nervous afflictions, such as hemiplegia, facial paralysis, and head-
ache, root is used either by itself or with asafetida and rock salt. The roots are also
used as cardiac stimulant (tonic) and for the treatment of asthma.XXI,XL,CV Roots
infusion is used in nervous (insanity, facial palsy) and urinary diseases, bleeding
piles, strangury and hematuria, gonorrhea, cystitis, leucorrhea, chronic dysentery,
and asthma.CV Roots of Sida species are also known in Indian traditional medicines
for their antitumor, anti-HIV, and hepatoprotective properties [21]. Seeds mixed
with other ingredients are used to relieve muscular pain, and crushed leaves and
root juice are used to promote wound healing.LXXXIV The plant is also reportedly
used for the management of neurodegenerative diseases such as Parkinson’s,
Alzheimer’s, loss of memory, degeneration of nerves and other neuronal disorders
Sida cordifolia L. 1659

Fig. 1 Sida cordifolia, Plant, J.M. Garg, WikimediaCommons; ShareAlike 4.0 International CC
BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Sida_cordifolia_(Bala)_in_Hyderabad,_
AP_W_IMG_9423.jpg; https://creativecommons.org/licenses/by-sa/4.0/

Fig. 2 Sida cordifolia, Flower, J.M. Garg, WikimediaCommons; ShareAlike 4.0 International CC
BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Sida_cordifolia_(Bala)_in_Hyderabad,_
AP_W_IMG_9420.jpg; https://creativecommons.org/licenses/by-sa/4.0/
1660 Sida cordifolia L.

by Ayurvedic practitioners [2]. Muslim physicians in India consider the drug

aphrodisiac.XL Fresh leaves are bruised and applied to boils to promote suppuration,
and cooked and eaten for bleeding piles, and the juice of whole plant is used for
gonorrhea and nocturnal emissions.CV In the Philippines, leaves decoction is con-
sidered emollient and diuretic.LVI,CXVII Seeds are considered aphrodisiac, and also
used for gonorrhea, cystitis, colic and tenesmus.XXI,CV In East Africa, roots are
pounded, and mixed with fat are rubbed-in as a cure for lumbago. Bark is chewed to
stimulate menstruation, and the plant is used as abortifacient.LXXXV In Burkina
Faso (West Africa), leaf decoction is traditionally used in the treatment of coughs,
rheumatic and abdominal pain, diarrhea, fever and to prevent miscarriage (the
opposite to what bark is reportedly used in East Africa) [1, 14, 15], for abdominal
infections and associated diseases [10]. The genus Sida is also reportedly used in
traditional medicines of China, Africa and American countries for prevention and
treatment of diarrhea, dysentery, gastrointestinal and urinary infections, malarial
and other fevers, childbirth and miscarriage problems, skin ailments, cardiac and
neural problems, asthma, bronchitis and other respiratory afflictions, as weight loss
aid, for rheumatic and other inflammations, and tuberculosis [1, 4].CL It is popularly
known in Brazil as Malva-branca or Malva-branca sedosa and is used in folk
medicine for the treatment of inflammation of oral mucosa (stomatits), blennorrhea,
asthmatic bronchitis and nasal congestion [3, 5, 6]. The ilima wreath, a favorite of
the Hawaiians is made from this plant, and the flowers are used as laxatives in
babies as young as five days old; the flowers, young shoots and the bark of roots are
used for uterine complaints, general debility and asthma.LXXVI
Phytoconstituents: Predominant of the reported 142 chemical constituents isolated
from this genus are alkaloids, flavonoids and ecdysteroids [4]. Ethanol extract of
roots of S. cordifolia shows the presence of reducing sugar, alkaloids, steroids and
saponins [7, 13]. From this genus, Sida cordifolia reportedly possesses the highest
total phenolic content, total flavonoid content and the highest antioxidant activity
[21]. An alkaloid, 1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-3-ylamine, isolated
from the plant showed significant analgesic and anti-inflammatory activities [23, 24].
Pharmacology: Ethyl acetate extract of the root showed anti-inflammatory activity
comparable to indomethacin, and ethyl acetate extract of both root and aerial parts
also exhibited significant central and peripheral analgesic activities; whereas
methanol root extract exerted hypoglycemic activity [8]. Successive extracts of
leaves in ethanol, chloroform and methanol showed pronounced antinociceptive
activity on glutamate and formalin-induced orofacial nociception in mice [3].
Methanol extract of aerial parts reduced pyrexia and exhibited antiulcerogenic effect
against aspirin and ethanol induced gastric damage [17]. Aqueous, aqueous-acetone
and ethanol extracts of leaves also exhibited analgesic activity [6, 10, 13], and
inhibition of carrageenan-induced rat paw edema, but not AA-induced edema [6].
Alkaloidal fraction shows significant antioxidant and antifungal activities against C.
albicans, C. parapsilosis, C. krusei, and C. tropicalis [15]. Ethanol extract of the
plant possesses a very potent antioxidant activity [2], and its topical application as
Sida cordifolia L. 1661

ointment improved healing of incision and burn wounds [16]. Ethanol root extract
reduced LPO and activities of markers of inflammatory responses, such as COX
and LOX [25].
Hydroalcohol extract of leaves showed CNS depressant activity in mice [5], and
ethanol root extract demonstrated significant antistress and adaptogenic activities
[22]. Aqueous fraction of hydroalcohol leaf extract lowered BP and HR in nor-
motensive, nonanesthetized rats, that were completely abolished by atropine [12],
and hydroalcohol leaf extract was also protective against isoproterenol-induced MI
in rats [11]. Aqueous extract attenuated rotenone-induced oxidative damage,
increased levels of DA, GSH and CAT enzyme in the mid brain region of rats,
comparable to l-deprenyl [9]. Aqueous leaf extract stimulated liver regeneration
after 67% partial hepatectomy in rats [20], whereas concurrent administration of
50% ethanol extract was potently protective against alcohol-hepatotoxicity [18].
Mechanism of Action: Hepatoprotective effect is mediated through reduced LPO
and downregulation of transcription factors for CYP2E1, NF-jB, TNF-a and trans-
forming growth factor-b1 [18]. Endothelium-derived factors (mainly NO, PGI2) and
K+ channels are suggested to be involved in the vasorelaxation [19].
Human A/Es, Allergy and Toxicity: An herbal supplement containing chromium
picolinate, Sida cordifolia, synephrine, and guarana is reported to have caused acute
renal failure in an adult patient after two-weeks of consumption. The patient
required hemodialysis but recovered with normal renal function [26].
Animal Toxicity: Leaf aqueous extract reportedly showed low acute toxicity in
mice [6]. LD50 (i.p.) of aqueous-acetone extract in mice was reported to be
3,400 mg/kg [10].
Commentary: Different parts of the plant exert paradoxical effects; while the bark
is chewed to stimulate menstruation and as abortifacient in East Africa, leaves
decoction is used to prevent abortion in West Africa. This is a clear example of
different plant parts eliciting different results. Liver regenerating capacity of the
aqueous leaf extract is of significance and should be further explored. There are no
published clinical data available on this plant in English literature listed on
PubMed.

References
1. Anonymous. Sida cordifolia. Pacific Island Ecosystems at Risk (PIER).
2006-10-25. Retrieved 18 July 2010.
2. Auddy B, Ferreira M, Blasina F, et al. Screening of antioxidant activity of
three Indian medicinal plants, traditionally used for the management of
neurodegenerative diseases. J Ethnopharmacol. 2003;84:131–8.
3. Bonjardim LR, Silva AM, Oliveira MG, et al. Sida cordifolia leaf extract
reduces the orofacial nociceptive response in mice. Phytother Res. 2011;25:
1236–41.
1662 Sida cordifolia L.

4. Dinda B, Das N, Dinda S, Dinda M, SilSharma I. The genus Sida L. a

traditional medicine: its ethnopharmacological, phytochemical and pharma-
cological data for commercial exploitation in herbal drugs industry.
J Ethnopharmacol. 2015;176:135–76.
5. Franco CI, Morais LC, Quintans-Júnior LJ, et al. CNS pharmacological
effects of the hydroalcoholic extract of Sida cordifolia L. leaves. J Ethnophar-
macol. 2005;98:275–9.
6. Franzotti EM, Santos CV, Rodrigues HM, et al. Anti-inflammatory, analgesic
activity and acute toxicity of Sida cordifolia L. (Malva-branca). J Ethnophar-
macol. 2000;72:273–7.
7. Ghosal S, Chauhan RBPS, Mehta R. Alkaloids of Sida Cordifolia.
Phytochem. 1975;14:830–2.
8. Kanth VR, Diwan PV. Analgesic, anti-inflammatory and hypoglycaemic
activities of Sida cordifolia. Phytother Res. 1999;13:75–7.
9. Khurana N, Gajbhiye A. Ameliorative effect of Sida cordifolia in rotenone
induced oxidative stress model of Parkinson’s disease. Neurotoxicology.
2013;39:57–64.
10. Konaté K, Bassolé IH, Hilou A, et al. Toxicity assessment and analgesic
activity investigation of aqueous acetone extracts of Sida acuta Burn f. and
Sida cordifolia L. (Malvaceae), medicinal plants of Burkina Faso. BMC
Complement Altern Med. 2012;12:120.
11. Kubavat JB, Asdaq SM. Role of Sida cordifolia L. leaves on biochemical
and antioxidant profile during myocardial injury. J Ethnopharmacol. 2009;
124:162–5.
12. Medeiros IA, Santos MR, Nascimento NM, Duarte JC. Cardiovascular
effects of Sida cordifolia leaves extract in rats. Fitoterapia. 2006;77:19–27.
13. Momin MA, Bellah SF, Rahman SM, et al. Phytopharmacological evaluation
of ethanol extract of Sida cordifolia L. roots. Asian Pac J Trop Biomed.
2014;4:18–24.
14. Nacoulma OG. Medicinal plants and their traditional uses in Burkina Faso.
Ph.D. thesis. University of Ouagadougou;1996:328.
15. Ouédraogo M, Konaté K, Lepengué AN, et al. Free radical scavenging
capacity, anticandicidal effect of bioactive compounds from Sida cordifolia
L., in combination with nystatin and clotrimazole and their effect on specific
immune response in rats. Ann Clin Microbiol Antimicrob. 2012;11:33.
16. Pawar RS, Chaurasiya PK, Rajak H, et al. Wound healing activity of Sida
cordifolia Linn. in rats. Indian J Pharmacol. 2013;45:474–8.
17. Philip BK, Muralidharan A, Natarajan B, et al. Preliminary evaluation of
antipyretic and antiulcerogenic activities of Sida cordifolia methanolic
extract. Fitoterapia. 2008;79:229–31.
18. Rejitha S, Prathibha P, Indira M. Amelioration of alcohol-induced hepato-
toxicity by the administration of ethanolic extract of Sida cordifolia Linn.
Br J Nutr. 2012;108:1256–63.
19. Santos MR, Nascimento NM, Antoniolli AR, Medeiros IA. Endothelium-
derived factors and K+ channels are involved in the vasorelaxation induced
Sida cordifolia L. 1663

by Sida cordifolia L. in the rat superior mesenteric artery. Pharmazie. 2006;

61:466–9.
20. Silva RL, Melo GB, Melo VA, et al. Effect of the aqueous extract of Sida
cordifolia on liver regeneration after partial hepatectomy. Acta Cirurgica
Bras. 2006;21 Suppl 1:37–9.
21. Subramanya MD, Pai SR, Upadhya V, et al. Total polyphenolic contents
and in vitro antioxidant properties of eight Sida species from Western
Ghats, India. J Ayurveda Integr Med. 2015;6:24–8.
22. Sumanth M, Mustafa SS. Antistress, adoptogenic activity of Sida cordifo-
lia roots in mice. Indian J Pharm Sci. 2009;71:323–4.
23. Sutradhar RK, Matior Rahman AKM, Ahmad M, et al. Bioactive alkaloid
from Sida cordifolia Linn. with analgesic and anti-inflammatory activities.
Iranian J Pharmacol Therapeut. 2006;5:175–8.
24. Sutradhar RK, Rahman AM, Ahmad M, et al. Anti-inflammatory and
analgesic alkaloid from Sida cordifolia linn. Pak J Pharm Sci. 2007;20:
185–8.
25. Swathy SS, Panicker S, Nithya RS, et al. Antiperoxidative and anti-inflamma-
tory effect of Sida cordifolia Linn. on quinolinic acid induced neurotoxicity.
Neurochem Res. 2010;35:1361–7.
26. Wani S, Weskamp C, Marple J, Spry L. Acute tubular necrosis associated with
chromium picolinate-containing dietary supplement. Ann Pharmacother.
2006;40:563–6.
Smilax china L.
(Smilacaceae)

(Syns.: S. japonica (Kunth) A. Gray; S. pteropus Miq.; Coprosmanthus japonicus

Kunth)

Abstract
A climbing shrub or woody vine, native of southern China, India, Nepal, Japan,
Taiwan, Korea, the Philippines, Myanmar, Vietnam, and Thailand. Tubers are used
as food in some parts of China, and in TCM as diuretic, and for the treatment of
syphilis, rheumatic arthritis, detoxication, lumbago, gout, tumor, and inflammatory
diseases. Chinese often eat the root instead of rice, because it contributes to make
them lusty. Muslim writers consider it antirheumatic, antisyphilitic, aphrodisiac and
demulcent. In Europe, after the China root produced good effect on the Emperor
Charles V, who was suffering from gout, it acquired the status of a celebrity, and
several works were written in praise of its virtues. In Indian medicine, the rhizome is
described as diaphoretic, stimulant, alterative and resolvent. Its decoction is used as
depurative, diaphoretic, stimulant, alterative, antisyphilitic, in leprosy, kidney and
bladder diseases, paralysis, headache, convulsions, and as aphrodisiac, and is also
described as sudorific and demulcent, and used for rheumatism. In the Philippines,
decoction of roots and rhizomes is used as a depurative and as a remedy for
herpetism (predisposition to herpes infections), syphilis and similar afflictions.
Rhizomes contain crystalline saponin smilacin, tannin, and a resin, a flavonoid
compound, astilbin, a triflavanoid, an isonarthogenin glycoside, b-sitosterol,
b-daucosterol, resveratrol, b-secretase inhibitors, kaempferol, dihydrokaempferol,
rutin, engeletin, isoengeletin, vanillic acid, cytotoxic polyphenols, and dioscin, a
synergistic tyrosinase inhibitor. Rhizomes exhibit anti-inflammatory, anticancer and
antioxidant activities. Methanol extract of rhizomes and isolated flavonoid quercetin
from it showed significant antipsoriatic activity, inhibiting leukocyte migration,
producing significant orthokeratosis, and reducing epidermal thickness. Ethanol
extract, rich in resveratrol and oxyresveratrol, reduces cellular oxidative stress,
increases nicotine metabolism by induction of hepatic CYP2A6, and also exerts
antimetastatic effect on human breast cancer cells.

© Springer Nature Switzerland AG 2020 1665

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_172
1666 Smilax china L.

Keywords




Bá qiā Chinawortel Chinawurzel Chinese sarsaparilla
Chobchini





Dwipautra Esquine Kasbussini Madhusnuhi Tu-fu-ling

Vernaculars: Urd.: Chobchini; Hin.: Chobchinni; San.: Dvipata, Dwipautra,

Madhusnuhi, Rasna, Suganda-mula, Wacha; Ben.: Shook china; Mal.: Chinapaivu;
Mar.: Chopa chinni; Tam.: Parangichekkai, Paringay, Paringai-puttai, Parinkipatte,
Shuk-china; Tel.: Gali-chekka, Pirangi-chakka; Ara.: Kasbussini, Kashab-chinae,
Khashabus-sini; Chi.: Bá qiā, Chin-kang t’eng, Jin gang ten, Po-his, Too-fup,
Tu-fu-ling; Dut.: Chinawortel; Eng.: China root, Chinese sarsaparilla, Chinese
smilax, Bamboo briar root; Fre.: Esquine, Racine de Chine, Salsepareille de Chine,
Smilace de Chine, Squine; Ger.: Chinawurzel, Chinesische stechwinde; Jap.:
Saru-tori-ibara; Per.: Chob-chini; Tag.: Sarsaparillang-China.
Description: A native of southern China, India, Nepal, Japan, Taiwan, Korea, the
Philippines, Myanmar, Vietnam, and Thailand. A climbing shrub or woody vine
with thorny stems. Leaves alternate, oval or orbiculate, 5–8 cm long and 2.5–4 cm
wide, cartilagenous and shiny, with tendrils at the base of the petiole. Flowers
small, very numerous, axillary, solitary, dioecious, yellowish-green (flowers in
summer). Roots are generally flat, more or less gnarled, brown on the outside,
pinkish-white inside, texture sometimes light and spongy, sometimes compact and
very hard, and sometimes resinous. Berries are red, globose, and 0.6–1.5 cm in
diameter. Roots are available in pieces 15–20 cm long and 4–5 cm thick; odorless
and slightly bitter in taste (Figs. 1 and 2).LXXIX,CXVII
Actions and Uses: Dymock et al.XL quoted Ainslie that the Chinese often eat the
root instead of rice, and that it contributes to make them lusty. Muslim writers
consider it antirheumatic, antisyphilitic, aphrodisiac and demulcent. In Europe, after
the China root produced good effect on the Emperor Charles V, who was suffering
from gout, it acquired the status of a celebrity, and several works were written in
praise of its virtues.XL In Indian medicine, the rhizome (temperament, hot 1° and dry
1°) is described as diaphoretic, stimulant, alterative and resolvent. Its decoction is
used as depurative, diaphoretic, stimulant, alterative, antisyphilitic, in leprosy,
kidney and bladder diseases, paralysis, headache, convulsions, and as aphrodisiac,CV
and is also described as sudorific and demulcent, and used for rheumatism.XXI
Chobchini with mastaki (Pistacia lentiscus), elaichi (Elletaria cardomomum) and
taja (Cinnamomum zeylanicum) boiled with milk is used for rheumatism, gout,
epilepsy, and in general cachexia, scrofula, seminal debility and constitutional ter-
tiary syphilis.LXXXI Tubers are used as food in some parts of China, and in TCM as
diuretic, and for the treatment of syphilis, rheumatic arthritis, detoxication, lumbago,
gout, tumor, and inflammatory diseases [28].LXVI KeysLXXIX also mentioned it as
alterative and diuretic and used for the treatment of syphilis, gout, skin disorders, and
rheumatism. The root is also used for syphilitic gummata, some forms of leprosy and
Smilax china L. 1667

Fig. 1 Smilax china, Leaves and Unripe Fruits, Hasso Wetland, Japan, Alpsdake, Wikime-
diaCommons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/
File:Smilax_china_s7.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

Fig. 2 Smilax china, Ripe Fruits in Fukushima Pref., Japan, Qwert1234, WikimediaCommons,
https://commons.wikimedia.org/wiki/Smilax_china#/media/File:Smilax_china_071117.JPG
1668 Smilax china L.

yaws in Indonesia [4]. In the Philippines, decoction of roots and rhizomes is used as
a depurative and as a remedy for herpetism (predisposition to herpes infections),
syphilis and similar afflictions.LVI,CXVII
Phytoconstituents: Rhizomes contain crystalline saponin smilacin, tannin, and a
resin,LXXIX a flavonoid compound, astilbin [2], a triflavanoid, kandelin B-5 [31], an
isonarthogenin glycoside [19], dihydrokaempferol-5-O-b-D-glucoside, b-sitosterol,
b-daucosterol [18], resveratrol [25], b-secretase inhibitors (trans/cis-resveratrol
mixture, oxyresveratrol, veraphenol, and cis-scirpusin A) [6], kaempferol, dihy-
drokaempferol, kaemperol-7-O-b-D-glucopyranoside, dihydrokaempferol-5-O-P-D-
glucopyranoside, kaempferol-5-O-b-D-glucopyranoside, 3,5,4′-trihydroxystibene,
3,5-dimethoxy4-O-b-D-glucopyranosylcinnamic acid, rutin, engeletin, isoengeletin,
vanillic acid [30], cytotoxic polyphenols [28], and dioscin, a synergistic tyrosinase
inhibitor [13]. Resveratrol content differed in samples from different habitats in
China, being higher in samples from Qianshan (Anhui Province) than from other
habitats [25]. Phenylpropanoid glycosides, smilasides A–F, smiglaside E, helo-
niosides B, and 2ʹ,6ʹ-diacetyl-3,6-diferuloylsucrose have been isolated from the
stem [9].
Pharmacology: Rhizomes exhibit anti-inflammatory, anticancer and antioxidant
activities [1, 7, 11, 14, 20–22]. Methanol extract of rhizomes and isolated flavonoid
quercetin from it showed significant antipsoriatic activity, inhibiting leukocyte
migration, producing significant orthokeratosis, and reducing epidermal thickness
[24]. Ethyl acetate fraction of rhizome extract exhibits strong antihyperuricemic
activity in potassium oxonate-induced hyperuricemia in mice, prevents renal
damage in fructose-induced hyperuricemic rats [3], and significantly inhibits uterine
inflammation in rats with experimental chronic pelvic inflammatory disease [15,
16]. Astilbin, the flavonoid compound, significantly decreased serum uric acid
levels by increasing urinary excretion of uric acid and fractional excretion of urate,
but showing no effect on XO activity [2]. Astilbin also significantly ameliorated
ConA-induced hepatitis in rats, reducing TNF-a production, and improving histo-
logical changes, including inflammatory infiltration, hepatocyte necrosis and
degeneration and Kupffer cell hyperplasia [26]. Ethyl acetate extract and phenolic
compounds, dihydrokaempferol and kaempferol-7-O-b-D-glucoside, demonstrated
moderate in vitro anti-HIV-1 activities [27].
Ethanol extract, rich in resveratrol and oxyresveratrol, reduces cellular oxidative
stress, increases nicotine metabolism by induction of hepatic CYP2A6 [8], and also
exerts in vitro antimetastatic effect on human breast cancer cells, which may involve
modulation of extracellular matrix degradation [17]. Aqueous extract completely
inhibited mutagenic effect of B(a)P [10]. Kaempferol-7-O-b-D-glucoside displays
marked anticancer effects on human cancer cell lines [12], inducing G2/M phase
arrest and causing apoptosis of HeLa cells [29], and ovarian cancer cells [5].
Ethanol extract also exhibited significant anticonvulsant activity in mice [23],
whereas the methanol extract prevented amyloid b-protein-induced neuronal cell
damage in vitro [1].
Smilax china L. 1669

Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.

Animal Toxicity: No animal toxicity studies are reported in the literature.
CYP450 and Potential for Drug-Herb Interaction: Induction of hepatic
CYP2A6 by ethanol extract may interact with prescription drugs metabolized by
CYP2A6 [8].
Commentary: There are no published reports available on human or animal
toxicity, and clinical trials on any of its potential traditional therapeutic uses.

References
1. Ban JY, Cho SO, Koh SB, et al. Protection of amyloid beta protein (25–35)-
induced neurotoxicity by methanol extract of Smilacis chinae rhizome in
cultured rat cortical neurons. J Ethnopharmacol. 2006;106:230–7.
2. Chen L, Lan Z, Zhou Y, et al. Astilbin attenuates hyperuricemia and amelio-
rates nephropathy in fructose-induced hyperuricemic rats. Planta Med. 2011;
77:1769–73.
3. Chen L, Yin H, Lan Z, et al. Antihyperuricemic and nephroprotective effects
of Smilax china L. J Ethnopharmacol. 2011;135:399–405.
4. Hirschhorn HH. Constructing a phytotherapeutic concordance based upon
tropical American and Indonesian examples. J Ethnopharmacol. 1983;7:
157–67.
5. Hu LL, Chen DS, Wang YY, et al. Smilax China L. rhizome extract inhibits
nuclear factor-jB and induces apoptosis in ovarian cancer cells. Chin J
Integr Med. 2015;21:907–15.
6. Jeon SY, Kwon SH, Seong YH, et al. Beta-secretase (BACE1)-inhibiting
stilbenoids from Smilax rhizoma. Phytomedicine. 2007;14:403–8.
7. Khan I, Nisar M, Ebad F et al. Anti-inflammatory activities of sieboldogenin
from Smilax china Linn.: experimental and computational studies. J Ethno-
pharmacol. 2009;121:175–7.
8. Kim KM, Suh JW, Yang SH, et al. Smilax china root extract detoxifies
nicotine by reducing reactive oxygen species and inducing CYP2A6. J Food
Sci. 2014;79:H2132–9.
9. Kuo YH, Hsu YW, Liaw CC, et al. Cytotoxic phenylpropanoid glycosides
from the stems of Smilax china. J Nat Prod. 2005;68:1475–8.
10. Lee H, Lin JY. Antimutagenic activity of extracts from anticancer drugs in
Chinese medicine. Mutation Res. 1988;204:229–34.
11. Lee SE, Ju EM, Kim JH. Free radical scavenging and antioxidant enzyme
fortifying activities of extracts from Smilax china root. Exp Mol Med. 2001;
33:263–8.
12. Li YL, Gan GP, Zhang HZ, et al. A flavonoid glycoside isolated from
Smilax china L. rhizome in vitro anticancer effects on human cancer cell
lines. J Ethnopharmacol. 2007;113:115–24.
1670 Smilax china L.

13. Liang C, Lim JH, Kim SH, Kim DS. Dioscin: a synergistic tyrosinase
inhibitor from the roots of Smilax china. Food Chem. 2012;134:1146–8.
14. Lü Y, Chen D, Deng J, Tian L. Effect of Smilax china on adjunctive arthritis
mouse. Zhong Yao Cai. 2003;26:344–6 (Chinese).
15. Luo Y, Ma Y, Song L, Luo H, Hou L. Effect of Smilax china bioactive
fraction on tumor necrosis factor-a and interleukin-4 contents in uterine
tissue of rats with chronic pelvic inflammatory disease. Nan Fang Yi Ke Da
Xue Xue Bao. 2014;34:236–40 (Chinese).
16. Ma Y, Luo Y, Song L, et al. Pharmaceutical screening of the effective
fraction from Smilax for treatment of chronic pelvic inflammatory disease.
Nan Fang Yi Ke Da Xue Xue Bao. 2013;33:145–9 (Chinese).
17. Nho KJ, Chun JM, Kim HK. Antimetastatic effect of Smilax china L. extract
on MDA-MB-231 cells. Mol Med Rep. 2015;11:499–502.
18. Ruan J, Zou J, Cai Y. Studies on chemical constituents of Smilax china.
Zhong Yao Cai. 2005;28:24–6 (Chinese).
19. Sashida Y, Kubo S, Mimaki Y, et al. Steroidal saponins from Smilax riparia
and S. china. Phytochemistry. 1992;31:2439–43.
20. Shao B, Guo H, Cui Y, et al. Steroidal saponins from Smilax china and their
anti-inflammatory activities. Phytochemistry. 2007;68:623–30.
21. Shu XS, Gao ZH, Yang XL. The anti-inflammation effects of Smilax china
ethylacetate extract in rats and mice. Zhongguo Zhong Yao Za Zhi. 2006;
31:239–43 (Chinese).
22. Shu XS, Gao ZH, Yang XL. Anti-inflammatory and antinociceptive activities
of Smilax china L. aqueous extract. J Ethnopharmacol. 2006;103:327–32.
23. Vijayalakshmi A, Ravichandiran V, Anbu J, et al. Anticonvulsant and
neurotoxicity profile of the rhizome of Smilax china Linn. in mice. Indian J
Pharmacol 2011;43:27–30.
24. Vijayalakshmi A, Ravichandiran V, Malarkodi V, et al. Screening of
flavonoid “quercetin” from the rhizome of Smilax china Linn. for
antipsoriatic activity. Asian Pac J Trop Biomed. 2012;2:269–75.
25. Wang GZ, Xu SZ, Gan GP, Liu YW. Comparison of resveratrol content of
Smilax china from different habitats. Zhongguo Zhong Yao Za Zhi. 2006;
31:1054–5 (Chinese).
26. Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver
injury by reducing TNF-alpha production and T lymphocytes adhesion.
J Pharm Pharmacol. 2004;56:495–502.
27. Wang WX, Qian JY, Wang XJ, Jiang AP, Jia AQ. Anti-HIV-1 activities of
extracts and phenolics from Smilax china L. Pak J Pharm Sci. 2014;27:
147–51.
28. Wu LS, Wang XJ, Wang H, et al. Cytotoxic polyphenols against breast
tumor cell in Smilax china L. J Ethnopharmacol. 2010;130:460–4.
Smilax china L. 1671

29. Xu W, Liu J, Li C, et al. Kaempferol-7-O-beta-D-glucoside (KG) isolated

from Smilax china L. rhizome induces G2/M phase arrest and apoptosis on
HeLa cells in a p 53-independent manner. Cancer Lett. 2008;264:229–40.
30. Xu Y, Liang JY, Zou ZM. Studies on chemical constituents of rhizomes of
Smilax china. Zhongguo Zhong Yao Za Zhi. 2008;33:2497–9 (Chinese).
31. Zhong C, Hu D, Hou LB, et al. Phenolic compounds from the rhizomes of
Smilax china L. and their anti-inflammatory activity. Molecules. 2017;22:
pii:E515.
Solanum americanum Mill.
(Solanaceae)

(Syns.: S. nigrum L.; S. nigrum auct. non L.; S. caribaeum Dunal)

Abstract
A perennial herb or shrub, that has been recorded in history by both Pliny and
Dioscorides, is a native to Eurasia but now widely distributed. Dioscorides stated
that it may be eaten without danger and described it as very cooling whether
applied externally or used internally; and the fruits are extremely diuretic and
through diuresis excrete matter causing jaundice. It was chiefly used by the
Greeks as a local application to inflammed parts. In traditional systems of
medicine, it is used as hepatoprotective, diuretic, anti-inflammatory, antioxidant,
antipyretic and antitumor agent; also reported to be used for the treatment of skin
and mucosal ulcers, liver cirrhosis and edema. It is one of the best drugs for the
treatment of organ inflammation, especially liver and stomach inflammations,
where it is used both internally and as a poultice. Heated leaves are also applied
to painful and swollen testicles. In Ayurveda, berries are regarded tonic, diuretic,
and useful in anasarca and heart diseases. Leaves are consumed as vegetable in
many parts of the Indian subcontinent, and other places, as they are rich in
nutrients. It is also one of the suspected causative substances for the endemic
esophageal cancer in Transkei region of South Africa, where it is extensively
used as a wild vegetable. In Mexico, decoction of the plant is applied as fomen-
tation to sore eyes and various skin diseases, and for vaginal irrigation. In East
Africa, raw fruit is chewed and swallowed for treatment of stomach ulcers or for
general abdominal upsets leading to continued stomachache. In the Philippines,
fruit is reputed as a cure for diabetes, and the leaves applied as poultice have
sedative and healing properties, and an alcoholate made with leaves alleviate
neuralgic pain. The plant has been used for centuries in Chinese medicine for its
diuretic, antipyretic, and hepatoprotective effects, and for the treatment of
digestive system cancers; its root and seeds are also used as medicine. Leaves are
richer in polyphenols than stem and fruits, and contain highest concentration of
gentisic acid, luteolin, apigenin, kaempferol, and m-coumaric acid.

© Springer Nature Switzerland AG 2020 1673

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_173
1674 Solanum americanum Mill.

Keywords



Anabuddeeb Anabussalab Angur shifah Brède morelle

Inuhôzuki





Itüzümü Kakamachi Longkuei Makoh Nightshade

Vernaculars: Urd.: Anabussalab, Makoh; Hin.: Gurkamai, Kaag ajhi, Kali bhan-
bulan, Kamini, Mako, Makoi; San.: Dhavanksha-machi, Kakamachi, Kovida-raha,
Krishna-ko, Vidaraha; Ben.: Gurkamai, Kakamachi, Kovida-raha, Tulidun; Mal.:
Manatta-kali, Tudavalam; Mar.: Kala kanguna, Kamuni ghati; Tam.: Karuppu,
Manattakkali, Manithakkali, Milagu-takkali, Munna-takali-pullum; Tel.: Kachi,
Kamanchi-chettu, Kanchi-pundu; Ara.: Anabuddeeb, Anabussalab, Kharma,
Uyoob; Chi.: Longkuei, Yehaijiao, Yeh la-chiaw; Eng.: Black nightshade, Deadly
nightshade, Glossy nightshade, Nightshade; Fre.: Brède morelle, Herbe à calalou,
Morelle d’Amérique; Ind.: Kampai; Jap.: Inuhôzuki, Teriminoinuhozuki; Per.:
Angur shaghal, Angure rubah, Angur shifah, Rubah turbak, Sag-angur, Tajrizi; Por.:
Maria-pretinha (Br.); Spa.: Hierba mora, Metagallina; Tag.: Anti, Gamagamatisan,
Kamkamatisan, Konti, Kunti, Lubi-lubi; Tha.: Ma waeng nok, Ya tomtok; Tur.:
Itüzümü; Vie.: Hôt mít, Lù lù duc, Thu lù duc.
Description: A perennial herb or shrub, that has been recorded in history by both
Pliny and Dioscorides, is a native to Eurasia but now widely distributed. It is an
erect, branched, smooth or nearly smooth herb up to a meter high. The stems are
green and somewhat 3-angled; the leaves are ovate to oblong, 5–8 cm long and
pointed at both ends, with subentire or undulately toothed or lobed margins.
Flowers are umbellately disposed, 5–8 on each peduncle, nodding, and borne on
extra-axillary inflorescences 1–2.5 cm long. The calyx is green, with ovate-oblong
lobes. The corolla is white and about 8 mm in diameter. Fruit (berry) is dark-purple
or black, smooth, shining, rounded, and about 5 mm in diameter. Seeds are yellow
and minutely pitted.CXVII Solanum americanum (S. nigrum) berries may some-
times be confused with deadly nightshade, Atropa belladonna. Fruits (berries) of
S. nigrum grow in bunches, whereas the deadly nightshade berries grow individ-
ually (Figs. 1, 2 and 3).
Actions and Uses: Dioscorides stated that it may be eaten without danger
and described it as very cooling whether applied externally or used internally;
and the fruits are extremely diuretic and through diuresis excrete matter causing
jaundice.LXIX It was chiefly used by the Greeks as a local application to inflamed
parts.XL Avicenna in Canon of Medicine classified it as one of the drugs for the
treatment of abnormal uterine bleeding [32]. In traditional systems of medicine, it is
used as hepatoprotective, diuretic, anti-inflammatory, antioxidant, antipyretic and
antitumor agent [12, 28]; also reported to be used for the treatment of skin and
mucosal ulcers, liver cirrhosis and edema [23]. In Unani medicine, it (temperament,
cold 2° and dry 2°) is described as astringent, counterirritant, drying, softener,
anti-inflammatory and heat-soother. It is one of the best drugs for the treatment of
organ inflammation, especially liver and stomach inflammations, where it is used
both internally and as a poultice. For liver and stomach inflammation, the extracted
Solanum americanum Mill. 1675

Fig. 1 Solanum americanum, Foliage and Berries of Black Variety, David Eickhoff, Wiki-
mediaCommons; 2.0 Generic CC BY 2.0, https://commons.wikimedia.org/wiki/File:Solanum_
americanum_(4898754585).jpg; https://creativecommons.org/licenses/by/2.0/deed.en

Fig. 2 Solanum americanum, Flowers, David Eickhoff, WikimediaCommons; 2.0 Generic CC

BY 2.0, https://commons.wikimedia.org/wiki/File:Solanum_americanum_(4899345876).jpg; https://
creativecommons.org/licenses/by/2.0/deed.en

juice of leaves is heated, filtered (murawwaq) and then orally used.LXXVII The herb
is alterative, sedative, diaphoretic, diuretic, hydragogue and expectorant, and
locally anodyne. As alterative, the herb is given in skin diseases, such as psoriasis,
eczema, and in syphilis; as a diuretic in gout, rheumatism, dropsy, gonorrhea, renal
and vesical catarrh, coughs, splenic and hepatic enlargements.LXXXI,CV Leaves are
employed as a poultice over rheumatic and gouty joints, and as a remedy for skin
diseases. A fluid extract of the stem and leaves is recommended in dropsy, in heart
1676 Solanum americanum Mill.

Fig. 3 Solanum americanum, Ripe and Unripe Berries of Red Variety, Vishal Sharma, Wiki-
mediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/
File:Solanum_Nigrum_Berries.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

diseases, skin diseases, piles, inflammatory swellings, gonorrhea, and chronic

enlargement of liver and spleen. Heated leaves are applied to painful and swollen
testicles.CV In Adilabad district of Andhra Pradesh (India), tribals grind together
equal quantities of leaves with leaves of Ricinus communis (Amudamu) and
Boerhavia diffusa (Tellaku) and use orally in a dose of 10 g daily for seven-days to
treat jaundice [11]. In Ayurveda, berries are regarded tonic, diuretic, and useful in
anasarca and heart diseases; also used in fever, diarrhea, eye diseases, and
hydrophobia,LXXXIV and for the treatment of asthma [34]. Leaves are consumed as
vegetable in many parts of the Indian subcontinent [2], as wild vegetable in South
Africa [4], and other places, as they are rich in nutrients, containing high amounts
of crude protein, lipid, fiber, carbohydrate, electrolytes and minerals [20]. It is also
one of the suspected causative substances (Relative Risk 3.6) for the endemic
esophageal cancer in Transkei region of South Africa, where it is extensively used
as a wild vegetable [42, 43]. Since it contains protease inhibitors, and suppression
of proteases can lead to overexpression of growth factors in the esophagus,
resulting in a proliferative and oncogenic drive [44]. In traditional Iranian medicine,
it is known as Tajrizi and has been used for the treatment of inflammatory bowel
diseases [38]. In parts of Nigeria leaves are claimed useful in the treatment of
epilepsy in traditional medical practice [57]. Mature fruits are also used by tribals in
India as oral contraceptives [21].
Berries are considered diuretic and are used for eye diseases, fevers and
hydrophobia; juice of the plant is considered cathartic, diuretic, hydragogue, lax-
ative, alterative, emollient and is used for chronic enlargement of liver, in blood
spitting, piles and dysentery. Juice prepared in various manner is a remedy for
tumors and cancer. A poultice of the root is a remedy for scirrhous tumors of the
rectum.XXXVIII In Mexico, decoction of the plant is applied as fomentation to sore
Solanum americanum Mill. 1677

eyes and various skin diseases, and for vaginal irrigation.XCVI,CXXXI In East Africa,
raw fruit is chewed and swallowed for the treatment of stomach ulcers or for general
abdominal upsets leading to continued stomachache. Infusion of leaves and seeds is
rubbed onto the gums of children in cases of development of crooked teeth.
Pounded leaves are soaked in water, fermented and used for the treatment of boils,
ulcers and swollen glands.LXXXV The root bark is described as abortifacient [41]. In
the Philippines, fruit is reputed as a cure for diabetes, and the leaves applied as
poultice have sedative and healing properties, and an alcoholate made with leaves
alleviate neuralgic pain.CXVII The plant known as Longkui, has been used for
centuries in Chinese medicine for its diuretic, antipyretic [26], and hepatoprotective
effects [15], and for the treatment of digestive system cancers [15, 19]; its root and
seeds are also used as medicine. The plant has a bitter taste and cold property. It
possesses latent-heat-clearing, antipyretic, detoxicant, blood-stimulant, detumes-
cent, anti-inflammatory, diuretic, mucolytic and antipruritic activities, and is mainly
prescribed to treat furuncles, carbuncles, poisonous snake bites, dermatitis, eczema,
UTI, dysuria, chronic bronchitis, hypertension, and carcinoma.XVIII Boiled young
shoots are eaten, and are considered to be corrective, cooling and tonic to men
(increase virility), and women (regulating menstruation). Stalks, leaves and roots
are used in decoction for wounds and cancerous sores, and as diuretic and astrin-
gent.CXXXIV During summer time, the plant is heavily used to supplement bever-
ages to quench thirst on hot days in Taiwan [15]. According to Kirtikar and Basu
[31], Chinese also use leaves juice to alleviate pain of inflammation of kidneys
(nephritis) and bladder (cystitis), and in virulent gonorrhea.
Phytoconstituents: Leaves are richer in polyphenols than stem and fruits, and
contain highest concentration of gentisic acid, luteolin, apigenin, kaempferol, and m-
coumaric acid [15]. It contains glycoalkaloids solanine, solasonine, and solamargine;
the latter two are principle components and their amounts are 0.2 and 0.25%,
respectively. Glycoalkaloid content is highest in unripe fruit; it can reach up to 4.2%.
Solasodine is the aglycone of solasonine and solamargine; solanidine is the aglycone
of solanine. The herb also contains small amounts of atropine and saponins.XVIII
Leaves contain 39–45 calories, 85–88 g water, 3.2–5 g protein, 0.4–1 g fat, 6.4–
8.9 g total carbohydrate, 1.1–2.2 g fiber, 199–216 mg Ca, 54–88 mg P, 0.3–9.9 mg
Fe, 460–3,660 ug b-carotene equivalent, 0.12–0.18 mg thiamine, 0.05–0.24 mg
riboflavin, 1–1.3 mg niacin and 24–61 mg ascorbic acid per 100 g.XXXVIII Vita-
min C values of Indian variety range from 11–40 mg for leaves, of Pakistani variety
158–186 mg; stems 24–27 mg, fruits 47–59 mg/100 g.IV Fruits contain diosgenin,
tigonenin, solanine, solasodine, solasonine, solamargine, b-solamargine and
a–b-solansodamine, -(L-rhamnosyl-D-glucosyl)-solasoidine, solanigrine, gitogenin,
traces of saponins and 7–10% tannin.IV,XC Steroidal glycosides, b2-solamargine,
solamargine, degalactotigonin [14], steroidal saponins: nigrumnins I and II [16],
solanigrosides C–H, degalactotigonin [64], pregnane saponins, solanigroside A and
B [65]; nonsaponin compounds, 6-methoyhydroxycoumarin, syringaresinol-4-O-b-
D-glucopyranoside, pinoresinol-4-O-b-D-glucopyranoside, 3,4-dihydroxybenzoic acid,
1678 Solanum americanum Mill.

p-hydroxybenzoic acid, 3-methoxy-4-hydroxybenzoic acid, adenosine [56], disac-

charides [8], (+)-pinoresinol, (+)-syringaresinol, (+)-medioresinol, scopoletin, tetra-
cosanoic acid and b-sitosterol [63], and spirostanol glycoside, inunigroside A [35],
have been isolated from Solanum nigrum.
Pharmacology: Aqueous and chloroform extracts of leaves exhibited significant
antinociceptive, anti-inflammatory and antipyretic effects in rats [61, 62], and the
ethanol leaf extract demonstrated antihistamine and anti-inflammatory properties
[31]. Anti-inflammatory compounds are suggested to exist preferentially in non-
polar fraction, which rules out the possibility of diosgenin and a-solanine being the
likely candidates [23]. Petroleum ether extract antagonized histamine on isolated
guinea pig ileum, significantly inhibited milk allergen-increased leukocyte and
eosinophil counts and protected against mast cell degranulation. b-Sitosterol is
suggested to be the active constituent [34]. Feeding leaves along with glucose to
mice did not have any significant blood glucose-lowering effect [52]. However,
aqueous fruit extract returned to normal plasma glucose, LDL-C, VLDL-C, TC, and
TGs, and decreased alteration in vascular reactivity to vasoconstrictor agents in
diabetic rats [47, 48], and restored lipid profile to near normal and improved
antioxidant status of chronic ethanol-fed rats [7]. A glycoprotein lowered triton- or
corn oil-induced increase in plasma lipoprotein levels (TG, TC and LDL), reduced
HMG-CoA reductase activity, and improved antioxidant enzymes in mice [24].
Ethanol and aqueous fruit extracts also showed remarkable protection against CCl4-
hepatotoxicity in rats [28, 39], thioacetamide-induced liver fibrosis [12], and
ethanol-liver toxicity in mice [30]. Fruits in diet and their ethanol extract also
protect rats from cadmium chloride toxicity [3]. Aqueous extract alleviates CCl4-
and AAF-induced hepatic injury and early hepatocarcinogenesis, as well as the
AAF/NaNO2-induced lethal hepatoma in rats [13]; suppressed cervical carcinoma
growth via modulating immune response of tumor-bearing mice and tumor cell
cycle arrest in G0/G1 phase, as well as inducing apoptosis with little toxicity to the
animals [25]. Aqueous leaf extract exhibits tumor suppression and improves tumor
suppression efficiency of cisplatin, doxorubicin, and docetaxel in human ovarian
cancer cells [53], induces autophagic cell death, enhances docetaxel-induced
cytotoxicity of human endometrial carcinoma cells [50], and enhances cytotoxicity
of cisplatin, doxorubicin, docetaxel, and 5-FU in human colorectal carcinoma cells
[51], significantly inhibits melanoma cell migration and invasion [55], and
polyphenol-rich extract of ripe fruits decreased tumor weight and volume by 90% in
hepatocellular carcinoma-bearing mice [54]. Aqueous leaf extract also protects
against chemoradiotherapy- and MTX-induced oral mucositis in rats [36]. Methanol
fruit extract is cytotoxic to leukemic cell lines, Jurkat and human promyelocytic
leukemia cells [10]. Solanine, a steroid alkaloid, possesses antitumor activity [19].
Immature fruit extract was strongly cytotoxic to S. typhimurium [59], whereas
ethanol extract of ripe fruits strongly suppressed growth of MCF-7 human breast
cancer cells [49].
Ethanol fruit extract (i.p.) exhibited CNS-depressant activity, and significantly
prolonged pentobarbital-induced sleeping time [37], whereas aqueous leaf extract
Solanum americanum Mill. 1679

significantly protected against seizures in various animal models [57], and signif-
icantly modulated immobilization stress-induced changes in GSH, LPO, and free
radical scavenging enzymes activities of rat brain tissues [60]. Aqueous fruit extract
shows presence of ACh-like substance [9]. Aerial parts powder and its methanol
extract [6], and fruits extract significantly protected against various ulcerogenic
agents-induced gastric ulcers in rats [17], and a glycoprotein isolated from fruits
also protected against experimental colitis in mice [22]. Methanol fruit extract
demonstrated significant antimicrobial activity against both Gram-positive and
Gram-negative bacteria and against fungi, including S. aureus, S. typhi, E. coli,
K. pneumoniae, V. cholerae, A. niger, A. flavus and A. fumigatus [1], moderate
activity against MDR S. typhi [40], and aqueous leaf extract protected against
S. mansoni infection of mice [5]. Methanol and chloroform seed extracts in vitro
inhibited HCV at nontoxic concentrations [18].
Mechanism of Action: A glycoprotein isolated from fruits inhibited NO produc-
tion and free radical formation, suppressed activities of NF-jB and modulated
expression of iNOS and Cox-2 [38]. Ethanol extract of ripe fruits exerts cytotoxic
effect on HepG2 cells by inducing apoptosis [29, 45], and polyphenol-rich extract
of ripe fruits also selectively inhibited cellular proliferation and accelerated apop-
tosis in prostate cancer cells [33]. Inhibition of hepatocarcinogenesis is mediated
through overexpression of GST and antioxidant enzymes [13], by inducing G2/M
phase arrest and apoptosis [54]. Total alkaloids fraction induced apoptosis of HeLa
cells, with much lower toxicity to human normal lymphocytes [27]. Inhibition of
H(+)K(+)ATPase and decrease of gastrin secretion are credited for its gastric
antiulcer activity [17].
Human A/Es, Allergy and Toxicity: Fruits (berries) have caused toxicity in
humans but the toxicity varies with different varieties, and as the berries mature,
their toxicity potential declines, and the ripe berries contain no more or perhaps
only nontoxic amount of solanine. That’s why ripe berries are extensively eaten,
especially by children, and used to make jams and puddings.CXXXIII However,
attractive berries have been implicated in poisoning of children due to their alkaloid
content. Abdominal pain with constipation or diarrhea and general gastrointestinal
irritation may occur together with weakness, trembling, drowsiness and paralysis,
depending on the amount eaten.CXXXV Symptoms of poisoning may also include
vomiting accompanied by headache and colic, followed by depression.CL Solanine
in doses of 200–400 mg induces gastroenterosis, tachycardia, dyspnea, vertigo,
sleepiness, lethargy, twitching of the extremities and cramps.XC
Animal Toxicity: Toxicity of decoction of whole plant is rather low. No deaths
occurred after intragastric dose of 100 g/kg to mice [58]. It has been reported that
carrots, added to decoction or in the diet, could reduce toxic effects of the herb [46].
Commentary: This herb, both the leaves and berries, are regarded extremely useful
for liver disorders like jaundice, in traditional medicines and extensively used for
this purpose. However, there are no systematic RCTs to objectively validate those
claims.
1680 Solanum americanum Mill.

References
1. Abbas K, Niaz U, Hussain T, et al. Antimicrobial activity of fruits of
Solanum nigrum and Solanum xanthocarpum. Acta Pol Pharm. 2014;71:
415–21.
2. Abbasi AM, Khan MA, Shah MH, et al. Ethnobotanical appraisal and
cultural values of medicinally important wild edible vegetables of Lesser
Himalayas-Pakistan. J Ethnobiol Ethnomed. 2013;9:66.
3. Abdel-Rahim EA, Abdel-Mobdy YE, Ali RF, Mahmoud HA. Hepatopro-
tective effects of Solanum nigrum Linn. fruits against cadmium chloride
toxicity in albino rats. Biol Trace Elem Res. 2014;160:400–8.
4. Afolayan AJ, Jimoh FO. Nutritional quality of some wild leafy vegetables in
South Africa. Int J Food Sci Nutr. 2009;60:424–31.
5. Ahmed AH, Rifaat MM. Effects of Solanum nigrum leaves water extract on
the penetration and infectivity of Schistosoma mansoni cercariae. J Egypt
Soc Parasitol. 2005;35:33–40.
6. Akhtar MS, Munir M. Evaluation of the gastric antiulcerogenic effects of
Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats.
J Ethnopharmacol. 1989;27:163–76.
7. Arulmozhi V, Krishnaveni M, Karthishwaran K, et al. Antioxidant and
antihyperlipidemic effect of Solanum nigrum fruit extract on the experi-
mental model against chronic ethanol toxicity. Pharmacogn Mag. 2010;6:
42–50.
8. Chen R, Feng L, Li HD, et al. Two novel oligosaccharides from Solanum
nigrum. Carbohydr Res. 2009;344:1775–7.
9. de Melo AC, Perec CJ, Rubio MC. Acetylcholine-like activity in the fruit of
the black nightshade (Solanaceae). Acta Physiol Lat Am. 1978;28:19–26.
10. Gabrani R, Jain R, Sharma A, et al. Antiproliferative effect of Solanum
nigrum on human leukemic cell lines. Indian J Pharm Sci. 2012;74:451–3.
11. Hemadri K, Rao SS. Jaundice: tribal medicine. Ancient Sci Life. 1984;3:
209–12.
12. Hsieh CC, Fang HL, Lina WC. Inhibitory effect of Solanum nigrum on
thioacetamide-induced liver fibrosis in mice. J Ethnopharmacol. 2008;119:
117–21.
13. Hsu JD, Kao SH, Tu CC, et al. Solanum nigrum L. extract inhibits
2-acetylaminofluorene-induced hepatocarcinogenesis through overexpres-
sion of glutathione S-transferase and antioxidant enzymes. J Agric Food
Chem. 2009;57:8628–34.
14. Hu K, Kobayashi H, Dong A, et al. Antineoplastic agents. III: steroidal
glycosides from Solanum nigrum. Planta Med. 1999;65:35–8.
15. Huang HC, Syu KY, Lin JK. Chemical composition of Solanum nigrum
Linn. extract and induction of autophagy by leaf water extract and its major
flavonoids in AU565 breast cancer cells. J Agric Food Chem. 2010;58:
8699–708.
Solanum americanum Mill. 1681

16. Ikeda T, Tsumagari H, Nohara T. Steroidal oligoglycosides from Solanum

nigrum. Chem Pharm Bull (Tokyo). 2000;48:1062–4.
17. Jainu M, Devi CS. Antiulcerogenic and ulcer healing effects of Solanum
nigrum (L.) on experimental ulcer models: possible mechanism for the
inhibition of acid formation. J Ethnopharmacol. 2006;104:156–63.
18. Javed T, Ashfaq UA, Riaz S, et al. In-vitro antiviral activity of Solanum
nigrum against Hepatitis C Virus. Virol J. 2011;8:26.
19. Ji YB, Gao SY, Ji CF, Zou X. Induction of apoptosis in HepG2 cells by
solanine and Bcl-2 protein. J Ethnopharmacol. 2008;115:194–202.
20. Jimoh FO, Adedapo AA, Afolayan AJ. Comparison of the nutritional value
and biological activities of the acetone, methanol and water extracts of the
leaves of Solanum nigrum and Leonotis leonorus. Food Chem Toxicol.
2010;48:964–71.
21. Jisha S, Sreeja S, Manjula S. In vitro & in vivo estrogenic activity of
glycoside fractions of Solanum nigrum fruit. Indian J Med Res. 2011;134:
369–74.
22. Joo HY, Lim K, Lim KT. Phytoglycoprotein (150 kDa) isolated from
Solanum nigrum Linne has a preventive effect on dextran sodium sulfate-
induced colitis in A/J mouse. J Appl Toxicol. 2009;29:207–13.
23. Kang H, Jeong HD, Choi HY. The chloroform fraction of Solanum
nigrum suppresses nitric oxide and tumor necrosis factor-a in LPS-
stimulated mouse peritoneal macrophages through inhibition of p38, JNK
and ERK1/2. Am J Chin Med. 2011;39:1261–73.
24. Lee SJ, Ko JH, Lim K, Lim KT. 150 kDa glycoprotein isolated from
Solanum nigrum Linne enhances activities of detoxicant enzymes and
lowers plasmic cholesterol in mouse. Pharmacol Res. 2005;51:399–408.
25. Li J, Li Q, Feng T, Li K. Aqueous extract of Solanum nigrum inhibit growth
of cervical carcinoma (U14) via modulating immune response of tumor
bearing mice and inducing apoptosis of tumor cells. Fitoterapia. 2008;79:
548–56.
26. Li J, Li Q, Feng T, et al. Antitumor activity of crude polysaccharides
isolated from Solanum nigrum Linne on U14 cervical carcinoma bearing
mice. Phytother Res. 2007;21:832–40.
27. Li J, Li QW, Gao DW, et al. Antitumor effects of total alkaloids isolated
from Solanum nigrum in vitro and in vivo. Pharmazie. 2008;63:534–8.
28. Lin HM, Tseng HC, Wang CJ, et al. Hepatoprotective effects of Solanum
nigrum Linn. extract against CCl(4)-induced oxidative damage in rats.
Chem Biol Interact. 2008;171:283–93.
29. Lin HM, Tseng HC, Wang CJ, et al. Induction of autophagy and apoptosis
by the extract of Solanum nigrum Linn. in HepG2 cells. J Agric Food Chem.
2007;55:3620–8.
30. Liu FP, Ma X, Li MM, et al. Hepatoprotective effects of Solanum
nigrum against ethanol-induced injury in primary hepatocytes and mice with
analysis of glutathione S-transferase A1. J Chin Med Assoc. 2016;79:65–71.
1682 Solanum americanum Mill.

31. Lomash V, Parihar SK, Jain NK, Katiyar AK. Effect of Solanum nigrum and
Ricinus communis extracts on histamine and carrageenan-induced inflam-
mation in the chicken skin. Cell Mol Biol (Noisy-le-grand). 2010;56(Suppl):
OL1239–51.
32. Mobli M, Qaraaty M, Amin G, et al. Scientific evaluation of medicinal
plants used for the treatment of abnormal uterine bleeding by Avicenna.
Arch Gynecol Obstet. 2015;292:21–35.
33. Nawab A, Thakur VS, Yunus M, et al. Selective cell cycle arrest and
induction of apoptosis in human prostate cancer cells by a polyphenol-rich
extract of Solanum nigrum. Int J Mol Med. 2012;29:277–84.
34. Nirmal SA, Patel AP, Bhawar SB, Pattan SR. Antihistaminic and antiallergic
actions of extracts of Solanum nigrum berries: possible role in the treatment
of asthma. J Ethnopharmacol. 2012;142:91–7.
35. Ohno M, Murakami K, El-Aasr M, et al. New spirostanol glycosides from
Solanum nigrum and S. jasminoides. J Nat Med. 2012;66:658–63.
36. Patel A, Biswas S, Shoja MH, Ramalingayya GV, Nandakumar K.
Protective effects of aqueous extract of Solanum nigrum Linn. leaves in
rat models of oral mucositis. Sci World J. 2014;2014:345939.
37. Perez RM, Perez JA, Garcia LM, Sossa H. Neuropharmacological activity
of Solanum nigrum fruit. J Ethnopharmacol. 1998;62:43–8.
38. Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of
traditional Iranian medicine for inflammatory bowel disease. World J
Gastroenterol. 2010;16:4504–14.
39. Raju K, Anbuganapathi G, Gokulakrishnan V, et al. Effect of dried fruits of
Solanum nigrum Linn. against CCl4-induced hepatic damage in rats. Biol
Pharm Bull. 2003;26:1618–9.
40. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for
their antienteric potential against multidrug resistant Salmonella typhi.
Phytother Res. 2004;18:670–3.
41. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
42. Sammon AM. A case-control study of diet and social factors in cancer of the
esophagus in Transkei. Cancer. 1992;69:860–5.
43. Sammon AM. Carcinogens and endemic squamous cancer of the oesophagus
in Transkei, South Africa. Environmental initiation is the dominant factor;
tobacco or other carcinogens of low potency or concentration are sufficient
for carcinogenesis in the predisposed mucosa. Med Hypotheses. 2007;69:
125–31.
44. Sammon AM. Protease inhibitors and carcinoma of the esophagus. Cancer.
1998;83:405–8.
45. Shokrzadeh M, Azadbakht M, Ahangar N, et al. Cytotoxicity of hydroalco-
holic extracts of Cucurbitapepo and Solanum nigrum on HepG2 and CT26
cancer cell lines. Pharmacogn Mag. 2010;6:176–9.
46. Smerha J. Chem Abstr. 1949;43:8538c.
Solanum americanum Mill. 1683

47. Sohrabipour S, Kharazmi F, Soltani N, Kamalinejad M. Biphasic effect

of Solanum nigrum fruit aqueous extract on vascular mesenteric beds in
nondiabetic and streptozotocin-induced diabetic rats. Pharmacognosy Res.
2014;6:148–52.
48. Sohrabipour S, Kharazmi F, Soltani N, Kamalinejad M. Effect of the
administration of Solanum nigrum fruit on blood glucose, lipid profiles, and
sensitivity of the vascular mesenteric bed to phenylephrine in streptozotocin-
induced diabetic rats. Med Sci Monit Basic Res. 2013;19:133–40.
49. Son YO, Kim J, Lim JC, et al. Ripe fruit of Solanum nigrum L. inhibits cell
growth and induces apoptosis in MCF-7 cells. Food Chem Toxicol. 2003;
41:1421–8.
50. Tai CJ, Wang CK, Chang YJ, et al. Aqueous extract of Solanum nigrum leaf
activates autophagic cell death and enhances docetaxel-induced cytotoxicity
in human endometrial carcinoma cells. Evid Based Complement Alternat
Med. 2012;2012:859185.
51. Tai CJ, Wang CK, Tai CJ, et al. Aqueous extract of Solanum nigrum leaves
induces autophagy and enhances cytotoxicity of cisplatin, doxorubicin,
docetaxel, and 5-fluorouracil in human colorectal carcinoma cells. Evid
Based Complement Alternat Med. 2013;2013:514719.
52. Villaseñor IM, Lamadrid MR. Comparative antihyperglycemic potentials of
medicinal plants. J Ethnopharmacol. 2006;104:129–31.
53. Wang CW, Chen CL, Wang CK, et al. Cisplatin-, doxorubicin-, and
docetaxel-induced cell death promoted by the aqueous extract of Solanum
nigrumin human ovarian carcinoma cells. Integr Cancer Ther. 2015;14:
546–55.
54. Wang HC, Chung PJ, Wu CH, et al. Solanum nigrum L. polyphenolic
extract inhibits hepatocarcinoma cell growth by inducing G2/M phase arrest
and apoptosis. J Sci Food Agric. 2011;91:178–85.
55. Wang HC, Wu DH, Chang YC, et al. Solanum nigrum Linn. water extract
inhibits metastasis in mouse melanoma cells in vitro and in vivo. J Agric
Food Chem. 2010;58:11913–23.
56. Wang LY, Wang NL, Yao XS. Nonsaponins from Solanum nigrum L.
Zhong Yao Cai. 2007;30:792–4 (Chinese).
57. Wannang NN, Anuka JA, Kwanashie HO, et al. Antiseizure activity of the
aqueous leaf extract of Solanum nigrum Linn. (solanaceae) in experimental
animals. Afr Health Sci. 2008;8:74–9.
58. Xu WF, et al. Fujian J Trad Med. 1963;8:15 (cited by Chang and But,
1986).XVIII
59. Yen GC, Chen HY, Peng HH. Evaluation of the cytotoxicity, mutagenicity
and antimutagenicity of emerging edible plants. Food Chem Toxicol. 2001;
39:1045–53.
60. Zaidi SK, Hoda MN, Tabrez S, et al. Protective effect of Solanum nigrum
leaves extract on immobilization stress induced changes in rat’s brain. Evid
Based Complement Alternat Med. 2014;2014:912450.
1684 Solanum americanum Mill.

61. Zakaria ZA, Gopalan HK, Zainal H, et al. Antinociceptive, anti-inflammatory

and antipyretic effects of Solanum nigrum chloroform extract in animal models.
Yakugaku Zasshi. 2006;126:1171–8.
62. Zakaria ZA, Sulaiman MR, Morsid NA, et al. Antinociceptive, anti-inflam-
matory and antipyretic effects of Solanum nigrum aqueous extract in animal
models. Methods Find Exp Clin Pharmacol. 2009;31:81–8.
63. Zhao Y, Liu F, Lou HX. Studies on the chemical constituents of Solanum
nigrum. Zhong Yao Cai. 2010;33:555–6 (Chinese).
64. Zhou X, He X, Wang G, et al. Steroidal saponins from Solanum nigrum.
J Nat Prod. 2006;69:1158–63.
65. Zhou XL, He XJ, Zhou GX, et al. Pregnane glycosides from Solanum
nigrum. J Asian Nat Prod Res. 2007;9:517–23.
Sterculia urens Roxb.
(Malvaceae)

(Syns.: Cavallium urens Schott & Endl.; Clompanus urens Kuntze; Kavalama urens
Rafin)

Abstract
A small to medium-sized deciduous tree, native to India and Malaysia. Gum is
obtained from damaged bark, or commercially by cutting or peeling back the
bark, or by making deep gashes at the base of the trunk. Unani physicians regard
it mugharri and laxative; it soothes irritation and moderates heat and especially
useful for nosebleed, as emolient, mucolytic, sedative and styptic; and used in the
treatment of hemoptysis, cough, throat irritation, intestinal and urinary tract
ulcers, hypersensitivity and phthisis. Commercially the gum is used as a thickener
in cosmetics and medications, and added as a binder, emulsifier and stabiliser in
the preparation of beverages and foods. Dietary gum karaya is neither digested
nor degraded by enteric bacteria and is not absorbed to any significant extent
in man. Gum acts as a laxative as it swells after absorbing water, and the increase
in bulk in the intestine stimulates gut to expel waste material. Sterculia had
beneficial effects on constipation and reduced transit times, and relieved
symptoms of diverticular disease. Addition of 15 g of sterculia bulk to the diet
of patients with ileostomy increased the viscosity of stomal output by roughly
100% in 9 out of 12 patients, thus facilitating the management of stoma. Gum
karaya is accepted as Generally Recognized as Safe (GRAS) in the USA since
1961, and as a food additive by the EEC since 1974.

Keywords





Bali Balika Gulu Bassora Tragacanth Indian tragacanth
Karaya gamu





Karaya-gummibaum Kateera Pandrúk Valley putali

Vernaculars: Urd.: Kateera; Hin.: Bali, Gulu, Karai, Katira, Kulu, Kur katila;
San.: Balika; Ben.: Buli; Mar.: Bhutia, Kavali, Kundúl, Pandrúk; Tam.: Valley
putali; Tel.: Kalvi, Thabsú; Eng.: Bassora tragacanth, Ghost tree, Gum karaya,
Indian tragacanth, Kateera gum; Ger.: Karaya-gummibaum; Jap.: Karaya gamu.

© Springer Nature Switzerland AG 2020 1685

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_174
1686 Sterculia urens Roxb.

Description: A small to medium-sized deciduous tree with horizontally-spreading

branches and pale-colored trunk, growing to a maximum height of about 15 m; native
to India and Malaysia. Leaves are alternate, simple, hairy beneath and have three to
five palmate lobes, and clustered at the tips of the twigs. Bark is smooth, fibrous and
thick, greenish-grey, with surface layer peeling off in large flakes. Gum is obtained
from damaged bark, or commercially by cutting or peeling back the bark, or by
making deep gashes at the base of the trunk with an axe. It is a soft solid mass, soluble
in cold water, forming a milky solution.LXXXI However, KabeeruddinLXXVII says that
it swells in water but is not soluble like gum Arabica. Dymock et al.XL described
Katira under Astragalus heratensis and Katira-e-Hindi under Cochlospermum
gossypium (Pili-kapas). They also mentioned that in Bombay, gum of Sterculia
urens, called ‘Karai gond’ by the Guzurathi (Gujarati) shopkeepers is used as country
Tragacanth, and Muslim druggists sell it as katira. The urens in the name refers to the
stinging hairs that are present on its flowers (Figs. 1, 2 and 3).

Fig. 1 Sterculia urens, Tree, Pushkar04, WikimediaCommons; ShareAlike 4.0 International CC

BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Sterculia_urens_raigad_maharashtra_2.jpg;
https://creativecommons.org/licenses/by-sa/4.0/deed.en

Fig. 2 Sterculia urens, Young Fruits, Harikrishnan S., WikimediaCommons; ShareAlike 4.0
International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Sterculia_urens_fruits_
Bengaluru.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
Sterculia urens Roxb. 1687

Fig. 3 Sterculia urens, Gum, Prof. Akbar, Original

Actions and Uses: Unani physicians regard it (temperament, cold 1° and dry 1°)
mugharri and laxative; it soothes irritation and moderates heat and especially useful
for nosebleed,LXXVII emolient, mucolytic, sedative and styptic; and used in the
treatment of hemoptysis, cough, throat irritation, intestinal and urinary tract ulcers,
hypersensitivity and phthisis.1 Commercially the gum is used as a thickener in
cosmetics and medications, and added as a binder, emulsifier and stabiliser in the
preparation of beverages and foods.
Phytoconstituents: Gum karaya (10 g) contains 20 µg rhamnose [2].
Pharmacology: Dietary gum karaya is neither digested nor degraded by enteric
bacteria and is not absorbed to any significant extent in man [2].
Clinical Studies: Sterculia had beneficial effects on constipation and reduced
transit times, and relieved symptoms of diverticular disease [6]. Addition of 15 g of
sterculia bulk to the diet of patients with ileostomy increased the viscosity of stomal
output by roughly 100% in 9 out of 12 patients, thus facilitating the management of
stoma [4]. However, ingestion of 10.5 g gum karaya daily for 21-days by 5 male
volunteers did not have significant effects on intestinal transit time, fecal wet,
concentrations of fecal fat, bile acids and neutral sterols, glucose tolerance, serum
cholesterol, HDL-C, TGs and phospholipids, and no metabolic action of any
consequence [5]. It has also been used in combination with kaolin, meprobamate
and magnesium salts in IBS [3].
Mechanism of Action: Gum acts as a laxative as it swells after absorbing water,
and the increase in bulk in the intestine stimulates gut to expel waste material.

1
Tayyab M: Personal Communication.
1688 Sterculia urens Roxb.

Human A/Es, Allergy and Toxicity: Gum karaya is accepted as Generally Recog-
nized as Safe (GRAS) in the USA since 1961, and as a food additive by the EEC since
1974 [1].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Clinical studies reported are limited in number, and have not been
reproduced.

References
1. Anderson DM. Evidence for the safety of gum karaya (Sterculia spp.) as a
food additive. Food Addit Contam. 1989;6:189–99.
2. Anderson AW, Brydon WJ, Eastwood MA, McDougall FJ, Anderson DM.
The absence of rhamnose in human urine following the ingestion of gum
karaya (Sterculia). Food Addit Contam. 1985;2:33–6.
3. Capron JP, Zeitoun P, Julien D. A multicenter controlled trial of a combi-
nation of kaolin, sterculia gum, meprobamate, and magnesium salts, in the
irritable bowel syndrome (author’s transl). Gastroenterol Clin Biol. 1981;5:
67–72 (French).
4. Dalhamn T, Graf W, Nilsson LH. The effect of sterculia bulk on the
viscosity of stomal output from twelve patients with ileostomy. Scand J
Gastroenterol. 1978;13:485–8.
5. Eastwood MA, Brydon WG, Anderson DM. The effects of dietary gum
karaya (Sterculia) in man. Toxicol Lett. 1983;17:159–66.
6. Srivastava GS, Smith AN, Painter NS. Sterculia bulk-forming agent with
smooth-muscle relaxant versus bran in diverticular disease. Br Med J. 1976;
1:315–8.
Strychnos nux-vomica L.
(Loganiaceae)

(Syn.: S. spireana Dop.)

Abstract
It is a tall deciduous tree, native to India, Sri Lanka, Myanmar, Thailand, and
southern Vietnam. As medicine, seeds are considered by Unani physicians as
nervine and cardiac tonic, stomachic, expectorant, aphrodisiac, blood purifier,
anti-inflammatory, urinary bladder tonic and laxative. They are mainly used for
phlegmatic nervous diseases, such as paralysis, facial palsy, arthritis, dyspnea,
pleurisy and tuberculosis. The bark is also used as tonic and antipyretic. In small
doses, it stimulates stomach and intestines, increases gastric, pancreatic,
intestinal and biliary secretions. Therapeutic uses include paralytic and neuralgic
afflictions, atonic diarrhea, chronic dysentery, prolapse of rectum, incontinence
of urine, nocturnal emissions, debility or inactivity of spinal nerve system. Other
uses include intermittent fevers, epilepsy, diabetes, anemia, and chlorosis. In
Ayurveda, seeds are extensively advocated for nervous debility, paralysis, and
weakness of limbs, sexual weakness, dyspepsia, and dysentery and in
rheumatism. Dried seeds extract has been used as a circulatory and respiratory
stimulant but effective doses are nearly equivalent to toxic doses. In Chinese
traditional medicine, it is known as Maqianzi, which are seeds of three Strychnos
species (Strychnos nux-vomica, S. pierrana, S. wallichiana), with bitter taste and
cold property and is highly toxic. It is considered as channel-deobstruent,
antirheumatic, detumescent, analgesic, and fortifies muscles, tendons and bones,
and is indicated in rheumatism, paralysis or flaccidity of limbs or body, sequelae
of poliomyelitis, rheumatoid arthritis, injuries due to falls, fractures, contusions,
strains, and in schizophrenia. Seeds contain alkaloids (major poisonous alkaloids
being strychnine and brucine); other constituents include minor alkaloids,
glycoside, chlorogenic acid mannosan, and galactan, strynuxlines A and B, and
iridoid glucosides. S. nux vomica seeds must be purified before their use in
Unani and Ayurvedic medicines, and TCM. The purpose of purification process
is to reduce its toxicity by reducing contents of strychnine and brucine. Low
doses of seed ethanol extract effectively neutralized Daboia russelii venom-
induced lethality, hemorrhage, defibrinogenating and PLA2 enzyme activities
© Springer Nature Switzerland AG 2020 1689
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_175
1690 Strychnos nux-vomica L.

and Naja kaouthia venom-induced lethality, cardiotoxicity, neurotoxicity, and

PLA2 enzyme activity in animals. Aqueous and 50% ethanol seed extracts also
demonstrated significant antidiabetic activity in diabetic rats.

Keywords





Azaraqi Braeknoed Brechnuss Izaraqi Khaniq al-kalb
Kuchla




Ma qian zi Nux-vomica Vishamushti Vomiquier

Vernaculars: Urd.: Azaraqi, Izaraqi, Kuchla; Hin.: Jahar, Karerua, Kuchla; San.:
Kulaka, Kunch, Kupilu, Kurachilla, Vishamushti, Vishatin duka; Ben.: Kachila,
Kuchila, Thalkesur; Guj.: Kuchla; Mal.: Kanjera, Kanjiram, Kannirakkuru; Mar.:
Kajra-jher-katchura, Kara, Karo; Tam.: Eddikunchera, Etti, Kanchurai, Yettie,
Yettie-kottai; Tel.: Kushti, Musadi, Mushidi, Mushte-vittulu; Ara.: Azaraqi, Hab-
bul gharaab, Jouz-el-mathil, Khaniq al-kalb; Bur.: Khaboung; Chi.: 马钱子, Ma
qian zi; Dan.: Braeknoed; Dut.: Braaknoot, Kraanoog; Eng.: Nux-vomica, Poison
nut, Quaker button, Strychnine tree; Fre.: Arbre à noix vomique, Vomiquier; Ger.:
Brechnuss, Gewöhnlicher brechnußbaum, Strychninbaum; Ita.: Albero del noce
vomica, Noce vomica, Stricnina; Jap.: Machin; Per.: Fulas mahi; Por.: Noz-
vãmica; Spa.: Árbol de la nuez vomica; Tag.: Strychnine plant; Vie.: Cãy mã tiền,
Mã tiền.
Description: Native to India, Sri Lanka, Myanmar, Thailand, and southern Vietnam,
it is a tall deciduous tree, up to 12 m high. Leaves are leathery, smooth, opposite,
entire, shiny, broadly elliptic or ovate, 7.5–15 cm long and 6–8 cm wide. Flowers are
greenish-white, numerous, small, and borne on small, terminal, hairy cymes,
2.5–5 cm in diameter. Fruit is a globular berry 4 cm in diameter containing about 15
seeds embedded in a white pulp; seeds are flat, disc-shaped, 10–30 mm in diameter,
lenticular to oblong, smooth, shiny, gray to yellowish-gray or green in color, odorless,
having a strong bitter taste, and are used medicinally (Figs. 1, 2 and 3).LXXIX,CXVII
Actions and Uses: As medicine, seeds (temperament, hot 3° and dry 3°) are con-
sidered by Unani physicians as nervine and cardiac tonic, stomachic, expectorant,
aphrodisiac, blood purifier, anti-inflammatory, urinary bladder tonic and laxative.
They are mainly used for phlegmatic nervous diseases, such as paralysis, facial palsy,
arthritis, dyspnea, pleurisy and tuberculosis.LXXVII The bark is also used as tonic and
antipyretic.CV In small doses, it stimulates stomach and intestines, increases gastric,
pancreatic, intestinal and biliary secretions.LXXXI Therapeutic uses include paralytic
and neuralgic afflictions, atonic diarrhea, chronic dysentery, prolapse of rectum,
incontinence of urine, nocturnal emissions, debility or inactivity of spinal nerve
system. Other uses include intermittent fevers, epilepsy, diabetes, anemia, and
chlorosis.VII In Ayurveda, seeds are extensively advocated for nervous debility,
paralysis, and weakness of limbs, sexual weakness, dyspepsia, and dysentery and in
rheumatism [25]. In rural areas of southern parts of Tamil Nadu state of India, seeds
are used to treat snakebites [30]. KeysLXXIX also mentioned uses of seeds as
Strychnos nux-vomica L. 1691

Fig. 1 Strychnos nux-vomica, Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,

WikimediaCommons, https://commons.wikimedia.org/wiki/File:Strychnos_nux-vomica_-_K%C3%
B6hler%E2%80%93s_Medizinal-Pflanzen-266.jpg

Fig. 2 Strychnos nux-vomica, Foliage, J.M. Garg, WikimediaCommons; ShareAlike 4.0 Inter-
national CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Strychnos_nux-vomica_in_
Kinnarsani_WS,_AP_W_IMG_6021.jpg; https://creativecommons.org/licenses/by-sa/4.0/

stomachic, nerve tonic and spinal stimulant, and in laryngitis and laryngoparalysis.
Dried seeds extract has been used as a circulatory and respiratory stimulant but
effective doses are nearly equivalent to toxic doses.XXIV,CXI,CXVIII,CXXXII,CXXXXI The
seeds [23] and fruit [29] are also reported as emmenagogue. In Chinese traditional
1692 Strychnos nux-vomica L.

Fig. 3 Strychnos nux-vomica, Seeds, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Strychnos_nux-vomica_001.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

medicine, it is known as Maqianzi, which are seeds of three Strychnos species

(Strychnos nux-vomica, S. pierrana, S. wallichiana), with bitter taste and cold
property and is highly toxic. It is considered as channel-deobstruent, antirheumatic,
detumescent, analgesic, and fortifies muscles, tendons and bones, and is indicated in
rheumatism, paralysis or flaccidity of limbs or body, sequelae of poliomyelitis,
rheumatoid arthritis, injuries due to falls, fractures, contusions, strains, and in
schizophrenia.XVIII It has also been used in the treatment of cancer, for improving
blood circulation, and reducing swellings [12]. Nux vomica preparations are also
extensively used in homeopathic medicine [4, 18].
Purification: S. nux vomica seeds (azaraqi) must be purified (mudabbar) before
their use in Unani and Ayurvedic medicines, and TCM. The purpose of purification
process is to reduce its toxicity by reducing contents of strychnine and brucine, the
two main poisonous alkaloids [2]. The method used in Unani is to soak seeds in
water for 7-days, changing water daily, then washed and the outer coat peeled off.
The embryo part is then washed, dried, and tied in a clean cloth bag which is hung
in a vessel (without touching the bottom) containing 1 L of milk. The milk is then
boiled until it completely evaporates, the azaraqi is now removed from the bag and
washed thoroughly with water to obtain azaraqi mudabbar. Strychnine and brucine
contents were reduced from 0.175 and 0.16 to 0.051 and 0.045%, respectively after
this process [3]. In Ayurveda, purification is performed using different media, such
as cow’s urine, cow’s milk, cow’s ghee, or Kanji (sour gruel); castor oil, ginger
juice, are also used in the purification process [24]. Heating or frying in butter or oil
is also used as the purification process in TCM; the alkaloid composition (strych-
nine and brucine) of heat-treated seeds also declines significantly, but with an
increase in the amounts of isostrychnine, isobrucine, strychnine N-oxide and bru-
cine N-oxide [8]. The contents of strychnine and brucine are about the same in
Strychnos nux-vomica L. 1693

decoction but the contents of vomicine, strychnine N-oxide and brucine N-oxide are
increased, and the contents are greater under scalding with hot sand than
deep-frying with sesame oil [9]. Seeds processed in milk, compared to processing
with aloe and ginger juices, or frying in cow ghee, contain the lowest strychnine
content, exhibit a marked inhibition of PTZ-induced convulsions and maximal
potentiation of hypnosis, and are the safest based upon LD50 in mice [21]. Pro-
cessing of seeds with Ephedra sinica is also reported to reduce toxicity and promote
curative effect [13].
Phytoconstituents: Phytoconstituents isolated from seeds are alkaloids; major
alkaloids being strychnine (1.23%) and brucine (dimethoxystrychnine) (1.55%);CLI
other constituents, including minor alkaloids include struxine, a- and b-colubrine,
pseudostrychnine, strychnine N-oxide, protostrychnine, n-oxystrychnine, brucine
N-oxide, novacine, icajine, vomicine, isostrychnine, isobrucine, isobrucine N-oxide,
and isostrychnine N-oxide [5, 35, 36], the glycoside longanin,CXI chlorogenic acid
mannosan, and galactan,CXXXXI strynuxlines A and B [17], iridoid glucosides:
loganic acid, 7-O-acetylloganic acid, 6ʹ-O-acetylloganic acid, 4ʹ-O-acetylloganic acid
and 3ʹ-O-acetylloganic acid [38]. Three bisindolomonoterpenic alkaloids that exhibit
in vitro antiplasmodial activity against chloroquine-sensitive and resistant strains,
together with strychnochrysine, from the stem bark [20], strychnochrysine from roots
[6], and five phenolic compounds, kaempferol 7-glucoside, 7-hydroxycoumarin,
quercetin-3-rhamnoside, kaempferol 3-rutinoside, and rutin from leaves [15] have
been isolated. Dried ripe seeds (Maqianzi) contain 1–1.4% each of strychnine and
brucine [10].
Pharmacology: Both raw and kanji-purified powdered seeds demonstrated highly
significant anti-inflammatory activity against formaldehyde-induced paw edema, but
not against carrageenan-induced edema in rats [24]. Alkaloid fraction of seeds after
treatment with licorice-, oil-, vinegar and sand-processing exhibited significant
antinociceptive effects in mice [7]. Total alkaloid fraction devoid of most of its
strychnine content dissolved in hydrogel and after transdermal administration
showed significant analgesic activity in the chemical-, thermal- and physical-induced
nociception models, and significant anti-inflammatory activity against xylene-
induced ear edema, indicating presence of both central and peripherally mediated
activities [12]. Methanol seed extract in vitro inhibited XO more than 50%, but
without a significant hypouricemic activity in hyperuricemic mice [34].
Low doses of whole seed ethanol extract effectively neutralized Daboia russelii
venom-induced lethality, hemorrhage, defibrinogenating and PLA2 enzyme activ-
ities and Naja kaouthia venom-induced lethality, cardiotoxicity, neurotoxicity, and
PLA2 enzyme activity in animals [11]. Aqueous and 50% ethanol seed extracts also
demonstrated significant antidiabetic activity in alloxan-diabetic rats [5]. Methanol
extract of root bark was more effective than aqueous extract against castor oil-
induced diarrhea in mice [32]. Aqueous seed extract inhibits growth of human
gastric carcinoma cells by G2/M phase arrest and causes apoptosis [22]. The root
extract also exhibits antiproliferative activity of human multiple myeloma cells,
causing apoptosis [27, 28].
1694 Strychnos nux-vomica L.

Clinical Studies: In China, various diseases were treated with Miqianzi during
1950s, 60s and 70s with reportedly good success rate, as cited by Chang and But.XVIII
Effective rate after treatment with the injection of Miqianzi was described to be 90.8%
in more than 20,000 patients with various neurological diseases, including paraple-
gia, cerebral thrombosis with hemiplegia, infantile paralysis, sequelae of meningitis,
and sciatica [16]. Seeds soaked and cut into thin slices (18–24 slices per 3.5 g) and set
on a zinc oxide plaster, may be applied onto the paralyzed area of face, and changed
every 7 to 10-days until the symptoms and signs have disappeared. Generally,
two applications were sufficient for mild cases. In more than 2,000 patients with
facial paralysis, recovery rate was 80% [14, 31]. The herb was effective in both
the depressive and paranoid types of schizophrenia. Strychnos-chlorpromazine
regimen was employed in 20 cases; being effective in 15 cases, but not effective in
mania [19].
Mechanism of Action: CNS stimulant action of the seeds is mainly due to
strychnine and to a lesser extent, to brucine. Brucine and brucine N-oxide exert
their antinociceptive and anti-inflammation effects through both central and
peripheral mechanisms [37]. Presence of strychnine, in alcoholic seed extract is
credited for its antilipid peroxidative property [33].
Human A/Es, Allergy and Toxicity: Strychnine is one of the most powerful
poisons acting on nervous and muscular systems, with human lethal doses being
30–120 mg, though patients have survived ingestion of substantially higher doses.
It causes, generally sudden, tetanic tonic contractions that last from a few seconds
to many minutes and are repeated in quick succession. In severe poisoning, there is
hardly any interval between contractions and the whole body becomes rigid,
immovable, and hard as a board. Brucine has similar property but is less active than
strychnine.CV Purified seeds can still cause poisoning if the recommended dose is
exceeded, resulting in tonic contractions of all limb muscles, carpopedal spasm,
difficulty in breathing, chest discomfort, hyperventilation, perioral numbness,
convulsions and death; muscle pain and tiredness still remain after discontinuation
[10]. Even decoction of tree bark (the tree may be confused for Alstonia scholaris)
is reported to cause widespread muscle spasms and convulsions, acute renal failure
and rhabdomyolysis [1, 26].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: All clinical data presented here was indirectly quoted, as reported
by Chang and ButXVIII from studies at Chinese hospitals. There are no RCTs
reported in any of the conditions the seeds are suggested to benefit in traditional
folk medicines.
Strychnos nux-vomica L. 1695

References
1. Achappa B, Madi D, Babu YP, Mahalingam S. Rituals can kill—a fatal case
of brucine poisoning. Australas Med J. 2012;5:421–3.
2. Akbar S, Khan SA, Masood A, Iqbal M. Use of Strychnos nux-vomica
(Azraqi) seeds in Unani system of medicine: role of detoxification. Afr J
Tradit Complement Altern Med. 2010;7:286–90.
3. Anwar N, Khan MS, Kabir H, Ahmad S. Effect of detoxification (tadbeer) in
content of toxic metabolites of Strychnos nux-vomica: a Unani approach for
its use in human. J Pharm Bioallied Sci. 2015;7:314–6.
4. Bell IR, Howerter A, Jackson N, et al. Effects of homeopathic medicines on
polysomnographic sleep of young adults with histories of coffee-related
insomnia. Sleep Med. 2011;12:505–11.
5. Bhati R, Singh A, Saharan VA, et al. Strychnos nux-vomica seeds:
pharmacognostical standardization, extraction, and antidiabetic activity.
J Ayurveda Integr Med. 2012;3:80–4.
6. Biala RG, Tits M, Penelle J, et al. Strychnochrysine, a new bisindole
alkaloid from the roots of Strychnos nux-vomica L. J Nat Prod. 1998;61:
139–41.
7. Cai B, Nagasawa T, Kadota S et al. Processing of nux vomica. VII.
Antinociceptive effects of crude alkaloids from the processed and unpro-
cessed seeds of Strychnos nux-vomica in mice. Biol Pharm Bull. 1996;19:
127–31.
8. Cai BC, Hattori M, Namba T. Processing of nux vomica. II. Changes in
alkaloid composition of the seeds of Strychnos nux-vomica on traditional
drug-processing. Chem Pharmaceut Bull. 1990;38:1295–8.
9. Cai BC, Yang WX, Zhu WY et al. Effect of processing on the extraction of
alkaloids from Strychnos, China. J Chinese Mat Med. 1993;18:23–4, 62
(Chinese).
10. Chan TY. Herbal medicine causing likely strychnine poisoning. Hum Exp
Toxicol. 2002;21:467–8.
11. Chatterjee I, Chakravarty AK, Gomes A. Antisnake venom activity of
ethanolic seed extract of Strychnos nux vomica Linn. Indian J Exp Biol.
2004;42:468–75.
12. Chen J, Wang X, Qu YG, et al. Analgesic and anti-inflammatory activity
and pharmacokinetics of alkaloids from seeds of Strychnos nux-vomica after
transdermal administration: effect of changes in alkaloid composition.
J Ethnopharmacol. 2012;139:181–8.
13. Chen X, Gui X, Xie Z. Influence of processing methods on alkaloid, toxicity
and effect of Strychnos nux-vomica L. Zhongguo Zhong Yao Za Zhi. 1998;
23:151–3, 191 (Chinese).
14. Du YG. Zhejiang J. Traditional Chinese Med. 1980;1:32 (as cited by Chang
and But, 1986).XVIII
1696 Strychnos nux-vomica L.

15. Eldahshan OA, Abdel-Daim MM. Phytochemical study, cytotoxic, anal-

gesic, antipyretic and anti-inflammatory activities of Strychnos nux-vomica.
Cytotechnology. 2015;67:831–44.
16. Fangzhuang Hospital of Guzheng County. Scientific and technological
achievements in Hengshui district (1966–1971). Hengshui District Health
Bureau; 1972. p. 70 (as cited by Chang and But, 1986).XVIII
17. Fu Y, Zhang Y, He H, et al. Strynuxlines A and B, alkaloids with an
unprecedented carbon skeleton from Strychnos nux-vomica. J Nat Prod.
2012;75:1987–90.
18. Gupta R, Manchanda RK. Reiter’s disease treated with Nux vomica.
Homeopathy. 2006;95:103–4.
19. Heze District Mental Hospital. Heze Yiyao (Heze Med J). 1976;2:47 (as
cited by Chang and But, 1986).XVIII
20. Jonville MC, Dive G, Angenot L, et al. Dimeric bisindole alkaloids from the
stem bark of Strychnos nux-vomica L. Phytochemistry. 2013;87:157–63.
21. Katiyar C, Kumar A, Bhattacharya SK, Singh RS. Ayurvedic processed seeds
of nux-vomica: neuropharmacological and chemical evaluation. Fitoterapia.
2010;81:190–5.
22. Lee SM, Kwon JI, Choi YH, et al. Induction of G2/M arrest and apoptosis
by water extract of Strychni Semen in human gastric carcinoma AGS cells.
Phytother Res. 2008;22:752–8.
23. Malhi BS, Trivedi VP. Vegetable antifertility drugs of India. Quart J Crude
Drug Res. 1972;12:1922.
24. Mitra S, Kumar V, Ashok B, et al. A comparative anti-inflammatory activity
of raw and processed Kupeelu (Strychnos nux-vomica Linn.) seeds on
albino rats. Anc Sci Life. 2011;31:73–5.
25. Mitra S, Shukla VJ, Acharya R. Effect of Shodhana (processing) on
Kupeelu (Strychnos nux-vomica Linn.) with special reference to strychnine
and brucine content. Ayu. 2011;32:402–7.
26. Naik BS, Chakrapani M. A rare case of brucine poisoning complicated by
rhabdomyolysis and acute renal failure. Malays J Pathol. 2009;31:67–9.
27. Rao PS, Prasad MN. Strychnos nux-vomica root extract induces apoptosis in
the human multiple myeloma cell line-U266B1. Cell Biochem Biophys.
2013;66:443–50.
28. Rao PS, Ramanadham M, Prasad MN. Antiproliferative and cytotoxic
effects of Strychnos nux-vomica root extract on human multiple myeloma
cell line-RPMI 8226. Food Chem Toxicol. 2009;47:283–8.
29. Saha JC, Savini EC, Kasinathan S. Ecbolic properties of Indian medicinal
plants. I. Indian J Med Sci. 1961;49:130.
30. Samy RP, Thwin MM, Gopalakrishnakone P, Ignacimuthu S. Ethnobotan-
ical survey of folk plants for the treatment of snakebites in Southern part of
Tamilnadu, India. J Ethnopharmacol. 2008;115:302–12.
31. Shenyang College of Pharmacy. New Pharmaceut Commun. 1971;55 (as
cited by Chang and But, 1986).XVIII
Strychnos nux-vomica L. 1697

32. Shoba FG, Thomas M. Study of antidiarrhoeal activity of four medicinal

plants in castor oil-induced diarrhoea. J Ethnopharmacol. 2001;76:73–6.
33. Tripathi YB, Chaurasia S. Interaction of Strychnos nux-vomica-products and
iron: with reference to lipid peroxidation. Phytomedicine. 2000;7:523–8.
34. Umamaheswari M, AsokKumar K, Somasundaram A, et al. Xanthine
oxidase inhibitory activity of some Indian medical plants. J Ethnopharmacol.
2007;109:547–51.
35. Yang GM, Tu X, Liu LJ, Pan Y. Two new bisindole alkaloids from the
seeds of Strychnos nux-vomica. Fitoterapia. 2010;81:932–6.
36. Yang XW, Yan ZK. Studies on the chemical constituents of alkaloids in
seeds of Strychnos nux-vomica L. Zhongguo Zhong Yao Za Zhi. 1993;18:
739–40, 763–4 (Chinese).
37. Yin W, Wang TS, Yin FZ, Cai BC. Analgesic and anti-inflammatory
properties of brucine and brucine N-oxide extracted from seeds of Strychnos
nux-vomica. J Ethnopharmacol. 2003;88:205–14.
38. Zhang X, Xu Q, Xiao H, Liang X. Iridoid glucosides from Strychnos
nux-vomica. Phytochemistry. 2003;64:1341–4.
Swertia chirata Buck.-Ham. ex Wall.
Swertia chirayita (Roxb.) H. Karsten
(Gentianaceae)

Abstract
An annual herb, native to India, that grows at high altitudes in the subtemperate
regions of the Himalayas. The plant has been in use by Hindu physicians for
centuries due to its tonic, anthelmintic and febrifuge properties. It is prescribed
in masked forms of malarial fever in which the chief symptoms are dyspepsia,
and is usually combined with aromatics, such as ginger and lemon-grass; it is
also considered laxative and alterative. Muslim physicians of India mentioned it
as a remedy for cold and bilious affections, burning of the body and the fever,
called sannipat (fever with delirium), arising from derangement of the three
humours. Galen described it as diuretic and emmenagogue. It is a bitter tonic,
stomachic, laxative, anthelmintic and febrifuge; stimulates appetite, digestion,
diminishes flatulence, hyperacidity, and biliousness, and used in the treatment of
atonic dyspepsia, liver affections, and intermittent fevers. In Nepal it is
considered an important medicinal plant and is used for various diseases
including type-2 diabetes. European practitioners in India used it as a substitute
for official gentiana preparations. Its usefulness in Unani medicine as a bitter
tonic, febrifuge, stomachic, laxative and blood purifier, used for leprosy,
gonorrhea, and skin diseases, and also as a beneficial remedy for lung, liver,
stomach and kidney ailments is well recognized. It is one of the most frequently
used species in traditional Tibetan medicine for the treatment of liver diseases. In
China, Swertia pseudochinensis is known as Dangyao, whose properties are
described similar to S. chirata, such as it tastes bitter, has a cold property, clears
up “damp-heat” and is reputed as stomachic, chloretic and cholagogue; used in
infectious hepatitis, acute and chronic bacillary dysentery, and anorexia.
Phytoconstituents isolated from the plant include a large number of xanthones,
glycosides, alkaloids and other compounds, like chiratin, ophelic acid, palmitic
acid, oleic acid, and stearic acid. Ethanol extract of whole plant produced
significant blood glucose-lowering effect in fed, fasted and glucose-loaded rats,

© Springer Nature Switzerland AG 2020 1699

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_176
1700 Swertia chirata Buck.-Ham. ex Wall.

and enhanced hypoglycemic effect of tolbutamide in rats. Various extracts of the

plant and their fractions demonstrated protective activity against CCl4-,
galactosamine-, and APAP-induced hepatotoxicity in rats and mice.

Keywords




Bhunimba Buch-ham Chirayta Dangyao Dowa-i-pachish

Kalmegh





Kirayat-charaytah Kiriyattu Kuch-chi Qasab-uz-zarira

Vernaculars: Urd.: Chirayta; Hin.: Chirata, Kalapnath, Kalmegh, Kirayat-

charaytah; San.: Anarya-tikta, Bhunimba, Jwaranthakah, Kirata-tikta, Kuch-chi;
Ben.: Chireta, Kalapnath, Kalmegh, Mahatita; Mal.: Kiriyattu, Nila veppa; Mar.:
Chirata, Kalapnath, Kalmegh; Tam.: Nila vembu, Shirat; Tel.: Nila vemu; Ara.:
Qasab-uz-zarira; Chi.: Dangyao; Eng.: Buch-Ham; Per.: Dowa-i-pachish.
Description: An annual herb, native to India, grows at high altitudes in the sub-
temperate regions of the Himalayas [11]. The entire plant is collected when in flower,
or more commonly when the capsules are fully formed. The stem, 5–7.5 mm in
thickness, is orange-brown, sometimes of a dark-purplish color; the tapering simple
root often much exceeding the stem in thickness, is 5–10 cm long and up to 12 mm
thick. It is less frequently branched, but always provided with some rootlets. In
stronger specimens, the root is somewhat oblique or geniculate; perhaps the stem is in
this case the product of a second year’s growth, and the plant not strictly annual. Each
plant usually consists of a single stem, yet occasionally two or more spring from a
single root. The stem usually rises to a height of 60–90 cm, and is cylindrical in its
lower and middle portions, but bluntly quadrangular in the upper, the four edges being
each marked with a prominent decurrent line, as in Erythroea centorium and many
other plants of the order. Numerous smooth and glabrous, greenish or brownish-grey
color slender axillary and opposite branches are elongated, and thus constitute a dense
umbellate panicle. Leaves are ovate, acuminate, cordate at the base, entire, sessile, the
largest 2.5 cm or more in length, 3–5 or 7-nerved, the midrib being strongest. At each
division of the panicle there are two small bracts. The yellow corolla is rotate, 4-lobed,
with glandular pits above the base; the calyx is one-third the length of petals, which
are about 12 mm long. The one-celled bivalve capsule contains numerous seeds;
flowers share the intense bitterness of the whole drug (Fig. 1).XL
Actions and Uses: The plant has been in use by Hindu physicians for centuries due
to its tonic, anthelmintic and febrifuge properties. It is prescribed in masked forms
of malarial fever in which the chief symptoms are dyspepsia, and is usually com-
bined with aromatics, such as ginger and lemon-grass; it is also considered laxative
and alterative.XL Muslim physicians of India also mentioned it as a remedy for cold
and bilious affections, burning of the body and the fever, called sannipat (fever with
delirium), arising from derangement of the three humours.XL Galen described it as
diuretic and emmenagogue.LXIX It is a bitter tonic, stomachic, laxative, anthelmintic
and febrifuge; stimulates appetite, digestion, diminishes flatulence, hyperacidity,
and biliousness, and used in the treatment of atonic dyspepsia, liver affections, and
Swertia chirata Buck.-Ham. ex Wall. 1701

Fig. 1 Swertia chirata, Plant, Prasanths, WikimediaCommons; 3.0 Unported CC BY 3.0, https://
commons.wikimedia.org/wiki/File:%E0%B4%95%E0%B4%BF%E0%B4%B0%E0%B4%BF%
E0%B4%AF%E0%B4%BE%E0%B4%A4%E0%B5%8D%E0%B4%A4%E0%B5%8D(chiretta_
plant).JPG; https://creativecommons.org/licenses/by/3.0/deed.en

intermittent fevers.LXXXI NadkarniCV quoted Fleming that Chiretta possesses all the
stomachic, tonic, febrifuge and antidiarrheal virtues of gentian and in greater
degree; and it comes to India from Europe. European practitioners in India used it
as a substitute for official gentiana preparations [9, 20]. In Ayurveda, the plant is
used as stomachic, febrifuge, anthelminthic, diuretic, and for the treatment of
certain types of mental disorders; and is an important component of the Ayurvedic
tonic Sudarshana Churna [33]. In Nepal it is considered an important medicinal
plant and is used for various diseases including type-2 diabetes [26]. Its usefulness
in Unani medicine (temperament, hot 2° and dry 2°) as a bitter tonic, febrifuge,
stomachic, laxative and blood purifier, used for leprosy, gonorrhea, and skin dis-
eases, and also as a beneficial remedy for lung, liver, stomach and kidney ailments
is well recognized.LXXI,LXXVII It is one of the most frequently used species in
traditional Tibetan medicine for the treatment of liver diseases [17]. In China,
Swertia pseudochinensis is known as Dangyao, whose properties are described
similar to S. chirata, such as it tastes bitter, has a cold property, clears up
“damp-heat” and is reputed as stomachic, chloretic and cholagogue; used in
infectious hepatitis, acute and chronic bacillary dysentery, and anorexia.XVIII
Phytoconstituents: Phytoconstituents isolated from the plant include a large
number of xanthones [10], glycosides [27], alkaloids and other compounds, like
1702 Swertia chirata Buck.-Ham. ex Wall.

chiratin, ophelic acid, palmitic acid, oleic acid, and stearic acid. Phytochemical
analysis of plant samples from Nepal revealed the presence of alkaloids, flavonoids,
saponins, ascorbic acid, glycosides, steroids and triterpenoids [18]. First isolated
dimeric xanthone was chiratanin; other important constituents include swerchirin,
swertiamarin, swertanone, mangiferin, amarogentin, gentiopicrin and chiratol.
Swertiamarin, the bitter secoiridoid glycoside, is the representative bitter constituent
and the herb is normally evaluated by its contents. Its methanol extract possesses
antidiabetic activity and contains secoiridoid glycosides consisting of mangiferin,
amarogentin, amaroswerin, sweroside and swertiamarin as active constituents [41,
42], with amarogentin showing potent inhibitory activity of type I DNA topoiso-
merase from Leishmania [27]. Four compounds swertiachiralatone A, swertia-
choside A, swertiachirdiol A and swertiachoside B were isolated from ethanol
extract [46]. Three metabolites, namely gentianine, xanthone and swerchirin were
found to occupy the same binding pocket in the ligand binding domain of the
glucocorticoid receptor as dexamethasone, and gentianine and swerchirin activated
the receptor [34]. Aqueous extract contains two polar compounds, amerogentin and
mangiferin but is devoid of swerchirin, chiratol, methyl swetianin, and swertanone
[15]. Hydroalcohol extract was reported to contain 2.66% of ursolic acid [1].
Acetone: water extract with the highest total phenolic content and radical-
scavenging activity yielded decussatin, swertianin, isobellidifolin, bellidifolin,
amarogentin, swertianolin and mangiferin as active components [40]. The plant also
contains trace elements, such as Ca, more than 1.346 g/kg and other elements in
descending order of K > Ca > Fe > Na > Mn > Zn > Co > Cu > Li [24]. From
petroleum ether extract of Tibetan variety of Chirayita, swerchirin, decussatin,
bellidifolin, erythrodiol, oleanolic acid, methylswertianin, gnetiolactone, sina-
paldehyde, syringaldehyde, b-sitosterol, 1,8-dihydroxy-3,5,7-trimethoxyxanthone,
1-hydroxy-3,5,7,8-tetramethoxyxanthone, scopoletin, 1-hydroxy-3,7-dimethoxy-
xanthone, and 1-hydroxy-3,5-dimethoxyxanthone were isolated [45].
Pharmacology: Ethanol extract of whole plant, in an oral dose of 250 mg/kg,
produced a significant blood glucose-lowering effect in fed, fasted and glucose-
loaded rats, and enhanced hypoglycemic effect of tolbutamide in rats [12, 21, 38].
Hexane fraction [7], and swerchirin also significantly lowered blood sugar in fasted,
fed, glucose loaded, tolbutamide pretreated [4], and STZ-diabetic rats [35]. Ethanol
extract also demonstrated strong in vitro antioxidant activity, comparable to vitamin
E, and significantly prevented decrease in SOD, CAT, and GSH levels, and increase
in MDA levels in liver and kidneys of CCl4-intoxicated mice [8]. Various extracts
of the plant and their fractions demonstrated protective activity against CCl4-,
galactosamine-, and APAP-induced hepatotoxicity in rats and mice [13, 14, 18, 22,
23, 28]. Two xanthones: 1-hydroxy-2,3,4,6-tetramethoxyxanthone and 1,5,8-
trihydroxy-3-methoxyxanthone, are considered primary natural neuroprotective
antioxidants in S. chirayita. They markedly decreased infarct size in cerebral I/R
injury in rats to below 5%, and significantly improved activities of SOD, GPx, and
decreased LPO and the content of MDA [39]. Methanol leaf extract possesses
significant antibacterial as well as antidiabetic potential [29].
Swertia chirata Buck.-Ham. ex Wall. 1703

Oral administration of aqueous extract produced a dose-dependent reduction in

TNF-a, IL-b and IFN-c, and elevated IL-10 in joint homogenates of adjuvant-
induced arthritic mice; at higher doses (23.72 and 35.58 mg/kg) IL-6 was also
significantly reduced. Mangiferin was reported to possess potent anti-inflammatory
property [15]. The distance traveled and resting time of arthritic mice correlated
with levels of IL-1a, TNF-a and IL-10 in the joint homogenates [16]. Decoction of
the plant also significantly inhibits NF-kB/DNA interactions and reduced
proinflammatory IL-8 expression in cystic fibrosis cells [11]. Ethanol extract of leaf
and stem showed moderate analgesic activity in acetic acid-induced writhing in
mice [2].
Aqueous extract showed significant in vitro antiviral activity against HSV type-1
[43], while dichloromethane fraction of ethanol extract showed significant
antimicrobial activity against S. aureus [3], and methanol extract was active against
S. marcesens and C. albicans [44]. Treatment with water infusions as well as crude
and purified components increased activity of phase-II enzymes, GST, GPx, SOD,
and CAT, caused significant reduction in LPO [30], and reduced incidence and
multiplicity of DMBA-induced skin papillomas in mice [31, 32]. Amarogentin
treatment also arrested progression of CCl4/NDEA-induced liver carcinogenesis in
mice at mild dysplastic stage [25]. Amarogentin in both liposomal and niosomal
forms is an active leishmanicidal agent than the free amarogentin [19].
Gentianine, in small doses (10–20 mg/kg i.p.), markedly diminished sponta-
neous motility and produced sedation in mice and rats, but in high doses (50–
100 mg/kg i.p.) caused hind limb paralysis and catalepsy, significantly potentiated
hexobarbital-induced sleeping time in mice; antagonized amphetamine-induced
stereotypy in rats, and diminished amphetamine toxicity in aggregated mice.
Gentianine also potentiated analgesic activity of subanalgesic dose of morphine
without showing any activity per se, and significantly potentiated anticonvulsant
activity of subanticonvulsant dose of diphenylhydantoin [5]. Swertiamarin signifi-
cantly reversed mangiferin-induced CNS-stimulating effects in mice and rats,
antagonizing CNS effects of each other in vivo [6].
Mechanism of Action: Blood glucose-lowering effect of swerchirin is due to
stimulation of insulin release from islets of Langerhans [36, 37]. Crude aqueous and
ethanol (12%) extracts also show moderate-to-high a-glucosidase inhibitory
activity. Among the compounds present in the extracts (mangiferin, swertiamarin,
and amarogentin), mangiferin also possess a-glucosidase and antioxidant activities
[26].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: LD50 of gentianine for rats was reported as 276 mg/kg [5].
CYP450 and Potential for Drug-Herb Interactions: Hydroalcohol extract,
standardized for its content of ursolic acid, moderately inhibited CYP3A4 and
CYP2D6 isozymes in rat liver microsomes [1]. If similar inhibition is observed
under clinical use, then interactions with drugs metabolized by these enzymes might
be a concern.
1704 Swertia chirata Buck.-Ham. ex Wall.

Commentary: There are no dearth of anecdotal use of this significant and important
plant in traditional medicines in many clinical states, but no formal clinical studies are
reported in any published journal.

References
1. Ahmmed SM, Mukherjee PK, Bahadur S, et al. CYP450 mediated
inhibition potential of Swertia chirata: an herb from Indian traditional
medicine. J Ethnopharmacol. 2016;178:34–9.
2. Alam KD, Ali MS, Mahjabeen S, et al. Report: analgesic activities of
ethanol extract of leaf, stem and their different fractions of Swertia chirata.
Pak J Pharm Sci. 2010;23:455–7.
3. Alam KD, Ali MS, Parvin S, et al. In vitro antimicrobial activities of
different fractions of Swertia chirata ethanolic extract. Pak J Biol Sci. 2009;
12:1334–7.
4. Bajpai MB, Asthana RK, Sharma NK, et al. Hypoglycemic effect of
swerchirin from the hexane fraction of Swertia chirayita. Planta Med.
1991;57:102–4.
5. Bhattacharya SK, Ghosal S, Chaudhuri RK, et al. Chemical constituents of
Gentianaceae XI: antipsychotic activity of gentianine. J Pharm Sci. 1974;
63:1341–2.
6. Bhattacharya SK, Reddy PK, Ghosal S, et al. Chemical constituents of
Gentianaceae XIX: CNS-depressant effects of swertiamarin. J Pharm Sci.
1976;65:1547–9.
7. Chandrasekar B, Bajpai MB, Mukherjee SK. Hypoglycemic activity of
Swertia chirayita (Roxb. ex Flem) Karst. Indian J Exp Biol. 1990;28:616–8.
8. Chen Y, Huang B, He J, et al. In vitro and in vivo antioxidant effects of the
ethanolic extract of Swertia chirayita. J Ethnopharmacol. 2011;136:309–15.
9. Chopra RN, Chopra IC. A review of work on Indian Medicinal Plant. In:
ICMR special report series, vol. 30. New Delhi; 1955.
10. Ghosal S, Sharma PV, Chaudhuri RK, Bhattacharya SK. Chemical
constituents of the gentianaceae V: tetraoxygenated xanthones of Swertia
chirata Buch.-Ham. J Pharm Sci. 1973;62:926–30.
11. Guerrini A, Mancini I, Maietti S, et al. Expression of proinflammatory
interleukin-8 is reduced by Ayurvedic decoctions. Phytother Res. 2014;28:
1173–81.
12. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
13. Karan M, Vasisht K, Handa SS. Antihepatotoxic activity of Swertia chirata
on carbon tetrachloride induced hepatotoxicity in rats. Phytother Res.
1999;13:24–30.
Swertia chirata Buck.-Ham. ex Wall. 1705

14. Karan M, Vasisht K, Handa SS. Antihepatotoxic activity of Swertia chirata

on paracetamol and galactosamine induced hepatotoxicity in rats. Phytother
Res. 1999;13:95–101.
15. Kumar IV, Paul BN, Asthana R, et al. Swertia chirayita mediated
modulation of interleukin-1beta, interleukin-6, interleukin-10, interferon-
gamma, and tumor necrosis factor-alpha in arthritic mice. Immunopharma-
col Immunotoxicol. 2003;25:573–83.
16. Kumar P, Paul B, Kumar S, et al. Correlation of cytokine and mobility in
mice with arthritis and during therapy with Swertia chirayita. J Herb
Pharmacother. 2004;4:33–45.
17. Li Q, Li HJ, Xu T, et al. Natural medicines used in the traditional Tibetan
medical system for the treatment of liver diseases. Front Pharmacol. 2018;
9:29.
18. Mahmood S, Hussain S, Tabassum S, Malik F, Riaz H. Comparative
phytochemical, hepatoprotective and antioxidant activities of various
samples of Swertia chirayita collected from various cities of Pakistan.
Pak J Pharm Sci. 2014;27:1975–83.
19. Medda S, Mukhopadhyay S, Basu MK. Evaluation of the in-vivo activity
and toxicity of amarogentin, an antileishmanial agent, in both liposomal and
niosomal forms. J Antimicrob Chemother. 1999;44:791–4.
20. Mukerji B. Indian pharmaceutical code I, vol. 64. 1953.
21. Mukherjee B, Mukherjee SK. Blood sugar lowering activity of Swertia
chirata (Buch-Ham) extract. Int J Crude Drug Res. 1987;25:97–102.
22. Mukherjee S, Sur A, Maiti BR. Hepatoprotective effect of Swertia chirata
on rat. Indian J Exp Biol. 1997;35:384–8.
23. Nagalekshmi R, Menon A, Chandrasekharan DK, Nair CK. Hepatoprotec-
tive activity of Andrographis paniculata and Swertia chirayita. Food Chem
Toxicol. 2011;49:3367–73.
24. Negi JS, Singh P, Rawat MS, Geeta J. Study on the trace elements in Swertia
chirayita (Roxb.) H. Karsten. Biol Trace Elem Res. 2010;133:350–6.
25. Pal D, Sur S, Mandal S, et al. Prevention of liver carcinogenesis by
amarogentin through modulation of G1/S cell cycle check point and
induction of apoptosis. Carcinogenesis. 2012;33:2424–31.
26. Phoboo S, Pinto Mda S, Barbosa AC, et al. Phenolic-linked biochemical
rationale for the antidiabetic properties of Swertia chirayita (Roxb. ex.
Flem.) Karst. Phytother Res. 2013;27:227–35.
27. Ray S, Majumder HK, Chakravarty AK, et al. Amarogentin, a naturally
occurring secoiridoid glycoside and a newly recognized inhibitor of
topoisomerase I from Leishmania donovani. J Nat Prod. 1996;59:27–9.
28. Reen RK, Karan M, Singh K, et al. Screening of various Swertia species extracts
in primary monolayer cultures of rat hepatocytes against carbon tetrachloride-
and paracetamol-induced toxicity. J Ethnopharmacol. 2001;75:239–47.
1706 Swertia chirata Buck.-Ham. ex Wall.

29. Roy P, Abdulsalam FI, Pandey DK, et al. Evaluation of antioxidant,

antibacterial, and antidiabetic potential of two traditional medicinal plants of
India: Swertia cordata and Swertia chirayita. Pharmacognosy Res. 2015;7
Suppl 1:S57–62.
30. Saha P, Das S. Regulation of hazardous exposure by protective exposure:
modulation of phase II detoxification and lipid peroxidation by Camellia
sinensis and Swertia chirata. Teratog Carcinog Mutagen Suppl. 2003;1:
313–22.
31. Saha P, Mandal S, Das A, Das S. Amarogentin can reduce hyperprolifer-
ation by downregulation of COX-II and upregulation of apoptosis in mouse
skin carcinogenesis model. Cancer Lett. 2006;244:252–9.
32. Saha P, Mandal S, Das A, et al. Evaluation of the anticarcinogenic activity
of Swertia chirata Buch. Ham, an Indian medicinal plant, on DMBA-
induced mouse skin carcinogenesis model. Phytother Res. 2004;18:373–8.
33. Saha P, Das S. Highlighting the anticarcinogenic potential of an Ayurvedic
medicinal plant, Swertia chirata. Asian Pac J Cancer Prev. 2010;11:1445–9.
34. Sarmah R. Insights from the predicted interactions of plant derived
compounds to the glucocorticoid receptor as an alternative to dexametha-
sone. Bioinformation. 2012;8:963–9.
35. Saxena AM, Bajpai MB, Mukherjee SK. Swerchirin induced blood sugar
lowering of streptozotocin treated hyperglycemic rats. Indian J Exp Biol.
1991;29:674–5.
36. Saxena AM, Bajpai MB, Murthy PS, Mukherjee SK. Mechanism of blood
sugar lowering by a swerchirin-containing hexane fraction (SWI) of Swertia
chirayita. Indian J Exp Biol. 1993;31:178–81.
37. Saxena AM, Murthy PS, Mukherjee SK. Mode of action of three
structurally different hypoglycemic agents: a comparative study. Indian J
Exp Biol. 1996;34:351–5.
38. Sekar BC, Mukherjee B, Chakravarti RB, Mukherjee SK. Effect of different
fractions of Swertia chirayita on the blood sugar level of albino rats.
J Ethnopharmacol. 1987;21:175–81.
39. Shi GF, Wang GY, Chen XF. Screening of radical-scavenging natural
neuroprotective antioxidants from Swertia chirayita. Acta Biol Hung. 2013;
64:267–78.
40. Singh PP. Ambika, Chauhan SM. Activity-guided isolation of antioxidant
xanthones from Swertia chirayita (Roxb.) H. Karsten (Gentianaceae). Nat
Prod Res. 2012;26:1682–6.
41. Suryawanshi S, Asthana RK, Gupta RC. Assessment of systemic interaction
between Swertia chirata extract and its bioactive constituents in rabbits.
Phytother Res. 2009;23:1036–8.
42. Suryawanshi S, Mehrotra N, Asthana RK, Gupta RC. Liquid chromatography/
tandem mass spectrometric study and analysis of xanthone and secoiridoid
glycoside composition of Swertia chirata, a potent antidiabetic. Rapid Commun
Mass Spectrom. 2006;20:3761–8.
Swertia chirata Buck.-Ham. ex Wall. 1707

43. Verma H, Patil PR, Kolhapure RM, Gopalkrishna V. Antiviral activity of the
Indian medicinal plant extract Swertia chirata against herpes simplex viruses:
a study by in-vitro and molecular approach. Indian J Med Microbiol. 2008;
26:322–6.
44. Wazir A. Mehjabeen, Jahan N, Sherwani SK, Ahmad M. Antibacterial,
antifungal and antioxidant activities of some medicinal plants. Pak J Pharm
Sci. 2014;27(6(Special)):2145–52.
45. You RR, Chen XQ, He DD, et al. Chemical constituents from petroleum
ether fraction of Swertia chirayita and their activities in vitro. Zhongguo
Zhong Yao Za Zhi. 2017;42:3764–9 (Chinese).
46. Zhou NJ, Geng CA, Huang XY, et al. Antihepatitis B virus active constituents
from Swertia chirayita. Fitoterapia. 2015;100:27–34.
Symplocos racemosa Roxb.
(Symplocaceae)

(Syns.: S. intermedia Brand; S. macrostachya Brand; S. propinqua Hance)

Abstract
A small evergreen tree, found throughout the tropical and subtropical countries,
especially South Asia, but also in Australia and America. In Indian traditional
medicines, the stem bark is mainly used in the treatment of eye, skin and ear
diseases, liver and bowel complaints (diarrhea, dysentery), tumors, uterine
disorders, spongy and bleeding gums, asthma, fever, snakebites, gonorrhea and
arthritis, and for various female disorders, such as menorrhagia, dysmenorrhea,
leucorrhea, inflammation of the uterus, and as a uterine relaxant. Unani physi-
cians consider it astringent and styptic, and also use it to thicken semen, and
externally as an analgesic and anti-inflammatory. Stem-bark is cooling and mildly
astringent. In Ayurveda, it is mentioned in Nighantas as hot, alterative, and useful
in phlegmatic diseases and leprosy; and in the Bhávaprakása it is said to be
absorbent, stomachic, refrigerant, astringent, expectorant and hemostatic, and
useful in eye and liver diseases, fever, dysentery and dropsy. A decoction of the
bark is used as a gargle when gums are spongy and bleeding (Sushruta). In
Europe, it is known as ‘Lotur bark’ and used in 1.3 g doses mixed with sugar as a
remedy for menorrhagia due to relaxation of uterine tissue. Phenolic glycosides
with PDE-I and thymidine phosphorylase inhibiting activities, salirepin, sym-
plocuronic acid and sympocemoside; locoracemosides A, B and C with
a-chymotrypsin inhibitory activity, and b-amyrin, oleonolic acid, b-sitosterol
and b-sitosterol glycoside, triterpenes, betulin and oleanolic acid are reported
from the stem bark. Bark also contains alkaloids (loturine, isoloturine, and
harmane), flavanol glucosides, flavonol glycoside, and triterpenoids. Ethanol
stem bark extract significantly reduced TC, TG, VLDL, and LDL, restored the
decreased HDL, and decreased elevated HMG-CoA reductase activity and
improved atherogenic index in hyperlipidemic rats, and protected rats against
CCl4-hepatotoxicity. Aqueous bark extract increased serum FSH and LH levels
and enhanced folliculogenesis in immature female rats.

© Springer Nature Switzerland AG 2020 1709

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_177
1710 Symplocos racemosa Roxb.

Keywords


Lodh Lodhpathani
Lodhra
Lotur-bark
Moogama
Pachotti
Velli

Zhu zi shu

Vernaculars: Urd.: Lodh gujarati, Lodhpathani; Hin.: Bodhra, Hoora, Lodh,

Tilak; San.: Lodhra, Rodhra, Savura lodhra, Srinata, Tillaka; Ben.: Hoora, Lodhra;
Guj.: Lodhaz; Mal.: Pachotti; Mar.: Hoora, Lodhra; Tam.: Erra lodduga, Velli,
Velli-lothi, Vellilothram; Tel.: Lodhuga-chettu; Ara.: Moogama; Chi.: 珠仔树,
Zhu zi shu; Eng.: Lodh tree, Lotur-bark (Bark); Rus.: Simplocos kististyi.
Description: A small evergreen tree, up to 8 m tall, found throughout the tropical
and subtropical countries, especially South Asia, but also in Australia and America.
It is found in north and east India, ascending in the Himalayas up to an elevation of
1,400 m. Leaves simple, alternate, spiral, oblanceolate to narrow elliptic, 6–12.5 cm
long and 3–4.5 cm wide, apex narrowly acuminate with base acute to attenuate [6].
The bark is very soft and friable, of a light fawn color; the external surface corky and
much fissured transversely; the internal of a lighter color and fibrous texture
(Fig. 1).XL

Fig. 1 Symplocos racemosa, Plant with Fruits, Vinayaraj, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/Category:Symplocos_racemosa#/
media/File:Symplocos_Racemosa_04.JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en
Symplocos racemosa Roxb. 1711

Actions and Uses: In Indian traditional medicines, the stem bark is mainly used in
the treatment of eye, skin and ear diseases, liver and bowel complaints (diarrhea,
dysentery), tumors, uterine disorders, spongy and bleeding gums, asthma, fever,
snakebites, gonorrhea and arthritis, and for various female disorders, such as men-
orrhagia, dysmenorrhea, leucorrhea, inflammation of the uterus, and as a uterine
relaxant [2, 6].LXXVII,LXXXI,CV Unani physicians consider it (temperament, cold 2°
and dry 2°) astringent and styptic, and also use it to thicken semen, and externally as
an analgesic and anti-inflammatory.1 Stem-bark is cooling and mildly astringent.CV
In Ayurveda, it is mentioned in Nighantas as hot, alterative, and useful in phlegmatic
diseases and leprosy; and in the Bhávaprakása it is said to be absorbent, stomachic,
refrigerant, astringent, expectorant and hemostatic, and useful in eye and liver dis-
eases, fever, dysentery and dropsy. A decoction of the bark is used as a gargle when
gums are spongy and bleeding (Sushruta). In Europe, it is known as ‘Lotur bark’ and
used in 1.3 g doses mixed with sugar as a remedy for menorrhagia due to relaxation
of uterine tissue; it should be used two to three times a day for three or four days.XL
Phytoconstituents: Phenolic glycosides (symplocomoside, symponoside, symplo-
veroside, symplososide, benzoylsalireposide and salireposide) with in vitro PDE-I
and thymidine phosphorylase inhibiting activities [1, 3], salirepin, symplocuronic
acid and sympocemoside [4]; locoracemosides A, B and C with a-chymotrypsin
inhibitory activity [13], and b-amyrin, oleonolic acid, b-sitosterol and b-sitosterol
glycoside [3], triterpenes: 28-hydroxy-20a-urs-12,18(19)-dien-3b-yl acetate, 3-oxo-
urs-20a-12,18(19)-dien-28-oic acid and 24-hydroxyolean-12-en-3-one, and betulin
and oleanolic acid [5] are reported from the stem bark. A novel isoflavone glycoside,
sympracemoside [10], and three anthraquinone secondary metabolites from aerial
parts [9] have been isolated. Bark also contains alkaloids: loturine, isoloturine, and
harmane; flavanol glucosides: symplocoside, symposide, leucopelargonidine 3-gluco-
side, and ellagic acid; flavonol glycoside: rhamnetin 3-digalactoside; triterpenoids: 19
a-hydroxyarjunolic acid-3, 28-O-bis-b-glucopyranosides, 19a-hydroxyasiatic acid-3,
and a-amyrin [6].
Pharmacology: Ethanol stem bark extract significantly reduced TC, TG, VLDL, and
LDL, restored the decreased HDL, and decreased elevated HMG-CoA reductase
activity and improved atherogenic index in triton- and high-fat diet-induced hyper-
lipidemic rats [8], and protected rats against CCl4-hepatotoxicity [15]. Aqueous bark
extract increased serum FSH and LH levels and enhanced folliculogenesis in immature
female rats [7]; however, Kamat et al. [11] found no estrogenic activity in aqueous
extract, and Sandeep et al. [14] reported in vitro androgenic property. The stem bark
extract also exhibited significant anti-inflammatory and analgesic effects [12].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.

1
Tayyab M: Personal Communication.
1712 Symplocos racemosa Roxb.

Animal Toxicity: No animal toxicity studies are reported in the literature.

Commentary: This plant has not been much investigated pharmacologically in
animals or in vitro systems, especially for its traditional uses, and no organized
clinical studies are reported.

References
1. Abbasi MA, Ahmad VU, Zubair M, et al. Phosphodiesterase and thymidine
phosphorylase-inhibiting salirepin derivatives from Symplocos racemosa.
Planta Med. 2004;70:1189–94.
2. Acharya N, Acharya S, Shah U, Shah R, Hingorani L. A comprehensive
analysis on Symplocos racemosa Roxb.: traditional uses, botany, phyto-
chemistry and pharmacological activities. J Ethnopharmacol. 2016;181:
236–51.
3. Ahmad VU, Abbasi MA, Hussain H, et al. Phenolic glycosides from
Symplocos racemosa: natural inhibitors of phosphodiesterase I. Phytochem-
istry. 2003;63:217–20.
4. Ahmad VU, Rashid MA, Abbasi MA, Rasool N, Zubair M. New salirepin
derivatives from Symplocos racemosa. J Asian Nat Prod Res. 2007;9:209–15.
5. Ali M, Bhutani KK, Srivastava TN. Triterpenoids from Symplocos
racemosa bark. Phytochemistry. 1990;29:3601–4.
6. Bhusnar HU, Nagore DH, Nipanikar SU. Phytopharmacological profile of
Symplocos racemosa: a review. Pharmacologia. 2014;5:76–83.
7. Bhutani KK, Jadhav AN, Kalia V. Effect of Symplocos racemosa Roxb. on
gonadotropin release in immature female rats and ovarian histology.
J Ethnopharmacol. 2004;94:197–200.
8. Durkar AM, Patil RR, Naik SR. Hypolipidemic and antioxidant activity of
ethanolic extract of Symplocos racemosa Roxb. in hyperlipidemic rats: an
evidence of participation of oxidative stress in hyperlipidemia. Indian J Exp
Biol. 2014;52:36–45.
9. Farooq U, Naz S, Khan A, et al. Isolation and characterisation of three new
anthraquinone secondary metabolites from Symplocos racemosa. Nat Prod
Res. 2016;30:168–73.
10. Jung M, Choi J, Chae HS, et al. Flavonoids from Symplocos racemosa.
Molecules. 2014;20:358–65.
11. Kamat SK, Barde PJ, Raut SB. Evaluation of the estrogenic activity of
Indian medicinal plants in immature rats. Anc Sci Life. 2015;35:90–5.
12. Mehjabeen, Ahmad M, Jahan N, et al. Antidiarrhoeal, anti-inflammatory
and analgesic activities of Symplocos racemesa Roxb. bark. Pak J Pharm
Sci. 2014;27:2221–6.
Symplocos racemosa Roxb. 1713

13. Rashid MA, Ahmad VU, Abbasi MA, et al. a-Chymotrypsin inhibiting
benzylated glycosides from Symplocos racemosa. Phytochem Lett. 2008;1:
54–8.
14. Sandeep PM, Bovee TF, Sreejith K. Antiandrogenic activity of Nardostachys
jatamansi DC and Tribulus terrestris L. and their beneficial effects on
polycystic ovary syndrome-induced rat models. Metab Syndr Relat Disord.
2015;13:248–54.
15. Wakchaure D, Jain D, Singhai AK, Somani R. Hepatoprotective activity of
Symplocos racemosa bark on carbon tetrachloride-induced hepatic damage
in rats. J Ayurveda Integr Med. 2011;2:137–43.
Syzygium cumini (L.) Skeels
(Myrtaceae)

(Syns.: Eugenia cumini (L.) Druce; E. jambolana Lam.)

Abstract
The tree native to India is widely found in Asia and other tropical regions, South
America and Madagascar, and in the states of Florida and Hawaii of the United
States. Ibn Batuta who visited India in 1332 A.D., described Jamun as one of the
fruits of Delhi. Bark is astringent and is used alone or in combination with other
drugs to prepare astringent decoctions, gargles and washes. Expressed juice of
leaves, and fresh bark juice are used with goat’s milk in cases of dysentery. Ripe
fruit juice or syrup is stomachic, astringent and diuretic, and is used in oliguria.
Extract of powdered seeds and dried fruits are used to treat diabetes. A paste of
leaves is used to promote healthy discharges from indolent sores and ulcers. In
Unani medicine, the kernel is used to strengthen stomach and liver, and to treat
bloody and bilious diarrhea. Ayurvedic texts described antidysentery and
antidiarrheal properties of the bark. A ready to serve herbal drink, prepared with
the aqueous bark decoction and used in Ayurveda for diabetes patients contains
gallic and ellagic acids with antioxidant, antiproliferative and antiglycation
properties. At the turn of 20th century and before the discovery of insulin,
S. cumini was one of the most commonly marketed and recommended medicinal
plants as antidiabetic agents in Europe. It is one of the two most common
antidiabetic plant drugs, and the leaves are widely used in Brazilian folk
medicine to treat diabetes; diabetics use teas prepared from leaves and seeds in
Porto Alegre, Brazil. It is also widely used in Brazilian folk medicine against
leishmaniasis, inflammation, chronic diarrhea, and ulcers. In the Philippines, it is
one of the most popular fruits, and its juice is used to make red wine, ‘tinto
dulce.’ Fresh fruit-pulp (Indian variety) contains anthocyanins, total phenolics,
flavonoid, carbohydrates, protein and minerals, no significant amount of fat, but
rich in calcium; kernel and seed coat contain higher amounts of total phenolics.
In a double-blind, double-dummy RCT, administration of a tea prepared from
leaves for 28-days did not meaningfully lower blood glucose in Brazilian
patients with type-2 DM.

© Springer Nature Switzerland AG 2020 1715

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_178
1716 Syzygium cumini (L.) Skeels

Keywords





Ciruelo de java Giambolana Jamblon Jamelão Jambolanapflaume Jambu






Jambula Jamun Java plum Meghaba Pomposia

Vernaculars: Urd.: Jamun; Hin.: Jamun; San.: Jambula, Meghaba, Meghavarna,

Nilaphala, Rajaphala; Ben.: Kálájám; Mal.: Hjaval, Kattuchampa, Naga, Naval,
Perinnaral, Porinjara; Mar.: Jámbú, Jambul; Tam.: Naval; Tel.: Naregar, Neredi;
Ara.: Pomposia; Chi.: 乌墨; Eng.: Indian blackberry, Indian black plum, Java
plum; Fre.: Faux-pistachier, Jamblon, Jamelonguier, Jamelonier; Ger.: Jam-
bolanapflaume, Wachsjambose; Ita.: Giambolana; Per.: Jambu; Por.: Jambolão
(sweet olive), Jambolan (Br.), Jamelão; Sin.: Madan; Spa.: Ciruelo de java, Ciruelo
jambolan; Tag.: Dúhat, Lómboi.
Description: The tree native to India is widely found in Asia and other tropical
regions, South America and Madagascar, and in the states of Florida and Hawaii of
the United States [39]. A large, long living tree can reach a height of 30 m, and is
usually planted for shade due to its dense foliage. Leaves are 8–16 cm long, ovate or
oblong, obtuse, more or less acuminate, pinkish when young, becoming glossy dark
green as they mature with turpentine-like aroma. It flowers from March to April, and
by May or June fruits like large berries start appearing; fruits are initially green,
turning pinkish to shining crimson red and finally dark purple or black when mature.
Fruit is sweet and astringent; encloses a large green kernel (Figs. 1, 2 and 3).XL

Fig. 1 Syzygium cumini, Trees, A Junaid Alam Khan, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Jaam_tree2.JPG
Syzygium cumini (L.) Skeels 1717

Fig. 2 Syzygium cumini, Flowers, Réunion Island, B. navez, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Syzygium_cumini_flowers.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Syzygium cumini, Fruits, from Goa, India, Fredericknoronha, WikimediaCommons; Share-
Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:India_Goa_Jambul_
Fruit.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Actions and Uses: Ibn Batuta who visited India in 1332 A.D., described Jamun as
one of the fruits of Delhi. Bark is astringent and is used alone or in combination
with other drugs to prepare astringent decoctions, gargles and washes. Expressed
juice of leaves, and fresh bark juice are used with goat’s milk in cases of dysentery.
Dymock et al.XL also referred to the experiments conducted by Dr. Graeser of Bonn
in 1889, where he observed that the fruit extract reduced blood sugar in diabetic
dogs. However, Dr. Iaveine obtained negative results with seeds extract in three
1718 Syzygium cumini (L.) Skeels

diabetic patients. Ripe fruit juice or syrup is stomachic, astringent and diuretic, and
is used in oliguria. Extract of powdered seeds and dried fruits are used to treat
diabetes. A paste of leaves is used to promote healthy discharges from indolent
sores and ulcers.LXXXI In Unani medicine, the kernel (temperament, cold 2° and dry
2°) is used to strengthen stomach and liver, and to treat bloody and bilious diar-
rhea.LXXVII Ayurvedic texts described antidysentery and antidiarrheal properties of
the bark.XXI A ready to serve herbal drink, prepared with the aqueous bark
decoction and used in Ayurveda for diabetes patients contains gallic and ellagic
acids with antioxidant, antiproliferative and antiglycation properties [56]. At the
turn of 20th century and before the discovery of insulin, S. cumini was one of the
most commonly marketed and recommended medicinal plants as antidiabetic agent
in Europe [32]. It is one of the two most common antidiabetic plant drugs, and the
leaves are widely used in Brazilian folk medicine to treat diabetes [7, 14, 58, 85];
diabetics use teas prepared from leaves and seeds in Porto Alegre, Brazil [83]. It is
also widely used in Brazilian folk medicine against leishmaniasis, inflammation,
chronic diarrhea, and ulcers [65]. In the Philippines, it is one of the most popular
fruits, and its juice is used to make red wine, ‘tinto dulce.’ Medicinally, ripe fruits
are considered an efficient remedy for diabetes. Bark decoction is used internally in
dysentery, as a mouthwash and to gargle with in ulceration of the mouth and gums,
and externally to cleanse ulcers. Expressed juice of the leaves is also used for the
treatment of dysentery.CXVII Seed powder is one of the most extensively studied
antidiabetic agents of plant origin [32].
Phytoconstituents: Fresh fruit-pulp (Indian variety) contains anthocyanins, total
phenolics, flavonoid, carbohydrates, protein and minerals, no significant amount of
fat, but rich in calcium; kernel and seed coat contain higher amounts of total
phenolics [9]. Anthocyanins are responsible for the purple color of the fruits [40],
and contribute to their antioxidant capacity [25]. Fruits contain flavonoids: myrcetin
and myrcetin deoxyhexoside, tannins, phenolic acids [26], anthocyanins [87], and
terpenes [88]; 19.7% carbohydrates, 0.7% proteins, 0.02% calcium, 0.1% fat,
0.01% phosphorous, 0.4% mineral matter, 0.1% iron and 0.9% fiber [9, 76]. Pulp-
powder reportedly contained 0.54% anthocyanins (the anthocyanidins include
malvidin, petunidin, delphinidin, cyanidin, and peonidin), 0.17% ellagic acid/
ellagitannins, and 1.15% total polyphenolics, whereas seeds contained no detectable
anthocyanins but had higher amounts of ellagic acid/ellagitannins (0.5%) and total
polyphenolics (2.7%) than the pulp powder [3]. A peptidylglycan and an oligo-
saccharide, with molecular weights of 6.0 and 12.0 kD, respectively, were identi-
fied as the antidiabetic compounds of fruit-pulp [37]. Fruits from Brazil were also
reported to contain significant amounts of carotenoids, all-trans-lutein (43.7%) and
all-trans-b-carotene (25.4%) [25]. Chemical constituents of seeds were reported to
be jamboline, ellagic acid, tannin (19%), gallic acid, chlorophyll, fatty oil, resin,
sugar and traces of essential oil. NadkarniCV had suggested the glycoside jamboline
responsible for the antidiabetic activity [48]. Seeds are reported to contain flavo-
noids (quercetin, rutin, 3,5,7,4-tetrahydroxyflavanone) [10, 36], phenolic acids,
tannins [10], and terpenes [36]. Seeds have higher total phenolic contents and high
Syzygium cumini (L.) Skeels 1719

antioxidant activity [6]; gallic acid, ellagic acid, cinnamic acid, quercetin, syringic
acid and ferulic acid were identified as the major polyphenols present in seeds [81].
Tannins complex of seeds also include chebulic acid, corilagin and related ellagi-
tannins, 3,6-hexahydroxydiphenoylglucose and its two isomeric forms, galloyl-
glucose and quercetin [10]. New hydrolyzable tannins jamutannins A and B, and
iso-oenothein C were isolated from seeds [50]. Leaves contain flavonols [84],
acylated flavonol glycosides and polyphenols [42]. Essential oil of leaves from
Brazil had high abundance of monoterpenes, especially a-pinene, (Z)-b-ocimene,
and (E)-b-ocimene [22]; whereas, leaves EO from Egypt contained a-pinene,
b-pinene, trans-caryophyllene, 1,3,6-octatriene, delta-3-carene, a-caryophyllene,
and a-limonene [44].
Pharmacology: Feeding diet containing 15% powdered seeds to alloxan-diabetic
rats for 21-days significantly lowered blood glucose and improved oral glucose
tolerance [51]. Aqueous fruit-pulp extract was more effective than ethanol extract in
reducing FBG of diabetic rabbits [72]. A flavonoids-rich extract significantly
reduced FBG in mild and severely diabetic rats, stimulated insulin release from
pancreatic islets, and significantly decreased levels of LDL and TGs and increased
HDL [70]. Lyophilized fruit-pulp extract to STZ-diabetic rats for 41-days produced
no significant difference in body weight, food or water intake, urine volume, gly-
cemia, urinary urea and glucose, hepatic glycogen, or serum levels of TC, HDL-C
or TGs [55]. However, high carbohydrate high-fat diet of rats supplemented with
2.5% seed powder significantly prevented oxidative stress, reduced body weight
gain, and inflammatory cell infiltration and liver fibrosis, and normalized levels of
glucose and insulin [86]. Three-weeks treatment of STZ-diabetic rats with aqueous
seed extract ameliorated LPO, reduced hyperglycemia and hyperlipidemia without
altering insulin-sensitivity (IR) [13], but Sharma et al. [69] also reported normal-
ization of IR, that could be due to a higher dose (400 mg/kg vs. 100 mg/kg) used.
A 4 g/kg oral dose of aqueous suspension of dried seed kernel powder produced
maximum hypoglycemic effect (42%) in normal rabbits, and a significant decrease
(17%) in blood sugar of alloxan diabetic rats [48]. Lyophilized powder of kernels
(200 mg/kg per day for 21-days) produced a maximum reduction of 73% in glucose
levels of mildly diabetic animals [30], aqueous kernel extract for 15-days sub-
stantially prevented high fructose-induced hyperglycemia and hyperinsulinemia in
rats [89], and lyophilized aqueous extract produced 60% fall in glucose and
completely prevented cataract formation in alloxan-diabetic mice [60], and reduced
glucose, polyuria, urinary albumin, and significantly prevented renal hypertrophy in
STZ-diabetic mice [28, 29]. Teas prepared from leaves and seeds, administered as
water substitute for 14–95-days did not have any detectable antihyperglycemic
effect in normal or STZ-diabetic rats [83], and aqueous leaf decoction substituted
for water to STZ-diabetic rats for 17-days also failed to modify glycemia, serum
cholesterol, HDL-C, TGs and ACE [54]. Ethanol seed-kernel extract substantially
decreased blood glucose, blood urea [63], markedly lowered cholesterol, LDL-C,
VLDL-C, phospholipids, TGs, and FFAs of STZ-diabetic rats [61]; the seed coat
was devoid of hypoglycemic effect [63]. Single dose of ethanol seed extract
1720 Syzygium cumini (L.) Skeels

significantly lowered blood glucose of normal and diabetic rats [91], and diabetic
rabbits [2]. Repeated oral doses of ethanol seed extract also significantly reduced
hyperglycemia, hypercholesterolemia, hyperinsulinemia in mildly diabetic rats, and
prevented gastric ulcerations in rats caused by various methods [17], substantially
decreased lipids and improved antioxidant enzymes activities of alloxan-diabetic
rats [80], and diabetic rabbits [71]. Blood glucose of diabetic rats once normalized
with ethanol seed extract was not elevated when the extract was discontinued for
15-days [75]. The hypoglycemic effect of the pulp was reported in 30 min, whereas
the seeds required 24 h [1]. Seven-days oral treatment with ethanol leaf extract
reduced glycemia of nondiabetic mice, with reduction in food intake and body
weight [49]. Hydroalcohol leaf extract reduced oxidative stress, DNA damage,
glucose and TGs of high-fat diet and STZ-diabetic rats [7], and reduced body
weight gain, BMI, and insulin-resistance of monosodium L-glutamate-induced
obese rats [67]. Bark fed simultaneously with glucose exhibited antihyperglycemic
effect in mice [90]. Inorganic elements such as zinc, chromium, vanadium, potas-
sium, and sodium present in seed ash also exhibited hypoglycemic activity [62].
Hydroalcohol fruit-pulp extract protected against isoproterenol-induced oxida-
tive stress and myocardial damage in rats [73], and leaf extract for 8-weeks, time-
dependently reduced BP and HR in SHRs [64]. Ethanol fruit-pulp extract for
8-weeks significantly reduced (comparable to simvastatin) TC, LDL-C and TGs and
increased HDL-C of diet induced hyperlipidemic rats, and no increase in markers of
hepatotoxicity [11, 12]. Flavonoid-rich seed extract supplementation to atherogenic
diet of rats significantly prevented serum markers of LDL oxidation and minimized
aortic atheromatous plaque formation [34]. Aqueous leaf [15], ethanol bark [46, 47]
and seed extracts [24] demonstrated significant anti-inflammatory activity, whereas
ethanol leaf extract [58], and methanol bark extract showed analgesic effect [31].
Methanol fruit-pulp extract ameliorated bile-duct ligation-induced hepatic inflam-
mation, oxidative stress, macrophage infiltration, fibrosis and necrosis in mice [23].
Essential oil of leaves also exhibited anti-inflammatory activity by inhibiting
eosinophils migration, which was credited to the presence of b-pinene and b-caryo-
phyllene in the oil; however, both constituents were individually lesser effective
than the oil [74]. Ethanol seed extract [68], and methanol leaf extract [66] demon-
strated significant in vitro antioxidant activity. A Trivandrum (a city in Kerala
state of India) variant showed higher antioxidant potential due to higher phenolic
contents [57]. Aqueous leaf [45], methanol [77], and ethanol seed extracts [24]
protected against CCl4-hepatotoxicity in rats, and seed extract protected against
alcohol-induced oxidative stress in the liver [33]. Ethanol seed extract and aqueous
leaf extract [16] were also protective against induced gastric ulcers [19, 24], and
reversed the delayed healing of gastric ulcers in diabetic rats [18]. However,
administration of ethanol seed extract (200 mg/kg daily) to rats for 30-days was
also reported to cause hepatotoxicity with focal areas of hepatocytes necrosis and
lymphocytic infiltration [59].
Ethanol fruit extract showed no clinically relevant activity against E. coli, but
was synergistic with aminoglycosides [21]. Ethanol, acetone and aqueous seed
extracts significantly inhibited growth of S. aureus, E. coli, K. pneumoniae, and
Syzygium cumini (L.) Skeels 1721

P. aeruginosa, with ethanol extract being most effective and the aqueous extract the
least [5], and methanol seed extract inhibited growth of b-lactamase-producing
drug-resistant bacteria [35]. Hydroalcohol extract of fresh leaves (s.c.) increased
survival of mice and the neutrophil migration to infection site after polymicrobial
infection induced by cecal ligation and puncture [41]. Cold and hot aqueous bark
extracts, and hot aqueous leaf extract exhibited 100% virucidal activity against
avian influenza virus (H5N1) [78]. Water-soluble fraction of ethanol bark (5 years
old tree) extract inhibited growth of S. dysenteriae and S. boydii [43]. Aqueous seed
extract also significantly protected against DMBA-induced oxidative stress and
chromosomal damage [4], and oral administration of hydroalcohol seed extract in
both peri-initiation and promotion stages significantly reduced the incidence and
tumor burden of DMBA-induced skin carcinogenesis [52, 53], and B(a)P-induced
gastric carcinogenesis in mice [27]. Methanol extract of partially ripe fruit skin
inhibited growth and induced apoptosis in HeLa cervical cancer cell lines [8], and
an anthocyanins-rich standardized fruit extract exhibited proapoptotic effects
against breast cancer cells, but not toward the normal breast cells [39].
Clinical Studies: In a double-blind, double-dummy RCT, administration of a tea
prepared from leaves for 28-days did not meaningfully lower blood glucose in
Brazilian patients with type-2 DM [82].
Mechanism of Action: A potent dipeptidyl peptidase-4 (DPP-4) inhibitory activ-
ity, and an increase in plasma active glucagon-like peptide-1 (GLP-1) [38], and
3–4-folds upregulation of PPARa and PPARc levels by a flavonoid-rich extract are
suggested to be involved in the hypoglycemic action [70]. Aqueous seed extract
significantly inhibited in vitro porcine pancreatic a-amylase [36], and water-soluble
gummy fiber in seeds was also suggested to play a role in the hypoglycemic effect
[51]. Adenosine deaminase (ADA) activity in hyperglycemic serum is higher than
in normoglycemic serum; aqueous leaf extract in vitro inhibited ADA activity and
reduced levels both in erythrocytes and in hyperglycemic serum [14].
Human A/Es, Allergy and Toxicity: There are no published reports about A/Es or
toxicity.
Animal Toxicity: Single oral dose of up to 5,000 mg/kg seed powder to rats caused
no mortality or other abnormalities [79]. Ethanol bark extract to mice up to an oral
dose of 10,000 mg/kg [47], and ethanol extracts of both seeds and pericarp were
nonlethal and nontoxic to rats up to 5,000 mg/kg [19, 24]. Aqueous stem bark
extract in a single oral dose of up to 5,000 mg/kg to mice, and daily doses up to
2,000 mg/kg for 4-weeks to rats were also nonlethal and nontoxic [92].
CYP450 and Potential for Drug-Herb Interactions: Ethanol fruit extract exhib-
ited in vitro inhibition of CYP2C9, CYP3A4, and CYP2D6 in descending order
[20]. A dose of 200 mg/kg of ethanol seed extract with glimepiride (10 and
20 mg/kg) caused lethal hypoglycemia in normal rats [91]; glimepiride is metabo-
lized by CYP2C9. If the ethanol fruit extract or other clinically used jamun forms
also inhibit CYP450s in humans, then other drugs metabolized by the inhibited
1722 Syzygium cumini (L.) Skeels

CYP450s are likely to have drug interactions. Any component of this plant with
blood glucose lowering effect will have additive and/or synergistic effect with other
antihyperglycemic drugs.
Commentary: Despite the universal acceptance of the antidiabetic effects of seed
kernel and fruits of this plant, substantiated by numerous animal studies and
widespread clinical use in traditional medicines the world over, there are no pub-
lished reports of formal RCTs. Ironically, the only RCT reported was conducted on
a tea prepared from leaves which are not the primary part of the plant used as
antidiabetic. Substantial clinical studies in blinded RCTs are needed to validate the
anecdotal use and claims of its antidiabetic effects.

References
1. Achrekar S, Kaklij GS, Pote MS, Kelkar SM. Hypoglycemic activity of
Eugenia jambolana and Ficus bengalensis: mechanism of action. In Vivo.
1991;5:143–7.
2. Akhtar N, Khan BA, Majid A, et al. Pharmaceutical and biopharmaceutical
evaluation of extracts from different plant parts of indigenous origin for their
hypoglycemic responses in rabbits. Acta Pol Pharm. 2011;68:919–25.
3. Aqil F, Gupta A, Munagala R, et al. Antioxidant and antiproliferative activi-
ties of anthocyanin/ellagitannin-enriched extracts from Syzygium cumini L.
(Jamun, the Indian Blackberry). Nutr Cancer. 2012;64:428–38.
4. Arun R, Prakash MV, Abraham SK, Premkumar K. Role of Syzygium
cumini seed extract in the chemoprevention of in vivo genomic damage and
oxidative stress. J Ethnopharmacol. 2011;134:329–33.
5. Bag A, Bhattacharyya SK, Pal NK, Chattopadhyay RR. In vitro antibacterial
potential of Eugenia jambolana seed extracts against multidrug-resistant
human bacterial pathogens. Microbiol Res. 2012;167:352–7.
6. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and antioxidant
activity of some food and medicinal plants. Int J Food Sci Nutr. 2005;56:287–91.
7. Baldissera G, Sperotto ND, Rosa HT, et al. Effects of crude hydroalcoholic
extract of Syzygium cumini (L.) Skeels leaves and continuous aerobic
training in rats with diabetes induced by a high-fat diet and low doses of
streptozotocin. J Ethnopharmacol. 2016;194:1012–21.
8. Barh D, Viswanathan G. Syzygium cumini inhibits growth and induces
apoptosis in cervical cancer cell lines: a primary study. Ecancermedicalscience.
2008;2:83.
9. Benherlal PS, Arumughan C. Chemical composition and in vitro antioxidant
studies on Syzygium cumini fruit. J Sci Food Agric. 2007;87:2560–9.
10. Bhatia IS, Bajaj KL. Tannins in black-plum (Syzygium cumini L.) seeds.
Biochem J. 1972;128:56P.
11. Bilal R, Zakaria M, Usman A, Aftab S, Zia A. Antihyperlipidaemic effects
of Eugenia jambolana fruit in diet induced hyperlipidaemic rats. J Pak Med
Assoc. 2011;61:433–7.
Syzygium cumini (L.) Skeels 1723

12. Bilal R, Zakaria M, Usman A, Zia A. Comparison of simvastatin with

Eugenia Jambolana fruit pulp in their effects on alanine transferase,
aspartate aminotransferase and creatinine phosphokinase levels of hyper-
lipidaemic rats. J Pak Med Assoc. 2011;61:1190–4.
13. Bitencourt PE, Bona KS, Cargnelutti LO, et al. Syzygium cumini seed
extract ameliorates adenosine deaminase activity and biochemical param-
eters but does not alter insulin sensitivity and pancreas architecture in a
short-term model of diabetes. J Complement Integr Med. 2015;12:187–93.
14. Bopp A, De Bona KS, Bellé LP, Moresco RN, Moretto MB. Syzygium
cumini inhibits adenosine deaminase activity and reduces glucose levels in
hyperglycemic patients. Fundam Clin Pharmacol. 2009;23:501–7.
15. Brito FA, Lima LA, Ramos MF, et al. Pharmacological study of anti-
allergic activity of Syzygium cumini (L.) Skeels. Braz J Med Biol Res. 2007;
40:105–15.
16. Chanudom L, Tangpong J. Anti-inflammation property of Syzygium cumini
(L.) Skeels on indomethacin-induced acute gastric ulceration. Gastroenterol
Res Pract. 2015;2015:343642.
17. Chaturvedi A, Bhawani G, Agarwal PK, et al. Antidiabetic and antiulcer
effects of extract of Eugenia jambolana seed in mild diabetic rats: study on
gastric mucosal offensive acid-pepsin secretion. Indian J Physiol Pharmacol.
2009;53:137–46.
18. Chaturvedi A, Bhawani G, Agarwal PK, et al. Ulcer healing properties of
ethanolic extract of Eugenia jambolana seed in diabetic rats: study on gastric
mucosal defensive factors. Indian J Physiol Pharmacol. 2009;53:16–24.
19. Chaturvedi A, Kumar MM, Bhawani G, et al. Effect of ethanolic extract of
Eugenia jambolana seeds on gastric ulceration and secretion in rats. Indian J
Physiol Pharmacol. 2007;51:131–40.
20. Chinni S, Dubala A, Kosaraju J, et al. Effect of crude extract of Eugenia
jambolana Lam. on human cytochrome P450 enzymes. Phytother Res.
2014;28:1731–4.
21. Coutinho HD, Costa JG, Falcão-Silva VS, Siqueira-Júnior JP, Lima EO.
Potentiation of antibiotic activity by Eugenia uniflora and Eugenia
jambolanum. J Med Food. 2010;13:1024–6.
22. Dias CN, Rodrigues KA, Carvalho FA, et al. Molluscicidal and leishmani-
cidal activity of the leaf essential oil of Syzygium cumini (L.) SKEELS from
Brazil. Chem Biodivers. 2013;10:1133–41.
23. Donepudi AC, Aleksunes LM, Driscoll MV, Seeram NP, Slitt AL. The
traditional Ayurvedic medicine, Eugenia jambolana (Jamun fruit), decreases
liver inflammation, injury and fibrosis during cholestasis. Liver Int. 2012;32:
560–73.
24. El-Shenawy SM. Evaluation of some pharmacological activities of ethanol
extracts of seeds, pericarp and leaves of Eugenia Jamolana in rats.
Inflammopharmacology. 2009;17:85–92.
1724 Syzygium cumini (L.) Skeels

25. Faria AF, Marques MC, Mercadante AZ. Identification of bioactive

compounds from jambolão (Syzygium cumini) and antioxidant capacity
evaluation in different pH conditions. Food Chem. 2011;126:1571–8.
26. Gordon A, Jungfer E, da Silva BA, Maia JG, Marx F. Phenolic constituents
and antioxidant capacity of four underutilized fruits from the Amazon
region. J Agric Food Chem. 2011;59:7688–99.
27. Goyal PK, Verma P, Sharma P, Parmar J, Agarwal A. Evaluation of
anticancer and antioxidative potential of Syzygium cumini against benzo[a]
pyrene (BaP) induced gastric carcinogenesis in mice. Asian Pac J Cancer
Prev. 2010;11:753–8.
28. Grover JK, Rathi SS, Vats V. Amelioration of experimental diabetic
neuropathy and gastropathy in rats following oral administration of plant
(Eugenia jambolana, Mucuna pruriens and Tinospora cordifolia) extracts.
Indian J Exp Biol. 2002;40:273–6.
29. Grover JK, Vats V, Rathi SS, Dawar R. Traditional Indian antidiabetic
plants attenuate progression of renal damage in streptozotocin induced
diabetic mice. J Ethnopharmacol. 2001;76:233–8.
30. Grover JK, Vats V, Rathi SS. Antihyperglycemic effect of Eugenia
jambolana and Tinospora cordifolia in experimental diabetes and their
effects on key metabolic enzymes involved in carbohydrate metabolism.
J Ethnopharmacol. 2000;73:461–70.
31. Hegde SV, Yarappa RL, Rai PS. Anti-inflammatory and analgesic activities
of stem bark extracts of Eugenia jambolana. J Pharmacol Pharmacother.
2011;2:202–4.
32. Helmstädter A. Antidiabetic drugs used in Europe prior to the discovery of
insulin. Pharmazie. 2007;62:717–20.
33. Hossain S, Chowdhury IH, Basunia MA, et al. Syzygium cumini seed extract
protects the liver against lipid peroxidation with concurrent amelioration of
hepatic enzymes and lipid profile of alcoholic rats. J Complement Integr
Med. 2011;8.
34. Jadeja RN, Thouaojam MC, Sankhari JM, et al. Standardized flavonoid-rich
Eugenia jambolana seed extract retards in vitro and in vivo LDL oxidation
and expression of VCAM-1 and P-selectin in atherogenic rats. Cardiovasc
Toxicol. 2012;12:73–82.
35. Jasmine R, Selvakumar BN, Daisy P, Ignacimuthu S. Activity of Eugenia
jambolana, an ethnomedical plant, against drug-resistant bacteria. Pharm
Biol. 2010;48:405–10.
36. Karthic K, Kirthiram KS, Sadasivam S, Thayumanavan B. Identification of
alpha amylase inhibitors from Syzygium cumini Linn seeds. Indian J Exp
Biol. 2008;46:677–80.
37. Kelkar SM, Kaklij GS. A simple two-step purification of antidiabetic
compounds from Eugenia jambolana fruit-pulp: proteolytic resistance and
other properties. Phytomedicine. 1997;3:353–9.
Syzygium cumini (L.) Skeels 1725

38. Kosaraju J, Dubala A, Chinni S, et al. A molecular connection of Pterocarpus

marsupium, Eugenia jambolana and Gymnema sylvestre with dipeptidyl
peptidase-4 in the treatment of diabetes. Pharm Biol. 2014;52:268–71.
39. Li L, Adams LS, Chen S, et al. Eugenia jambolana Lam. berry extract
inhibits growth and induces apoptosis of human breast cancer but not
nontumorigenic breast cells. J Agric Food Chem. 2009;57:826–31.
40. Li L, Zhang Y, Seeram NP. Structure of anthocyanins from Eugenia
jambolana fruit. Nat Prod Commun. 2009;4:217–9.
41. Maciel MC, Farias JC, Maluf MJ, et al. Syzygium jambolanum treatment
improves survival in lethal sepsis induced in mice. BMC Complement
Altern Med. 2008;8:57.
42. Mahmoud II, Marzouk MS, Moharram FA, El-Gindi MR, Hassan AM.
Acylated flavonol glycosides from Eugenia jambolana leaves. Phytochem-
istry. 2001;58:1239–44.
43. Maiti AP, Pal SC, Chattopadhyay D, De S, Nandy A. Comparison of
minimum inhibitory concentration of water soluble extracts of Eugenia
jambolana Lam. (Fam. Myrtaceae) barks of different ages on dysentery and
diarrhoea forming microorganisms. Anc Sci Life. 1985;5:113–5.
44. Mohamed AA, Ali SI, El-Baz FK. Antioxidant and antibacterial activities of
crude extracts and essential oils of Syzygium cumini leaves. PLoS ONE.
2013;8:e60269.
45. Moresco RN, Sperotto RL, Bernardi AS, Cardoso RF, Gomes P. Effect of
the aqueous extract of Syzygium cumini on carbon tetrachloride-induced
hepatotoxicity in rats. Phytother Res. 2007;21:793–5.
46. Muruganandan S, Pant S, Srinivasan K, et al. Inhibitory role of Syzygium
cumini on autacoid-induced inflammation in rats. Indian J Physiol Pharmacol.
2002;46:482–6.
47. Muruganandan S, Srinivasan K, Chandra S, et al. Anti-inflammatory
activity of Syzygium cumini bark. Fitoterapia. 2001;72:369–75.
48. Nair RB, Santhakumari G. Antidiabetic activity of the seed kernel of
Syzygium cumini Linn. Anc Sci Life. 1986;6:80–4.
49. Oliveira AC, Endringer DC, Amorim LA, et al. Effect of the extracts and
fractions of Baccharis trimera and Syzygium cumini on glycaemia of
diabetic and nondiabetic mice. J Ethnopharmacol. 2005;102:465–9.
50. Omar R, Li L, Yuan T, Seeram NP. a-Glucosidase inhibitory hydrolyzable
tannins from Eugenia jambolana seeds. J Nat Prod. 2012;75:1505–9.
51. Pandey M, Khan A. Hypoglycaemic effect of defatted seeds and water
soluble fibre from the seeds of Syzygium cumini (Linn.) skeels in alloxan
diabetic rats. Indian J Exp Biol. 2002;40:1178–82.
52. Parmar J, Sharma P, Verma P, Goyal PK. Chemopreventive action of
Syzygium cumini on DMBA-induced skin papillomagenesis in mice. Asian
Pac J Cancer Prev. 2010;11:261–5.
53. Parmar J, Sharma P, Verma P, Sharma P, Goyal PK. Elimination of
deleterious effects of DMBA-induced skin carcinogenesis in mice by
Syzygium cumini seed extract. Integr Cancer Ther. 2011;10:289–97.
1726 Syzygium cumini (L.) Skeels

54. Pepato MT, Folgado VB, Kettelhut IC, Brunetti IL. Lack of antidiabetic
effect of a Eugenia jambolana leaf decoction on rat streptozotocin diabetes.
Braz J Med Biol Res. 2001;34:389–95.
55. Pepato MT, Mori DM, Baviera AM, et al. Fruit of the jambolan tree
(Eugenia jambolana Lam.) and experimental diabetes. J Ethnopharmacol.
2005;96:43–8.
56. Perera PRD, Ekanayake S, Ranaweera KKDS. Antidiabetic compounds in
Syzygium cumini decoction and ready to serve herbal drink. Evid Based
Complement Alternat Med. 2017;2017:1083589.
57. Priya SH, Prakasan N, Purushothaman J. Antioxidant activity, phenolic-
flavonoid content and high-performance liquid chromatography profiling of
three different variants of Syzygium cumini seeds: a comparative study.
J Intercult Ethnopharmacol. 2017;6:107–14.
58. Quintans JS, Brito RG, Aquino PG, et al. Antinociceptive activity of Syzyg-
ium cumini leaves ethanol extract on orofacial nociception protocols in
rodents. Pharm Biol. 2014;52:762–6.
59. Rasheed S, Tahir M, Sami W, Munir B. Histological effects of Eugenia
jambolana seed extract on liver of adult albino rats. J Ayub Med Coll
Abbottabad. 2009;21:148–51.
60. Rathi SS, Grover JK, Vikrant V, Biswas NR. Prevention of experimental
diabetic cataract by Indian Ayurvedic plant extracts. Phytother Res. 2002;16:
774–7.
61. Ravi K, Rajasekaran S, Subramanian S. Antihyperlipidemic effect of Eugenia
jambolana seed kernel on streptozotocin-induced diabetes in rats. Food
Chem Toxicol. 2005;43:1433–9.
62. Ravi K, Sekar DS, Subramanian S. Hypoglycemic activity of inorganic
constituents in Eugenia jambolana seed on streptozotocin-induced diabetes
in rats. Biol Trace Elem Res. 2004;99:145–55.
63. Ravi K, Sivagnanam K, Subramanian S. Antidiabetic activity of Eugenia
jambolana seed kernels on streptozotocin-induced diabetic rats. J Med
Food. 2004;7:187–91.
64. Ribeiro RM, Pinheiro Neto VF, Ribeiro KS, et al. Antihypertensive effect of
Syzygium cumini in spontaneously hypertensive rats. Evid Based Comple-
ment Alternat Med. 2014;2014:605452.
65. Rodrigues KA, Amorim LV, Dias CN, et al. Syzygium cumini (L.) Skeels
essential oil and its major constituent a-pinene exhibit antileishmania
activity through immunomodulation in vitro. J Ethnopharmacol. 2015;160:
32–40.
66. Ruan ZP, Zhang LL, Lin YM. Evaluation of the antioxidant activity of
Syzygium cumini leaves. Molecules. 2008;13:2545–56.
67. Sanches JR, França LM, Chagas VT, et al. Polyphenol-rich extract of
Syzygium cumini leaf dually improves peripheral insulin sensitivity and
pancreatic islet function in monosodium l-glutamate- induced obese rats.
Front Pharmacol. 2016;7:48.
Syzygium cumini (L.) Skeels 1727

68. Santos AK, Costa JG, Menezes IR, et al. Antioxidant activity of five
Brazilian plants used as traditional medicines and food in Brazil. Pharma-
cogn Mag. 2010;6:335–8.
69. Sharma AK, Bharti S, Kumar R, et al. Syzygium cumini ameliorates insulin
resistance and b-cell dysfunction via modulation of PPAR, dyslipidemia,
oxidative stress, and TNF-a in type 2 diabetic rats. J Pharmacol Sci. 2012;
119:205–13.
70. Sharma B, Balomajumder C, Roy P. Hypoglycemic and hypolipidemic
effects of flavonoid rich extract from Eugenia jambolana seeds on
streptozotocin induced diabetic rats. Food Chem Toxicol. 2008;46:2376–83.
71. Sharma SB, Nasir A, Prabhu KM, Murthy PS, Dev G. Hypoglycaemic and
hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in
alloxan-induced diabetic rabbits. J Ethnopharmacol. 2003;85:201–6.
72. Sharma SB, Nasir A, Prabhu KM, Murthy PS. Antihyperglycemic effect of
the fruit-pulp of Eugenia jambolana in experimental diabetes mellitus.
J Ethnopharmacol. 2006;104:367–73.
73. Shukla SK, Sharma SB, Singh UR, et al. Eugenia jambolana pretreatment
prevents isoproterenol-induced myocardial damage in rats: evidence from
biochemical, molecular, and histopathological studies. J Med Food. 2014;
17:244–53.
74. Siani AC, Souza MC, Henriques MG, Ramos MF. Anti-inflammatory
activity of essential oils from Syzygium cumini and Psidium guajava. Pharm
Biol. 2013;51:881–7.
75. Singh N, Gupta M. Effects of ethanolic extract of Syzygium cumini (Linn.)
seed powder on pancreatic islets of alloxan diabetic rats. Indian J Exp Biol.
2007;45:861–7.
76. Singh S, Krishnamurthi S, Katyal SL. Fruit culture in India. New Delhi:
Indian Council of Agriculture Research; 1967. p. 225.
77. Sisodia SS, Bhatnagar M. Hepatoprotective activity of Eugenia jambolana
Lam. in carbon tetrachloride treated rats. Indian J Pharmacol. 2009;41:23–7.
78. Sood R, Swarup D, Bhatia S, et al. Antiviral activity of crude extracts of
Eugenia jambolana Lam. against highly pathogenic avian influenza (H5N1)
virus. Indian J Exp Biol. 2012;50:179–86.
79. Sridhar SB, Sheetal UD, Pai MR, Shastri MS. Preclinical evaluation of the
antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-
diabetic rats. Braz J Med Biol Res. 2005;38:463–8.
80. Stanely Mainzen Prince P, Kamalakkannan N, Menon VP. Syzigium cumini
seed extracts reduce tissue damage in diabetic rat brain. J Ethnopharmacol.
2003;84:205–9.
81. Syama HP, Arya AD, Dhanya R, et al. Quantification of phenolics in
Syzygium cumini seed and their modulatory role on tertiary butyl-hydrogen
peroxide-induced oxidative stress in H9c2 cell lines and key enzymes in
cardioprotection. J Food Sci Technol. 2017;54:2115–25.
1728 Syzygium cumini (L.) Skeels

82. Teixeira CC, Fuchs FD, Weinert LS, Esteves J. The efficacy of folk medicines
in the management of type 2 diabetes mellitus: results of a randomized
controlled trial of Syzygium cumini (L.) Skeels. J Clin Pharm Ther. 2006;
31:1–5.
83. Teixeira CC, Pinto LP, Kessler FH, et al. The effect of Syzygium cumini (L.)
Skeels on postprandial blood glucose levels in nondiabetic rats and rats
with streptozotocin-induced diabetes mellitus. J Ethnopharmacol. 1997;56:
209–13.
84. Timbola AK, Szpoganicz B, Branco A, Monache FD, Pizzolatti MG. A new
flavonol from leaves of Eugenia jambolana. Fitoterapia. 2002;73:174–6.
85. Trojan-Rodrigues M, Alves TL, Soares GL, Ritter MR. Plants used as
antidiabetics in popular medicine in Rio Grande do Sul, southern Brazil.
J Ethnopharmacol. 2012;139:155–63.
86. Ulla A, Alam MA, Sikder B, et al. Supplementation of Syzygium cumini
seed powder prevented obesity, glucose intolerance, hyperlipidemia and
oxidative stress in high carbohydrate high fat diet induced obese rats. BMC
Complement Altern Med. 2017;17:289.
87. Veigas JM, Narayan MS, Laxman PM, Neelwarne B. Chemical nature,
stability and bioefficacies of anthocyanins from fruit peel of Syzygium
cumini Skeels. Food Chem. 2007;105:619–27.
88. Vernin G, Vernin G, Metzger J, Roque C, Pieribattesti J-C. Volatile
constituents of the jamrosa aroma Syzygium jambos L. aston from Reunion
Island. J Essent Oil Res. 1991;3:83–97.
89. Vikrant V, Grover JK, Tandon N, Rathi SS, Gupta N. Treatment with extracts
of Momordica charantia and Eugenia jambolana prevents hyperglycemia and
hyperinsulinemia in fructose fed rats. J Ethnopharmacol. 2001;76:139–43.
90. Villaseñor IM, Lamadrid MR. Comparative antihyperglycemic potentials of
medicinal plants. J Ethnopharmacol. 2006;104:129–31.
91. Yadav M, Lavania A, Tomar R, et al. Complementary and comparative study on
hypoglycemic and antihyperglycemic activity of various extracts of Eugenia
jambolana seed, Momordica charantia fruits, Gymnema sylvestre, and
Trigonella foenum graecum seeds in rats. Appl Biochem Biotechnol. 2010;160:
2388–400.
92. Yele SU, Veeranjaneyulu A. Toxicological assessments of aqueous extract
of Eugenia jambolana stem bark. Pharm Biol. 2010;48:849–54.
Tamarindus indica L.
(Fabaceae/Leguminosae)

(Syns.: T. occidentalis Gaertn.; T. officinalis Hook.; T. umbrosa Salisb.)

Abstract
A large tree native to India, Asia, tropical Africa, widespread in the Amazonia and
the Caribbean. The fruit is valued in India as being refrigerant, digestive,
carminative and laxative, and useful in febrile states and costiveness. Pulp and
leaves are applied externally as a paste or poultice on inflammatory swellings.
Muslim authors described two kinds of tamarind; the red, small-seeded, and the
very common reddish-brown variety; the first being the best. Muslim physicians
consider the fruit-pulp cardiacal, astringent, and aperient, useful for checking
bilious vomiting, and for purging the system of bile and adust humours. When used
as an aperient it should be given with a very small quantity of fluid. The seeds are
said to be good astringent, boiled they are used as a poultice to boils; pounded with
water they are applied to the crown of the head in cough and relaxation of the uvula.
Leaves crushed with water and expressed yield an acid fluid, which is said to be
useful in bilious fevers, and scalding of the urine. The bark is considered to possess
astringent and tonic properties. The fruit-pulp is purgative of bile and reduces
blood heat, and quenches thirst. Seed-pulp is astringent and is useful to treat
nocturnal emissions and thinness of semen. Besides India, it is used in traditional
medicines of Africa, Pakistan, Bangladesh, Nigeria, and other tropical countries
for treatment of abdominal pain, diarrhea and dysentery, helminths infections,
wound healing, malaria and fever, constipation, inflammation, gonorrhea, and eye
diseases. It is one of the most commonly used plant drugs in traditional medicines
of Africa; the fruits are used as laxative or febrifuge throughout the Sahel and
Sudan; while the leaves are used to treat diarrhea in East Africa, the West Africans
use bark for the same purpose, and both leaves and bark are used to treat wounds in
central West Africa. It contains glycosides, flavonoids and saponins. Significant
amount of total phenolics are found in fruits that correlate with their high
antioxidant activity. Dried and pulverized fruit-pulp significantly reduced TC and
LDL-C, and DBP in healthy Bangladeshi volunteers.

© Springer Nature Switzerland AG 2020 1729

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_179
1730 Tamarindus indica L.

Keywords







Amli Amalika Ardeib Assem Imli Hint hurması Khurma-e-hindi Luo




huang zi Tamarind Tambarina

Vernaculars: Urd.: Imli; Hin.: Amli, Amlica, Anbli, Imbli, Imli; San.: Amalika,
Ambia, Amlavraksha, Tintidi, Tintili, Tintiri, Tintrani; Ben.: Ambli, Tentul, Tetai,
Tintri amali; Guj.: Ambla, Amli; Mal.: Amlam, Amlika, Madhurappuli, Neghka,
Puli, Pulimaram, Valanpuli; Mar.: Ambali, Chintz; Tam.: Ambilam, Amilam,
Pulie, Puliyan, Puliyam-palam, Puliyam-pazham; Tel.: Amlika, Asek,
Chinta-chettu, Chinta-pandu; Ara.: Aradeib, Ardeib, Humara, Sabara, Tamar hindi;
Bur.: Ma gyi, Ma jee pen, Ma gyi thi; Chi.: 大瑪琳, Da ma lin, Luo huang zi, Luo
wang zi, Suan dou; Cze.: Tamarind; Dan.: Tamarind; Dut.: Assem, Indische dadel,
Tamarindeboom, Tamarijn; Eng.: Indian date, Tamarind; Fin.: Tamarindi; Fre.:
Tamarin, Tamarinier, Tamarinier d’Inde; Ger.: Indische dattel, Indischer
tamarindenbaum, Sauerdattel, Tamarinde; Gre.: Tamarin; Hun.: Indiai datolya,
Tamarindusz; Ind.: Asam jawa, Asam kuning; Ita.: Tamarindo, Tamarindo dolce,
Tamarandizio; Jap.: Tamarindo; Kor.: Ta ma rin du; Maly.: Asam, Asam java;
Nep.: Amilii, Titrii; Per.: Ambala, Khurma-e-hindi, Tamre hendi; Pol.: Tamarynd;
Por.: Tamarindo (Br.), Tamarindeiro, Tambarina; Rus.: Finik indiiskii, Tamarind
indiiskii; Sin.: Siyambala, Siyambula; Spa.: Tamarindo, TamarÃ-ndo de la India;
Swe.: Tamarind; Tag.: Kalamagi, Kamalagui, Salomagi, Salunagi, Sampalok;
Tha.: Bakham somkham, Kham, Ma kham, Ma kham peak, Met ma kham; Tur.:
Demirhindi, Hind hurma, Hint hurması, Temir hindi ağacı; Vie.: Cây me, Me chua,
Trái me.
Description: A large tree native to India, Asia, tropical Africa, widespread in the
Amazonia and the Caribbean. Leaves pinnate, linear oblong, obtuse, and of a dark
green color; leaflets linear, very short, petioled and oblique at both ends. Fruit a
pendulous legume, from 13 to 15 cm long, linear-oblong, slightly compressed,
curved or nearly straight, as thick as middle finger, and supported by a woody stalk.
Outer shell or pericarp thin and hard, brittle and of a cinnamon color containing
within the shell acid and juicy pulp of a dark red or brownish dark color. It is
traversed by strong woody ramifying fibers, which starting from the stalk, extend
along the edges and sides. Seeds, 4–12 in number, are each enclosed in a tough,
membranous cell (endocarp), surrounded by pulp. They are flattened, and of
irregular outline, being roundish ovate, or obtusely four-sided, about 15 mm in
length by 7 mm thick, with edge broadly keeled or more often slightly furrowed
(Figs. 1, 2 and 3).XL
Actions and Uses: The fruit is valued in India as being refrigerant, digestive,
carminative and laxative, and useful in febrile states and costiveness. Pulp and
leaves are applied externally as a paste or poultice on inflammatory swellings.
Muslim authors described two kinds of tamarind; the red, small-seeded, and the
very common reddish-brown variety; the first being the best. Muslim physicians
consider the fruit-pulp (temperament, cold 2° and dry 2°) cardiacal, astringent, and
Tamarindus indica L. 1731

Fig. 1 Tamarindus indica, Leaves and Fruit Pod, Tauʻolunga, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Tamarindus_indica,_
leaves,_pod.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Tamarindus indica, Unripe Fruits, Mlvalentin, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Tamarind2.jpg

aperient, useful for checking bilious vomiting, and for purging the system of bile
and adust humours. When used as an aperient it should be given with a very small
quantity of fluid. The seeds (temperament, cold 3° and dry 3°) are said to be good
astringent, boiled they are used as a poultice to boils; pounded with water they are
applied to the crown of the head in cough and relaxation of the uvula. Leaves
crushed with water and expressed yield an acid fluid, which is said to be useful in
1732 Tamarindus indica L.

Fig. 3 Tamarindus indica, Flowers, Jim Conrad, WikimediaCommons, https://commons.wiki-

media.org/wiki/File:Tamarindus_indica-flowers.jpg; http://www.backyardnature.net/n/08/080818tm.
jpg

bilious fevers, and scalding of the urine. The bark is considered to possess
astringent and tonic properties.XL The fruit-pulp is purgative of bile and reduces
blood heat, and quenches thirst.LXIX Roasted and salted seeds are also eaten as food
in various parts of the world, and used for the treatment of diabetes, snakebites,
chronic diarrhea, dysentery, jaundice, eye diseases, and ulcers [7]. Unripe fruit is
highly acidic, the pulp of ripe fruit is sweet or acid, is refrigerant, carminative,
digestive and laxative; tender leaves and flowers are cooling and antibilious.CV
KabeeruddinLXXVII describes fruit-pulp as refrigerant, yellow bile excreter and
blood moderator. Fruit-pulp syrup is used to quench thirst in bilious fevers and as
antinauseant. Seed-pulp is astringent and is useful to treat nocturnal emissions and
thinness of semen. In Ayurveda, the fruit-pulp is described as antiascorbutic,
refrigerant, and laxative, and used to quench thirst in fever, sunstroke and in bilious
vomiting. Hot paste of leaves and pulp is topically applied to inflammatory swel-
lings;LXXXI the wood (Kasta) is also used to prepare an alkaline extract (Kshara) in
Ayurvedic dosage form [34]. Besides India, it is used in traditional medicines of
Africa, Pakistan, Bangladesh, Nigeria, and other tropical countries for treatment of
abdominal pain, diarrhea and dysentery, helminths infections, wound healing,
malaria and fever, constipation, inflammation, gonorrhea, and eye diseases [7]. It is
one of the most commonly used plant drugs in traditional medicines of Africa; the
fruits are used as laxative or febrifuge throughout the Sahel (where the fruit is called
tsamiya biri) and Sudan; while the leaves are used to treat diarrhea in East Africa,
the West Africans use bark for the same purpose, and both leaves and bark are used
to treat wounds in central West Africa [22]. It is a highly valued tree by the majority
of eastern Ugandan population, and is utilized for food, medicinal, cultural, social,
environmental amelioration and income generation purposes [15]. In the Caribbean
and the Amazon, decoction of leaves is a useful remedy for hepatitis, jaundice, and
gallbladder disorders [67]. In Nigeria, stem-bark extract is traditionally used for the
Tamarindus indica L. 1733

management of diabetes [87]. It was once used to treat constipation in psychiatric

patients [9]. Tamarind fruit-pulp extract is rich in polyphenols with demonstrated
antiatherosclerotic, antioxidant and immunomodulatory activities [58]. In Burkina
Faso, it is used to treat kidney ailments [40], in Trinidad and Tobago, traditional
healers use it to treat hypertension [39], while in North African countries it is used
for inflammations [66]. All parts are used in Brazil, but the fruits are often con-
sumed for their therapeutic effects, such as laxative, digestive and antidiabetes [65].
In the Philippines, a decoction of leaves is used as a bath in fevers, puerperium and
convalescence; the pulp is used as a mild laxative, to calm thirst in fevers after
dissolving in sweetened water and in bilious vomiting and cholera. The leaves are
used in fomentations for rheumatism and applied to sores and wounds. A gargle
with tamarind pulp water relieves sore-throat and helps in healing of aphthous
ulcers.CXVII
Phytoconstituents: It was reported devoid of alkaloids, but contains glycosides,
flavonoids and saponins [63]. However, fruit-pulp from Nigeria was reported to
contain alkaloids, flavonoids, saponins, anthraquinones, carbohydrates, cyanogenic
glycosides, reducing sugars, and tannins [56]. Significant amount of total phenolics
are found in fruits that correlate with their high antioxidant activity [38].
Polyphenols in seed pericarp are mainly proanthcyanidins in the forms of (+)-
catechin, procyanidin B2, (−)-epicatechin, procyanidins, taxifolin, apigenin, erio-
dictyol, luteolin and naringenin [77]. Methanol extract of fruits also yielded cyto-
toxic principle L-(−)-di-n-butyl malate [33]. Yadava and Yadav [86] isolated a
cardenolide from acetone soluble fraction of ethanol extract of seeds. Two triter-
penes, lupanone and lupeol were isolated from leaves [24]. Aqueous extract of fresh
leaves contains higher concentration of phenols but low levels of flavonoids,
compared to higher level of flavonoids and lower concentration of phenols in dried
leaves’ decoction [16]. Mineral composition (Zn, Fe, Mg, P, Na, K, and Ca) was
reported generally higher in seeds than in pulp [57]. Stem-bark showed the presence
of carbohydrates, glycosides, saponins, flavonoids, cardiac glycosides, tannins,
alkaloids and triterpenes [87].
Pharmacology: Supplementation of seed powder in diet lowered serum choles-
terol and glucose in SHRs, and enhanced liver glycogen storage [81]. Aqueous seed
extract significantly decreased FBG, TC, LDL-C and TGs levels [45, 46], improved
pancreatic b-cell neogenesis [21], and improved GLUT-4 protein and mRNA
expression in skeletal muscles of diabetic rats [74]. A polyphenol rich hydroethanol
seed coat extract lowered blood glucose in normoglycemic, glucose-loaded and
alloxan-diabetic rats [6]. Methanol seed extract also lowers serum fasting and
overall blood glucose and shows antioxidant effects in diabetic mice [54]. Serum
cholesterol, TGs, creatinine, albumin, total proteins and body weight were restored
to normal levels by the ethanol bark extract in diabetic rats [1]. Methanol stem-bark
extract also significantly lowered blood glucose in diabetic rats and prevented
glucose load-induced hyperglycemia [87]. Aqueous seed extract also ameliorates
metabolic syndrome in hyperinsulinemic rats, preventing increases in fasting serum
insulin, TG, TC, VLDL, and LDL [72]. A trypsin inhibitor isolated from seeds
1734 Tamarindus indica L.

significantly elevates cholecystokinin levels, reduces food consumption and weight

gain [65]. Methanol seed coat extract administered daily to high-fat diet-fed rats for
6-weeks, attenuated hepatomegaly, elevated hepatic lipid and LPx, serum alanine
aminotransferase, and FFA levels, and improved insulin resistance index [71].
Aqueous and ethanol fruit-pulp extracts significantly reduced weight, TC, LDL-C
and TGs, and increased HDL-C in diet-induced obese and hypercholesterolemic
animals [5, 27, 47]. Aqueous fruit extract was protective against antitubercular
drugs-induced oxidative liver damage in rats [3]; the aqueous leaf extract also
protected against acute ethanol- [19], and CCl4-hepatotoxicity in rats [67]. A pro-
cyanidin-rich tamarind seed extract prevented arthritis-associated oxidative liver
damage [79], and a polysaccharide was also reported hepatoprotective [69].
Ethanol and hydroethanol leaf extracts demonstrated anti-inflammatory and
analgesic effects better than aspirin [8, 80]. Aqueous fruit extract also showed
significant analgesic activity that was modified by naloxone pretreatment [30].
However, Rimbau et al. [66] reported weaker anti-inflammatory activity in aqueous,
ethanol and chloroform extracts. The seeds extract mitigates arthritis-mediated
cartilage/bone degradation, inflammation and associated stress in rats, alleviating
increased levels of ROS and hydroperoxides and improving endogenous antioxi-
dant status [78]. Fruit-pulp ameliorated fluoride toxicity in rabbits [62], mice [85],
and rats [20], and hydromethanol fruit extract reduced fluoride concentration in
blood and bone and enhanced urinary excretion in rats [14]. Supplementation of
fluoride-rich diet to rats with tamarind leaves significantly reversed fluoride-
induced increase in plasma glucose and lipid levels, and improved antioxidant
profiles of both hepatic and renal tissues [84]. Aqueous-ethanol fruit extract pro-
tected against gentamicin-nephrotoxicity in rabbits [82]. Antioxidant activity of
various parts, inhibition of LPO and ROS production, and enhancement of
antioxidant enzyme activities have been widely reported [11, 17, 29, 35, 38, 55, 61,
64, 70].
Aqueous extract of aerial parts showed significant antibacterial activity against S.
aureus, E. coli, S. typhi, P. aeruginosa, P. vulgaris, K. aerogenes and Sh. boydii
[12], and hydroethanol leaf extract inhibited growth of S. aureus and P. aeruginosa
[42], and B. subtilis [53]. Methanol leaf extract was also active against S. aureus and
E. coli [51], and P. pseudomallei, an organism that causes melioidosis, a
life-threatening infection among paddy workers in southeast Asian countries [53].
The leaf essential oil showed activity against S. aureus, B. subtilis, E. faecalis,
E. coli, S. typhymurium and C. albicans [16]. Fruit-pulp hot water extract was active
against B. subtilis, E. coli, S. typhi, S. aureus, B. cereus, and P. aeruginosa,
comparable to ciprofloxacin [56, 59], and against L. monocytogenes, and Salmonella
sp. [59]; and strongly active against fresh clinical isolates of P. falciparum [37].
Methanol and acetone seed extracts were active against S. paratyphi A and S. epi-
dermidis [36]. Ethanol and aqueous bark extract also demonstrated significant
anthelmintic activity against P. posthuma and T. tubifex [13].
Aqueous fruit-pulp extract exhibited aphrodisiac effect, and increased sperm
count and motility in rats [60]. Methanol fruits extract relaxes KCl-induced con-
tractions of isolated rabbit jejunum [2]; whereas aqueous stem-bark extract exerted
Tamarindus indica L. 1735

spasmogenic effect that did not involve cholinergic mechanism [75], and methanol
seed coat extract reduced gastric ulcer index, total volume of gastric juice, free and
total acidity of gastric secretion in gastric ulcer models, comparable to ranitidine
[28]. It was first reported active against C3H mammary carcinoma by McKenna and
associates [50] and later Lopez-Abraham and colleagues [43] reported about its
anticancer potentials. Fruit-pulp extract ameliorated liver damage in hypercholes-
terolemic hamsters exposed to the carcinogen DMH, reduced LPO and increased
antioxidant defenses [48]. A crude hydroalcohol fruit-pulp extract modulated
human neutrophils oxidative metabolism [58], and polysaccharides isolated from
seed kernel and aerial parts demonstrated immunomodulatory effects, such as
phagocytic enhancement, inhibition of leukocyte migration and cell proliferation
[76], and tumor inhibitory activities against a number of human and murine cancer
cell lines [4]. Ethanol seed extract also inhibits Russell’s viper venom-induced
activities of PLA2, hyaluronidase, protease, l-amino acid oxidase and 5’-nucleoti-
dase enzyme [83], and increases survival of mice [49].
Clinical Studies: Dried and pulverized fruit-pulp, at a dose of 15 mg/kg body
weight, significantly reduced TC and LDL-C, and DBP in healthy Bangladeshi
volunteers [23]. Topical application of tamarind seed polysaccharide solution (1%)
for 90-days relieved subjective symptoms, trouble blinking, ocular burning and
foreign body sensation of dry eye syndrome, better than hyaluronic acid [68].
Tamarind ingestion enhanced fluoride excretion, and decreased urinary excretion of
Mg, Zn [32], Ca and Cu in children [31].
Mechanism of Action: Significant improvement in the GLUT-2 protein and
SREBP-1c mRNA expression in liver and GLUT-4 protein and mRNA expression
in the skeletal muscles [74], and anti-inflammatory action on b-cells of islets are
suggested to contribute toward its antidiabetic activity [73]. Methanol extract also
shows potent in vitro antilipase and the aqueous extract a high antiamylase activity
[10]. Presence of significant amounts of phenolic and flavonoid contents in
fruit-pulp and their antioxidant activity contributes to its antihypercholesterolemic
effect [41].
Human A/Es, Allergy and Toxicity: Consumption of tamarind more than 3 times
a week is associated with significant risk of gallstone formation in adults [26].
Animal Toxicity: Aqueous fruit-pulp extract was generally safe after treatment
with 1,000 mg/kg per day for six-months [25], nonlethal and nontoxic to Wistar rats
up to an oral single dose of 2,000 mg/kg [60]. Oral LD50 of methanol bark extract in
rats was greater than 5,000 mg/kg [87].
Potential for Drug-Herb Interactions: Coadministration of chloroquin with a
tamarind beverage (Ardaib®) manufactured in Sudan, to healthy volunteers resulted
in a significant decrease in AUC and Cmax of chloroquin, indicating a potential for
treatment failure with chloroquin [44]. Contrarily, tamarind fruit extract increased
bioavailability of aspirin [52], and ibuprofen [18], probably due to its acidic nature.
1736 Tamarindus indica L.

Commentary: All parts of tamarind tree are valued and widely used in Asia, Africa,
South America, and other parts of the world. Especially in the Indian subcontinent
fruit-pulp is used to make chutni, a sweet-sour sauce, and to make cooling drinks
during summer. Urbanization has greatly reduced the number of trees in urban pop-
ulated areas, and thus use of its leaves in home-made remedies for inflammation.
There are no blinded RCTs reported on its lipid-lowering effects in hypercholes-
terolemia or other traditional uses. This tree has the potential to offer great inexpensive
medicinal benefits if its use is formalized after systematic clinical trials.

References
1. Agnihotri A, Singh V. Effect of Tamarindus indica Linn. and Cassia fistula
Linn. stem bark extracts on oxidative stress and diabetic conditions. Acta
Pol Pharm. 2013;70:1011–119.
2. Ali N, Shah S. Spasmolytic activity of fruits of Tamarindus indica L.
J Young Pharm. 2010;2:261–4.
3. Amir M, Khan MA, Ahmad S, et al. Ameliorating effects of Tamarindus
indica fruit extract on antitubercular drugs induced liver toxicity in rats. Nat
Prod Res. 2016;30:715–9.
4. Aravind SR, Joseph MM, Varghese S, et al. Antitumor and immunopoten-
tiating activity of polysaccharide PST001 isolated from the seed kernel of
Tamarindus indica: an in vivo study in mice. Sci World J. 2012;2012:
361382.
5. Azman KF, Amom Z, Azlan A, et al. Antiobesity effect of Tamarindus
indica L. pulp aqueous extract in high-fat diet-induced obese rats. J Nat
Med. 2012;66:333–42.
6. Bhadoriya SS, Ganeshpurkar A, Bhadoriya RPS, Sahu SK, Patel JR.
Antidiabetic potential of polyphenolic-rich fraction of Tamarindus indica
seed coat in alloxan-induced diabetic rats. J Basic Clin Physiol Pharmacol.
2018;29:37–45.
7. Bhadoriya SS, Ganeshpurkar A, Narwaria J, et al. Tamarindus indica:
extent of explored potential. Pharmacogn Rev. 2011;5:73–81.
8. Bhadoriya SS, Mishra V, Raut S, et al. Anti-Inflammatory and antinoci-
ceptive activities of a hydroethanolic extract of Tamarindus indica leaves.
Sci Pharm. 2012;80:685–700.
9. Bourjala J. Tamarine in the treatment of constipation in a psychiatric
environment. Rev Neuropsych Inf Hyg Ment Enf. 1972;20:497–501 (French).
10. Buchholz T, Melzig MF. Medicinal plants traditionally used for treatment of
obesity and diabetes mellitus—Screening for pancreatic lipase and a-amylase
inhibition. Phytother Res. 2016;30:260–6.
11. Choudhary RK, Swarnkar PL. Antioxidant activity of phenolic and
flavonoid compounds in some medicinal plants of India. Nat Prod Res.
2011;25:1101–9.
Tamarindus indica L. 1737

12. Dabur R, Gupta A, Mandal TK, et al. Antimicrobial activity of some Indian
medicinal plants. Afr J Tradit Complement Altern Med. 2007;4:313–8.
13. Das SS, Dey M, Ghosh AK. Determination of anthelmintic activity of the
leaf and bark extract of Tamarindus indica linn. Indian J Pharm Sci.
2011;73:104–7.
14. Dey S, Swarup D, Saxena A, Dan A. In vivo efficacy of tamarind (Tamarindus
indica) fruit extract on experimental fluoride exposure in rats. Res Vet Sci.
2011;91:422–5.
15. Ebifa-Othieno E, Mugisha A, Nyeko P, Kabasa JD. Knowledge, attitudes
and practices in tamarind (Tamarindus indica L.) use and conservation in
Eastern Uganda. J Ethnobiol Ethnomed. 2017;13:5.
16. Escalona-Arranz JC, Péres-Roses R, Urdaneta-Laffita I, et al. Antimicrobial
activity of extracts from Tamarindus indica L. leaves. Pharmacogn Mag.
2010;6:242–7.
17. Escalona-Arranz JC, Perez-Rosés R, Rodríguez-Amado J, et al. Antioxidant
and toxicological evaluation of a Tamarindus indica L. leaf fluid extract.
Nat Prod Res. 2016;30:456–9.
18. Garba M, Yakasai IA, Bakare MT, Munir HY. Effect of Tamarindus indica
L. on the bioavailability of ibuprofen in healthy human volunteers. Eur J
Drug Metab Pharmacokinet. 2003;28:179–84.
19. Ghoneim AI, Eldahshan OA. Antiapoptotic effects of tamarind leaves
against ethanol-induced rat liver injury. J Pharm Pharmacol. 2012;64:430–8.
20. Gupta AR, Dey S, Saini M, Swarup D. Toxic effect of sodium fluoride on
hydroxyproline level and expression of collagen-1 gene in rat bone and its
amelioration by Tamrindus indica L. fruit pulp extract. Interdiscip Toxicol.
2016;9:12–6.
21. Hamidreza H, Heidari Z, Shahraki M, Moudi B. A stereological study of
effects of aqueous extract of Tamarindus indica seeds on pancreatic islets in
streptozotocin-induced diabetic rats. Pak J Pharm Sci. 2010;23:427–34.
22. Havinga RM, Hartl A, Putscher J, et al. Tamarindus indica L. (Fabaceae):
patterns of use in traditional African medicine. J Ethnopharmacol. 2010;127:
573–88.
23. Iftekhar AS, Rayhan I, Quadir MA, et al. Effect of Tamarindus indica fruits
on blood pressure and lipid-profile in human model: an in vivo approach.
Pak J Pharm Sci. 2006;19:125–9.
24. Imam S, Azhar I, Hasan MM, et al. Two triterpenes lupanone and lupeol
isolated and identified from Tamarindus indica Linn. Pak J Pharm Sci.
2007;20:125–7.
25. Iskandar I, Setiawan F, Sasongko LD, Adnyana IK. Six-month chronic
toxicity study of tamarind pulp (Tamarindus indica L.) water extract. Sci
Pharm. 2017;85. pii: E10.
26. Jayanthi V, Anand L, Ashok L, Srinivasan V. Dietary factors in pathogenesis
of gallstone disease in southern India—a hospital-based case-control study.
Indian J Gastroenterol. 2005;24:97–9.
1738 Tamarindus indica L.

27. Jindal V, Dhingra D, Sharma S, et al. Hypolipidemic and weight reducing

activity of the ethanolic extract of Tamarindus indica fruit pulp in cafeteria
diet- and sulpiride-induced obese rats. J Pharmacol Pharmacother. 2011;2:
80–4.
28. Kalra P, Sharma S. Suman, Kumar S. Antiulcer effect of the methanolic
extract of Tamarindus indica seeds in different experimental models. J Pharm
Bioallied Sci. 2011;3:236–41.
29. Khairunnuur FA Jr, Zulkhairi A, Azrina A, et al. Nutritional composition,
in vitro antioxidant activity and Artemia salina L. lethality of pulp and seed
of Tamarindus indica L. extracts. Malays J Nutr. 2009;15:65–75.
30. Khalid S, Shaik Mossadeq WM, Israf DA, et al. In vivo analgesic effect of
aqueous extract of Tamarindus indica L. fruits. Med Princ Pract. 2010;19:
255–9.
31. Khandare AL, Kumar PU, Shanker RG, et al. Additional beneficial effect of
tamarind ingestion over defluoridated water supply to adolescent boys in a
fluorotic area. Nutrition. 2004;20:433–6.
32. Khandare AL, Rao GS, Lakshmaiah N. Effect of tamarind ingestion on
fluoride excretion in humans. Eur J Clin Nutr. 2002;56:82–5.
33. Kobayashi A, Adenan MI, Kajiyama S, et al. A cytotoxic principle of
Tamarindus indica, di-n-butyl malate and the structure-activity relationship
of its analogues. Z Naturforsch. 1996;51:233–42.
34. Kodlady N, Patgiri BJ, Harisha CR, Shukla VJ. Pharmacognostical and
physicochemical analysis of Tamarindus indica Linn. stem. J Ayurveda
Integr Med. 2012;3:6–9.
35. Komutarin T, Azadi S, Butterworth L, et al. Extract of the seed coat of
Tamarindus indica inhibits nitric oxide production by murine macrophages
in vitro and in vivo. Food Chem Toxicol. 2004;42:649–58.
36. Kothari V, Seshadri S. In vitro antibacterial activity in seed extracts of
Manilkara zapota, Anona squamosa, and Tamarindus indica. Biol Res.
2010;43:165–8.
37. Koudouvo K, Karou SD, Ilboudo DP, et al. In vitro antiplasmodial activity
of crude extracts from Togolese medicinal plants. Asian Pac J Trop Med.
2011;4:129–32.
38. Lamien-Meda A, Lamien CE, Compaoré MM, et al. Polyphenol content and
antioxidant activity offourteen wild edible fruits from Burkina Faso. Molecules.
2008;13:581–94.
39. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary
problems and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2:45.
40. Lengani A, Lompo LF, Guissou IP, Nikiema JB. Traditional medicine in
kidney diseases in Burkina Faso. Nephrol Ther. 2010;6:35–9 (French).
41. Lim CY, Mat Junit S, Abdulla MA, Abdul Aziz A. In vivo biochemical and
gene expression analyses of the antioxidant activities and hypocholestero-
laemic properties of Tamarindus indica fruit pulp extract. PLoS ONE. 2013;
8:e70058.
Tamarindus indica L. 1739

42. Lima ZM, da Trindade LS, Santana GC, et al. Effect of Tamarindus indica
L. and Manihot esculenta extracts on antibiotic-resistant bacteria. Pharma-
cognosy Res. 2017;9:195–9.
43. Lopez-Abraham AM, Rojas-Hernandez NM, Jimenez-Misas CA. Extracts
of plants growing in Cuba having antitumor potential, 3. Rev Cubana Farm.
1980;14:35–42.
44. Mahmoud BM, Ali HM, Homeida MM, Bennett JL. Significant reduction in
chloroquine bioavailability following coadministration with the Sudanese
beverages Aradaib, Karkadi and Lemon. J Antimicrob Chemother. 1994;33:
1005–9.
45. Maiti R, Das UK, Ghosh D. Attenuation of hyperglycemia and hyperlipi-
demia in streptozotocin-induced diabetic rats by aqueous extract of seed of
Tamarindus indica. Biol Pharm Bull. 2005;28:1172–6.
46. Maiti R, Jana D, Das UK, Ghosh D. Antidiabetic effect of aqueous extract of
seed of Tamarindus indica in streptozotocin-induced diabetic rats. J Ethno-
pharmacol. 2004;92:85–91.
47. Martinello F, Soares SM, Franco JJ, et al. Hypolipemic and antioxidant
activities from Tamarindus indica L. pulp fruit extract in hypercholes-
terolemic hamsters. Food Chem Toxicol. 2006;44:810–8.
48. Martinello F, Kannen V, Franco JJ, et al. Chemopreventive effects of a
Tamarindus indica fruit extract against colon carcinogenesis depends on the
dietary cholesterol levels in hamsters. Food Chem Toxicol. 2017;107(Pt A):
261–9.
49. Maung KM, Lynn Z. Effects of tamarind (Tamarindus indicus Linn.) seed
extract on Russell’s viper (Daboia russelli siamensis) venom. Trop Biomed.
2012;29:580–7.
50. McKenna GF, Taylor A, Carmichael N. Cancer chemotherapy with plant
extracts. Texas Rept Biol Med. 1958;16:203–14.
51. Meléndez PA, Capriles VA. Antibacterial properties of tropical plants from
Puerto Rico. Phytomedicine. 2006;13:272–6.
52. Mustapha A, Yakasai IA, Aguye IA. Effect of Tamarindus indica L. on the
bioavailability of aspirin in healthy human volunteers. Eur J Drug Metab
Pharmacokinet. 1996;21:223–6.
53. Muthu SE, Nandakumar S, Rao UA. The effect of methanolic extract of
Tamarindus indica Linn. on the growth of clinical isolates of Burkholderia
pseudomallei. Indian J Med Res. 2005;122:525–8.
54. Nahar L, Nasrin F, Zahan R, et al. Comparative study of antidiabetic activity
of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice
with a reference to in vitro antioxidant activity. Pharmacognosy Res. 2014;6:
180–7.
55. Nakchat O, Meksuriyen D, Pongsamart S. Antioxidant and antilipid peroxi-
dation activities of Tamarindus indica seed coat in human fibroblast cells.
Indian J Exp Biol. 2014;52:125–32.
1740 Tamarindus indica L.

56. Nwodo UU, Obiiyeke GE, Chigor VN, Okoh AI. Assessment of
Tamarindus indica extracts for antibacterial activity. Int J Mol Sci. 2011;
12:6385–96.
57. Okello J, Okullo JBL, Eilu G, Nyeko P, Obua J. Mineral composition of
Tamarindus indica Linn. (tamarind) pulp and seeds from different
agro-ecological zones of Uganda. Food Sci Nutr. 2017;5:959–66.
58. Paula FS, Kabeya LM, Kanashiro A, et al. Modulation of human neutrophil
oxidative metabolism and degranulation by extract of Tamarindus indica L.
fruit pulp. Food Chem Toxicol. 2009;47:163–70.
59. Paz M, Gúllon P, Barroso MF, et al. Brazilian fruit pulps as functional foods
and additives: evaluation of bioactive compounds. Food Chem. 2015;172:
462–8.
60. Rai A, Das S, Chamallamudi MR, et al. Evaluation of the aphrodisiac
potential of a chemically characterized aqueous extract of Tamarindus
indica pulp. J Ethnopharmacol. 2018;210:118–24.
61. Ramos A, Visozo A, Piloto J, et al. Screening of antimutagenicity via
antioxidant activity in Cuban medicinal plants. J Ethnopharmacol. 2003;87:
241–6.
62. Ranjan R, Swarup D, Patra RC, Chandra V. Tamarindus indica L. and
Moringa oleifera M. extract administration ameliorates fluoride toxicity in
rabbits. Indian J Exp Biol. 2009;47:900–5.
63. Rasul N, Saleem B, Nawaz R. Preliminary phytochemical screening of four
common plants of family Caesalpiniaceae. Pak J Pharm Sci. 1989;2:55–7.
64. Razali N, Abdul Aziz A, Lim CY, Mat Junit S. Investigation into the effects
of antioxidant-rich extract of Tamarindus indica leaf on antioxidant enzyme
activities, oxidative stress and gene expression profiles in HepG2 cells.
PeerJ. 2015;3:e1292.
65. Ribeiro JA, Serquiz AC, Silva PF, et al. Trypsin inhibitor from Tamarindus
indica L. seeds reduces weight gain and food consumption and increases
plasmatic cholecystokinin levels. Clinics (Sao Paulo). 2015;70:136–43.
66. Rimbau V, Cerdan C, Vila R, Iglesias J. Anti-inflammatory activity of some
extracts from plants used in the traditional medicine of North-African
countries (II). Phytother Res. 1999;13:128–32.
67. Rodriguez Amado JR, Lafourcade Prada A, Escalona Arranz JC, et al.
Antioxidant and hepatoprotective activity of a new tablets formulation from
Tamarindus indica L. Evid Based Complement Alternat Med. 2016;2016:
3918219.
68. Rolando M, Valente C. Establishing the tolerability and performance of
tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of
a clinical study. BMC Ophthalmol. 2007;7:5.
69. Samal PK, Dangi JS. Isolation, preliminary characterization and hepato-
protective activity of polysaccharides from Tamarindus indica L. Carbohydr
Polym. 2014;102:1–7.
Tamarindus indica L. 1741

70. Sandesh P, Velu V, Singh RP. Antioxidant activities of tamarind (Tamarindus

Indica) seed coat extracts using in vitro and in vivo models. J Food Sci
Technol. 2014;51:1965–73.
71. Sasidharan SR, Joseph JA, Anandakumar S, et al. Ameliorative potential of
Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease
in rats. Sci World J. 2014;2014:507197.
72. Shahraki MR, Harati M, Shahraki AR. Prevention of high fructose-induced
metabolic syndrome in male wistar rats by aqueous extract of Tamarindus
indica seed. Acta Med Iran. 2011;49:277–83.
73. Sole SS, Srinivasan BP, Akarte AS. Anti-inflammatory action of Tamarind
seeds reduces hyperglycemic excursion by repressing pancreatic b-cell
damage and normalizing SREBP-1c concentration. Pharm Biol. 2013;51:
350–60.
74. Sole SS, Srinivasan BP. Aqueous extract of tamarind seeds selectively
increases glucose transporter-2, glucose transporter-4, and islets’ intracel-
lular calcium levels and stimulates b-cell proliferation resulting in improved
glucose homeostasis in rats with streptozotocin-induced diabetes mellitus.
Nutr Res. 2012;32:626–36.
75. Souza A, Aka KJ. Spasmogenic effect of the aqueous extract of Tamarindus
indica L. (Caesalpiniaceae) on the contractile activity of guinea-pig taenia
coli. Afr J Tradit Complement Altern Med. 2007;4:261–6.
76. Sreelekha TT, Vijayakumar T, Ankanthil R, et al. Immunomodulatory effects
of a polysaccharide from Tamarindus indica. Anticancer Drugs. 1993;4:
209–12.
77. Sudjaroen Y, Haubner R, Würtele G, et al. Isolation and structure elucidation
of phenolic antioxidants from tamarind (Tamarindus indica L.) seeds and
pericarp. Food Chem Toxicol. 2005;43:1673–82.
78. Sundaram MS, Hemshekhar M, Santhosh MS, et al. Tamarind seed
(Tamarindus indica) extract ameliorates adjuvant-induced arthritis via
regulating the mediators of cartilage/bone degeneration, inflammation and
oxidative stress. Sci Rep. 2015;5:11117.
79. Sundaram MS, Hemshekhar M, Thushara RM, et al. Tamarind seed extract
mitigates the liver oxidative stress in arthritic rats. Food Funct. 2014;5:587–97.
80. Thomas A, Gangadharan R, Amma SV. Anti-inflammatory and analgesic
properties of the leaves of Tamarindus indicus. Anc Sci Life. 1998;18:120–6.
81. Uchenna UE, Shori AB, Baba AS. Tamarindus indica seeds improve
carbohydrate and lipid metabolism: an in vivo study. J Ayurveda Integr
Med. 2017. pii: S0975-9476(16)30508-3.
82. Ullah N, Azam Khan M, Khan T, Ahmad W. Protective potential of
Tamarindus indica against gentamicin-induced nephrotoxicity. Pharm Biol.
2014 (Epub ahead of print).
83. Ushanandini S, Nagaraju S, Harish Kumar K, et al. The antisnake venom
properties of Tamarindus indica (leguminosae) seed extract. Phytother Res.
2006;20:851–8.
1742 Tamarindus indica L.

84. Vasant RA, Narasimhacharya AV. Ameliorative effect of tamarind leaf on

fluoride-induced metabolic alterations. Environ Health Prev Med. 2012;17:
484–93.
85. Yadav N, Sharma S, Sharma KP, et al. Protective role of diet supplements
Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed
Swiss albino mice: histological and biochemical indices. Indian J Exp Biol.
2016;54:44–55.
86. Yadava RN, Yadav S. A new cardenolide uzarigenen-3-O-beta-D-
xylopyranosyl (1!2)-alpha-L-rhamnopyranoside. J Asian Nat Prod Res.
1999;1:245–9.
87. Yerima M, Anuka JA, Salawu OA, Abdu-Aguye I. Antihyperglycaemic
activity of the stem-bark extract of Tamarindus indica L. on experimentally
induced hyperglycaemic and normoglycaemic Wistar rats. Pak J Biol Sci.
2014;17:414–8.
Taraxacum officinale (L.) Weber ex F.H. Wigg
(Asteraceae/Compositae)

(Syns.: T. dens-leonis Desf.; T. vulgare (Lam.) Schrank)

Abstract
A temperate zone perennial weed and a native of Europe, widely distributed in
warmer temperate zones of the Northern Hemisphere, and naturalized through-
out North and South America, southern Africa, New Zealand, Australia, and
India. It has been known since ancient times for its curative properties for
various ailments such as dyspepsia, heartburn, spleen and liver complaints,
hepatitis and anorexia. Avicenna mentioned a kind of wild endive with the name
Tarkhashkun. Taraxacum was popular in India in cases of hepatic congestion
due to or associated with atonic dyspepsia and constipation. The plant was
largely cultivated in India for its roots, which are believed to be diuretic, tonic
and slightly aperient, and are considered chiefly useful for kidney and liver
complaints. In large doses powdered root is a hepatic stimulant, and very
beneficial in obstructions of liver, chronic hepatic and splenic congestion, and
visceral diseases. In Jordanian folk medicine, it is commonly used for the
treatment of panophthalmitis, chronic constipation, diabetes, and to treat male
infertility, and is used as a remedy for anemia, to purify blood, and for immune
modulation in Iranian traditional medicine. In TCM, it is regarded as a nontoxic
herb with exceptional values for its choleretic, diuretic, antirheumatic and
anti-inflammatory properties, while in Korean folk medicine it is used to
improve energy levels and health. In Mexican and North American traditional
medicines and home recipes, it is used for loss of appetite, dyspepsia, flatulence,
gallstones, bile stimulation, as laxative, diuretic, circulatory tonic, skin toner,
blood tonic, digestive tonic, and for the treatment of viral and bacterial infections
and cancer, and lactagogue, and the juice of fresh plant is applied to snakebites.
It is consumed as food in southern Italy, as people from these regions appreciate
wild vegetables that have a strong and bitter taste, and in central Italy it is used
to treat warts. In Netherland, the plant extract was a common remedy for
intermittent fevers and agues. Dandelion contains sesquiterpenes, saponins,

© Springer Nature Switzerland AG 2020 1743

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_180
1744 Taraxacum officinale (L.) Weber ex F.H. Wigg

phenolic compounds, sugars, and flavonoids. Pretreatment of mice with aqueous

and ethanol root extracts offers complete prevention of alcohol- and CCl4-
hepatotoxicity.

Keywords




Amargón Dandelion Dudhal Dughdapheni Kanphal

Kettenblume





Mælkebotte Paardebloem Tarassaco Tarkhashkun

Vernaculars: Urd.: Bathur, Dudal; Hin.: Baran, Dudhal, Dudh-batthal, Dudli,

Kanphal, Shamuke; San.: Dughdapheni, Lootari, Payasvini; Ben.: Pitachumki;
Mal.: Dugddhapheni; Mar.: Bathur; Tel.: Patri; Cze.: Pampeliška lékařská, Pam-
peliška obecná; Dan.: Almindelig mælkebøtte, Mælkebotte; Dut.: Paardebloem;
Eng.: Dandelion, Lion’s tooth, Milk gowan, Swine snout, White wild endive; Fin.:
Voikukka; Fre.: Chicorée, Chopine, Couronne de moine, Dent de lion, Liondent,
Pissenlit, Salade de taupe; Ger.: Frühlingslöwenzahn, Gemeine kuhblume, Gemei-
ner löwenzahn, Gewöhnlicher löwenzahn, Kettenblume, Wiesenlöwenzahn; Hun.:
Gyermekláncfű, Gyógynövények; Ita.: Dente di leone, Pisciacane, Radichiella,
Soffione, Tarassaco, Tarassaco comune; Jap.: Seiyo tanpopo; Nor.: Løvetann; Per.:
Tarkhashkun; Pol.: Mniszek pospolity; Por.: Dente-de-leão, Taraxaco; Rus.: Odu-
vanchik; Spa.: Achicoria amarga, Amargón, Chicoria amarilla, Chinite del campo,
Diente de león, Radicheta, Taraxacón; Swe.: Maskros; Tag.: Dandelion.
Description: A temperate zone perennial weed and a native of Europe, widely
distributed in warmer temperate zones of the Northern Hemisphere [35], and nat-
uralized throughout North and South America, southern Africa, New Zealand,
Australia, and India. An acaulose herb with milky juice; leaves basal, in rosette,
glabrous, base attenuate, runcinate, pinnatified, the segments triangular-lanceolate.
Flowers completely ligular, yellow (April–October). Rhizomes and roots occur as a
mixture of entire and broken fragments measuring up to 16 cm in length and 3 cm
in diameter at the crown, texture waxy, color light gray to dark reddish brown,
irregularly wrinkled longitudinally. The taste is bitter-sweet (Figs. 1, 2 and 3).LXXIX
Actions and Uses: It has been known since ancient times for its curative properties
for various ailments such as dyspepsia, heartburn, spleen and liver complaints,
hepatitis and anorexia [35]. Avicenna mentioned a kind of wild endive with the name
Tarkhashkun. Taraxacum was popular in India in cases of hepatic congestion due to
or associated with atonic dyspepsia and constipation. Experiments revealed it to be a
feeble hepatic stimulant but a powerful diuretic. It was cultivated as an annual crop at
Saharanpur (U.P., India) for the use of the Government sanitary establishments.XL
The plant was largely cultivated in India for its roots, which are believed to be
diuretic, tonic and slightly aperient, and are considered chiefly useful for kidney and
liver complaints [3]. In large doses powdered root is a hepatic stimulant, and very
beneficial in obstructions of liver, chronic hepatic and splenic congestion, and vis-
ceral diseases,CV hepatic inflammation, especially among residents of the tropics;
Taraxacum officinale (L.) Weber ex F.H. Wigg 1745

Fig. 1 Taraxacum officinale, Illustration, Walther Otto Müller (1833–1887), Köhler’s Medizinal-
Pflanzen, WikimediaCommons, https://commons.wikimedia.org/wiki/File:Taraxacum_officinale_-
_K%C3%B6hler%E2%80%93s_Medizinal-Pflanzen-135.jpg

Fig. 2 Taraxacum officinale, Full Bloom, Willow, WikimediaCommons; ShareAlike 2.5 Generic
CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Taraxacum_sect_Ruderalia_020.jpg;
https://creativecommons.org/licenses/by-sa/2.5/deed.en
1746 Taraxacum officinale (L.) Weber ex F.H. Wigg

Fig. 3 Taraxacum officinale, Dandelion Root as sold in the U.S., Prof. Akbar, Original

also, used in dyspepsia, constipation and dropsy.LXXXI It is one of the most com-
monly used plants by women of Udhampur district of Jammu and Kashmir of India
for gynecological disorders, such as dysmenorrhea, menorrhagia, itching, foul smell,
and leucorrhea [2]. In Jordanian folk medicine, it is commonly used for the treatment
of panophthalmitis, chronic constipation, diabetes, and to treat male infertility [39,
40], and is used as a remedy for anemia, to purify blood, and for immune modulation
in Iranian traditional medicine [30]. In TCM, it is regarded as a nontoxic herb with
exceptional values for its choleretic, diuretic, antirheumatic and anti-inflammatory
properties [4], while in Korean folk medicine it is used to improve energy levels and
health [23]. In Mexican and North American traditional medicines and home recipes,
it is used for loss of appetite, dyspepsia, flatulence, gallstones, bile stimulation, as
laxative, diuretic, circulatory tonic, skin toner, blood tonic, digestive tonic, and for
the treatment of viral and bacterial infections and cancer [34], and lactagogue, and
the juice of fresh plant is applied to snakebites.LXXIX It is consumed as food in
southern Italy, as people from these regions appreciate wild vegetables that have a
strong and bitter taste [9], and in central Italy it is used to treat warts [10]. In
Netherland, the plant extract was a common remedy for intermittent fevers and
agues.CXVII ConwayXXVI described it as: the medicinal value of the dandelion was
prized by the Myddfai (a small village in Carmarthenshire, Wales) physicians who
recommended it for the treatment of all kidney complaints, liver troubles and cir-
culatory disorders. It is widely used for treating arthritis as it disperses acid deposits
from the affected joints. To benefit from this herb, the leaves should be eaten raw in
salads, or prepare an infusion. The ‘milk’ from the hollow stalks of this plant may be
applied with good effect to all pimples and spots. In Europe it is approved for use in
GI disorders since Sep. 2007 by the HMPC of the European Medicines Agency.
Taraxacum officinale (L.) Weber ex F.H. Wigg 1747

Phytoconstituents: Dandelion contains sesquiterpenes, saponins, phenolic com-

pounds, sugars, and flavonoids [28], quercetin, luteolin, luteolin-7-O-glucoside,
p-hydroxyphenyl acetic acid, germacranolide acids, chlorogenic acid, chicoric acid,
monocaffeyltartaric acid, scopoletin, aesculetin, aesculin, cichoriin, arnidiol, fara-
diol, caffeic acid, taraxacoside, taraxasterol, and large amounts of the polysaccha-
ride, inulin (24%), and high potassium content [14, 15, 36, 43]. Total phenol
contents of the root (9.4%) are higher than in the leaf (7.9%) [20]. Sitosterol is the
most abundant free sterol, followed by stigmasterol, and campesterol; sitosterol and
cycloartenol ester levels are higher with sunshine and warm temperatures, while
free 4-demethyl sterols are maximal during winter months [42]. Germacrane- and
guaiane-type sesquiterpene lactones: 11b,13-dihydrolactucin, ixerin D and ain-
slioside together with benzyl glucoside, dihydroconiferin, syringin, and dihy-
drosyringin were isolated from the roots [21]. From methanol root extract, 14-O-b-
D-glucosyl-11,13-dihydrotaraxinic acid and 14-O-b-D-glucosyltaraxinic acid were
isolated [19]. Novel peptides with high antimicrobial activity against fungal and
bacterial pathogens were reported from flowers [1]. From hexane and ethyl acetate
extracts of leaves, sesquiterpene lactones (a-santonin, glabellin, arborescin, and
estafiatin), monoterpene (9,10-dimethyltricycle [4.2.1.1(2,5)]decane-9,10-diol),
phytosterol (stigmasta-5,22-dien-3b-ol acetate), terpenes (lupeol acetate, pregn-
5-en-20-one-3b-acetyloxy-17-hydroxy,2-hydroxy-4-methoxy benzaldehyde), and
coumarin (benzofuranone 5,6,7,7-a-tetraaldehyde-4,4,7a-trimethyl) were isolated
[7]. The plant also contains an essential oil, resinous matter, fatty acids, choline,
levulin, and pectin.LXXIX
Pharmacology: Pretreatment of mice with aqueous and ethanol root extracts offers
complete prevention of alcohol- and CCl4-hepatotoxicity [8, 27, 44]. Leaf extracts
were also protective against CCl4- [11], APAP- [6], and sodium dichromate-
induced hepatotoxicity and oxidative stress in rats [13]. Two polysaccharides iso-
lated from the plant also protected from CCl4-induced oxidative stress and
inflammation in rats [31]. Aqueous dried leaf extract pretreatment of rats was
protective against cholecystokinin-induced acute pancreatitis [36]. Ethanol leaf
extract in vitro inhibited porcine pancreatic lipase activity, and a single oral dose of
the extract significantly prevented increase in plasma TGs of corn oil-fed mice [46].
Supplementation of cholesterol-rich diet of rabbits with root and leaves showed a
significant reduction in LDL-C and TGs, and increase in HDL-C in leaf-fed rabbits
[4]. Addition of the plant in diet did not affect parameters of glucose homeostasis in
normal or STZ-diabetic mice [38]. However, aqueous dried leaf extract to mice for
6-weeks improved body weight gain, swimming capacity and blood glucose levels,
and significantly lowered blood lactate and BUN concentrations [17, 23]. Aqueous
leaf and root extracts also exhibited antidepressant-like effects in mice [25], and
hydroalcohol leaf extract treatment of mice for 20-days significantly increased
RBCs, WBCs, lymphocytes and Hb, and significantly decreased the number of
platelets [30].
Ethanol root extract inhibited carrageenan-induced inflammation in rats by 25%
[29], and exhibited antiangiogenic, anti-inflammatory and antinociceptive activities
1748 Taraxacum officinale (L.) Weber ex F.H. Wigg

through inhibition of NO production and COX-2 expression and/or antioxidative

activity [16]. It attenuated LPS-induced acute lung injury in mice, and inhibited
production of inflammatory cytokines TNF-a and IL-6 [26], and the methanol leaf
extract also inhibited LPS-induced production of NO, proinflammatory cytokines, and
PGE2 in mouse macrophage cell line [22]. Aqueous leaf extract decreased growth of
breast cancer cells [37], and strongly inhibited HIV-1 replication and its reverse
transcriptase activity [12]. Hexane leaf extract was highly active against S. aureus and
moderately active against E. coli and K. pneumoniae [7]. Taraxasterol improved liver
function, maintained antioxidant environment, and reduced crystal deposition in
ammonium chloride- and ethylene glycol-induced urolithiasis in rats [45].
Clinical Studies: Hydroethanol fresh leaf extract significantly increased frequency
of urination in the 5-hour period after the first dose, and again for a 5-h period after
the 2nd dose, but the 3rd dose failed further increase, in 17 healthy volunteers [5].
Human A/Es, Allergy and Toxicity: In sensitive individuals, contact with dan-
delion can cause contact dermatitis, erythema multiforme or an anaphylactic
reaction [18, 32]. In general, moderately severe allergic reactions are associated
with dandelion [33]. Chrysanthemum and dandelion are frequently cosensitized
with mugwort in patients with respiratory allergic diseases [24].
Animal Toxicity: Aqueous leaf extract administered to rats for 60-days signifi-
cantly decreased testes weight, sperm count, sperm motility and morphology, and
pregnancy rate [40], and reduced serum testosterone [39].
CYP450 and Potential for Drug-Herb Interactions: Dandelion is reported to
inhibit CYP1A2 [41]. However, coadministration of Taraxacum mongolicum, a
different species of Taraxicum, with ciprofloxacin in rats significantly reduced
plasma concentration of ciprofloxacin by 73% [47]. Due to its high potassium
contents, it may also cause hyperkalemia with potassium-sparing diuretics [34].
Commentary: Hepatoprotective effects of this plant have been validated in animal
studies, and diuretic activity was observed in healthy volunteers. However, RCTs
on most of its traditional uses are still lacking for it to be recommended for clinical
uses.

References
1. Astafieva AA, Rogozhin EA, Odintsova TI, et al. Discovery of novel
antimicrobial peptides with unusual cysteine motifs in dandelion Tarax-
acum officinale Wigg. flowers. Peptides. 2012;36:266–71.
2. Bhatia H, Pal Sharma Y, Manhas RK, Kumar K. Traditional phytoremedies
for the treatment of menstrual disorders in district Udhampur, J&K, India.
J Ethnopharmacol. 2015;160:202–10.
3. Caius JF. The medicinal and poisonous composites of India. J Bombay Nat
Hist Soc. 1940;41:607.
Taraxacum officinale (L.) Weber ex F.H. Wigg 1749

4. Choi UK, Lee OH, Yim JH, et al. Hypolipidemic and antioxidant effects of
dandelion (Taraxacum officinale) root and leaf on cholesterol-fed rabbits.
Int J Mol Sci. 2010;11:67–78.
5. Clare BA, Conroy RS, Spelman K. The diuretic effect in human subjects of
an extract of Taraxacum officinale folium over a single day. J Altern
Complement Med. 2009;15:929–34.
6. Colle D, Arantes LP, Gubert P, et al. Antioxidant properties of Taraxacum
officinale leaf extract are involved in the protective effect against hepa-
toxicity induced by acetaminophen in mice. J Med Food. 2012;15:549–56.
7. Díaz K, Espinoza L, Madrid A, Pizarro L, Chamy R. Isolation and
identification of compounds from bioactive extracts of Taraxacum officinale
Weber ex F. H. Wigg (dandelion) as a potential source of antibacterial
agents. Evid Based Complement Alternat Med. 2018;2018:2706417.
8. Domitrović R, Jakovac H, Romić Z, et al. Antifibrotic activity of Tarax-
acum officinale root in carbon tetrachloride-induced liver damage in mice.
J Ethnopharmacol. 2010;130:569–77.
9. Ghirardini MP, Carli M, del Vecchio N, et al. The importance of a taste.
A comparative study on wild food plant consumption in twenty-one local
communities in Italy. J Ethnobiol Ethnomed. 2007;3:22.
10. Guarrera PM. Traditional phytotherapy in Central Italy (Marche, Abruzzo,
and Latium). Fitoterapia. 2005;76:1–25.
11. Gulfraz M, Ahamd D, Ahmad MS, et al. Effect of leaf extracts of
Taraxacum officinale on CCl4 induced hepatotoxicity in rats, in vivo study.
Pak J Pharm Sci. 2014;27:825–9.
12. Han H, He W, Wang W, Gao B. Inhibitory effect of aqueous dandelion
extract on HIV-1 replication and reverse transcriptase activity. BMC
Complement Altern Med. 2011;11:112.
13. Hfaiedh M, Brahmi D, Zourgui L. Hepatoprotective effect of Taraxacum
officinale leaf extract on sodium dichromate-induced liver injury in rats.
Environ Toxicol. 2016;31:339–49.
14. Hu C, Kitts D. Luteolin and luteolin-7-O-glucoside from dandelion flower
suppress iNOS and COX-2 in RAW264.7 cells. Mol Cell Biochem. 2004;
265:107–13.
15. Hu C, Kitts DD. Antioxidant, prooxidant and cytotoxic activities of solvent
fractionated dandelion (Taraxacum officinale) flower extracts in vitro. J Agric
Food Chem. 2003;52:301–10.
16. Jeon HJ, Kang HJ, Jung HJ, et al. Anti-inflammatory activity of Taraxacum
officinale. J Ethnopharmacol. 2008;115:82–8.
17. Jinchun Z, Jie C. The effects of Taraxacum officinale extracts (TOE) sup-
plementation on physical fatigue in mice. Afr J Tradit Complement Altern
Med. 2011;8:128–33.
1750 Taraxacum officinale (L.) Weber ex F.H. Wigg

18. Jovanović M, Poljacki M, Mimica-Dukić N, et al. Sesquiterpene lactone

mix patch testing supplemented with dandelion extract in patients with
allergic contact dermatitis, atopic dermatitis and nonallergic chronic
inflammatory skin diseases. Contact Dermatitis. 2004;51:101–10.
19. Kashiwada Y, Takanaka K, Tsukada H, et al. Sesquiterpene glucosides from
antileukotriene B4 release fraction of Taraxacum officinale. J Asian Nat
Prod Res. 2001;3:191–7.
20. Kim YC, Rho JH, Kim KT, et al. Phenolic acid contents and ROS
scavenging activity of dandelion (Taraxacum officinale). Korean J Food
Preserv. 2008;15:325–31.
21. Kisiel W, Barszcz B. Further sesquiterpenoids and phenolics from
Taraxacum officinale. Fitoterapia. 2000;71:269–73.
22. Koh YJ, Cha DS, Ko JS, et al. Anti-inflammatory effect of Taraxacum
officinale leaves on lipopolysaccharide-induced inflammatory responses in
RAW 264.7 cells. J Med Food. 2010;13:870–8.
23. Lee BR, Lee JH, An HJ. Effects of Taraxacum officinale on fatigue and
immunological parameters in mice. Molecules. 2012;17:13253–65.
24. Lee YW, Choi SY, Lee EK, et al. Cross-allergenicity of pollens from the
Compositae family: Artemisia vulgaris, Dendranthema grandiflorum, and
Taraxacum officinale. Ann Allergy Asthma Immunol. 2007;99:526–33.
25. Li YC, Shen JD, Li YY, Huang Q. Antidepressant effects of the water
extract from Taraxacum officinale leaves and roots in mice. Pharm Biol.
2014;52:1028–32.
26. Liu L, Xiong H, Ping J, et al. Taraxacum officinale protects against
lipopolysaccharide-induced acute lung injury in mice. J Ethnopharmacol.
2010;130:392–7.
27. Mahesh A, Jeyachandran R, Cindrella L, et al. Hepatocurative potential of
sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride-
induced liver toxicity in mice. Acta Biol Hung. 2010;61:175–90.
28. Martinez M, Poirrier P, Chamy R, et al. Taraxacum officinale and related
species—an ethnopharmacological review and its potential as a commercial
medicinal plant. J Ethnopharmacol. 2015;169:244–62.
29. Mascolo N, Autore G, Capasso F. Biological screening of Italian medicinal
plants for anti-inflammatory activity. Phytother Res. 1987;1:28–31.
30. Modaresi M, Resalatpour N. The effect of Taraxacum officinale hydroal-
coholic extract on blood cells in mice. Adv Hematol. 2012;2012:653412.
31. Park CM, Youn HJ, Chang HK, Song YS. TOP1 and 2, polysaccharides
from Taraxacum officinale, attenuate CCl(4)-induced hepatic damage
through the modulation of NF-kappaB and its regulatory mediators. Food
Chem Toxicol. 2010;48:1255–61.
32. Poljacki M, Jovanović M, Boza P, et al. Is Vojvodina a risk area for contact
weed allergies? Med Pregl. 2005;58:123–6.
33. Posadzki P, Watson LK, Ernst E. Adverse effects of herbal medicines: an
overview of systematic reviews. Clin Med. 2013;13:7–12.
Taraxacum officinale (L.) Weber ex F.H. Wigg 1751

34. Rodriguez-Fragoso L, Reyes-Esparza J, Burchiel SW, et al. Risks and

benefits of commonly used herbal medicines in Mexico. Toxicol Appl
Pharmacol. 2008;227:125–35.
35. Schütz K, Carle R, Schieber A. Taraxacum—a review on its phytochemical
and pharmacological profile. J Ethnopharmacol. 2006;107:313–23.
36. Seo SW, Koo HN, An HJ, et al. Taraxacum officinale protects against
cholecystokinin-induced acute pancreatitis in rats. World J Gastroenterol.
2005;11:597–9.
37. Sigstedt SC, Hooten CJ, Callewaert MC, et al. Evaluation of aqueous
extracts of Taraxacum officinale on growth and invasion of breast and
prostate cancer cells. Int J Oncol. 2008;32:1085–90.
38. Swanston-Flatt SK, Day C, Flatt PR, et al. Glycaemic effects of traditional
European plant treatments for diabetes. Studies in normal and streptozotocin
diabetic mice. Diabetes Res. 1989;10:69–73.
39. Tahtamouni LH, Al-Khateeb RA, Abdellatif RN, et al. Antispermatogenic
activities of Taraxacum officinale whole plant and leaves aqueous extracts.
Vet Res Forum. 2016;7:89–97.
40. Tahtamouni LH, Alqurna NM, Al-Hudhud MY, Al-Hajj HA. Dandelion
(Taraxacum officinale) decreases male rat fertility in vivo. J Ethnopharmacol.
2011;135:102–9.
41. Tsai HH, Lin HW, Lu YH, Chen YL, Mahady GB. A review of potential
harmful interactions between anticoagulant/antiplatelet agents and Chinese
herbal medicines. PLoS ONE. 2013;8:e64255.
42. Westerman L, Roddick JG. Annual variation in sterol levels in leaves of
Taraxacum officinale Weber. Plant Physiol. 1981;68:872–5.
43. Williams CA, Goldstone F, Greenham J. Flavonoids, cinnamic acids and
coumarins from the different tissues and medicinal preparations of
Taraxacum officinale. Phytochemistry. 1996;42:121–7.
44. You Y, Yoo S, Yoon HG, et al. In vitro and in vivo hepatoprotective effects
of the aqueous extract from Taraxacum officinale (dandelion) root against
alcohol-induced oxidative stress. Food Chem Toxicol. 2010;48:1632–7.
45. Yousefi Ghale-Salimi M, Eidi M, Ghaemi N, Khavari-Nejad RA.
Antiurolithiatic effect of the taraxasterol on ethylene glycol-induced kidney
calculi in male rats. Urolithiasis. 2018;46:419–28.
46. Zhang J, Kang MJ, Kim MJ, et al. Pancreatic lipase inhibitory activity of
Taraxacum officinale in vitro and in vivo. Nutr Res Pract. 2008;2:200–3.
47. Zhu M, Wong PY, Li RC. Effects of Taraxacum mongolicum on the bio-
availability and disposition of ciprofloxacin in rats. J Pharm Sci. 1999;88:
632–4.
Taxus baccata L.
(Taxaceae)

(Syns.: T. adpressa Carrière; T. aurea K. Koch)

Abstract
A small to medium-sized evergreen tree, native to southwest Asia, northern Iran,
Europe, and northwest Africa. Yew was known to the Greeks and Romans as a
poisonous plant. Modern research has shown that the leaves and seeds are
poisonous, but not the red pulp surrounding the seeds. Leaves have been
recommended in epilepsy and other spasmodic conditions. In India, Sanskrit
writers described it as carminative, stomachic, expectorant, tonic and astringent;
and useful in phthisis, asthma, bronchitis and vesical catarrh. Powdered leaves
are used with the juice of Adhatoda vasica and honey in cough, asthma and
hemoptysis. Yew played an important role in the mythology of ancient Germans
and Medieval Europeans; they knew about its poisonous nature and made their
arrows poisonous with its juice for hunting, and used the leaves for homicide and
suicide. In Central Italy it was once used during pregnancy, for parturition, nursing
and abortion. In Unani medicine, leaves are described as cardiotonic, nervine and
brain tonic, carminative and stomachic, and used to treat cardiac debility,
palpitation, nervous diseases and gastric debility. Paclitaxel and docetaxel were
the first representatives of a new class of antitumor compounds, called taxoids,
clinically active against breast, ovarian and lung cancers. Paclitaxel, a diterpene
with exceptional anticancer activity, occurs as a very minor component in several
species of Taxus, and is mainly found in the bark but has been reported from roots,
wood, branches, leaves/needles, twigs and seedlings; leaves show the maximum
amount. Four taxoids and five lignans were isolated from the heartwood, and all
lignans except one exhibit significant antiulcerogenic activity. Ethanol extract of
dried powdered bark exhibited potent anti-inflammatory activity, and alcohol leaf
extract significantly protected against histamine and ACh aerosol-induced
bronchospasm in guinea pigs, and significantly decreased total and differential
leukocyte count in sensitized guinea pigs. Methanol leaf and stem extracts
significantly decreased total leukocyte count, lymphocytes and cholesterol level of
mice and rats treated for up to 30-days.

© Springer Nature Switzerland AG 2020 1753

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_181
1754 Taxus baccata L.

Keywords




Eibe English yew Ifreteau Manduparni
Talisfar
Talispatra
Tasso



Teixo Yaygın porsuk Zarnab

Vernaculars: Urd.: Zarnab; Hin.: Barambhi, Talispatra, Thuneer, Thuno, Zarnab,

Zirnubbirmi; San.: Barahmi, Manduparni, Sthauneyaka, Talispatra; Ben.: Bar-
ambhi, Bhirmie, Birmi, Burmie, Sugandh, Talispatra, Thuneer, Zarnab; Ara.:
Zarnab; Dut.: Gewone taxus, Taxus; Eng.: English yew, European yew, Himalayan
yew; Fre.: If, If à baies, If commun, If d’Europe, Ifreteau; Ger.: Beereneibe, Eibe,
Gemeine eibe, Ifenbaum; Ita.: Libo, Tasso, Tasso comune; Per.: Talisfar; Por.:
Teixo; Spa.: Taxo, Tejo, Tejo común, Tejón; Tur.: Yaygın porsuk.
Description: A small to medium-sized evergreen tree, native to southwest Asia,
northern Iran, Europe, and northwest Africa, that grows to a height of 10–20 m with
a large trunk up to 2 m in diameter. Leaves are dark green, flat, 1–4 cm long and
2–3 mm wide, arranged spirally on stem, with the leaf bases twisted to align leaves
in two flat rows on either side of the stem. The drug consists of the small branches
of the tree with their linear-lanceolate, rigid, veinless leaves cut up into short
length (2.5–5 cm). Male flowers are found upon some of the sprigs and resemble
those of the common yew.XL Taxonomically yews should be considered as a single
species because significant intraspecific differences were found between varieties of
T. baccata, but no sufficiently distinctive interspecific differences of taxonomic
value are obvious between the species [10] (Figs. 1, 2 and 3).

Fig. 1 Taxus baccata, 1600 Years Old Yew at Normandy, Roi.dagobert, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:If_Estry.jpg;
https://creativecommons.org/licenses/by-sa/3.0/deed.en
Taxus baccata L. 1755

Fig. 2 Taxus baccata, Irish Yew, Leaves and Arils, Sannse, WikimediaCommons; ShareAlike
3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:English_Yew_close_250.
jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Taxus baccata, Shoots with Mature and Immature Cones, Didier Descouens, Wikimedia-
Commons; ShareAlike 4.0 International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/
File:Taxus_baccata_MHNT.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
1756 Taxus baccata L.

Actions and Uses: Yew was known to the Greeks and Romans as a poisonous
plant. Modern research has shown that the leaves and seeds are poisonous, but not
the red pulp surrounding the seeds. Leaves have been recommended in doses of
60–300 mg in epilepsy and other spasmodic conditions. In India, Sanskrit writers
described it as carminative, stomachic, expectorant, tonic and astringent; and useful
in phthisis, asthma, bronchitis and vesical catarrh. Powdered leaves are used with
the juice of Adhatoda vasica and honey in cough, asthma and hemoptysis. A con-
fection called Talisadya or Talisadi churna is prepared with Talispatra (Abies
Webbiana), black pepper, long pepper, ginger, bamboo-manna, cardamoms, cin-
namon, and sugar, and is used for the above-mentioned conditions. Avicenna
speaks of it as an Indian bark and described the properties as those by Sanskrit
writers; he stated that Galen considered it to be possessed of hot and cold properties
in equal proportions, but that other say it is hot and dry.XL Yew played an important
role in the mythology of ancient Germans and Medieval Europeans; they knew
about its poisonous nature and made their arrows poisonous with its juice for
hunting, and used the leaves for homicide and suicide [47]. In central Italy it was
once used during pregnancy, for parturition, nursing and abortion [27]. In Unani
medicine, leaves (temperament, hot 2° and dry 2°) are described as cardiotonic,
nervine and brain tonic, carminative and stomachic, and used to treat cardiac
debility, palpitation, nervous diseases and gastric debility.LXXVII Khory and
KatrakLXXXI mentioned its uses in asthma, hemoptysis, epilepsy and other spas-
modic affections due to its antispasmodic property, whereas Nadkarni,CV quoting
Chopra, described it as carminative, expectorant, stomachic and tonic. It is a very
poisonous plant due to its taxine content, a mixture of toxic alkaloids.
Phytoconstituents: Paclitaxel (Taxol®) and docetaxel (Taxotere®) were the first
representatives of a new class of antitumor compounds, called taxoids, clinically
active against breast, ovarian and lung cancers. Taxoids are highly complex
diterpenoids of natural origin [32]. Paclitaxel, a diterpene with exceptional anti-
cancer activity, occurs as a very minor component in several species of Taxus, and
is mainly found in the bark but has been reported from roots, wood, branches,
leaves/needles, twigs and seedlings; leaves show the maximum amount [46]. To
obtain 1 kg of paclitaxel requires about 1,000 kg of bark, and several thousand trees
must be cut to get this quantity of bark. Average annual paclitaxel contents of shoots
with dark green needles from Irish Yew (Taxus baccata var. fastigiata) were esti-
mated as 0.0075% [21], and in the bark of trees growing in a homogenous environ-
ment in central Himalaya, average paclitaxel concentration was 0.0558 ± 0.008%
(of dry wt.), and was about 64% higher for male compared to female trees,
and maximum paclitaxel contents were found in the bark samples collected from trees
of >110 years age [35].
Four taxoids: taxusin, baccatin VI, baccatin III and 1b-hydroxybaccatin I, and five
lignans: lariciresinol, 3′-demethylisolariciresinol-9′-hydroxyisopropylether, isolari-
ciresinol, taxiresinol, and 3-demethylisolariciresinol were isolated from the heart-
wood [31], and all lignans except 3′-demethylisolariciresinol-9′-hydroxyisopro-
pylether exhibit significant antiulcerogenic activity [25]. Guo et al. [24] isolated 4 a,7
Taxus baccata L. 1757

b-diacetoxy-2 a,9 a-dibenzoxy-5 b,20-epoxy-10 b, 13 a, 15-trihydroxy-11

(15 ! 1)-abeo-tax-11-ene, taxol, cephalomannine, baccatin III, and taxol C, from
stem bark of T. Baccata. Five other taxoids, among which two were new derivatives, a
taxine B derivative and a xyloside of taxol D were also isolated from stem bark [23].
Biflavones, bilobetin and 4′′′-O-methylamentoflavone [29], taxoids, taxine A, B and
C [33], teixidol [41], p-coumaric acid ester [11], flavonoids: 3-O-rutinosides quer-
cetin, myricetin and kaempferol [30] have been reported from the needles. Essential
oil of the twigs and needles of T. baccata from Serbia showed the presence of 91
compounds, mainly aliphatic alcohols, terpenes, aliphatic hydrocarbons, and ali-
phatic aldehydes [42]. Needles from a series of wild yews from Sardinia, despite
common geographical origin, showed variations in taxoid profile, and several sam-
ples being completely devoid of taxines might explain that most of these plants are
actively grazed by goats without toxicity [3].
Pharmacology: Ethanol extract of dried powdered bark exhibited potent anti-
inflammatory activity [12], and alcohol leaf extract significantly protected against
histamine and ACh aerosol-induced bronchospasm in guinea pigs, and significantly
decreased total and differential leukocyte count in sensitized guinea pigs [37].
Methanol leaf and stem extracts significantly decreased total leukocyte count,
lymphocytes and cholesterol level of mice and rats treated for up to 30-days [40].
Methanol extract of needles significantly inhibited growth of S. aureus [1], the
ethanol extract of heartwood was active against Gram-negative bacteria and fungi
[13], while the biflavone, 10-deacetylbaccatin III selectively inhibited growth of
L. donovani intracellular amastigotes within murine macrophages, and the growth
of promastigotes at higher concentrations [19].
Taxine has calcium channel blocking effect that is about 13X more selective for
heart than for blood vessels and 51X more selective than for the intestine [43].
Paclitaxel, a diterpene, isolated from needles showed highly significant antitumor
activity against human tumors implanted as xenografts in athymic mice [28, 38].
Docetaxel is prepared from a noncytotoxic precursor [6, 17], it promotes assembly
of microtubules and inhibits their depolymerization [17, 18], and is FDA approved
for the treatment of a number of localized and advanced cancers, such as locally
advanced or metastatic breast cancer, head and neck cancer, gastric cancer,
hormone-refractory prostate cancer [5, 50] and nonsmall cell lung cancer [20].
Mechanism of Action: Paclitaxel and docetaxel bind to microtubules, and stabi-
lize them preventing depolymerization, and cell division.
Human A/Es, Allergy and Toxicity: Taxines, an alkaloidal mixture of taxine A
and taxine B, are the active poisonous constituents, and their derivatives have been
implicated in animal and human poisonings [49]. Fatal and nonfatal human poi-
soning due to consumption of leaves decoction for deliberate self-harm have reg-
ularly been reported from around the world for over fifty years [2, 4, 7, 8, 15, 16,
22, 26, 36, 44, 48]. Typical clinical signs of poisoning include dizziness (onset 1 h
after ingestion), nausea, diffuse abdominal pain, unconsciousness, weak breathing,
tachycardia, brief ventricular flutter/fibrillation followed by slow pulse, and finally
1758 Taxus baccata L.

death by respiratory arrest and diastolic cardiac standstill [39]. Patients who survive
are reported to have long-standing excessive diuresis and hypokalemia [14]. Even
breast cancer patient treated with docetaxel reportedly develop allergy and poisoning
due to hypersensitivity [9]. Main substance in harvested yew leaves, stomach content
and cardiac blood of poisoning victim was identified as 3,5-dimethoxyphenol
(3,5-DMP) and was suggested as a marker for yew poisoning [34]. Arens et al. [2]
reported serum and gastric concentrations of 3,5-DMP of 86.9 ng/mL, and taxine B of
80.9 ug/mL, after perimortem of a victim of yew poisoning. Toxicity with paclitaxel
therapy is associated with neutropenia, peripheral neuropathy, and, rarely, car-
diotoxicity; whereas docetaxel toxicity produces myelosuppression and a cumulative
dose fluid retention syndrome [45].
Animal Toxicity: Moderate doses of leaves given to animals produced rapid
breathing and palpitation of the heart, followed by recovery, while larger doses
produced similar effects, followed by death from syncope. Very large doses appear
to produce death by syncope without pain or spasm.XL
Commentary: This plant is now recognized only for the taxanes or toxoids, and
there are no reports of RCTs on any of its traditional medicines uses.

References
1. Afsharzadeh M, Naderinasab M, Tayarani Najaran Z, Barzin M, Emami SA.
In-vitro antimicrobial activities of some Iranian conifers. Iran J Pharm Res.
2013;12:63–74.
2. Arens AM, Anaebere TC, Horng H, Olson K. Fatal Taxus baccata ingestion
with perimortem serum taxine B quantification. Clin Toxicol (Phila). 2016;
54:878–80.
3. Ballero M, Loi MC, van Rozendaal EL, et al. Analysis of pharmaceutically
relevant taxoids in wild yew trees from Sardinia. Fitoterapia. 2003;74:34–9.
4. Baum C, Bohnen S, Sill B, et al. Prolonged resuscitation and cardiogenic
shock after intoxication with European yew (Taxus baccata): complete
recovery after intermittent mechanical circulatory support. Int J Cardiol.
2015;181:176–8.
5. Beer TM, El-Geneidi M, Eilers KM. Docetaxel (taxotere) in the treatment of
prostate cancer. Expert Rev Anticancer Ther. 2003;3:261–8.
6. Bissery MC, Guénard D, Guéritte-Voegelein F, Lavelle F. Experimental
antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue.
Cancer Res. 1991;51:4845–52.
7. Czerwek H, Fischer W. A fatal case of poisoning with Taxus baccata.
Experiments on demonstration of Taxus alkaloid in the cadaver organs. Arch
Toxikol. 1960;18:88–92 (German).
8. Dahlqvist M, Venzin R, König S, et al. Haemodialysis in Taxus baccata
poisoning: a case report. QJM. 2012;105:359–61.
Taxus baccata L. 1759

9. de Vos FY, van Laarhoven HM. Taxus baccata allergy in a breast cancer
patient. Neth J Med. 2012;70:249–50.
10. Dempsey D, Hook I. Yew (taxus) species—chemical and morphological
variations. Pharm Biol. 2000;38:274–80.
11. Dittrich P, Danböck T. Isolation and characterization of a novel p-coumaric
acid ester of myoinositol from needles of Taxus baccata. Plant Physiol.
1977;59:279–81.
12. Dutta S, Mariappan G, Sarkar D, Sarkar P. Assessment of anti-inflammatory
activity of Taxus baccata Linn. bark extract. Anc Sci Life. 2010;29:19–21.
13. Erdemoglu N, Sener B. Antimicrobial activity of the heartwood of Taxus
baccata. Fitoterapia. 2001;72:59–61.
14. Feldman R, Chrobak J, Liberek Z, Szajewski J. 4 cases of poisoning with
the extract of yew (Taxus baccata) needles. Pol Arch Med Wewn. 1988;
79:26–9 (Polish).
15. Frohne D, Pribilla O. Fatal poisoning with Taxus baccata. Arch Toxikol.
1965;21:150–62 (German).
16. Fuchs J, Rauber-Lüthy C, Kupferschmidt H, et al. Acute plant poisoning:
analysis of clinical features and circumstances of exposure. Clin Toxicol
(Phila). 2011;49:671–80.
17. Fumoleau P, Seidman AD, Trudeau ME, et al. Docetaxel: a new active
agent in the therapy of metastatic breast cancer. Expert Opin Investig Drugs.
1997;6:1853–65.
18. Fumoleau P, Chevallier B, Kerbrat P, et al. Current status of taxotere
(docetaxel) as a new treatment in breast cancer. Breast Cancer Res Treat.
1995;33:39–46.
19. Georgopoulou K, Smirlis D, Bisti S, et al. In vitro activity of 10-deacetylbaccatin
III against Leishmania donovani promastigotes and intracellular amastigotes.
Planta Med. 2007;73:1081–8.
20. Georgoulias V. Docetaxel (taxotere) in the treatment of nonsmall cell lung
cancer. Curr Med Chem. 2002;9:869–77.
21. Griffin J, Hook I. Taxol content of Irish yews. Planta Med. 1996;62:370–2.
22. Grobosch T, Schwarze B, Felgenhauer N, et al. Eight cases of fatal and
nonfatal poisoning with Taxus baccata. Forensic Sci Int. 2013;227:118–26.
23. Guo Y, Diallo B, Jaziri M, et al. Two new taxoids from the stem bark of
Taxus baccata. J Nat Prod. 1995;58:1906–12.
24. Guo Y, Vanhaelen-Fastré R, Diallo B, et al. Immunoenzymatic methods
applied to the search for bioactive taxoids from Taxus baccata. J Nat Prod.
1995;58:1015–23.
25. Gurbuz I, Erdemoglu N, Yesilada E, Sener B. Antiulcerogenic lignans from
Taxus baccata L. Z Naturforsch. 2004;59:233–6.
26. Hurard J. Taxus baccata poisoning. Homeopath Fr. 1952;40:568 (Undeter-
mined Language).
27. Idolo M, Motti R, Mazzoleni S. Ethnobotanical and phytomedicinal
knowledge in a long-history protected area, the Abruzzo, Lazio and Molise
National Park (Italian Apennines). J Ethnopharmacol. 2010;127:379–95.
1760 Taxus baccata L.

28. Jacrot M, Riondel J, Picot F, et al. Action of taxol on human tumors

transplanted in athymic mice. C R Seances Acad Sci III. 1983;297:597–600
(French).
29. Krauze-Baranowska M, Wiwart M. Antifungal activity of biflavones from
Taxus baccata and Ginkgo biloba. Z Naturforsch. 2003;58:65–9.
30. Krauze-Baranowska M. Flavonoids from the genus Taxus. Z Naturforsch.
2004;59:43–7.
31. Küpeli E, Erdemoğlu N, Yeşilada E, Sener B. Anti-inflammatory and
antinociceptive activity of taxoids and lignans from the heartwood of Taxus
baccata L. J Ethnopharmacol. 2003;89:265–70.
32. Lavelle F, Combeau C, Commerçon A. Taxoids: structural and experimental
properties. Bull Cancer. 1995;82:249–64 (French).
33. Lythgoe B. The alkaloids. In: Manske RHF, editor. Chemistry and physiology,
vol. 10. New York: Academic Press; 1968. p. 597–626.
34. Musshoff F, Jacob B, Fowinkel C, Daldrup T. Suicidal yew leave ingestion—
phloroglucindimethylether (3,5-dimethoxyphenol) as a marker for poisoning
from Taxus baccata. Int J Legal Med. 1993;106:45–50.
35. Nadeem M, Rikhari HC, Kumar A, et al. Taxol content in the bark of
Himalayan Yew in relation to tree age and sex. Phytochemistry. 2002;60:
627–31.
36. Panzeri C, Bacis G, Ferri F, et al. Extracorporeal life support in a severe
Taxus baccata poisoning. Clin Toxicol (Phila). 2010;48:463–5.
37. Patel P, Patel K, Gandhi T. Evaluation of effect of Taxus baccata leaves
extract on bronchoconstriction and bronchial hyperreactivity in experimen-
tal animals. J Young Pharm. 2011;3:41–7.
38. Riondel J, Jacrot M, Picot F, et al. Therapeutic response to taxol of six
human tumors xenografted into nude mice. Cancer Chemother Pharmacol.
1986;17:137–42.
39. Schulte T. Lethal intoxication with leaves of the yew tree (Taxus baccata)
(author’s transl). Arch Toxicol. 1975;34:153–8 (German).
40. Shanker K, Pathak NK, Trivedi VP, et al. An evaluation of toxicity of Taxus
baccata Linn. (Talispatra) in experimental animals. J Ethnopharmacol.
2002;79:69–73.
41. Soto J, Fuentes M, Castedo L. Teixidol, an abeotaxane from European yew,
Taxus baccata. Phytochemistry. 1996;43:313–4.
42. Stefanović M, Ristić M, Popović Z, et al. Chemical composition and
interpopulation variability of essential oils of Taxus baccata L. from Serbia.
Chem Biodivers. 2016;13:943–53.
43. Tekol Y, Göğüsten B. Comparative determination of the cardioselectivity of
taxine and verapamil in the isolated aorta, atrium and jejunum preparations
of rabbits. Arzneimittelforschung. 1999;49:673–8.
44. Tranca S, Petrisor CL. A fatal case of Taxus poisoning. Clujul Med. 2013;
86:279–81.
Taxus baccata L. 1761

45. Vaishampayan U, Parchment RE, Jasti BR, Hussain M. Taxanes: an

overview of the pharmacokinetics and pharmacodynamics. Urology. 1999;
54(6A Suppl):22–9.
46. Vidensek N, Lim P, Campbell A, Carlson C. Taxol content in bark, wood,
root, leaf, twig, and seedling from several Taxus species. J Nat Prod.
1990;53:1609–10.
47. Wehner F, Gawatz O. Suicidal yew poisoning—from Caesar to today—or
suicide instructions on the internet. Arch Kriminol. 2003;211:19–26 (German).
48. Willaert W, Claessens P, Vankelecom B, Vanderheyden M. Intoxication
with Taxus baccata: cardiac arrhythmias following yew leaves ingestion.
Pacing Clin Electrophysiol. 2002;25(4 Pt 1):511–2.
49. Wilson CR, Sauer J, Hooser SB. Taxines: a review of the mechanism and
toxicity of yew (Taxus spp.) alkaloids. Toxicon. 2001;39:175–85.
50. Wolff JM. Significance of docetaxel in the chemotherapy of hormone-
refractory prostate cancer. Onkologie. 2003;26 Suppl 7:37–40 (German).
Tephrosia purpurea (L.) Pers.
(Fabaceae/Leguminosae)

(Syns.: T. hamiltonii Gamb.; T. piscatoria Ait.)

Abstract
A profusely branched, herbaceous perennial herb, native to India, China, Malaysia,
the Philippines, and Australia. Indian authors have described it as deobstruent and
diuretic, and the aerial parts used as a remedy for cough, tightness in the chest,
bilious febrile attacks, and obstruction of the liver, spleen and kidneys, as blood
purifier for boils, pimples and other skin disorders; the root is bitter and used for
dyspepsia and diarrhea. It is also described as antibacterial, and choleretic/
hepatotonic. In Unani medicine it is considered blood purifier and beneficial for
bleeding piles and other disorders due to putrified blood. In Ayurveda, it is used
to treat splenomegaly, cirrhosis, cough and cold, and abdominal swellings; is
attributed the properties of stomachic, emmenagogue, anthelmintic, alexiteric,
antipyretic, alterative, diuretic, resolve kidney stones, and useful in the treatment
of leprosy, ulcers, asthma, tumors, diseases of the liver, spleen, heart and blood.
Flavonoids including quercetin, rutin, an isoflavone, a chalcone, (+)-tephrorins A
and B and (+)-tephrosone, tephropurpulin A, isoglabratephrin and glabratephrin,
an aromatic ester, a sesquiterpene, lupeol, and b-sitosterol have been isolated from
the whole plant. Flavonoids contents vary seasonally, being highest in samples
collected during August, the flowering season, and leaves exhibit the highest
antioxidant activity compared to root, stem and seeds. Oral ethanol seeds extract
significantly lowered hyperglycemia in diabetic rats and showed antilipidperox-
idative effects, with increased activities of enzymatic antioxidants and levels of
nonenzymatic antioxidants, comparable to glibenclamide. Aqueous seed, and
leaf extracts also demonstrably reduced blood glucose and increased plasma
insulin, normalized lipids and lipoproteins profile, and prevented increase in BP,
creatinine, cardiac enzymes, reduced HR and cardiac hypertrophy in diabetic rats.
Bronchodilatory, hepatoprotective and nephroprotective effects against arsenic-
and gentamicin-nephrotoxicity, and wound healing potential of ethanol leaf
extract, have been reported.

© Springer Nature Switzerland AG 2020 1763

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_182
1764 Tephrosia purpurea (L.) Pers.

Keywords




Balbalatong Chilapate Fish poison Hui mao dou Kozhinnila

Matapez




Purple goat’s rue Sarphoka Sarphunkha Shapunkha

Vernaculars: Urd.: Sarphoka; Hin.: Sarphonk, Sarphunkha, Sarpunkha; San.:

Puleehashtree, Sarapunkha, Shapunkha, Sharaphunkkha; Ben.: Bon-nil, Bon-nil-
gachh; Mal.: Kazlunnilla, Kolinil, Kozhinnila; Mar.: Sarpakha, Unhali; Tam.: Klinji,
Kolluk-kay-velai; Tel.: Surpunkh, Vempali; Chi.: Hui mao dou; Eng.: Fish poison,
Purple goat’s rue, Purple tephrosia; Spa.: Chilapate, Matapez; Tag.: Balatong-pula,
Balbalatong.
Description: It is a profusely branched, suberect, slender, herbaceous perennial
herb, native to India, China, Malaysia, the Philippines, and Australia. Stems are
smooth or finely downy, 30–60 cm in height; the leaves are odd-pinnate, 7.5–15 cm
long, with 13–21 leaflets which are narrow and oblanceolate. The recemes are long,
all leaf-opposed, and 7.5–15 cm in length. Lower flowers are fascicled; the corolla
is red (the photographs show the flowers to be purplish) and the calyx is covered
with silky hair, has narrow teeth, and is as long as the tube. Pods are 3.5–5 cm long
and slightly recurved and contain 6–10 seeds.CXVII Dymock et al.,XL described it as
a shrubby, erect, much-branched plant about 60 cm high; leaves pinnated; leaflets
5–9 pairs with an odd one, the largest 2.5 cm long, and 7 mm broad, cuneate
oblong; racemes peduncled, longer than the leaves; legumes slightly compressed,
spreading, linear falcate, obtuse with a short point; seeds 4 to 6 in each pod, small,
kidney-shaped; testa mottled; cotyledons yellow. All parts of the plant are slightly
bitter (Figs. 1 and 2).
Actions and Uses: Kirtikar and BasuLXXXIV described it as deobstruent and diuretic,
and the aerial parts used as a remedy for cough, tightness in the chest, bilious febrile

Fig. 1 Tephrosia purpurea, Plant with Flowers, Johnjsingh, WikimediaCommons; ShareAlike 4.0
International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:TephrosiaPurpurea.jpg; https://
creativecommons.org/licenses/by-sa/4.0/deed.en
Tephrosia purpurea (L.) Pers. 1765

Fig. 2 Tephrosia purpurea, Wild Indigo, J.M. Garg, WikimediaCommons; ShareAlike 4.0
International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Tephrosia_purpurea_
(Wild_Indigo)_in_Narshapur,_AP_W_IMG_0765.jpg; https://creativecommons.org/licenses/by-
sa/4.0/deed.en

attacks, and obstruction of the liver, spleen and kidneys, as blood purifier for boils,
pimples and other skin disorders; the root is bitter and used for dyspepsia and diarrhea.
It is also described as antibacterial, and choleretic/hepatotonic.CXXVI In Unani
medicine it (temperament, hot and moist, but NadkarniCV mentioned it hot 3° and dry
3°) is considered blood purifier and beneficial for bleeding piles and other disorders
due to putrified blood,LXXVII Mir Mohammad Hussain recommends the powder of
two parts of it with one part of Cannabis indica leaves, as a remedy for bleeding piles;
given with black pepper he says it is diuretic and useful for gonorrhea.XL,LXXXI In
Ayurveda, it is used to treat splenomegaly, cirrhosis, cough and cold, and abdominal
swellings [28]; is attributed the properties of stomachic, emmenagogue, anthelmintic,
alexiteric, antipyretic, alterative, diuretic, resolve kidney stones, and useful in the
treatment of leprosy, ulcers, asthma, tumors, diseases of the liver, spleen, heart and
blood. A root decoction is given in dyspepsia and chronic diarrhea, and with pepper
powder added is given in bilious febrile attacks, enlargement and obstruction of liver,
spleen and kidneys.CV
Phytoconstituents: Phytochemical screening showed the presence of semiglabrin,
pongamole, lanceolatins A and B, rutin, lupeol, and b-sitosterol [28]. Flavonoids
including quercetin [24], rutin [4], an isoflavone, 7,4′-dihydroxy-3′,5′-dimethox-
yisoflavone and a chalcone, (+)-tephropurpurin [6], (+)-tephrorins A and B and
(+)-tephrosone [5, 36], tephropurpulin A, isoglabratephrin and glabratephrin [15],
an aromatic ester, a sesquiterpene [20], and (+)-purpurin, dioxypterocarpan, (−)-
maackiain, (−)-3-hydroxy-4-methoxy-8,9-methylenedioxypterocarpan, (−)-medi-
carpin, an isoflavone, isoglabratephrin B and a 1,2-ethanedione benzofuran deriva-
tive, purpdione B [7] have been isolated from the whole plant. Flavonoids contents
1766 Tephrosia purpurea (L.) Pers.

vary seasonally, being highest in samples collected during August, the flowering
season [29], and leaves exhibit the highest antioxidant activity compared to root, stem
and seeds [26].
Pharmacology: Oral ethanol seed extract significantly lowered hyperglycemia in
STZ-diabetic rats and showed antilipidperoxidative effects, with increased activities
of enzymatic antioxidants and levels of nonenzymatic antioxidants, comparable to
glibenclamide [32]. Aqueous seed [33], and leaf extracts also significantly reduced
blood glucose and increased plasma insulin, normalized lipids and lipoproteins
profile [31], and prevented increase in BP, creatinine, cardiac enzymes, reduced HR
and cardiac hypertrophy [3] in STZ-diabetic rats. Ethanol leaf extract ameliorated
selenite-induced [2], and STZ-diabetic cataracts in rats [4]. As antioxidant, it pre-
vented NDEA and potassium bromate-induced renal oxidative stress and carcino-
genesis in rats [21]. Ethanol root extract [9], and aqueous and ethanol leaf extracts
[30] also show in vitro antioxidant activity. Methanol shoot extract exhibited
in vitro anti-inflammatory and XO inhibitory activities [25]. Ethanol leaf extract
demonstrated cytotoxic activities against HepG2 cells [27] and colorectal cancer
cells [26]. Several fractions show in vitro anticancer activity against human MCF 7
cells [14]. Topical application one hour prior to croton oil application significantly
protected against DMBA-induced skin tumor in mice [34]. Oral administration of the
extract prevented LPO, suppressed tumor burden, and promoted enzymatic and
nonenzymatic antioxidant defenses against NDEA-induced hepatocarcinogenesis [16].
Methanol leaf extract demonstrated activity against clinical isolates and standard
strains of H. pylori, including metronidazole-resistant strains [8], and significant
diuretic [1], spasmolytic, vasorelaxant and bronchodilatory [18], and antidiarrheal
[19] activities. Bronchodilatory [35], hepatoprotective [12, 22] and nephroprotec-
tive effects against arsenic-[13] and gentamicin-nephrotoxicity [17], and wound
healing potential of ethanol leaf extract [23], have been reported. Ethanolic extract
also inhibits degranulation of mast cells by a mechanism other than membrane
stabilization [11], and a flavonoid fraction modulate both cell-mediated and the
humoral immunity [10].
Mechanism of Action: Anticataract effect is suggested to be due to the presence of
rutin and quercetin, and their significant aldose reductase enzyme inhibitory and
antioxidant activities [4]. Anticancer activity against HepG2 cells was reported due
to apoptosis mediated cell death [27]. A 5% w/w ointment of ethyl acetate fraction
was more effective than isolated flavonoids in wound healing which may be due to
synergistic interactions between the flavonoids and other constituents [24].
Human A/Es, Allergy and Toxicity: No known A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It is usually described as a blood purifier, which is a nonspecific,
ill-defined term from scientific perspective. Since there are no published clinical
studies, some of its purported medicinal benefits need to be investigated thoroughly
both pharmacologically and in RCTs.
Tephrosia purpurea (L.) Pers. 1767

References
1. Ashokkumar D, Narayana TV, Vidyasagar, et al. Exploration of diuretic
potential and electrolyte excretion of Tephrosia purpurea (Fabaceae) in rats.
J Diet Suppl. 2012;9:9–18.
2. Bhadada SV, Bhadada VJ, Goyal RK. Preventive effect of Tephrosia
purpurea on selenite-induced experimental cataract. Curr Eye Res. 2016;41:
222–31.
3. Bhadada SV, Goyal RK. Effect of aqueous extract of Tephrosia purpurea
on cardiovascular complications and cataract associated with streptozotocin-
induced diabetes in rats. Indian J Pharm Sci. 2015;77:522–9.
4. Bhadada SV, Vyas VK, Goyal RK. Protective effect of Tephrosia purpurea
in diabetic cataract through aldose reductase inhibitory activity. Biomed
Pharmacother. 2016;83:221–8.
5. Chang LC, Chávez D, Song LL, et al. Absolute configuration of novel bioactive
flavonoids from Tephrosia purpurea. Org Lett. 2000;2:515–8.
6. Chang LC, Gerhäuser C, Song L, et al. Activity-guided isolation of
constituents of Tephrosia purpurea with the potential to induce the phase II
enzyme, quinone reductase. J Nat Prod. 1997;60:869–73.
7. Chen YN, Peng Y, Gao CH, et al. Two new secondary metabolites from
Tephrosia purpurea. Nat Prod Commun. 2015;10:921–2.
8. Chinniah A, Mohapatra S, Goswami S, et al. On the potential of Tephrosia
purpurea as anti-Helicobacter pylori agent. J Ethnopharmacol. 2009;124:
642–5.
9. Choudhary GP. In vitro antioxidant studies of the ethanolic extract of
Tephrosia purpurea L. Anc Sci Life. 2007;27:26–30.
10. Damre AS, Gokhale AB, Phadke AS, et al. Studies on the immunomod-
ulatory activity of flavonoidal fraction of Tephrosia purpurea. Fitoterapia.
2003;74:257–61.
11. Gokhale AB, Dikshit VJ, Damre AS, et al. Influence of ethanolic extract of
Tephrosia purpurea Linn. on mast cells and erythrocytes membrane integrity.
Indian J Exp Biol. 2000;38:837–40.
12. Gora RH, Baxla SL, Kerketta P, Patnaik S, Roy BK. Hepatoprotective
activity of Tephrosia purpurea against arsenic induced toxicity in rats.
Indian J Pharmacol. 2014;46:197–200.
13. Gora RH, Kerketta P, Baxla SL, et al. Ameliorative effect of Tephrosia
purpurea in arsenic-induced nephrotoxicity in rats. Toxicol Int. 2014;21:
78–83.
14. Gulecha V, Sivakuma T. Anticancer activity of Tephrosia purpurea and Ficus
religiosa using MCF 7 cell lines. Asian Pac J Trop Med. 2011;4:526–9.
15. Hegazy ME, Abd el-Razek MH, Nagashima F, et al. Rare prenylated
flavonoids from Tephrosia purpurea. Phytochemistry. 2009;70:1474–7.
16. Hussain T, Siddiqui HH, Fareed S, et al. Chemopreventive evaluation of
Tephrosia purpurea against N-nitrosodiethylamine-induced hepatocarcino-
genesis in Wistar rats. J Pharm Pharmacol. 2012;64:1195–205.
1768 Tephrosia purpurea (L.) Pers.

17. Jain A, Nahata A, Singhai AK. Effect of Tephrosia purpurea (L.) Pers.
leaves on gentamicin-induced nephrotoxicity in rats. Sci Pharm. 2013;81:
1071–87.
18. Janbaz KH, Jan A, Qadir MI, Gilani AH. Spasmolytic, bronchodilator and
vasorelaxant activity of methanolic extract of Tephrosia purpurea. Acta Pol
Pharm. 2013;70:261–9.
19. Janbaz KH, Qadir MI, Jan A, Gilani AH. Antidiarrheal activity of
methanolic extract of Tephrosia purpurea. Acta Pol Pharm. 2013;70:345–7.
20. Khalafalah AK, Yousef AH, Esmail AM, et al. Chemical constituents of
Tephrosia purpurea. Pharmacognosy Res. 2010;2:72–5.
21. Khan N, Sharma S, Alam A, et al. Tephrosia purpurea ameliorates
N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress
and toxicity in Wistar rats. Pharmacol Toxicol. 2001;88:294–9.
22. Khatri A, Garg A, Agrawal SS. Evaluation of hepatoprotective activity of
aerial parts of Tephrosia purpurea L. and stem bark of Tecomella undulata.
J Ethnopharmacol. 2009;122:1–5.
23. Lodhi S, Pawar RS, Jain AP, Singhai AK. Wound healing potential of
Tephrosia purpurea (Linn.) Pers. in rats. J Ethnopharmacol. 2006;108:
204–10.
24. Lodhi S, Jain A, Jain AP, Pawar RS, Singhai AK. Effects of flavonoids from
Martynia annua and Tephrosia purpurea on cutaneous wound healing.
Avicenna J Phytomed. 2016;6:578–91.
25. Nile SH, Khobragade CN. In vitro anti-inflammatory and xanthine oxidase
inhibitory activity of Tephrosia purpurea shoot extract. Nat Prod Commun.
2011;6:1437–40.
26. Padmapriya R, Ashwini S, Raveendran R. In vitro antioxidant and cytotoxic
potential of different parts of Tephrosia purpurea. Res Pharm Sci. 2017;
12:31–7.
27. Padmapriya R, Gayathri L, Ronsard L, Akbarsha MA, Raveendran R. In
vitro antiproliferative effect of Tephrosia purpurea on human hepatocellular
carcinoma cells. Pharmacogn Mag. 2017;13:S16–21.
28. Palbag S, Dey BK, Singh NK. Ethnopharmacology, phytochemistry and
pharmacology of Tephrosia purpurea. Chin J Nat Med. 2014;12:1–7.
29. Pandey MM, Khatoon S, Rastogi S, Rawat AK. Determination of
flavonoids, polyphenols and antioxidant activity of Tephrosia purpurea: a
seasonal study. J Integr Med. 2016;14:447–55.
30. Patel A, Patel A, Patel A, Patel NM. Determination of polyphenols and free
radical scavenging activity of Tephrosia purpurea Linn. leaves (Legumi-
nosae). Pharmacognosy Res. 2010;2:152–8.
31. Pavana P, Manoharan S, Renju GL, Sethupathy S. Antihyperglycemic and
antihyperlipidemic effects of Tephrosia purpurea leaf extract in streptozo-
tocin induced diabetic rats. J Environ Biol. 2007;28:833–7.
32. Pavana P, Sethupathy S, Manoharan S. Antihyperglycemic and antilipid-
peroxidative effects of Tephrosia purpurea seed extract in streptozotocin
induced diabetic rats. Indian J Clin Biochem. 2007;22:77–83.
Tephrosia purpurea (L.) Pers. 1769

33. Pavana P, Sethupathy S, Santha K, Manoharan S. Effects of Tephrosia

purpurea aqueous seed extract on blood glucose and antioxidant enzyme
activities in streptozotocin induced diabetic rats. Afr J Tradit Complement
Altern Med. 2008;6:78–86.
34. Saleem M, Ahmed S, Alam A, Sultana S. Tephrosia purpurea alleviates
phorbol ester-induced tumor promotion response in murine skin. Pharmacol
Res. 2001;43:135–44.
35. Soni KK, Khare ML, Saxena RC. Spasmolytic activity of a herbal drug
isolated from Tephrosia purpurea in guinea pigs. Anc Sci Life. 2004;23:
59–65.
36. Sumbul S, Ahmad MA, Mohd A, Mohd A. Role of phenolic compounds in
peptic ulcer: an overview. J Pharm Bioallied Sci. 2011;3:361–7.
Terminalia bellirica (Gaertn.) Roxb.
(Combretaceae)

(Syns.: T. angustifolia Blanco, nonJacq.; T. attenuata Edgew.; T. edulis Blanco;

T. moluccana Roxb.; T. punctata Roth; Myrobalanus bellirica Gart.; M. laurinoides
(Teijsm. & Binn.) Kuntze)

Abstract
A large deciduous tree common on plains and lower hills of India, and southeast
Asia. It is usually antidiarrheal but may act as a mild laxative. In the Middle
East, it is used to stimulate appetite; and in Egypt it is known as Sananīr, and
employed as styptic, antidiarrheal and purgative. Ibn Jazlah considered it good
for strengthening the stomach, and eyesight, and to prevent lacrimation. Al-Kindi
used it in a prescription for depression, and for the treatment of stomach and liver
diseases. Fruits are tonic to brain and stomach, liquify matter, act as astringent,
expel black-bile and yellow-bile, dry up secretions, and are useful in headache,
piles, and chronic diarrhea. Fruit is used for the treatment of diarrhea, dropsy,
piles, leprosy, and spleen enlargement. Dried roasted pulp is used as lozenges in
sore throat, hoarseness of voice, and dyspepsia. Major active compounds present
in fruits are phenols and flavonoids; fruits are a rich source of gallic acid and
ellagic acid, contain significant amounts of K and Mn. Its seed oil has been
explored as an alternate bioresource for biodiesel synthesis, as its fatty acids
composition shows predominance of oleic acid glycerides along with linoleic and
palmitic glycerides. Supplementation of atherogenic diet with powdered fruits
ameliorated diet-induced increase in body weight, serum TC, TGs, thickening of
aortic walls and shrinkage of aortic lumen of rabbits, and decreased liver and
heart lipids. Hot-water extract also prevented obesity, insulin resistance, and
hyperlipidemia in spontaneously obese diabetic mice. Treatment of patients
suffering from acute and chronic diarrhea and dysentery with a bioactive fraction
for a maximum period of 14-days resulted in significant improvement in 11 out
of 12 patients. Seven patients positive for amoeba cyst, or E. coli at the start of
the treatment became negative at the end of treatment.

Keywords


Bahera Baherabaum Baheri

Balela
Balelaj
Balisáyin
Barro
Beleric


myrobalan Bibhitaki Jaha

© Springer Nature Switzerland AG 2020 1771
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_183
1772 Terminalia bellirica (Gaertn.) Roxb.

Vernaculars: Urd.: Bahera, Balela; Hin.: Baheda, Bahera, Bhaira, Bharla, Bib-
hitaki, Buhura, Karak phal, Sagona; San.: Aksha, Anilaghnaka, Bahira, Bahuvirya,
Bhuta-vasah, Bibhitakah, Bibhitaki, Kalidruma, Kaligrvamah, Karshapalah, Vib-
hīdaka, Vibhitaki, Vipitakaha; Ben.: Baherâ, Baheri, Bhairah, Bohorâ, Boyra,
Buhuru; Guj.: Baheda; Mal.: Adamarutha, Taanni, Taannikka, Tanni, Tannikai,
Thaanni, Thani, Thannymathan, Tusham; Mar.: Beda, Behadâ, Bhenda, Bhulvaso,
Bibhītaka, Kalidruma, Karsba-phal, Vehala; Tam.: Chattu-elupa, Kattu-elupay,
Tamkai, Tandi-tonda, Tani, Tanikoi, Tankrikkai, Tanrik-kay, Thaandrikkai, Thani,
Vallaimurdu; Tel.: Bahadraha, Bhutavasamu, Karshaphalamu, Kattu-olupoe, Tadi,
Tandi, Tandra-kayi, Tani; Ara.: Balelaj, Sananīr (Egypt); Eng.: Bastard myrobalan,
Bedda-nuts, Beleric myrobalan; Ger.: Baherabaum, Belerische myrobalane; Jap.:
Taaminaria beririka; Maly.: Jaha, Jaha kebo; Nep.: Barro; Per.: Balela; Rus.:
Terminaliia belericheskaia; Tag.: Balisáyin, Basal, Dalinson, Kalamai, Kalúmpit;
Tha.: Samo phi phek.
Description: A large deciduous tree common on plains and lower hills of India,
and southeast Asia; leaves are about 15 cm long and crowded toward the ends of
the branches; nuts or fruits of the tree are rounded but with five flatter sides. Fruit is
externally brown, slightly wrinkled with a small stalk at the bottom. The rind of the
fruit becomes yellow after drying and tastes bitter and astringent. Two varieties, one
with globular fruits, and the other larger and ovate in shape have been described.
The stone (kernel) is hard, oval in shape, of a pale-yellow color, and containing an
almond-like seed (Figs. 1 and 2).LXXXI
Actions and Uses: Avicenna quoted by Ibn-BaitarLXIX said: being astringent, it is
useful in dilatation and moistness of stomach, and strengthens its function. It is
usually antidiarrheal but may act as a mild laxative. In the Middle East, it is used to
stimulate appetite; and in Egypt it is known as Sananīr, and employed as styptic,
antidiarrheal and purgative.LIII Ibn Jazlah considered it good for strengthening the

Fig. 1 Terminalia bellirica, Tree, Vengolis, WikimediaCommons, https://commons.wikimedia.

org/wiki/File:Terminalia_bellirica_04390.jpg
Terminalia bellirica (Gaertn.) Roxb. 1773

Fig. 2 Terminalia bellirica, Dried Fruits, Prof. Akbar, Original

stomach, and eyesight, and to prevent lacrimation. Al-Kindi used it in a prescription

for depression, and for the treatment of stomach and liver diseases.LIII In Unani
medicine, it (temperament, cold 1° and dry 2°) is regarded as astringent, stomachic,
antidiarrheal, brain tonic and to improve eyesight, and can act both to cause laxation
and to stop diarrhea.LXXVII Fruits are tonic to brain and stomach, liquify matter, act
as astringent, expel black-bile and yellow-bile, dry up secretions, and are useful
in headache, piles, and chronic diarrhea.CV Fruit is used for the treatment of diar-
rhea, dropsy, leprosy, and spleen enlargement. Dried roasted pulp is used as
lozenges in sore throat, hoarseness of voice, and dyspepsia.LXXXI The kernels are
intoxicating and are eaten by the Lodha people of the Indian subcontinent for their
mind-altering qualities [18]. In the Philippines, it is used in lotions for humid
herpetism or eczema.CXVII GuerreroLVI reported the fruits used in eyewashes in
similar manner as the fruits of Acacia farnesiana.
Phytoconstituents: Major active compounds present in fruits are phenols and
flavonoids [3]; fruits are a rich source of gallic acid and ellagic acid [5], contain
significant amounts of K and Mn [32]. Its seed oil (yield 31% dry weight basis) has
been explored as an alternate bioresource for biodiesel synthesis, as its fatty acids
composition shows predominance of oleic acid glycerides along with linoleic and
palmitic glycerides [24]. Phytochemical screening of the aqueous extract showed
the presence of flavonoids, hydrolysable tannins, saponin and terpenes [20].
Pharmacology: Supplementation of atherogenic diet with powdered fruits ame-
liorated diet-induced increase in body weight, serum TC, TGs, thickening of aortic
walls and shrinkage of aortic lumen of rabbits [31], and decreased liver and heart
lipids [26, 27]. Hot-water extract also prevented obesity, insulin resistance, and
hyperlipidemia in spontaneously obese type-2 diabetic mice [17]. Oral adminis-
tration of 75% methanol [21, 22], and ethanol [13] fruit extracts significantly
1774 Terminalia bellirica (Gaertn.) Roxb.

prevented alloxan-induced hyperglycemia and oxidative stress in rats and expressed

antioxidant and free radicals’ scavenging activities in vitro [9]. Methanol extract
also suppressed ethanol- and aspirin-induced peptic ulcers, reduced gastric free
acidity, total acidity, ulcer index, protein and pepsin content and increased mucus
content in pylorus ligated rats [11]. Ethanol fruit extract showed significant antioxi-
dant activity [29], and antioxidant activity of acetone fruit extract was reportedly
stronger than a-tocopherol, which was correlated to total phenolic and flavonoid
contents [23, 25], and protected against CCl4-oxidative stress and hepatotoxicity in
rats [15]. Aqueous and ethanol fruit extracts, administered for 10 successive days,
exhibited significant antidepressant-like effects in male Swiss mice, similar to imi-
pramine and fluoxetine, without affecting locomotor activity [6].
Aqueous fruit extract significantly inhibited growth of S. aureus, B. subtilis,
E. coli, P. vulgaris and E. aerogenes [8]. Alcohol extract was reportedly more active
antibacterial than the aqueous extract against several pathogenic and opportunistic
microorganisms [1], with a broad-spectrum activity against clinical isolates of
b-lactamase producing MRSA and MSSA; the extracts also showed in vitro syn-
ergistic effect with tetracycline [3]. Ethanol and aqueous extracts were also signif-
icantly active against S. typhimurium, being bactericidal at high concentrations and
bacteriostatic at low concentrations. Pretreatment of mice with aqueous extract
protected against lethal doses of S. typhimurium [16], and aqueous extract exhibited
broad-spectrum vibriocidal activity against various strains of V. cholera [28], and
exhibited highly significant in vitro and in vivo antiplasmodial activity [20].
Hydroalcohol extract was also active against MDR uropathogenic bacteria [4], and
hot-water and methanol fruit extracts inhibited in vitro retroviral reverse transcrip-
tase [7, 30].
Clinical Studies: Treatment of patients suffering from acute and chronic diarrhea
and dysentery with a bioactive fraction (150 mg three times a day) for a maximum
period of 14-days resulted in significant improvement in 11 out of 12 patients. Seven
patients positive for amoeba cyst, or E. coli at the start of the treatment became
negative at the end of treatment. No side effects of any nature were observed [19].
Mechanism of Action: Hypoglycemic effect is due to increased insulin secretion,
enhanced insulin action and inhibition of both protein glycation and starch diges-
tion [14]. Gallic acid was primarily responsible for the inhibition of pancreatic
lipase activity that suppressed absorption of meal-derived lipids [17], and was also
identified as the active constituent that protected against CCl4-hepatotoxicity in rats
[2, 10].
Human A/Es, Allergy and Toxicity: Fruits are very safe in humans, with no
known A/Es, allergy or toxicity.
Animal Toxicity: Aqueous-acetone fruit extract was nonlethal and nontoxic to
female Wistar albino rats in a single oral dose of up to 2,000 mg/kg [12].
Terminalia bellirica (Gaertn.) Roxb. 1775

Commentary: It is a very commonly used fruit both in Unani and Ayurveda, as

antioxidant and to strengthen digestive function, and in cases of chronic diarrhea and
dysentery, especially in combination with black myrobalan and emblic myrobalan
(called Triphala). Blinded RCTs would be helpful to establish its effectiveness in
chronic diarrhea and other gastrointestinal diseases.

References
1. Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal
plants for their antimicrobial properties. J Ethnopharmacol. 1998;62:183–93.
2. Anand KK, Singh B, Saxena AK, et al. 3,4,5-Trihydroxy benzoic acid
(gallic acid), the hepatoprotective principle in the fruits of Terminalia
belerica-bioassay guided activity. Pharmacol Res. 1997;36:315–21.
3. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant
extracts on clinical isolates of beta-lactamase producing methicillin resistant
Staphylococcus aureus. J Basic Microbiol. 2005;45:106–14.
4. Bag A, Bhattacharyya SK, Pal NK. Antibacterial potential of hydroalcoholic
extracts of triphala components against multidrug-resistant uropathogenic
bacteria—a preliminary report. Indian J Exp Biol. 2013;51:709–14.
5. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and
antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr.
2005;56:287–91.
6. Dhingra D, Valecha R. Evaluation of antidepressant-like activity of aqueous
and ethanolic extracts of Terminalia bellirica Roxb. fruits in mice. Indian J
Exp Biol. 2007;45:610–6.
7. El-Mekkawy S, Meselhy MR, Kusumoto IT, et al. Inhibitory effects of
Egyptian folk medicines on human immunodeficiency virus (HIV) reverse
transcriptase. Chem Pharm Bull (Tokyo). 1995;43:641–8.
8. Ghosh A, Das BK, Roy A, et al. Antibacterial activity of some medicinal
plant extracts. Nat Med (Tokyo). 2008;62:259–62.
9. Hazra B, Sarkar R, Biswas S, Mandal N. Comparative study of the antioxidant
and reactive oxygen species scavenging properties in the extracts of the fruits
of Terminalia chebula, Terminalia belerica and Emblica officinalis. BMC
Complement Altern Med. 2010;10:20.
10. Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica
Roxb. and gallic acid against carbon tetrachloride induced damage in albino
rats. J Ethnopharmacol. 2007;109:214–8.
11. Jawanjal H, Rajput MS, Agrawal P, Dange V. Pharmacological evaluation
of fruits of Terminalia belerica Roxb. for antiulcer activity. J Complement
Integr Med. 2012;9:Article 9.
12. Jayesh K, Helen LR, Vysakh A, Binil E, Latha MS. In vivo toxicity evaluation
of aqueous acetone extract of Terminalia bellirica (Gaertn.) Roxb. fruit. Regul
Toxicol Pharmacol. 2017;86:349–55.
1776 Terminalia bellirica (Gaertn.) Roxb.

13. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of

hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
14. Kasabri V, Flatt PR, Abdel-Wahab YH. Terminalia bellirica stimulates the
secretion and action of insulin and inhibits starch digestion and protein
glycation in vitro. Br J Nutr. 2010;103:212–7.
15. Kuriakose J, Lal Raisa H, A V, Eldhose B, M S L. Terminalia bellirica
(Gaertn.) Roxb. fruit mitigates CCl4 induced oxidative stress and hepato-
toxicity in rats. Biomed Pharmacother. 2017;93:327–33.
16. Madani A, Jain SK. Anti-Salmonella activity of Terminalia belerica:
in vitro and in vivo studies. Indian J Exp Biol. 2008;46:817–21.
17. Makihara H, Shimada T, Machida E, et al. Preventive effect of Terminalia
bellirica on obesity and metabolic disorders in spontaneously obese type 2
diabetic model mice. J Nat Med. 2012;66:459–67.
18. Pal DC, Jain SK. Notes on Lodha medicine in Midnapur District, West
Bengal, India. Eco Bot. 1989;43:464–70.
19. Patwardhan B, Bhutani KK, Patki PS, et al. Clinical evaluation of Terminalia
belerica in diarrhoea. Anc Sci Life. 1990;10:94–7.
20. Pinmai K, Hiriote W, Soonthornchareonnon N, et al. In vitro and in vivo
antiplasmodial activity and cytotoxicity of water extracts of Phyllanthus
emblica, Terminalia chebula, and Terminalia bellerica. J Med Assoc Thai.
2010;93 Suppl 7:S120–6.
21. Sabu MC, Kuttan R. Antidiabetic activity of medicinal plants and its
relationship with their antioxidant property. J Ethnopharmacol. 2002;81:
155–60.
22. Sabu MC, Kuttan R. Antidiabetic and antioxidant activity of Terminalia
belerica. Roxb. Indian J Exp Biol. 2009;47:270–5.
23. Saleem A, Ahotupa M, Pihlaja K. Total phenolics concentration and antiox-
idant potential of extracts of medicinal plants of Pakistan. Z Naturforsch C.
2001;56:973–8.
24. Sarin R, Sharma M, Khan AA. Terminalia belerica Roxb. seed oil: a
potential biodiesel resource. Bioresour Technol. 2010;101:1380–4.
25. Sarkar R, Mandal N. Hydroalcoholic extracts of Indian medicinal plants can
help in amelioration from oxidative stress through antioxidant properties.
J Complement Integr Med. 2012;9:Article 7.
26. Shaila HP, Udupa AL, Udupa SL. Preventive actions of Terminalia belerica
in experimentally induced atherosclerosis. Int J Cardiol. 1995;49:101–6.
27. Shaila HP, Udupa SL, Udupa AL. Hypolipidemic activity of three indigenous
drugs in experimentally induced atherosclerosis. Int J Cardiol. 1998;67:
119–24.
28. Sharma A, Patel VK, Chaturvedi AN. Vibriocidal activity of certain
medicinal plants used in Indian folklore medicine by tribals of Mahakoshal
region of central India. Indian J Pharmacol. 2009;41:129–33.
Terminalia bellirica (Gaertn.) Roxb. 1777

29. Soubir T. Antioxidant activities of some local bangladeshi fruits (Artocar-

pus heterophyllus, Annona squamosa, Terminalia bellirica, Syzygium sama-
rangense, Averrhoa carambola and Olea europa). Sheng Wu Gong Cheng
Xue Bao. 2007;23:257–61.
30. Suthienkul O, Miyazaki O, Chulasiri M, Kositanont U, Oishi K. Retroviral
reverse transcriptase inhibitory activity in Thai herbs and spices: screening
with Moloney murine leukemia viral enzyme. Southeast Asian J Trop Med
Public Health. 1993;24:751–5.
31. Thakur CP, Thakur B, Singh S, et al. The Ayurvedic medicines Haritaki,
Amala and Bahira reduce cholesterol-induced atherosclerosis in rabbits.
Int J Cardiol. 1988;21:167–75.
32. Waheed S, Fatima I. Instrumental neutron activation analysis of Emblica
officinalis, Terminalia belerica and Terminalia chebula for trace element
efficacy and safety. Appl Radiat Isot. 2013;77:139–44.
Terminalia chebula Retz.
(Combretaceae)

(Syn.: T. zelanica Van Heurck & Müll. Arg.)

Abstract
The tree is a native of India, Bangladesh, Myanmar, Nepal, Pakistan, Sri Lanka,
Cambodia, Indonesia, Malaysia, Vietnam, and southwestern China. Fruits are
highly astringent, more intensely in the large intestine than in the small intestine or
stomach; used in diarrhea, enterorrhagia, metrorrhagia and leucorrhea. The ripe
fruit is chiefly used as purgative, and is considered to remove bile, phlegm, and
adust bile; it should be combined with aromatics, such as fennel seeds, caraway,
etc. Arabs say: “Halilaj is in the stomach like an intelligent housewife who is a
good manager of the house.” The unripe fruit (Halileh-i-hindi) is most valued on
account of its astringent and aperient properties and is a useful medicine in
dysentery and diarrhea. The best way of using myrobalans as purgative is to make
an infusion or decoction of fruit pulp with the addition of a pinch of caraway seeds
and a little honey or sugar. Unani physicians consider it tonic to brain and vision,
and use it in the treatment of diarrhea, piles, paralysis, headache, epilepsy, loss of
memory, and to purge yellow-bile. The unripe fruit is a brain and gastrointestinal
tonic, blood purifier and also black-bile remover; hence used for mental
sluggishness and to enhance mental acuity, and in the treatment of melancholia,
leprosy and piles. The infusion of almost mature fruit is stronger in effects than its
powder or decoction. This drug can be used with benefit in people who may be
suffering from ill effects of reckless eating and drinking. In Ayurveda, Bala-harade
is successfully used in chronic diarrhea and dysentery, flatulence, vomiting,
hiccup, colic, and enlarged spleen and liver. In Chinese medicine, it was first
recorded in Tang Pen Tsao (659 A.D.), called Ho-tzu, and ascribed with astringent,
expectorant, hemostatic, and antitussive properties, and used for prolonged
diarrhea, night sweats, nocturnal emissions, and leucorrhea. It is known as the
“king” of Mongolian and Tibetan medicines, and used in the treatment of asthma,
sore throat, vomiting, hiccough, diarrhea, dysentery, bleeding piles, ulcers, gout,
heart and bladder diseases. Fruits contain chebulic acid, fatty oil, tannins, and
triterpenoids.

© Springer Nature Switzerland AG 2020 1779

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_184
1780 Terminalia chebula Retz.

Keywords




Black myrobalan Halilah siah Halilah kabli Harada Haritaki

He zi





Ijas-Hindi Mirobolano Myrobolanenbaum Myrobolanier

Vernaculars: Urd.: Halilah kabuli, Halilah siah, Halilah zard; Hin.: Bal-har, Bari
harh, Harad, Harada, Harh, Kale-har, Pile-hard; San.: Abhaya, Amritha, Bhishak-
priya, Haimavathi, Haritaki, Jivanthi, Pathya, Shakra-srishta, Suddha, Vayastha,
Vijaya; Ben.: Harītakī, Hora, Horitoky; Mal.: Kadukka, Kadukkai; Mar.: Bala-
hirade, Hirada; Tam.: Kaddukkai (mature), Kaduk-kay-pinji (fruit), Pinchu-kaddukai
(immature); Tel.: Karaka, Karakkaya, Pinda-karakkay (fruit); Ara.: Halilaj asfar,
Halilaj aswad, Halilaj-hindi, Ijas-hindi; Bur.: Pangah; Chi.: 诃 子, He zi, Ho-tzu;
Eng.: Black myrobalan, Chebulic myrobalan, Indian gall-nut, Yellow myrobalan;
Fre.: Badamier chebule, Myrobolanier; Ger.: Chebulische myrobalane, Myrobola-
nenbaum, Rispiger myrobalanenbaum; Ind.: Manja lawai; Ita.: Mirobolano; Jap.:
Haritaki, Mirobaran no ki; Maly.: Buah kaduka; Nep.: Harro, Thuulo harro; Per.:
Halilah-zangi, Halilaj, Halilah-e-zarda, Halileh; Rus.: Kharitaki; Sin.: Aralu; Spa.:
Mirobolano; Tag.: Apunga, Bangias, Hinabuad, Hinabuan, Komintana; Tha.: Kot
phung pla.
Description: A native of India, Bangladesh, Myanmar, Nepal, Pakistan, Sri Lanka,
Cambodia, Indonesia, Malaysia, Vietnam, and southwestern China, the tree reaches
a height of 25 m or more, and a trunk diameter of 80 cm; leaves alternate, ovate,
5–15 cm long, pointed at the tip and somewhat rounded at the base, with fairly long
stalks. Flowers are somewhat yellow and fragrant and are borne in large numbers in
compound inflorescence. Fruit is yellow, elliptical with five longitudinal ridges, and
about 2–4 cm long and 1–2.5 cm wide.CXVII In Unani medicine, the unripe fruit,
when small in size, is called Halilah siah; when ripened and turning yellow, it is
called Halilah zard; and after growing bigger in size, it is known as Halilah kabli
(Big Halilah). All these three stages of the same fruit are endowed with different
actions, both qualitatively and quantitatively; very large fruits are particularly
valuable. Myrobalans were known to Arabs and through them to Greeks, they
described five kinds of them. These are the same fruit at different stages of maturity.
The author of Makhzan-al-Adwiya described this classification as: the very young
about the size of cumin seeds are called Halileh-i-zira; when about the size of a
grain of barley, Halileh-i-jawi; when of the size of a raisin, Halileh-i-zangi or
Halileh-i-hindi; when half-mature and yellowish, Halileh-i-chini; when further
advanced, Halileh-i-asfar; and lastly, when quite mature, Halileh-i-kabuli. Mature
myrobalan is of an ovoid form, from 25 to 38 mm long, sometimes tapering
towards the lower extremity, obscurely 5 or 6-sided, more or less furrowed lon-
gitudinally, covered with a smooth yellowish-brown epidermis, within which is an
astringent pulp, enclosing a large rough bony, one-celled endocarp. The unripe
fruits are shriveled, black, ovoid, brittle bodies, from 8 to 19 mm in length, having a
shining fracture and an astringent taste (Figs. 1 and 2).XL
Terminalia chebula Retz. 1781

Fig. 1 Terminalia chebula, Fruit on the Tree, Zhangzhugang, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Terminalia_chebula_-_
South_China_Botanical_Garden_2013.11.02_11-07-25.jpg; https://creativecommons.org/licenses/
by-sa/3.0/deed.en

Fig. 2 Terminalia chebula, Dried Fruits, Prof. Akbar, Original

Actions and Uses: Fruits are highly astringent, more intensely in the large intestine
than in the small intestine or stomach; used in diarrhea, enterorrhagia, metrorrhagia
and leucorrhea.LXXIX The ripe fruit (temperament, cold 1° and dry 2°) is chiefly used
as purgative, and is considered to remove bile, phlegm, and adust bile; it should be
combined with aromatics, such as fennel seeds, caraway, etc. Arabs say: “Halilaj is
1782 Terminalia chebula Retz.

in the stomach like an intelligent housewife who is a good manager of the house.”
The unripe fruit (Halileh-i-hindi) is most valued on account of its astringent and
aperient properties and is a useful medicine in dysentery and diarrhea; it should also
be used with aromatics. The best way of administering myrobalans as a purgative is
to make an infusion or decoction of from 7 to 14 g of fruit pulp with the addition of a
pinch of caraway seeds and a little honey or sugar.XL Unani physicians consider it
tonic to brain and vision, and use it in the treatment of diarrhea, piles, paralysis,
headache, epilepsy, loss of memory, and to purge Safra (yellow-bile). The unripe
fruit or Halilah siah is a brain and gastrointestinal tonic, blood purifier and black-bile
remover (Mushil-e-sauda); hence used for mental sluggishness and to enhance
mental acuity,LXXVII and in the treatment of melancholia, leprosy and piles.CV The
infusion of almost mature fruit (Halileh-i-asfar or Halileh-zard) is stronger in effects
than its powder or decoction.LXXVII This drug can be used with benefit in people who
may be suffering from ill effects of reckless eating and drinking.LXXXI In Ayurveda,
Bala-harade is successfully used in chronic diarrhea and dysentery, flatulence,
vomiting, hiccup, colic, and enlarged spleen and liver.CV It is one of the main
ingredients of a polyherbal Ayurvedic medicine, that is highly efficaciously and
widely used for gastrointestinal and rejuvenative treatment [67]. In Chinese medi-
cine, it was first recorded in Tang Pen Tsao (659 A.D.), called Ho-tzu, and ascribed
with astringent, expectorant, hemostatic, and antitussive properties, and used for
prolonged diarrhea, night sweats, nocturnal emissions, and leucorrhea.LXVI It is
known as the “king” of Mongolian and Tibetan medicines [9, 113], and traditionally
used in the treatment of asthma, sore throat, vomiting, hiccough, diarrhea, dysentery,
bleeding piles, ulcers, gout, heart and bladder diseases [9]. It is one of the most
commonly used plants by a tribal community for gastrointestinal disorders in
Bangladesh [33], and by Kani tribals in Tirunelveli hills of western Ghats of India
[8], and for kidney and urinary disorders by the Amchis of cold desert of Ladakh
[12]. Tribal practitioners of the Marakh sect of the Garos indigenous community of
Bangladesh also use it for the treatment of diabetes [76]. In Samahni valley of
Kashmir, it is traditionally used to cure chronic ulcers, caries, tooth pain, and heart
problems [29]. In the Philippines, the fruit decoction was used to treat thrush and
obstinate diarrhea.LVI
Phytoconstituents: Phytochemical screening of aqueous fruit extract revealed the
presence of flavonoids, hydrolysable tannins, saponin and terpenes [70]. Fruits
contain 3.5% chebulic acid, 37% fatty oil, and 27–39% tannin;LXXIX they are a rich
source of ellagic acid [11], and oleanane-type triterpenoids [108]. Aqueous fruit
extract affords the greatest yield of total phenolic and tannin contents [17]. Hydro-
lysable tannins isolated from fruits are gallic acid, chebulic acid, punicalagin,
chebulanin, corilagin, neochebulinic acid, ellagic acid, chebulagic acid, chebumeinin
A and B, chebulinic acid and 1,2,3,4,6-penta-O-galloyl-b-D-glucose [3, 26, 32].
Chebulagic acid is a dual inhibitor of COX-2 and 5-LOX [79], a potent a-glucosidase
inhibitor [22], and protective of rat hepatocytes against oxidative stress [48]. It also
contains significant amounts of chlorine and zinc [107]. Two types of T. chebula
fruits are encountered in the Indian markets. Fruits derived from T. chebula. var.
Terminalia chebula Retz. 1783

parviflora are round-shaped, compared to the oval-shaped fruits from T. chebula.

Fruits derived from T. chebula. var. parviflora contain higher concentrations of
chebulinic acid and 1,2,3,4,6-penta-O-galloyl-b-D-glucose but lower levels of
chebulagic acid [32].
Pharmacology: It is one of the most potent antioxidant plants. Various extracts
showed in vitro antioxidant [11, 16, 18, 27, 42, 46, 49, 54, 60, 61, 68, 83, 86],
free radical scavenging [27, 37, 38, 55] and LPO inhibiting activities [82]. The
fruit extract exhibits immunostimulant and adaptogenic properties [81], anti-
inflammatory activity in carrageenan-induced inflammation [10], reduced joint
swelling in both formaldehyde-induced and Freund’s adjuvant-induced arthritis in
rats, and reduced serum TNF-a level and synovial expression of TNF-R1, IL-6 and
IL-1b [62]. The extract also exhibits strong inhibitory activity on secretion of IL-8
from H. pylori-infected gastric epithelial cells [112], and ethanol extract produced
analgesic response to acute and chronic pain stimuli in mice [35]. Chebulagic acid
suppresses onset and progression of collagen-induced arthritis in mice [51]. Ethanol
extract pretreatment in a dose of 1 g/kg prevented PTZ and MES-induced seizures
in 66–83% rats, but offered complete protection with subtherapeutic doses of val-
proate and phenytoin [44]. Ethyl acetate fruit extract also exhibited potent AChE
and BChE inhibitory activities comparable to donepezil [77].
Supplementation of atherogenic diet of rabbits and mice with powdered fruits,
ameliorated diet-induced increase in body weight, serum TC, TGs, thickening of
aortic walls and shrinkage of aortic lumen [78, 103]. Oral fruit extracts significantly
lower FBG in diabetic rats [40, 59, 96], inhibit a-glucosidase, reduce HbA1c and
decrease serum insulin levels [58]. A commercial preparation, and a methanol bark
extract also significantly reduced TC and TGs, and increased HDL-C of hyper-
lipidemic rats [56, 80]. Ethanol fruit extract pretreatment ameliorated effect of
isoproterenol on LPO and significantly decreased activity of myocardial marker
enzymes [98], and maintained heart mitochondrial ultrastucture [99]. Aqueous fruit
extract protected against t-BHP-acute liver injury in mice, improved antioxidant
status and reduced levels of proinflammatory cytokines [19]. Ethanol fruit extract
protected against antituberculosis drugs (rifampicin + isoniazid + pyrazinamide)-
induced hepatotoxicity [102], APAP-induced hepatoxicity and nephrotoxicity [25],
and cisplatin-nephrotoxicity in rats [34]. Methanol extract produced iron chelating
effects in mice and protected against iron overload-hepatotoxicity [85]. Aqueous
extract demonstrated prokinetic activity, comparable to metoclopromide [101],
antioxidant, anti-inflammatory, immunomodulatory, and free radical scavenging and
healing effects in acetic acid-induced colitis in rats [23]. Conversely, Sheng et al. [92]
reported significant antidiarrheal activity of aqueous extract and its ethyl acetate
fraction, that also protected mice against castor oil-induced morphological alterations
in small intestine and the liver. Alcohol extract shows healing activity against gastric
ulceration in rats [13, 91].
Fruit extracts show potent and wide-spectrum antimicrobial activity, including
against Salmonella spp., Shigella spp., and S. mutans [2, 30, 31, 50, 64, 69, 75,
105]. Ethanol fruit extract exhibited broad-spectrum antibacterial activity against
1784 Terminalia chebula Retz.

b-lactamase producing MRSA and MSSA [6], synergistic interaction with tetra-
cycline, chloramphenicol and ciprofloxacin against S. aureus and/or E. coli [5], and
exhibited activity against K. pneumonae, P. aeruginosa, and E. faecalis; acetone
extract was also active against E. coli [90]. Gallic acid and its ethyl ester were
identified as the active antimicrobial agents against MRSA [88]. Ethanedioic acid, a
compound isolated from fruit’s butanol fraction, showed strong and moderate
inhibitory activity against C. perfringens and E. coli, respectively [39]. Methanol
and aqueous fruit extracts also significantly inhibited HIV-1-reverse transcriptase
enzyme [21]. Aqueous extract had stronger anti-HSV-1 activity in combination
with acyclovir in vitro and in vivo [45], and inhibited replication of human CMV
and murine CMV (MCMV) in vitro, and significantly suppressed MCMV yields in
lungs of immunosuppressed mice infected with MCMV [94, 111]. Ethanol extract,
chebulagic and chebulinic acids have higher direct antiviral activity against HSV-2
and efficacy to inhibit virus attachment and penetration to host cells as compared to
acyclovir [36]. Aqueous extract also exhibited in vitro and in vivo antiplasmodial
activity [70], and had better inhibitory effects than ethanol extract on three der-
matophytes (Trichophyton spp.) and three yeasts (Candida spp.); tannins were
suspected for its antidermatophytic effects, but chebulinic acid was found ineffec-
tive [106]. Methanol leaf extract showed highly significant antibacterial activity
against S. aureus, B. subtilis, E. coli, P. vulgaris and E. aerogenes, comparable to
fluoroquinolones and aminoglycosides [2, 24], and methanol extract of ripe seeds
showed most potent activity against Clotrimazole-resistant C. albicans [14].
The fruit extract decreased cell viability, inhibited cell proliferation, and induced
cell death in several malignant cell lines [84], reduced chemically-induced car-
cinogenesis and oxidative stress in animals [73, 74]. Chebulagic acid increased
in vitro accumulation of doxorubicin and enhanced its cytotoxicity of hepatocellular
carcinoma cell line (HepG2) by 20 folds [1]. Administration of fruit extract to male
rats for 60-days caused significant decrease in motility, count and increase in
morphological abnormalities of epididymal spermatozoa, and reduction in fertility
(*100%), and highly significant inhibition of hyaluronidase inhibitory activity of
human spermatozoa and rat caudal epididymal spermatozoa in vitro [97]. Topical
application of ethanol extract and tannins extracted from fruits promote skin wound
healing in rats [52, 63], and exhibit antimicrobial activity against S. aureus and
K. pneumoniae [52]. Topical application of an alcohol extract of leaves produced
similar wound healing and antimicrobial effects [100]. Ethanol fruit extract also
protected skin against photodamage [109], and a formulation containing concen-
trated extract had rejuvenating effect on human skin [4].
Clinical Studies: Aqueous fruit extract markedly lowered serum uric acid levels of
individuals with hyperuricemia, in a double-blind RCT of 24-weeks [104]. In
healthy volunteers, standardized aqueous fruit extract significantly increased pain
threshold and pain tolerance time compared to placebo in double-blinded RCTs
[43, 71]. In a double-blind RCT of healthy but overweight U.S. males and females,
12-weeks treatment with a patented standardized aqueous extract (AyuFlex®)
improved symptoms of joint health and function [53]. Mouth rinse of aqueous
Terminalia chebula Retz. 1785

extracts showed anticaries effect by inhibiting oral bacterial growth of S. mutans

[15, 65, 66, 89].
Mechanism of Action: Hydrolyzable tannins, isolated from fruits have shown
significant a-glucosidase inhibiting activity [47]. Chebulinic acid and corilagin
[87], and chebulagic acid are potent a-glucosidase inhibitors [22, 28]. Chebulagic
acid and corilagin also enhance PPARa and/or PPARc signaling [110]. Chebulagic
acid is a dual inhibitor of COX-2 and 5-LOX enzymes [79]. Water soluble fraction
also significantly inhibited compound 48/80-induced histamine release from rats
peritoneal mast cells [93]. Chebulinic acid may be responsible for gastric antiulcer
activity as it significantly reduces free acidity, total acidity, upregulates mucin
secretion in gastric ulcers in rats, and significantly inhibits proton pump activity
in vitro [57].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Fruits lack pyrrolizidine alkaloids but are reported to produce
hepatic lesions with central vein abnormalities and marked renal lesions [7]. Single
oral dose of 5,000 mg/kg of hydrolysable tannin-rich fraction of fruits was non-
lethal and nontoxic to rats; however, 28-days treatment with 1,000 mg/kg/day
reduced body weight, food and water intake, and increased serum urea, glucose and
AST [20]. Acute oral LD50 of hydroalcohol extract in rats was reported
>2,000 mg/kg [62], and daily oral administration of an extract containing chebulic
acid to rats for 14-days was also nontoxic up to a dose of 2,000 mg/kg [41]. LD50
of chebulic acid (a transformed form of chebulagic acid or chebulinic acid) in rats
was reported as 251 mg/kg [95].
CYP450 and Potential for Drug-Herb Interactions: Hydroalcohol extract of
fruit pulp in vitro inhibits CYP450 [72].
Commentary: The fruits are mainly used in polyherbal Unani and Ayurvedic
formulations, most importantly as part of triphala, to improve gastric and mental
capacities. Formal clinical trials as a single drug or in combination for these con-
ditions may help delineate the beneficial role of myrobalans.

References
1. Achari C, Reddy GV, Reddy TC, Reddanna P. Chebulagic acid synergizes
the cytotoxicity of doxorubicin in human hepatocellular carcinoma through
COX-2 dependent modulation of MDR-1. Med Chem. 2011;7:432–42.
2. Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal
plants for their antimicrobial properties. J Ethnopharmacol. 1998;62:183–93.
3. Ajala OS, Jukov A, Ma CM. Hepatitis C virus inhibitory hydrolysable
tannins from the fruits of Terminalia chebula. Fitoterapia. 2014;99:117–23.
4. Akhtar N, Khan AB, Muhammad S, et al. Formulation and characterization
of a cream containing Terminalia chebula extract. Forsch Komplementmed.
2012;19:20–5.
1786 Terminalia chebula Retz.

5. Aqil F, Ahmad I. Antibacterial properties of traditionally used Indian

medicinal plants. Methods Find Exp Clin Pharmacol. 2007;29:79–92.
6. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant
extracts on clinical isolates of beta-lactamase producing methicillin resistant
Staphylococcus aureus. J Basic Microbiol. 2005;45:106–14.
7. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies of medicinal
plants of Sri Lanka. Part 14: toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–35.
8. Ayyanar M, Ignacimuthu S. Ethnobotanical survey of medicinal plants
commonly used by Kani tribals in Tirunelveli hills of Western Ghats,
India. J Ethnopharmacol. 2011;134:851–64.
9. Bag A, Bhattacharyya SK, Chattopadhyay RR, Rashid RA. The develop-
ment of Terminalia chebula Retz. (Combretaceae) in clinical research.
Asian Pac J Trop Biomed. 2013;3:244–52.
10. Bag A, Kumar Bhattacharyya S, Kumar Pal N, Ranjan Chattopadhyay R.
Anti-inflammatory, antilipidperoxidative, antioxidant and membrane stabi-
lizing activities of hydroalcoholic extract of Terminalia chebula fruits.
Pharm Biol. 2013;51:1515–20.
11. Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and anti-
oxidant activity of some food and medicinal plants. Int J Food Sci Nutr.
2005;56:287–91.
12. Ballabh B, Chaurasia OP, Ahmed Z, Singh SB. Traditional medicinal
plants of cold desert Ladakh used against kidney and urinary disorders.
J Ethnopharmacol. 2008;118:331–9.
13. Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK.
Healing properties of some Indian medicinal plants against indomethacin-
induced gastric ulceration of rats. J Clin Biochem Nutr. 2007;41:106–14.
14. Bonjar GH. Inhibition of Clotrimazole-resistant Candida albicans by plants
used in Iranian folkloric medicine. Fitoterapia. 2004;75:74–6.
15. Carounanidy U, Satyanarayanan R, Velmurugan A. Use of an aqueous
extract of Terminalia chebula as an anticaries agent: a clinical study.
Indian J Dent Res. 2007;18:152–6.
16. Chalise JP, Acharya K, Gurung N, et al. Antioxidant activity and polyphenol
content in edible wild fruits from Nepal. Int J Food Sci Nutr. 2010;61:
425–32.
17. Chang CL, Lin CS. Phytochemical composition, antioxidant activity, and
neuroprotective effect of Terminalia chebula Retzius extracts. Evid Based
Complement Alternat Med. 2012;2012:125247.
18. Cheng HY, Lin TC, Yu KH, et al. Antioxidant and free radical scavenging
activities of Terminalia chebula. Biol Pharm Bull. 2003;26:1331–5.
19. Choi MK, Kim HG, Han JM, et al. Hepatoprotective effect of Terminalia
chebula against t-BHP-induced acute liver injury in C57/BL6 mice. Evid
Based Complement Alternat Med. 2015;2015:517350.
Terminalia chebula Retz. 1787

20. Ekambaram SP, Babu KB, Perumal SS, Rajendran D. Repeated oral dose
toxicity study on hydrolysable tannin rich fraction isolated from fruit
pericarps of Terminalia chebula Retz. in Wistar albino rats. Regul Toxicol
Pharmacol. 2018;92:182–8.
21. El-Mekkawy S, Meselhy MR, Kusumoto IT, et al. Inhibitory effects of
Egyptian folk medicines on human immunodeficiency virus (HIV) reverse
transcriptase. Chem Pharm Bull (Tokyo). 1995;43:641–8.
22. Gao H, Huang YN, Gao B, Kawabata J. Chebulagic acid is a potent alpha-
glucosidase inhibitor. Biosci Biotechnol Biochem. 2008;72:601–3.
23. Gautam MK, Goel S, Ghatule RR, et al. Curative effect of Terminalia
chebula extract on acetic acid-induced experimental colitis: role of antioxi-
dants, free radicals and acute inflammatory marker. Inflammopharmacol-
ogy. 2013;21:377–83.
24. Ghosh A, Das BK, Roy A, et al. Antibacterial activity of some medicinal
plant extracts. Nat Med (Tokyo). 2008;62:259–62.
25. Gopi KS, Reddy AG, Jyothi K, Kumar BA. Acetaminophen-induced
hepato- and nephrotoxicity and amelioration by silymarin and Terminalia
chebula in rats. Toxicol Int. 2010;17:64–6.
26. Han Q, Song J, Qiao C, et al. Preparative isolation of hydrolysable tannins
chebulagic acid and chebulinic acid from Terminalia chebula by
high-speed countercurrent chromatography. J Sep Sci. 2006;29:1653–7.
27. Hazra B, Sarkar R, Biswas S, Mandal N. Comparative study of the antioxidant
and reactive oxygen species scavenging properties in the extracts of the fruits
of Terminalia chebula, Terminalia belerica and Emblica officinalis. BMC
Complement Altern Med. 2010;10:20.
28. Huang YN, Zhao DD, Gao B, et al. Antihyperglycemic effect of chebulagic
acid from the fruits of Terminalia chebula Retz. Int J Mol Sci. 2012;
13:6320–33.
29. Ishtiaq M, Hanif W, Khan MA, et al. An ethnomedicinal survey and
documentation of important medicinal folklore food phytonims of flora
of Samahni valley, (Azad Kashmir) Pakistan. Pak J Biol Sci. 2007;10:
2241–56.
30. Jagtap AG, Karkera SG. Potential of the aqueous extract of Terminalia
chebula as an anticaries agent. J Ethnopharmacol. 1999;68:299–306.
31. Jebashree HS, Kingsley SJ, Sathish ES, Devapriya D. Antimicrobial
activity of few medicinal plants against clinically isolated human cariogenic
pathogens—an in vitro study. ISRN Dent. 2011;2011:541421.
32. Juang LJ, Sheu SJ. Chemical identification of the sources of commercial
Fructus Chebulae. Phytochem Anal. 2005;16:246–51.
33. Kadir MF, Bin Sayeed MS, Mia MM. Ethnopharmacological survey of
medicinal plants used by indigenous and tribal people in Rangamati,
Bangladesh. J Ethnopharmacol. 2012;144:627–37.
34. Kalra P, Karwasra R, Gupta YK, Ray SB, Singh S. Terminalia chebula
supplementation attenuates cisplatin-induced nephrotoxicity in Wistar rats
through modulation of apoptotic pathway. Nat Prod Res. 2018;17:1–5.
1788 Terminalia chebula Retz.

35. Kaur S, Jaggi RK. Antinociceptive activity of chronic administration of

different extracts of Terminalia bellerica Roxb. and Terminalia chebula
Retz. fruits. Indian J Exp Biol. 2010;48:925–30.
36. Kesharwani A, Polachira SK, Nair R, et al. Anti-HSV-2 activity of Terminalia
chebula Retz. extract and its constituents, chebulagic and chebulinic acids.
BMC Complement Altern Med. 2017;17:110.
37. Khazaeli P, Goldoozian R, Sharififar F. An evaluation of extracts of five
traditional medicinal plants from Iran on the inhibition of mushroom
tyrosinase activity and scavenging of free radicals. Int J Cosmet Sci. 2009;
31:375–81.
38. Kim BJ, Kim JH, Kim HP, Heo MY. Biological screening of 100 plant
extracts for cosmetic use (II): antioxidative activity and free radical
scavenging activity. Int J Cosmet Sci. 1997;19:299–307.
39. Kim HG, Cho JH, Jeong EY, et al. Growth-inhibiting activity of active
component isolated from Terminalia chebula fruits against intestinal
bacteria. J Food Prot. 2006;69:2205–9.
40. Kim JH, Hong CO, Koo YC, et al. Oral administration of ethyl acetate-soluble
portion of Terminalia chebula conferring protection from streptozotocin-
induced diabetic mellitus and its complications. Biol Pharm Bull. 2011;
34:1702–9.
41. Kim JH, Koo YC, Hong CO, et al. Mutagenicity and oral toxicity studies
of Terminalia chebula. Phytother Res. 2012;26:39–47.
42. Ko SH, Choi SW, Ye SK, et al. Comparison of antioxidant activities of
seventy herbs that have been used in Korean traditional medicine. Nutr Res
Pract. 2008;2:143–51.
43. Kumar CU, Pokuri VK, Pingali U. Evaluation of the analgesic activity of
standardized aqueous extract of Terminalia chebula in healthy human
participants using hot air pain model. J Clin Diagn Res. 2015;9:FC01-4.
44. Kumar R, Arora R, Agarwal A, Gupta YK. Protective effect of Terminalia
chebula against seizures, seizure-induced cognitive impairment and
oxidative stress in experimental models of seizures in rats. J Ethnophar-
macol. 2018;215:124–31.
45. Kurokawa M, Nagasaka K, Hirabayashi T, et al. Efficacy of traditional
herbal medicines in combination with acyclovir against herpes simplex
virus type 1 infection in vitro and in vivo. Antiviral Res. 1995;27:19–37.
46. Kusirisin W, Srichairatanakool S, Lerttrakarnnon P, et al. Antioxidative
activity, polyphenolic content and antiglycation effect of some Thai
medicinal plants traditionally used in diabetic patients. Med Chem. 2009;
5:139–47.
47. Lee DY, Kim HW, Yang H, Sung SH. Hydrolyzable tannins from the
fruits of Terminalia chebula Retz. and their a-glucosidase inhibitory
activities. Phytochemistry. 2017;137:109–16.
48. Lee HS, Jung SH, Yun BS, Lee KW. Isolation of chebulic acid from
Terminalia chebula Retz. and its antioxidant effect in isolated rat hepato-
cytes. Arch Toxicol. 2007;81:211–8.
Terminalia chebula Retz. 1789

49. Lee HS, Won NH, Kim KH, et al. Antioxidant effects of aqueous extract
of Terminalia chebula in vivo and in vitro. Biol Pharm Bull. 2005;28:
1639–44.
50. Lee J, Nho YH, Yun SK, Hwang YS. Use of ethanol extracts of Terminalia
chebula to prevent periodontal disease induced by dental plaque bacteria.
BMC Complement Altern Med. 2017;17:113.
51. Lee SI, Hyun PM, Kim SH, et al. Suppression of the onset and progression
of collagen-induced arthritis by chebulagic acid screened from a natural
product library. Arthritis Rheum. 2005;52:345–53.
52. Li K, Diao Y, Zhang H, et al. Tannin extracts from immature fruits of
Terminalia chebula Fructus Retz promote cutaneous wound healing in
rats. BMC Complement Altern Med. 2011;11:86.
53. Lopez HL, Habowski SM, Sandrock JE, et al. Effects of dietary supple-
mentation with a standardized aqueous extract of Terminalia chebula fruit
(AyuFlex®) on joint mobility, comfort, and functional capacity in healthy
overweight subjects: a randomized placebo-controlled clinical trial. BMC
Complement Altern Med. 2017;17:475.
54. Mahesh R, Bhuvana S, Begum VM. Effect of Terminalia chebula aqueous
extract on oxidative stress and antioxidant status in the liver and kidney of
young and aged rats. Cell Biochem Funct. 2009;27:358–63.
55. Manosroi A, Jantrawut P, Akihisa T, et al. In vitro antiaging activities of
Terminalia chebula gall extract. Pharm Biol. 2010;48:469–81.
56. Maruthappan V, Shree KS. Hypolipidemic activity of haritaki (Terminalia
chebula) in atherogenic diet induced hyperlipidemic rats. J Adv Pharm
Technol Res. 2010;1:229–35.
57. Mishra V, Agrawal M, Onasanwo SA, et al. Antisecretory and cytopro-
tective effects of chebulinic acid isolated from the fruits of Terminalia
chebula on gastric ulcers. Phytomedicine. 2013;20:506–11.
58. Murali YK, Anand P, Tandon V, et al. Long-term effects of Terminalia
chebula Retz. on hyperglycemia and associated hyperlipidemia, tissue
glycogen content and in vitro release of insulin in streptozotocin induced
diabetic rats. Exp Clin Endocrinol Diabetes. 2007;115:641–6.
59. Murali YK, Chandra R, Murthy PS. Antihyperglycemic effect of water
extract of dry fruits of Terminalia chebula in experimental diabetes
mellitus. Indian J Clin Biochem. 2004;19:202–4.
60. Naik GH, Priyadarsini KI, Naik DB, et al. Studies on the aqueous extract
of Terminalia chebula as a potent antioxidant and a probable radiopro-
tector. Phytomedicine. 2004;11:530–8.
61. Naik GH, Priyadarsini KI, Satav JG, et al. Comparative antioxidant activity
of individual herbal components used in Ayurvedic medicine. Phytochem-
istry. 2003;63:97–104.
62. Nair V, Singh S, Gupta YK. Antiarthritic and disease modifying activity of
Terminalia chebula Retz. in experimental models. J Pharm Pharmacol.
2010;62:1801–6.
1790 Terminalia chebula Retz.

63. Nasiri E, Hosseinimehr SJ, Azadbakht M, et al. The effect of Terminalia

chebula extract vs. silver sulfadiazine on burn wounds in rats. J Complement
Integr Med. 2015;12:127–35.
64. Nayak SS, Ankola AV, Metgud SC, Bolmal U. Effectiveness of mouthrinse
formulated from ethanol extract of Terminalia chebula fruit on sali-
vary Streptococcus mutans among 12 to 15-year old school children of
Belgaum city: a randomized field trial. J Indian Soc Pedod Prev Dent.
2012;30:231–6.
65. Nayak SS, Kumar BR, Ankola AV, Hebbal M. The efficacy of Terminalia
chebula rinse on Streptococcus mutans count in saliva and its effect on
salivary pH. Oral Health Prev Dent. 2010;8:55–8.
66. Palit M, Hegde SK, Bhat SS. Effectiveness of mouthrinse formulated from
aqueous extract of Terminalia chebula on salivary Streptococcus mutans
count and pH among 8- to 12-year-old school children of Karnataka: a
randomized clinical trial. Int J Clin Pediatr Dent. 2016;9:349–54.
67. Peterson CT, Denniston K, Chopra D. Therapeutic uses of Triphala in
Ayurvedic medicine. J Altern Complement Med. 2017;23:607–14.
68. Pfundstein B, El Desouky SK, Hull WE, et al. Polyphenolic compounds in
the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia
chebula and Terminalia horrida): characterization, quantitation and
determination of antioxidant capacities. Phytochemistry. 2010;71:1132–48.
69. Phadke SA, Kulkarni SD. Screening of in vitro antibacterial activity of
Terminalia chebula, Eclapta alba and Ocimum sanctum. Indian J Med Sci.
1989;43:113–7.
70. Pinmai K, Hiriote W, Soonthornchareonnon N, et al. In vitro and in vivo
antiplasmodial activity and cytotoxicity of water extracts of Phyllanthus
emblica, Terminalia chebula, and Terminalia bellerica. J Med Assoc Thai.
2010;93 Suppl 7:S120–6.
71. Pokuri VK, Kumar CU, Pingali U. A randomized, double-blind, placebo-
controlled, crossover study to evaluate analgesic activity of Terminalia
chebula in healthy human volunteers using a mechanical pain model.
J Anaesthesiol Clin Pharmacol. 2016;32:329–32.
72. Ponnusankar S, Pandit S, Venkatesh M, et al. Cytochrome P450 inhibition
assay for standardized extract of Terminalia chebula Retz. Phytother Res.
2011;25:151–4.
73. Prasad L, Husain Khan T, Jahangir T, Sultana S. Chemomodulatory effects
of Terminalia chebula against nickel chloride induced oxidative stress and
tumor promotion response in male Wistar rats. J Trace Elem Med Biol.
2006;20:233–9.
74. Prasad L, Khan TH, Jahangir T, Sultana S. Abrogation of DEN/Fe-NTA
induced carcinogenic response, oxidative damage and subsequent cell
proliferation response by Terminalia chebula in kidney of Wistar rats.
Pharmazie. 2007;62:790–7.
75. Pratap GM, Manoj KM, Sai SA, et al. Evaluation of three medicinal plants
for antimicrobial activity. Ayu. 2012;33:423–8.
Terminalia chebula Retz. 1791

76. Rahmatullah M, Azam MN, Khatun Z, et al. Medicinal plants used for
treatment of diabetes by the Marakh sect of the Garo tribe living in
Mymensingh district, Bangladesh. Afr J Tradit Complement Altern Med.
2012;9:380–5.
77. Rajmohamed MA, Natarajan S, Palanisamy P, Abdulkader AM, Govindaraju
A. Antioxidant and cholinesterase inhibitory activities of ethyl acetate extract
of Terminalia chebula: cell-free in vitro and in silico studies. Pharmacogn
Mag. 2017;13 Suppl 3:S437–45.
78. Rathore HS, Soni S, Bhatnagar D. Hypocholesterolemic effect of Termi-
nalia chebula fruit (Myrobalan) in mice. Anc Sci Life. 2004;23:11–5.
79. Reddy DB, Reddy TC, Jyotsna G, et al. Chebulagic acid, a COX-LOX
dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces
apoptosis in COLO-205 cell line. J Ethnopharmacol. 2009;124:506–12.
80. Reddy MM, Dhas Devavaram J, Dhas J, Adeghate E, Starling Emerald B.
Antihyperlipidemic effect of methanol bark extract of Terminalia chebula
in male albino Wistar rats. Pharm Biol. 2015;53:1133–40.
81. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six rasayana
herbs used in Ayurvedic medicine. Phytother Res. 1999;13:275–91.
82. Sabu MC, Kuttan R. Antidiabetic activity of medicinal plants and its
relationship with their antioxidant property. J Ethnopharmacol. 2002;81:
155–60.
83. Saleem A, Ahotupa M, Pihlaja K. Total phenolics concentration and antioxi-
dant potential of extracts of medicinal plants of Pakistan. Z Naturforsch.
2001;56:973–8.
84. Saleem A, Husheem M, Härkönen P, Pihlaja K. Inhibition of cancer cell
growth by crude extract and the phenolics of Terminalia chebula retz. fruit.
J Ethnopharmacol. 2002;81:327–36.
85. Sarkar R, Hazra B, Mandal N. Reducing power and iron chelating property
of Terminalia chebula (Retz.) alleviates iron induced liver toxicity in mice.
BMC Complement Altern Med. 2012;12:144.
86. Sarkar R, Mandal N. Hydroalcoholic extracts of Indian medicinal plants can
help in amelioration from oxidative stress through antioxidant properties.
J Complement Integr Med 2012;9:Article 7.
87. Sasidharan I, Sundaresan A, Nisha VM, et al. Inhibitory effect of
Terminalia chebula Retz. fruit extracts on digestive enzyme related to
diabetes and oxidative stress. J Enzyme Inhib Med Chem. 2012;27:578–86.
88. Sato Y, Oketani H, Singyouchi K, et al. Extraction and purification of
effective antimicrobial constituents of Terminalia chebula RETS against
methicillin-resistant Staphylococcus aureus. Biol Pharm Bull. 1997;20:
401–4.
89. Saxena S, Lakshminarayan N, Gudli S, Kumar M. Antibacterial efficacy of
Terminalia chebula, Terminalia bellirica, Embilica officinalis and triphala
on salivary Streptococcus mutans count—a linear randomized crossover
trial. J Clin Diagn Res. 2017;11:ZC47–51.
1792 Terminalia chebula Retz.

90. Sharma A, Chandraker S, Patel VK, Ramteke P. Antibacterial activity of

medicinal plants against pathogens causing complicated urinary tract
infections. Indian J Pharm Sci. 2009;71:136–9.
91. Sharma P, Prakash T, Kotresha D, et al. Antiulcerogenic activity of
Terminalia chebula fruit in experimentally induced ulcer in rats. Pharm
Biol. 2011;49:262–8.
92. Sheng Z, Yan X, Zhang R, et al. Assessment of the antidiarrhoeal properties
of the aqueous extract and its soluble fractions of Chebulae Fructus
(Terminalia chebula fruits). Pharm Biol. 2016;54:1847–56.
93. Shin TY, Jeong HJ, Kim DK, et al. Inhibitory action of water soluble frac-
tion of Terminalia chebula on systemic and local anaphylaxis. J Ethnophar-
macol. 2001;74:133–40.
94. Shiraki K, Yukawa T, Kurokawa M, Kageyama S. Cytomegalovirus
infection and its possible treatment with herbal medicines. Nihon Rinsho.
1998;56:156–60 (Article in Japanese).
95. Silawat N, Gupta VB. Chebulic acid attenuates ischemia reperfusion
induced biochemical alteration in diabetic rats. Pharm Biol. 2013;51:23–9.
96. Singh I, Singh PK, Bhansali S, et al. Effects of three different doses of a
fruit extract of Terminalia chebula on metabolic components of metabolic
syndrome, in a rat model. Phytother Res. 2010;24:107–12.
97. Srivastav A, Chandra A, Singh M, et al. Inhibition of hyaluronidase
activity of human and rat spermatozoa in vitro and antispermatogenic
activity in rats in vivo by Terminalia chebula, a flavonoid rich plant.
Reprod Toxicol. 2010;29:214–24.
98. Suchalatha S, Shyamala Devi CS. Protective effect of Terminalia chebula
against experimental myocardial injury induced by isoproterenol. Indian J
Exp Biol. 2004;42:174–8.
99. Suchalatha S, Srinivasan P, Devi CS. Effect of T. chebula on mitochondrial
alterations in experimental myocardial injury. Chem Biol Interact. 2007;
169:145–53.
100. Suguna L, Singh S, Sivakumar P, et al. Influence of Terminalia chebula on
dermal wound healing in rats. Phytother Res. 2002;16:227–31.
101. Tamhane MD, Thorat SP, Rege NN, Dahanukar SA. Effect of oral
administration of Terminalia chebula on gastric emptying: an experimental
study. J Postgrad Med. 1997;43:12–3.
102. Tasduq SA, Singh K, Satti NK, et al. Terminalia chebula (fruit) prevents
liver toxicity caused by subchronic administration of rifampicin, isoniazid
and pyrazinamide in combination. Hum Exp Toxicol. 2006;25:111–8.
103. Thakur CP, Thakur B, Singh S, et al. The Ayurvedic medicines Haritaki,
Amala and Bahira reduce cholesterol-induced atherosclerosis in rabbits.
Int J Cardiol. 1988;21:167–75.
Terminalia chebula Retz. 1793

104. Usharani P, Nutalapati C, Pokuri VK, Kumar CU, Taduri G. A randomized,

double-blind, placebo-, and positive-controlled clinical pilot study to
evaluate the efficacy and tolerability of standardized aqueous extracts of
Terminalia chebula and Terminalia bellerica in subjects with hyper-
uricemia. Clin Pharmacol. 2016;8:51–9.
105. Velmurugan A, Madhubala MM, Bhavani S, et al. An in-vivo comparative
evaluation of two herbal extracts Emblica officinalis and Terminalia
chebula with chlorhexidine as an anticaries agent: a preliminary study.
J Conserv Dent. 2013;16:546–9.
106. Vonshak A, Barazani O, Sathiyamoorthy P, et al. Screening South Indian
medicinal plants for antifungal activity against cutaneous pathogens.
Phytother Res. 2003;17:1123–5.
107. Waheed S, Fatima I. Instrumental neutron activation analysis of Emblica
officinalis, Terminalia belerica and Terminalia chebula for trace element
efficacy and safety. Appl Radiat Isot. 2013;77:139–44.
108. Wang W, Ali Z, Li XC, et al. Triterpenoids from two Terminalia species.
Planta Med. 2010;76:1751–4.
109. Yakaew S, Itsarasook K, Ngoenkam J, et al. Ethanol extract of Terminalia
chebula fruit protects against UVB-induced skin damage. Pharm Biol.
2016;54:2701–7.
110. Yang MH, Vasquez Y, Ali Z, Khan IA, Khan SI. Constituents from
Terminalia species increase PPARa and PPARc levels and stimulate
glucose uptake without enhancing adipocyte differentiation. J Ethnophar-
macol. 2013;149:490–8.
111. Yukawa TA, Kurokawa M, Sato H, et al. Prophylactic treatment of
cytomegalovirus infection with traditional herbs. Antiviral Res. 1996;32:
63–70.
112. Zaidi SF, Muhammad JS, Shahryar S, et al. Anti-inflammatory and
cytoprotective effects of selected Pakistani medicinal plants in Helicobac-
ter pylori-infected gastric epithelial cells. J Ethnopharmacol. 2012;141:
403–10.
113. Zhang XJ, He LJ, Lu Q, Li DY. Pharmacological activity of Terminalia
chebula. Zhongguo Zhong Yao Za Zhi. 2016;41:619–23 (Chinese).
Thymus vulgaris L.
(Lamiaceae)

(Syns.: T. chinensis K. Koch; T. ilerdensis González ex Costa; T. sublaxus Rouy)

Abstract
Thymus vulgaris is a bushy, evergreen subshrub, that was known to ancient
Egyptians, Greeks and Romans. It was used for embalming by Egyptians, used in
baths by Greeks, and Romans purified their rooms with it. It was also used as
incense by the Greeks and placed in coffins to assure passage into the next life. In
Unani medicine, aerial parts are regarded analgesic, anti-inflammatory, expec-
torant, digestive, carminative, emmenagogue, anthelmintic, lithotriptic, diuretic,
aphrodisiac, and to improve digestion and appetite. As a nervine tonic, it is used
in the treatment of epilepsy, and also used in dyspnea and asthma, diarrhea,
dyspepsia with flatulence, gonorrhea, leucorrhea, and visceral catarrh. It is also an
anesthetic, and irritant to skin and mucous membranes. Thyme oil is used as a
disinfectant and antiseptic, probably due to its phenolic content; and for scenting
soaps, making perfumes, and as a flavoring agent for food. Aerial parts contain
volatile oil, flavonoids, sterols/triterpenes, tannins, anthraquinones, and cyano-
genic glycosides. Most important constituent of the plant is the EO which is used
for many purposes. It contains thymol, carvacrol, p-cymene, a-pinene, terpineol,
v-terpinene, geraniol, linalool and traces of cineole. Thymus vulgaris and its
volatile extracts possess high antioxidant activity and rosmarinic acid is identified
as the predominant phenolic compound. Both thymol and carvacrol have also
been suggested being responsible for the antioxidant activity; while others
attributed the antioxidative action to labiate acid and rosmarinic acid. Aqueous
extract showed high antiviral activity against HSV-1, HSV-2 and an acyclovir-
resistant strain of HSV-1. Thyme extract significantly reduces production and
gene expression of proinflammatory mediators, TNF-a, IL-1B, and IL-6, and
carvacrol is reported to activate PPARa and PPARc and suppresses COX-2
expression, and inhibits AChE. Thymol is suggested to potentiate GABAA
receptors through an allosteric binding site. Thymol also acts as agonist on a1, a2
and b-adrenergic receptors.

© Springer Nature Switzerland AG 2020 1795

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_185
1796 Thymus vulgaris L.

Keywords


Gartenquendel Hasha Kekik

Pepolino
Saa’tar
Timian
Timjan




Tomentelo Tomillo Zaa’tar

Vernaculars: Urd.: Saa’tar, Zaa’tar; Hin.: Bona jowan, Ipar, Qar; Ara.: Saa’tar,
Zaa’tar; Chi.: 百里香, Bai li xiang; Dan. : Almindelig timian, Have-timian, Timian;
Dut.: Echte keukentijm, Echte tijm, Gewone keukentijm; Eng.: Garden thyme,
German thyme, Thyme; Fin.: Tarha-ajuruoho, Timjami; Fre.: Barigoule, Faligoule,
Farigoule, Frigoule, Mignotise des genevois, Pote, Thym, Thym des jardins, Thym
vulgaire; Ger.: Echter quendel, Echter thymian, Gartenquendel, Gartenthymian,
Gewürzthymian, Kuttelkraut, Römischer quendel, Thymian; Hun.: Balzsamfű,
Kakucskafű, Kakukkfű; Ita.: Pepolino, Timo, Timo comune, Timo maggiore; Jap.:
Tachijako-sô, Taimu, Timusu; Maly.: Timi; Nor.: Hagetimian, Kryddertimian,
Timian; Per.: Hasha, Saa’tar, Zaa’tar; Pol.: Tymianek pospolity, Tymianek właś-
ciwy; Por.: Tomelo, Tomentelo, Tomilho, Tomilho-comum, Tomilho-ordinário,
Tomilho-vulgar; Rus.: Mashcherka gradinska, Tim’ian obyknovennyi; Spa.:
Estremoncillo, Farigola, Tomillo, Tomillo ansero, Tomillo borde, Tomillo caliza,
Tomillo común, Tomillo negrillo, Tomillo rojo, Tomillo royo, Tomillo salsero,
Tomillo vulgar, Tomizo, Tremoncillo; Swe.: Kryddtimjan, Timjan; Tur.: Dağ kekiği,
Kekik; Vie.: Cỏ xạ hương.
Description: Thymus vulgaris is a bushy, evergreen subshrub, with numerous,
somewhat woody stems growing up 15–30 cm tall, with small, highly aromatic,
linear to elliptic, pointed, distinctively revolute, grey-green leaves and clusters of
purple or pink flowers in early summer (May to July). It is a native of southern
Europe, from the western Mediterranean to southern Italy. Some have described
Zataria multiflora as the Saa’tar or Zaa’tar of Arabs. This plant is a native to
Iran, Afghanistan, Pakistan, and Kashmir, and Saa’tar Farsi (means grown in Iran)
is supposed to be the best (Figs. 1, 2 and 3).
Actions and Uses: It was known to ancient Egyptians, Greeks and Romans, was
used by Egyptians for embalming, used in baths by Greeks, and Romans purified
their rooms with it. It was also used as incense by the Greeks and placed in coffins
to assure passage into the next life. In Unani medicine, aerial parts (temperament,
hot 2° and dry 2°) are regarded analgesic, anti-inflammatory, expectorant, digestive,
carminative, emmenagogue, anthelmintic, lithotriptic, diuretic, aphrodisiac, and to
improve digestion and appetite.LXXVII As a nervine tonic, it is used in the treatment
of epilepsy, and also used in dyspnea and asthma, diarrhea, dyspepsia with flatu-
lence, gonorrhea, leucorrhea, and visceral catarrh. It is also an anesthetic, and
irritant to skin and mucous membranes.LXXXI Thyme oil is used as a disinfectant
and antiseptic, probably due to its phenolic content; and for scenting soaps, making
perfumes, and as a flavoring agent for many types of food products [48].
Phytoconstituents: Studies on the constituents useful for chemotaxonomic purposes
have been reported by various investigators [4–6, 52, 88, 107]. Phytochemical
Thymus vulgaris L. 1797

Fig. 1 Thymus vulgaris, Garden Thyme in France, Henry Brisse, WikimediaCommons; Share-
Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Thymus_vulgaris1.
JPG; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Thymus vulgaris, Flowering Thyme, Greenmars, WikimediaCommons; ShareAlike 3.0

Unported, CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Flowering_thyme.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

analysis of aerial parts revealed the presence of volatile oil, flavonoids, sterols/triter-
penes, tannins, anthraquinones, and cyanogenic glycosides [14, 16, 60]. Four flavo-
noids (quercetin, eriodictyol, cirsilineol and 5,6,4′-trihydroxy-7,8,3′-trimethoxy-
flavone) [79], acetophenone glycosides [122], an acidic polysaccharide [30], the
radical scavengers, rosmarinic acid 1, eriodictyol, taxifolin, luteolin 7-glucuronide,
p-cymene 2,3-diol, p-cymene 2,3-diol 6-6′-dimer, carvacrol (the monoterpenic phenol),
and thymol [31], monoterpene glucosides ((R)-p-cymen-9-yl b-D-glucopyranoside,
1798 Thymus vulgaris L.

Fig. 3 Thymus vulgaris, Dried Leaves as sold in the U.S., Prof. Akbar, Original

2- and 5-b-D-glucopyranosyl-thymoquinols, and (-)-angelicoidenol-b-D-glucopyrano-

side) [114], monoterpenoid glycosides [64], and a hydroxyjasmone glucoside [65],
have been reported from thyme leaves. Alonso and Corteau [13] isolated monoterpene
cyclase and c-terpinene synthase, and three methylated flavones, 5,6,4′-trihydroxy-
7,8,3′-trimethoxyflavone (thymonin), 5,4′-dihydroxy-6,7,3′-trimethoxyflavone (cirsi-
lineol) and 5,4′-dihydroxy-6,7,8,3′-tetramethoxy-flavone [119]. were isolated from the
leaves. The plant also contains 32.9 mg% of ascorbic acid [47]. Thymol and carvacrol
are the key compounds contributing to the aroma of thyme leaves [34].
Most important constituent of the plant is the EO which is used for many pur-
poses. It contains thymol, carvacrol, p-cymene, a-pinene, terpineol, v-terpinene,
geraniol, linalool and traces of cineole [9, 88]. Based on the presence of these
constituents the oil was differentiated into 7 chemotypes [88]. Six chemotypes of
T. vulgaris, characterized by the major constituent of their EO, were found to possess
same antibacterial spectrum [106]. Essential oils are now classified into four
chemotypes: thymol (41.0%), geraniol (26.4%), linalool (72.5%) and 4-thujanol/
terpinen-4-ol (42.2% cis- and 7.3% trans-sabinene hydrate, 6.5% terpinen-4-ol). All
chemotypes are potent antimicrobials and useful additives in food products as well
as for therapeutic applications [98]. Essential oil obtained from Nyons, France was
of linalool chemotype (linalool, 76.2%; linalyl acetate, 14.3%) and the one from
Richerenches, France was of thymol chemotype (thymol, 47.1%; p-cymene,
20.1%); the oil sample from Jablanicki, Serbia of the geraniol chemotype (geraniol,
59.8%; geranyl acetate, 16.7%), and the sample from Pomoravje District, Serbia was
of the sabinene hydrate chemotype (cis-sabinene hydrate, 30.8%; trans-sabinene
hydrate, 5.0%) [97]. The oil content and constituents vary during various stages of
growth, time of flowering and harvesting of the plant. Normally the oil contents are
high in mature plants at the time of flowering [70, 87, 100]; however, the oil yield
Thymus vulgaris L. 1799

and its composition were reported maximum when the plant was harvested at the
early growth stage [3].
Thyme oil contains monoterpenes (carvacrol, p-cymene, linalool, a-terpinene and
thymol). a-Terpinene and carvacrol showed significantly greater mosquito repellent
activity than N,N-diethyl-m-methylbenzamide (DEET), whereas thymol had similar
mosquito repellency as DEET [86]. Supercritical fluid extraction (SFE) and isolation
of EO by hydrodistillation (HD) show quantitative and qualitative differences, such
as p-cymene (10–42.6% for SFE and 28.9–34.8% for HD), c-terpinene (0.8–6.9%
for SFE and 5.1–7% for HD), linalool (2.3–5.3% for SFE and 2.8–3.1% for HD),
thymol (19.5–40.8% for SFE and 35.4–41.6% for HD), and carvacrol (1.4–3.1% for
SFE and 2.6–3.1% for HD); also thymoquinone was absent in the EO from Portugal
[53]. Thymol and p-cymene are generally higher in amounts by simultaneous
distillation-extraction than by supercritical fluid extraction [34]. Thyme oil from
Iranian plant reportedly contained 22 compounds representing 98.2% of the EO;
main components being thymol (43.8%), p-cymene (15.2%), germacrene-D (11.7%),
terpinolene (3.4%), carvacrol (3.2%), b-caryophyllene (2.8%) and a-thujene (2.2%)
[15]; whereas Thymus vulgaris cultivated in Romania yielded 1.25% EO by steam
distillation and contained thymol (47.59%), c-terpinene (30.90%), and p-cymene
(8.41%) as the major components [23]. Essential oils obtained from plant samples
collected from five different areas of the Campania region of southern Italy showed
the presence of 134 compounds, and the total phenol contents ranged from 77.6 to
165.1 mg gallic acid equivalents/g [75]. Thymol (48.9%) and p-cymene (19.0%)
were the main components of EO of thyme from Serbia [110].
Pharmacology: Thymus vulgaris and its volatile extracts possess high antioxidant
activity, and rosmarinic acid is identified as the predominant phenolic compound
[7, 12, 25, 29, 36, 59, 68, 71, 93–95, 124]. Both thymol and carvacrol have also been
suggested being responsible for the antioxidant activity [1]; while others attributed
the antioxidative action to labiate acid and rosmarinic acid [46]. A biphenyl com-
pound, 3,4,3′,4′-tetrahydroxy-5,5′-diisopropyl-2,2′-dimethylbiphenyl, and a flavo-
noid, eriodicytol, isolated from leaves are also potent antioxidants [55]. A significant
decline occurs in the antioxidant status of old rats, and lifetime supplementation of
diet with thyme oil prevented decline in antioxidant status [123]. Thyme (5%)
supplemented in high-fat diet to rats for 12-weeks produced significant antithrom-
botic effect, without prolonging bleeding time [80]. Inhalation of thyme oil by mice
reduced immobility, even in overagitated mice, a test indicative of antidepressant-like
activity [72]. Essential oil and its constituents also inhibit AChE in the following
order: thymohydroquinone > carvacrol > thymoquinone > essential oil > thy-
mol > linalool [62]. Thymol and 3,4,3′,4′-tetrahydroxy-5,5′-diisopropyl-2,2′-dime-
thylbiphenyl inhibit collagen-, ADP-, and AA-induced platelet aggregation [84].
Aqueous extract showed high antiviral activity against HSV-1, HSV-2 and an
acyclovir-resistant strain of HSV-1 [82]; methanol extract potently inhibiting
clotrimazole-resistant C. albicans [22], and the ethanol extract being active against
1800 Thymus vulgaris L.

strains of A. flavus and A. ochraceus [28], and against S. aureus, S. dysenteriae,

S. typhimurium, E. coli, S. epidermidis, B. subtilis, MRSA and P. aeruginosa [74].
Acetone and water extracts also inhibited growth of M. tuberculosis [69]. Thyme
EO exhibits strong inhibitory activity against both Gram-positive and Gram-
negative bacteria [2, 8, 10, 21, 32, 35, 40, 41, 44, 54, 57, 73, 78, 81, 85, 102, 104,
109, 115, 116], and MDR strains [105]. Tested bacteria included: Gram-positive
(L. monocytogenes, MSSA, and MRSA, S. epidermidis, S. mutans, S. pyogenes, B.
subtilis, B. cereus, and E. faecalis), Gram-negative (E. coli, P. vulgaris, P. mirabilis,
Y. enterocolitica, P. aeruginosa, K. pneumoniae, K. oxytoca, S. typhimurium,
S. choleraesuis, S. enteritidis, H. pylori, E. cloacae), molds (P. islandicum and
A. flavus), and the yeast, C. albicans. The oil from thyme in full flower is the most
effective bacteriostatic, and E. coli is the most sensitive species [76], also S. pyo-
genes and S. mutans are highly sensitive oral pathogens to EO [43]. The EO is strong
bactericidal against P. acnes, killing all bacteria within 5 min, and also strongly
cytotoxic to human lung carcinoma, human prostate carcinoma and human breast
cancer cells [125], and antiproliferative on two melanoma cell lines [11]. Essential
oil is also strongly active against different Aspergillus and Penicillium species [103],
completely inhibiting growth of A. flavus, A. parasiticus, A. ochraceus and F. monili-
forme [111]. The EO was reported to in vitro antagonize the effect of amphotericin
B against C. albicans [120]; however, thymol chemotype T. vulgaris in higher
concentrations (0.01, 0.1, 0.2, 0.3 µg/mL) decreased the MIC of amphotericin B by
80%, but in lower concentrations (0.00031–0.0025 µg/mL) antagonized the effect of
amphotericin B on C. albicans [49]. An extract of leaves, and the isolated active
constituent, baicalein greatly reduced MIC of tetracycline against MRSA [45].
Essential oil was virucidal to acyclovir-resistant strain of HSV-1 [66, 99], and
potently active against Candida spp. [26, 90, 117], against fluconazole-resistant
C. albicans [91], completely inhibiting production of aflatoxins B1 and B2 from
A. flavus [67], and against Rhizopus oryzae [33]. Essential oil and thymol also
potentiate antifungal effects of fluconazole against drug-resistant strains of T. rubrum
and Aspergillus spp [63]. Hydroalcohol and hexane extracts, and the EO also
inhibited E. histolytica; the EO being the most potent [19]. Ethanol extract exhibited
significant prophylactic and curative activity in T. gondii-infected mice [39]. The EO
completely inhibited development of aerobic and anaerobic microorganisms
obtained from infected root canals [89]. Thymol completely inhibited growth of both
A. flavus and A. versicolor at 0.4 mg/ml or less [58, 101]. Topical application of a 1%
solution of EO and thymol cured rats experimentally infected with T. mentagro-
phytes, T. rubrum, and T. tonsurans [108].
Hydroalcohol extract and carvacrol possess antinociceptive activity that does not
involve opioid system or NO pathway [27, 113]. Essential oil and carvacrol also
exhibit anti-inflammatory effect in carrageenan-induced pleurisy which was
attributed to inhibition of leukocyte migration [42]. Vetvicka and Vetvickova [121],
however, found limited effects of seven EOs on phagocytosis, cytokine production,
chemotaxis, edema inhibition, and liver protection, and no correlation between
composition and biological effects. Ethanol extract was also hypolipidemic and
protective against alcohol-hepatotoxicity [37]. Thyme extract inhibits contractions
Thymus vulgaris L. 1801

of isolated guinea pig ileum [17], and of isolated trachea [24, 38, 77]; flavonoids,
isolated from leaves and flowering tops, also exhibited spasmolytic activity in
guinea pig ileum and trachea [118, 119].
Mechanism of Action: Thyme extract significantly reduces in vitro production and
gene expression of proinflammatory mediators, TNF-a, IL-1B, and IL-6 [83], and
carvacrol is reported to activate PPARa and PPARc and suppresses COX-2
expression [61], and inhibits AChE [62]. Thymol is suggested to potentiate
GABAA receptors through an allosteric binding site [92]. Thymol also acts as
agonist on a1, a2 and b-adrenergic receptors [18].
Human A/Es, Allergy and Toxicity: Occupational airborne contact dermatitis
caused by thyme dust [112], and other allergic symptoms, such as nasal congestion,
dry cough and general weakness [50], and respiratory symptoms [51] have been
reported in Polish thyme farmers. In large doses, it paralyzes the end organs of
sensory nerves, and nerve centers in the spinal cord and medulla.LXXXI In toxic
doses, it produces a sensation of heat in the epigastrum, ringing in the ears, deaf-
ness, profuse sweating, increased urination of dark greenish color, respiratory
distress, extreme prostration, coma and death.LXXXI
Animal Toxicity: T. vulgaris leaves (2% or 10%) fed in diet for 6-weeks were
nontoxic to rats [56]. Rats intraperitoneally injected with thyme extract for 4-days
produced no histopathological changes in liver and kidneys; BUN, creatinine, and uric
acid were significantly increased in animals treated with polyphenolic extract [20].
Potential for Drug-Herb Interactions: Thyme leaves, thymol and carvacrol
administration to mice significantly increased activities of phase I and phase II
metabolizing enzymes [96], that could affect metabolism of prescription drugs.
Commentary: Thyme is very commonly used as a spice (seasoning) the world
over. Nevertheless, despite broad-spectrum antimicrobial profile of the essential oil
and extracts of the plant, there are no systematic clinical trials reported.

References
1. Aazza S, Lyoussi B, Miguel MG. Antioxidant and antiacetylcholinesterase
activities of some commercial essential oils and their major compounds.
Molecules. 2011;16:7672–90.
2. Abu-Darwish MS, Al-Ramamneh EA, Kyslychenko VS, Karpiuk UV. The
antimicrobial activity of essential oils and extracts of some medicinal
plants grown in Ash-shoubak region—south of Jordan. Pak J Pharm Sci.
2012;25:239–46.
3. Abu-Darwish MS, Alu’datt MH, Al-Tawaha AR, et al. Seasonal variation in
essential oil yield and composition from Thymus vulgaris L. during different
growth stages in the south of Jordan. Nat Prod Res. 2012;26:1310–7.
4. Adzet T, Granger R, Passet J, San Martin R. Chemical polymorphism in the
genus Thymus: taxonomic importance. Biochem Syst Ecol. 1977;5:269.
1802 Thymus vulgaris L.

5. Adzet T, Martinez-Verges F. Flavonoids in the leaves of Thymus: a

chemotaxonomic survey. Biochem Syst Ecol. 1981;9:293.
6. Adzet T, Martinez-Verges F. Luteolin and 6-hydroxyluteolin: taxonomically
important flavones in the genus Thymus. Planta Med. 1980;(Suppl.):52.
7. Agbor GA, Oben JE, Ngogang JY, et al. Antioxidant capacity of some
herbs/spices from cameroon: a comparative study of two methods. J Agric
Food Chem. 2005;53:6819–24.
8. Agnihotri S, Vaidya AD. A novel approach to study antibacterial properties
of volatile components of selected Indian medicinal herbs. Indian J Exp
Biol. 1996;34:712–5.
9. Albasini A, Bianchi A, Melegari M, et al. Studies of plants of the genus
Thymus. Atti Soc Nat Mat Modena. 1984;115:1.
10. Al-Bayati FA. Synergistic antibacterial activity between Thymus vulgaris
and Pimpinella anisum essential oils and methanol extracts. J Ethnophar-
macol. 2008;116:403–6.
11. Alexa E, Sumalan RM, Danciu C, et al. Synergistic antifungal, allelopatic
and antiproliferative potential of Salvia officinalis L., and Thymus vulgaris
L. essential oils. Molecules. 2018;23. pii: E185.
12. Alinkina ES, Misharina TA, Fatkullina LD. Antiradical properties of
oregano, thyme, and savory essential oils. Prikl Biokhim Mikrobiol. 2013;
49:82–7 (Russian).
13. Alonso WR, Croteau R. Purification and characterization of the monoter-
pene cyclase gamma-terpinene synthase from Thymus vulgaris. Arch
Biochem Biophys. 1991;286:511–7.
14. Al-Yahya MA, Tariq M, Al-Meshal IA, Mossa JS. Phytochemical and
pharmacological studies on Thymus vulgaris Linn. In: Proceedings of
International Symposium on Chinese Medicine and Materials Research,
Hong Kong, 48; 1984.
15. Asbaghian S, Shafaghat A, Zarea K, et al. Comparison of volatile
constituents, and antioxidant and antibacterial activities of the essential
oils of Thymus caucasicus, T. kotschyanus and T. vulgaris. Nat Prod
Commun. 2011;6:137–40.
16. Aynehchi Y, Sormaghi MHS, Amin GH, et al. Survey of Iranian plants for
saponins, alkaloids, flavonoids and tannins. II. Int J Crude Drug Res.
1982;20:61.
17. Babaei M, Abarghoei ME, Ansari R, et al. Antispasmodic effect of
hydroalcoholic extract of Thymus vulgaris on the guinea-pig ileum. Nat
Prod Res. 2008;22:1143–50.
18. Beer AM, Lukanov J, Sagorchev P. Effect of Thymol on the spontaneous
contractile activity of the smooth muscles. Phytomedicine. 2007;14:65–9.
19. Behnia M, Haghighi A, Komeylizadeh H, et al. Inhibitory effects of Iranian
Thymus vulgaris extracts on in vitro growth of Entamoeba histolytica.
Korean J Parasitol. 2008;46:153–6.
Thymus vulgaris L. 1803

20. Benourad F, Kahvecioglu Z, Youcef-Benkada M, Colet JM. Prospective

evaluation of potential toxicity of repeated doses of Thymus vulgaris L.
extracts in rats by means of clinical chemistry, histopathology and
NMR-based metabonomic approach. Drug Test Anal. 2014;6:1069–75.
21. Bogavac M, Karaman M, Janjušević L, et al. Alternative treatment of
vaginal infections—in vitro antimicrobial and toxic effects of Coriandrum
sativum L. and Thymus vulgaris L. essential oils. J Appl Microbiol. 2015;
119:697–710.
22. Bonjar GH. Inhibition of Clotrimazole-resistant Candida albicans by
plants used in Iranian folkloric medicine. Fitoterapia. 2004;75:74–6.
23. Borugă O, Jianu C, Mişcă C, et al. Thymus vulgaris essential oil: chemical
composition and antimicrobial activity. J Med Life. 2014;7(Spec No. 3):
56–60.
24. Boskabady MH, Aslani MR, Kiani S. Relaxant effect of Thymus vulgaris
on guinea pig tracheal chains and its possible mechanism(s). Phytother
Res. 2006;20:28–33.
25. Bozin B, Mimica-Dukic N, Simin N, Anackov G. Characterization of the
volatile composition of essential oils of some lamiaceae spices and the
antimicrobial and antioxidant activities of the entire oils. J Agric Food
Chem. 2006;54:1822–8.
26. Braga PC, Sasso MD, Culici M, Alfieri M. Eugenol and thymol, alone or
in combination, induce morphological alterations in the envelope of
Candida albicans. Fitoterapia. 2007;78:396–400.
27. Cavalcante Melo FH, Rios ER, Rocha NF, et al. Antinociceptive activity of
carvacrol (5-isopropyl-2-methylphenol) in mice. J Pharm Pharmacol. 2012;
64:1722–9.
28. Centeno S, Calvo MA, Adelantado C, Figueroa S. Antifungal activity of
extracts of Rosmarinus officinalis and Thymus vulgaris against Aspergillus
flavus and A. ochraceus. Pak J Biol Sci. 2010;13:452–5.
29. Chizzola R, Michitsch H, Franz C. Antioxidative properties of Thymus
vulgaris leaves: comparison of different extracts and essential oil chemo-
types. J Agric Food Chem. 2008;56:6897–904.
30. Chun H, Shin DH, Hong BS, et al. Purification and biological activity of
acidic polysaccharide from leaves of Thymus vulgaris L. Biol Pharm Bull.
2001;24:941–6.
31. Dapkevicius A, van Beek TA, Lelyveld GP, et al. Isolation and structure
elucidation of radical scavengers from Thymus vulgaris leaves. J Nat Prod.
2002;65:892–6.
32. de Carvalho RJ, de Souza GT, Honório VG, et al. Comparative inhibitory
effects of Thymus vulgaris L. essential oil against Staphylococcus aureus,
Listeria monocytogenes and mesophilic starter coculture in cheese-
mimicking models. Food Microbiol. 2015;52:59–65.
1804 Thymus vulgaris L.

33. de Lira Mota KS, de Oliveira Pereira F, de Oliveira WA, et al. Antifungal
activity of Thymus vulgaris L. essential oil and its constituent phytochem-
icals against Rhizopus oryzae: interaction with ergosterol. Molecules.
2012;17:14418–33.
34. Díaz-Maroto MC, Díaz-Maroto Hidalgo IJ, Sánchez-Palomo E, Pérez-
Coello MS. Volatile components and key odorants of fennel (Foeniculum
vulgare Mill.) and thyme (Thymus vulgaris L.) oil extracts obtained by
simultaneous distillation-extraction and supercritical fluid extraction. J Agric
Food Chem. 2005;53:5385–9.
35. Dorman HJ, Deans SG. Antimicrobial agents from plants: antibacterial
activity of plant volatile oils. J Appl Microbiol. 2000;88:308–16.
36. El-Nekeety AA, Mohamed SR, Hathout AS, et al. Antioxidant properties
of Thymus vulgaris oil against aflatoxin-induce oxidative stress in male
rats. Toxicon. 2011;57:984–91.
37. El-Newary SA, Shaffie NM, Omer EA. The protection of Thymus vulgaris
leaves alcoholic extract against hepatotoxicity of alcohol in rats. Asian
Pac J Trop Med. 2017;10:361–71.
38. Engelbertz J, Schwenk T, Kinzinger U, et al. Thyme extract, but not
thymol, inhibits endothelin-induced contractions of isolated rat trachea.
Planta Med. 2008;74:1436–40.
39. Eraky MA, El-Fakahany AF, El-Sayed NM, Abou-Ouf EA, Yaseen DI.
Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a
mouse model. Parasitol Res. 2016;115:2863–71.
40. Esmaeili D, Mobarez AM, Tohidpour A. Anti-Helicobacter pylori activities
of shoya powder and essential oils of Thymus vulgaris and Eucalyptus
globulus. Open Microbiol J. 2012;6:65–9.
41. Essawi T, Srour M. Screening of some Palestinian medicinal plants for
antibacterial activity. J Ethnopharmacol. 2000;70:343–9.
42. Fachini-Queiroz FC, Kummer R, Estevão-Silva CF, et al. Effects of
thymol and carvacrol, constituents of Thymus vulgaris L. essential oil,
on the inflammatory response. Evid Based Complement Alternat Med.
2012;2012:657026.
43. Fani M, Kohanteb J. In vitro antimicrobial activity of Thymus vulgaris
essential oil against major oral pathogens. J Evid Based Complementary
Altern Med. 2017;22:660–6.
44. Fournomiti M, Kimbaris A, Mantzourani I, et al. Antimicrobial activity of
essential oils of cultivated oregano (Origanum vulgare), sage (Salvia
officinalis), and thyme (Thymus vulgaris) against clinical isolates of
Escherichia coli, Klebsiella oxytoca, and Klebsiella pneumoniae. Microb
Ecol Health Dis. 2015;26:23289.
45. Fujita M, Shiota S, Kuroda T, et al. Remarkable synergies between baicalein
and tetracycline, and baicalein and beta-lactams against methicillin-resistant
Staphylococcus aureus. Microbiol Immunol. 2005;49:391–6.
Thymus vulgaris L. 1805

46. Gerhardt U, Schroeter A. Rosmarinic acid—a naturally occurring anti-

oxidant in spices. Fleischwirtschaft. 1983;63:1628.
47. Gerhardt U, Windmueller R. Polarography in the determination of ascorbic
acid in seasonings. Fleischwirtschaft. 1981;61:1389.
48. Gerhardt U, Wolff M. Examining the essential oil content of new species of
thyme for their suitability in meat product manufacture. Fleischwirtschaft.
1976;56:1305.
49. Giordani R, Regli P, Kaloustian J, et al. Antifungal effect of various
essential oils against Candida albicans. Potentiation of antifungal action of
amphotericin B by essential oil from Thymus vulgaris. Phytother Res.
2004;18:990–5.
50. Golec M, Skórska C, Mackiewicz B, Dutkiewicz J. Health effects of
exposure to thyme dust in a group of thyme growing farmers. Ann Univ
Mariae Curie Sklodowska [Med]. 2003;58:195–203.
51. Golec M, Skórska C, Mackiewicz B, et al. Respiratory effects of exposure
to dust from herbs. Ann Agric Environ Med. 2005;12:5–10.
52. Granger R, Passet J. Thymus vulgaris native of France. Chemical varieties
and chemotaxonomy. Phytochemistry. 1973;12:1683.
53. Grosso C, Figueiredo AC, Burillo J, et al. Composition and antioxidant
activity of Thymus vulgaris volatiles: comparison between supercritical
fluid extraction and hydrodistillation. J Sep Sci. 2010;33:2211–8.
54. Hammad M, Sallal AK, Darmani H. Inhibition of Streptococcus mutans
adhesion to buccal epithelial cells by an aqueous extract of Thymus
vulgaris. Int J Dent Hyg. 2007;5:232–5.
55. Haraguchi H, Saito T, Ishikawa H, et al. Antiperoxidative components in
Thymus vulgaris. Planta Med. 1996;62:217–21.
56. Haroun EM, Mahmoud OM, Adam SE. Effect of feeding Cuminum
cyminum fruits, Thymus vulgaris leaves or their mixture to rats. Vet Hum
Toxicol. 2002;44:67–9.
57. Hersch-Martínez P, Leaños-Miranda BE, Solórzano-Santos F. Antibacte-
rial effects of commercial essential oils over locally prevalent pathogenic
strains in Mexico. Fitoterapia. 2005;76:453–7.
58. Hitokoto H, Morozumi S, Wauke T, et al. Inhibitory effects of spices on
growth and toxin production of toxigenic fungi. Appl Environ Microbiol.
1980;39:818–22.
59. Horváthová E, Srančíková A, Regendová-Sedláčková E, et al. Enriching
the drinking water of rats with extracts of Salvia officinalis and Thymus
vulgaris increases their resistance to oxidative stress. Mutagenesis. 2016;
31:51–9.
60. Hossain MA, AL-Raqmi KA, AL-Mijizy ZH, Weli AM, Al-Riyami Q.
Study of total phenol, flavonoids contents and phytochemical screening of
various leaves crude extracts of locally grown Thymus vulgaris. Asian
Pac J Trop Biomed. 2013;3:705–10.
1806 Thymus vulgaris L.

61. Hotta M, Nakata R, Katsukawa M, et al. Carvacrol, a component of thyme

oil, activates PPARalpha and gamma and suppresses COX-2 expression.
J Lipid Res. 2010;51:132–9.
62. Jukic M, Politeo O, Maksimovic M, et al. In vitro acetylcholinesterase
inhibitory properties of thymol, carvacrol and their derivatives thymo-
quinone and thymohydroquinone. Phytother Res. 2007;21:259–61.
63. Khan MS, Ahmad I, Cameotra SS. Carum copticum and Thymus vulgaris
oils inhibit virulence in Trichophyton rubrum and Aspergillus spp. Braz J
Microbiol. 2014;45:523–31.
64. Kitajima J, Ishikawa T, Urabe A, Satoh M. Monoterpenoids and their
glycosides from the leaf of thyme. Phytochemistry. 2004;65:3279–87.
65. Kitajima J, Ishikawa T, Urabe A. A new hydroxyjasmone glucoside and its
related compounds from the leaf of thyme. Chem Pharm Bull (Tokyo).
2004;52:1013–4.
66. Koch C, Reichling J, Schneele J, Schnitzler P. Inhibitory effect of essential
oils against herpes simplex virus type 2. Phytomedicine. 2008;15:71–8.
67. Kohiyama CY, Yamamoto Ribeiro MM, Mossini SA, et al. Antifungal
properties and inhibitory effects upon aflatoxin production of Thymus
vulgaris L. by Aspergillus flavus Link. Food Chem. 2015;173:1006–10.
68. Kulisić T, Krisko A, Dragović-Uzelac V, et al. The effects of essential oils
and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum),
thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the
copper-induced oxidation of human low-density lipoproteins. Int J Food
Sci Nutr. 2007;58:87–93.
69. Lall N, Meyer JJ. In vitro inhibition of drug-resistant and drug-sensitive
strains of Mycobacterium tuberculosis by ethnobotanically selected South
African plants. J Ethnopharmacol. 1999;66:347–54.
70. Lamy J. Thyme breeding in the Drome region (France). Cosmet Aromes.
1983;51:73.
71. Lee KG, Shibamoto T. Determination of antioxidant potential of volatile
extracts isolated from various herbs and spices. J Agric Food Chem.
2002;50:4947–52.
72. Lim WC, Seo JM, Lee CI, et al. Stimulative and sedative effects of
essential oils upon inhalation in mice. Arch Pharm Res. 2005;28:770–4.
73. López P, Sanchez C, Batlle R, Nerín C. Vapor-phase activities of
cinnamon, thyme, and oregano essential oils and key constituents against
foodborne microorganisms. J Agric Food Chem. 2007;55:4348–56.
74. Mahboubi A, Kamalinejad M, Ayatollahi AM, Babaeian M. Total phenolic
content and antibacterial activity of five plants of Labiatae against four
food borne and some other bacteria. Iran J Pharm Res. 2014;13:559–66.
75. Mancini E, Senatore F, Del Monte D, et al. Studies on chemical compo-
sition, antimicrobial and antioxidant activities of five Thymus vulgaris L.
essential oils. Molecules. 2015;20:12016–28.
Thymus vulgaris L. 1807

76. Marino M, Bersani C, Comi G. Antimicrobial activity of the essential oils

of Thymus vulgaris L. measured using a bioimpedometric method. J Food
Prot. 1999;62:1017–23.
77. Meister A, Bernhardt G, Christoffel V, Buschauer A. Antispasmodic
activity of Thymus vulgaris extract on the isolated guinea pig trachea:
discrimination between drug and ethanol effects. Planta Med. 1999;65:
512–6.
78. Mohsenzadeh M. Evaluation of antibacterial activity of selected Iranian
essential oils against Staphylococcus aureus and Escherichia coli in
nutrient broth medium. Pak J Biol Sci. 2007;10:3693–7.
79. Morimitsu Y, Yoshida K, Esaki S, Hirota A. Protein glycation inhibitors
from thyme (Thymus vulgaris). Biosci Biotechnol Biochem. 1995;59:
2018–21.
80. Naemura A, Ura M, Yamashita T, et al. Long-term intake of rosemary and
common thyme herbs inhibits experimental thrombosis without prolonga-
tion of bleeding time. Thromb Res. 2008;122:517–22.
81. Nguefack J, Budde BB, Jakobsen M. Five essential oils from aromatic
plants of Cameroon: their antibacterial activity and ability to permeabilize
the cytoplasmic membrane of Listeria innocua examined by flow
cytometry. Lett Appl Microbiol. 2004;39:395–400.
82. Nolkemper S, Reichling J, Stintzing FC, et al. Antiviral effect of aqueous
extracts from species of the Lamiaceae family against Herpes simplex virus
type 1 and type 2 in vitro. Planta Med. 2006;72:1378–82.
83. Ocaña A, Reglero G. Effects of thyme extract oils (from Thymus vulgaris,
Thymus zygis, and Thymus hyemalis) on cytokine production and gene
expression of oxLDL-stimulated THP-1-macrophages. J Obes. 2012;2012:
104706.
84. Okazaki K, Kawazoe K, Takaishi Y. Human platelet aggregation inhibitors
from thyme (Thymus vulgaris L.). Phytother Res. 2002;16:398–9.
85. Panizzi L, Flamini G, Cioni PL, Morelli I. Composition and antimicrobial
properties of essential oils of four Mediterranean Lamiaceae. J Ethnophar-
macol. 1993;39:167–70.
86. Park BS, Choi WS, Kim JH, et al. Monoterpenes from thyme (Thymus
vulgaris) as potential mosquito repellents. J Am Mosq Control Assoc. 2005;
21:80–3.
87. Passet J: Chemical differentiation of oil of thyme, its properties and
significance. Dragoco Rep (Ger. Fragrance Ed.). 1980;27:234.
88. Passet J. Chemical variability within thyme, its manifestations and its
significance. Parfums Cosmet Aromes. 1979;28:39.
89. Pellecuer J, Jacob M, Simeon de Buochberg M, et al. Tests on the use of
the essential oils of Mediterranean aromatic plants in conservative
odontology. Plant Med Phytother. 1980;14:83.
90. Pina-Vaz C, Gonçalves Rodrigues A, Pinto E, et al. Antifungal activity of
thymus oils and their major compounds. J Eur Acad Dermatol Venereol.
2004;18:73–8.
1808 Thymus vulgaris L.

91. Pozzatti P, Scheid LA, Spader TB, et al. In vitro activity of essential oils
extracted from plants used as spices against fluconazole-resistant and
fluconazole-susceptible Candida spp. Can J Microbiol. 2008;54:950–6.
92. Priestley CM, Williamson EM, Wafford KA, Sattelle DB. Thymol, a
constituent of thyme essential oil, is a positive allosteric modulator of
human GABA(A) receptors and a homo-oligomeric GABA receptor from
Drosophila melanogaster. Br J Pharmacol. 2003;140:1363–72.
93. Proestos C, Chorianopoulos N, Nychas GJ, Komaitis M. RP-HPLC
analysis of the phenolic compounds of plant extracts. Investigation of their
antioxidant capacity and antimicrobial activity. J Agric Food Chem. 2005;
53:1190–5.
94. Ramkissoon J, Mahomoodally M, Ahmed N, Subratty A. Antioxidant and
antiglycation activities correlates with phenolic composition of tropical
medicinal herbs. Asian Pac J Trop Med. 2013;6:561–9.
95. Rana P, Soni G. Antioxidant potential of thyme extract: alleviation of
N-nitrosodiethylamine-induced oxidative stress. Hum Exp Toxicol. 2008;
27:215–21.
96. Sasaki K, Wada K, Tanaka Y, et al.: Thyme (Thymus vulgaris L.) leaves
and its constituents increase the activities of xenobiotic-metabolizing
enzymes in mouse liver. J Med Food. 2005;8:184–9.
97. Satyal P, Murray BL, McFeeters RL, Setzer WN. Essential oil character-
ization of Thymus vulgaris from various geographical locations. Foods.
2016;5. pii: E70.
98. Schmidt E, Wanner J, Hiiferl M, et al. Chemical composition, olfactory
analysis and antibacterial activity of Thymus vulgaris chemotypes geran-
iol, 4-thujanol/terpinen-4-ol, thymol and linalool cultivated in southern
France. Nat Prod Commun. 2012;7:1095–8.
99. Schnitzler P, Koch C, Reichling J. Susceptibility of drug-resistant clinical
herpes simplex virus type 1 strains to essential oils of ginger, thyme, hyssop,
and sandalwood. Antimicrob Agents Chemother. 2007;51:1859–62.
100. Schratz E, Hoerster H. Composition of essential oils of Thymus vulgaris
and Thymus marschallianus in relation to leaf age and season of the year.
Planta Med. 1970;19:160.
101. Segvić Klarić M, Kosalec I, Mastelić J, et al. Antifungal activity of thyme
(Thymus vulgaris L.) essential oil and thymol against moulds from damp
dwellings. Lett Appl Microbiol. 2007;44:36–42.
102. Sfeir J, Lefrançois C, Baudoux D, et al. In vitro antibacterial activity of
essential oils against Streptococcus pyogenes. Evid Based Complement
Alternat Med. 2013;2013:269161.
103. Sharifzadeh A, Jebeli Javan A, Shokri H, Abbaszadeh S, Keykhosravy K.
Evaluation of antioxidant and antifungal properties of the traditional plants
against foodborne fungal pathogens. J Mycol Med. 2016;26:e11–7.
104. Sienkiewicz M, Łysakowska M, Ciećwierz J, et al. Antibacterial activity of
thyme and lavender essential oils. Med Chem. 2011;7:674–89.
Thymus vulgaris L. 1809

105. Sienkiewicz M, Łysakowska M, Denys P, Kowalczyk E. The antimicrobial

activity of thyme essential oil against multidrug resistant clinical bacterial
strains. Microb Drug Resist. 2012;18:137–48.
106. Simeon de Bouchberg M, Allegrini J, Bessiere C, et al. Microbiological
properties of essential oils of Thymus vulgaris Linneaus Chemotypes. Riv
Ital Essenze Profumi Piante Off, Aromi, Saponi, Cosmet Aerosol. 1976;
58:527.
107. Simonyan AV, Shinkarenko AL, Litvinenko VI. Flavonoid glycosides of
some species of thyme cultivated in the Caucasus. Rast Resur. 1973;9:395.
108. Soković M, Glamoclija J, Cirić A, et al. Antifungal activity of the essential
oil of Thymus vulgaris L. and thymol on experimentally induced dermato-
mycoses. Drug Dev Ind Pharm. 2008;34:1388–93.
109. Soković M, Glamočlija J, Marin PD, et al. Antibacterial effects of the
essential oils of commonly consumed medicinal herbs using an in vitro
model. Molecules. 2010;15:7532–46.
110. Soković MD, Vukojević J, Marin PD, et al. Chemical composition of
essential oils of Thymus and Mentha species and their antifungal activities.
Molecules. 2009;14:238–49.
111. Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants
on different mycotoxigenic fungi. Food Chem Toxicol. 2002;40:1669–75.
112. Spiewak R, Skorska C, Dutkiewicz J. Occupational airborne contact
dermatitis caused by thyme dust. Contact Dermatitis. 2001;44:235–9.
113. Taherian AA, Babaei M, Vafaei AA, et al. Antinociceptive effects of
hydroalcoholic extract of Thymus vulgaris. Pak J Pharm Sci. 2009;22:83–9.
114. Takeuchi H, Lu ZG, Fujita T. New monoterpene glucoside from the aerial
parts of thyme (Thymus vulgaris L.). Biosci Biotechnol Biochem. 2004;
68:1131–4.
115. Tohidpour A, Sattari M, Omidbaigi R, et al. Antibacterial effect of
essential oils from two medicinal plants against methicillin-resistant
Staphylococcus aureus (MRSA). Phytomedicine. 2010;17:142–5.
116. Tsai ML, Lin CC, Lin WC, Yang CH. Antimicrobial, antioxidant, and
anti-inflammatory activities of essential oils from five selected herbs.
Biosci Biotechnol Biochem. 2011;75:1977–83.
117. Tullio V, Mandras N, Allizond V, et al. Positive interaction of thyme
(red) essential oil with human polymorphonuclear granulocytes in
eradicating intracellular Candida albicans. Planta Med. 2012;78:1633–5.
118. Van den Broucke CO, Lemli JA. Spasmolytic activity of the flavonoids
from Thymus vulgaris. Pharm Weekbl, Sci Ed. 1983;5:9–14.
119. Van den Broucke CO. New pharmacologically important flavonoids of
Thymus vulgaris. World Crops: Prod Util Descr. 1982;7:271.
120. van Vuuren SF, Suliman S, Viljoen AM. The antimicrobial activity of four
commercial essential oils in combination with conventional antimicrobials.
Lett Appl Microbiol. 2009;48:440–6.
1810 Thymus vulgaris L.

121. Vetvicka V, Vetvickova J. Essential oils from thyme (Thymus vulgaris):

chemical composition and biological effects in mouse model. J Med Food.
2016;19:1180–7.
122. Wang M, Kikuzaki H, Lin CC, et al. Acetophenone glycosides from thyme
(Thymus vulgaris L.). J Agric Food Chem.1999;47:1911–4.
123. Youdim KA, Deans SG. Dietary supplementation of thyme (Thymus
vulgaris L.) essential oil during the lifetime of the rat: its effects on the
antioxidant status in liver, kidney and heart tissues. Mech Ageing Dev.
1999;109:163–75.
124. Zheng W, Wang SY. Antioxidant activity and phenolic compounds in
selected herbs. J Agric Food Chem. 2001;49:5165–70.
125. Zu Y, Yu H, Liang L, et al. Activities of ten essential oils towards
Propionibacterium acnes and PC-3, A-549 and MCF-7 cancer cells.
Molecules. 2010;15:3200–10.
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms
(Menispermaceae)

(Syns.: T. sinensis (Lour.) Merr.; T. cordifolia (D.C.) Miers, T. cordifolia (Willd.)

Miers.; Cocculus cordifolius (Willd.) DC.; Menispermum cordifolium Willd.)

Abstract
A large, perennial, deciduous, climbing herbaceous vine, that is distributed
throughout India, Myanmar, Sri Lanka and China. In Ayurveda, it is mentioned as
rasayan and is traditionally used for the treatment of asthma, chronic cough, to
improve immune system, as a general tonic, antiperiodic in fevers, antispasmodic,
anti-inflammatory, antiarthritic and antidiabetic agent, and is also credited with
aphrodisiac property. Fresh plant is said to be more efficient than the dried one. It is
taken with milk in rheumatism, acidity of the urine and dyspepsia. The stem of this
very bitter herbaceous vine is used medicinally in Unani medicine as a bitter tonic,
astringent, stomachic, anthelmintic, blood purifier, diuretic, and antipyretic for all
types of fevers, including tuberculous fever. Water extracted from fresh plant is
more potent. It is also used for chronic diarrhea, and in diseases, such as syphilis,
and leprosy. In the Philippines and Malaysia, this is the most popular medicinal
plant, and is considered a universal medicine. Its aqueous extract is used as a
remedy for stomach trouble, indigestion and diarrhea. A preparation with coconut
oil is considered an effective cure for rheumatism and for flatulence in children.
Various constituents, such as alkaloids, diterpenoid lactones, cardiac glycosides,
steroids, sesquiterpenoid, phenolics, aliphatic compounds and polysaccharides
have been reported from the plant. The yield and physicochemical profile of the
starchy material extracted from stem used in Ayurvedic preparations vary due to the
plant stem size, collection time, season and maturity of the plant. Total alkaloidal
contents are a bit higher in rainy and spring seasons. Aqueous, alcohol and
chloroform extracts exerted significant hypoglycemic and antihyperglycemic
effects in normal and diabetic animals. Aqueous extract significantly stimulates
glucose uptake in 3T3-L1 adipocytes, comparable to insulin and greater than
pioglitazone. Aqueous extract also prevented hyperalgesia of diabetic neuropathy,
and inhibited aldose reductase. Ethanol extract of aerial parts offered significant
neuroprotection against 6-OHDA-induced Parkinson’s disease-like lesions in rat
model, and decreased locomotor activity but did not affect amphetamine-induced
hyperactivity in mice.
© Springer Nature Switzerland AG 2020 1811
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_186
1812 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

Keywords





Gilo Giloe Guduchi Guduchi-kräutertee Gulancha tinospora
Gulbel





Guricha Jivantika Makabúhaí Xin ye qing niu dan

Vernaculars: Urd.: Giloe; Hin.: Giloe, Guduchi, Gulach, Gulancha, Guruch; San.:
Amurta, Bhishakpriya, Chinnaruha, Giloy, Guduchi, Jivantika, Nirjara, Pittaghni,
Soma-valli; Ben.: Gadancha, Giloe, Gulach, Gulancha, Palo (extract); Guj.: Galo;
Mal.: Amrita, Amruthu, Chitramruta; Mar.: Gharol, Guduchi, Gulavel, Guloe;
Tam.: Amirthavalli, Kunali, Seenthil kodi, Shindilakodi, Shindil-shakkarai (extract);
Tel.: Guluchi, Guricha, Manapala, Tippa-teega, Tippa-tige-satu (extract), Tippatege-
veru (root); Ara.: Gilo; Chi.: 心叶青牛胆, Xin ye qing niu dan; Eng.: Gulancha
tinospora, Heartleaf moonseed; Fre.: Guduchi, Tinofolin; Ger.: Guduchi-kräutertee;
Nep.: Gurjo; Per.: Gulbel; Tag.: Makabúhaí; Tha.: Ching cha chali.
Description: It is a large, glabrous, perennial, deciduous, climbing herbaceous vine
of weak and fleshy stem spreading on trees of Mangifera indica and Azadirachta
indica. It is distributed throughout India, Myanmar, Sri Lanka and China. Fresh stem
has a green succulent bark, covered by a thin brown epidermis, which peels off in
flakes. It is studded with warty prominences, and gives off roots here and there, and
branches bearing smooth heart-shaped leaves, and bunches of red berries. When dry it
shrinks very much, and the bark separates from the wood, and becomes of a
dull-brown color; the latter consists of a number of wedge-shaped bundles; the taste is
very bitter, the odor is not in any way peculiar.XL Flowers are typically greenish-
yellow, and the flowering season extends from summer to winter; male flowers are
clustered, while the female flowers are solitary [99]. According to Narkhede et al. [51],
T. sinensis closely resembles the description of guduchi in Ayurvedic literature rather
than the commonly available T. cordifolia, but may be used as a substitute for
T. sinensis; T. cordifolia growing on Azadirachta indica is called Neem-guduchi and
has better immunomodulatory potential (Figs. 1 and 2).
Actions and Uses: In Ayurveda, it (temperament, cold and dry) is mentioned as
rasayan and is traditionally used for the treatment of asthma, chronic cough, to
improve immune system, as a general tonic, antiperiodic in fevers, antispasmodic,
anti-inflammatory, antiarthritic and antidiabetic agent, and is also credited with
aphrodisiac property [73, 98]. Fresh plant is said to be more efficient than the dried
one. It is taken with milk in rheumatism, acidity of the urine and dyspepsia. It is said
that if the stem is placed upon a bush in the open air, will retain its vitality through the
hot season, and when the rains start, put forth leaves and long whipcord-like roots,
which soon reach the ground, hence the Sanskrit synonym Chinnaruha, or growing
when cut.XL The stem (temperament, hot 1° and dry 1°) of this very bitter herbaceous
vine is used medicinally in Unani medicine as a bitter tonic, astringent, stomachic,
anthelmintic, blood purifier, diuretic, and antipyretic for all types of fevers, including
tuberculous fever. Water extracted from fresh plant is more potent. It is also used for
chronic diarrhea, and in diseases, such as syphilis, and leprosy.LXXVII It is also
described as alterative, and demulcent, and used in dyspepsia, secondary syphilis,
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms 1813

Fig. 1 Tinospora cordifolia, Plant, Tmd, WikimediaCommons, https://commons.wikimedia.org/

wiki/File:Tinospora_cordifolia.jpg

Fig. 2 Tinospora cordifolia, Fruits, Vinayaraj, WikimediaCommons; ShareAlike 4.0 Interna-

tional CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Tinospora_cordifolia_fruits_03.
JPG; https://creativecommons.org/licenses/by-sa/4.0/deed.en

rheumatism, skin diseases (such as impetigo), jaundice, debility caused by repeated

attacks of fever,LXXXI,CV urinary disorders, diabetes and anemia [8]. Water extract is
used as a febrifuge and is referred to as ‘Indian quinine.’CV Whole plant pounded with
water is used for spermatorrhea and gonorrhea.CXVII In Ramgiri, Koraput district of
Orissa (India), tribals orally administer 8 g starch obtained from stem, mixed in water
1814 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

with equal quantity of sugar, daily for seven days to treat jaundice [24]. The Boxa tribe
of Nainital district (India), use stem decoction bath in postdelivery fever [84]. It is
also considered antihepatotoxic, antistress, immunomodulatory, and antioxidant [52].
In the Philippines and Malaysia, this is the most popular medicinal plant, and is
considered a universal medicine. The aqueous extract is used as a remedy for stomach
trouble, indigestion and diarrhea. A preparation with coconut oil is considered an
effective cure for rheumatism and for flatulence in children.CXVII
Phytoconstituents: Various constituents, such as alkaloids, diterpenoid lactones,
cardiac glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds and
polysaccharides have been reported from the plant [47, 99]. The yield and physico-
chemical profile of the starchy material extracted from stem used in Ayurvedic
preparations vary due to the plant stem size, collection time, season and maturity of the
plant. Total alkaloidal contents are a bit higher in rainy and spring seasons [79]. Ethanol
leaf extract showed the presence of steroids, anthraquinones, flavonoids, cardiac
glycosides, tannins and phenolics [94]. Seven compounds, 11-hydroxymustakone,
N-methyl-2-pyrrolidone, N-formylannonain, magnoflorine, cordifolioside A, tinocor-
diside, and syringin, with immunomodulatory activity were isolated, and the activity is
assumed to be due to their synergistic effect [80]. Bala et al. [8] also isolated jatror-
rhizine, palmatine, and yangambin from stem. The isoquinoline alkaloids, jatror-
rhizine, palmatine and magnoflorine demonstrated significant inhibitory activity
against aldose reductase isolated from male rats [56]. A novel sulfur-containing
clerodane diterpene glycoside, cordifolide A, and two diterpene glycosides, cordi-
folides B and C were also isolated from the stem [53]. Ahmad et al. [4] isolated
tinosporafuranol, tinosporafurandiol, tinosporaclerodanol, and tinosporaclerodanoid,
along with b-sitosterol from stem bark. Two aporphine alkaloids (Tinoscorside A and
B), a clerodane diterpene, tinoscorside C and a phenylpropanoid, tinoscorside D were
isolated from methanol extract of aerial parts [100], while four clerodane furan-
oditerpene glucosides (Amritosides A, B, C and D) [46], three norditerpene furang-
lycosides, cordifolisides A, B and C [16], and two diterpinoid furonolactones,
tinosporide [92] and columbin [93] were isolated from the stem. An immunologically
active arabinogalactan with polyclonal mitogenic activity against B-cells was also
reported from the stem [13]. Several other immunomodulating compounds have been
reported from the plant. Syringin and cordiol inhibit in vitro immunohaemolysis of
antibody-coated sheep erythrocytes by guinea pig serum; while cordioside, cordio-
folioside A and cordiol activate macrophages [36]. A polysaccharide from stem is
composed of glucose (98%), xylose (0.8%), arabinose (0.5%), galactose (0.3%),
rhamnose (0.2%) and mannose (0.2%) [30]. Jatrorrhizine is also reported from the root
of the plant [74].
Pharmacology: Aqueous, alcohol and chloroform extracts exerted significant
hypoglycemic and antihyperglycemic effects in normal and diabetic animals [19, 21,
37, 39, 48, 58, 103]. Aqueous extract also prevented hyperalgesia of diabetic neu-
ropathy, and in vitro inhibited aldose reductase [49]. Overexpression of angio-
genic and inflammatory mediators, markers of diabetic retinopathy, was inhibited,
retinal oxidative stress reduced and antioxidant enzyme levels of diabetic rats was
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms 1815

restored [3]. Treatment of diabetic animals also prevents polyuria and reduces urinary
albumin [20], rise in insulin, TGs and glucose-insulin index, improves antioxidant
status [66, 67, 71], inhibits a-glucosidase [14], and significantly prevents cataract
formation [3, 65]. Oral administration of an a-glucosidase inhibitor constituent,
saponarin, to maltose-fed rats produced hypoglycemic activity in doses of 20–
80 mg/kg, comparable to 100–200 mg/kg of acarbose [76]. The isoquinoline alkaloid
rich fraction of the stem and three alkaloids viz., palmatine, jatrorrhizine and mag-
noflorine significantly decreased FBG, and increased serum insulin level in glucose-
fed rats [55]. Aqueous and ethanol root extracts also significantly reduced serum and
tissue cholesterol, phospholipids, FFAs, and glucose of diabetic rats [60, 61, 90], and
ethanol extract also improved antioxidant status [59, 62]. The plant is an immunos-
timulator [5, 40, 50, 81, 89, 91, 101]; the aqueous extract improved cellular immunity
and significantly reduced rats’ mortality following cholestasis and E. coli infection
[69]; and the ethanol extract improved phagocytic function without affecting humoral
or cell-mediated immune system [6], protected against CP-induced myelosuppression
and leucopenia [44, 95], and against gamma radiation exposure [18, 52, 85]. Acti-
vation of macrophages by the extract [75] leads to increase in GM-CSF, resulting in
leucocytosis and improved neutrophil function [96]. Various extracts exhibit anal-
gesic and anti-inflammatory activities [17, 25, 57]. In a mouse model of asthma,
hydroalcohol extract protected against oxidative stress, proinflammatory cytokines
release and redox signaling, and reduced airway hyperresponsiveness [98].
Ethanol extract of aerial parts offered significant neuroprotection against 6-
OHDA-induced Parkinson’s disease-like lesions in rat model [41], and decreased
locomotor activity but did not affect amphetamine-induced hyperactivity in mice
[31]. Methanol stem extract significantly inhibited in vitro AChE [102], and petro-
leum ether extract at a relatively low dose produced significant antidepressant-like
effect in mice, comparable to imipramine and sertraline, without significantly
affecting locomotor functions and reducing activities of MAOs of whole brain [15].
Pretreatment with ethanol extract of whole plant reduced the infarct size and lipid
peroxide levels of serum and heart tissue in surgically-induced myocardial I/R injury
in rats [63], and normalized calcium chloride-induced cardiac arrhythmia in rats,
comparable to verapamil [77]. Aqueous extracts of stem and leaves also reversed
hematological changes in lead-treated mice [82]. Pretreatment with stem and leaves
extracts protects from lead nitrate-hepatotoxicity, increased activities of antioxidant
enzymes [83], CCl4-liver damage [9], and whole plant powder protected against
antitubercular drugs-hepatotoxicity [1, 54]. Ethanol extract of stems and leaves also
showed antioxidant activity and decreased LPO in NDEA-induced liver cancer in rats
[32], in diabetic rats [88], and CP-induced toxicity in mice [45].
Exposure of HeLa cells to methanol, aqueous, methylene chloride and dichlor-
omethane extracts caused significant dose-dependent increase in cell killing [27, 28].
Dichloromethane extract increased tumor-free survival of mice transplanted with
Ehrlich ascites carcinoma, with optimum effect when the extract was administered
within five days of tumor inoculation [29, 64]. Hydroethanol extract also increased
survival time and decreased peritoneal ascitic fluid content of Dalton’s lymphoma
ascites in Swiss mice [2], due to augmentation of function of macrophages [86].
1816 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

Significant reduction by the extract in cumulative number, tumor yield, tumor burden,
and tumor weight, along with significant elevation of phase II detoxifying enzymes,
and inhibition of LPO was reported in skin carcinogenesis model [12]. The extract
also inhibits melanoma cell-induced capillary formation in animals [42]; octacosanol
has been identified as the antiangiogenic compound [97]. A polysaccharide fraction
produced 72% inhibition in metastases formation of melanoma cells in the lungs of
syngeneic C57BL/6 mice [43].
Sequential petroleum ether, chloroform, ethyl acetate, acetone, and ethanol extracts
exhibited activity against Pseudomonas spp., while acetone, ethanol and aqueous
extracts were active against K. pneumonia; Proteus spp. were inhibited by petroleum
ether and benzene extracts, and E. coli was susceptible to ethyl acetate and acetone
extracts [47]. Ethanol extract was inhibitory against E. coli, P. vulgaris, E. faecalis,
S. typhi, S. aureus and S. marcesenses [33], and clinical isolates of MRSA and
carbapenemase-producing K. pneumoniae [10]. Oral administration of methanol
extract of stem to male rats for 60-days significantly decreased weight of testes,
epididymis, seminal vesicle and ventral prostate, significantly reduced sperm motility
and density, and serum testosterone levels, resulting in complete infertility [23].
A standardized aqueous extract reversed effects of cisplatin on gastric emptying,
normalized intestinal hypermotility and the phagocytic function irrespective to the
direction of change, complying to the definition of an adaptogen [70]. Ethanol and
aqueous extracts of stem-bark produced dose-dependent antidiarrheal effect, and
gastric antiulcer activity in rats [38].
Clinical Studies: In thirty Indian patients with malignant obstructive jaundice,
addition of aqueous extract to conventional treatment with vitamin K, antibiotics and
biliary drainage in half of the patients normalized the neutrophils phagocytic activity,
completely resolved clinical signs of septicemia, and improved postoperative survival
to near complete, compared to the control group with 40% survival rate [68]. Sup-
plementation with aqueous extract to chronic asymptomatic moderate alcohol drinker
with no chronic liver disease was still significantly protective against alcohol-induced
damage [78]. Addition of aqueous extract as adjunct to chloroquine in partially/slow
responding three Indian patients with malarial splenomegaly significantly regressed
spleen size by two-third after six-months of treatment [87]. Sixty percent HIV positive
Indian participants treated with a standardized aqueous extract for six-months reported
relief from various symptoms compared to 20% in the placebo group of a double-blind
RCT [35]. In a double-blinded RCT of patients with allergic rhinitis, eight-weeks
treatment with the extract was effective in completely relieving sneezing in 83% and in
more than two-thirds from nasal discharge and nasal obstruction, compared to those
treated with placebo, who showed no relief in more than 80% patients [7, 22]. Topical
application of a T. cordifolia lotion was comparably effective with permethrin in
scabies-infected pediatric patients [11].
Mechanism of Action: Aqueous extract significantly stimulates glucose uptake in
3T3-L1 adipocytes, comparable to insulin and greater than pioglitazone [34].
Dichloromethane extract of stem in vitro inhibited 100% of a-glucosidase, 75% of
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms 1817

salivary amylase and 83% pancreatic amylase [14]. Anti-inflammatory effect in rat
adjuvant-induced arthritis is mediated via reduction of proinflammatory cytokines
[72].
Human A/Es, Allergy and Toxicity: Commonly reported adverse effects of a
standardized aqueous extract in HIV positive patients were anorexia, nausea, vomiting
and weakness [35].
Animal Toxicity: Oral LD50 of ethanol extract in mice is reported to be 2,650 mg
(range 2,209–3,091 mg/kg). Oral doses of hexane- and chloroform-soluble extracts of
the stem produced no significant toxic or adverse effects in rabbits up to the highest
dose of 1,600 mg/kg [26].
Commentary: Significant protective and therapeutic effects of the aqueous extract
on liver, spleen and HIV have been documented in RCTs, that should be further
investigated in larger clinical trials and diverse patient populations to firmly validate
its therapeutic efficiency. Other significant effects observed in animal studies also
need further exploration in systematic clinical trials.

References
1. Adhvaryu MR, Reddy N, Parabia MH. Effects of four Indian medicinal
herbs on isoniazid-, rifampicin- and pyrazinamide-induced hepatic injury
and immunosuppression in guinea pigs. World J Gastroenterol. 2007;13:
3199–205.
2. Adhvaryu MR, Reddy N, Parabia MH. Antitumor activity of four Ayurvedic
herbs in Dalton lymphoma ascites bearing mice and their short-term in vitro
cytotoxicity on DLA-cell-line. Afr J Tradit Complement Altern Med. 2008;
5:409–18.
3. Agrawal SS, Naqvi S, Gupta SK, Srivastava S. Prevention and management
of diabetic retinopathy in STZ diabetic rats by Tinospora cordifolia and its
molecular mechanisms. Food Chem Toxicol. 2012;50:3126–32.
4. Ahmad F, Ali M, Alam P. New phytoconstituents from the stem bark
of Tinospora cordifolia Miers. Nat Prod Res. 2010;24:926–34.
5. Aranha I, Clement F, Venkatesh YP. Immunostimulatory properties of the
major protein from the stem of the Ayurvedic medicinal herb, guduchi
(Tinospora cordifolia). J Ethnopharmacol. 2012;139:366–72.
6. Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of
plant origin. I: preliminary screening. J Ethnopharmacol. 1986;18:133–41.
7. Badar VA, Thawani VR, Wakode PT, et al. Efficacy of Tinospora cordifolia
in allergic rhinitis. J Ethnopharmacol. 2005;96:445–9.
8. Bala M, Pratap K, Verma PK, Singh B, Padwad Y. Validation of ethno-
medicinal potential of Tinospora cordifolia for anticancer and immuno-
modulatory activities and quantification of bioactive molecules by HPTLC.
J Ethnopharmacol. 2015;175:131–7.
1818 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

9. Bishayi B, Roychowdhury S, Ghosh S, Sengupta M. Hepatoprotective and

immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated
mature albino rats. J Toxicol Sci. 2002;27:139–46.
10. Bonvicini F, Mandrone M, Antognoni F, Poli F, Gentilomi GA. Ethanolic
extracts of Tinospora cordifolia and Alstonia scholaris show antimicrobial
activity towards clinical isolates of methicillin-resistant and carbapenemase-
producing bacteria. Nat Prod Res. 2014;28:1438–45.
11. Castillo AL, Osi MO, Ramos JD, et al. Efficacy and safety of Tinospora
cordifolia lotion in Sarcoptes scabiei var. hominis-infected pediatric
patients: a single blind, randomized controlled trial. J Pharmacol Pharma-
cother. 2013;4:39–46.
12. Chaudhary R, Jahan S, Goyal PK. Chemopreventive potential of an Indian
medicinal plant (Tinospora cordifolia) on skin carcinogenesis in mice.
J Environ Pathol Toxicol Oncol. 2008;27:233–43.
13. Chintalwar G, Jain A, Sipahimalani A, et al. An immunologically active
arabinogalactan from Tinospora cordifolia. Phytochemistry. 1999;52:
1089–93.
14. Chougale AD, Ghadyale VA, Panaskar SN, Arvindekar AU. Alpha
glucosidase inhibition by stem extract of Tinospora cordifolia. J Enzyme
Inhib Med Chem. 2009;24:998–1001.
15. Dhingra D, Goyal PK. Evidences for the involvement of monoaminergic
and GABAergic systems in antidepressant-like activity of Tinospora cordi-
folia in mice. Indian J Pharm Sci. 2008;70:761–7.
16. Gangan VD, Pradhan P, Sipahimalani AT, Banerji A. Cordifolisides A, B,
C: norditerpene furan glycosides from Tinospora cordifolia. Phytochem-
istry. 1994;37:781–6.
17. Goel B, Pathak N, Nim DK, et al. Clinical evaluation of analgesic activity
of guduchi (Tinospora cordifolia) using animal model. J Clin Diagn Res.
2014;8:HC01–4.
18. Goel HC, Prasad J, Singh S, et al. Radioprotective potential of an herbal
extract of Tinospora cordifolia. J Radiat Res (Tokyo). 2004;45:61–8.
19. Grover JK, Rathi SS, Vats V. Amelioration of experimental diabetic
neuropathy and gastropathy in rats following oral administration of plant
(Eugenia jambolana, Mucuna pruriens and Tinospora cordifolia) extracts.
Indian J Exp Biol. 2002;40:273–6.
20. Grover JK, Vats V, Rathi SS, Dawar R. Traditional Indian antidiabetic plants
attenuate progression of renal damage in streptozotocin induced diabetic
mice. J Ethnopharmacol. 2001;76:233–8.
21. Grover JK, Vats V, Rathi SS. Antihyperglycemic effect of Eugenia jam-
bolana and Tinospora cordifolia in experimental diabetes and their effects on
key metabolic enzymes involved in carbohydrate metabolism. J Ethnophar-
macol. 2000;73:461–70.
22. Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic
rhinitis: a systematic review. Ann Allergy Asthma Immunol. 2007;99:483–95.
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms 1819

23. Gupta RS, Sharma A: Antifertility effect of Tinospora cordifolia (Willd.)

stem extract in male rats. Indian J Exp Biol. 2003;41:885–9.
24. Hemadri K, Rao SS. Jaundice: tribal medicine. Ancient Sci Life. 1984;3:
209–12.
25. Hussain L, Akash MS, Ain NU, Rehman K, Ibrahim M. The analgesic,
anti-Inflammatory and antipyretic activities of Tinospora cordifolia. Adv
Clin Exp Med. 2015;24:957–64.
26. Ikram M, Khattak SG, Gilani SN. Antipyretic studies on some indigenous
Pakistani medicinal plants: II. J Ethnopharmacol. 1987;19:185–92.
27. Jagetia GC, Nayak V, Vidyasagar MS. Evaluation of the antineoplastic
activity of guduchi (Tinospora cordifolia) in cultured HeLa cells. Cancer
Lett. 1998;127:71–82.
28. Jagetia GC, Rao SK. Evaluation of cytotoxic effects of dichloromethane
extract of guduchi (Tinospora cordifolia Miers ex Hook. F. & Thoms.) on
cultured HeLa cells. Evid Based Complement Alternat Med. 2006;3:267–72.
29. Jagetia GC, Rao SK. Evaluation of the antineoplastic activity of guduchi
(Tinospora cordifolia) in Ehrlich ascites carcinoma bearing mice. Biol
Pharm Bull. 2006;29:460–6.
30. Jahfar M. Glycosyl composition of polysaccharide from Tinospora cordi-
folia. Acta Pharm. 2003;53:65–9.
31. Jain BN, Jain VK, Shete A. Antipsychotic activity of aqueous ethanolic
extract of Tinospora cordifolia in amphetamine challenged mice model.
J Adv Pharm Technol Res. 2010;1:30–3.
32. Jayaprakash R, Ramesh V, Sridhar MP, Sasikala C. Antioxidant activity of
ethanolic extract of Tinospora cordifolia on N-nitrosodiethylamine (di-
ethylnitrosamine) induced liver cancer in male Wister albino rats. J Pharm
Bioallied Sci. 2015;7 Suppl 1:S40–5.
33. Jeyachandran R, Xavier TF, Anand SP. Antibacterial activity of stem
extracts of Tinospora cordifolia (Willd.) Hook. f & Thomson. Anc Sci Life.
2003;23:40–3.
34. Kalekar SA, Munshi RP, Bhalerao SS, Thatte UM. Insulin sensitizing effect
of 3 Indian medicinal plants: an in vitro study. Indian J Pharmacol. 2013;
45:30–3.
35. Kalikar MV, Thawani VR, Varadpande UK, et al. Immunomodulatory
effect of Tinospora cordifolia extract in human immunodeficiency virus
positive patients. Indian J Pharmacol. 2008;40:107–10.
36. Kapil A, Sharma S. Immunopotentiating compounds from Tinospora
cordifolia. J Ethnopharmacol. 1997;58:89–95.
37. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
38. Kaur M, Singh A, Kumar B. Comparative antidiarrheal and antiulcer effect
of the aqueous and ethanolic stem bark extracts of Tinospora cordifolia in
rats. J Adv Pharm Technol Res. 2014;5:122–8.
1820 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

39. Khan V, Najmi AK, Akhtar M, et al. A pharmacological appraisal of

medicinal plants with antidiabetic potential. J Pharm Bioallied Sci. 2012;4:
27–42.
40. Koppada R, Norozian FM, Torbati D, et al. Physiological effects of a novel
immune stimulator drug, (1,4)-alpha-d-glucan, in rats. Basic Clin Phar-
macol Toxicol. 2009;105:217–21.
41. Kosaraju J, Chinni S, Roy PD, et al. Neuroprotective effect of Tinospora
cordifolia ethanol extract on 6-hydroxydopamine induced Parkinsonism.
Indian J Pharmacol. 2014;46:176–80.
42. Leyon PV, Kuttan G. Effect of Tinospora cordifolia on the cytokine profile
of angiogenesis-induced animals. Int Immunopharmacol. 2004;4:1569–75.
43. Leyon PV, Kuttan G. Inhibitory effect of a polysaccharide from Tinospora
cordifolia on experimental metastasis. J Ethnopharmacol. 2004;90:233–7.
44. Manjrekar PN, Jolly CI, Narayanan S. Comparative studies of the
immunomodulatory activity of Tinospora cordifolia and Tinospora sinensis.
Fitoterapia. 2000;71:254–7.
45. Mathew S, Kuttan G. Antioxidant activity of Tinospora cordifolia and its
usefulness in the amelioration of cyclophosphamide induced toxicity.
J Exp Clin Cancer Res. 1997;16:407–11.
46. Maurya R, Manhas LR, Gupta P, et al. Amritosides A, B, C and D: clerodane
furano diterpene glucosides from Tinospora cordifolia. Phytochemistry.
2004;65:2051–5.
47. Mishra A, Kumar S, Pandey AK. Scientific validation of the medici-
nal efficacy of Tinospora cordifolia. ScientificWorldJournal. 2013;2013:
292934.
48. Modak M, Dixit P, Londhe J, et al. Indian herbs and herbal drugs used for
the treatment of diabetes. J Clin Biochem Nutr. 2007;40:163–73.
49. Nadig PD, Revankar RR, Dethe SM, et al. Effect of Tinospora cordifolia on
experimental diabetic neuropathy. Indian J Pharmacol. 2012;44:580–3.
50. Nair PK, Melnick SJ, Ramachandran R, et al. Mechanism of macrophage
activation by (1,4)-alpha-D-glucan isolated from Tinospora cordifolia. Int
Immunopharmacol. 2006;6:1815–24.
51. Narkhede AN, Jagtap SD, Kasote DM, Kulkarni OP, Harsulkar AM. Com-
parative immunomodulation potential of Tinospora cordifolia (Willd.) Miers
ex Hook. F., Tinospora sinensis (Lour.) Merrill and Tinospora cordifolia
growing on Azadirachta indica A. Juss. Indian J Exp Biol. 2014;52:808–13.
52. Pahadiya S, Sharma J. Alteration of lethal effects of gamma rays in Swiss
albino mice by Tinospora cordifolia. Phytother Res. 2003;17:552–4.
53. Pan L, Terrazas C, Lezama-Davila CM, et al. Cordifolide A, a sulfur-
containing clerodane diterpene glycoside from Tinospora cordifolia. Org
Lett. 2012;14:2118–21.
54. Panchabhai TS, Ambarkhane SV, Joshi AS, et al. Protective effect of
Tinospora cordifolia, Phyllanthus emblica and their combination against
antitubercular drugs induced hepatic damage: an experimental study.
Phytother Res. 2008;22:646–50.
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms 1821

55. Patel MB, Mishra S. Hypoglycemic activity of alkaloidal fraction of

Tinospora cordifolia. Phytomedicine. 2011;18:1045–52.
56. Patel MB, Mishra S. Isoquinoline alkaloids from Tinospora cordifolia in-
hibit rat lens aldose reductase. Phytother Res. 2012;26:1342–7.
57. Patgiri B, Umretia BL, Vaishnav PU, et al. Anti-inflammatory activity of
Guduchi Ghana (aqueous extract of Tinospora cordifolia Miers.). Ayu.
2014;35:108–10.
58. Patil RN, Patil RY, Ahirwar B, Ahirwar D. Evaluation of antidiabetic and
related actions of some Indian medicinal plants in diabetic rats. Asian Pac J
Trop Med. 2011;4:20–3.
59. Prince PS, Kamalakkannan N, Menon VP. Restoration of antioxidants by
ethanolic Tinospora cordifolia in alloxan-induced diabetic Wistar rats.
Acta Pol Pharm. 2004;61:283–7.
60. Prince PS, Menon VP, Gunasekaran G. Hypolipidaemic action of Tinospora
cordifolia roots in alloxan diabetic rats. J Ethnopharmacol. 1999;64:53–7.
61. Prince PS, Menon VP. Hypoglycaemic and hypolipidaemic action of
alcohol extract of Tinospora cordifolia roots in chemical induced diabetes
in rats. Phytother Res. 2003;17:410–3.
62. Prince PS, Padmanabhan M, Menon VP. Restoration of antioxidant
defence by ethanolic Tinospora cordifolia root extract in alloxan-induced
diabetic liver and kidney. Phytother Res. 2004;18:785–7.
63. Rao PR, Kumar VK, Viswanath RK, Subbaraju GV. Cardioprotective
activity of alcoholic extract of Tinospora cordifolia in ischemia-reperfusion
induced myocardial infarction in rats. Biol Pharm Bull. 2005;28:2319–22.
64. Rao SK, Rao PS, Rao BN. Preliminary investigation of the radiosensitizing
activity of guduchi (Tinospora cordifolia) in tumor-bearing mice. Phytother
Res. 2008;22:1482–9.
65. Rathi SS, Grover JK, Vikrant V, Biswas NR. Prevention of experimental
diabetic cataract by Indian Ayurvedic plant extracts. Phytother Res. 2002;
16:774–7.
66. Reddy SS, Ramatholisamma P, Karuna R, Saralakumari D. Preventive
effect of Tinospora cordifolia against high fructose diet-induced insulin
resistance and oxidative stress in male Wistar rats. Food Chem Toxicol.
2009;47:2224–9.
67. Reddy SS, Ramatholisamma P, Ramesh B, et al. Beneficiary effect of
Tinospora cordifolia against high-fructose diet induced abnormalities in
carbohydrate and lipid metabolism in Wistar rats. Horm Metab Res. 2009;
41:741–6.
68. Rege N, Bapat RD, Koti R, et al. Immunotherapy with Tinospora cordifolia:
a new lead in the management of obstructive jaundice. Indian J Gastroen-
terol. 1993;12:5–8.
69. Rege NN, Nazareth HM, Bapat RD, Dahanukar SA. Modulation of immuno-
suppression in obstructive jaundice by Tinospora cordifolia. Indian J Med
Res Sect A—Infect Dis. 1989;90:478–83.
1822 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

70. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six rasa-
yana herbs used in Ayurvedic medicine. Phytother Res. 1999;13:275–91.
71. Sangeetha MK, Balaji Raghavendran HR, Gayathri V, Vasanthi HR.
Tinospora cordifolia attenuates oxidative stress and distorted carbohydrate
metabolism in experimentally induced type 2 diabetes in rats. J Nat Med.
2011;65:544–50.
72. Sannegowda KM, Venkatesha SH, Moudgil KD. Tinospora cordifolia in-
hibits autoimmune arthritis by regulating key immune mediators of inflam-
mation and bone damage. Int J Immunopathol Pharmacol. 2015;28:521–31.
73. Sarala M, Velu V, Anandharamakrishnan C, Singh RP. Spray drying of
Tinospora cordifolia leaf and stem extract and evaluation of antioxidant
activity. J Food Sci Technol. 2012;49:119–22.
74. Sarma DN, Khosa RL, Sahai M. Isolation of jatrorrhizine from Tinospora
cordifolia roots. Planta Med. 1995;61:98–9.
75. Sengupta M, Sharma GD, Chakraborty B. Effect of aqueous extract of
Tinospora cordifolia on functions of peritoneal macrophages isolated from
CCl4 intoxicated male albino mice. BMC Complement Altern Med. 2011;
11:102.
76. Sengupta S, Mukherjee A, Goswami R, Basu S. Hypoglycemic activity of
the antioxidant saponarin, characterized as alpha-glucosidase inhibitor
present in Tinospora cordifolia. J Enzyme Inhib Med Chem. 2009;24:
684–90.
77. Sharma AK, Kishore K, Sharma D, et al. Cardioprotective activity of
alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-
induced cardiac arrhythmia in rats. J Biomed Res. 2011;25:280–6.
78. Sharma B, Dabur R. Protective effects of Tinospora cordifolia on hepatic
and gastrointestinal toxicity induced by chronic and moderate alcoholism.
Alcohol Alcohol. 2016;51:1–10.
79. Sharma R, Amin H, Prajapati PK. Seasonal variations in physicochemical
profiles of Guduchi Satva (starchy substance from Tinospora cordifolia
[Willd.] Miers). J Ayurveda Integr Med. 2013;4:193–7.
80. Sharma U, Bala M, Kumar N, et al. Immunomodulatory active compounds
from Tinospora cordifolia. J Ethnopharmacol. 2012;141:918–26.
81. Sharma U, Bala M, Saini R, et al. Polysaccharide enriched immunomod-
ulatory fractions from Tinospora cordifolia (Willd.) miers ax hook. f. &
Thoms. Indian J Exp Biol. 2012;50:612–7.
82. Sharma V, Pandey D. Beneficial effects of Tinospora cordifolia on blood
profiles in male mice exposed to lead. Toxicol Int. 2010;17:8–11.
83. Sharma V, Pandey D. Protective role of Tinospora cordifolia against
lead-induced hepatotoxicity. Toxicol Int. 2010;17:12–7.
84. Sing H, Bisht GS. Some novel folk treatments among the tribes of Uttar
Pradesh. Anc Sci Life. 1999;18:250–3.
85. Singh L, Tyagi S, Rizvi MA, Goel HC. Effect of Tinospora cordifolia
on gamma ray-induced perturbations in macrophages and splenocytes. J
Radiat Res (Tokyo). 2007;48:305–15.
Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms 1823

86. Singh N, Singh SM, Shrivastava P. Immunomodulatory and antitumor

actions of medicinal plant Tinospora cordifolia are mediated through
activation of tumor-associated macrophages. Immunopharmacol Immuno-
toxicol. 2004;26:145–62.
87. Singh RK. Tinospora cordifolia as an adjuvant drug in the treatment of
hyperreactive malarious splenomegaly—case reports. J Vector Borne Dis.
2005;42:36–8.
88. Sivakumar V, Rajan MS. Antioxidant effect of Tinospora cordifolia ex-
tract in alloxan-induced diabetic rats. Indian J Pharm Sci. 2010;72:795–8.
89. Spelman K, Burns J, Nichols D, et al. Modulation of cytokine expression
by traditional medicines: a review of herbal immunomodulators. Altern
Med Rev. 2006;11:128–50.
90. Stanely P, Prince M, Menon VP. Hypoglycaemic and other related actions
of Tinospora cordifolia roots in alloxan-induced diabetic rats. J Ethnophar-
macol. 2000;70:9–15.
91. Sudhakaran DS, Srirekha P, Devasree LD, et al. Immunostimulatory effect
of Tinospora cordifolia Miers leaf extract in Oreochromis mossambicus.
Indian J Exp Biol. 2006;44:726–32.
92. Swaminathan K, Sinha UC, Bhatt RK, et al. Structure of tinosporide, a
diterpenoid furanolactone from Tinospora cordifolia Miers. Acta Crystal-
lographica—Section C—Crystal Struct Commun. 1989;45:134–6.
93. Swaminathan K, Sinha UC, Ramakumar S, et al. Structure of columbin, a
diterpenoid furanolactone from Tinospora cordifolia Miers. Acta Crystal-
lographica—Section C—Crystal Struct Commun. 1989;45:300–3.
94. Tambekar DH, Khante BS, Chandak BR, et al. Screening of antibacterial
potentials of some medicinal plants from Melghat forest in India. Afr J
Tradit Complement Altern Med. 2009;6:228–32.
95. Thatte UM, Dahanukar SA. Comparative study of immunomodulating
activity of Indian medicinal plants, lithium carbonate and glucan. Methods
Findings Exp Clin Pharmacol. 1988;10:639–44.
96. Thatte UM, Rao SG, Dahanukar SA. Tinospora cordifolia induces colony
stimulating activity in serum. J Postgrad Med. 1994;40:202–3.
97. Thippeswamy G, Sheela ML, Salimath BP. Octacosanol isolated from
Tinospora cordifolia downregulates VEGF gene expression by inhibiting
nuclear translocation of NF-jB and its DNA binding activity. Eur J
Pharmacol. 2008;588:141–50.
98. Tiwari M, Dwivedi UN, Kakkar P. Tinospora cordifolia extract modulates
COX-2, iNOS, ICAM-1, proinflammatory cytokines and redox status in
murine model of asthma. J Ethnopharmacol. 2014;153:326–37.
99. Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia
(Willd.) Hook. f. and Thoms. (Guduchi)-validation of the Ayurvedic pharma-
cology through experimental and clinical studies. Int J Ayurveda Res. 2012;1:
112–21.
1824 Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms

100. Van Kiem P, Van Minh C, Dat NT, et al. Aporphine alkaloids, clerodane
diterpenes, and other constituents from Tinospora cordifolia. Fitoterapia.
2010;81:485–9.
101. Velazquez EA, Kimura D, Torbati D, et al. Immunological response to
(1,4)-alpha-D-glucan in the lung and spleen of endotoxin-stimulated
juvenile rats. Basic Clin Pharmacol Toxicol. 2009;105:301–6.
102. Vinutha B, Prashanth D, Salma K, et al. Screening of selected Indian
medicinal plants for acetylcholinesterase inhibitory activity. J Ethnophar-
macol. 2007;109:359–63.
103. Wadood N, Wadood A, Shah SA. Effect of Tinospora cordifolia on blood
glucose and total lipid levels of normal and alloxan-diabetic rabbits. Planta
Med. 1992;58:131–6.
Trachyspermum ammi (L.) Sprague
(Apiaceae/Umbelliferae)

(Syns.: T. copticum (L.) Link.; Ammi copticum L.; Carum copticum (L.) Benth. &
Hook. f.; Ptychotis coptica (L.) DC.)

Abstract
The plant is native to Mediterranean countries, India, and Iran. Galen described it as
anti-inflammatory and diuretic, and Dioscorides mentioned it as emmenagogue and
diuretic, while Tabri said that it ‘purifies’ urinary tract and expels stones. The drug
has a reputation for its antiseptic properties, and is used to promote healing of foul
sores, and to remove offensive odor of the discharges from them. The fruits combine
the powerful stimulant qualities of mustard or capsicum, the bitter property of
chiraita and the antispasmodic virtues of asafetida. As stomachic they increase flow
of saliva, and augment gastric secretions, and used in the treatment of atonic
dyspepsia, eructations, heartburn, flatulency, intestinal colic and diarrhea. A poul-
tice of crushed fruits is applied to painful rheumatic joints, and hot fomentation to
the chest in bronchitis and asthma. In Iranian traditional medicine, they are used for
the treatment of headache and joint pains. They are also prescribed in the traditional
systems of medicine for the treatment of immune disorders, such as asthma and
rheumatism. During World War I, the fruits were in much demand for their thymol
content, which is antiseptic. Fruits contain carbohydrates, glycosides, saponins,
phenolic compounds, volatile oil, protein, fat, fiber, minerals including Ca, P, Fe
and nicotinic acid, alkaloids, flavonoids, tannins, saponins and cardiac glycosides.
Cultivation conditions, location, time of cultivation, and different extracting
methods all contribute to the variations in the yield and composition of the EO.
Ajwain seeds (fruits) demonstrated antioxidant, antimicrobial, antinociceptive,
cytotoxic, hypolipidemic, antihypertensive, bronchodilation, abortifacient, antilithi-
asis, diuretic, antitussive, antifungal, nematicidal, anthelmintic, antifilarial, anal-
gesic, anti-inflammatory, anxiolytic and antispasmodic activities. Aqueous fruit
extract demonstrated significant anticonvulsant, sedative and anxiolytic effects in
rats, while hydroalcohol and polyphenolic extracts suppressed naloxone-induced
withdrawal symptoms in morphine dependent mice. Boiled aqueous fruit extract to
patients with bronchial asthma significantly improved pulmonary function, but
significantly lower than theophylline.

© Springer Nature Switzerland AG 2020 1825

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_187
1826 Trachyspermum ammi (L.) Sprague

Keywords





Adžvajen Ajmoda Ajmodam Ajwain desi Anîsûn barrî Bishop’s weed






Carom Mısır anason Nankhwah Yin du zang hui xiang

Vernaculars: Urd.: Ajwain desi; Hin.: Ajawa, Ajmoda, Ajmud, Ajwain, Ajwán,
Jevain, Omum (fruit), Randhuni; San.: Ajmodam, Brahmadarbha, Deepyaka, Tava-
naka, Ugragandha, Yamini, Yaminiki, Yaváni, Yavaniai; Ben.: Ajowán, Ajwain,
Javan, Joán, Juvan, Baro-joan, Yamani, Yauvan, Yavan, Yavani, Yoyana; Guj.:
Ajamo; Mal.: Ayanodakan, Omam; Mar.: Ajma, Ajma vovasieda, Jamain, Onva,
Ova; Tam.: Amam, Asampadam, Asamtavomam, Omam; Tel.: Ajumoda, Omamu,
Vámamu, Vaman chettu, Vamu; Ara.: Ajwân, Amus, Anîsûn barrî, Kammûn habashî,
Kamún-el-mulúki, Nankhwah; Chi.: 印度藏茴香, Yin du zang hui xiang; Cze.:
Adžvajen; Dut.: Ajowan; Eng.: Ajawa seeds, Ajowan, Bishop’s weed, Carom; Fin.:
Koptilainen kumina; Fre.: Ajouan, Ajowan, Ammi Égyptien; Ger.: Adiowan, Ägyp-
tischer ajowan, Ägyptisches ammei, Indischer kümmel, Königskümmel, Scharfsame;
Hun.: Ajovan; Ind.: Jintan; Ita.: Ajowan, Ammi, Sisone; Jap.: Ajowan; Nep.: Agn-
imanthaa, Jvaanuu; Per.: Nanavva, Nankhwah, Zenyân, Zhinian; Pol.: Adżwan,
Ajowan, Kminek koptyjski; Por.: Ajowan, Orégano-semente, Semente-de-orégano;
Rus.: Aiova, Azhgon; Sin.: Asamodagam, Assamodum; Spa.: Ajowan, Ajwain,
Ayowam; Tag.: Damóro, Lamudio; Tha.: Phak chi; Tur.: Emmus, Mısır anason,
Mısır anisonu.
Description: The plant is native to Mediterranean countries, India (Gujarat, Rajas-
than), and Iran. It is an erect, annual herb growing up to a height of 90 cm; leaves are
distant, 2 or 3 pinnate, the ultimate segments being linear, 1.2–2.5 cm long; flowers
are white growing in compound umbels. The oval-shaped very small fruits, often
referred to as seeds, resemble caraway and cumin fruits, are pale-brown in color with
a bitter and pungent taste, and a flavor similar to anise and oregano. The surface is
highly tubercled, marked with five or ten prominent ridges, the intervening spaces
dark brown; on bruising the odor is strong. Dioscorides described a small African seed
(ammi), with odor like origanon (origanum), of a very hot and dry nature that is
carminative. Avicenna described it as nankhwah, and Pliny mentioned that ammi and
King’s cumin are identical.XL Haji Zein-el-Attar (1368 A.D.) also identified nankh-
wah with the ammi of Dioscorides and Paul Ægienta. Due to their thymol content,
they smell like thyme, but more aromatic and less subtle in taste, even a small number
of fruits tend to dominate the flavor of a dish (Figs. 1, 2 and 3).
Actions and Uses: The drug has a reputation for its antiseptic properties, and is used
to promote healing of foul sores, and to remove offensive odor of the discharges from
them.XL Galen described it as anti-inflammatory and diuretic, and Dioscorides men-
tioned it as emmenagogue and diuretic, while Tabri said that it ‘purifies’ urinary tract
and expels stones.LXIX The fruits combine the powerful stimulant qualities of mustard
or capsicum, the bitter property of chiraita and the antispasmodic virtues of asafetida.
As stomachic they increase flow of saliva, and augment gastric secretions, and used in
the treatment of atonic dyspepsia, eructations, heartburn, flatulency, intestinal colic
Trachyspermum ammi (L.) Sprague 1827

Fig. 1 Trachyspermum ammi, Flowers, Bames24, WikimediaCommons; ShareAlike 3.0 Unported

CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Carom_Flowers.jpg; https://creative-
commons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Trachyspermum ammi, Fruits (Seeds), Sanjay Acharya, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Carom.jpg; https://creative-
commons.org/licenses/by-sa/3.0/deed.en

and diarrhea. A poultice of crushed fruits is applied to painful rheumatic joints, and hot
fomentation to the chest in bronchitis and asthma.LXXXI,LXXXIV In Indian traditional
medicines the fruits are also used for the treatment of piles, bronchial asthma, as
galactagogue, and for amenorrhea [4]. In Iranian traditional medicine, they are used
for the treatment of headache and joint pains [11]. Unani physicians of India regard
the seeds (temperament, hot 3° and dry 3°) rubefacient, resolvent, analgesic, drying,
deobstruent, detergent, carminative, appetizer, emmenagogue, diuretic, anthelmintic,
spamsmolytic, antidote and antiseptic; and use them in the treatment of chronic fevers,
flatulence, stomachache, loss of appetite, ascites, whooping cough, liver and spleen
1828 Trachyspermum ammi (L.) Sprague

Fig. 3 Trachyspermum ammi, Carum Fruits (Seeds), Prof. Akbar, Original

hardness, in inflammations and epidemic diseases.LXXVII Ajowan is used as a carmi-

native, either alone or in combination with rock salt, asafetida, or myrobalan. It checks
chronic discharges, and is prescribed in bronchitis with copious expectorations, and to
make lotions and collyria. A plaster or poultice of crushed seeds (fruits) relieves
pain.XL They are also prescribed in the traditional systems of medicine for the treat-
ment of immune disorders, such as asthma and rheumatism [52]. During World War I,
the fruits were in much demand for their thymol content, which is antiseptic.CXVII
Phytoconstituents: Fruits contain carbohydrates, glycosides, saponins, phenolic
compounds, volatile oil (thymol, c-terpinene, p-cymene, and a- and b-pinene) [28],
protein, fat, fiber, minerals including Ca, P, Fe and nicotinic acid [4, 6, 49]; alkaloids
(2.80–4.23%), flavonoids (8.58–15.06%), tannins (19.71–27.77%), saponins (0.55–
0.70%) and cardiac glycosides [25], but Khan et al. [32] reported the absence of
flavonoids. Aqueous, methanol, and acetone fruit extracts also tested positive for
alkaloids, carbohydrates, phytosterols, phenols, tannins, and flavonoids [16]. From
the water-soluble portion of methanol fruit extract, 25 compounds, including
monoterpenoid, monoterpenoid glucosides, aromatic compound glucosides, and
glucides, were isolated [23]. Kaur et al. [27] reported isolation of an anticalcifying
protein from fruits; and presence of ACh and choline in roasted seed extract was also
reported [12].
Cultivation conditions, location, time of cultivation, and different extracting
methods all contribute to the variations in the yield and composition of the EO [52].
Ten Iranian samples of oil showed yields between 2.2 and 4.8% (v/w), with thymol,
p-cymene and c-terpinene being the major components. However, five of the samples
had thymol (35.04–63.31%), four had p-cymene (40.20–57.31%), and one sample
had c-terpinene (37.43%) as the main constituent of the total oil. Based on these
Trachyspermum ammi (L.) Sprague 1829

observations, they suggested three different chemotypes: thymol, p-cymene and

c-terpinene. c-Terpinene (48.07%), p-cymene (33.73%), and thymol (17.41%) were
reported as the major constituents by Moein et al. [35], whereas, thymol (36.7–
40.25%), c-terpinene (36.5–38.7%), and p-cymene (15.8–21.1%) as the major
compounds [19, 28], and thymol 70%, p-cymene 16%, and c-terpinene 7% as the
major components (90%) were all reported in EOs from Iran [21]. c-Terpinolene
(53.63%), thymol (16.77%), p-cymene (13.5%), and b-pinene (8.95%) were reported
in EO from India [47], whereas, thymol (63.4%), p-cymene (19%) and c-terpinene
(16.9%) were found as the most abundant constituents by Sharifzadeh and colleagues
from Iran [43]. Major components in hydrodistilled oil reported by Khajeh et al. [30]
were thymol (49.0%), c-terpinene (30.8%), p-cymene (15.7), b-pinene (2.1%),
myrcene (0.8%), and limonene (0.7%), but only three components constituted more
than 99% of the oil obtained by SCCD. The GC-MS analysis of the EO from India
revealed thymol constituting 22.82% [31].
Pharmacology: Ajwain seeds (fruits) demonstrated antioxidant, antimicrobial, anti-
nociceptive, cytotoxic, hypolipidemic, antihypertensive, bronchodilation, abortifa-
cient, antilithiasis, diuretic, antitussive, antifungal, nematicidal, anthelmintic, anti-
filarial [4], analgesic, anti-inflammatory, anxiolytic and antispasmodic activities
[14, 28]. Aqueous fruit extract demonstrated significant anticonvulsant, sedative and
anxiolytic effects in rats [40], while hydroalcohol and polyphenolic extracts sup-
pressed naloxone-induced withdrawal symptoms in morphine dependent mice [14].
Ethanol fruit extract produced short duration analgesic effect in mice comparable to
1 mg/kg of morphine [11]. Ether extract inhibited AA-, Epi- and collagen-induced
platelet aggregation, by inhibiting COX and reducing platelet TxB2 production [48].
Methanol fraction showed highest antioxidant activity and no mutagenicity [51], and
ethanol extract and EO possessed significant radical scavenging activity [28, 36].
Acetone extract contained comparatively high amount of total phenolics whereas
methanol extracts had the highest amount of total flavonoids, but both extracts showed
high antioxidant activity [16]. Oral administration of crude alcohol extract, n-hexane
fraction, and EO to mice produced immunostimulatory effect [46].
Hot-water fruit extract showed considerably good antibacterial activity against
S. aureus, E. faecalis, P. aeruginosa, S. typhimurium 2, and Sh. flexneri; and
acetone and ethanol extracts were active against all of the above plus E. coli,
K. pneumoniae, and S. typhi [25]. Methanol extract significantly inhibited P. aerugi-
nosa [5], and petroleum ether extract showed best activity against MDR strain of
C. albicans [32]. Methanol, acetone and chloroform extracts exert high antibacterial
effect on regular and IMP-producing P. aeruginosa strains collected from hospitalized
burn patients, in 6.25 mg/ml concentration [13]. Methanol extract also inhibited HCV
protease [22], and showed antifilarial activity [33]. Chloroform and isoamyl alcohol
extracts were not significantly active against S. pyogenes, S. epidermidis, K. pneu-
moniae, S. marcescens, S. aureus, and P. aeruginosa [3]. The EO significantly
inhibited growth of several MDR strains of S. aureus, but no activity against
P. aeruginosa [21], significant activity against S. aureus, P. vulgaris, B. subtilis,
B. megaterium, K. pneumoniae and E. coli [47], C. albicans, C. dubliniensis,
1830 Trachyspermum ammi (L.) Sprague

C. glabrata, C. tropicalis, C. krusei, and S. pyogenes [35], and clinical isolates of

C. albicans from HIV positive patients that were susceptible and resistant to
fluconazole [43]. The oil was also active against E. cloacae, Salmonella, Citrobacter,
V. cholerae, K. pasteurella, A. baumanii [34], against S. typhi, E. coli, S. aureus, B.
subtilis, and A. niger, with lowest MICs against the fungi [28, 45]; also exhibited mild
inhibitory activity against basidiomycetous yeast Trichosporon species i.e. T. asahii,
T. cutaneum and T. ovoides [42, 50], and potential antiviral activity against Japanese
encephalitis virus [41]. The EO selectively inhibited growth of potential intestinal
pathogens at concentrations that did not affect beneficial bacteria [17], inhibited
growth of Aspergillus species [2], growth and virulence of drug-resistant strains of
Aspergillus spp. and T. rubrum [31], A. parasiticus [24], A. flavus and A. niger [29],
and prevented aflatoxin production by them [28].
Aqueous and macerated fruit extracts produced antitussive effect in guinea pigs
better than codeine, which was not due to the presence of carvacrol, its main
constituent [8]. Aqueous-methanol extract lowered arterial BP, protected against
APAP- and CCl4-hepatotoxicity in rats [15], and inhibited K+-induced contractions
of isolated rabbit aorta and jejunum, and produced a nonspecific bronchodilator
effect of isolated guinea pig tracheal chain [1, 15]. The anticalcifying protein iso-
lated from fruits maintained renal functioning, reduced renal injury and decreased
crystal excretion in ethylene glycol- and ammonium chloride-induced urolithiasis in
rats [26]. Diet supplemented with fruits significantly reduced DMBA-induced skin
and B(a)P-induced forestomach papillomagenesis, with significant increase in the
activities of phase I and phase II, and antioxidant enzymes [44]. Essential oil and
1% aqueous extract showed an inhibitory effect on ACh-induced contraction of
isolated rat’s ileum [18, 20]. Aqueous extract of roasted fruits, however, exhibited
cholinomimetic effects on rabbit duodenum, guinea pig ileum and rat jejunum, and
nicotinic effects on skeletal muscle and BP of rat and cat [12]. Exposure of human
sperms to EO at a concentration of 125 lg/mL induced instant irreversible
immobilization and rendered them nonviable within 10 min [37]; treated sperm
significantly lost functional mitochondria and CAT [38].
Clinical Studies: Boiled aqueous fruit extract to patients with bronchial asthma
significantly improved pulmonary function, but significantly lower than theophylline
[7]. A four-week, double-blind RCT of Ajwain 10% topical cream on neuropathic
pain significantly reduced feet burning scores as well as numbness, tingling and
allodynia, compared to placebo [39].
Mechanism of Action: Hypotensive and bradycardiac effects are suggested to be
due to the presence of thymol, which produces a dose-dependent fall in BP and HR,
not blocked by atropine, and does not modify presser response of NE, and likely
produces its effects through calcium channel blocking activity [1]. While a com-
petitive antagonism of histamine H1 receptors, and/or a b-adrenergic stimulatory
effect and an anticholinergic property of EO were suggested for their dilatory effects
on isolated guinea-pig tracheal chain [10], smooth muscle relaxant effect of EO was
suggested mainly due to carvacrol and not due to anticholinergic or b-adrenergic
stimulatory effects [9].
Trachyspermum ammi (L.) Sprague 1831

Human A/Es, Allergy and Toxicity: It reduces milk and semen production.LXXVII
Animal Toxicity: Oral LD50 of 95% alcohol extract in mice was 4,500 mg/kg, and
for p-cymene, carvacrol, and a-pinene, the values are reported to be 4,750, 810, and
3,700 mg/kg, respectively [46].
Commentary: Variations in the chemical constituents of EO add unpredictability in
its expected clinical effects. Nevertheless, EO shows significant broad-spectrum
antimicrobial activity, that deserves to be exploited for topical uses, if not for sys-
tematic use. Also, its effects on GIT are legendary which should be further explored
in RCTs.

References
1. Aftab K, Atta-Ur-Rahman, Usmanghani K. Blood pressure lowering action
of active principle from Trachyspermum ammi (L.) sprague. Phytomedicine.
1995;2:35–40.
2. Alizadeh A, Zamani E, Sharaifi R, Javan-Nikkhah M, Nazari S. Antifungal
activity of some essential oils against toxigenic Aspergillus species. Commun
Agric Appl Biol Sci. 2010;75:761–7.
3. Awan UA, Andleeb S, Kiyani A, et al. Antibacterial screening of traditional
herbal plants and standard antibiotics against some human bacterial
pathogens. Pak J Pharm Sci. 2013;26:1109–16.
4. Bairwa R, Sodha RS, Rajawat BS. Trachyspermum ammi. Pharmacogn Rev.
2012;6:56–60.
5. Bora L. Anticandidal activity of medicinal plants and Pseudomonas aerug-
inosa strains of clinical specimens. J Microbiol Immunol Infect. 2016;49:
276–80.
6. Boskabady MH, Alitaneh S, Alavinezhad A. Carum copticum L.: a herbal
medicine with various pharmacological effects. Biomed Res Int. 2014;2014:
569087.
7. Boskabady MH, Alizadeh M, Jahanbin B. Bronchodilatory effect of Carum
copticum in airways of asthmatic patients. Therapie. 2007;62:23–9.
8. Boskabady MH, Jandaghi P, Kiani S, Hasanzadeh L. Antitussive effect
of Carum copticum in guinea pigs. J Ethnopharmacol. 2005;97:79–82.
9. Boskabady MH, Ramazani M, Tabei T. Relaxant effects of different fractions
of essential oil from Carum copticum on guinea pig tracheal chains. Phytother
Res. 2003;17:1145–9.
10. Boskabady MH, Shaikhi J. Inhibitory effect of Carum copticum on histamine
(H1) receptors of isolated guinea-pig tracheal chains. J Ethnopharmacol. 2000;
69:217–27.
11. Dashti-Rahmatabadi MH, Hejazian SH, Morshedi A, Rafati A. The analgesic
effect of Carum copticum extract and morphine on phasic pain in mice.
J Ethnopharmacol. 2007;109:226–8.
1832 Trachyspermum ammi (L.) Sprague

12. Devasankaraiah G, Hanin I, Haranath PSRK, Ramanamurthy PSV. Choli-

nomimetic effects of aqueous extracts from Carum copticum seeds. Br J
Pharmacol. 1974;52:613–4.
13. Fallah F, Taherpour A, Borhan RS, et al. Evaluation of Zataria Multiflora
Boiss and Carum copticum antibacterial activity on IMP-type metallo-beta-
lactamase-producing Pseudomonas aeruginosa. Ann Burns Fire Disasters.
2013;26:193–8.
14. Ghannadi A, Hajhashemi V, Abrishami R. Effects of the Persian Carum
copticum fruit extracts on morphine withdrawal syndrome in mice. Res
Pharm Sci. 2012;7:127–31.
15. Gilani AH, Jabeen Q, Ghayur MN, Janbaz KH, Akhtar MS. Studies on the
antihypertensive, antispasmodic, bronchodilator and hepatoprotective activ-
ities of the Carum copticum seed extract. J Ethnopharmacol. 2005;98:127–35.
16. Goswami N, Chatterjee S. Assessment of free radical scavenging potential
and oxidative DNA damage preventive activity of Trachyspermum ammi L.
(carom) and Foeniculum vulgare Mill. (fennel) seed extracts. Biomed Res
Int. 2014;2014:582767.
17. Hawrelak JA, Cattley T, Myers SP. Essential oils in the treatment of intestinal
dysbiosis: a preliminary in vitro study. Altern Med Rev. 2009;14:380–4.
18. Hejazian SH, Bagheri SM, Safari F. Spasmolytic and antispasmodic action
of Trachyspermum ammi essence on rat’s ileum contraction. N Am J Med
Sci. 2014;6:643–7.
19. Hejazian SH. Analgesic effect of essential oil (EO) from Carum copticum in
mice. World J Med Sci. 2006;1:95–9.
20. Hejazian-Y SH, Dashti-R MH, Mahdavi SM, Qureshi MA. The effect of
Carum copticum extract on acetylcholine induced contraction in isolated
rat’s ileum. J Acupunct Meridian Stud. 2009;2:75–8.
21. Hosseinkhani F, Jabalameli F, Banar M, et al. Monoterpene isolated from
the essential oil of Trachyspermum ammi is cytotoxic to multidrug-resistant
Pseudomonas aeruginosa and Staphylococcus aureus strains. Rev Soc Bras
Med Trop. 2016;49:172–6.
22. Hussein G, Miyashiro H, Nakamura N, et al. Inhibitory effects of Sudanese
medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res.
2000;14:510–6.
23. Ishikawa T, Sega Y, Kitajima J. Water-soluble constituents of ajowan. Chem
Pharm Bull (Tokyo). 2001;49:840–4.
24. Kahkha MR, Amanloo S, Kaykhaii M. Antiaflatoxigenic activity of Carum
copticum essential oil. Environ Chem Lett. 2014;12:231–4.
25. Kaur GJ, Arora DS. Antibacterial and phytochemical screening of Anethum
graveolens, Foeniculum vulgare and Trachyspermum ammi. BMC Com-
plement Altern Med. 2009;9:30.
26. Kaur T, Bijarnia RK, Singla SK, Tandon C. In vivo efficacy of Trachysper-
mum ammi anticalcifying protein in urolithiatic rat model. J Ethnopharmacol.
2009;126:459–62.
Trachyspermum ammi (L.) Sprague 1833

27. Kaur T, Bijarnia RK, Singla SK, Tandon C. Purification and characterization
of an anticalcifying protein from the seeds of Trachyspermum ammi (L.).
Protein Pept Lett. 2009;16:173–81.
28. Kavoosi G, Tafsiry A, Ebdam AA, Rowshan V. Evaluation of antioxidant
and antimicrobial activities of essential oils from Carum copticum seed and
Ferula assafoetida latex. J Food Sci. 2013;78:T356–61.
29. Kazemi M. Effect of Carum copticum essential oil on growth and aflatoxin
formation by Aspergillus strains. Nat Prod Res. 2015;29:1065–8.
30. Khajeh M, Yamini Y, Sefidkon F, Bahramifar N. Comparison of essential
oil of Carum copticum obtained by supercritical carbon dioxide extraction
and hydrodistillation methods. Food Chem. 2004;86:587–91.
31. Khan MS, Ahmad I, Cameotra SS. Carum copticum and Thymus vulgaris
oils inhibit virulence in Trichophyton rubrum and Aspergillus spp. Braz J
Microbiol. 2014;45:523–31.
32. Khan R, Zakir M, Afaq SH, Latif A, Khan AU. Activity of solvent extracts of
Prosopis spicigera, Zingiber officinale and Trachyspermum ammi against
multidrug resistant bacterial and fungal strains. J Infect Dev Ctries. 2010;4:
292–300.
33. Mathew N, Misra-Bhattacharya S, Perumal V, Muthuswamy K. Antifilarial
lead molecules isolated from Trachyspermum ammi. Molecules. 2008;13:
2156–68.
34. Mayaud L, Carricajo A, Zhiri A, Aubert G. Comparison of bacteriostatic
and bactericidal activity of 13 essential oils against strains with varying
sensitivity to antibiotics. Lett Appl Microbiol. 2008;47:167–73.
35. Moein MR, Zomorodian K, Pakshir K, et al. Trachyspermum ammi (L.)
sprague: chemical composition of essential oil and antimicrobial activities of
respective fractions. J Evid Based Complementary Altern Med. 2015;20:
50–6.
36. Nickavar B, Abolhasani FA. Screening of antioxidant properties of seven
Umbelliferae fruits from Iran. Pak J Pharm Sci. 2009;22:30–5.
37. Paul S, Kang SC. In vitro determination of the contraceptive spermicidal
activity of essential oil of Trachyspermum ammi (L.) Sprague ex Turrill
fruits. N Biotechnol. 2011;28:684–90.
38. Paul S, Kang SC. Studies on the viability and membrane integrity of human
spermatozoa treated with essential oil of Trachyspermum ammi (L.) Sprague
ex Turrill fruit. Andrologia. 2012;44 Suppl 1:117–25.
39. Petramfar P, Moein M, Samani SM, Tabatabaei SH, Zarshenas MM.
Trachyspermum ammi 10% topical cream versus placebo on neuropathic
pain, a randomized, double-blind, placebo-controlled trial. Neurol Sci.
2016;37:1449–55.
40. Rezvani ME, Roohbakhsh A, Mosaddegh MH, et al. Anticonvulsant and
depressant effects of aqueous extracts of Carum copticum seeds in male
rats. Epilepsy Behav. 2011;22:220–5.
1834 Trachyspermum ammi (L.) Sprague

41. Roy S, Chaurvedi P, Chowdhary A. Evaluation of antiviral activity of

essential oil of Trachyspermum ammi against Japanese encephalitis virus.
Pharmacognosy Res. 2015;7:263–7.
42. Saxena S, Uniyal V, Bhatt RP. Inhibitory effect of essential oils against
Trichosporon ovoides causing Piedra Hair Infection. Braz J Microbiol.
2012;43:1347–54.
43. Sharifzadeh A, Khosravi AR, Shokri H, Sharafi G. Antifungal effect of
Trachyspermum ammi against susceptible and fluconazole-resistant strains
of Candida albicans. J Mycol Med. 2015;25:143–50.
44. Singh B, Kale RK. Chemomodulatory effect of Trachyspermum ammi on
murine skin and forestomach papillomagenesis. Nutr Cancer. 2010;62:74–84.
45. Singh G, Kapoor IP, Pandey SK, et al. Studies on essential oils: part 10;
antibacterial activity of volatile oils of some spices. Phytother Res. 2002;16:
680–2.
46. Sonar PK, Singh R, Saraf SK. Phytochemical, chromatographic and spectro-
scopic investigation of Carum copticum seeds and their potential as immuno-
modulatory agents. Pharm Biol. 2016;54:494–502.
47. Soni R, Sharma G, Jasuja ND. Essential oil yield pattern and antibacterial
and insecticidal activities of Trachyspermum ammi and Myristica fragrans.
Scientifica (Cairo). 2016;1428194:2016.
48. Srivastava KC. Extract of a spice—omum (Trachyspermum ammi)-shows
antiaggregatory effects and alters arachidonic acid metabolism in human
platelets. Prostaglandins Leukot Essent Fatty Acids. 1988;33:1–6.
49. Uma Pradeep K, Geervani P, Eggum BO. Common Indian spices: nutrient
composition, consumption and contribution to dietary value. Plant Foods
Hum Nutr. 1993;44:137–48.
50. Uniyal V, Saxena S, Bhatt RP. Screening of some essential oils against
Trichosporon species. J Environ Biol. 2013;34:17–22.
51. Zahin M, Ahmad I, Aqil F. Antioxidant and antimutagenic activity of Carum
copticum fruit extracts. Toxicol In Vitro. 2010;24:1243–9.
52. Zarshenas MM, Samani SM, Petramfar P, Moein M. Analysis of the essential
oil components from different Carum copticum L. samples from Iran. Pharma-
cognosy Res. 2014;6:62–6.
Tribulus terrestris L.
(Zygophyllaceae)

(Syns.: T. lanuginosus L.; T. saharae A. Chev.)

Abstract
An annual herb, found in India, Iran, Mediterranean region, China, Black Sea,
Australia, Africa, and generally in all tropical countries. The plant was known to
Dioscorides and Pliny, as both mentioned it in their writings. Dioscorides and
Galen stated that it increases semen, relieves dysuria and urinary bladder pain, and
disintegrates both kidney and bladder stones. Hindus in India medicinally use both
the fruit and the root, as they regard them having cooling, diuretic, tonic and
aphrodisiac properties, and use them in the treatment of gonorrhea and dysuria. In
Ayurveda, leaves are considered useful in urinary calculi, the stem is astringent and
its infusion is used in gonorrhea, and the roots are aperients, demulcent and tonic.
Being alterative, diuretic, demulcent and aphrodisiac, an infusion is used to relieve
painful micturition, to increase flow of urine, and as a vehicle for diuretic medicines
in dysuria, gonorrhea, urinary disorders, and for the relief of nocturnal emmisions,
incontinence of urine and impotence. It is generally used with hyoscyamus and
opium. The fruit is bitter and pungent in taste, and is used as tonic in nocturnal
emissions, neuroasthenia, vertigo, and as astringent for oral inflammations, and as
an analgesic for relieving rheumatic pain. It is one of the most commonly used
plants by Siddha practitioners of Tamil Nadu state in India, for urinary ailments. It
is commonly used in folk medicine of Turkey as diuretic and against colicky pains,
hypertension and hypercholesterolemia. In modern times, it is marketed as herbal
supplement used by athletes and bodybuilders in the belief that it can enhance
testosterone concentrations. In TCM, it is described as astringent and tonic, under
the name Chi-li. Chemical composition varies with geographical location and in
different parts of the plant. Plants grown on different soils do not consistently
produce protodioscin. Protodioscin improves sexual desire and enhances erection
via the conversion of protodioscine to DHEA. Its sugar, starch and nitrate contents
also vary under different physiological conditions. Steroidal saponins are
considered to be responsible for the biological activity, the concentration and
composition of which vary by geographical origin of the plant.

© Springer Nature Switzerland AG 2020 1835

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_188
1836 Tribulus terrestris L.

Keywords



Bürzeldorn Chausse-trape Ҫobançökerten Gokhru

Jí lí
Kharkhasak





Puncture vine Sharshar Tribolo Trikantaka

Vernaculars: Urd.: Kharkhasak; Hin.: Bara gokhru, Bhakri, Gokhru; San.: Gok-
shura, Ikshugandha, Trikantaka, Vanasrangata; Ben.: Gokhuri; Mal.: Nerinnil, Ner-
ungil; Mar.: Lahana gokhru; Tam.: Cherunerinche, Kokullah, Nerinjal, Nerinji,
Nerunjil; Tel.: Chiru-palleru, Nirunji, Palleru-mullu; Ara.: Akhwas-ul-ajooz,
Al-gutub, Hasak, Hitraab, Kharshum-annajah, Khasak, Qutiba, Sharshar, Shirsheer;
Chi.: Jí lí, Peh-tsih-li, Yingjili; Eng.: Devil’s eyelashes, Devil’s thorn, Devil’s weed,
Goathead, Puncture vine, Small caltrops; Fre.: Chausse-trape, Corniche, Croix de
Malte, Escarbot, Macre, Saligot, Tribule terrestre, Trident; Ger.: Bürzeldorn,
Erdbürzeldorn, Zwillingsblatt; Ita.: Basapie, Caciarello, Tribolo, Tribolo comune;
Jap.: Hamabishi; Per.: Gokhru-khurd, Khar-e-khasak; Por.: Abrolhos, Abrolhos-
terrestres, Abroma; Spa.: Abreojos, Abrepies, Abrojo terrestre, Alforjo, Diablito,
Duros, Esparceta cornuda, Espigón, Gata rabiosa, Mata pinchosa, Mormaga, Muelas
de gato, Pinchosos, Rabiosa, Roseta francesa, Toboso, Tríbulo; Tur.: Ҫobançökerten,
Demir dikeni.
Description: An annual procumbent 10–50 cm tall herb, found in India, Iran,
Mediterranean region, China, Black Sea, Australia, Africa, and generally in all
tropical countries. Leaves opposite, briefly petiolate, 4–5 cm long; leaflets 5–8 pairs,
elliptical, somewhat oblique, 1 cm long, 6 mm wide. Flowers axillary, solitary, on
short peduncles which are shorter than the leaves; flowers May thru September.LXXIX
Flowers are composed of five broad, obtuse, yellow petals; these are succeeded by a
roundish five-cornered fruit, about the size of a marble, armed with prickles; this
ripening fruit divides into five cells, each armed with four strong sharp thorns and
containing several seeds. The cocci are wedge-shaped, yellowish when ripe, the
external convex surface being rough between the thorns. It has a slender, fibrous root,
10–12 cm long, cylindrical, and of a light-brown color; the odor is faintly aromatic
and the taste sweetish and astringent. From the root springs four to five delicate stalks,
spreading flat on the ground; these are hairy and extend 80 cm in length (Figs. 1, 2
and 3).XL
Actions and Uses: The plant was known to Dioscorides and Pliny, as both men-
tioned it in their writings. Hindus in India medicinally use both the fruit and the root,
as they regard them having cooling, diuretic, tonic and aphrodisiac properties, and use
them in the treatment of gonorrhea and dysuria.XL In Ayurveda, leaves are considered
useful in urinary calculi, the stem is astringent and its infusion is used in gonorrhea,
and the roots are aperients, demulcent and tonic [114]. Being alterative, diuretic,
demulcent and aphrodisiac, an infusion is used to relieve painful micturition, to
increase flow of urine, and as a vehicle for diuretic medicines in dysuria, gonorrhea,
urinary disorders, and for the relief of nocturnal emmisions, incontinence of urine and
impotence. It is generally used with hyoscyamus and opium.LXXXI Ibn al-BaitarLXIX
quoting Dioscorides and Galen stated that it (temperament, cold and moist) increases
Tribulus terrestris L. 1837

Fig. 1 Tribulus terrestris, Foliage with Flower, Forest and Kim Starr, Plants of Hawaii, Wiki-
mediaCommons; ShareAlike 3.0 Unported, CC BY-SA 3.0, https://commons.wikimedia.org/wiki/
File:Starr_030612-0063_Tribulus_terrestris.jpg; https://creativecommons.org/licenses/by-sa/3.0/
deed.en; Image 030612-0063 from http://www.starrenvironmental.com/plants/images/image/?q=
030612-0063

Fig. 2 Tribulus terrestris, Unripe Fruit, Forest and Kim Starr, Plants of Hawaii, WikimediaCom-
mons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Starr_
030612-0067_Tribulus_terrestris.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en; Image
030612-0067 from http://www.starrenvironmental.com/plants/images/image/?q=030612-0067

semen, relieves dysuria and urinary bladder pain, and disintegrates both kidney and
bladder stones,CV and in a dose of 7 g is beneficial for snakebites. In addition to ease
urination, Ibn Jazlah used it as an antidote against poisonous snakebites and poisonous
drugs.LIII In Unani medicine also, the fruit is regarded diuretic, emmenagogue,
1838 Tribulus terrestris L.

Fig. 3 Tribulus terrestris, Dried Fruits, Steve Hurst @ USDA-NRCS PLANTS Database, Wiki-
mediaCommons, https://commons.wikimedia.org/wiki/File:Trte_003_lhp.jpg

lithotriptic for kidney and bladder stones; and useful for oliguria and anuria. Also used
as a single remedy and with other drugs as aphrodisiac.LXXVII The fruit is bitter and
pungent in taste, and is used as tonic in nocturnal emissions, neuroasthenia, vertigo,
and as astringent for oral inflammations,LXXIX and as an analgesic for relieving
rheumatic pain [45]. It is one of the most commonly used plants by Siddha practi-
tioners of Tamil Nadu state in India, for urinary ailments [75]; and a decoction of
whole plant is used for urogenital tract infection by traditional healer of the Terai
forest of western Nepal [96]. It is also used as a nonconventional food in some parts of
India, and is a rich source of calcium, and noticeable amounts of phosphorus and iron
[31], and as a feed for livestock in arid regions, such as Rajasthan (India), due to its
nutritive value [73, 77]. It is commonly used in folk medicine of Turkey as diuretic
and against colicky pains, hypertension and hypercholesterolemia [10], and is used
alone or in combination with Zea mays by Iraqi herbalists to expel urinary stones [6].
A natural product from the aerial parts containing steroidal saponins mainly furostanol
bisglycosides is used to stimulate spermatogenesis, sertoli cell activity and increasing
libido [43, 76, 107]. Clinical studies suggest it to help with desire disorder of female
sexual dysfunctions [74]. In modern times, it is marketed as herbal supplement
used by athletes and bodybuilders in the belief that it can enhance testosterone
concentrations [86]. In TCM, it is described as astringent and tonic, under the name
Chi-li.LXVI
Phytoconstituents: Chemical composition varies with geographical location and in
different parts of the plant. Plants grown on different soils do not consistently produce
protodioscin [2]. Protodioscin improves sexual desire and enhances erection via the
conversion of protodioscine to DHEA. Its sugar, starch and nitrate contents vary under
different physiological conditions. Steroidal saponins are considered to be responsible
for the biological activity, the concentration and composition of which vary by geo-
graphical origin of the plant. Composition of steroidal saponins (protodioscin, pro-
totribestin, pseudoprotodioscin, dioscin, tribestin and tribulosin), and the flavonoid
Tribulus terrestris L. 1839

rutin in plant samples from Bulgaria, Turkey, Greece, Serbia, Macedonia, Georgia and
Iran is similar, with protodioscin and prototribestin being the major components.
Vietnamese and Indian samples lack prototribestin and tribestin, but tribulosin is
present in high amounts [29]. From the leaves and fruits, flavonoids kampferol,
kampferol 3-glucoside, kaempferol 3-rutinoside and tribuloside were reported [15],
and a flavonoid substance identical to rutin was also isolated [80]. A number of
flavonoid glycosides have been detected in the plant [90]. Steroidal saponins, dios-
genin [50, 58, 84, 85, 109, 111], chlorogenin and gitogenin [38, 39], ruscogenin [49],
hecogenin [110], neotigogenin [71] and 3-deoxy-ws 3-diosgenin [106] have been
reported from the plant. Saponins and flavonoids are present more than 2.61 times in
leaves than in other parts of the plant [128]. Saponins found in the leaves and roots are
very hemolytic but not those found in the stem or seeds [47]. A furostanol glycoside
saponin [108], b-sitosterol and stigmasterol [71], and steroid glycoside dioscin, trillin,
diosgenin-D-glycoside and gracillin have been isolated from aerial parts [81, 82].
Harman and harmine alkaloids have been reported from the aerial parts and the seeds
of the plant [28, 41, 68, 69].
Eight steroid saponins were isolated from aerial parts, two of which showed
remarkable antifungal activity against C. albicans and C. neoformans [129, 130].
A number of steroidal saponins [12, 13, 18, 21, 22, 102, 125, 126], furostanol saponins,
tribufurosides B–E, I–J [66, 67, 120–124], terrestroside A and B, chloromaloside E,
terrestrinin B and terrestroneoside A [117], a cinnamic imide derivative, tribulusimide
C [70], flavonoid glycosides (kaempferol-3-gentiobioside and isorhamnetin-3-
gentiobioside) [103], a lignanamides, named tribulusamide C [132], and two hepato-
protective lignanamides, tribulusamides A and B [63] were isolated from fruits.
Steroidal saponins [25, 48, 53, 104, 119], furostanol saponins [24, 59], and oligosac-
charides [44] have also been isolated from aerial parts. Some spirostanol-based ster-
oidal saponins exhibit remarkable activity against a number of human cancer cell lines
[12]. Flowers contain sterols (stigmasterol, campesterol and b-sitosterol), sapogenins
(diosgenin, gitogenin, enogitogenin), flavonoidal aglycons (kaempferol, quercetin)
and reducing sugars (D-glucose, D-arabinose and L-rhamnose) [95]. From root nod-
ules, 22 free amino acids were identified, glutamic acid, glutamine, aspartic acid and
asparagine being the major ones [11]. An antisclerotic agent, tribusponin, was isolated
from leaves [56]. Presence of tannins, resin, sterols, alkaloids and potassium in addition
to fixed oil in fruit has been reported [16].
Pharmacology: Aqueous extract of dried fruits produced improvement in sexual
behavior of rats; the improved sexual behavior was more prominent on chronic
administration that produced significant increase in serum testosterone levels
without any significant effect on sperm count [1, 35, 36, 99]. A report from Brazil
indicated that 4-weeks treatment with T. terrestris of male rats did not stimulate
endocrine sensitive tissues such as prostate and seminal vesicle, and did not change
testosterone levels [72]. However, another study reported significant increases in
testosterone, DHT and DHEA in primates after a bolus dose, and in testosterone and
DHT in rabbits and castrated rats after 8-weeks administration of the extract [37].
Ethanol fruit extract induced relaxation of corpus cavernosum of rabbit ex vivo,
1840 Tribulus terrestris L.

after oral administration of the extract for a month [30, 51]. Diet supplemented with
ground plant material to morphine-addicted rats for 4-weeks also resulted in sig-
nificant increase in LH, testosterone and estrogen levels, that were significantly
decreased by morphine administration [40]. Fruit extract also completely restored
metronidazole-induced alterations in testicular weight, spermatogenesis, activities
of antioxidant enzymes, LDH, ALP, and level of LPO in mice [61].
Aqueous fruit extract exhibited moderate diuretic activity in rats [42] and dogs
[54], significantly lowered SBP in hypertensive rats, lowered ACE activity in all
tissues, especially in kidneys [94], and relaxed arterial smooth muscle, possibly
involving NO release and membrane hyperpolarization [83]; the extract also
inhibited Epi-induced platelet aggregation [89]. Alkaloid fraction depressed intact
frog heart but did not affect BP of dogs; whereas the aqueous extract produced mild
hypotension [16], and saponins from the plant increased amplitude of cardiac
contraction and decreased HR [113]. Seth and Jagdish [93] also reported car-
diotonic effect of the plant. The fruit ether extract induced diuresis and increased
creatinine renal clearance in dog, which suggested increase in the glomerular fil-
tration rate [97]. Ethanol fruit extract significantly protected against urolithiasis in
rats [9], and reversed Cd-induced hepatotoxicity and nephrotoxicity in rats [62].
Aqueous extract significantly decreased urinary oxalate excretion, and increased
urinary glyoxylate excretion in sodium glycolate-fed rats [91], reduced excretion of
oxalate, calcium, and phosphate with decreased levels of BUN, uric acid and cre-
atinine in ethylene-fed rats and restored antioxidant enzymes activity [52], inhibited
in vitro growth of calcium oxalate crystals [3, 4], produced diuresis in rats [6], and
protected against mercuric chloride-nephrotoxicity [55].
The decoction significantly inhibited gluconeogenesis and influenced gly-
cometabolism, and reduced levels of TGs and TC in normal mice [64], significantly
decreased serum levels of ALT and creatinine in diabetic rats and lowered liver MDA
in diabetic and nondiabetic rats, and significantly increased levels of reduced GSH in
liver of diabetic rats, an indication of antagonizing oxidative stress [8]; and alcohol
extract significantly decreased FBG, HbA1c, TC, TGs and LDL-C in diabetic rats [32,
34]. The extract also significantly lowered serum TC, LDL-C, and TGs in hyper-
lipidemic rabbits [112], protected ultrastructural alterations in neurons, axonal
structures and mitochondria of brains of hyperlipidemic rabbits [14], and the saponin
fraction prevented increase in serum TC, LDL-C, and liver TC and TGs, and increased
activities of SOD in liver of hypercholesterolemic mice [23]. The saponin fraction
also significantly reduced serum glucose, TGs and TC, and increased serum SOD
activity both in normal and diabetic mice [65], and saponins inhibited postprandial
blood glucose by inhibiting activity of a-glucosidase in small intestines [131].
A standardized aqueous extract significantly attenuated diabetic neuropathic pain and
increased pain threshold in rats, inhibited TNF-a and IL-1b levels, comparable to
pregabalin; increased SOD, CAT, GPx, and GSH, and decreased LPx levels [87].
Methanol fruit extract also exhibited potent analgesic activity with lesser gastric
ulcerogenic potential than indomethacin, was not antagonized by naloxone [45]; and
potently inhibited (>80%) COX-2 activity in LPS-induced cultured mouse macro-
phages [46]. Fruit extract also showed protective effect against haloperidol-induced
Tribulus terrestris L. 1841

catalepsy, comparable to trihexyphenidyl [79]. The saponins protected against

chronic mild stress and produce antidepressant effects in rats [118]. The bitter prin-
ciple from the plant considerably increased gastric secretions in humans, and is also
reported to possess anthelmintic property [20, 26].
Aqueous extracts of the root and fruits significantly reduced tumor incidence,
tumor burden and cumulative number of DMBA-induced papillomas in male
Swiss mice, with a significant increase in average latent period [60]. The saponins
attenuated UVB-induced programmed cell death of normal human keratinocytes,
but did not increase resistance of malignant keratinocytes to UVB [100]. Ethanol
fruit extract also demonstrated significant antimicrobial activity against B. subtilis,
B. cereus, P. vulgaris and C. diphtheria, and strong antifungal activity against
C. albicans [7], and against S. mutans, S. sanguis, A. viscosus, E. faecalis, S. aureus,
and E. coli [101]. The decoction enhances tyrosinase activity at high concentrations
(100 mg/ml) but inhibits it at low concentrations (10 mg/ml) [27], and significantly
increases melanocyte stimulating hormone expression in hair follicle melanocytes by
activating tyrosinase activity and promoting melanocyte proliferation and melanin
synthesis [127].
Clinical Studies: In a Brazilian study of 144 women, mean age 41 years, with sexual
dysfunction, subdivided into six domains: sexual desire, arousal, lubrication, orgasm,
satisfaction and pain, treatment with a commercial extract for 90-days resulted in
significant improvement in 88% patients in terms of desire, arousal, orgasm, and
satisfaction [33]. Similar results were reported from an Iranian, double-blind RCT of
sixty women with hypoactive sexual desire disorder during their fertile years, who
were treated with the ethanol leaf extract (5.25 g/day) or placebo for 4-weeks.
Treatment group experienced significant improvement in total Female Sexual Func-
tion Index, in terms of desire, arousal, lubrication, satisfaction and pain [5]. However,
in a prospective, double-blinded RCT including thirty healthy men,  40 years of
age, presenting with spontaneous erectile dysfunction, fifteen subjects treated with
T. terrestris for thirty-days did not significantly differ from placebo in improvement of
erectile dysfunction symptoms or serum total testosterone level [92]. A Chinese study
reported 82.3% remission in angina pectoris pain and 52.7% improvement in ECG of
406 patients treated with saponin fraction, which was attributed to improved coronary
circulation [116].
Mechanism of Action: The mechanism(s) underlying its aphrodisiac and proerectile
activities is exclusively not due to its androgen enhancing properties and is largely
unknown. Experimental studies in animals indicate possible endothelium and
NO-dependent mechanisms [30, 78]. The hypotensive effect involves inhibition of
ACE activity in all tissues, especially the kidneys [94], and increased membrane
hyperpolarization resulting in arterial smooth muscle relaxation, possibly involving
NO release [83]. Aqueous extract blocks proliferation and induces apoptosis in human
liver cancer cells through inhibition of NF-jB signaling [57]. The saponins attenuate
UVB-induced programmed cell death in normal human keratinocytes through inhi-
bition of intrinsic apoptotic pathway. The photoprotective effect of saponins is also
suggested due to block of UVB-mediated NF-jB activation. Therefore, saponins may
have a preventive efficacy against UVB-induced carcinogenesis [100].
1842 Tribulus terrestris L.

Human A/Es, Allergy and Toxicity: An Iranian male patient developed symp-
toms of hepatotoxicity, nephrotoxicity and neurotoxicity after consuming herbal
water extract for 2-days to prevent kidney stone formation; presenting with seizures
and very high serum aminotransferases and creatinine [105]. Another young healthy
male in the U.S. is reported to have developed signs of acute nephrotoxicity and
hyperbilirubinemia as a result of T. terrestris herbal supplement consumption
[88]. A 36-year-old Caucasian Italian man developed 72-h-lasting priapism after
consuming herbal supplement based on Tribulus terrestris [19].
Animal Toxicity: The plant contains photosensitizing and toxic substances, which
are responsible for a toxic condition known as geeldikkop or tribulosis in sheep and
goats that leads to death. Experimental toxicity studies in sheep have been reported
by Van Tonder et al. [115], and Brown [17] described hematology, chemical
pathology, biochemical disturbances and the histopathology of geeldikkop caused
by grazing on T. terrestris. LD50 (i.p.) of saponin mixture in Swiss mice is reported
to be 813 mg/kg [10]. Fruit powder was toxic to bitches due to water-soluble salts
particularly the nitrates, but the water-washed powder showed no toxicity even in a
dose of 5,000 mg/kg body weight [98].
Commentary: Two RCTs in Brazilian and Iranian women with sexual dysfunction
demonstrated significant symptomatic improvement. However, it did not show any
significant improvement in erectile dysfunction in men, for which it is widely mar-
keted. Variation in chemical constituents, especially steroidal saponins (protodioscin,
prototribestin, dioscin, pseudoprotodioscin, tribestin and tribulosin), could be partly
responsible for the inconsistent results. More clinical studies with known composi-
tions of the chemical make up of the part used are, therefore, required to validate these
findings.

References
1. Adaikan PG, Gauthaman K, Prasad RN, Ng SC. Proerectile pharmacological
effects of Tribulus terrestris extract on the rabbit corpus cavernosum. Ann
Acad Med Singapore. 2000;29:22–6.
2. Adimoelja A. Phytochemicals and the breakthrough of traditional herbs in
the management of sexual dysfunctions. Int J Androl. 2000;23 Suppl 2:82–4.
3. Aggarwal A, Tandon S, Singla SK, Tandon C. A novel antilithiatic protein
from Tribulus terrestris having cytoprotective potency. Protein Pept Lett.
2012;19:812–9.
4. Aggarwal A, Tandon S, Singla SK, Tandon C. Diminution of oxalate
induced renal tubular epithelial cell injury and inhibition of calcium
oxalate crystallization in vitro by aqueous extract of Tribulus terrestris. Int
Braz J Urol. 2010;36:480–8.
5. Akhtari E, Raisi F, Keshavarz M, et al. Tribulus terrestris for treatment of
sexual dysfunction in women: randomized double-blind placebo-controlled
study. Daru. 2014;22:40.
Tribulus terrestris L. 1843

6. Al-Ali M, Wahbi S, Twaij H, Al-Badr A. Tribulus terrestris: preliminary

study of its diuretic and contractile effects and comparison with Zea mays.
J Ethnopharmacol. 2003;85:257–60.
7. Al-Bayati FA, Al-Mola HF. Antibacterial and antifungal activities of
different parts of Tribulus terrestris L. growing in Iraq. J Zhejiang Univ
Sci B. 2008;9:154–9.
8. Amin A, Lotfy M, Shafiullah M, Adeghate E. The protective effect of
Tribulus terrestris in diabetes. Ann N Y Acad Sci. 2006;1084:391–401.
9. Anand R, Patnaik GK, Kulshreshtha DK, Dhawan BN. Activity of certain
fractions of Tribulus terrestris fruits against experimentally induced
urolithiasis in rats. Indian J Exp Biol. 1994;32:548–52.
10. Arcasoy HB, Erenmemisoglu A, Tekol Y, et al. Effect of Tribulus terrestris
L. saponin mixture on some smooth muscle preparations: a preliminary
study. Boll Chim Farm. 1998;137:473–5.
11. Athar M, Mahmood A. Qualitative estimation of free amino acids from the
root nodules of Tribulus terrestris L. Pakistan J Bot. 1980;12:91.
12. Bedir E, Khan IA, Walker LA. Biologically active steroidal glycosides
from Tribulus terrestris. Pharmazie. 2002;57:491–3.
13. Bedir E, Khan IA. New steroidal glycosides from the fruits of Tribulus
terrestris. J Nat Prod. 2000;63:1699–701.
14. Berkman Z, Tanriover G, Acar G, et al. Changes in the brain cortex of
rabbits on a cholesterol-rich diet following supplementation with a herbal
extract of Tribulus terrestris. Histol Histopathol. 2009;24:683–92.
15. Bhutani SP, Chibber SS, Seshadri TR. Flavonoids of the fruits and leaves of
Tribulus terrestris: constitution of tribuloside. Phytochemistry. 1969;8:299.
16. Bose BC, Saifi AQ, Vijayvargiya R, Bhatnagar JN. Some aspects of
chemical and pharmacological studies of Tribulus terrestris. Indian J Med
Sci. 1963;17:291–3.
17. Brown JM. Biochemical lesions in the pathogenesis of geeldikkop (Tribu-
losis ovis) and enzootic icterus in sheep in South Africa. Ann N Y Acad Sci.
1963;104:504–38.
18. Cai L, Wu Y, Zhang J, et al. Steroidal saponins from Tribulus terrestris.
Planta Med. 2001;67:196–8.
19. Campanelli M, De Thomasis R, Tenaglia RL. Priapism caused by
‘Tribulus terrestris’. Int J Impot Res. 2016;28:39–40.
20. Chakraborty B, Ray NM, Sikdar S. Study of anthelmintic property of
Tribulus terrestris L. (to control Ascardia galli). Indian J Anim Health.
1979;18:23–5.
21. Chen G, Liu T, Lu X, et al. New steroidal glycosides from Tribulus
terrestris L. J Asian Nat Prod Res. 2012;14:780–4.
22. Chen G, Su L, Feng SG, et al. Furostanol saponins from the fruits of
Tribulus terrestris. Nat Prod Res. 2013;27:1186–90.
23. Chu S, Qu W, Pang X, et al. Effect of saponin from Tribulus terrestris on
hyperlipidemia. Zhong Yao Cai. 2003;26:341–4 (Chinese).
1844 Tribulus terrestris L.

24. Conrad J, Dinchev D, Klaiber I, et al. A novel furostanol saponin from

Tribulus terrestris of Bulgarian origin. Fitoterapia. 2004;75:117–22.
25. De Combarieu E, Fuzzati N, Lovati M, Mercalli E. Furostanol saponins
from Tribulus terrestris. Fitoterapia. 2003;74:583–91.
26. Deepak M, Dipankar G, Prashanth D, et al. Tribulosin and beta-sitosterol-
D-glucoside, the anthelmintic principles of Tribulus terrestris. Phytomedicine.
2002;9:753–6.
27. Deng Y, Yang L, An SL. Effect of Tribulus terrestris L. decoction of
different concentrations on tyrosinase activity and the proliferation of
melanocytes. Di Yi Jun Yi Da Xue Xue Bao. 2002;22:1017–9 (Chinese).
28. Denliev PD, Meshcheryakov AA, Orazkuliev I. The search for biologically
active compounds in plants of the flora of the Turkmenian USSR. Izv Akad
Nauk Turk SSR Ser Biol Nauk. 1969;1:81.
29. Dinchev D, Janda B, Evstatieva L, et al. Distribution of steroidal saponins
in Tribulus terrestris from different geographical regions. Phytochemistry.
2008;69:176–86.
30. Do J, Choi S, Choi J, Hyun JS. Effects and mechanism of action of a Tribulus
terrestris extract on penile erection. Korean J Urol. 2013;54:183–8.
31. Duhan A, Chauhan BM, Punia D. Nutritional value of some nonconven-
tional plant foods of India. Plant Foods Hum Nutr. 1992;42:193–200.
32. El-Tantawy WH, Hassanin LA. Hypoglycemic and hypolipidemic effects
of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic
rats: a comparative study with T. terrestris (caltrop). Indian J Exp Biol.
2007;45:785–90.
33. Gama CR, Lasmar R, Gama GF, et al. Clinical assessment of Tribulus
terrestris extract in the treatment of female sexual dysfunction. Clin Med
Insights Womens Health. 2014;7:45–50.
34. Gandhi S, Srinivasan BP, Akarte AS. Potential nephrotoxic effects produced
by steroidal saponins from hydroalcoholic extract of Tribulus terrestris in
STZ-induced diabetic rats. Toxicol Mech Methods. 2013;23:548–57.
35. Gauthaman K, Adaikan PG, Prasad RN. Aphrodisiac properties of Tribulus
terrestris extract (protodioscin) in normal and castrated rats. Life Sci.
2002;71:1385–96.
36. Gauthaman K, Ganesan AP, Prasad RN. Sexual effects of puncturevine
(Tribulus terrestris) extract (protodioscin): an evaluation using a rat model.
J Altern Complement Med. 2003;9:257–65.
37. Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris
and its role in the management of male erectile dysfunction—an evaluation
using primates, rabbit and rat. Phytomedicine. 2008;15:44–54.
38. Gheorghiu A, Ionescu-Matiu E. Presence of Chlorogenin beside the
diosgenin and gitogenin in Tribulus terrestris. Ann Pharm Fr. 1968;26:
745–8.
39. Gheorghiu A, Ionescu-Matiu E. Steroid sapogenins. Presence of chloro-
genin in Tribulus terrestris. Stud Cercet Biochem. 1968;11:269.
Tribulus terrestris L. 1845

40. Ghosian Moghaddam MH, Khalili M, Maleki M, Ahmad Abadi ME. The
effect of oral feeding of Tribulus terrestris L. on sex hormone and
gonadotropin levels in addicted male rats. Int J Fertil Steril. 2013;7:57–62.
41. Gill S, Raszeja W. Chromatographic analysis of harman derivatives in
some plant raw materials. Gdansk Tow Nauk, Rozpr Wydz. 1971;3:137.
42. Gujral ML, Saxena PN, Mishra SS. An experimental study of the comparative
activity of indigenous diuretics. J Indian Med Assoc. 1955;25:49.
43. Gyulemetova R, Tomova M, Slimova M, et al. Determination of furostanol
saponins in the preparation tribestan. Pharmazie. 1982;37:296.
44. Hammoda HM, Ghazy NM, Harraz FM, et al. Chemical constituents
from Tribulus terrestris and screening of their antioxidant activity.
Phytochemistry. 2013;92:153–9.
45. Heidari MR, Mehrabani M, Pardakhty A, et al. The analgesic effect of
Tribulus terrestris extract and comparison of gastric ulcerogenicity of the
extract with indomethacine in animal experiments. Ann N Y Acad Sci.
2007;1095:418–27.
46. Hong CH, Hur SK, Oh OJ, et al. Evaluation of natural products on
inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase
(iNOS) in cultured mouse macrophage cells. J Ethnopharmacol. 2002;83:
153–9.
47. Hsu Chuen-Chin. Odell GV, Williams T. Characterization of the saponin
fraction of Tribulus terrestris. Proc Okla Acad Sci. 1968;47:21.
48. Huang JW, Tan CH, Jiang SH, Zhu DY. Terrestrinins A and B, two new
steroid saponins from Tribulus terrestris. J Asian Nat Prod Res. 2003;5:
285–90.
49. Iskenderov GB. Steroidal sapogenins from Tribulus terrestris. Khim Prir
Soedin. 1970;6:488.
50. Kachukhashvili TN. Tribulus terrestris as a source of steroid saponins
containing diosgenin and the prospects for its use in medicine. Sb Tr
Tbilissk Nauchn Issled Khim-Farmatsev Inst. 1960;9:179–89.
51. Kam SC, Do JM, Choi JH, et al. In vivo and in vitro animal investigation of
the effect of a mixture of herbal extracts from Tribulus terrestris and
Cornus officinalis on penile erection. J Sex Med. 2012;9:2544–51.
52. Kamboj P, Aggarwal M, Puri S, Singla SK. Effect of aqueous extract
of Tribulus terrestris on oxalate-induced oxidative stress in rats. Indian J
Nephrol. 2011;21:154–9.
53. Kang LP, Wu KL, Yu HS, et al. Steroidal saponins from Tribulus
terrestris. Phytochemistry. 2014;107:182–9.
54. Karandikar GK, Gulati OD, Gokhale SD. Effect of some Ayurvedic remedies
on the urine output in rats and dogs. Indian J Med Sci. 1960;14:585–9.
55. Kavitha AV, Jagadeesan G. Role of Tribulus terrestris (Linn.) (Zygo-
phyllacea) against mercuric chloride induced nephrotoxicity in mice, Mus
musculus (Linn.). J Environ Biol. 2006;27:397–400.
56. Kemertelidze EP, Pkheidze TA, Kachukhashvili TN, et al. Tribusponin: an
antisclerotic agent. U.S.S.R. 567, 449 (Cl. A61K35/78). 5 Aug 1977.
1846 Tribulus terrestris L.

57. Kim HJ, Kim JC, Min JS, et al. Aqueous extract of Tribulus terrestris Linn.
induces cell growth arrest and apoptosis by downregulating NF-jB
signaling in liver cancer cells. J Ethnopharmacol. 2011;136:197–203.
58. Kintya PK, Perepelitsa ED, Chrva V Ya, Kretsu LG. Steroid saponins II.
Glycosides of Tribulus terrestris. Khim Prir Soedin. 1972;8:475.
59. Kostova I, Dinchev D, Rentsch GH, et al. Two new sulfated furostanol
saponins from Tribulus terrestris. Z Naturforsch. 2002;57:33–8.
60. Kumar M, Soni AK, Shukla S, Kumar A. Chemopreventive potential of
Tribulus terrestris against 7,12- dimethylbenz (a) anthracene induced skin
papillomagenesis in mice. Asian Pac J Cancer Prev. 2006;7:289–94.
61. Kumari M, Singh P. Tribulus terrestris ameliorates metronidazole-induced
spermatogenic inhibition and testicular oxidative stress in the laboratory
mouse. Indian J Pharmacol. 2015;47:304–10.
62. Lakshmi GD, Kumar PR, Bharavi K, et al. Protective effect of Tribulus
terrestris Linn. on liver and kidney in cadmium intoxicated rats. Indian J
Exp Biol. 2012;50:141–6.
63. Li JX, Shi Q, Xiong QB, et al. Tribulusamide A and B, new hepatoprotective
lignanamides from the fruits of Tribulus terrestris: indications of cytopro-
tective activity in murine hepatocyte culture. Planta Med. 1998;64:628–31.
64. Li M, Qu W, Chu S, et al. Effect of the decoction of Tribulus terrestris on
mice gluconeo-genesis. Zhong Yao Cai. 2001;24:586–8 (Chinese).
65. Li M, Qu W, Wang Y, et al. Hypoglycemic effect of saponin from Tribulus
terrestris. Zhong Yao Cai. 2002;25:420–2 (Chinese).
66. Liu T, Chen G, Yi GQ, et al. New pregnane and steroidal glycosides
from Tribulus terrestris L. J Asian Nat Prod Res. 2010;12:209–14.
67. Liu T, Lu X, Wu B, et al. Two new steroidal saponins from Tribulus
terrestris L. J Asian Nat Prod Res. 2010;12:30–5.
68. Lutomski J, Kowalwski Z, Drost K, Schmidt K. Simple carboline
alkaloids. I. Thin-layer chromatography of harman alkaloids occuring in
plant material and in preparations. Herba Pol. 1967;13:44.
69. Lutomski J, Nowicka B. Simple carboline alkaloids. VI. Comparative
chemical evaluation of alkaloid fractions from different sources. Herba Pol.
1968;14:235.
70. Lv AL, Zhang N, Sun MG, et al. One new cinnamic imide derivative from
the fruits of Tribulus terrestris. Nat Prod Res. 2008;22:1013–6.
71. Mahato SB, Sahu NP, Pal BC, et al. Screening of Tribulus terrestris plants
for diosgenin. J Inst Chem (India). 1978;50:49.
72. Martino-Andrade AJ, Morais RN, Spercoski KM, et al. Effects of Tribulus
terrestris on endocrine sensitive organs in male and female Wistar rats.
J Ethnopharmacol. 2010;127:165–70.
73. Mathur CS, Nag TN, Goyal SC. Nutritive status of ‘Gokhru’ as livestock
feed in the arid zones of Rajasthan. Food Farming Agric. 1977;9:11.
74. Mazaro-Costa R, Andersen ML, Hachul H, Tufik S. Medicinal plants as
alternative treatments for female sexual dysfunction: utopian vision or
possible treatment in climacteric women? J Sex Med. 2010;7:3695–714.
Tribulus terrestris L. 1847

75. Mutheeswaran S, Pandikumar P, Chellappandian M, Ignacimuthu S.

Documentation and quantitative analysis of the local knowledge on
medicinal plants among traditional Siddha healers in Virudhunagar district
of Tamil Nadu, India. J Ethnopharmacol. 2011;137:523–33.
76. Naplatanova D. Effect of some factors on the production of Tribestan
tablets. Farmatsiya (Sofia). 1984;34:29.
77. Nath K, Malik NS. Chemical composition and nutritive value of Tribulus
terrestris L. Indian J Animal Sci. 1970;40:434.
78. Neychev V, Mitev V. Prosexual and androgen enhancing effects of Tribu-
lus terrestris L.: fact or fiction. J Ethnopharmacol. 2016;179:345–55.
79. Nishchal BS, Rai S, Prabhu MN, et al. Effect of Tribulus terrestris on
haloperidol-induced catalepsy in mice. Indian J Pharm Sci. 2014;76:564–7.
80. Panova D, Tomova M. Tribulus terrestris for producing phenol com-
pounds. Farmatsiya (Sofia). 1970;20:29.
81. Perepelitsa ED, Kintya PK. Chemical study of steroid glycosides of
Tribulus terrestris. IV. Steroid saponins. Khim Prir Soedin. 1975;11:260.
82. Perepelitsa ED, Kintya PK. Dioscin, a steroid glycoside from Tribulus
terrestris. Izv Akad Nauk Mold SSR, Ser Biol Khim Nauk. 1974;6:76.
83. Phillips OA, Mathew KT, Oriowo MA. Antihypertensive and vasodilator
effects of methanolic and aqueous extracts of Tribulus terrestris in rats.
J Ethnopharmacol. 2006;104:351–5.
84. Pkheidze TA, Kereselidze EV, Kachukhashvili TN, Kemertelidze EP.
Steroid sapogenins of some Georgian plants. Tr. 1-go Vses S’ezda Farm.
1967;215 (Pub. 1970).
85. Pkheidze TA. Steroid sapogenins in plants growing in Georgian SSR.
Izuch Ispol’z Lekarstv Rastit Resursov Sb. 1964;328.
86. Qureshi A, Naughton DP, Petroczi A. A systematic review on the herbal ex-
tract Tribulus terrestris and the roots of its putative aphrodisiac and
performance enhancing effect. J Diet Suppl. 2014;11:64–79.
87. Ranjithkumar R, Prathab Balaji S, Balaji B, et al. Standardized aqueous
Tribulus terristris (Nerunjil) extract attenuates hyperalgesia in experimen-
tally induced diabetic neuropathic pain model: role of oxidative stress and
inflammatory mediators. Phytother Res. 2013;27:1646–57.
88. Ryan M, Lazar I, Nadasdy GM, Nadasdy T, Satoskar AA. Acute kidney
injury and hyperbilirubinemia in a young male after ingestion of Tribulus
terrestris. Clin Nephrol. 2015;83:177–83.
89. Sajid TM, Rashid S, Saeed SA. Inhibition of adrenaline-induced aggre-
gation of human platelets by Pakistani medicinal plants. Pak J Pharm Sci.
1991;4:145–52.
90. Saleh NAM, Ahmad AA, Abdalla MF. Flavonoid glycosides of Tribulus
pentadrus and T. terrestris. Phytochemistry. 1982;21:1995.
91. Sangeeta D, Sidhu H, Thind SK, Nath R. Effect of Tribulus terrestris on
oxalate metabolism in rats. J Ethnopharmacol. 1994;44:61–6.
1848 Tribulus terrestris L.

92. Santos CA Jr, Reis LO, Destro-Saade R, Luiza-Reis A, Fregonesi A.

Tribulus terrestris versus placebo in the treatment of erectile dysfunction:
a prospective, randomized, double blind study. Actas Urol Esp. 2014;38:
244–8 (Article in English, Spanish).
93. Seth SD, Jagdeesh G. Cardiac action of Tribulus terrestris L. Indian J Med
Res. 1976;61:1821–5.
94. Sharifi AM, Darabi R, Akbarloo N. Study of antihypertensive mechanism
of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE
activity. Life Sci. 2003;73:2963–71.
95. Sharma HC, Narula JL. Chemical investigations of flowers of Tribulus
terrestris. Chem Era. 1977;13:15.
96. Singh AG, Kumar A, Tewari DD. An ethnobotanical survey of medicinal
plants used in Terai forest of western Nepal. J Ethnobiol Ethnomed. 2012;
8:19.
97. Singh RCP, Sisodia CS. Effect of Tribulus terrestris fruit extracts on chloride
and creatinine renal clearance in dogs. Indian J Physiol Pharmacol. 1971;15:
93–6.
98. Singh RCP, Sisodia CS. Toxicological studies with indigenous diuretic
plants (Tribulus terrestris fruit and Cucumis melo Seed) on dog. J Res
Punjab Agric Univ. 1972;9 Suppl 1:144.
99. Singh S, Nair V, Gupta YK. Evaluation of the aphrodisiac activity of
Tribulus terrestris Linn. in sexually sluggish male albino rats. J Pharmacol
Pharmacother. 2012;3:43–7.
100. Sisto M, Lisi S, D’Amore M, et al. Saponins from Tribulus terrestris L.
protect human keratinocytes from UVB-induced damage. J Photochem
Photobiol B. 2012;117:193–201.
101. Soleimanpour S, Sedighinia FS, Safipour Afshar A, Zarif R, Ghazvini K.
Antibacterial activity of Tribulus terrestris and its synergistic effect with
Capsella bursa-pastoris and Glycyrrhiza glabra against oral pathogens: an
in-vitro study. Avicenna J Phytomed. 2015;5:210–7.
102. Su L, Chen G, Feng SG, et al. Steroidal saponins from Tribulus terrestris.
Steroids. 2009;74:399–403.
103. Su L, Feng SG, Qiao L, et al. Two new steroidal saponins from Tribulus
terrestris. J Asian Nat Prod Res. 2009;11:38–43.
104. Sun W, Gao J, Tu G, et al. A new steroidal saponin from Tribulus
terrestris Linn. Nat Prod Lett. 2002;16:243–7.
105. Talasaz AH, Abbasi MR, Abkhiz S, Dashti-Khavidaki S. Tribulus terrestris-
induced severe nephrotoxicity in a young healthy male. Nephrol Dial
Transplant. 2010;25:3792–3.
106. Tombesi OL. Steroidal sapogenins of Tribulus terrestris. An Asoc Quim
Argent. 1983;71:501.
107. Tomova M, Gyulemetova R, Zarkova S, et al. Steroidal saponins from
Tribulus terrestris L. with a stimulating action on the sexual functions. In:
1st International Conference of Chemistry and Biotechnology of Biolog-
ically Active Natural Products; 1981. p. 298.
Tribulus terrestris L. 1849

108. Tomova M, Gyulemetova R. Steroidsaponins and steroidsapogenins. VI.

Furostanol bisglycoside from Tribulus terrstris L. Planta Med. 1978;34:188.
109. Tomova M, Panova D. Steroid sapogenins. III. Isolation of diosgenin from
Tribulus terrestris. Farmatsiya (Sofia). 1955;15:210.
110. Tomova MP, Bocheva D, Zaikin VG, Wol’fson NS. Steroid saponins and
sapogenins. V. Hecogenin from Tribulus terrestris L. Planta Med. 1977;
32:223.
111. Tomova MP, Panova D, Wolfson NS. Steroid saponines and sapogenins.
IV. Saponins from Tribulus terrestris. Planta Med. 1974;25:231–7.
112. Tuncer MA, Yaymaci B, Sati L, et al. Influence of Tribulus terrestris
extract on lipid profile and endothelial structure in developing atheroscle-
rotic lesions in the aorta of rabbits on a high-cholesterol diet. Acta
Histochem. 2009;111:488–500.
113. Turova AD, Skachkova NI. Comparative study of the cardiotonic activity
of plant steroids. Vestn Akad Nauk Kaz SSR. 1974;11:68.
114. Ukani MD, Nanavati DD, Mehta NK. A review on the Ayurvedic
herb Tribulus terrestris L. Anc Sci Life. 1997;17:144–50.
115. Van Tonder EM, Basson PA, Van Rensberg IBJ. Experimental induction
by feeding the plant Tribulus terrestris L. (Zygophyllaceae). J S Afric Vet
Assoc. 1972;43:363.
116. Wang B, Ma L, Liu T. 406 cases of angina pectoris in coronary heart
disease treated with saponin of Tribulus terrestris. Zhong Xi Yi Jie He Za
Zhi. 1990;10:85–7 (Chinese).
117. Wang J, Zu X, Jiang Y. Five furostanol saponins from fruits of Tribulus
terrestris and their cytotoxic activities. Nat Prod Res. 2009;23:1436–44.
118. Wang Z, Zhang D, Hui S, et al. Effect of Tribulus terrestris saponins on
behavior and neuroendocrine in chronic mild stress depression rats.
J Tradit Chin Med. 2013;33:228–32.
119. Wu G, Jiang S, Jiang F, et al. Steroidal glycosides from Tribulus terrestris.
Phytochemistry. 1996;42:1677–81.
120. Xu T, Xu Y, Liu Y, et al. Two new furostanol saponins from Tribulus
terrestris L. Fitoterapia. 2009;80:354–7.
121. Xu TH, Xu YJ, Xie SX, et al. Two new furostanol saponins from Tribulus
terrestris L. J Asian Nat Prod Res. 2008;10:419–23.
122. Xu Y, Liu Y, Xu T, et al. A new furostanol glycoside from Tribulus
terrestris. Molecules. 2010;15:613–8.
123. Xu YJ, Xu TH, Liu Y, et al. Two new steroidal glucosides from Tribulus
terrestris L. J Asian Nat Prod Res. 2009;11:548–53.
124. Xu YJ, Xu TH, Zhou HO, et al. Two new furostanol saponins
from Tribulus terrestris. J Asian Nat Prod Res. 2010;12:349–54.
125. Xu YX, Chen HS, Liang HQ, et al. Three new saponins from Tribulus
terrestris. Planta Med. 2000;66:545–50.
126. Yan W, Ohtani K, Kasai R, Yamasaki K. Steroidal saponins from fruits of
Tribulus terrestris. Phytochemistry. 1996;42:1417–22.
1850 Tribulus terrestris L.

127. Yang L, Lu JW, An J, Jiang X. Effect of Tribulus terrestris extract on

melanocyte-stimulating hormone expression in mouse hair follicles. Nan
Fang Yi Ke Da Xue Xue Bao. 2006;26:1777–9 (Chinese).
128. Yang L, Wang C, Han M, Yang L. Feasibility study for whole plant
medicinal use of Tribulus terrestris. Zhongguo Zhong Yao Za Zhi. 2009;34:
2163–6 (Chinese).
129. Zhang JD, Cao YB, Xu Z, et al. In vitro and in vivo antifungal activities of the
eight steroid saponins from Tribulus terrestris L. with potent activity against
fluconazole-resistant fungal pathogens. Biol Pharm Bull. 2005;28:2211–5.
130. Zhang JD, Xu Z, Cao YB, et al. Antifungal activities and action mechanisms
of compounds from Tribulus terrestris L. J Ethnopharmacol. 2006;103:
76–84.
131. Zhang SJ, Qu WJ, Zhong SY. Inhibitory effects of saponins from Tribulus
terrestris on alpha-glucosidase in small intestines of rats. Zhongguo Zhong
Yao Za Zhi. 2006;31:910–3 (Chinese).
132. Zhang X, Wei N, Huang J, et al. A new feruloyl amide derivative from the
fruits of Tribulus terrestris. Nat Prod Res. 2012;26:1922–5.
Trigonella foenum-graecum L.
(Fabaceae/Leguminosae)

(Syns.: T. graeca St.-Lag.; T. tibetana (Alef.) Vassilcz.)

Abstract
An annual herb grown in India, Pakistan, Afghanistan, Bangladesh, Nepal, Iran,
Egypt, Morocco, Turkey, Spain, southern China, North Africa and southern
Europe. It is one of the most commonly used plants since ancient times. Medical
Papyri from Egypt mentioned its use as antipyretic and food, and in compounds
used as incense for fumigation and embalming. Dioscorides recommended seed
powder in the form of a poultice for inflammatory affections. Arab Muslim writers
described the plant and seeds as suppurative, aperient, diuretic, emmenagogue,
useful in dropsy, enlargements of spleen and liver, and chronic cough. A poultice
of the leaves is used for external and internal swellings, and to prevent hair loss.
According to Rhazes, it is beneficial in phlegmatic diseases, relieves cough and
asthma, and is aphrodisiac; as a vegetable, it is beneficial for backache, oliguria,
and uterine pain. In Ayurveda, seeds are considered demulcent, tonic and
carminative, and used in dyspepsia with loss of appetite, flatulence, rheumatism,
diabetes and to puerperal women during confinement; in leucorrhea, the pessaries
of its powder are used. It is also identified as one of the most effective antidiabetic
plants, used by traditional healers of northern Europe to treat diabetes, as stimulant
and carminative, and in renal disorders. In Danish folk medicine, it is used to treat
depression and anxiety. The seeds are used as condiment and carminative, for
rheumatism, wound dressing, stomachache, and leprosy, and have shown uterine
stimulant activity. Fenugreek seeds contain 45.4% dietary fiber that blunts glucose
and cholesterol absorption after a meal and regulate cholesterol production in
liver. Seeds contain alkaloids, trypsine and chymotrypsine inhibitors, flavonoids,
spirostanol saponins, anti-inflammatory steroidal saponin glycosides, furostanol
steroidal saponins, flavone C-glycosides, and seventeen amino acids, seven of
them being essential amino acids. Aqueous seed extract significantly lowered
blood glucose, TGs, TC of diabetic animals and in normal mice, and improved
antioxidant status. Addition of 15 g powdered fenugreek seeds soaked in water to
diet significantly reduced postprandial glucose levels in Israeli patients with
NIDDM.
© Springer Nature Switzerland AG 2020 1851
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_189
1852 Trigonella foenum-graecum L.

Keywords
Alfarva
Bockshornklee
Bukkehornsfrø
Çemen
Fenogreco
Fenugreek

Hulbah
Hú lú bā
Medhika
Methi

Vernaculars: Urd.: Methi; Hin.: Kasoorii methii (leaves-dried), Methi (seeds);

San.: Medhika, Methi; Ben.: Mathi; Guj.: Methi; Mal.: Uluwa, Venthayam; Mar.:
Methi; Tam.: Mathai, Menthiyam, Meti, Uluvaarisi, Vendayam, Venthayam; Tel.:
Memnti akulu, Menthulu; Ara.: Darajraaj, Haleeb, Hilaab, Hilba, Hulbah, Shamleez;
Bur.: Penantazi; Chi.: 葫蘆巴, Hú lú bā; Cze.: Pískavice řecké seno, Senenka; Dan.:
Bukkehorn, Bukkehornsfrø, Bukkehornskløver; Dut.: Bokshoorn, Fenegriek,
Fenegriekzaad bokshoornklaver; Eng.: Fenugreek; Fin.: Sarviapila; Fre.: Fenugrec,
Foin grec, Sénegré, Trigonelle; Ger.: Bockshornklee, Gelblicher bockshornklee,
Griechischer bockshornklee, Griechischer schabzigerklee, Griechisch heu, Hel-
blicher bockshornklee; Gre.: Sporos moschositaro, Sporos trigonella; Hun.: Gör-
ögszéna; Ita.: Fieno greco, Seme di fieno greco; Jap.: Fenuguriiku; Kor.: Horopa, Pe
ni geu rig; Maly.: Kelabet; Per.: Shamlit, Shanbelileh; Pol.: Kozieradka pospolita,
Nasiona kozieradki; Por.: Alfarva, Alforna, Alforvas, Caroba, Ervinha, Fenacho,
Feno-grego, Garoba; Rus.: Pazhitnik grecheski, Shambala; Sin.: Asumodhagam,
Uluhal; Spa.: Aholva, Albolba, Alforva, Allorbe, Arbilluala, Fenogreco, Heno
griego, Lorba; Swe.: Bockhornsklöver; Tur.: Boyotu, Boy tohumu, Buyotu, Çemen,
Ҫemenotu, Çimen, Hülbe, Hulebe; Vie.: Cỏ ca ri, Hồ lô ba.
Description: India is the major producer; also grown in Pakistan, Afghanistan,
Bangladesh, Nepal, Iran, Egypt, Morocco, Turkey, Spain, southern China, North
Africa and southern Europe. An annual herb 10–40 cm high, the stems not branched.
Leaves petiolate, trifoliate; leaflets oboval or oblong, the upper part denticulate;
stipules entire. Flowers whitish, solitary or geminate, sessile in the leaf axils,
12–15 mm long; calyx a campanulate tube, 5 teeth and covered with soft hairs.LXXIX
The pod is sickle-shaped, 7–10 cm long, slightly flattened and ending in a long
point; it contains from 10 to 20 rhomboidal seeds, yellow or yellowish-brown,
semitransparent, about 2–3 mm wide by 3–5 mm long, somewhat compressed, with
the hilum on the sharper edge, and a deep furrow running from it and almost dividing
the seed into two unequal lobes, the surface is finely tubercular; the testa consists of
two layers, the inner of which is mucilaginous and encloses the cotyledons and their
large hooked radicle; the taste is bitter, oily and aromatic (Figs. 1, 2 and 3).XL
Actions and Uses: It is one of the most commonly used plants since ancient times.
Medical Papyri from Egypt mentioned its use as antipyretic and food, and in com-
pounds used as incense for fumigation and embalming [54]. Dioscorides recom-
mended seed powder in the form of a poultice for inflammatory affections. Arab
Muslim writers described the plant and seeds as suppurative, aperient, diuretic,
emmenagogue, useful in dropsy, enlargements of spleen and liver, and chronic cough.
A poultice of the leaves is used for external and internal swellings, and to prevent hair
loss.XL According to Rhazes, it is beneficial in phlegmatic diseases, relieves cough
and asthma, and is aphrodisiac; as a vegetable, it is beneficial for backache, oliguria,
Trigonella foenum-graecum L. 1853

Fig. 1 Trigonella foenum-graecum, Illustration, Prof. Dr. Otto Wilhelm Thomé Flora von
Deutschland, Österreich und der Schweiz 1885, Gera, Germany, WikimediaCommons, https://
commons.wikimedia.org/wiki/File:Illustration_Trigonella_foenum-graecum0_clean.jpg

Fig. 2 Trigonella foenum-graecum, Plant, Yercaud-elango, WikimediaCommons, https://commons.

wikimedia.org/wiki/File:Trigonella_foenum_graecum-1-bangalore-India.jpg
1854 Trigonella foenum-graecum L.

Fig. 3 Trigonella foenum-graecum, Seeds, Takeaway, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:2017_0102_fenugreek_
seeds.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en

and uterine pain.LXXIX In Unani medicine, it (temperament, hot 2° and dry 2°) is
considered nerve tonic, anti-inflammatory, aphrodisiac, expectorant, stomachic,
carminative, laxative, uterine stimulant and emmenagogue,LXXVII and aerial parts
decoction used as shampoo cures dandruff and makes hair curly.LXXIX In Ayurveda,
seeds are considered demulcent, tonic and carminative, and used in dyspepsia with
loss of appetite, flatulence, rheumatism, diabetes and to puerperal women during
confinement; in leucorrhea, the pessaries of its powder are used.LXXXI,CV It is also
identified as one of the most effective antidiabetic plants [23, 80, 100, 137], used by
traditional healers of northern Europe to treat diabetes [142], as stimulant and
carminative, and in renal disorders.LXXIX In the traditional medicines of Egypt [37],
Iran [123, 131], North Africa [45], and Morocco [167], it is one of the most commonly
used antidiabetic plants, and almost one quarter of Jordanian diabetic patients use it as
adjunct to their standard antidiabetic drugs, and most with the knowledge of their
physicians [92]. In Danish folk medicine, it is used to treat depression and anxiety
[53]. The seeds are used as condiment and carminative, for rheumatism, wound
dressing, stomachache, and leprosy, and have shown uterine stimulant activity [4].
Phytoconstituents: Fenugreek seeds contain 45.4% dietary fiber that blunts glucose
and cholesterol absorption after a meal and regulate cholesterol production in liver
[20, 120]. Seeds contain alkaloids (trigonelline), trypsine and chymotrypsine inhibi-
tors [158–160], flavonoids [128, 157], spirostanol saponins [95], anti-inflammatory
steroidal saponin glycosides [64], furostanol steroidal saponins [86, 148, 164], flavone
Trigonella foenum-graecum L. 1855

C-glycosides [114], and seventeen amino acids, seven of them being essential amino
acids [129]. Unique and major amino acid 4-hydroxyisoleucine (4-OH-Ile) has been
characterized as one of the active ingredients responsible for blood glucose control
[36]. The seeds and leaves are also rich sources of vitamin C [122]. Sapogenin and
total steroid yields from the seeds are 0.45–1.02% and 0.58–1.26% respectively [154];
major sapogenins are diosgenin and yamogenin [27, 35, 99, 108]. The leaves extract
indicated the presence of alkaloids, cardiac glycosides, and phenols as the major
component [5]; c-schizandrin and scopoletin were isolated from leaves and stem
[156], and flavonol glycosides from stems [46]. Boiling seeds in water causes gradual
increase in total solids and a decrease in the content of total sugars, protein com-
pounds, Ca, Mg, P, phytic acid, and amino acids [3].
Pharmacology: The seed powder, its methanol extract, and the residue remaining
after methanol extraction all produced significant hypoglycemic effects when fed
simultaneously with glucose to rats [9]; seed powder also prevented diabetic
retinopathy and other ocular disorders [106], and was neuroprotective in diabetic rats
[72, 73]. Aqueous seed extract significantly lowered blood glucose [144, 163], TGs,
TC of diabetic animals [7, 77, 162], and in normal mice [166], and improved
antioxidant status [79, 161]. Alcohol seed extract lowered blood glucose in both
normal and diabetic rats [149], prevented increase in renal weight, partially corrected
alterations in enzymes such as glucokinase, hexokinase, and PFK of diabetic rats
[150], reduced high-fat diet-induced metabolic changes, weight gain and decreased
plasma TGs and TC [45, 47, 87, 124]. Fenugreek seeds-supplemented diet of obese
rats significantly lowered fasting plasma cholesterol and TNF-a levels [110], pro-
moted adipocyte differentiation and inhibited inflammation in adipose tissues [147].
Dietary supplementation with fenugreek leaves showed significant effect on hyper-
glycemia, hypoinsulinemia and HbA1c in STZ-diabetic rats [31], and their aqueous
extract also exhibited significant hypoglycemic effect in normoglycemic and
alloxan-diabetic rats [1]. Enhanced LPO and increased susceptibility to oxidative
stress associated with depletion of antioxidants in diabetic rats was normalized by seed
powder treatment [18]. Soluble dietary fiber fraction also reduced postprandial
hyperglycemia in diabetic rats by delaying digestion of sucrose, and significantly
decreased TGs, TC and LDL-C, with no significant change in insulin level [48, 49,
136]. Acetone seed extract, and water and acetone extracts of stems and leaves were
inactive in lowering blood glucose in normal animals; however, acetone seed extract
at room temperature exhibited hypoglycemic effect, and antagonized Cd and alloxan-
induced hyperglycemia [39]. Ribes et al. [119] reported that defatted seed material,
rich in fibers, saponins and proteins possesses antidiabetic property, and yielded two
subfractions, subfraction “a” rich in fibers (79.6%), and subfraction “b” rich in
saponins (7.2%) and proteins (52.8%). Subfraction “a” decreased hyperglycemia and
glycosuria and reduced high plasma glucagon and somatostatin levels in alloxan-
diabetic dogs [118]. While rats treated chronically with seed extract were reported to
show an increase in plasma insulin [102], no significant effect of fenugreek treatment
for 28-days on glucose homeostasis was reported in normal and STZ-diabetic mice
[142]. Diet of diabetic rats supplemented with fenugreek leaves for 45-days, lowered
1856 Trigonella foenum-graecum L.

lipid profile [16]. 4-Hydroxyisoleucine decreased plasma TGs by 33%, TC by 22%,

and FFAs by 14%, and increased HDL-C/TC ratio by 39% in dyslipidemic hamsters
[90]. Dietary fenugreek seeds reduced serum cholesterol, hepatic cholesterol, and
biliary cholesterol, and markedly reduced high-cholesterol diet-induced formation
and regressed preformed gallstones in mice [115–117]. Aqueous seed extract offered
significant protection against MSG-induced dyslipidemia and oxidative stress in rats
[71], and chronic feeding of alcohol seed extract to hyperlipidemic rats lowered
plasma and hepatic lipid levels [25]. Both in normal and diabetic rats, and in diabetic
dogs, steroid saponins were credited for the hypocholesterolemic effect of fenugreek
seeds and enhancing food consumption and motivation to eat [103, 126, 138].
Various crude and semipurified seed extracts have shown significant anti-
inflammatory and analgesic activities in experimental animals [21, 66, 67, 76, 83, 140,
155]; and the seed mucilage ameliorated inflammatory and oxidative effects of
adjuvant-induced arthritis in rats [133]. Leaves extracts also exhibit anti-
inflammatory, antipyretic and analgesic properties [5, 56, 97, 98]. In vitro antioxi-
dant activity of seeds and leaves extracts [33, 42, 62] and in diabetic rats and other
oxidative stress conditions has been reported [17, 30, 43, 51, 85, 113, 145]. Aqueous
and polyphenol seed extracts exhibited appreciable antioxidant effect and significant
protection against ethanol- and other chemicals-induced hepatotoxicity and nephro-
toxicity [59–61, 63, 121, 141, 143]. Ethanol leaf extract also exhibited antioxidant
activity and protected goat liver against H2O2- and CCl4-induced damage [78]. Tri-
gonelline, the major alkaloid, exhibits hypolipidemic, sedative, antimigraine,
memory-improving, neuroprotective, antibacterial, antiviral, and antitumor activities
and reduces diabetic auditory neuropathy and platelet aggregation [165]. Fenugreek
seed extract is cytotoxic and growth inhibitory to breast, pancreatic and prostate
cancer cells but not to normal cells [127], and significantly inhibited DMBA-induced
mammary hyperplasia [15], and methanol extract reduced rate of tumor incidence,
cumulative number and tumor burden of DMBA-induced skin papillomas [24].
Ethanol extract inhibited (70%) tumor cell growth of Ehrlich ascites carcinoma [139].
Inclusion of fenugreek in diet significantly decreased LPO, and enhanced circulating
antioxidants [28], and decreased activities of b-glucuronidase and mucinase during
DMH colon carcinogenesis [29]. Chloroform extract of the whole plant effectively
killed MCF-7 human immortalized breast cells through induction of apoptosis [68].
Oral administration of ethanol seed extract with 20% 4-OH-Ile to mice for
4-weeks significantly increased swimming endurance, plasma nonesterified fatty
acid and plasma glucose, and significantly decreased fat accumulation by increasing
utilization of fatty acids as energy source [52]. Ethanol seed extract produced
antidepressant effect and also highly significantly inhibited MAO-A and MAO-B
enzymes activity, both in vitro and in rat’s whole brain, as target for its antide-
pressant effect [53, 69]. Hydroalcohol seed extract also reversed motor symptoms in
an animal model of Parkinson’s Disease [38]. Dietary supplementation with seeds
for 8-weeks, increased pancreatic lipase and chymotrypsin activities [104], and
decreased intestinal levels of phosphatases and sucrase [105]. Aqueous seed extract
showed cytoprotective effects against ethanol-induced gastric ulcers in rats [94],
and significantly reduced amount of calcification in kidneys and the total calcium
Trigonella foenum-graecum L. 1857

amount of renal tissue due to ethylene glycol and ammonium chloride-induced

nephrolithiasis in rats [74]. Ethanol extract also significantly attenuated CP-induced
nephro- and hepatotoxicity and the associated biochemical and histopathological
alterations [50]. Petroleum ether, benzene and chloroform extracts of leaves ex-
hibited significant antibacterial activity against clinical isolates of S. aureus,
P. vulgaris, P. mirabilis, K. pneumonia and E. coli [96].
Clinical Studies: Addition of 15 g powdered fenugreek seeds soaked in water to diet
significantly reduced postprandial glucose levels in Israeli patients with NIDDM [75].
In a placebo-controlled study fenugreek seeds, in a dose of 2.5 g twice daily for
3-months to healthy Indian volunteers did not affect blood lipids and blood sugar
(fasting and postprandial); however, in mild cases of NIDDM (non-CAD), it signif-
icantly reduced blood sugar, and in NIDDM patients with CAD, it significantly
decreased TC and TGs without affecting HDL-C [22]. Defatted seed powder (50 g)
incorporated into diet during lunch and dinner of Indian patients with IDDM (Type-1)
for 10-days, significantly reduced FBG and improved GTT with a 54% reduction in
24-h urinary glucose excretion; and significant reduction in serum TC, LDL-C,
VLDL-C and TGs [130]. In a double-blinded RCT of twenty-five newly diagnosed
Indian patients with type-2 diabetes, hydroalcoholic seed extract (1 g/day) for
two-months did not significantly affect FBG and two-hour post-glucose blood glucose
levels; however, insulin-resistance and serum TGs decreased and HDL-C increased
significantly in the treated group [40]. In another clinical trial, 24 type-2 diabetic
Iranian patients used 10 g/day of powdered seeds mixed with yoghurt or soaked in hot
water for 8-weeks. Fasting blood glucose, TGs and VLDL-C decreased significantly
(25%, 30% and 30.6% respectively) when seeds were used soaked in hot-water;
whereas no significant changes occurred in patients who consumed them mixed with
yoghurt [58]. In a triple-blind RCT of 88 type 2 diabetic Iranian patients, powdered
seeds (10 g/day) were consumed by half of the patients and the control were given
5 g/day of wheat starch for 8-weeks. Fenugreek seeds significantly decreased FBG
and HbA1c, serum levels of insulin, TC and TGs and significantly increased serum
levels of adiponectin compared to placebo [109]. Administration of leaf powder
40 mg/kg in 10 mL distilled water to 20 male healthy Iraqi volunteers aged 20–
30 years, significantly lowered blood glucose level by 13.4% and decreased potas-
sium level by 14.1% four-hours after ingestion [2]. Consumption of germinated seed
powder (18 g/day) in diet by twenty Indian adults for one-month significantly lowered
TC and LDL-C, with no significant changes in HDL, VLDL and TGs levels [135].
Significant decrease in daily fat consumption and a significant decrease in insulin/
glucose ratio was reported in thirty-nine healthy overweight French male volunteers
who were administered a fixed dose of a fenugreek seed hydroalcoholic extract for
6-weeks in a double-blind, randomized, placebo-controlled parallel trial [26]. Use of a
fenugreek fiber product taken 30 min before two meals/day for 2-weeks diminished
heartburn severity in U.S. subjects with frequent heartburn, similar to the results
produced by ranitidine 75 mg twice/day [32]. In a single-blinded, randomized,
placebo-controlled, and crossover design, healthy overweight Korean women given
1858 Trigonella foenum-graecum L.

fenugreek tea, followed by a lunch buffet showed decreased hunger, and increased
feelings of fullness compared with placebo tea [19].
A single site, double blind RCT on 80 healthy Australian women aged 20–
49 years with low sex-drive reported a significant increase in free testosterone and
estradiol in the treated group, as well as sexual desire and arousal after an oral dose
of a standardized seed extract at a dose of 600 mg/day for two menstrual cycles,
compared to placebo-treated group [112]. Consumption of herbal tea containing
fenugreek by Turkish mothers in the first week of postnatal period resulted in
significantly higher volume of breast milk, significantly lower maximum weight loss
in their infants and regained birth weight earlier than in infants of mothers from a
control and placebo groups [146]. A standardized extract of fenugreek (300 mg,
twice daily) administered as a nutritional adjuvant to 50 Indian patients of Parkin-
son’s disease stabilized on L-Dopa therapy, for 6-months in a double-blind,
placebo-controlled clinical study showed significant improvement with an excellent
safety and tolerability profile, and as a useful adjuvant treatment with L-Dopa of PD
patients [91].
Mechanism of Action: Aqueous seed extract corrects metabolic alterations associ-
ated with diabetes by exhibiting insulin-like properties [151], and stimulates cellular
glucose uptake in a dose-dependent manner by translocation of GLUT4 from intra-
cellular space to the plasma membrane [55, 57, 81, 152]. The antidiabetic effects are
attributed mainly to galactomannan, 4-OH-Ile, diosgenin and trigonelline. These
constituents have demonstrated direct antidiabetic effect by increasing insulin secre-
tion (4-OH-Ile), decreasing insulin-resistance and glucose absorption from GIT
(galactomannan) [8]; trigonelline improves b-cells regeneration, insulin secretion,
activities of enzymes involved in glucose metabolism, and ROS [165]. 4-
Hydroxyisoleucine increases glucose-induced insulin release through a direct effect
on isolated islets of Langerhans from both rats and humans, which is strictly glucose
dependent [44, 125, 134]. Moorthy et al. [82] isolated an active antihyperglycemic
compound other than diosgenin and 4-OH-Ile from seeds. Seed powder lowered to
almost control values the increased activities of G-6-Pase and fructose-1,6-
bisphosphatase enzymes in diabetic liver [41, 111]. Puri et al. [107] also suggested
an insulinotropic and extrapancreatic mechanism for the blood glucose lowering effect.
Human A/Es, Allergy and Toxicity: Allergic reactions to fenugreek are extre-
mely rare, but there are some reports of human allergic reactions, especially with
peanut cross-allergy [34, 89, 101]. Approximately one-third of 20 healthy male
volunteers experienced feelings of hunger, frequency of micturition or dizziness
during the 24 h after ingestion of leaf powder 40 mg/kg in 10 mL distilled water
[2]. It may also cause nausea and headache.LXXVII
Animal Toxicity: Oral administration of ethanol seed extract in a dose of 3 g/kg
body weight to mice and rats for 10-days was nontoxic [84]; however, administration
of seed extract for 15-days to both mice and rats, significantly decreased serum T3 and
T3/T4 ratio, but increased T4 levels and body weight [93]. Another study reported no
acute or subacute toxicity or death in rats or mice after feeding seed powder up to a
Trigonella foenum-graecum L. 1859

dose of 5,000 mg/kg body weight [88]. LD50 (i.p.) of leaves extract in mice is close
to 4,000 mg/kg [56], but Abdel-Barry et al. [1] reported LD50 of aqueous leaf extract
in mice to be 1,900 mg/kg (i.p.) and 10,000 mg/kg (oral). However, aqueous seed
extract may have deleterious toxic effects on reproductive performance and potential
teratogenic effects in fetuses of rats [65]. Anaphylactic reaction in mice [153], and
myopathy in ruminants have also been reported [132].
CYP450 and Potential for Drug-Herb Interactions: Coadministration of fenu-
greek seed powder in dogs reduced AUC of phenytoin by about 72% [13], and
significantly reduced the Cmax and AUC of sildenafil [14] and theophylline [10].
Fenugreek did not significantly affect pharmacokinetics of cyclosporine and car-
bamazepine in rabbits, two CYP3A4 substrates [11]. Ahmmed et al. [6] and
Al-Jenoobi et al. [12] also reported no substantial inhibitory activity of fenugreek of
CYP3A4 and CYP2D6, though it significantly inhibited mRNA and protein
expression of CYP2C11 in rats [70].
Commentary: There are sufficient clinical studies indicating a positive effect of
fenugreek seeds on blood glucose and lipids, validating its traditional uses. The
lactogenic effects of seeds are also well-recognized as a home remedy in the Indian
subcontinent. Improvement in sex drive of women is also an encouraging obser-
vation. This common vegetable/spice could be a simple answer for many of the
modern-day health problems, if more large-scale RCTs in patients of various eth-
nicities further validate these results.

References
1. Abdel-Barry JA, Abdel-Hassan IA, Al-Hakiem MH. Hypoglycaemic and
antihyperglycaemic effects of Trigonella foenum-graecum leaf in normal
and alloxan induced diabetic rats. J Ethnopharmacol. 1997;58:149–55.
2. Abdel-Barry JA, Abdel-Hassan IA, Jawad AM, al-Hakiem MH. Hypo-
glycaemic effect of aqueous extract of the leaves of Trigonella foenum-
graecum in healthy volunteers. East Mediterr Health J. 2000;6:83–8.
3. Abdel-Nabey AA, Damir AA. Changes in some nutrients of fenugreek
(Trigonella foenum-graecum L.) seeds during water boiling. Plant Foods
Human Nutr. 1990;40:267–74.
4. Abdo MS. al-Kafawi AA. Experimental studies on the effect of Trigonella
foenum-graecum. Planta Med. 1969;17:14–8.
5. Ahmadiani A, Javan M, Semnanian S, et al. Anti-inflammatory and
antipyretic effects of Trigonella foenum-graecum leaves extract in the rat.
J Ethnopharmacol. 2001;75:283–6.
6. Ahmmed SM, Mukherjee PK, Bahadur S, et al. Interaction potential of
Trigonella foenum-graecum through cytochrome P450 mediated inhibi-
tion. Indian J Pharmacol. 2015;47:530–4.
1860 Trigonella foenum-graecum L.

7. Alarcon-Aguilara FJ, Roman-Ramos R, Perez-Gutierrez S, et al. Study of

the antihyperglycemic effect of plants used as antidiabetics. J Ethnophar-
macol. 1998;61:101–10.
8. Al-Habori M, Raman A, Lawrence MJ, Skett P. In vitro effect of fenugreek
extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen
phosphorylase A. Int J Exp Diabetes Res. 2001;2:91–9.
9. Ali L, Azad Khan AK, Hassan Z, et al. Characterization of the hypoglycemic
effects of Trigonella foenum-graecum seed. Planta Med. 1995;61:358–60.
10. Al-Jenoobi FI, Ahad A, Mahrous GM, et al. Effects of fenugreek, garden
cress, and black seed on theophylline pharmacokinetics in beagle dogs.
Pharm Biol. 2015;53:296–300.
11. Al-Jenoobi FI, Alam MA, Alkharfy KM, et al. Pharmacokinetic interaction
studies of fenugreek with CYP3A substrates cyclosporine and carba-
mazepine. Eur J Drug Metab Pharmacokinet. 2014;39:147–53.
12. Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. Effect of Trigonella
foenum-graecum L. on metabolic activity of CYP2D6 and CYP3A4. Forsch
Komplementmed. 2015;22:180–4.
13. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium
sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin
pharmacokinetics in beagle dogs. Phytother Res. 2013;27:1800–4.
14. Al-Mohizea AM, Ahad A, El-Maghraby GM, et al. Effects of Nigella sativa,
Lepidium sativum and Trigonella foenum-graecum on sildenafil disposition
in beagle dogs. Eur J Drug Metab Pharmacokinet. 2015;40:219–24.
15. Amin A, Alkaabi A, Al-Falasi S, Daoud SA. Chemopreventive activities of
Trigonella foenum-graecum (Fenugreek) against breast cancer. Cell Biol
Int. 2005;29:687–94.
16. Annida B, Stanely Mainzen Prince P. Supplementation of fenugreek leaves
lower lipid profile in streptozotocin-induced diabetic rats. J Med Food.
2004;7:153–6.
17. Annida B, Stanely Mainzen Prince P. Supplementation of fenugreek leaves
reduces oxidative stress in streptozotocin-induced diabetic rats. J Med
Food. 2005;8:382–5.
18. Anuradha CV, Ravikumar P. Restoration on tissue antioxidants by fenugreek
seeds (Trigonella foenum-graecum) in alloxan-diabetic rats. Indian J Physiol
Pharmacol. 2001;45:408–20.
19. Bae J, Kim J, Choue R, Lim H. Fennel (Foeniculum vulgare) and Fenugreek
(Trigonella foenum-graecum) tea drinking suppresses subjective short-term
appetite in overweight women. Clin Nutr Res. 2015;4:168–74.
20. Basch E, Ulbricht C, Kuo G, et al. Therapeutic applications of fenugreek.
Altern Med Rev. 2003;8:20–7 (Review).
21. Biswal S, Das MC, Nayak P. Antinociceptive activity of seeds of Trigonella
foenum-graecum in rats. Indian J Physiol Pharmacol. 2003;47:479–80.
22. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale
Rosc.) and fenugreek (Trigonella foenum-graecum L.) on blood lipids,
Trigonella foenum-graecum L. 1861

blood sugar and platelet aggregation in patients with coronary artery

disease. Prostaglandins Leukot Essent Fatty Acids. 1997;56:379–84.
23. Cefalu WT, Ye J, Wang ZQ. Efficacy of dietary supplementation with
botanicals on carbohydrate metabolism in humans. Endocr Metab Immune
Disord Drug Targets. 2008;8:78–81 (Review).
24. Chatterjee S, Kumar M, Kumar A. Chemomodulatory effect of Trigonella
foenum-graecum (L.) seed extract on two stage mouse skin carcinogenesis.
Toxicol Int. 2012;19:287–94.
25. Chaturvedi U, Shrivastava A, Bhadauria S, et al. A mechanism-based
pharmacological evaluation of efficacy of Trigonella foenum-graecum
(Fenugreek) seeds in regulation of dyslipidemia and oxidative stress in
hyperlipidemic rats. J Cardiovasc Pharmacol. 2013;61:505–12.
26. Chevassus H, Gaillard JB, Farret A, et al. A fenugreek seed extract
selectively reduces spontaneous fat intake in overweight subjects. Eur J
Clin Pharmacol. 2009;65:1175–8.
27. Dawidar AM, Saleh AA, El-Motei SL. Steroid sapogenin constituents of
fenugreek seeds. Planta Med. 1973;24:367–70.
28. Devasena T, Menon VP. Enhancement of circulatory antioxidants by
fenugreek during 1,2-dimethylhydrazine-induced rat colon carcinogenesis.
J Biochem Mol Biol Biophys. 2002;6:289–92.
29. Devasena T, Menon VP. Fenugreek affects the activity of beta-glucuronidase
and mucinase in the colon. Phytother Res. 2003;17:1088–91.
30. Devasena T, Venugopal Menon P. Fenugreek seeds modulate 1,2-dimethyl-
hydrazine-induced hepatic oxidative stress during colon carcinogenesis.
Ital J Biochem. 2007;56:28–34.
31. Devi BA, Kamalakkannan N, Prince PS. Supplementation of fenugreek
leaves to diabetic rats. Effect on carbohydrate metabolic enzymes in diabetic
liver and kidney. Phytother Res. 2003;17:1231–3.
32. DiSilvestro RA, Verbruggen MA, Offutt EJ. Antiheartburn effects of a
fenugreek fiber product. Phytother Res. 2011;25:88–91.
33. Dixit P, Ghaskadbi S, Mohan H, Devasagayam TP. Antioxidant properties
of germinated fenugreek seeds. Phytother Res. 2005;19:977–83.
34. Faeste CK, Namork E, Lindvik H. Allergenicity and antigenicity of
fenugreek (Trigonella foenum-graecum) proteins in foods. J Allergy Clin
Immunol. 2009;123:187–94.
35. Fazli FRY, Hardman R. Isolation and characterization of steroids and other
constituents from Trigonella foenum-graecum. Phytochemistry. 1971;10:
2497–503.
36. Flammang AM, Cifone MA, Erexson GL, Stankowski LF Jr. Genotoxicity
testing of a fenugreek extract. Food Chem Toxicol. 2004;42:1769–75.
37. Gad MZ, El-Sawalhi MM, Ismail MF, El-Tanbouly ND. Biochemical study
of the antidiabetic action of the Egyptian plants fenugreek and balanites. Mol
Cell Biochem. 2006;281:173–83.
1862 Trigonella foenum-graecum L.

38. Gaur V, Bodhankar SL, Mohan V, Thakurdesai PA. Neurobehavioral

assessment of hydroalcoholic extract of Trigonella foenum-graecum seeds
in rodent models of Parkinson’s disease. Pharm Biol. 2013;51:550–7.
39. Ghafghazi T, Sheriat HS, Dastmalchi T, Barnett RC. Antagonism of
cadmium and alloxan-induced hyperglycemia in rats by Trigonella
foenum-graecum. Pahlavi Med J. 1977;8:14–25.
40. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek)
seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a
double blind placebo controlled study. J Assoc Physicians India. 2001;49:
1057–61.
41. Gupta D, Raju J, Baquer NZ. Modulation of some gluconeogenic enzyme
activities in diabetic rat liver and kidney: effect of antidiabetic compounds.
Indian J Exp Biol. 1999;37:196–9.
42. Gupta S, Prakash J. Studies on Indian green leafy vegetables for their
antioxidant activity. Plant Foods Hum Nutr. 2009;64:39–45.
43. Gupta SK, Kalaiselvan V, Srivastava S, et al. Trigonella foenum-
graecum (fenugreek) protects against selenite-induced oxidative stress in
experimental cataractogenesis. Biol Trace Elem Res. 2010;136:258–68.
44. Haeri MR, Limaki HK, White CJ, White KN. Noninsulin dependent
antidiabetic activity of (2S, 3R, 4S) 4-hydroxyisoleucine of fenugreek
(Trigonella foenum-graecum) in streptozotocin-induced type I diabetic rats.
Phytomedicine. 2012;19:571–4.
45. Hamza N, Berke B, Cheze C, et al. Preventive and curative effect
of Trigonella foenum-graecum L. seeds in C57BL/6 J models of type 2
diabetes induced by high-fat diet. J Ethnopharmacol. 2012;142:516–22.
46. Han Y, Nishibe S, Noguchi Y, Jin Z. Flavonol glycosides from the stems
of Trigonella foenum-graecum. Phytochemistry. 2001;58:577–80.
47. Handa T, Yamaguchi K, Sono Y, Yazawa K. Effects of fenugreek seed
extract in obese mice fed a high-fat diet. Biosci Biotechnol Biochem.
2005;69:1186–8.
48. Hannan JM, Ali L, Rokeya B, et al. Soluble dietary fibre fraction of
Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis
in animal models of type 1 and type 2 diabetes by delaying carbohydrate
digestion and absorption, and enhancing insulin action. Br J Nutr.
2007;97:514–21.
49. Hannan JM, Rokeya B, Faruque O, et al. Effect of soluble dietary fibre
fraction of Trigonella foenum-graecum on glycemic, insulinemic, lipidemic
and platelet aggregation status of Type 2 diabetic model rats. J Ethnophar-
macol. 2003;88:73–7.
50. Hegazy MG, Emam MA. Ethanolic extract of Trigonella foenum-
graecum attenuates cisplatin-induced nephro- and hepatotoxicities in rats.
Cell Mol Biol (Noisy-le-grand). 2015;61:81–7.
51. Hfaiedh N, Alimi H, Murat JC, Elfeki A. Protective effects of fenugreek
(Trigonella foenum-graecum L.) upon dieldrin-induced toxicity in male
rat. Gen Physiol Biophys. 2012;31:423–30.
Trigonella foenum-graecum L. 1863

52. Ikeuchi M, Yamaguchi K, Koyama T, et al. Effects of fenugreek seeds

(Trigonella foenum graecum) extract on endurance capacity in mice. J Nutr
Sci Vitaminol (Tokyo). 2006;52:287–92.
53. Jäger AK, Gauguin B, Andersen J, et al. Screening of plants used in
Danish folk medicine to treat depression and anxiety for affinity to the
serotonin transporter and inhibition of MAO-A. J Ethnopharmacol. 2013;
145:822–5.
54. Jain SC, Agrawal M, Sharma RA. The genus Trigonella—phytochemistry
and biology. Anc Sci Life. 1996;16:108–17.
55. Jaiswal N, Maurya CK, Venkateswarlu K, et al. 4-Hydroxyisoleucine
stimulates glucose uptake by increasing surface GLUT4 level in skeletal
muscle cells via phosphatidyl-inositol-3-kinase-dependent pathway. Eur J
Nutr. 2012;51:893–8.
56. Javan M, Ahmadiani A, Semnanian S, Kamalinejad M. Antinociceptive
effects of Trigonella foenum-graecum leaves extract. J Ethnopharmacol.
1997;58:125–9.
57. Kadan S, Saad B, Sasson Y, Zaid H. In vitro evaluations of cytotoxicity of
eight antidiabetic medicinal plants and their effect on GLUT4 transloca-
tion. Evid Based Complement Alternat Med. 2013;2013:549345.
58. Kassaian N, Azadbakht L, Forghani B, Amini M. Effect of fenugreek seeds
on blood glucose and lipid profiles in type 2 diabetic patients. Int J Vitam
Nutr Res. 2009;79:34–9.
59. Kaviarasan S, Anuradha CV. Fenugreek (Trigonella foenum-graecum)
seed polyphenols protect liver from alcohol toxicity: a role on hepatic
detoxification system and apoptosis. Pharmazie. 2007;62:299–304.
60. Kaviarasan S, Ramamurty N, Gunasekaran P, et al. Fenugreek (Trigonella
foenum-graecum) seed extract prevents ethanol-induced toxicity and
apoptosis in Chang liver cells. Alcohol Alcohol. 2006;41:267–73.
61. Kaviarasan S, Sundarapandiyan R, Anuradha CV. Protective action of
fenugreek (Trigonella foenum-graecum) seed polyphenols against alcohol-
induced protein and lipid damage in rat liver. Cell Biol Toxicol. 2008;24:
391–400.
62. Kaviarasan S, Vijayalakshmi K, Anuradha CV. Polyphenol-rich extract of
fenugreek seeds protect erythrocytes from oxidative damage. Plant Foods
Hum Nutr. 2004;59:143–7.
63. Kaviarasan S, Viswanathan P, Anuradha CV. Fenugreek seed (Trigonella
foenum-graecum) polyphenols inhibit ethanol-induced collagen and lipid
accumulation in rat liver. Cell Biol Toxicol. 2007;23:373–83.
64. Kawabata T, Cui MY, Hasegawa T, et al. Anti-inflammatory and antime-
lanogenic steroidal saponin glycosides from Fenugreek (Trigonella foenum-
graecum L.) seeds. Planta Med. 2011;77:705–10.
65. Khalki L, M’hamed SB, Bennis M, et al. Evaluation of the developmental
toxicity of the aqueous extract from Trigonella foenum-graecum (L.) in
mice. J Ethnopharmacol. 2010;131:321–5.
1864 Trigonella foenum-graecum L.

66. Khare AK, Srivastava MC, Tiwari JP, et al. A preliminary study of anti-
inflammatory activity of seeds of Trigonella foenum-graecum. Indian J
Physiol Pharmacol. 1981;25:98.
67. Khare AK, Srivastava MC, Tiwari JP, et al. Experimental evaluation of
anti-inflammatory activity of ‘Methi’ seeds. Indian Drugs. 1982;19:191.
68. Khoja KK, Shaf G, Hasan TN, et al. Fenugreek, a naturally occurring
edible spice, kills MCF-7 human breast cancer cells via an apoptotic
pathway. Asian Pac J Cancer Prev. 2011;12:3299–304.
69. Khursheed R, Rizwani GH, Sultana V, Ahmed M, Kamil A. Antidepressant
effect and categorization of inhibitory activity of monoamine oxidase type A
and B of ethanolic extract of seeds of Trigonella foenum-graecum Linn.
Pak J Pharm Sci. 2014;27(5 Spec no), 1419–25.
70. Korashy HM, Al-Jenoobi FI, Raish M, et al. Impact of herbal medicines
like Nigella sativa, Trigonella foenum-graecum, and Ferula asafoetida, on
CytochromeP450 2C11 gene expression in rat liver. Drug Res (Stuttg).
2015;65:366–72.
71. Kumar P, Bhandari U. Protective effect of Trigonella foenum-graecum
Linn. on monosodium glutamate-induced dyslipidemia and oxidative stress
in rats. Indian J Pharmacol. 2013;45:136–40.
72. Kumar P, Kale RK, Baquer NZ. Antihyperglycemic and protective effects
of Trigonella foenum-graecum seed powder on biochemical alterations in
alloxan diabetic rats. Eur Rev Med Pharmacol Sci. 2012;16 Suppl 3:18–27.
73. Kumar P, Kale RK, McLean P, Baquer NZ. Antidiabetic and neuropro-
tective effects of Trigonella foenum-graecum seed powder in diabetic rat
brain. Prague Med Rep. 2012;113:33–43.
74. Laroubi A, Touhami M, Farouk L, et al. Prophylaxis effect of Trigonella
foenum-graecum L. seeds on renal stone formation in rats. Phytother Res.
2007;21:921–5.
75. Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek
in noninsulin dependent diabetics. Eur J Clin Nutr. 1988;42:51–4.
76. Mandegary A, Pournamdari M, Sharififar F, et al. Alkaloid and flavonoid
rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with
antinociceptive and anti-inflammatory effects. Food Chem Toxicol. 2012;
50:2503–7.
77. Marzouk M, Soliman AM, Omar TY. Hypoglycemic and antioxidative
effects of fenugreek and termis seeds powder in streptozotocin-diabetic rats.
Eur Rev Med Pharmacol Sci. 2013;17:559–65.
78. Meera R, Devi P, Kameswari B, et al. Antioxidant and hepatoprotective
activities of Ocimum basilicum Linn. and Trigonella foenum-graecum
Linn. against H2O2 and CCL4 induced hepatotoxicity in goat liver. Indian J
Exp Biol. 2009;47:584–90.
79. Middha SK, Bhattacharjee B, Saini D, et al. Protective role of Trigonella
foenum-graceum extract against oxidative stress in hyperglycemic rats. Eur
Rev Med Pharmacol Sci. 2011;15:427–35.
Trigonella foenum-graecum L. 1865

80. Modak M, Dixit P, Londhe J, et al. Indian herbs and herbal drugs used for
the treatment of diabetes. J Clin Biochem Nutr. 2007;40:163–73.
81. Mohammad S, Taha A, Akhtar K, et al. In vivo effect of Trigonella
foenum-graecum on the expression of pyruvate kinase, phosphoenolpyru-
vate carboxykinase, and distribution of glucose transporter (GLUT4) in
alloxan-diabetic rats. Can J Physiol Pharmacol. 2006;84:647–54.
82. Moorthy R, Prabhu KM, Murthy PS. Antihyperglycemic compound
(GII) from fenugreek (Trigonella foenum-graecum Linn.) seeds, its purifi-
cation and effect in diabetes mellitus. Indian J Exp Biol. 2010;48:1111–8.
83. Morani AS, Bodhankar SL, Mohan V, Thakurdesai PA. Ameliorative
effects of standardized extract from Trigonella foenum-graecum L. seeds
on painful peripheral neuropathy in rats. Asian Pac J Trop Med. 2012;5:
385–90.
84. Mowla A, Alauddin M, Rahman MA, Ahmed K. Antihyperglycemic effect
of Trigonella foenum-graecum (fenugreek) seed extract in alloxan-induced
diabetic rats and its use in diabetes mellitus: a brief qualitative phytochemical
and acute toxicity test on the extract. Afr J Tradit Complement Altern Med.
2009;6:255–61.
85. Mukthamba P, Srinivasan K. Protective effect of dietary fenugreek
(Trigonella foenum-graecum) seeds and garlic (Allium sativum) on induced
oxidation of low-density lipoprotein in rats. J Basic Clin Physiol Pharmacol.
2016;27:39–47.
86. Murakami T, Kishi A, Matsuda H, Yoshikawa M. Medicinal foodstuffs.
XVII. Fenugreek seed. (3): structures of new furostanol-type steroid
saponins, trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa, from the seeds
of Egyptian Trigonella foenum-graecum L. Chem Pharm Bull (Tokyo).
2000;48:994–1000.
87. Muraki E, Chiba H, Tsunoda N, Kasono K. Fenugreek improves
diet-induced metabolic disorders in rats. Horm Metab Res. 2011;43:950–5.
88. Muralidhara, Narasimhamurthy K, Viswanatha S, Ramesh BS. Acute and
subchronic toxicity assessment of debitterized fenugreek powder in the
mouse and rat. Food Chem Toxicol. 1999;37:831–8.
89. Namork E, Fæste CK, Stensby BA, et al. Severe allergic reactions to food
in Norway: a ten-year survey of cases reported to the food allergy register.
Int J Environ Res Public Health. 2011;8:3144–55.
90. Narender T, Puri A, Shweta, et al. 4-hydroxyisoleucine an unusual amino
acid as antidyslipidemic and antihyperglycemic agent. Bioorg Med Chem
Lett. 2006;16:293–6.
91. Nathan J, Panjwani S, Mohan V, Joshi V, Thakurdesai PA. Efficacy and
safety of standardized extract of Trigonella foenum-graecum L seeds as an
adjuvant to L-Dopa in the management of patients with Parkinson’s
disease. Phytother Res. 2014;28:172–8.
92. Otoom SA, Al-Safi SA, Kerem ZK, Alkofahi A. The use of medicinal
herbs by diabetic Jordanian patients. J Herb Pharmacother. 2006;6:31–41.
1866 Trigonella foenum-graecum L.

93. Panda S, Tahiliani P, Kar A. Inhibition of triiodothyronine production by

fenugreek seed extract in mice and rats. Pharmacol Res. 1999;40:405–9.
94. Pandian RS, Anuradha CV, Viswanathan P. Gastroprotective effect of
fenugreek seeds (Trigonella foenum-graecum) on experimental gastric
ulcer in rats. J Ethnopharmacol. 2002;81:393–7.
95. Pang X, Cong Y, Yu HS, et al. Spirostanol saponins derivated from the
seeds of Trigonella foenum-graecum by b-glucosidase hydrolysis and their
inhibitory effects on rat platelet aggregation. Planta Med. 2012;78:276–85.
96. Panghal M, Kaushal V, Yadav JP. In vitro antimicrobial activity of ten
medicinal plants against clinical isolates of oral cancer cases. Ann Clin
Microbiol Antimicrob. 2011;10:21.
97. Parvizpur A, Ahmadiani A, Kamalinejad M. Probable role of spinal
purinoceptors in the analgesic effect of Trigonella foenum-graecum (TFG)
leaves extract. J Ethnopharmacol. 2006;104:108–12.
98. Parvizpur A, Ahmadiani A, Kamalinejad M. Spinal serotonergic system is
partially involved in antinociception induced by Trigonella foenum-
graecum (TFG) leaf extract. J Ethnopharmacol. 2004;95:13–7.
99. Pasich B, Terminska K, Przygoda U. Spectrophotometric determination of
diosgenin and yamogenin in seeds of fenugreek—Trigonella foenum-
graecum. Farm Pol. 1983;39:599–602.
100. Patel D, Prasad S, Kumar R, Hemalatha S. An overview on antidiabetic
medicinal plants having insulin mimetic property. Asian Pac J Trop
Biomed. 2012;2:320–30.
101. Patil SP, Niphadkar PV, Bapat MM. Allergy to fenugreek (Trigonella
foenum-graecum). Ann Allergy Asthma Immunol. 1997;78:297–300.
102. Petit P, Sauvaire Y, Ponsin G, et al. Effects of a fenugreek seed extract on
feeding behaviour in the rat: metabolic-endocrine correlates. Pharmacol
Biochem Behav. 1993;45:369–74.
103. Petit PR, Sauvaire YD, Hillaire-Buys DM, et al. Steroid saponins from
fenugreek seeds: extraction, purification, and pharmacological investigation
on feeding behavior and plasma cholesterol. Steroids. 1995;60:674–80.
104. Platel K, Srinivasan K. Influence of dietary spices and their active principles
on pancreatic digestive enzymes in albino rats. Nahrung. 2000;44:42–6.
105. Platel K, Srinivasan K. Influence of dietary spices or their active principles
on digestive enzymes of small intestinal mucosa in rats. Int J Food Sci
Nutr. 1996;47:55–9.
106. Preet A, Siddiqui MR, Taha A, et al. Long-term effect of Trigonella foenum-
graecum and its combination with sodium orthovanadate in preventing
histopathological and biochemical abnormalities in diabetic rat ocular tissues.
Mol Cell Biochem. 2006;289:137–47.
107. Puri D, Prabhu KM, Murthy PS. Mechanism of action of a hypoglycemic
principle isolated from fenugreek seeds. Indian J Physiol Pharmacol.
2002;46:457–62.
108. Puri HS, Jefferies TM, Hardman R. Diosgenin and yamogenin levels in
some Indian plant samples. Planta Med. 1976;30:118–21.
Trigonella foenum-graecum L. 1867

109. Rafraf M, Malekiyan M, Asghari-Jafarabadi M, Aliasgarzadeh A. Effect of

fenugreek seeds on serum metabolic factors and adiponectin levels in type
2 diabetic patients. Int J Vitam Nutr Res. 2014;84:196–205.
110. Raju J, Bird RP. Alleviation of hepatic steatosis accompanied by
modulation of plasma and liver TNF-alpha levels by Trigonella
foenum-graecum (fenugreek) seeds in Zucker obese (fa/fa) rats. Int J
Obes (Lond). 2006;30:1298–307.
111. Raju J, Gupta D, Rao AR, et al. Trigonella foenum-graecum (fenugreek)
seed powder improves glucose homeostasis in alloxan diabetic rat tissues
by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes.
Mol Cell Biochem. 2001;224:45–51.
112. Rao A, Steels E, Beccaria G, Inder WJ, Vitetta L. Influence of a specialized
Trigonella foenum-graecum seed extract (Libifem), on testosterone, estradiol
and sexual function in healthy menstruating women, a randomised placebo
controlled Study. Phytother Res. 2015;29:1123–30.
113. Ravikumar P, Anuradha CV. Effect of fenugreek seeds on blood lipid
peroxidation and antioxidants in diabetic rats. Phytother Res. 1999;13:
197–201.
114. Rayyan S, Fossen T, Andersen ØM. Flavone C-glycosides from seeds of
fenugreek, Trigonella foenum-graecum L. J Agric Food Chem. 2010;58:
7211–7.
115. Reddy RL, Srinivasan K. Dietary fenugreek seed regresses preestablished
cholesterol gallstones in mice. Can J Physiol Pharmacol. 2009;87:684–93.
116. Reddy RL, Srinivasan K. Fenugreek seeds reduce atherogenic diet-induced
cholesterol gallstone formation in experimental mice. Can J Physiol Pharma-
col. 2009;87:933–43.
117. Reddy RR, Srinivasan K. Dietary fenugreek and onion attenuate choles-
terol gallstone formation in lithogenic diet-fed mice. Int J Exp Pathol.
2011;92:308–19.
118. Ribes G, Sauvaire Y, Da Costa C, et al. Antidiabetic effects of subfractions
from fenugreek seeds in diabetic dogs. Proc Soc Exp Biol Med. 1986;182:
159–66.
119. Ribes G, Sauvaire Y, Baccou JC, et al. Effects of fenugreek seeds on
endocrine pancreatic secretions in dogs. Ann Nutr Metab. 1984;28:37–43.
120. Roberts KT. The potential of fenugreek (Trigonella foenum-graecum) as a
functional food and nutraceutical and its effects on glycemia and lipidemia.
J Med Food. 2011;14:1485–9.
121. Sakr SA, Abo-El-Yazid SM. Effect of fenugreek seed extract on
adriamycin-induced hepatotoxicity and oxidative stress in albino rats.
Toxicol Ind Health. 2012;28:876–85.
122. Saleh N, El-Hawary Z, El-Shobaki FA, et al. Vitamins content of fruits and
vegetables in common use in Egypt. Z Ernahrungswiss. 1977;16:158–62.
123. Salehi Nowbandegani A, Kiumarcy S, Rahmani F, et al. Ethnopharma-
cological knowledge of Shiraz and Fasa in Fars region of Iran for diabetes
mellitus. J Ethnopharmacol. 2015;172:281–7.
1868 Trigonella foenum-graecum L.

124. Sankar P, Subhashree S, Sudharani S. Effect of Trigonella foenum-

graecum seed powder on the antioxidant levels of high fat diet and low
dose streptozotocin induced type II diabetic rats. Eur Rev Med Pharmacol Sci.
2012;16 Suppl 3:10–7.
125. Sauvaire Y, Petit P, Broca C, et al. 4-Hydroxyisoleucine: a novel amino
acid potentiator of insulin secretion. Diabetes. 1998;47:206–10.
126. Sauvaire Y, Ribes G, Baccou JC, Loubatieères-Mariani MM. Implication
of steroid saponins and sapogenins in the hypocholesterolemic effect of
fenugreek. Lipids. 1991;26:191–7.
127. Shabbeer S, Sobolewski M, Anchoori RK, et al. Fenugreek: a naturally
occurring edible spice as an anticancer agent. Cancer Biol Ther. 2009;8:
272–8.
128. Shang M, Cai S, Han J, et al. Studies on flavonoids from fenugreek
(Trigonella foenum- graecum L). Zhongguo Zhong Yao Za Zhi. 1998;23:
614–6, 639 (Chinese).
129. Shang M, Cai S, Wang X. Analysis of amino acids in Trigonella
foenum-graecum seeds. Zhong Yao Cai. 1998;21:188–90 (Chinese).
130. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood
glucose and serum lipids in type I diabetes. Eur J Clin Nutr. 1990;44:301–6.
131. Shojaii A, Dabaghian FH, Goushegir A, Fard MA. Antidiabetic plants of
Iran. Acta Med Iran. 2011;49:637–42.
132. Sholsberg A, Egyead MN. Examples of poisonous plants in Israel of
importance to animals and man. Arch Toxicol (Suppl.) (W.Ger.). 1983;6:
194–6.
133. Sindhu G, Ratheesh M, Shyni GL, et al. Anti-inflammatory and antioxidative
effects of mucilage of Trigonella foenum-graecum (Fenugreek) on adjuvant
induced arthritic rats. Int Immunopharmacol. 2012;12:205–11.
134. Singh AB, Tamarkar AK, Narender T, Srivastava AK. Antihyperglycaemic
effect of an unusual amino acid (4-hydroxyisoleucine) in C57BL/KsJ-db/db
mice. Nat Prod Res. 2010;24:258–65.
135. Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated
fenugreek seeds in human subjects. Plant Foods Hum Nutr. 1999;53:359–65.
136. Srichamroen A, Field CJ, Thomson AB, Basu TK. The modifying effects
of galactomannan from Canadian-grown fenugreek (Trigonella foenum-
graecum L.) on the glycemic and lipidemic status in rats. J Clin Biochem
Nutr. 2008;43:167–74.
137. Srinivasan K. Plant foods in the management of diabetes mellitus: spices as
beneficial antidiabetic food adjuncts. Int J Food Sci Nutr. 2005;56:399–414.
138. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek
(Trigonella foenum-graecum) on bile acid absorption and cholesterol
levels in rats. Br J Nutr. 1993;69:277–87.
139. Sur P, Das M, Gomes A, et al. Trigonella foenum-graecum (fenugreek)
seed extract as an antineoplastic agent. Phytother Res. 2001;15:257–9.
Trigonella foenum-graecum L. 1869

140. Suresh P, Kavitha ChN, Babu SM, et al. Effect of ethanol extract of
Trigonella foenum-graecum (fenugreek) seeds on Freund’s adjuvant-
induced arthritis in albino rats. Inflammation. 2012;35:1314–21.
141. Sushma N, Devasena T. Aqueous extract of Trigonella foenum-graecum
(fenugreek) prevents cypermethrin-induced hepatotoxicity and nephrotox-
icity. Hum Exp Toxicol. 2010;29:311–9.
142. Swanston-Flatt SK, Day C, Flatt PR, et al. Glycaemic effects of traditional
European plant treatments for diabetes. Studies in normal and streptozo-
tocin diabetic mice. Diabetes Res Clin Exp. 1989;10:69–73.
143. Thirunavukkarasu V, Anuradha CV, Viswanathan P. Protective effect of
fenugreek (Trigonella foenum-graecum) seeds in experimental ethanol
toxicity. Phytother Res. 2003;17:737–43.
144. Tripathi UN, Chandra D. Antihyperglycemic and antioxidative effect of
aqueous extract of Momordica charantia pulp and Trigonella foenum-
graecum seed in alloxan-induced diabetic rats. Indian J Biochem Biophys.
2010;47:227–33.
145. Tripathi UN, Chandra D. The plant extracts of Momordica charantia
and Trigonella foenum-graecum have antioxidant and antihyperglycemic
properties for cardiac tissue during diabetes mellitus. Oxid Med Cell
Longev. 2009;2:290–6.
146. Turkyılmaz C, Onal E, Hirfanoglu IM, et al. The effect of galactagogue herbal
tea on breast milk production and short-term catch-up of birth weight in the
first week of life. J Altern Complement Med. 2011;17:139–42.
147. Uemura T, Hirai S, Mizoguchi N, et al. Diosgenin present in fenugreek
improves glucose metabolism by promoting adipocyte differentiation and
inhibiting inflammation in adipose tissues. Mol Nutr Food Res. 2010;54:
1596–608.
148. Varshney IP, Jain DC, Srivastava HC. Saponins from Trigonella foenum-
graecum leaves. J Nat Prod. 1984;47:44–6.
149. Vats V, Grover JK, Rathi SS. Evaluation of antihyperglycemic and
hypoglycemic effect of Trigonella foenum-graecum Linn., Ocimum sanctum
Linn. and Pterocarpus marsupium Linn. in normal and alloxanized diabetic
rats. J Ethnopharmacol. 2002;79:95–100.
150. Vats V, Yadav SP, Grover JK. Effect of T. foenum graecum on glycogen
content of tissues and the key enzymes of carbohydrate metabolism.
J Ethnopharmacol. 2003;85:237–42.
151. Vijayakumar MV, Bhat MK. Hypoglycemic effect of a novel dialysed
fenugreek seeds extract is sustainable and is mediated, in part, by the
activation of hepatic enzymes. Phytother Res. 2008;22:500–5.
152. Vijayakumar MV, Singh S, Chhipa RR, Bhat MK. The hypoglycaemic
activity of fenugreek seed extract is mediated through the stimulation of an
insulin signalling pathway. Br J Pharmacol. 2005;146:41–8.
153. Vinje NE, Namork E, Løvik M. Anaphylactic reactions in mice with
Fenugreek allergy. Scand J Immunol. 2011;74:342–53.
1870 Trigonella foenum-graecum L.

154. Voloshina DA, Kiselev VP, Rumyantseva GN. Content of sapogenins and
their yield from Trigonella foenum-graecum seeds. Rastit Resur. 1977;13:
655–7.
155. Vyas S, Agrawal RP, Solanki P, Trivedi P. Analgesic and anti-inflammatory
activities of Trigonella foenum-graecum (seed) extract. Acta Pol Pharm.
2008;65:473–6.
156. Wang D, Sun H, Han Y, et al. Chemical constituents of the stems and
leaves of Trigonella foenum-graecum L. Zhongguo Zhong Yao Za Zhi.
1997;22:486–7, 512 (Chinese).
157. Wang GR, Tang WZ, Yao QQ, et al. New flavonoids with 2BS cell
proliferation promoting effect from the seeds of Trigonella foenum-
graecum L. J Nat Med. 2010;64:358–61.
158. Weder JK, Haussner K. Inhibitors of human and bovine trypsin and
chymotrypsin in fenugreek (Trigonella foenum-graecum L.) seeds. Isolation
and characterization. Zeitschrift fur Lebensmittel-Untersuchung und-
Forschung. 1991;192:535–40.
159. Weder JK, Haussner K. Inhibitors of human and bovine trypsin and
chymotrypsin in fenugreek (Trigonella foenum-graecum L.) seeds. Reactive
sites and C-terminal sequences. Zeitschrift fur Lebensmittel-Untersuchung
und-Forschung. 1991;193:242–6.
160. Weder JK, Haussner K. Inhibitors of human and bovine trypsin and
chymotrypsin in fenugreek (Trigonella foenum-graecum L.) seeds. Reac-
tion with the human and bovine proteinases. Zeitschrift fur Lebensmittel-
Untersuchung und-Forschung. 1991;193:321–5.
161. Xue W, Lei J, Li X, Zhang R. Trigonella foenum-graecum seed extract
protects kidney function and morphology in diabetic rats via its antioxidant
activity. Nutr Res. 2011;31:555–62.
162. Xue WL, Li XS, Zhang J, et al. Effect of Trigonella foenum-graecum
(fenugreek) extract on blood glucose, blood lipid and hemorheological
properties in streptozotocin-induced diabetic rats. Asia Pac J Clin Nutr.
2007;16 Suppl 1:422–6.
163. Yadav M, Lavania A, Tomar R, et al. Complementary and comparative
study on hypoglycemic and antihyperglycemic activity of various extracts
of Eugenia jambolana seed, Momordica charantia fruits, Gymnema
sylvestre, and Trigonella foenum-graecum seeds in rats. Appl Biochem
Biotechnol. 2010;160:2388–400.
164. Yoshikawa M, Murakami T, Komatsu H, et al. Medicinal foodstuffs. IV.
Fenugreek seed. (1): structures of trigoneosides Ia, Ib, IIa, IIb, IIIa, and
IIIb, new furostanol saponins from the seeds of Indian Trigonella foenum-
graecum L. Chem Pharm Bull (Tokyo). 1997;45:81–7.
165. Zhou J, Chan L, Zhou S. Trigonelline: a plant alkaloid with therapeutic
potential for diabetes and central nervous system disease. Curr Med Chem.
2012;19:3523–31.
Trigonella foenum-graecum L. 1871

166. Zia T, Hasnain SN, Hasan SK. Evaluation of the oral hypoglycaemic effect
of Trigonella foenum-graecum L. (methi) in normal mice. J Ethnopharma-
col. 2001;75:191–5.
167. Ziyyat A, Legssyer A, Mekhfi H, et al. Phytotherapy of hypertension and
diabetes in oriental Morocco. J Ethnopharmacol. 1997;58:45–54.
Tussilago farfara L.
(Asteraceae/Compositae)

(Syns.: T. alpestris Hegetschw.; T. umbertina Borbás; Farfara radiata Gilib.; Cineraria

farfara Bernh.)

Abstract
A perennial herb that grows in western Himalayas, northern China, Persia and
Europe. The plant was known to both Greeks and Romans, and from earlier times it
was esteemed useful in cough and other pectoral affections. Hippocrates
recommended the root with honey in ulcerations of the lungs, while Dioscorides,
Pliny and Galen mentioned that smoke of the leaves inhaled through a funnel or
reed was efficacious in cough and dyspepsia. Arab and Persian medical writers
described it as Fanjiun or Afanjiun. Hindu physicians believe that the leaves expel
vata or wind, which is the cause of various disorders, especially rheumatism. In
Europe, Colt’s foot was smoked like tobacco, and used as decoction or infusion
internally as a domestic remedy for pectoral affections. Astringent and demulcent,
used in cough, and the cotton-like down is used as styptic dressing for wounds. It is
still one of the most common externally used plants for the treatment of wounds in
southeast Europe (Balkan region). and in eastern Pyrenees, Catalonia (Iberian
Peninsula). In folk medicine of Hungary, a tea is used in the treatment of
gastrointestinal diseases. It is one of the most commonly used plants in the
traditional medicine of northwest Turkey for respiratory disorders. The flower-
buds are traditionally used in Chinese medicine as antitussive and expectorant, for
the treatment of bronchitis and asthma, cough, wheezing, dysphagia, and
hemoptysis with pus. Tussilagone, tussfararins A–F, tussilagofarin, tussilagofarol,
farfaratin and other sesquiterpenoids are considered the main active principles. In
addition, flavonoids and phenolic acid derivatives, mixture of b sitosterol/
stigmasterol, trans-caffeic acid, kaempferol-3-O-glucoside, loliolide, a mixture of
p-coumaric acid/4-hydroxybenzoic acid, and p-coumaric acid have been isolated
from flower-buds. Both aqueous and ethanol extracts contain significant phenolic
and flavonoid contents and show significant antioxidant activity.

© Springer Nature Switzerland AG 2020 1873

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_190
1874 Tussilago farfara L.

Keywords



Békavirág Colt’s foot Fárfara Fanjiun

Fukitanpopo
Huflattich
Kuǎn



dōng Öksürükotu Vátapána Wátpán

Vernaculars: Hin.: Wátpán; San.: Vátapána; Alb.: Thundërmushka, Thundërza;

Ara.: Fanjiun; Bul.: Podbjal; Chi.: 款冬, Kuǎn dōng, Kuandong hua; Cro.: Proljetni
podbjel; Cze.: Podběl lékařský; Dan.: Følfod; Dut.: Kleinhoefblad; Eng.: Clayweed,
Colt’s foot, Coughwort, Horsehoof; Fin.: Leskenlehti; Fre.: Chou de vigne, Herbe
aux pattes, Herbe de Saint-Quirin, Pas d’âne, Pas de cheval; Ger.: Galitz, Huflattich,
Sauplotschen; Hun.: Békavirág, Martilapu; Ita.: Farfara, Farfugio, Paparacchio,
Tossilaggine, Unghia cavallina; Jap.: Fukitanpopo; Nor.: Hestehov; Per.: Afanjiun;
Pol.: Podbiał pospolity; Por.: Unha-de-asno, Unha-de-cavalo; Rus.: Mat-i-mačecha,
Podbeal,; Spa.: Fárfara, Pata de caballo, Pata de mulo; Swe.: Hästhov; Tur.:
Öksürükotu.
Description: A perennial herb that grows in western Himalayas, northern China,
Persia and Europe, 10 cm high, the stem downy and scaly. Leaves basal, petiolate,
nearly orbiculate, cordate, sinuate-dentate, surface green, underside white and densely
cottony, and tomentose; appearing after the flowers. Flower-heads erect, solitary,
terminal on the stem, bright yellow, blooms in March–April.LXXIX Peak vegetation
growth in Beijing was reported in early September, and the best time to collect
flower-buds was around the fifteenth day before the period of freezing weather or tenth
day after the thawing starts the following year [1] (Figs. 1 and 2).

Fig. 1 Tussilago farfara, Foliage, Bogdan, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Tussilago_farfara_bgiu.jpg; https://creative
commons.org/licenses/by-sa/3.0/deed.en
Tussilago farfara L. 1875

Fig. 2 Tussilago farfara, Flowers, Andreas Trepte, WikimediaCommons; ShareAlike 2.5 Generic
CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Coltsfoot.jpg; https://creativecommons.
org/licenses/by-sa/2.5/deed.en

Actions and Uses: The plant was known to both Greeks and Romans, and from
earlier times it was esteemed useful in cough and other pectoral affections. Hip-
pocrates recommended the root with honey in ulcerations of the lungs, while
Dioscorides, Pliny and Galen mentioned that smoke of the leaves inhaled through a
funnel or reed was efficacious in cough and dyspepsia. Arab and Persian medical
writers described it as Fanjiun or Afanjiun. Hindu physicians believe that the leaves
expel vata or wind, which is the cause of various disorders, especially rheumatism. In
Europe, Colt’s foot was smoked like tobacco, and used as decoction or infusion
internally as a domestic remedy for pectoral affections.XL Astringent and demulcent,
used in cough, and the cotton-like down is used as styptic dressing for wounds.LXXXI
It is still one of the most common externally used plants for the treatment of wounds in
southeast Europe (Balkan region) [6]. and in eastern Pyrenees, Catalonia (Iberian
Peninsula) [17]. In folk medicine of Hungary, a tea is used in the treatment of gas-
trointestinal diseases [22]. It is one of the most commonly used plants in the traditional
medicine of northwest Turkey for respiratory disorders [24]. The flower-buds are
traditionally used in Chinese medicine as antitussive and expectorant [15],LXXIX
for the treatment of bronchitis and asthma [2], cough, wheezing, dysphagia, and
hemoptysis with pus. A general drug recorded by Shen Nung in The Herbal, as dried,
young floral-buds of T. farfara.LXVI However, according to traditional Chinese
experience, the quality of the purple flower is considered better than that of yellow
flower-buds [13].
Phytoconstituents: Tussilagone, tussfararins A–F, tussilagofarin, tussilagofarol, far-
faratin and other sesquiterpenoids are considered the main active principles [5, 9, 11,
1876 Tussilago farfara L.

15, 25]. In addition, flavonoids: rutin, hyperoside, quercetin-3-O-b-D-glucopyranoside,

quercetin-4′-O-b-D-glucopyranoside, quercetin, kaempferol, kaempferol-3-O-a-L-
rhamnopyranosyl-(1-6)-b-D-glucopyranoside, and phenolic acid derivatives: caffeic acid,
methyl caffeate, ethyl caffeate, (E)-2,5-dihydroxycinnamic acid, 3,4-di-O-caffeoylquinic
acid, 4,5-di-O-caffeoylquinic acid, methyl 4,5-di-O-caffeoylquinate, chlorogenic acid
[26], methyl 3,4-O-dicaffeoylquinate, methyl 3,5-O-dicaffeoylquinate, methyl 4,5-O-
dicaffeoylquinate, 3,5-O-dicaffeoylquinic acid, methyl 3-O-caffeoylquinate, 3-O-caffeoyl-
quinic acid, kaempferol 3-O-b-D-glucopyranoside [12], mixture of b sitosterol/stigmasterol,
trans-caffeic acid, kaempferol-3-O-glucoside, loliolide, a mixture of p-coumaric acid/
4-hydroxybenzoic acid, and p-coumaric acid have been isolated from flower-buds [28].
Levels of threonine, proline, phosphatidylcholine, creatinine, 4,5-dicaffeoylquinic acid,
rutin, caffeic acid, kaempferol analogues, and tussilagone were higher in the purple
flower-buds than in the yellow buds [13], and a Farfarae folium et flos tea was found a rich
source of Ca, Cr, Mn and molybdenum [22]. Senkirkine, tussilagine and traces of sene-
cionine are the pyrrolizidine alkaloids reported from the flower-buds [3, 7, 18, 20]. A bis-
abolene epoxide with NO synthesis inhibitory activity in LPS-activated macrophages has
also been isolated [19].
Pharmacology: Both aqueous and ethanol extracts contain significant phenolic
and flavonoid contents and show significant antioxidant activity [16]. Ethanol
extract of flower-buds from Serbia was active against B. cereus, E. coli, S. aureus,
P. aeruginosa, and C. albicans [8], whereas aqueous leaf extract of Turkish origin
also significantly inhibited growth of S. pyogenes, S. aureus and S. epidermidis
[23]. Tussilagone potently inhibited rat liver and human hepatocellular carcinoma
HepG2 cells-derived microsomal acyl CoA:diacylglycerol acyltransferase and
significantly inhibited triglyceride synthesis [14]. Intravenous tussilagone produced
instant and dose-dependent pressor effect in anesthetized dogs, cats, and rats, and a
significant stimulation of respiration [10].
Mechanism of Action: Tussilagone exerts anti-inflammatory activity in murine
macrophages by inducing heme oxygenase-1 expression [4]. Caffeoylquinic acids
exhibit significant antitussive, expectorant, and anti-inflammatory effects, which
may act in a collective and synergistic way [27]. The antioxidant activity of the
plant is due to its phenolic contents [21].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Despite known hepatotoxicity of pyrrolizidine alkaloids, single
oral dose of up to 5,000 mg/kg of 50% aqueous suspension or repeated doses of
250 mg/kg for four-weeks were nonlethal and nontoxic to mice [20]. Rats sup-
plemented in diet 4% coltsfoot for 600-days caused no death or sarcoma of liver
and only one out of 10 rats fed 8% developed the tumor [3]. Acute LD50 (i.v.) of
tussilagone in mice was 28.9 mg/kg [10].
Commentary: This plant has very sparsely been investigated pharmacologically
and no clinical studies are reported in published English literature.
Tussilago farfara L. 1877

References
1. Chen J, Ding WL, Zhang LP, Chen Z. Investigation on growth and devel-
opment of Tussilago farfara L. in Beijing. Zhongguo Zhong Yao Za Zhi.
2000;25:84–6 (Chinese).
2. Cho J, Kim HM, Ryu JH, et al. Neuroprotective and antioxidant effects of
the ethyl acetate fraction prepared from Tussilago farfara L. Biol Pharm
Bull. 2005;28:455–60.
3. Hirono I, Mori H, Culvenor CC. Carcinogenic activity of coltsfoot,
Tussilago farfara L. Gan. 1976;67:125–9.
4. Hwangbo C, Lee HS, Park J, Choe J, Lee JH. The anti-inflammatory effect of
tussilagone, from Tussilago farfara, is mediated by the induction of heme
oxygenase-1 in murine macrophages. Int Immunopharmacol. 2009;9:1578–84.
5. Jang H, Lee JW, Lee C, et al. Sesquiterpenoids from Tussilago farfara in-
hibit LPS-induced nitric oxide production in macrophage RAW 264.7 cells.
Arch Pharm Res. 2016;39:127–32.
6. Jarić S, Kostić O, Mataruga Z, et al. Traditional wound-healing plants used in
the Balkan region (Southeast Europe). J Ethnopharmacol. 2018;211:311–28.
7. Jiang Z, Liu F, Goh JJ, et al. Determination of senkirkine and senecionine
in Tussilago farfara using microwave-assisted extraction and pressurized
hot water extraction with liquid chromatography tandem mass spectrometry.
Talanta. 2009;79:539–46.
8. Kokoska L, Polesny Z, Rada V, Nepovim A, Vanek T. Screening of some
Siberian medicinal plants for antimicrobial activity. J Ethnopharmacol. 2002;
82:51–3.
9. Li W, Huang X, Yang XW. New sesquiterpenoids from the dried flower
buds of Tussilago farfara and their inhibition on NO production in LPS-
induced RAW264.7 cells. Fitoterapia. 2012;83:318–22.
10. Li YP, Wang YM. Evaluation of tussilagone: a cardiovascular-respiratory
stimulant isolated from Chinese herbal medicine. Gen Pharmacol. 1988;19:
261–3.
11. Liu LL, Yang JL, Shi YP. Sesquiterpenoids and other constituents from the
flower buds of Tussilago farfara. J Asian Nat Prod Res. 2011;13:920–9.
12. Liu YF, Yang XW, Wu B. Studies on chemical constituents in the buds
of Tussilago farfara. Zhongguo Zhong Yao Za Zhi. 2007;32:2378–81.
13. Mi X, Li ZY, Qin XM, Zhang LZ. Monitoring of chemical components
with different color traits of Tussilago farfara using NMR-based metabo-
lomics. Yao Xue Xue Bao. 2013;48:1692–7 (Chinese).
14. Park HR, Yoo MY, Seo JH, et al. Sesquiterpenoids isolated from the flower
buds of Tussilago farfara L. inhibit diacylglycerol acyltransferase. J Agric
Food Chem. 2008;56:10493–7.
15. Qin ZB, Zhang J, Wu XD, et al. Sesquiterpenoids from Tussilago farfara and
their inhibitory effects on nitric oxide production. Planta Med. 2014;80:703–9.
1878 Tussilago farfara L.

16. Ravipati AS, Zhang L, Koyyalamudi SR, et al. Antioxidant and anti-
inflammatory activities of selected Chinese medicinal plants and their relation
with antioxidant content. BMC Complement Altern Med. 2012;12:173.
17. Rigat M, Vallès J, D’Ambrosio U, et al. Plants with topical uses in the
Ripollès district (Pyrenees, Catalonia, Iberian Peninsula): ethnobotanical
survey and pharmacological validation in the literature. J Ethnopharmacol.
2015;164:162–79.
18. Röder E, Wiedenfeld H, Jost EJ. Tussilagine—a new pyrrolizidine alkaloid
from Tussilago farfara. Planta Med. 1981;43:99–102 (German).
19. Ryu JH, Jeong YS, Sohn DH. A new bisabolene epoxide from Tussilago
farfara, and inhibition of nitric oxide synthesis in LPS-activated macro-
phages. J Nat Prod. 1999;62:1437–8.
20. Şeremet OC, Bărbuceanu F, Ionică FE, et al. Oral toxicity study of certain
plant extracts containing pyrrolizidine alkaloids. Rom J Morphol Embryol.
2016;57:1017–23.
21. Song FL, Gan RY, Zhang Y, et al. Total phenolic contents and antioxidant
capacities of selected chinese medicinal plants. Int J Mol Sci. 2010;11:
2362–72.
22. Szentmihályi K, May Z, Süle K, Then M. Mineral content of some herbs
and plant extracts with anti-inflammatory effect used in gastrointestinal
diseases. Orv Hetil. 2013;154:538–43 (Hungarian).
23. Turker AU, Usta C. Biological screening of some Turkish medicinal plant
extracts for antimicrobial and toxicity activities. Nat Prod Res. 2008;22:
136–46.
24. Uzun E, Sariyar G, Adsersen A, et al. Traditional medicine in Sakarya province
(Turkey) and antimicrobial activities of selected species. J Ethnopharmacol.
2004;95:287–96.
25. Wang CD, Takayanagi H, Mi CF, et al. Chemical studies of flower buds
of Tussilago farfara L. Yao Xue Xue Bao. 1989;24:913–6 (Chinese).
26. Wu D, Zhang M, Zhang C, Wang Z. Flavonoids and phenolic acid deriva-
tives from flos farfarae. Zhongguo Zhong Yao Za Zhi. 2010;35:1142–4
(Chinese).
27. Wu QZ, Zhao DX, Xiang J, et al. Antitussive, expectorant, and anti-
inflammatory activities of four caffeoylquinic acids isolated from Tussilago
farfara. Pharm Biol. 2016;54:1117–24.
28. Zhao J, Evangelopoulos D, Bhakta S, Gray AI, Seidel V. Antitubercular
activity of Arctium lappa and Tussilago farfara extracts and constituents.
J Ethnopharmacol. 2014;155:796–800.
Valeriana jatamansi Jones.
(Valerianaceae)

(Syn.: V. wallichii DC.)

Abstract
It is a knotty and fragrant root of an herb found in temperate Himalayas. In
Ayurveda, it is described as sweet, emollient, pungent, hot and light, and a remedy
for suppression of urine (oliguria), poisons, and for nervous conditions, such as
anxiety, overexcitement, epilepsy, fainting-fits and headaches. It is also beneficial
for menstrual cramps, and lowers BP and relieves palpitation. Muslim physicians
described the rhizomes as resolvent, deobstruent, anesthetic, nerve stimulant,
diuretic, emetic, emmenagogue and to increase libido, and especially use it for
cold brain and nervous afflictions, such as stroke, paralysis, amnesia, and for
inflammation of liver and pancreas, arthritis, gout, and sciatica pain. Two
flavonoids, 6-methylapigenin, and 2S(-)-hesperidin with sedative and sleep-
enhancing activity were isolated from rhizomes. It is also rich in catechin,
hydroxylbenzoic acid and caffeic acid. Jatamanvaltrates, iridolactones, a lignan,
valepotriates, and nardostachin were isolated from the whole plant. Aqueous
rhizome extract markedly attenuated I/R-induced cerebral injury in mice,
restricting the infarct size, decrease in short-term memory, and motor incoordi-
nation. Methanol and aqueous extracts also produced antidepressant-like effects,
which were not dependent on their terpenoid contents. In a randomized, parallel
study, valerian powder for a month significantly improved onset and duration of
sleep in Indian patients with primary insomnia. Valerian plant extract, twice daily
after meal to thirty-three Indian patients significantly attenuated stress and
anxiety, improved depression and enhanced willingness to adjust, without
altering memory, concentration or attention of the subjects.

Keywords





Asaroon Indischer baldrian Mushkbala Nard Pindi-tagara Rishai-wala





Sugandhbala Sumbul jabali Tagar Zhizhuxiang

© Springer Nature Switzerland AG 2020 1879

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_191
1880 Valeriana jatamansi Jones.

Vernaculars: Urd.: Asaroon, Tagar; Hin.: Bala taggar, Balchhadi mansi, Chhar
ganthona, Gilgiti valerian, Mushkwali, Muskbala, Sugandhbala, Tagar; San.: Jata-
mansi, Mushkbala, Nahushakhya, Nandini, Nandyavartha, Pindi-tagara, Tagara,
Varhini; Ben.: Mushkbala, Tagar, Taggera ganthoda; Mal.: Takaram; Mar.: Tagar,
Thagar mool; Tam.: Shadamangie, Suganthbala, Takaram; Tel.: Tagara; Ara.:
Asaruma, Sumbul jabali; Chi.: 大救驾, Zhizhuxiang; Eng.: Indian valerian, Nard;
Fre.: Nard Indien; Ger.: Echte narde, Indischer baldrian; Per.: Rishai-wala; Vie.:
Nu lang.
Description: It is a knotty and fragrant root of an herb found in temperate Hima-
layas. Rhizomes are crooked, about 5 cm long and from 6 to 12 mm in diameter, of a
dull-brown color, marked with transverse ridges and thickly studded with circular
prominent tubercules, to a few of which thick rootlets still remain attached. The
crown is marked by a number of bracts; the lower end is blunt. Rhizome is very hard
and tough, and the fractured surface greenish-brown. The odor is like that of
Valerian but much more powerful, with a pungent bitter taste (Fig. 1).XL
Actions and Uses: In Ayurveda, it is described as sweet, emollient, pungent, hot
and light, and a remedy for suppression of urine (oliguria), poisons, and for nervous
conditions, such as anxiety, overexcitement, epilepsy, fainting-fits and head-
aches.XL It is also beneficial for menstrual cramps, and lowers BP and relieves
palpitation. Muslim physicians described the rhizomes (temperament, hot 2° and

Fig. 1 Valeriana jatamansi, Plant, Kunming Botanical Garden, China, Daderot, Wikimedia-
Commons, https://commons.wikimedia.org/wiki/File:Valeriana_jatamansi_-_Kunming_Botanical_
Garden_-_DSC03047.JPG
Valeriana jatamansi Jones. 1881

dry 2°) as resolvent, deobstruent, anesthetic, nerve stimulant, diuretic, emetic,

emmenagogue and to increase libido, and especially use it for cold brain and
nervous afflictions, such as stroke, paralysis, amnesia, and for inflammation of liver
and pancreas, arthritis, gout, and sciatica pain.LXXVII In India, it is considered
stimulant, nervine tonic, antispasmodic, and sedative; used in hysteria, headache,
epilepsy, chorea, and also in oliguria.LXXXI,CV With rice spirit, it is given to people
suffering from smallpox, to lessen eruption of pustules.XL In TCM, it is one of the
most popular traditional medicines for treatment of malaise, abdominal distention,
insomnia, and rheumatism [38].
Phytoconstituents: Linarin-isovalerianate, a flavonoid, was first reported by Thies
in 1968 [27]. Two flavonoids, 6-methylapigenin, found in crude drug in a range of
0.0013–0.013% [30], and 2S(-)-hesperidin with sedative and sleep-enhancing acti-
vity [17] were isolated from rhizomes. It is also rich in catechin, hydroxylbenzoic
acid and caffeic acid [19]. Iridoids, valeriotetrates A [39], B and C, 8-methyl-
valepotriate, and 1,5-dihydroxy-3,8-epoxyvalechlorine A [29] were reported from
the roots. Decursidin, decursitin A and B, 3′(S)-acetoxy-4′(R)-angeloyloxy-3′,4′-
dihydroxanthyletin, 8-acetoxylpathchouli alcohol and dibutyl phthalate [16], and
iridoids: jatamandoid A, jatairidoids A–C, jatadoids A and B, jatamanvaltrates N
and O, valeriandoids A–F [31–35, 37], jatamanvaltrates R–S and jatamanin Q;
sesquiterpenoids: valeriananoids D–E and clovane-2b-isovaleroxy-9a-ol [3];
bakkenolides: valerilactones A and B, and two analogues, bakkenolide-H and
bakkenolide-B [36], were isolated from rhizomes/roots. Jatamanvaltrates A–M [15],
iridolactones: jatamanins A–M and a lignan, (+)-9′-isovaleroxylariciresinol [13],
and ten valepotriates: jatamanvaltrates P–Y and nardostachin [14] were isolated
from the whole plant.
Sesquiterpenes (>89.3%), comprising kanokonyl acetate, c-curcumene, ar-
curcumene, (Z)-b-farnesene, xanthorrhizol, 7-epi-a-selinene, valeranone and cur-
cuphenol are the main constituents of volatile oil of the Indian variety rhizomes
[18]. From Himachal Pradesh State (India), seven genetically diverse populations
were identified, which yielded EO from 0.6 to 1.66% [25]. Various populations
sampled from four habitat types of Uttarakhand, and west Himalaya (India) from
altitudes of 1,200–2,775 m showed significant variations in total phenolics, flavo-
noids, valerenic acid, and antioxidant activity in aerial and root portions and across
populations, but not related to altitudes [6].
Pharmacology: Aqueous rhizome extract markedly attenuated I/R-induced cere-
bral injury in mice, restricting the infarct size, decrease in short-term memory, and
motor incoordination [20]. Methanol and aqueous extracts produced antidepressant-
like effects, which were not dependent on their terpenoid contents [26]. Dichlor-
omethane extract of Indian valerian chemotype also produced antidepressant effect
in mice, and significantly increased levels of NE and DA in mouse forebrain [21].
6-Methylapigenin, a competitive ligand at brain’s GABAA receptors, and 2S(-)-
hesperidin are flavonoids responsible for the anxiolytic and sedative/anxiolytic pro-
perties, respectively, and 6-methylapigenin potentiates sleep-enhancing properties
1882 Valeriana jatamansi Jones.

of hesperidin [17]. The EO of Indian chemotype also produced antidepressant-like

effect that was suggested to be mediated involving NO pathway [23].
Methanol extract and EO of Indian valerian demonstrated significant analgesic
activity, inhibiting acetic acid-induced writing, and subeffective dose of EO sig-
nificantly potentiated the effect of aspirin, suggesting a peripheral analgesic effect
via inhibition of PG synthesis [22]. A topical formulation of methanol leaf extract
and its ethyl acetate fraction is also reported to exhibit significant anti-inflammatory
activity [11]. Methanol (50%) extract contains significant amounts of polyphenols
with moderate antioxidant activity and potential for preventing oxidative DNA
damage [7]. An aqueous extract containing hesperidin as one of its major con-
stituent, showed antioxidant activity significantly countering radiation-induced free
radicals [8]. An extract was reported to produce antidiarrheal and bronchodilatory
[9], spasmolytic and BP lowering effects [5]. Chloroform and ethyl acetate fractions
also possess significant inhibitory activity against AChE and BChE enzymes,
respectively [10]. Major constituents of the rhizomes, valepotriates (valtrate, iso-
valtrate and acevaltrate), are cytotoxic against human small-cell lung cancer cells,
and human colorectal cancer cells [2]. Methanol and chloroform root extracts are
active against L. donovani promastigotes and both promastigotes and amastigotes
of L. major [4]; whereas, chloroform and hexane fractions of aerial parts exhibited
significant activity against S. aureus and B. subtilus, respectively [12].
Clinical Studies: Valerian plant extract in an oral dose of 500 mg/capsule, twice
daily after meal to thirty-three Indian patients (20 males and 13 females; average
age 34.2 years) significantly attenuated stress and anxiety, improved depression and
enhanced willingness to adjust, without altering memory, concentration or attention
of the subjects [1]. In a randomized, parallel study, valerian powder in a dose of 4 g
thrice daily with milk for a month significantly improved onset and duration of
sleep in 15 Indian patients with primary insomnia, better than Nardostachys jata-
mansi powder-treated patients [28].
Mechanism of Action: The sleep quality improving effect of aqueous extract is
suggested to be dependent upon levels of monoamines in cortex and brainstem [24].
Human A/Es, Allergy and Toxicity: It is reported to be harmful to lungs.LXXVII
Animal Toxicity: Single oral dose of 3,200 mg/kg of iridoid-rich extract to mice,
and up to a 1,200 mg/kg dose for three-months to rats were nonlethal and nontoxic
[38].
Commentary: A sister species, Valeriana officinalis, is a widely available herbal
supplement marketed as a sedative and anxiolytic; this is an Indian variety with
similar properties. Two clinical trials conducted in Indian patients demonstrated its
anxiolytic and sedative properties, but have not been reproduced.
Valeriana jatamansi Jones. 1883

References
1. Bhattacharyya D, Jana U, Debnath PK, Sur TK. Initial exploratory
observational pharmacology of Valeriana wallichii on stress management:
a clinical report. Nepal Med Coll J. 2007;9:36–9.
2. Bos R, Hendriks H, Scheffer JJ, Woerdenbag HJ. Cytotoxic potential of
valerian constituents and valerian tinctures. Phytomedicine. 1998;5:219–25.
3. Dong FW, Liu Yang, Wu ZK, et al. Iridoids and sesquiterpenoids from the
roots of Valeriana jatamansi Jones. Fitoterapia. 2015;102:27–34.
4. Ghosh S, Debnath S, Hazra S, et al. Valeriana wallichii root extracts and
fractions with activity against Leishmania spp. Parasitol Res. 2011;108:
861–71.
5. Gilani AH, Khan AU, Jabeen Q, et al. Antispasmodic and blood pressure
lowering effects of Valeriana wallichii are mediated through K+ channel
activation. J Ethnopharmacol. 2005;100:347–52.
6. Jugran AK, Bahukhandi A, Dhyani P, et al. Impact of altitudes and habitats
on valerenic acid, total phenolics, flavonoids, tannins, and antioxidant
activity of Valeriana jatamansi. Appl Biochem Biotechnol. 2016;179:
911–26.
7. Kalim MD, Bhattacharyya D, Banerjee A, Chattopadhyay S. Oxidative DNA
damage preventive activity and antioxidant potential of plants used in Unani
system of medicine. BMC Complement Altern Med. 2010;10:77.
8. Katoch O, Kaushik S, Kumar MS, et al. Radioprotective property of an
aqueous extract from Valeriana wallichii. J Pharm Bioallied Sci. 2012;4:
327–32.
9. Khan AU, Gilani AH. Antidiarrhoeal and bronchodilatory potential of
Valeriana wallichii. Nat Prod Res. 2012;26:1045–9.
10. Khuda F, Iqbal Z, Khan A, et al. Report: screening of selected medicinal
plants for their enzyme inhibitory potential—a validation of their
ethnopharmacological uses. Pak J Pharm Sci. 2014;27:593–6.
11. Khuda F, Iqbal Z, Khan A, et al. Anti-inflammatory activity of the topical
preparation of Valeriana wallichii and Achyranthes aspera leaves. Pak J
Pharm Sci. 2013;26:451–4.
12. Khuda F, Iqbal Z, Zakiullah, et al. Antimicrobial and anti-inflammatory
activities of leaf extract of Valeriana wallichii DC. Pak J Pharm Sci. 2012;
25:715–9.
13. Lin S, Chen T, Liu XH, et al. Iridoids and lignans from Valeriana jata-
mansi. J Nat Prod. 2010;73:632–8.
14. Lin S, Fu P, Chen T, et al. Minor valepotriates from Valeriana jata-
mansi and their cytotoxicity against metastatic prostate cancer cells. Planta
Med. 2015;81:56–61.
15. Lin S, Shen YH, Li HL, et al. Acylated iridoids with cytotoxicity from
Valeriana jatamansi. J Nat Prod. 2009;72:650–5.
16. Mao CD, Song HZ, Yang B, et al. Chemical constituents from rhizome of
Valeriana jatamansi. Zhong Yao Cai. 2015;38:1665–7 (Chinese).
1884 Valeriana jatamansi Jones.

17. Marder M, Viola H, Wasowski C, et al. 6-Methylapigenin and hesperidin:

new valeriana flavonoids with activity on the CNS. Pharmacol Biochem
Behav. 2003;75:537–45.
18. Mathela CS, Padalia RC, Chanotiya CS. Kanokonyl acetate-rich Indian
valerian from north-western Himalaya. Nat Prod Commun. 2009;4:1253–6.
19. Rawat S, Jugran AK, Bahukhandi A, et al. Antioxidant and antimicrobial
properties of some ethnotherapeutically important medicinal plants of
Indian Himalayan region. 3 Biotech. 2016;6:154.
20. Rehni AK, Pantlya HS, Shri R, Singh M. Effect of chlorophyll and aqueous
extracts of Bacopa monniera and Valeriana wallichii on ischaemia and
reperfusion-induced cerebral injury in mice. Indian J Exp Biol. 2007;45:
764–9.
21. Sah SP, Mathela CS, Chopra K. Antidepressant effect of Valeriana
wallichii patchouli alcohol chemotype in mice: behavioural and biochem-
ical evidence. J Ethnopharmacol. 2011;135:197–200.
22. Sah SP, Mathela CS, Chopra K. Elucidation of possible mechanism of
analgesic action of Valeriana wallichii DC. chemotype (patchouli alcohol)
in experimental animal models. Indian J Exp Biol. 2010;48:289–93.
23. Sah SP, Mathela CS, Chopra K. Involvement of nitric oxide (NO) signalling
pathway in the antidepressant activity of essential oil of Valeriana
wallichii Patchouli alcohol chemotype. Phytomedicine. 2011;18:1269–75.
24. Sahu S, Ray K, Yogendra Kumar MS, et al. Valeriana wallichii root extract
improves sleep quality and modulates brain monoamine level in rats.
Phytomedicine. 2012;19:924–9.
25. Singh SK, Katoch R, Kapila RK. Genetic and biochemical diversity
among Valeriana jatamansi populations from Himachal Pradesh.
ScientificWorldJournal. 2015;2015:863913.
26. Subhan F, Karim N, Gilani AH, Sewell RD. Terpenoid content of Valeriana
wallichii extracts and antidepressant-like response profiles. Phytother Res.
2010;24:686–91.
27. Thies PW. Linarin-isovalerianate, a currently unknown flavonoid from
Valeriana wallichii DC. 6. Report on the active substances of Valeriana.
Planta Med. 1968;16:363–71.
28. Toolika E, Bhat NP, Shetty SK. A comparative clinical study on the effect
of Tagara (Valeriana wallichii DC.) and Jatamansi (Nardostachys jatamansi
DC.) in the management of Anidra (primary insomnia). Ayu. 2015;36:46–9.
29. Wang R, Xiao D, Bian YH, et al. Minor iridoids from the roots of Valeriana
wallichii. J Nat Prod. 2008;71:1254–7.
30. Wasowski C, Marder M, Viola H, et al. Isolation and identification of
6-methylapigenin, a competitive ligand for the brain GABA(A) receptors,
from Valeriana wallichii. Planta Med. 2002;68:934–6.
31. Xu J, Guo P, Fang LZ, Li YS, Guo YQ. Iridoids from the roots of Valeriana
jatamansi. J Asian Nat Prod Res. 2012;14:1–6.
32. Xu J, Guo P, Guo Y, et al. Iridoids from the roots of Valeriana jatamansi
and their biological activities. Nat Prod Res. 2012;26:1996–2001.
Valeriana jatamansi Jones. 1885

33. Xu J, Guo Y, Jin DQ, et al. Three new iridoids from the roots of
Valeriana jatamansi. J Nat Med. 2012;66:653–7.
34. Xu J, Guo Y, Xie C, et al. Isolation and neuroprotective activities of acylated
iridoids from Valeriana jatamansi. Chem Biodivers. 2012;9:1382–8.
35. Xu J, Li Y, Guo Y, et al. Isolation, structural elucidation, and neuroprotective
effects of iridoids from Valeriana jatamansi. Biosci Biotechnol Biochem.
2012;76:1401–3.
36. Xu J, Yang B, Guo Y, et al. Neuroprotective bakkenolides from the roots of
Valeriana jatamansi. Fitoterapia. 2011;82:849–53.
37. Xu J, Zhao P, Guo Y, et al. Iridoids from the roots of Valeriana jata-
mansi and their neuroprotective effects. Fitoterapia. 2011;82:1133–6.
38. Xu K, Lin Y, Zhang R, et al. Evaluation of safety of iridoids rich fraction
from Valeriana jatamansi Jones: acute and subchronic toxicity study in
mice and rats. J Ethnopharmacol. 2015;172:386–94.
39. Yu LL, Han CR, Huang R, et al. A new iridoid tetraester from Valeriana
jatamansi. Pharmazie. 2006;61:486–8.
Verbena officinalis L.
(Verbenaceae)

(Syns.: V. adulterina Hausskn.; V. domingensis Urb.; V. macrostachya F.Muell.;

V. riparia Raf. ex Small & A. Heller; V. rumelica Velen.; V. spuria L.; V. vulgaris
Bubani)

Abstract
A perennial herb native to Europe but naturalized to other countries in
subtemperate and subtropical regions, such as North Africa, China, Japan and
North America. Verbena was the classical Roman name for altar plants, but
especially for this species. It was one of the Seven Sacred Herbs of the Druids.
Pliny mentioned that the plant bruised in wine is used as a remedy for the stings
of serpents, and that it was revered among the Romans as Tulsi is among Hindus.
Dioscorides stated that the leaves have a reputation as a local sedative and
vulnerary. For centuries Vervain has led the botanical field in the treatment of
nervous disorders, epilepsy and asthma. It also fortifies liver, heart and spleen;
relieves mental strain and helps cure infectious diseases. The infusion may be
used as a gargle or mouth wash for sore throats and gums or as an eye lotion. It is
also used as an emmenagogue. In Italian folk medicine, the plant is used for the
treatment of rheumatic pains and wounds, and in the treatment of inflammatory
disorders, skin burns, abrasions, and gastric diseases. In Navarra region of Spain,
it has been used in traditional herbal medicine for the treatment of topical
inflammation. In traditional Austrian medicine, herbal tea is used for the
treatment of infections and fever. In Unani medicine, the plant is considered
tonic, astringent, and useful in paralysis and amenorrhea, and a plaster of leaves
promotes healing of wounds. In China, it has been used to treat acute dysentery,
enteritis, amenorrhea and depression; the stalks and leaves are thought to act on
blood, relieving congestion, obstructions, dropsical effusions, and hematocele,
and are also credited with emmenagogue, anthelmintic and antiscorbutic
properties. Citral, a key component of the lemon-scented essential oils extracted
from verbena is used as a food additive and as fragrance in cosmetics.
Twenty-one compounds including iridoid glycosides, triterpenoids, flavonoids,
phenylpropanoids and phenolic diterpenoids were identified in samples from
China, including carnosic acid, carnosol, rosmanol, isorosmanol, rosmarinic acid

© Springer Nature Switzerland AG 2020 1887

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_192
1888 Verbena officinalis L.

and acacetin-7-O-rutinoside. In a double-blind, multicenter RCT, rinsing mouth

with the decoction significantly ameliorated indices of chronic generalized
gingivitis.

Keywords


Algebrão Eisenkraut
Faristariun
Ijzerhard
Kumatsutsura
Lawayzat


khadima Mǎ biān cǎo
Pamukh
Verbena
Vervain

Vernaculars: Hin.: Pamukh; Ara.: Lawayzat khadima; Chi.: Mǎ biān cǎo; Dut.:
Ijzerhard; Eng.: Devil’s bane, Dovecote, Holyherb, Simpler’sjoy, Vervain, Wild
hyssop; Fre.: Herbe aux sorcières, Herbe sacrée, Herbe à tous maux, Verveine, Ver-
veine officinale, Verveine sauvage; Ger.: Echtes eisenkraut, Eisenkraut, Gemeines
eisenkraut, Gewöhnliches eisenkraut; Ita.: Berbena, Columbaria, Hrba buona, Ver-
bena, Verbena comune; Jap.: Kumatsutsura, Kumatsuzura; Nep.: Bhek paadee, Pitta
maaree; Per.: Baristariun, Faristariun; Por.: Algebão, Algebrado, Algebrão, Argebão,
Erva-dos-leprosos, Erva-sagrada, Gerbão, Gerivão, Gervão, Gervião, Gervivão, Gir-
bão, Giribão, Jarvão, Ulgebrão, Urgebão, Urgrabrão, Verbena; Spa.: Curasana, Hierba
de la ictericia, Hierba de los ribazos, Hierba de Santa Isabel, Hierba sagrada, Hierba
santa, Hierba verbena, Verbena, Verbena fina, Verbena macho, Verbena mayor,
Verbena oficinal; Tag.: Verbena; Tur.: Mineçiçeği.
Description: A perennial herb native to Europe but naturalized to other countries in
subtemperate and subtropical regions, such as North Africa, China, Japan and North
America. The plant is a more or less hairy herb growing up to 90 cm in height, erect
but decumbent at the base. Leaves are 5–10 cm long, variously lobed, and narrowed
to the base; lower ones are stalked, pinnatified or coarsely toothed, more or less
hairy, and usually hoary on the nerves beneath; the upper ones are without stalks and
3-lobed. Flowers (May to July) are small, 4–6 mm long, without stalks, and borne in
dense, bracteate heads which elongate as the fruit ripens. The fruit is dry, ultimately
spreading into four 1-seeded nutlets which are oblong and dorsally smooth, their
underfaces covered with minute, white flaking cells (Figs. 1 and 2).CXVII
Actions and Uses: Verbena was the classical Roman name for altar plants, but
especially for this species. It was one of the Seven Sacred Herbs of the Druids.
Pliny mentioned that the plant bruised in wine is used as a remedy for the stings
of serpents, and that it was revered among the Romans as Tulsi is among
Hindus. Dioscorides stated that the leaves have a reputation as a local sedative and
vulnerary.XL ConwayXXVI described it as “not a spectacular plant, having sparse,
greeny-grey leaves and small hooded mauve flowers. Even so Vervain has a sound
religious and magical pedigree, for it is the divine weed that was sprinkled on the
altars of Jupitor, the herba veneris employed in rites of love and a sacred plant of
the Druids. Latter-day magicians wear a crown of Vervain as protection during the
evocation of demons.” For centuries Vervain has led the botanical field in the
treatment of nervous disorders, epilepsy and asthma. It also fortifies liver, heart and
Verbena officinalis L. 1889

Fig. 1 Verbena officinalis, Plant, Konrad Lackerbeck, WikimediaCommons; ShareAlike 2.5

Generic CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Eisenkraut,_Passau.JPG; https://
creativecommons.org/licenses/by-sa/2.5/deed.en

Fig. 2 Verbena officinalis, Flowers, H. Zell, WikimediaCommons; ShareAlike 3.0 Unported CC

BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Verbena_officinalis_002.JPG; https://creative-
commons.org/licenses/by-sa/3.0/deed.en
1890 Verbena officinalis L.

spleen; relieves mental strain and helps cure infectious diseases. The infusion may
be used as a gargle or mouth wash for sore-throats and gums or as an eye lotion.XXVI
It is also used as an emmenagogue.LXXIX In Unani medicine, the plant is considered
tonic, astringent, and useful in paralysis and amenorrhea, and a plaster of leaves
promotes healing of wounds. In Indo-China, it is considered useful in nervous
complaints and as a deobstruent in dropsy. Fresh leaves are used as antipyretic and
tonic, and as a rubefacient in rheumatism and other diseases of joints.LXXXIV
Slightly bitter, aromatic, febrifuge and alterative,LXXXI useful in nerve complaints
and amenorrhea.CV In China, it has been used to treat acute dysentery, enteritis,
amenorrhea and depression [15]; the stalks and leaves are thought to act on blood,
relieving congestion, obstructions, dropsical effusions, and hematocele, and are also
credited with emmenagogue, anthelmintic and antiscorbutic properties. Root is
considered astringent and employed in dysentery.CXXXIV In Italian folk medicine,
the plant is used for the treatment of rheumatic pains and wounds [12], and in the
treatment of inflammatory disorders, skin burns, abrasions, and gastric diseases
[20]. In Navarra region of Spain, it has been used in traditional herbal medicine for
the treatment of topical inflammation [3]. In traditional Austrian medicine, herbal
tea is used for the treatment of infections and fever [23]. Citral, a key component of
the lemon-scented essential oils extracted from Verbena is used as a food additive
and as fragrance in cosmetics [9].
Phytoconstituents: Twenty-one compounds including iridoid glycosides, triter-
penoids, flavonoids, phenylpropanoids and phenolic diterpenoids were identified
in samples from China, including carnosic acid, carnosol, rosmanol, isorosmanol,
rosmarinic acid and acacetin-7-O-rutinoside [21]. Phytochemical screening of etha-
nol extract of aerial parts from Iran indicated the presence of alkaloids and gly-
coside; and absence of flavonoids, tannins, and saponins [17]. However, luteolin
7-diglucuronide, as the major flavonoid [4], 3,4-dihydroverbenalin, daucosterol [25],
apigenin, 4′-hydroxywogonin, verbenalin, hastatoside [22], and verbenoside A and B
[24] were reported from aerial parts of the plant from China. Five triterpenoids,
4-epi-barbinervic acid, 2a,3b-dihydroxyurs-12-en-28-oic acid, 3a,24- dihydroxyurs-
12-en-28-oic acid, 3a,24-dihydroxy-olean-12-en-28-oic acid, and ursolic acid [19],
and iridoids, verbenalin, verbeofflin I, 7-hydroxydehydrohastatoside, 3,4- dihydrover-
benalin, and hastatoside were also isolated from aerial parts [18]. Petroleum ether and
chloroform extracts of aerial parts yielded b-sitosterol, ursolic acid, oleanolic acid,
3-epiursolic acid, 3-epioleanolic acid, and minor triterpenoids of derivatives of
ursolic acid and oleanolic acids; whereas methanol extract yielded two iridoid glu-
cosides, verbenalin and hastatoside, a phenylpropanoid glycoside, verbascoside and
b-sitosterol-D-glucoside [7]. The plant contains an essential oil comprising of citral,
geraniol, limonene and verbenone, invertin, a bitter principle, verbenalol and the
glycoside verbenalin;LXXIX a total of 64 compounds were identified in the EO from the
Mediterranean region [10].
Pharmacology: Aqueous extract of aerial parts is reported to significantly decrease
sleep latency and increase sleeping time of rats which is reversed by flumazenil.
Pretreatment with water extract significantly attenuates the toxicity of b-amyloid
Verbena officinalis L. 1891

(Abeta) peptide and dithiothreitol in primary cultures of cortical neurons [15].

Ethanol extract exhibited significant anticonvulsant activity in mice, which was nulli-
fied by pretreatments with flumezanil and naloxone [17], and aqueous- methanol
extract also exhibited anxiolytic and sedative effects [13]. Methanol extract of the
leaves and essential oil have also shown excellent antioxidant activity [5, 6, 20].
The EO exhibits strong antibacterial activity against B. cereus and P. aeruginosa [6].
Both EO of the plant and citral induce apoptosis in lymphocytes collected from
normal blood donors and patients with chronic lymphocytic leukemia, but the
activity was greater in lymphocytes collected from CLL patients [6]; and citral also
induced apoptosis in several other hematopoietic cancer cell lines, that is accom-
panied with DNA fragmentation and caspase-3 catalytic activity induction [9]. The
extract also exhibits antitumor effect on H22 tumor-bearing mice with an inhibition
rate reaching 38.78% [14]. Various extracts exhibit remarkable anti-inflammatory
activity [20]. Methanol leaf extract is very effective in the TPA-induced ear inflam-
mation, and lesser effect in carrageenan-induced rat paw edema [2]. Anti-inflam-
matory effect of topical preparation containing the extract (3% w/w) was equivalent
to the effect of piroxicam gel 3 h after carrageenan injection. However, topical
analgesic activity was less than that of methyl salicylate ointment [3]. Successively
extracted aerial parts in petroleum ether, chloroform and methanol exhibit anti-
inflammatory activity in carrageenan-induced paw edema, with the chloroform
extract being the most active [7]. It was reported as a moderate inhibitor of COX-1
[16]. Various extracts have also exhibited significant gastroprotective activity [20].
Clinical Studies: In a double-blind, multicenter RCT, rinsing mouth with the
decoction of the plant for 28-days significantly ameliorated indices of chronic
generalized gingivitis in 130 test patients [11].
Mechanism of Action: The sedative and anticonvulsant effects are suggested
to involve GABA-ergic and opioidergic systems [17], and the analgesic and anti-
inflammatory effects could be due to COX-1 inhibitory activity [16].
Human A/Es, Allergy and Toxicity: It may cause allergic contact dermatitis [8].
Animal Toxicity: Ethanol extract of aerial parts was nonlethal and nontoxic to
mice up to an oral dose of 2,000 mg/kg [17].
Potential for Drug-Herb Interactions: Hydroalcohol extract contains vitamin K
and can lessen the effect of oral anticoagulant therapy; it should not be used or used
cautiously in patients on oral anticoagulant and/or antiplatelet therapy [1].
Commentary: This plant has a long history of use, and is still used in traditional
medicines of many European countries, chiefly for anti-inflammatory and analgesic
properties. However, there are no published systematic clinical studies on these
aspects.
1892 Verbena officinalis L.

References
1. Argento A, Tiraferri E, Marzaloni M. Oral anticoagulants and medicinal
plants. An emerging interaction. Ann Ital Med Int. 2000;15:139–43 (Italian).
2. Calvo MI, Vilalta N, San Julián A, Fernández M. Anti-inflammatory
activity of leaf extract of Verbena officinalis L. Phytomedicine. 1998;5:
465–7.
3. Calvo MI. Anti-inflammatory and analgesic activity of the topical prepa-
ration of Verbena officinalis L. J Ethnopharmacol. 2006;107:380–2.
4. Carnat A, Carnat AP, Chavignon O, et al. Luteolin 7-diglucuronide, the
major flavonoid compound from Aloysia triphylla and Verbena officinalis.
Planta Med. 1995;61:490.
5. Casanova E, García-Mina JM, Calvo MI. Antioxidant and antifungal
activity of Verbena officinalis L. leaves. Plant Foods Hum Nutr. 2008;63:
93–7.
6. De Martino L, D’Arena G, Minervini MM, et al. Verbena officinalis
essential oil and its component citral as apoptotic-inducing agent in chronic
lymphocytic leukemia. Int J Immunopathol Pharmacol. 2009;22:1097–104.
7. Deepak M, Handa SS. Anti-inflammatory activity and chemical composi-
tion of extracts of Verbena officinalis. Phytother Res. 2000;14:463–5.
8. Del Pozo MD, Gastaminza G, Navarro JA, et al. Allergic contact dermatitis
from Verbena officinalis L. Contact Dermatitis. 1994;31:200–1.
9. Dudai N, Weinstein Y, Krup M, et al. Citral is a new inducer of caspase-3 in
tumor cell lines. Planta Med. 2005;71:484–8.
10. Elshafie HS, Sakr S, Mang SM, et al. Antimicrobial activity and chemical
composition of three essential oils extracted from Mediterranean aromatic
plants. J Med Food. 2016;19:1096–103.
11. Grawish ME, Anees MM, Elsabaa HM, Abdel-Raziq MS, Zedan W.
Short-term effects of Verbena officinalis Linn. decoction on patients suffer-
ing from chronic generalized gingivitis: double-blind randomized controlled
multicenter clinical trial. Quintessence Int. 2016;47:491–8.
12. Guarrera PM, Forti G, Marignoli S. Ethnobotanical and ethnomedicinal uses
of plants in the district of Acquapendente (Latium, Central Italy). J Ethnophar-
macol. 2005;96:429–44.
13. Khan AW, Khan AU, Ahmed T. Anticonvulsant, anxiolytic, and sedative
activities of Verbena officinalis. Front Pharmacol. 2016;7:499.
14. Kou WZ, Yang J, Yang QH, et al. Study on in-vivo antitumor activity of
Verbena officinalis extract. Afr J Tradit Complement Altern Med. 2013;10:
512–7.
15. Lai SW, Yu MS, Yuen WH, Chang RC. Novel neuroprotective effects of the
aqueous extracts from Verbena officinalis Linn. Neuropharmacology. 2006;
50:641–50.
16. Lin GD, Li RW, Myers SP, Leach DN. A method of selecting plants with
anti-inflammatory potential for pharmacological study. Nat Prod Commun.
2008;3:71–6.
Verbena officinalis L. 1893

17. Rashidian A, Kazemi F, Mehrzadi S, et al. Anticonvulsant effects of aerial

parts of Verbena officinalis extract in mice: involvement of benzodiazepine
and opioid receptors. J Evid Based Complementary Altern Med. 2017;22:
632–6.
18. Shu J, Chou G, Wang Z. Two new iridoids from Verbena officinalis L.
Molecules. 2014;19:10473–9.
19. Shu JC, Liu JQ, Chou GX. A new triterpenoid from Verbena officinalis L.
Nat Prod Res. 2013;27:1293–7.
20. Speroni E, Cervellati R, Costa S, et al. Effects of differential extraction of
Verbena officinalis on rat models of inflammation, cicatrization and gastric
damage. Planta Med. 2007;73:227–35.
21. Sun Y, Wang Y, Cai R, Zhang H, Wang Y. Identification of the chemical
compositions of Verbena officinalis L. extract by high performance liquid
chromatography-photodiode array-high resolution mass spectrometry. Se
Pu. 2017;35:987–94 (Chinese).
22. Tian J, Zhao YM, Luan XH. Studies on the chemical constituents in herb of
Verbena officinalis. Zhongguo Zhong Yao Za Zhi. 2005;30:268–9 (Chinese).
23. Vogl S, Picker P, Mihaly-Bison J. Ethnopharmacological in vitro studies on
Austria’s folk medicine—an unexplored lore in vitro anti-inflammatory
activities of 71 Austrian traditional herbal drugs. J Ethnopharmacol. 2013;
149:750–71.
24. Xu W, Xin F, Sha Y, Fang J, Li YS. Two new secoiridoid glycosides from
Verbena officinalis. J Asian Nat Prod Res. 2010;12:649–53.
25. Zhang T, Ruan JL, Lu ZM. Studies on chemical constituents of aerial parts
of Verbena officinalis L. Zhongguo Zhong Yao Za Zhi. 2000;25:676–8
(Chinese).
Vernonia anthelmintica Willd.
(Asteraceae/Compositae)

(Syns.: Baccharoides anthelmintica (L.) Willd.; Centratherum anthelminticum (L.)

Kuntz)

Abstract
An annual plant, native to the temperate regions of Garhwal Himalayas, India. It is
a highly esteemed remedy for leucoderma and psoriasis, and also used as an
anthelmintic in combination with other drugs. It is described as sweet, pungent,
digestive, bitter, alterative, astringent, cold, cardiacal, dry, and antiphlegmatic, and
a remedy for cough, fevers and intestinal worms. Seeds are used in leucoderma,
leprosy, psoriasis, and other skin diseases. As anthelmintic, powdered seeds are
given for the removal of Ascaris, and as a stomachic in loss of appetite and
dyspepsia. Externally the drug is applied in skin diseases in a variety of forms, such
as paste, oil, etc.; a poultice or plaster is used to disperse cold tumors. In Siddha
system of medicine, it is used for the treatment of neurological disorders. In
traditional Uyghur and Chinese medicines, kaliziri extract has been used to treat
leucoderma (vitiligo) for centuries. Seeds contain vernodlin, vernodalol, and
vernolic acid, and are rich in Cl, Co, Cr and Zn content, and low in Fe content.
Ethanol extract demonstrated marked antioxidant activity, and lowered blood
glucose of diabetic rats; the active fraction of the extract given daily to diabetic rats
for 45-days significantly reduced glucose, HbA1c, TC, TGs, LDL, VLDL, FFAs,
phospholipids and HMG-CoA reductase, and normalized changes in plasma
insulin, protein, HDL and hepatic glycogen. Methanol seed extract also
significantly inhibited AChE and BChE.

Keywords






Atarital Bakchi Ghrajiri Ironweed Kadvi jire Kali-ziri Kanana-jiraka


Somaraja

Vernaculars: Urd.: Kali-ziri, Kamoon bari, Zeerajangli; Hin.: Bakchi, Ghrajiri,

Kali-jiri, Somraj; San.: Avulguja, Kanana-jiraka, Somaraja, Vakuchi atavi jiraka;
Ben.: Bukachi, Kalijiri, Kalouji, Somaraj; Mal.: Kattai jirakam, Kattukjiragam,
Krmisatru, Puvankuruntala; Mar.: Kali-jiri, Karalve, Rana-chajire; Tam.:
© Springer Nature Switzerland AG 2020 1895
S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_193
1896 Vernonia anthelmintica Willd.

Anantalavikum, Araniyakanam, Kattu-chira, Kattu-shiragam; Tel.: Adavi-jilakara,

Garitikamma, Kadvi Jire, Nelavavili, Vishakantakalu; Ara.: Atarital, Itrilal; Chi.:
驱虫斑鸠菊; Eng.: Ironweed, Kinka oil, Purple fleabane; Maly.: Justan-hutan;
Pers.: Itrital.
Description: An annual plant, 60–100 cm tall, native to the temperate regions of
Garhwal Himalayas, India. Stems are robust, erect, leafy with velvety branches;
alternately-arranged 5–8 cm long obovate to lance-shaped leaves. Achenes are
about 5 mm long, of a dark brown color, covered with whitish scattered hairs,
cylindrical, tapering towards the base, marked with about ten paler, longitudinal
ridges, and crowned with a circle of short brown scales. The taste is nauseous and
bitter (Figs. 1 and 2).XL
Actions and Uses: It is a highly esteemed remedy for leucoderma and psoriasis,
and also used as an anthelmintic in combination with other drugs. It is described as
sweet, pungent, digestive, bitter, alterative, astringent, cold, cardiacal, dry, and
antiphlegmatic, and a remedy for cough, fevers and intestinal worms. Seeds are
used in leucoderma, leprosy, psoriasis, and other skin diseases. As anthelmintic,
powdered seeds are given for the removal of Ascaris, and as a stomachic in loss of
appetite and dyspepsia.LXXXI For skin diseases, Chakradatta (a treatise on Hindu
medicine) directs the drug to be powdered with an equal quantity of black Sessa-
mum, and about 3.5 g of the powder to be taken in the morning with tepid water,
followed by perspiration induced by exercise or exposure to the sun. Externally the
drug is applied in skin diseases in a variety of forms, such as paste, oil, etc. The
author of Makhzan-al-Adwiya stated that it is given internally to remove phlegm
and worms from intestines, and that a poultice or plaster is used to disperse cold
tumors. He also mentions that the drug is not often prescribed internally, as it is
thought to have injurious effects, and is much used as a cattle medicine.XL In Unani
medicine, seeds are regarded as carminative, anthelmintic, anti-inflammatory, and
analgesic, and generally used as paste to relieve inflammation of boils, and rarely

Fig. 1 Vernonia anthelmintica, Seeds/achenes, Kingbossix, WikimediaCommons; ShareAlike 4.0

International CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:Vernonia_anthelmintica_
seeds,_achenes.jpg; https://creativecommons.org/licenses/by-sa/4.0/deed.en
Vernonia anthelmintica Willd. 1897

Fig. 2 Vernonia anthelmintica, Seeds as sold in Indian Stores, Prof. Akbar, Original

used internally.LXXVII NadkarniCV described seeds as anthelmintic, stomachic,

tonic, diuretic, antiperiodic and alterative, and used in the treatment of round
worms, that are expelled lifeless. In Siddha system of medicine, it is used for the
treatment of neurological disorders [9]. In traditional Uyghur and Chinese
medicines, kaliziri extract has been used to treat leucoderma (vitiligo) for centuries
[14, 17, 19].
Phytoconstituents: Seeds contain vernodlin, vernodalol, and vernolic acid [7], and
are rich in Cl, Co, Cr and Zn content, and low in Fe content [1]. Water decoction,
hexane and ethanol seed extracts showed the presence of flavonoids and terpenoids;
and alkaloids, tannins and fixed oils were present only in hexane and ethanol
extracts [8]. Elemanolides: vernonilide A and B [6], vernonilides D, E, and F, a
guaianolide, and a germacranolide [15], elemanolide dimers: vernodalidimers C, D,
and E [16], benzoylvernovan, 2-(4′-hydroxyphenyl)-6-methyl-4H-pyran-4-one,
biflavonoid, aurone [11], and several flavonoids [13] have been isolated from seeds.
Caffeic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic
acid, 3,4-di-O-caffeoylisoquinic acid, and 3,4-di-O-caffeoylquinic acid have also
been isolated from seeds [18]. Nine stigmastane-type steroids, vernoanthelcin A–I,
and two stigmastane-type steroidal glycosides, vernoantheloside A and B [5], and
vernoanthelsterone A [4], were reported from aerial parts. Abscisic acid has been
isolated from the leaves [12].
Pharmacology: A seed extract is reported to show potent analgesic activity [7],
and in higher doses, ethanol and hexane extracts exhibited strong anti-inflammatory
effect, and ethanol extract also demonstrated marked antioxidant activity [8].
Ethanol seed extract lowered blood glucose of STZ-diabetic rats to a maximum of
1898 Vernonia anthelmintica Willd.

82% 6 h after dosing; the active fraction of the extract given daily to diabetic rats
for 45-days significantly reduced plasma glucose, HbA1c, TC, TGs, LDL, VLDL,
FFAs, phospholipids and HMG-CoA reductase, and normalized changes in plasma
insulin, protein, HDL and hepatic glycogen [2]. Ethanol extract showed anthel-
mintic activity against infective larvae of H. contortus of up to 93% relative to
pyrantel tartrate [3]. Ethanol-water (80:20, v/v) extract dose-dependently increases
tyrosinase activity and melanin content and enhances expression of tyrosinase in
B16 cells. Major chemical constituents in the extract were flavonoids [14, 19]. At
higher concentrations the extract exhibited antiproliferative activity against MCF7
and MDA-MB-231 breast cancer cells [10]. Hydroalcohol (methanol) seed extract
also significantly inhibited AChE and BChE [9].
Mechanism of Action: The melanogenic activity is credited to methylflavonoids,
isorhamnetin and kaempferide, that significantly increased expression of melanin-
biosynthetic genes and the tyrosinase activity in melanoma cells [17], justifying its
traditional use in vitiligo. Cholesterol-lowering effect may involve decreased activity
of HMG-CoA reductase [2].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: Oral LD50s for ethanol and hexane extracts, and water decoc-
tion of seeds in mice are reported to be greater than 5,000 mg/kg [8].
Commentary: There are no systematic formal clinical studies published. Since the
seeds are mainly used internally as anthelmintic, but topically it has been used for
the treatment of vitiligo for centuries and has shown melanogenic activity; it should
be a good candidate for further investigations for this application.

References
1. Fatima I, Waheed S, Zaidi JH. Elemental analysis of Anethum graveolens,
Sismbrium irio Linn and Veronia anthelmintica seeds by instrumental
neutron activation analysis. Appl Radiat Isot. 2013;71:57–61.
2. Fatima SS, Rajasekhar MD, Kumar KV, et al. Antidiabetic and antihyper-
lipidemic activity of ethyl acetate:isopropanol (1:1) fraction of Vernonia
anthelmintica seeds in streptozotocin induced diabetic rats. Food Chem
Toxicol. 2010;48:495–501.
3. Hördegen P, Cabaret J, Hertzberg H, Langhans W, Maurer V. In vitro
screening of six anthelmintic plant products against larval Haemonchus
contortus with a modified methyl-thiazolyl-tetrazolium reduction assay.
J Ethnopharmacol. 2006;108:85–9.
4. Hua L, Li Y, Wang F, et al. Biologically active steroids from the aerial parts
of Vernonia anthelmintica Willd. Fitoterapia. 2012;83:1036–41.
5. Hua L, Qi WY, Hussain SH, et al. Highly oxygenated stigmastane-type
steroids from the aerial parts of Vernonia anthelmintica Willd. Steroids.
2012;77:811–8.
Vernonia anthelmintica Willd. 1899

6. Ito T, Aimaiti S, Win NN, Kodama T, Morita H. New sesquiterpene

lactones, vernonilides A and B, from the seeds of Vernonia anthelmintica in
Uyghur and their antiproliferative activities. Bioorg Med Chem Lett.
2016;26:3608–11.
7. Jahan N, Ahmad M, Mehjabeen, et al. Antinociceptive activity of seed
extract of Vernonia anthelmintica willd. Pak J Pharm Sci. 2014;27(6 Spec
No.):2177–81.
8. Jamil S, Khan RA, Afroz S, Ahmed S. Phytochemistry, Brine shrimp
lethality and mice acute oral toxicity studies on seed extracts of Vernonia
anthelmintica. Pak J Pharm Sci. 2016;29:2053–7.
9. Kadiyala M, Ponnusankar S, Elango K. Screening of Siddha medicinal plants
for its in-vitro acetylcholinesterase and butyrylcholinesterase inhibitory
activity. Pharmacogn Mag. 2014;10 Suppl 2:S294–8.
10. Lambertini E, Piva R, Khan MT, et al. Effects of extracts from Bangladeshi
medicinal plants on in vitro proliferation of human breast cancer cell lines
and expression of estrogen receptor alpha gene. Int J Oncol. 2004;24:
419–23.
11. Maimaiti Z, Turak A, Aisa HA. Two new compounds from the seeds of
Vernonia anthelmintica. J Asian Nat Prod Res. 2017;19:862–8.
12. Sanyal T, Ganguly SN, Sircar PK, Sircar SM. Abscisic acid in the leaf of
Vernonia anthelmintica. Planta. 1970;92:282–4.
13. Tian G, Zhang U, Zhang T, et al. Separation of flavonoids from the seeds of
Vernonia anthelmintica Willd. by high-speed countercurrent chromatogra-
phy. J Chromatogr A. 2004;1049:219–22.
14. Tuerxuntayi A, Liu YQ, Tulake A, et al. Kaliziri extract upregulates
tyrosinase, TRP-1, TRP-2 and MITF expression in murine B16 melanoma
cells. BMC Complement Altern Med. 2014;14:166.
15. Turak A, Aisa HA. Three new elemanolides from the seeds of Vernonia
anthelmintica. J Asian Nat Prod Res. 2018;20:313–20.
16. Turak A, Liu Y, Aisa HA. Elemanolide dimers from seeds of Vernonia
anthelmintica. Fitoterapia. 2015;104:23–30.
17. Wang JY, Chen H, Wang YY, et al. Network pharmacological mechanisms
of Vernonia anthelmintica (L.) in the treatment of vitiligo: isorhamnetin
induction of melanogenesis via upregulation of melanin-biosynthetic genes.
BMC Syst Biol. 2017;11:103.
18. Wang Y, Wang E, Shang J, Wang H. Caffeoylquinic acid derivatives from
the seeds of Vernonia anthelmintica. Zhongguo Zhong Yao Za Zhi. 2012;
37:1590–2 (Chinese).
19. Zhou J, Shang J, Ping F, Zhao G. Alcohol extract from Vernonia
anthelmintica (L.) Willd. seed enhances melanin synthesis through activa-
tion of the p38 MAPK signaling pathway in B16F10 cells and primary
melanocytes. J Ethnopharmacol. 2012;143:639–47.
Vigna unguiculata (L.) Walp
(Fabaceae/Leguminosae)

(Syns.: Dolichos biflorus L.; D. melanophthalmus deCand.; D. sinensis L.;

Vigna sinensis (L.) Hass)

Abstract
An annual herbaceous legume, that thrives in poor dry conditions, such as
semidesert regions of West Africa, but widely cultivated as food crop in Indian
subcontinent, China, Malaysia, and Australia. The plant is considered wholesome
for convalescing patients, and a soup of seed is prescribed as antilithic. In
traditional herbal medicine, seeds are mainly used as tonic, astringent, diuretic,
and are also recommended in asthma, bronchitis, urinary discharges, hiccups,
ozoena, heart trouble and diseases of brain. Seeds decoction is used for diarrhea,
in cases of leucorrhea and other menstrual irregularities, and administered to
women during childbirth to promote discharge of placenta. Seeds decoction is
also used in urinary diseases; and a powder of seeds is applied to skin to check
cold sweats. It is a rich source of minerals, vitamins, proteins and calories; and
also some antinutritional elements, such as phytic acid and protease inhibitors.
A novel dimeric antilithiatic protein from seeds has been purified based on its
ability to inhibit calcium oxalate crystallization. Polysaccharides containing
pentose and hexose sugars with antimicrobial activity have been isolated from
seeds. Methanol seed extract exhibited mild analgesic activity, significant diuretic
activity comparable to furosemide, and significant anti-inflammatory effects.
Methanol seed extract treatment of high-fat diet-fed rats decreased near to normal
levels of plasma and tissue TC, TGs, FFAs, phospholipids, plasma LDL-C and
increased level of plasma HDL-C; the effects were comparable to atorvastatin at
higher dose of the extract. Hydroalcohol seed extract prophylactically prevented
ethylene glycol-induced nephrolithiasis, and significantly decreased LPO and
restored antioxidant enzymes in kidneys of rats. In a comparative clinical study,
kulattha reduced recurrence of calcium oxalate stones with better results than the
conventional potassium citrate in Indian patients with recurring kidney stones.

© Springer Nature Switzerland AG 2020 1901

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_194
1902 Vigna unguiculata (L.) Walp

Keywords






Banette Cowpea Fagiolino Feijão-frade Habbul-qilt Jiāng dòu Kultha





Kundebohne Lobia Sang shikan

Vernaculars: Urd.: Habbul-qilt; Hin.: Kulattha, Kultha, Kulthi, Lobia; San.:

Culutu, Khalakula, Kulastha, Kulatha; Ben.: Kulthi, Kulti, Kurti-kalai; Mal.: Kollu,
Kullu, Maediri, Muthera, Mutira; Mar.: Kulitha, Kultha, Kulthi; Tam.: Kollu; Tel.:
Ulavalu, Wulawalli; Ara.: Lobia zafaria; Chi.: 豇豆,Jiāng dòu; Eng.: Black eye
pea, Cowpea, Horse gram; Fre.: Banette, Cornille, Mongette, Niébé, Pois à vache
commun; Ger.: Gemeine augenbohne, Gemeine kuhbohne, Gemeine kuherbse,
Kundebohne; Ita.: Cornetti, Faggiolino piccolo, Fagiolino, Fagiolino dall’occhio,
Fagiolino piccolo, Tegoline; Per.: Sang shikan; Por.: Feijão-frade, Feijão-miudo;
Spa.: Caupi común, Chichero de vaca, Frejol de vaca, Frejol de vaca común, Poroto
del ojo; Tag.: Katil; Tur.: Börülce, Karnıkara.
Description: An annual herbaceous legume, that thrives in poor dry conditions,
such as semidesert regions of West Africa, but widely cultivated as food crop in
Indian subcontinent, China, Malaysia, and Australia. The plant stems are 30–50 cm
in height, slender, erect, woody, little branched and densely hairy. Leaflets are
simple, linear-ligulate, and 2.5–5 cm in length; flower color varies through different
shades of purple, pink, yellow, and white and blue, 1 or 2, and borne in leaf axils;
pods are oblong, about 2 cm in length.CXVII Cultivated varieties have pods ranging
from 10 to 110 cm long; each containing 6–13 kidney-shaped seeds. Two varieties,
red and white, are described in India; red variety is Vigna catjang. Seeds vary in
color from light red to dark red and black; light red seeds are mottled green or dark
(Figs. 1, 2 and 3).

Fig. 1 Vigna unguiculata, Cowpeas Pods, HeraldDesa, WikimediaCommons; ShareAlike 3.0

Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Lobia.jpg; https://creativecom
mons.org/licenses/by-sa/3.0/deed.en
Vigna unguiculata (L.) Walp 1903

Fig. 2 Vigna unguiculata, Pods on the Plant in Hong Kong, Earth 100, WikimediaCommons;
ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Black-eyed_
pea_pods_on_plant_in_Hong_Kong.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Vigna unguiculata, Black-Eyed Peas, Toby Hudson, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:BlackEyedPeas.JPG; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Actions and Uses: The plant is considered wholesome for convalescing patients, and
a soup of seed is prescribed as antilithic.XL In traditional herbal medicine, seeds are
mainly used as tonic, astringent, diuretic, and are also recommended in asthma,
bronchitis, urinary discharges, hiccups, ozoena, heart trouble and diseases of brain [1].
1904 Vigna unguiculata (L.) Walp

Seeds decoction is used for diarrhea, in cases of leucorrhea and other menstrual
irregularities, and administered to women during childbirth to promote discharge of
placenta.CV,L,LXXVII Seeds decoction is also used in urinary diseases; and a powder of
seeds is applied to skin to check cold sweats.LXXXI In Unani medicine it (tempera-
ment, hot 2° and dry 2° by Kabeeruddin, and cold 2° and moist 1° according to
Avicenna) is used for eye diseases, as appetizer, lithotriptic, diuretic, emmenagogue,
expectorant, laxative, deobstruent, antispasmodic, beneficial for hiccups and piles,
and especially used for bladder and kidney stones.
Phytoconstituents: It is a rich source of minerals, vitamins, proteins and calories;
and also some antinutritional elements, such as phytic acid and protease inhibitors
[6]. A novel dimeric antilithiatic protein from seeds has been purified based on its
ability to inhibit calcium oxalate crystallization in vitro [4]. Polysaccharides con-
taining pentose and hexose sugars with antimicrobial activity have been isolated
from seeds [3]. A lectin was isolated from the roots of 7-day-old plants, which
differed from the seed lectin [16].
Pharmacology: Methanol seed extract exhibited mild analgesic activity, signifi-
cant diuretic activity comparable to furosemide, and significant anti-inflammatory
effects [1]. Hydroalcohol seed extract prophylactically prevented ethylene glycol-
induced nephrolithiasis, and significantly decreased LPO and restored antioxidant
enzymes in kidneys of rats [17]. Water-soluble, heat-stable, polar, nontannin and
nonproteinous fraction of seeds showed in vitro anticalcifying activity, which
markedly decreased with maturation of seeds or postharvest storage for 6 months
[5, 13]. Intragastric treatment of STZ-diabetic rats with D. biflorus for 30-days
significantly decreased FBG, TC and TGs levels [12]. Methanol seed extract
treatment of high-fat diet-fed rats decreased near to normal levels of plasma and
tissue TC, TGs, FFAs, phospholipids, and plasma LDL-C, and increased level of
plasma HDL-C; the effects were comparable to atorvastatin at higher dose of the
extract [10]. Lipid obtained from seeds are protective and promote gastric ulcer
healing in various models of peptic ulcers in rats, and inhibit mast cell degranu-
lation [7, 8].
Aqueous seed extract demonstrated significant antimicrobial activity against
S. aureus, B. subtilis, E. coli and P. aeruginosa [3]; methanol extract of defatted
seeds also exhibited activity against some microorganisms [2]. Administration of
seeds in diet significantly reduced tumor incidence, tumor multiplicity and tumor
volume in DMBA-induced skin papillomas in mice, and B(a)P-induced forestom-
ach papillomas; while significantly increasing hepatic carcinogen metabolizing
enzymes, GSH content and activities of antioxidant enzymes [11]. Extract of seeds
showed anti-implantation activity and inhibited pregnancy in 50–60% of rats [14],
and also exhibited possible antiandrogenic activity [9].
Clinical Studies: In a comparative clinical study, kulattha reduced recurrence of
calcium oxalate stones with better results than the conventional potassium citrate in
Indian patients with recurring kidney stones [18].
Vigna unguiculata (L.) Walp 1905

Human A/Es, Allergy and Toxicity: It may cause food allergy in certain atopic
individuals, due to the presence of lectins [15].
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: Its litholytic property has been demonstrated in a comparative
clinical trial. This property is well documented in traditional medicines, and should
be investigated in larger number of patients, as the drug-based treatment of renal
lithiasis obviates the need of surgical intervention.

References
1. Ahmad M, Sharif S, Mehjabeen, et al. Phytochemical and pharmacological
studies on methanolic seeds’ extract of Dolichos biflorus. Pak J Pharm Sci.
2014;27:335–41.
2. Basak B, Majumdar SG, Bhattacharya U, et al. Effect of different fractions of
methanolic extract of the seeds of Dolichos biflorus on some microorgan-
isms. Hindustan Antibiot Bull. 1992;34:100–3.
3. Basu S, Ghosh M, Bhunia RK, Ganguly J, Banik BK. Polysaccharides from
Dolichos biflorus Linn. and Trachyspermum ammi Linn. seeds: isolation,
characterization and remarkable antimicrobial activity. Chem Cent J. 2017;
11:118.
4. Bijarnia RK, Kaur T, Singla SK, Tandon C. A novel calcium oxalate crystal
growth inhibitory protein from the seeds of Dolichos biflorus (L.).
Protein J. 2009;28:161–8.
5. Garimella TS, Jolly CI, Narayanan S. In vitro studies on antilithiatic activity
of seeds of Dolichos biflorus Linn. and rhizomes of Bergenia ligulata Wall.
Phytother Res. 2001;15:351–5.
6. Gonçalves A, Goufo P, Barros A, et al. Cowpea (Vigna unguiculata L.
Walp), a renewed multipurpose crop for a more sustainable agri-food system:
nutritional advantages and constraints. J Sci Food Agric. 2016;96:2941–51.
7. Jayaraj AP, Tovey FI, Clark CG. Possible dietary protective factors in
relation to the distribution of duodenal ulcer in India and Bangladesh. Gut.
1980;21:1068–76.
8. Jayaraj AP, Tovey FI, Lewin MR, Clark CG. Duodenal ulcer prevalence:
experimental evidence for the possible role of dietary lipids. J Gastroenterol
Hepatol. 2000;15:610–6.
9. Murugan K, Vanithakumari G, Sampathraj R. Effects of combined extracts
of Dolichos biflorus seeds and Amaranthus spinosus roots on the accessory
sex organs of male rats. Anc Sci Life. 1993;12:351–7.
10. Muthu AK, Sethupathy S, Manavalan R, Karar PK. Hypolipidemic effect of
methanolic extract of Dolichos biflorus Linn. in high fat diet fed rats.
Indian J Exp Biol. 2005;43:522–5.
1906 Vigna unguiculata (L.) Walp

11. Nanta R, Kale RK. Chemomodulatory effect of Dolichos biflorus Linn. on

skin and forestomach papillomagenesis in Swiss albino mice. Indian J Exp
Biol. 2011;49:483–90.
12. Parthsarthi, Purwar B, Saxena Y. Effect of Dolichos biflorus on blood sugar
and lipids in diabetic rats. Indian J Physiol Pharmacol. 2013;57:63–71.
13. Peshin A, Singla SK. Anticalcifying properties of Dolichos biflorus (horse
gram) seeds. Indian J Exp Biol. 1994;32:889–91.
14. Prakash AO, Saxena V, Shukla S, et al. Anti-implantation activity of some
indigenous plants in rats. Acta Eur Fertil. 1985;16:441–8.
15. Pramod SN, Krishnakantha TP, Venkatesh YP. Effect of horse gram lectin
(Dolichos biflorus agglutinin) on degranulation of mast cells and basophils
of atopic subjects: identification as an allergen. Int Immunopharmacol.
2006;6:1714–22.
16. Quinn JM, Etzler ME. Isolation and characterization of a lectin from the
roots of Dolichos biflorus. Arch Biochem Biophys. 1987;258:535–44.
17. Saha S, Verma RJ. Antinephrolithiatic and antioxidative efficacy of Dolichos
biflorus seeds in a lithiasic rat model. Pharm Biol. 2015;53:16–30.
18. Singh RG, Behura SK, Kumar R. Litholytic property of Kulattha (Dolichous
biflorus) vs potassium citrate in renal calculus disease: a comparative study.
J Assoc Physicians India. 2010;58:286–9.
Viola odorata L.
(Violaceae)

(Syn.: V. wiedemannii Boiss.)

Abstract
A perennial herb, native to Europe and Asia, but pantropic in distribution, and
mainly cultivated in France and Egypt. Arab physicians became acquainted of
this herb through Greeks, who had been using it for long. The purple flowered
variety is considered the best; the flowers are used separately or as part of the
whole plant. It is especially valued as a diuretic and expectorant, and as a
purgative in bilious affections. It is certainly a first-rate chest herb, being strongly
decongestant and expectorant, also strengthens the heart and is frequently used in
Switzerland to treat angina pectoris. It is mostly prescribed with other drugs that
also have aperient property, such as tamarind or myrobalans. It moderates yellow-
bile, relieves fevers, quenches thirst and reduces blood heat. It is used as a
decoction for cough, cold and flu, pneumonia, pleurisy, and hot diseases of the
liver and stomach. In the early part of the 20th century it was included in many
European, Mexican, Chilean and Venezuelan Pharmacopoeias. Dried flowers
valued as diuretic and expectorant and as purgative in bilious afflictions are
considered antipyretic and diaphoretic, and used to relieve febrile symptoms and
excitement in all types of fevers; the petals of purple flowers are also refrigerant,
and laxatives. Leaves are emollient and an infusion of leaves or a syrup made of
the petals and a liquid extract of fresh leaves is beneficial for pain of cancerous
growths, especially of the throat, and is claimed to be a cure for cancer of the
tongue. In traditional Persian medicine, Violet Oil (VO), which is an almond or
sesame oil-based extract, is used for nasal or topical application for neurologic
and skin disorders, and to treat insomnia. Aqueous-methanol leaves extract tests
positive for the presence of alkaloids, saponins, tannins, phenolics, coumarins
and flavonoids. Aqueous extract contains substantial amount of vitexin, while the
ethanol extract contains rutin, vitexin, isovitexin, and kaempferol-6-glucoside. In
a comparison of post-test with pre-test state of Iranian patients with chronic
insomnia, two drops of VO in each nostril nightly for 30-days improved Insomnia
Severity Index.

© Springer Nature Switzerland AG 2020 1907

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_195
1908 Viola odorata L.

Keywords




Banafsaj Banafsha Benefes-da-beira Kokulu menekşe Maartsviooltje







März-veilchen Neelapushpa Viole de carême Violet Xiāng jǐn cài

Vernaculars: Urd.: Banafsha, Berg Banafsha (leaf), Gul Banafsha (flower); Hin.:
Banafsha; San.: Neelapushpa; Ben.: Bonosa; Mar.: Baga-banosa; Tam.: Vayilethe,
Vayilettu; Ara.: Banafsaj, Farfeer; Chi.: 香堇菜,Xiāng jǐn cài; Dan.: Marts-viol;
Dut.: Maartsviooltje, Welriekend viooltje; Eng.: English violet, Garden violet,
Sweet violet, Violet; Fin.: Tuoksuorvokki; Fre.: Fleur de mars, Jacée de printemps,
Viole de carême, Violette de mars, Violette des haies, Violette odorante, Violier
commun; Ger.: März-veilchen, März-viole, Wohlriechendes veilchen; Ita.: Rose-
viole, Viola zopa, Viola mammola, Violetta; Jap.: Nioisumire; Nor.: Marsfiol;
Per.: Banafsha, Gul-Banafshah (flowers), Kokash; Por.: Benefes-da-beira,
Benesses-da-beira, Bunefes, Munefes, Víolas, Víolas-roxas, Violetas, Violetas-
bravas, Violetas-de-cheiro; Spa.: Viola común, Viola de olor, Violeta, Violeta
común, Violeta de olor, Violeta perruna, Violeta silvestre; Swe.: Doftviol, Luktviol;
Tag.: Violeta; Tur.: Kokulu menekşe.
Description: A perennial herb, native to Europe and Asia, but pantropic in dis-
tribution, and mainly cultivated in France and Egypt [15]. It is found on sunny
banks, in woods and along hedge-grows, ‘half hiddden from the eye,’ the violet has
heart-shaped leaves and, in the spring, sweetly scented flowers of various shades
from blue to white appear.XXVI A brownish color dried herb without any stems,
consists of leaves and sometimes flowers, variegated, yellow, white, blue or pur-
plish, with long filiform stalks. Roots dry, thread-like, fibrous, pale-yellow, knotty,
slender some as thick as a quill, and slightly furrowed. Flowers purple, violet, blue
or pink and irregular; smell sweet, nauseous; taste nauseous, bitter and mucilagi-
nous.LXXXI The stems are very short or lacking, with slender stolons; leaves are
crowded at the ends of stems, orbicular to subreniform, 5–8 cm long, the base being
heart-shaped, the tip rounded, and with toothed margins. Flowers are fragrant and
1.5–1.8 cm long; the petals are violet with the throat marked with white spots or
lines; the sepals are green and 1 cm long. Dioscorides described its leaves smaller,
thinner and darker than those of Ivy (Figs. 1, 2 and 3).LIII
Actions and Uses: Arab physicians became acquainted of this herb through
Greeks, who had been using it for long. The purple flowered variety is considered the
best; the flowers are used separately or as part of the whole plant. It is especially
valued as a diuretic and expectorant, and as a purgative in bilious affections. It is
mostly prescribed with other drugs that also have aperient property, such as
tamarind or myrobalans.XL Fresh violet is assigned the temperament of cold 1° and
moist 2°, while the dried one is considered hot 1° and moist 2° in Unani medicine. It
moderates yellow-bile, relieves fevers, quenches thirst and reduces blood heat. It is
used as a decoction for cough, cold and flu, pneumonia, pleurisy, and hot diseases of
the liver and stomach.LXXVII Ibn Jazlah used its syrup for fevers, headaches, swel-
lings, epilepsy, cough, quinsy and hoarseness of voice.LIII Ibn al-BaitarLXIX quoted
Viola odorata L. 1909

Fig. 1 Viola odorata, Foliage, Kjetil Lenes, WikimediaCommons; 2.5 Generic CC BY 2.5,
https://commons.wikimedia.org/wiki/File:Viola_odorata_whole.png; https://creativecommons.org/
licenses/by/2.5/deed.en

Fig. 2 Viola odorata, Flowers, Fritz Geller-Grimm, WikimediaCommons; ShareAlike 2.5 Generic
CC BY-SA 2.5, https://commons.wikimedia.org/wiki/File:Viola_odorata_fg01.JPG; https://creati
vecommons.org/licenses/by-sa/2.5/deed.en

Avicenna that syrup of Banafshah is useful as diuretic and in kidney pain. Flowers
cleanse stomach and near organs of bilious humour and cure bilious diarrhea with 15
g powder for two to three days. In the early part of the 20th century it was included in
many European, Mexican, Chilean and Venezuelan Pharmacopoeias.XV Dried
flowers valued as diuretic and expectorant and as purgative in bilious afflictions are
considered antipyretic and diaphoretic, and used to relieve febrile symptoms and
excitement in all types of fevers;LXXXIV the petals of purple flowers are also
refrigerant, and laxatives.LXXXI NadkarniCV described flowers as astringent,
demulcent, diaphoretic, diuretic and aperient. Leaves are emollient and an infusion
of leaves or a syrup made of the petals and a liquid extract of fresh leaves is beneficial
1910 Viola odorata L.

Fig. 3 Viola odorata, Flower Close-up, Frank Vincentz, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Viola_odorata4_ies.jpg;
https://creativecommons.org/licenses/by-sa/3.0/us/

for pain of cancerous growths, especially of the throat, and is claimed to be a cure for
cancer of the tongue [2].CXVII The root is nauseating and diaphoretic.LXXXI It is used
in Iran in the forms of pills, decoction, sweet syrup, or semisolid oral preparations for
the management of cough, fever, common cold, headache, insomnia, epilepsy,
constipation, dyspnea, palpitation, dysuria, and skin diseases [5]. In traditional
Persian medicine, Violet Oil (VO), which is an almond or sesame oil-based extract,
is used for nasal or topical application for neurologic and skin disorders [5], and to
treat insomnia [7].
The Violet is one of nature’s most powerful dissolvent, being widely used in the
treatment of internal obstructions such as stones and gravels. It will also tackle
swollen glands, tumors, goiters and boils, particularly if the treatment is supple-
mented by the external application of an ointment or poultice composed of pulped
leaves. The Violet calms the nerves, quickens the intellect and will cure pleurisy. It
is certainly a first-rate chest herb, being strongly decongestant and expectorant, also
strengthens the heart and is frequently used in Switzerland to treat angina pectoris.
A tisane of leaves quickly dispels headaches. For an infusion, 2 teaspoonfuls of its
leaves are combined with a breakfast cupful of water.XXVI
Phytoconstituents: Aqueous-methanol leaves extract tests positive for the presence
of alkaloids, saponins, tannins, phenolics, coumarins and flavonoids [16]. Aqueous
extract contains substantial amount of vitexin, while the ethanol extract contains
rutin, vitexin, isovitexin, and kaempferol-6-glucoside [4]. Essential oil of leaves,
growing wild in central Iran, revealed the presence of 25 identified compounds,
representing 92.77% of the oil, with butyl-2-ethylhexylphthalate and 5,6,7,7a-
tetrahydro-4,4,7a-trimethyl-2(4H)-benzofuranone being the two main components
Viola odorata L. 1911

[1]. It also contains 166 cyclotide-like masses (cyclic cystine knotted macrocyclic
plant peptides) that vary in number with the tissue (leaves, petioles, flowers, runners,
and roots) and geographical locations in India [12]. Ethyl hexanoate and (2E,6Z)-
nona-2,6-dienol are specific volatile compounds of the French origin samples, while
(E,E)-hepta-2,4-dienal, hexanoic acid, limonene, tridecane, and eugenol were
specific of Egyptian samples [15].
Pharmacology: Hexane-, chloroform- and water-soluble extracts exhibit signifi-
cant antipyretic activity in yeast-induced pyrexia in rabbits; being more prominent
in the hexane-soluble fraction [10]. The plant shows weak antioxidant property [3],
and the aqueous-methanol extract produced fall in BP, and antidyslipidemic effect
[16]. Ethanol extract in vitro inhibited tyrosinase [4], and aqueous extract was
reported to exhibit significant diuretic activity in rats [9]. Naturally occurring macro-
cyclic peptides (cyclotides: Varv A, Varv F, and Cycloviolacin O2) in V. odorata
exhibited strong cytotoxic activities (cycloviolacin O2 being most potent), selec-
tively toxic to hematological chronic lymphocytic leukemia cells, poorly correlated
with the standard antitumor drugs in clinical use, doxorubicin, vincristine, cytara-
bine, melphalan, and topotecan [11]. Coexposure to cycloviolacin O2 increased
cellular internalization of doxorubicin in drug resistant breast cancer MCF-7/ADR
cells [8]. Cycloviolacin O2 also efficiently inhibits growth of S. enterica serovar,
Typhimurium LT2 and E. coli and shows bactericidal activity against K. pneumo-
niae and P. aeruginosa [13], and inhibits growth of S. aureus [18].
Clinical Studies: In a comparison of post-test with pre-test state of Iranian patients
with chronic insomnia, two drops containing 66 mg of VO in each nostril nightly
for 30-days improved Insomnia Severity Index (ISI) [6]. The findings were con-
firmed in a double-blind, three-armed RCT, in which VO improved sleep quality
more than almond oil and placebo, though all three significantly improved sleep
quality and ISI [7]. Supplementation with Violet syrup of standard treatment of
children, aged 2–12 years with intermittent asthma, significantly suppressed and
alleviated cough, with an inverse relationship with the age [14].
Mechanism of Action: The hypotensive effect is possibly mediated through
inhibition of membranous calcium channels, release of calcium from intracellular
stores and NO-mediated pathways; while the antihyperlipidemic effect is likely
mediated through inhibition of synthesis and/or absorption of lipids and antioxidant
activities [16]. Disruption of cell lipid membrane may play a crucial role in the
cytotoxic effect of cyclotide, cycloviolacin O2 [8, 17].
Human A/Es, Allergy and Toxicity: No known or reported A/Es or toxicity.
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: It is a very extensively used plant in the Indian subcontinent, for
common cold, flu and cough, even by the laymen. Its effectiveness has not been
formally tested, except in children with intermittent asthma, and patients with
chronic primary insomnia. More targeted clinical studies are needed to validate
many of the anecdotal clinical benefits of this plant.
1912 Viola odorata L.

References
1. Akhbari M, Batooli H, Kashi FJ. Composition of essential oil and biological
activity of extracts of Viola odorata L. from central Iran. Nat Prod Res.
2012;26:802–9.
2. Caius JF. Medicinal and poisonous plants of India. Capparids, Mignonettes,
Violets, Rockroses, Bixads. J Bombay Nat Hist Soc. 1939;41:123–42.
3. Ebrahimzadeh MA, Nabavi SM, Nabavi SF, et al. Antioxidant and free
radical scavenging activity of H. officinalis L. var. angustifolius, V. odorata,
B. hyrcana and C. speciosum. Pak J Pharm Sci. 2010;23:29–34.
4. Erdogan Orhan I, Senol FS, Aslan Erdem S, et al. Tyrosinase and
cholinesterase inhibitory potential and flavonoid characterization of Viola
odorata L. (sweet violet). Phytother Res. 2015;29:1304–10.
5. Feyzabadi Z, Ghorbani F, Vazani Y, Zarshenas MM. A critical review on
phytochemistry, pharmacology of Viola odorata L. and related multipotential
products in traditional Persian medicine. Phytother Res. 2017;31:1669–75.
6. Feyzabadi Z, Jafari F, Kamali SH, et al. Efficacy of Viola odorata in treat-
ment of chronic insomnia. Iran Red Crescent Med J. 2014;16:e17511.
7. Feyzabadi Z, Rezaeitalab F, Badiee S, et al. Efficacy of Violet oil, a
traditional Iranian formula, in patients with chronic insomnia: A random-
ized, double-blind, placebo-controlled study. J Ethnopharmacol. 2018;214:
22–8.
8. Gerlach SL, Rathinakumar R, Chakravarty G, et al. Anticancer and
chemosensitizing abilities of cycloviolacin 02 from Viola odorata and psyle
cyclotides from Psychotria leptothyrsa. Biopolymers. 2010;94:617–25.
9. Gujral ML, Saxena PN, Mishra SS. An experimental study of the
comparative activity of Indigenous diuretics. J Indian Med Assoc. 1955;
25:49.
10. Khattak SG, Gilani SN, Ikram M. Antipyretic studies on some indigenous
Pakistani medicinal plants. J Ethnopharmacol. 1985;14:45–51.
11. Lindholm P, Göransson U, Johansson S, et al. Cyclotides: a novel type of
cytotoxic agents. Mol Cancer Ther. 2002;1:365–9.
12. Narayani M, Chadha A, Srivastava S. Cyclotides from the Indian medicinal
plant Viola odorata (Banafsha): identification and characterization. J Nat
Prod. 2017;80:1972–80.
13. Pränting M, Lööv C, Burman R, et al. The cyclotide cycloviolacin O2 from
Viola odorata has potent bactericidal activity against Gram-negative
bacteria. J Antimicrob Chemother. 2010;65:1964–71.
14. Qasemzadeh MJ, Sharifi H, Hamedanian M, et al. The effect of Viola
odorata flower syrup on the cough of children with asthma: a double-blind,
randomized controlled trial. J Evid Based Complementary Altern Med.
2015;20:287–91.
15. Saint-Lary L, Roy C, Paris JP, et al. Volatile compounds of Viola odorata
absolutes: identification of odorant active markers to distinguish plants
originating from France and Egypt. Chem Biodivers. 2014;11:843–60.
Viola odorata L. 1913

16. Siddiqi HS, Mehmood MH, Rehman NU, Gilani AH. Studies on the
antihypertensive and antidyslipidemic activities of Viola odorata leaves
extract. Lipids Health Dis. 2012;11:6.
17. Svangård E, Burman R, Gunasekera S, et al. Mechanism of action of
cytotoxic cyclotides: cycloviolacin O2 disrupts lipid membranes. J Nat
Prod. 2007;70:643–7.
18. Zarrabi M, Dalirfardouei R, Sepehrizade Z, Kermanshahi RK. Comparison
of the antimicrobial effects of semipurified cyclotides from Iranian Viola
odorata against some of plant and human pathogenic bacteria. J Appl
Microbiol. 2013;115:367–75.
Viscum album L.
(Santalaceae)

Abstract
An evergreen, semiparasitic plant, native to Europe, central China, Japan, and
Iran. Mistletoe was chief of the Seven Sacred Herbs of the Druids and was
collected on the sixth day of the moon’s waning. Theopharastus and Dioscorides
considered it discutient, and Paracelsus recommended it in epilepsy and other
convulsive affections. In Europe, especially in Germany, water extracts of
Viscum album have been used as sole intervention or as adjunct to conventional
cancer therapies since 1910s. In Turkish traditional medicine, it is used for the
treatment of cardiovascular disorders, such as hypertension, tachycardia and
angina pectoris. Aqueous extracts are also utilized in traditional and official
medicine in Poland, among others, in treating hypertension and arthritis. In
Indian medicines, it is regarded as tonic, antispasmodic, narcotic, oxytocic,
emetic and purgative, and used to reduce splenic and hepatic enlargements, to
disperse swellings and in menorrhagia and hemorrhages. Like digitalis, it may be
given in palpitation or tumultuous action of the heart; and as an antispasmodic it
is also used in hysteria and epilepsy. In olden times mistletoe was the accepted
treatment for dropsy and epilepsy, although nowadays its commonest use is to
strengthen nerves and improve circulation. In Chinese medicine Hujisheng is the
whole plant of Viscum coloratum, or V. album. The herb is bitter and mild and
has antirheumatic, liver- and kidney-tonifying and muscle- and bone-fortifying
properties. It is used for the treatment of rheumatism, soreness and weakness of
lumber and knee, and for abnormal fecal movement. It is also described as Hu-
chi-seng, that is hypotensive, lactagogue, and anti-inflammatory. The lipophilic
extract shows the presence of triterpenoids: b-amyrin, b-amyrin acetate, lupeol,
lupeol acetate, b-sitosterol and stigmasterol, and the fatty acids: oleic acid,
linoleic acid, palmitic acid and stearic acid, in addition to viscin, betulinic acid,
oleanolic acid and ursolic acid. It also contains phenylpropanoids syringin,
syringenin-apiosylglucoside, eleutheroside E and the high molecular lectins and

© Springer Nature Switzerland AG 2020 1915

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_196
1916 Viscum album L.

viscotoxins. Mistletoe extracts, as complementary therapeutic regimen, report-

edly improved quality of life of cancer patients and reduced side effects of
conventional therapies in clinical trials.

Keywords


Banda Blondeau Dabaq

Hu-chi-seng
Mistel
Mistletoe
Muérdago



Muvezaj Őkseotu Rasna

Vernaculars: Urd.: Banda, Muvezaj; Hin.: Ban, Banda, Bhangra, Chuluka-banda;

San.: Rasna, Vandakah; Ben.: Mandala; Mar.: Banda, Haaddmodd; Ara.: Dabaq,
Dibk, Zabib-al-jabal; Chi.: 阔叶槲寄生, Hu-chi-seng, Hujisheng; Dut.: Maretak;
Eng.: Druid’s herb, European mistletoe, Mistletoe; Fin.: Misteli; Fre.: Blondeau,
Bois de la Sainte Croix, Bouchon, Glu, Gu, Gui, Gui blanc, Gui des feuillus,
Verquet, Vert de pommier; Ger.: Affolter, Gewöhnliche mistel, Heiligeskreuzholz,
Künst, Laubholzmistel, Mistel, Weißbeerige mistel, Weiße mistel; Ita.: Vischio
bianco, Vischio comune; Jap.: Yadorigi; Per.: Kishmish-kawali, Mawizak; Pol.:
Jemioła biała; Por.: Visco-branco; Rus.: Omela, Oмeлa бeлaя; Spa.: Almuérdago,
Arfuego, Liga, Liria, Marojo, Muérdago, Muérdago blanco, Tiña, Visca, Visco
viscol; Swe.: Mistel; Tur.: Őkseotu, Őkse out.
Description: An evergreen, semiparasitic plant, native to Europe, central China,
Japan, and Iran; 20–50 cm high growing chiefly on deciduous trees, most com-
monly on poplar, pear and the apple trees. Stem articulate, yellowish-green, glab-
rous; leaves oblong, obtuse, base attenuate, thick, coriaceous. It bears small
yellowish flowers in early spring (March–May), grouped at the tips of branches in
leaf axils, but better known are its pearly berries (fruits).XXVI,LXXIX The author of
Makhzan-al-Adwiya describes its berries smaller than the seed of Cicer arietinum,
green when fresh, but shriveled when dry, and brown in color, the contents are
moist and viscid, the seeds about the size of poppy seeds. The plant consists of
several branches, the leaves are like those of the pomegranate, and pale-green
(Figs. 1, 2 and 3).XL
Actions and Uses: Mistletoe was chief of the Seven Sacred Herbs of the Druids
and was collected on the sixth day of the moon’s waning. Theopharastus and
Dioscorides considered it discutient, and Paracelsus recommended it in epilepsy
and other convulsive affections.XL In Europe, especially in Germany, water extracts
of Viscum album have been used as sole intervention or as adjunct to conventional
cancer therapies since 1910s [25, 72, 82, 88]. Vysorel®/Isorel®/Iscador® are the
aqueous extracts of fresh mistletoe, and are recommended in all malignant diseases,
in ‘precancerous’ conditions, and for prevention of relapse [44]. Iscador® is the
oldest and the most commonly used oncological drug in Germany [27]. The drug is
supposed to be taken subcutaneously according to a rhythmic schedule. Novipharm
GmbH markets it as IsorelR and is approved in Austria since 1983, and is marketed
as Vysorel® in the Federal Republic of Germany, where it is approved since 1986.
Iscador Qu Spezial®, standardized for its lectin and viscotoxin content, is another
Viscum album L. 1917

Fig. 1 Viscum album, On Silver Birch Tree, Andrew Dunn, WikimediaCommons; ShareAlike
2.0 Generic CC BY-SA 2.0, https://commons.wikimedia.org/wiki/File:MistletoeInSilverBirch.jpg;
https://creativecommons.org/licenses/by-sa/2.0/deed.en; http://www.andrewdunnphoto.com

Fig. 2 Viscum album, On Apple Tree, Chilepine, WikimediaCommons; https://commons.wiki

media.org/wiki/File:Mistletoe.jpg
1918 Viscum album L.

Fig. 3 Viscum album, Fruits (The Berries), Nova, WikimediaCommons; ShareAlike 3.0 Unported
CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Viscum_album_fruit.jpg; https://creative
commons.org/licenses/by-sa/3.0/us/

product marketed by Weleda AG Schwäbisch Gmünd, Germany for unconventional

anticancer and immunomodulating therapy [111]. In 2003, the FDA approved
V. album extract for investigational use in solid tumors [72], though in 1983, the
American Cancer Society had strongly urged patients afflicted with cancer not to
participate in treatment with Iscador®. In Turkish traditional medicine, it is used for
the treatment of cardiovascular disorders, such as hypertension, tachycardia and
angina pectoris [99]. Aqueous extracts are also utilized in traditional and official
medicine in Poland, among others, in treating hypertension and arthritis [76].
The author of Makhzan-al-Adwiya described it as resolvent and laxative, a
solvent of corrupt humours which it withdraws from the system. Applied externally,
it promotes suppuration or causes dispersion of tumors or enlargements.XL In Indian
medicines, it is regarded as tonic, antispasmodic, narcotic, oxytocic, emetic and
purgative, and used to reduce splenic and hepatic enlargements, to disperse swellings
and in menorrhagia and hemorrhages. Like digitalis, it may be given in palpitation or
tumultuous action of the heart; and as an antispasmodic it is also used in hysteria and
epilepsy.LXXXI,CV In olden times mistletoe was the accepted treatment for dropsy
and epilepsy, although nowadays its commonest use is to strengthen nerves and
improve circulation. A good heart tonic and antisclerotic, it also reduces high blood
pressure. An infusion of leaves and young branches (diced) 60 g in 500 ml of
water is made by allowing it steep for only 30 min. The dosage is one tablespoonful
daily—increasing it to 3 if no improvement is shown. The juice from mistletoe
berries has its uses as well. Obstinate pimples will disappear if dabbed with the juice,
and it will also loosen stiff joints when massaged into the skin.XXVI The stems are
also used as hypotensive and lactagogue.LXXIX In Chinese medicine Hujisheng is
the whole plant of Viscum coloratum, or V. album. The herb is bitter and mild
and has antirheumatic, liver- and kidney-tonifying and muscle- and bone-fortifying
Viscum album L. 1919

properties. It is used for the treatment of rheumatism, soreness and weakness of

lumber and knee, and for abnormal fecal movement.XVIII It is also described as
Hu-chi-seng, that is hypotensive, lactagogue, and anti-inflammatory.LXVI
Phytoconstituents: The lipophilic extract showed the presence of triterpenoids:
b-amyrin, b-amyrin acetate, lupeol, lupeol acetate, b-sitosterol and stigmasterol,
and the fatty acids: oleic acid, linoleic acid, palmitic acid and stearic acid, in
addition to viscin, betulinic acid, oleanolic acid and ursolic acid [109]. It also
contains phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E
and the high molecular lectins and viscotoxins. Phenylpropanoids are found in all
alcoholic and aqueous extracts [113]. Biologically active compounds [90] and their
cytotoxicity are dependent on the manufacturing process, host tree, and the time of
harvest [9, 76]. For example, O-coumaric acid is only found in mistletoe hosted by
Quercus robur (European Oak tree), whereas digallic acid is only found in the plant
hosted by Acer plantanoides (known as Norway Maple). Presence of phenolic acids
is similar in mistletoes hosted by Malus domestica (Apple tree) and Pyrus com-
munis (Pear tree). Mistletoe hosted by Sorbus aucuparia contains considerable
contents of salicylic acid and vanillic acid [70]. Although mistletoe lectin
(ML) content of V. album extracts strongly correlate with their apoptosis-inducing
properties, the presence of these proteins does not guarantee its biological activity,
indicating the involvement of other components which may modulate ML cyto-
toxicity [9]. The triterpenic acids, such as betulinic (BA) and oleanolic (OA) acids
are also credited for its hypotensive and anticancer activities; OA contents are
reported to be *10 times higher than of BA and are highest in summer [115].
However, triterpenic acids being hydrophobic and low solubility are not extracted
in significant amounts in aqueous extracts [14]. Other reports hold phenolic acids,
phenylpropanoids and flavonoids with antioxidant and anti-inflammatory activities,
also responsible for hypotensive effect [76]. Unlike European mistletoe, no cyto-
toxic proteins were identified in the Korean mistletoe [46]. There are also seasonal
fluctuations in the chemical composition of mistletoe; maximal concentrations of
mistletoe lectins in leaves are in December and the viscotoxins in June [108].
Mistletoe tea made by maceration and infusion at room temperature showed dif-
ferences in the chemical constituents of the tea. Mistletoe lectins are inactivated by
thermal degradation but they were extracted in infusion by maceration. Infusion
extracts contained 43% of flavonoid-like substances and maceration only 31%.
Oleanolic acid and BA are extracted in higher concentrations (less than 2%)
in infusions compared with macerates. Phenylpropane derivatives are com-
pletely extracted by infusion and maceration; however, neither method dissolved
viscotoxins [41].
Pharmacology: Mistletoe extracts express significant in vivo antitumor activity
against murine tumors, Lewis lung carcinoma, colon adenocarcinoma and mammary
adenocarcinoma [45]. A toxic lectin, viscumin is regarded to play a major part in the
cytotoxic activity of mistletoe extracts [78]. Methanol extract downregulates
expression of Hsp27 and 14-3-3 chaperone proteins and induces apoptosis [107].
Cytotoxicity of the whole plant extracts produced from mistletoes grown on different
1920 Viscum album L.

host trees on cultured human lymphocytes is host tree-specific [10]. Also, the
cytotoxic properties of extracts, whose extent varied with the host tree, do not always
correlate with the corresponding mistletoe lectin content [39]. However, inhibition
of pediatric medulloblastoma cells by V. album extracts was due to cell death
through apoptosis and the growth-inhibition correlated with lectin content of the
preparation [117]. Lectin-rich mistletoe extracts produce immune-stimulation and
significantly enhance natural killer (NK)-cell-mediated glioblastoma cell lysis,
reduce the migratory and invasive potential of glioblastoma cells. In xenograft
glioblastoma mouse model, both pretreatment of tumor cells and intratumoral
therapy of subcutaneously growing glioblastoma cells delayed tumor growth [83].
Nontoxic concentrations of viscotoxins also increase NK cell-mediated killing of
tumor cells but spare nontarget cells from NK lysis [101]. Topical application of
V. album agglutinin-I twice a week is effective in sustaining the elevation of the
number and activity of peripheral blood NK cells [31]. Pretreatment of mice-bearing
Ehrlich ascites carcinoma with the extract caused a significant reduction in the
incidence of cancer, and also reduced numbers of EAC cells in animals with
developed carcinoma, and improved activities of antioxidative enzymes [13]. Pre-
treatment and administration of water extract five days after tumor induction inhib-
ited lung colony formation induced by B16F10 melanoma cells [2]. Intraperitoneal
injection of 1 mg Iscador® completely inhibited MCA-induced sarcoma formation in
mice and sarcoma-induced death [60, 61], and reduced radiation and CP-induced
leukocytopenia in animals [59]. Iscador® was also cytotoxic to animal tumor cells
such as Dalton’s Lymphoma Ascites (DLA) cells and Ehrlich ascites cells in vitro and
inhibited growth of lung fibroblasts, Chinese hamster ovary cells and human
nasopharyngeal carcinoma cells at very low concentrations. Administration of
Iscador® given either simultaneously, after tumor development or when given pro-
phylactically, reduced ascites tumors and solid tumors produced by DLA cells and
Ehrlich ascites cells [62]. Mistletoe recombinant lectin (aviscumine) exhibited
immunomodulatory and cytotoxic activity in phase I clinical studies, which appears
to have a positive effect on disease stabilization [118]. Viscin, BA, OA and ursolic
acid inhibit growth and induce apoptotic cell death in leukemia cells [109].
Dietary supplementation with 6.25% extract by weight for 9-days significantly
reduced diabetes-associated hyperphagia and polydipsia [100]. Methanol extract of
African mistletoe produced antihyperglycemic effect in STZ-diabetic rats and
increased HDL-C [1], while ethanol extract of Turkish mistletoe was reported to
increase blood glucose level in both normal and STZ-diabetic rats [104]. The leaves
extract did not lower blood glucose of normal rats but produced significant decrease
in STZ-diabetic rats. However, the insulin levels were increased in both normal
(>92%), and diabetic rats (>81%), and a mild suppression of glucagon in diabetic
rats [21]. Antihyperglycemic and antioxidant activity of aqueous and ethanol
extracts in STZ-diabetic rats depended on the host plant [80]. Insulin secretory
activity did not depend upon the use of heat during extract preparation and was not
mediated by lectins [26]. Inhibition of a-glucosidase by aqueous extract has also
been reported [79]. Korean whole plant extract exhibited pancreatic antilipase and
anti-PDE activities [66].
Viscum album L. 1921

Flavonoid fractions have shown remarkable antinociceptive and anti-inflam-

matory activities without inducing any apparent acute toxicity as well as gastric
damage [81]. The lectin, agglutinin-I which possesses antitumoral properties also
induces apoptosis of pre-activated neutrophils at a concentration that does not
induce a proinflammatory response and can inhibit LPS-induced proinflammatory
response in vivo [65]. However, subcutaneous injection of mistletoe extracts results
in dose-dependent local inflammatory reaction at the injection site. A dose-
dependent decrease of cellular viability and an increase of proinflammatory
cytokines IL-1a, IL-6, and TNFa as well as the release of IL-8 have been
demonstrated with some extracts [24]. In B16F1 melanoma implanted C57BL6
mice, inhibition of tumor growth by the extract was associated with enhancement of
splenocyte proliferation and upregulation of IL-12 secretion [110]. Three diaryl-
heptanoids and (+)-medioresinol significantly inhibited LPS-stimulated production
of TNF-a, IL-6, and IL-12p40 [77]. Aqueous extract is the most selective in vitro
inhibitor of HPIV-2 replication by more than 99% without any toxic effect on host
cells [42]. Both lyophilized aqueous and methanol leaf extracts showed
NO-dependent cardioprotection against I/R myocardial injury [99], and the aqueous
extract protected against isoproterenol-induced heart failure in rats [43]. Lyophi-
lized aqueous extract of Korean mistletoe lowered serum TC, LDL-C, and TGs,
improved HOMA-IR, and elevated HDL-C in ovariectomized rats with dyslipi-
demia [51].
Clinical Studies: Phytopreparations of mistletoe are used as complementary
therapeutic regimens for cancer therapy [10, 95], with both immunostimulatory and
DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic
properties at higher concentrations [10]. Mistletoe extracts reportedly improved
quality of life of cancer patients and reduced side effects of conventional therapies
in clinical trials, especially in coping fatigue, sleep, lack of energy and appetite,
exhaustion, nausea, vomiting, depression, anxiety, ability to work, and emotional
and functional well-being, and also in some cases pain, diarrhea, and general
performance [7, 16, 22, 29, 49, 50, 52, 67, 73]. Meta-analysis of clinical studies
suggests that supplemental treatment of cancer patients with mistletoe extracts
(Iscador® and Helixor®) enhances survival [47, 74, 82]. Twenty-five patients with
primary neoplasms of the ovary, and 20 women being in the advanced stages III
and IV, postoperative treatment with Iscador® had 100% five-year survival rates in
stages I and II, 23% in stage III and 0% in stage IV patients [36]. Survival rates are
significantly improved with addition of postoperative use of Iscador® in patients
with breast carcinoma, comparative to conventional treatment alone [68] and ADRs
of conventional treatment are significantly reduced [5, 28, 30]. However, in one
study from Germany of early stage breast cancer patients, additional mistletoe
therapy with chemotherapy did not influence the frequency of relapse or metastasis
within 5-years. Neutropenia occurred in 10% patients supplemented with mistletoe
therapy compared to 25% on chemotherapy alone, though statistically insignificant
[103].
1922 Viscum album L.

Patients with colorectal cancers treated with a combination of chemotherapy and

Isorel® had median survival significantly better and a cumulative proportion survival
superior to those of the patients receiving only postoperative chemotherapy [12], and
significantly less cancer-related fatigue postchemotherapy or radiochemotherapy [6].
An epidemiological cohort study involving prospective nonrandomized and ran-
domized matched-pair studies on 10,226 patients with carcinoma of the colon,
rectum, or stomach; breast carcinoma with or without axillary or remote metastases;
or small cell or nonsmall cell bronchogenic carcinoma, with 1,668 patients treated
with Iscador® and 8,475 as untreated controls, demonstrated that patients treated
with Iscador® had 40% longer survival than the controls of all cancer patients [27].
A 44-year-old man with follicular non-Hodgkin lymphoma and several cervical,
axillary, inguinal and infrainguinal lymphomas, continually treated with Iscador®
for 12-years, had improved quality of life throughout and complete regional lym-
phoma regression, but cessation of treatment led to progression [58]. It was observed
in B-cell lymphoma patients that half of the patients (6/12) with long-term treatment
had a continuous complete remission, whereas only 2/15 patients with short-term
treatment had a complete remission [55]. However, treatment of 14 patients with
earlier untreated histologically verified renal adenocarcinoma stage IV and lung
metastases did not significantly improve quality of life or survival of the patients
[53]. Intravesical injection of mistletoe extract in patients with superficial urothelial
bladder reduced the recurrence rate to 33% of the control group of patients who were
treated with adjuvant BCG [18]. Adjuvant treatment with s.c. mistletoe prolonged
postrelapse disease-free survival after second relapse in a small number (20) of
osteosarcoma patients [69]. In a phase III, prospective, open-label study, subcuta-
neous injections of V. album extracts, in a dose-escalating manner highly signifi-
cantly improved overall survival over a 12-month period of patients with locally
advanced or metastatic pancreatic cancer [102]. Adjunct intratumoral-application of
mistletoe improved median survival of 11 months of 39 patients with advanced,
inoperable pancreatic cancer [88].
Perioperative use of Isorel® improved immune competence and overall health
status of cancer patients undergoing surgery for carcinomas [19], prevented
surgery-associated inhibition of oxidative burst, minimizing the immune suppres-
sion triggered by anesthesia and operation stress [8, 11], and enhanced humoral and
cellular immune responses in cancer patients [23]. Concurrent treatment with
Iscador® also reduces adverse effects of radiotherapy and chemotherapy on
microcirculation and the immune system, and accelerates reconstitution processes
of patients with ear, nose and throat carcinomas [54]. In a phase I/II study mistletoe
extract induced immunomodulation in HIV-positive and healthy individuals and
inhibited progression of HIV disease [25]. Monotherapy with mistletoe extracts of
patients with chronic hepatitis C for one year significantly reduced the viral load
and liver inflammation [105, 106]. Injections (i.p.) of Iscador® in patients with
ascites due to end-stage malignancies significantly increased median time-interval
between peritoneal punctures to drain fluid due to reduced water accumulation [3].
A 4½-year-old girl with childhood absence epilepsy and delayed global develop-
ment became and remained seizure-free for 12-months follow-up, after mistletoe
Viscum album L. 1923

therapy was added to conventional treatment [112]. A homeopathy mother tincture

of V. album significantly lowered BP and TGs after 12-weeks of treatment of
hypertensive patients [84].
Mechanism of Action: Mechanisms for the antitumor activity involve apoptosis,
inhibition of angiogenesis and immunomodulation [17, 32, 33, 97, 98, 116]. Initial
inhibition of proliferation followed by induction of apoptosis is the main mecha-
nism of cell death [34, 35, 56, 91]; antiangiogenic effect through multiple inter-
dependent processes, such as gene expression, signal processing, and enzyme
activities is also involved [86]. Higher dosages of the extract up to a dose of
1,500 mg did not cause immunosuppression in humans [48], while Mansky et al.
[72] reported that preclinical data suggest immunostimulatory and cytotoxic effects.
Treatment of cancer patients with mistletoe extract leads to increase in cytokine
levels (IFN-c and IL-2), suggesting modification of cell-mediated immunity [57].
Immunomodulatory activities of mistletoe extracts differ according to their tree
origin. Mistletoe from apple or pine increases in vitro antitumor activity of activated
human macrophages [75], whereas a fermented mistletoe extract from V. album
grown on pine trees was less cytotoxic to peripheral blood mononuclear cells than
other preparations [96]. In addition to a direct cytotoxic effect, activation of mac-
rophages may contribute to the overall antitumor activity of the extract [63]. The
anti-inflammatory effect is exerted by selective downregulation of COX-2-mediated
cytokine-induced secretion of PGE2 via selective inhibition of COX-2 without
modulating COX-1 expression [37, 87].
Human A/Es, Allergy and Toxicity: No severe adverse effects have been reported
during many years of use by thousands of patients, and Iscador® has been shown to
be essentially safe [71, 89]. Local reactions and increased body temperature are
expected A/Es after subcutaneous mistletoe injection. However, some patients
treated with mistletoe extract developed severe anaphylactic reaction after the
injection [4, 40]. A multicenter, observational study involving 1,923 German cancer
patients treated with subcutaneous mistletoe extracts, reported moderate to severe
ADRs in 45.1 and 4.2%, respectively, that were nonserious and more common in
women [92]. Another study showed that patients were almost two times less likely
to experience an ADR to intravenous compared to subcutaneous use [93]. Intra-
venous use of aqueous extract from pine-mistletoe in German patients with
advanced cancers, once weekly for nine-weeks was well tolerated up to a dose of
2,000 mg, except for mild to moderate fever with the highest dose and one allergic
reaction [38]. Although ADRs of intratumoral injection were mild, such as body
temperature or immune-related, but the frequency was 3X and 5X higher than for
subcutaneous and intravenous applications, respectively. Immune-related ADRs
such as pyrexia and local inflammatory reactions are suggested to be critical for
tumor response [94].
Animal Toxicity: A dose-dependent and significant decrease in platelets count in
rats was observed after single dose of aqueous extract of mistletoe grown on kola
(Kola nitida) [64].
1924 Viscum album L.

CYP450 and Potential for Drug-Herb Interactions: Mistletoe inhibits CYP3A4

in vitro, but clinically relevant systemic or intestinal interactions are suggested to be
unlikely [15, 20]. Combined V. album extract with trastuzumab did not inhibit
in vitro antitumor efficacy of trastuzumab of Her-2 positive human breast carcinoma
cell line SK-BR-3 and showed additive inhibitory effects on VEGF secretion [114].
However, use of V. album with Hypericum perforatum (H. perforatum is an inducer
of CYP3A4 and CYP1A2) has resulted in serious herb-drug interactions, resulting
in transplant rejection, delayed emergence from anesthesia, cardiovascular collapse,
renal and liver toxicity, cardiotoxicity, bradycardia, hypovolemic shock, inflam-
matory reactions with organ fibrosis and death. Most commonly interacting drugs
were antiplatelet and anticoagulant drugs [85].
Commentary: More than a century of use of mistletoe extracts for the treatment of
cancers has established its efficacy, especially as an adjunct to conventional therapy.
However, its use in cancer has eclipsed any of its other therapeutic uses.

References
1. Adaramoye O, Amanlou M, Habibi-Rezaei M, et al. Methanolic extract of
African mistletoe (Viscum album) improves carbohydrate metabolism and
hyperlipidemia in streptozotocin-induced diabetic rats. Asian Pac J Trop
Med. 2012;5:427–33.
2. Antony S, Kuttan R, Kuttan G. Effect of Viscum album in the inhibition of
lung metastasis in mice induced by B16F10 melanoma cells. J Exp Clin
Cancer Res. 1997;16:159–62.
3. Bar-Sela G, Goldberg H, Beck D, et al. Reducing malignant ascites
accumulation by repeated intraperitoneal administrations of a Viscum album
extract. Anticancer Res. 2006;26:709–13.
4. Bauer C, Oppel T, Ruëff F, Przybilla B. Anaphylaxis to viscotoxins of
mistletoe (Viscum album) extracts. Ann Allergy Asthma Immunol. 2005;94:
86–9.
5. Bock PR, Friedel WE, Hanisch J, et al. Efficacy and safety of long-term
complementary treatment with standardized European mistletoe extract
(Viscum album L.) in addition to the conventional adjuvant oncologic therapy
in patients with primary non-metastasized mammary carcinoma. Results of a
multicenter, comparative, epidemiological cohort study in Germany and
Switzerland. Arzneimittelforschung. 2004;54:456–66 (German).
6. Bock PR, Hanisch J, Matthes H, Zänker KS. Targeting inflammation in
cancer-related-fatigue: a rationale for mistletoe therapy as supportive care in
colorectal cancer patients. Inflamm Allergy Drug Targets. 2014;13:105–11.
7. Brandenberger M, Simões-Wüst AP, Rostock M, et al. An exploratory
study on the quality of life and individual coping of cancer patients during
mistletoe therapy. Integr Cancer Ther. 2012;11:90–100.
Viscum album L. 1925

8. Büssing A, Bischof M, Hatzmann W, et al. Prevention of surgery-induced

suppression of granulocyte function by intravenous application of a fermented
extract from Viscum album L. in breast cancer patients. Anticancer Res. 2005;
25:4753–7.
9. Büssing A, Schietzel M. Apoptosis-inducing properties of Viscum album
L. extracts from different host trees, correlate with their content of toxic
mistletoe lectins. Anticancer Res. 1999;19:23–8.
10. Büssing A, Suzart K, Bergmann J, et al. Induction of apoptosis in human
lymphocytes treated with Viscum album L. is mediated by the mistletoe
lectins. Cancer Lett. 1996;99:59–72.
11. Büssing A. Immune modulation using mistletoe (Viscum album L.) extracts
Iscador. Arzneimittelforschung. 2006;56:508–15 (Review).
12. Cazacu M, Oniu T, Lungoci C, et al. The influence of Isorel on the
advanced colorectal cancer. Cancer Biother Radiopharm. 2003;18:27–34.
13. Cebović T, Spasić S, Popović M. Cytotoxic effects of the Viscum album L.
extract on Ehrlich tumour cells in vivo. Phytother Res. 2008;22:1097–103.
14. Delebinski CI, Twardziok M, Kleinsimon S, et al. A natural combination
extract of Viscum album L. containing both triterpene acids and lectins is
highly effective against AML in vivo. PLoS One. 2015;10:e0133892.
15. Doehmer J, Eisenbraun J. Assessment of extracts from mistletoe (Viscum
album) for herb-drug interaction by inhibition and induction of cytochrome
P450 activities. Phytother Res. 2012;26:11–7.
16. Eisenbraun J, Scheer R, Kröz M, et al. Quality of life in breast cancer
patients during chemotherapy and concurrent therapy with a mistletoe
extract. Phytomedicine. 2011;18:151–7.
17. Elluru S, Van Huyen JP, Delignat S, et al. Molecular mechanisms
underlying the immunomodulatory effects of mistletoe (Viscum album L.)
extracts Iscador. Arzneimittel-forschung. 2006;56:461–6 (Review).
18. Elsässer-Beile U, Leiber C, Wolf P, et al. Adjuvant intravesical treatment
of superficial bladder cancer with a standardized mistletoe extract. J Urol.
2005;174:76–9.
19. Enesel MB, Acalovschi I, Grosu V, et al. Perioperative application of the
Viscum album extract Isorel in digestive tract cancer patients. Anticancer
Res. 2005;25:4583–90.
20. Engdal S, Nilsen OG. In vitro inhibition of CYP3A4 by herbal remedies
frequently used by cancer patients. Phytother Res. 2009;23:906–12.
21. Eno AE, Ofem OE, Nku CO, et al. Stimulation of insulin secretion by
Viscum album (mistletoe) leaf extract in streptozotocin-induced diabetic
rats. Afr J Med Med Sci. 2008;37:141–7.
22. Evans M, Bryant S, Huntley AL, Feder G. Cancer patients’ experiences of
using mistletoe (Viscum album): a qualitative systematic review and
synthesis. J Altern Complement Med. 2016;22:134–44.
23. Gardin NE. Immunological response to mistletoe (Viscum album L.) in
cancer patients: a four-case series. Phytother Res. 2009;23:407–11.
1926 Viscum album L.

24. Gorter RW, Joller P, Stoss M. Cytokine release of a keratinocyte model

after incubation with two different Viscum album L. extracts. Am J Ther.
2003;10:40–7.
25. Gorter RW, van Wely M, Reif M, Stoss M. Tolerability of an extract of
European mistletoe among immunocompromised and healthy individuals.
Altern Ther Health Med. 1999;5:47–8.
26. Gray AM, Flatt PR. Insulin-secreting activity of the traditional antidiabetic
plant Viscum album (mistletoe). J Endocrinol. 1999;160:409–14.
27. Grossarth-Maticek R, Kiene H, Baumgartner SM, Ziegler R. Use of Iscador,
an extract of European mistletoe (Viscum album), in cancer treatment:
prospective nonrandomized and randomized matched-pair studies nested
within a cohort study. Altern Ther Health Med. 2001;7:57–66, 68–72, 74–6
passim.
28. Grossarth-Maticek R, Ziegler R. Prospective controlled cohort studies on
long-term therapy of breast cancer patients with a mistletoe preparation
(Iscador). Forsch Komplementmed. 2006;13:285–92.
29. Grossarth-Maticek R, Ziegler R. Prospective controlled cohort studies on
long-term therapy of ovarian cancer patients with mistletoe (Viscum album L.)
extracts iscador. Arzneimittelforschung. 2007;57:665–78.
30. Grossarth-Maticek R, Ziegler R. Randomised and nonrandomised prospec-
tive controlled cohort studies in matched-pair design for the long-term
therapy of breast cancer patients with a mistletoe preparation (Iscador): a
re-analysis. Eur J Med Res. 2006;11:485–95.
31. Hajto T, Hostanska K, Saller R. Mistletoe therapy from the pharmacologic
perspective. Forsch Komplementarmed. 1999;6:186–94 (Article in German).
32. Hajto T. Immunomodulatory effects of iscador: a Viscum album prepara-
tion. Oncology. 1986;43 Suppl 1:51–65.
33. Hamprecht K, Handgretinger R, Voetsch W, Anderer FA. Mediation of
human NK-activity by components in extracts of Viscum album. Int J
Immunopharmacol. 1987;9:199–209.
34. Harmsma M, Grommé M, Ummelen M, et al. Differential effects of Viscum
album extract IscadorQu on cell cycle progression and apoptosis in cancer
cells. Int J Oncol. 2004;25:1521–9.
35. Harmsma M, Ummelen M, Dignef W, et al. Effects of mistletoe (Viscum
album L.) extracts Iscador on cell cycle and survival of tumor cells.
Arzneimittelforschung. 2006;56:474–82.
36. Hassauer W, Gutsch J, Burkhardt R. What prospects of success does
Iscador therapy offer in advanced ovarian cancer? Onkologie. 1979;2:28–
36 (German).
37. Hegde P, Maddur MS, Friboulet A, Bayry J, Kaveri SV. Viscum album
exerts anti-inflammatory effect by selectively inhibiting cytokine-induced
expression of cyclooxygenase-2. PLoS ONE. 2011;6:e26312.
Viscum album L. 1927

38. Huber R, Schlodder D, Effertz C, Rieger S, Tröger W. Safety of intra-

venously applied mistletoe extract—results from a phase I dose escalation
study in patients with advanced cancer. BMC Complement Altern Med.
2017;17:465.
39. Hunziker-Basler N, Zuzak TJ, Eggenschwiler J, et al. Prolonged cytotoxic
effect of aqueous extracts from dried Viscum album on bladder cancer
cells. Pharmazie. 2007;62:237–8.
40. Hutt N, Kopferschmitt-Kubler M, Cabalion J, et al. Anaphylactic reactions
after therapeutic injection of mistletoe (Viscum album L.). Allergol Immuno-
pathol. (Madr) 2001;29:201–3.
41. Jäger S, Beffert M, Hoppe K, et al. Preparation of herbal tea as infusion or
by maceration at room temperature using mistletoe tea as an example. Sci
Pharm. 2011;79:145–55.
42. Karagöz A, Onay E, Arda N, Kuru A. Antiviral potency of mistletoe
(Viscum album ssp. album) extracts against human parainfluenza virus type
2 in Vero cells. Phytother Res. 2003;17:560–2.
43. Karagöz A, Kesici S, Vural A, et al. Cardioprotective effects of Viscum
album L. ssp. album (Loranthaceae) on isoproterenol-induced heart failure
via regulation of the nitric oxide pathway in rats. Anatol J Cardiol. 2016;16:
923–30.
44. Kast A, Hauser SP. Vysorel/Isorel—cancer drug from Viscum album. Docu-
mentation No. 20. Schweiz Rundsch Med Prax. 1990;79:332–4 (German).
45. Khwaja TA, Dias CB, Pentecost S. Recent studies on the anticancer
activities of mistletoe (Viscum album) and its alkaloids. Oncology. 1986;43
Suppl 1:42–50 (Review).
46. Khwaja TA, Varven JC, Pentecost S, Pande H. Isolation of biologically
active alkaloids from Korean mistletoe Viscum album, coloratum. Expe-
rientia. 1980;36:599–600.
47. Kienle GS, Glockmann A, Schink M, Kiene H. Viscum album L. extracts
in breast and gynaecological cancers: a systematic review of clinical and
preclinical research. J Exp Clin Cancer Res. 2009;28:79.
48. Kienle GS, Grugel R, Kiene H. Safety of higher dosages of Viscum album
L. in animals and humans—systematic review of immune changes and
safety parameters. BMC Complement Altern Med. 2011;11:72.
49. Kienle GS, Kiene H. Review article: influence of Viscum album L (European
mistletoe) extracts on quality of life in cancer patients: a systematic review of
controlled clinical studies. Integr Cancer Ther. 2010;9:142–57.
50. Kim KC, Yook JH, Eisenbraun J, et al. Quality of life, immunomod-
ulation and safety of adjuvant mistletoe treatment in patients with gastric
carcinoma—a randomized, controlled pilot study. BMC Complement
Altern Med. 2012;12:172.
51. Kim MJ, Park JH, Kwon DY, et al. The supplementation of Korean
mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis,
and muscle loss in ovariectomized rats. Exp Biol Med (Maywood). 2015;
240:477–87.
1928 Viscum album L.

52. Kirsch A, Hajto T. Case reports of sarcoma patients with optimized lectin-
oriented mistletoe extract therapy. J Altern Complement Med. 2011;17:
973–9.
53. Kjaer M. Misteltoe (Iscador) therapy in stage IV renal adenocarcinoma.
A phase II study in patients with measurable lung metastases. Acta Oncol.
1989;28:489–94.
54. Klopp R, Schmidt W, Werner E, et al. Influence of complementary Viscum
album (Iscador) administration on microcirculation and immune system of
ear, nose and throat carcinoma patients treated with radiation and chemother-
apy. Anticancer Res. 2005;25:601–10.
55. Kovacs E, Kuehn JJ. Measurements of IL-6, soluble IL-6 receptor and
soluble gp130 in sera of B-cell lymphoma patients. Does Viscum album
treatment affect these parameters? Biomed Pharmacother. 2002;56:152–8.
56. Kovacs E, Link S, Toffol-Schmidt U. Cytostatic and cytocidal effects of
mistletoe (Viscum album L.) quercus extract Iscador. Arzneimittelforschung.
2006;56:467–73.
57. Kovacs E. Serum levels of IL-12 and the production of IFN-gamma,
IL-2 and IL-4 by peripheral blood mononuclear cells (PBMC) in cancer
patients treated with Viscum album extract. Biomed Pharmacother. 2000;
54:305–10.
58. Kuehn JJ. Favorable long-term outcome with mistletoe therapy in a
patient with centroblastic-centrocytic non-Hodgkin lymphoma. Dtsch Med
Wochenschr. 1999;124:1414–8 (German).
59. Kuttan G, Kuttan R. Reduction of leukopenia in mice by “Viscum album”
administration during radiation and chemotherapy. Tumori. 1993;79:74–6.
60. Kuttan G, Menon LG, Antony S, Kuttan R. Anticarcinogenic and
antimetastatic activity of Iscador. Anticancer Drugs. 1997;8 Suppl 1:S15–6.
61. Kuttan G, Menon LG, Kuttan R. Prevention of 20-methylcholanthrene-
induced sarcoma by a mistletoe extract, Iscador. Carcinogenesis. 1996;17:
1107–9.
62. Kuttan G, Vasudevan DM, Kuttan R. Effect of a preparation from Viscum
album on tumor development in vitro and in mice. J Ethnopharmacol.
1990;29:35–41.
63. Kuttan G. Tumoricidal activity of mouse peritoneal macrophages treated
with Viscum album extract. Immunol Invest. 1993;22:431–40.
64. Ladokun O, Ojezele M, Arojojoye O. Comparative study on the effects of
aqueous extracts of Viscum album (mistletoe) from three host plants on
hematological parameters in albino rats. Afr Health Sci. 2015;15:606–12.
65. Lavastre V, Cavalli H, Ratthe C, Girard D. Anti-inflammatory effect of
Viscum album agglutinin-I (VAA-I): induction of apoptosis in activated
neutrophils and inhibition of lipopolysaccharide-induced neutrophilic
inflammation in vivo. Clin Exp Immunol. 2004;137:272–8.
66. Lee YM, Kim YS, Lee Y, et al. Inhibitory activities of pancreatic lipase
and phosphodiesterase from Korean medicinal plant extracts. Phytother
Res. 2012;26:778–82.
Viscum album L. 1929

67. Legnani W. Mistletoe in conventional oncological practice: exemplary

cases. Integr Cancer Ther. 2008;7:162–71.
68. Leroi R. Postoperative Viscum album therapy after surgery of breast
neoplasms. Helv Chir Acta. 1977;44:403–14 (German).
69. Longhi A, Reif M, Mariani E, Ferrari S. A randomized study on postrelapse
disease-free survival with adjuvant mistletoe versus oral etoposide in
osteosarcoma patients. Evid Based Complement Alternat Med. 2014;2014:
210198.
70. Luczkiewicz M, Cisowski W, Kaiser P, et al. Comparative analysis of
phenolic acids in mistletoe plants from various hosts. Acta Pol Pharm.
2001;58:373–9.
71. Maldacker J. Preclinical investigations with mistletoe (Viscum album L.)
extract Iscador. Arzneimittelforschung. 2006;56:497–507 (Review).
72. Mansky PJ, Grem J, Wallerstedt DB, et al. Mistletoe and gemcitabine in
patients with advanced cancer: a model for the phase I study of botanicals
and botanical-drug interactions in cancer therapy. Integr Cancer Ther.
2003;2:345–52.
73. Matthes H, Friedel WE, Bock PR, Zänker KS. Molecular mistletoe therapy:
friend or foe in established antitumor protocols? A multicenter, controlled,
retrospective pharmacoepidemiological study in pancreas cancer. Curr Mol
Med. 2010;10:430–9.
74. Melzer J, Iten F, Hostanska K, Saller R. Efficacy and safety of mistletoe
preparations (Viscum album) for patients with cancer diseases. A systematic
review. Forsch Komplementmed. 2009;16:217–26.
75. Mossalayi MD, Alkharrat A, Malvy D. Nitric oxide involvement in the
antitumor effect of mistletoe (Viscum album L.) extracts Iscador on human
macrophages. Arzneimittelforschung. 2006;56:457–60.
76. Nazaruk J, Orlikowski P. Phytochemical profile and therapeutic potential
of Viscum album L. Nat Prod Res. 2016;30:373–85.
77. Nhiem NX, Kiem PV, Minh CV, et al. Diarylheptanoids and flavonoids
from Viscum album inhibit LPS-stimulated production of proinflammatory
cytokines in bone marrow-derived dendritic cells. J Nat Prod. 2013;76:
495–502.
78. Olsnes S, Stirpe F, Sandvig K, Pihl A. Isolation and characterization of
viscumin, a toxic lectin from Viscum album L. (mistletoe). J Biol Chem.
1982;257:13263–70.
79. Onal S, Timur S, Okutucu B, Zihnioğlu F. Inhibition of alpha-glucosidase
by aqueous extracts of some potent antidiabetic medicinal herbs. Prep
Biochem Biotechnol. 2005;35:29–36.
80. Orhan DD, Aslan M, Sendogdu N, et al. Evaluation of the hypoglycemic
effect and antioxidant activity of three Viscum album subspecies (European
mistletoe) in streptozotocin-diabetic rats. J Ethnopharmacol. 2005;98:
95–102.
1930 Viscum album L.

81. Orhan DD, Küpeli E, Yesilada E, Ergun F. Anti-inflammatory and

antinociceptive activity of flavonoids isolated from Viscum album ssp.
album. Z Naturforsch. 2006;61:26–30.
82. Ostermann T, Raak C, Büssing A. Survival of cancer patients treated with
mistletoe extract (Iscador): a systematic literature review. BMC Cancer.
2009;9:451.
83. Podlech O, Harter PN, Mittelbronn M, et al. Fermented mistletoe extract as
a multimodal antitumoral agent in gliomas. Evid Based Complement
Alternat Med. 2012;2012:501796.
84. Poruthukaren KJ, Palatty PL, Baliga MS, Suresh S. Clinical evaluation of
Viscum album mother tincture as an antihypertensive: a pilot study. J Evid
Based Complementary Altern Med. 2014;19:31–5.
85. Posadzki P, Watson L, Ernst E. Herb-drug interactions: an overview of
systematic reviews. Br J Clin Pharmacol. 2013;75:603–18.
86. Sagar SM, Yance D, Wong RK. Natural health products that inhibit
angiogenesis: a potential source for investigational new agents to treat
cancer—Part 1. Curr Oncol. 2006;13:14–26.
87. Saha C, Hegde P, Friboulet A, Bayry J, Kaveri SV. Viscum album-
mediated COX-2 inhibition implicates destabilization of COX-2 mRNA.
PLoS One. 2015;10:e0114965.
88. Schad F, Atxner J, Buchwald D, et al. Intratumoral mistletoe (Viscum
album L.) therapy in patients with unresectable pancreas carcinoma: a
retrospective analysis. Integr Cancer Ther. 2014;13:332–40.
89. Schad F, Thronicke A, Merkle A, Matthes H, Steele ML. Immune-related
and adverse drug reactions to low versus high initial doses of Viscum
album L. in cancer patients. Phytomedicine. 2017;36:54–8.
90. Schaller G, Urech K, Grazi G, Giannattasio M. Viscotoxin composition of
the three European subspecies of Viscum album. Planta Med. 1998;64:
677–8.
91. Seifert G, Jesse P, Laengler A, et al. Molecular mechanisms of mistletoe
plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo
and in vitro. Cancer Lett. 2008;264:218–28.
92. Steele ML, Axtner J, Happe A, et al. Adverse drug reactions and expected
effects to therapy with subcutaneous mistletoe extracts (Viscum album L.)
in cancer patients. Evid Based Complement Alternat Med. 2014;2014:
724258.
93. Steele ML, Axtner J, Happe A, et al. Safety of intravenous application of
mistletoe (Viscum album L.) preparations in oncology: an observational
study. Evid Based Complement Alternat Med. 2014;2014:236310.
94. Steele ML, Axtner J, Happe A, et al. Use and safety of intratumoral
application of European mistletoe (Viscum album L.) preparations in
oncology. Integr Cancer Ther. 2015;14:140–8.
95. Stein GM, Berg PA. Characterisation of immunological reactivity of
patients with adverse effects during therapy with an aqueous mistletoe
extract. Eur J Med Res. 1999;4:169–77.
Viscum album L. 1931

96. Stein GM, Berg PA. Mistletoe extract-induced effects on immunocompe-

tent cells: in vitro studies. Anticancer Drugs. 1997;8 Suppl 1:S39–42.
97. Stein GM, Berg PA. Modulation of cellular and humoral immune
responses during exposure of healthy individuals to an aqueous mistletoe
extract. Eur J Med Res. 1998;3:307–14.
98. Stein GM, Pfüller U, Schietzel M. Viscotoxin-free aqueous extracts from
European mistletoe (Viscum album L.) stimulate activity of human
granulocytes. Anticancer Res. 1999;19:2925–8.
99. Suveren E, Baxter GF, Iskit AB, Turker AU. Cardioprotective effects of
Viscum album L. subsp. album (European misletoe) leaf extracts in myocar-
dial ischemia and reperfusion. J Ethnopharmacol. 2017;209:203–9.
100. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Evaluation of traditional
plant treatments for diabetes: studies in streptozotocin diabetic mice. Acta
Diabetol Lat. 1989;26:51–5.
101. Tabiasco J, Pont F, Fournié JJ, Vercellone A. Mistletoe viscotoxins increase
natural killer cell-mediated cytotoxicity. Eur J Biochem. 2002;269:
2591–600.
102. Tröger W, Galun D, Reif M, et al. Viscum album [L.] extract therapy in
patients with locally advanced or metastatic pancreatic cancer: a randomised
clinical trial on overall survival. Eur J Cancer. 2013;49:3788–97.
103. Tröger W, Zdrale Z, Stanković N, Matijašević M. Five-year follow-up of
patients with early stage breast cancer after a randomized study comparing
additional treatment with Viscum album (L.) extract to chemotherapy
alone. Breast Cancer (Auckl). 2012;6:173–80.
104. Turkkan A, Savas HB, Yavuz B, et al. The prophylactic effect of Viscum
album in streptozotocin-induced diabetic rats. North Clin Istanb. 2016;3:
83–9.
105. Tusenius KJ, Spoek AM, van Hattum J. Exploratory study on the effects of
treatment with two mistletoe preparations on chronic hepatitis C. Arzneimit-
telforschung. 2005;55:749–53.
106. Tusenius KJ, Spoek JM, Kramers CW. Iscador Qu for chronic hepatitis C:
an exploratory study. Complement Ther Med. 2001;9:12–6.
107. Uçar EÖ, Arda N, Aitken A. Extract from mistletoe, Viscum album L.,
reduces Hsp27 and 14-3-3 protein expression and induces apoptosis in C6
rat glioma cells. Genet Mol Res. 2012;11:2801–13.
108. Urech K, Schaller G, Jäggy C. Viscotoxins, mistletoe lectins and their
isoforms in mistletoe (Viscum album L.) extracts Iscador. Arzneimittel-
forschung. 2006;56:428–34.
109. Urech K, Scher JM, Hostanska K, Becker H. Apoptosis inducing activity
of viscin, a lipophilic extract from Viscum album L. J Pharm Pharmacol.
2005;57:101–9.
110. Van Huyen JP, Delignat S, Bayry J, et al. Interleukin-12 is associated with
the in vivo antitumor effect of mistletoe extracts in B16 mouse melanoma.
Cancer Lett. 2006;243:32–7.
1932 Viscum album L.

111. van Wely M, Stoss M, Gorter RW. Toxicity of a standardized mistletoe

extract in immunocompromised and healthy individuals. Am J Ther. 1999;
6:37–43.
112. von Schoen-Angerer T, Madeleyn R, Kienle G, Kiene H, Vagedes J. Viscum
album in the treatment of a girl with refractory childhood absence epilepsy.
J Child Neurol. 2015;30:1048–52.
113. Wagner H, Jordan E, Feil B. Studies on the standardization of mistletoe
preparations. Oncology. 1986;43 Suppl 1:16–22.
114. Weissenstein U, Kunz M, Urech K, Regueiro U, Baumgartner S.
Interaction of a standardized mistletoe (Viscum album) preparation with
antitumor effects of Trastuzumab in vitro. BMC Complement Altern Med.
2016;16:271.
115. Wójciak-Kosior M, Sowa I, Pucek K, et al. Evaluation of seasonal changes
of triterpenic acid contents in Viscum album from different host trees.
Pharm Biol. 2017;55:1–4.
116. Yoon TJ, Yoo YC, Kang TB, et al. Prophylactic effect of Korean mistletoe
(Viscum album coloratum) extract on tumor metastasis is mediated by
enhancement of NK cell activity. Int J Immunopharmacol. 1998;20:163–72.
117. Zuzak TJ, Rist L, Eggenschwiler J, et al. Paediatric medulloblastoma cells
are susceptible to Viscum album (mistletoe) preparations. Anticancer Res.
2006;26:3485–92.
118. Zwierzina H, Bergmann L, Fiebig H, et al. The preclinical and clinical
activity of aviscumine: a potential anticancer drug. Eur J Cancer. 2011;47:
1450–7.
Withania somnifera (L.) Dunal
(Solanaceae)

(Syns.: W. microphysalis Suess.; Physalis somnifera L.)

Abstract
A perennial shrub, cultivated in many parts of India; also native to Pakistan,
Sri Lanka, Nepal, China, Arabian Peninsula, western Asia, Mediterranean region,
tropical Africa and southern Europe, and naturalized in Australia. In Ayurveda, it
has been used for over 4000 years, and is described as tonic, alterative, pungent,
astringent, hot and aphrodisiac, and is recommended in rheumatism, cough,
dropsy, consumption, nervous exhaustion, insomnia, loss of memory, and senile
debility, and as an adaptogen that provides defense against diseases and adverse
environmental factors and arrests the aging process. Unani physicians use roots
and leaves and consider them aphrodisiac, diuretic, analgesic, fattening and
general tonic, and beneficial as antirheumatic, antileucorrhea and as uterine tonic.
In Kenya, traditional healers use root extract to treat malaria. Steeped in warm
castor oil, the leaves are applied to carbuncles, inflammations and swellings. In
Italy, it is very rare and grows spontaneously only in Sicily and in Sardinia. The
genetic difference between Indian and Sicilian variety is smaller than that
between Indian and Sardinian variety. Phytochemical analysis shows that the
Sardinian variety has higher withaferin A content. Characteristic constituents of
ashwagandha roots include withanolides such as withaferin A and withanolide A.
A number of withanolides have been isolated both from the leaves and the roots.
It is mainly described as an adaptogen and pharmacological studies in animals
show antistress activity, increasing endurance, and reduce stress-induced LPO.
Even a withanolide-free aqueous fraction exhibited antistress activity. Aqueous
extract of roots and leaves is reported to improve cognitive and psychomotor
performance of healthy individuals. Significant anxiolytic and antistress effects of
root extracts and decrease in blood cortisol levels have been observed in
double-blind RCTs in Indian patients.

© Springer Nature Switzerland AG 2020 1933

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_197
1934 Withania somnifera (L.) Dunal

Keywords




Alchechengi falso Asgandh Ashvagandha Bari behman Erva-moira-






sonífera Gelinfeneri Indian ginseng Oroval Rasbhari Summulfiraq

Vernaculars: Urd.: Asgandh nagori; Hin.: Asgandh, Punir, Rasbhari; San.:

Ashvagandha, Turagi, Turagi-gandha, Turangi, Varaha, Vrisha; Ben.: Asvagandha;
Mal.: Amukkuram, Pevette; Mar.: Askagandha, Asvagandha, Dorgunj, Kanchuki,
Tula; Tam.: Amkulang-kalang, Amukkara, Amukkilaachedi, Karappaan-thazhai;
Tel.: Asvagandhi, Penerr, Penerru-gadda, Vajigandha; Ara.: Abab aadi, Fuqeesh,
Sakraan, Summulfaar, Summulfiraq, Ubab; Chi.: 睡茄; Eng.: Indian ginseng,
Poisonous gooseberry, Rennet, Winter cherry; Fre.: Withania somnifère; Ita.:
Alchechengi falso, Vitania sonnifero; Per.: Bari behman; Por.: Erva-moira-
sonífera; Spa.: Oroval; Tur.: Gelinfeneri.
Description: A perennial shrub, cultivated in many parts of India; also native to
Pakistan, Sri Lanka, Nepal, China, Arabian Peninsula (Saudi Arabia, Oman,
Yemen), western Asia (Afghanistan, Iran, Iraq, Jordan), Mediterranean region
(Turkey), tropical Africa and southern Europe (Greece, Italy, Spain), and natural-
ized in Australia. The plant is 60 cm to 1.2 m high; branches very slender; leaves
alternate, petioled, obtuse, ovate, oblong, and sometimes oblique at the base,
5–10 cm long; young parts and nerves of the leaves covered with whitish starry
tomentum; the ripe fruit smooth pea-sized is orange-red.LXXXI Flowers axillary,
subsessile, crowded at the end of the branches; corolla campanulate, yellowish
green, very small, berry red, covered by a membranaceous closely-fitting calyx,
open at the apex; seeds numerous, yellowish-white, reniform, laterally compressed
about 1.5 mm long; testa honeycombed. Whole plant is covered with small bran-
ched and pointed white hairs, which give it a hoary appearance. The odor is pungent
and disagreeable like horse’s urine. The plant has a long tapering light-brown root,
which may attain the size of a carrot; it is surmounted by a knotty crown, from
which springs several shrubby, flexuose round branches, one to five feet in length.
Dried root, as available in the market is of very uniform appearance, being from 10
to 20 cm long, and from 6 to 12 mm in diameter at the thickest portion a little
below the crown. It is plump, smooth, tapering, and of a light yellowish-brown
color externally, white internally, brittle, fracture short and starchy. The root is
seldom branched; attached to the crown are the remains of several slender stems
(Figs. 1 and 2).XL
Actions and Uses: In Ayurveda, it has been used for over 4000 years [100], and is
described as tonic, alterative, pungent, astringent, hot and aphrodisiac, and is rec-
ommended in rheumatism, cough, dropsy, consumption, nervous exhaustion,
insomnia, loss of memory, and senile debility [70], and as an adaptogen that provides
defense against diseases and adverse environmental factors and arrests the aging
process [20]. Chakradatta (a treatise on Hindu medicine) recommended it as decoc-
tion with long pepper, butter and honey in consumption and scrofula. A medicinal
butter prepared by boiling together one part of the root with one part of clarified
Withania somnifera (L.) Dunal 1935

Fig. 1 Withania somnifera, Plant with Fruit, Wowbobwow12, WikimediaCommons; ShareAlike

3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:WithaniaFruit.jpg; https://
creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 2 Withania somnifera, Roots, Prof. Akbar, Original

1936 Withania somnifera (L.) Dunal

butter, and ten parts of milk may be used in such cases. As an aphrodisiac and as a
remedy for rheumatism the drug is usually combined with a number of aromatics,
each dose contains about 30 grains (*2 g) of the root.XL Unani physicians use roots
and leaves and consider them (temperament, hot 3° and dry 3°) aphrodisiac, diuretic,
analgesic, fattening and general tonic, and beneficial as antirheumatic, antileucorrhea
and as uterine tonic.LXXVII It has been described in Western literature as abortifacient,
amebicide, anodyne, bactericide, contraceptive, emmenagogue, diuretic, fungicide,
narcotic, pediculicide, poison, sedative, spasmolytic, and tonic, and is used for
adenopathy, anthrax, arthritis, asthma, bronchitis, cancer, candida, cold and cough,
cystitis, debility, diarrhea, dropsy, dyspepsia, erysepelas, fever, furuncle, gyneco-
pathy, hypertension, hiccups, inflammation, lumbago, marasmus, nausea, piles, proc-
titis, psoriasis, rheumatism, ringworm, scabies, senility, smallpox, sores, syphilis,
tuberculosis, tumors, typhoid, uterosis and wounds.CL In parts of rural India, the plant
extract is externally applied as an antidote to snakebite [78]. In Kenya, traditional
healers use root extract to treat malaria [69, 84]. Steeped in warm castor oil, the leaves
are applied to carbuncles, inflammations and swellings.LV In Italy, it is very rare and
grows spontaneously only in Sicily and in Sardinia. The genetic difference between
Indian and Sicilian variety is smaller than that between Indian and Sardinian
variety. Phytochemical analysis shows that the Sardinian variety has higher with-
aferin A content [109].
Phytoconstituents: Characteristic constituents of ashwagandha roots include with-
anolides such as withaferin A and withanolide A [95]. A number of withanolides
have been isolated both from the leaves and the roots [28, 60, 82, 121]. The order of
withaferin A contents varies leaf > bark > stem > roots [120]. The roots also
contain anahygrine, mesoanaferine, cuscohygrine, isopelletierine, tropine, hygrine,
pseudotropine, 3a-tigloxytropane, choline, withasomnine, 0.1% saccharose, 0.02%
b-sitosterol, somniferine, withanine, withaninine, nicotine, ipuranol, hentriacontane,
fatty oils, essential oils, and scopoletin.XC,CL The leaves contain withaferin A and
withanolide glycosides, reducing sugars, somnitol, withanone, glycine, cystine,
glutamic acid, a-alanine, proline and tryptophane.XC Elsakka et al. [46, 47] isolated
alkaloids, 18 fatty acids, b-sitosterol, polyphenols and phytosterols from the roots.
Pharmacology: It is mainly described as an adaptogen and pharmacological
studies in animals show antistress activity [13, 22, 64], increasing endurance [42,
50], and reduce stress-induced LPO [43]. Even a withanolide-free aqueous fraction
exhibited antistress activity [116, 117]. Other pharmacological studies indicated
that ashwagandha possesses anti-inflammatory, antitumor, immunomodulatory,
antioxidant, hemopoietic, and rejuvenating properties, exerts a positive influence on
the endocrine, cardiopulmonary, and central nervous systems [81]. A standardized
aqueous extract reversed effects of cisplatin on gastric emptying in rats, and pro-
duced immunostimulation [104]. Ethanol and methanol extracts reportedly showed
in vitro AChE inhibitory activity [65, 131]. The extract potentiated anxiolytic effect
of diazepam [53], anxiolytic action of subeffective dose of ethanol and markedly
antagonized ethanol withdrawal anxiety in rats [52], exhibited antidepressant-like
Withania somnifera (L.) Dunal 1937

effects [113], and prevented haloperidol and reserpine-induced orofacial dyskinesia

and cognitive dysfunction [85, 86]. Glycowithanolides normalized (anxiolytic)
effect of the anxiogenic agent PTZ, comparable to lorazepam, and also exhibited
antidepressant effect comparable to imipramine [20], and prevented haloperidol-
induced tardive dyskinesia in rats [21]. The extract increased PTZ-induced seizure
threshold for the onset of tonic extension phase in mice [6, 72], and was more
efficacious than scopolamine in reversing haloperidol-induced catalepsy [87]. The
extract prolongs morphine-induced analgesia and prevents the development of
morphine analgesic tolerance, and morphine-induced rebound hyperalgesia in mice,
probably through involvement of GABAA, GABAB, NMDA and d opioid receptors
[73, 88]. Pretreatment with hydroalcohol extract for 30-days prevented motor
impairment, and significantly attenuated the percentage of hemispheric lesion area
in MCA occlusion-induced stroke in rats [26, 99]. Pretreatment with extracts also
prevented or reduced kainic acid-induced [94], 6-OHDA-[4], and MPTP neuro-
toxicity in rats [100, 101, 105], and protected against stress-induced neurodegen-
eration of hippocampal region [58].
Ethanol extract demonstrated significant anti-inflammatory activity against
carrageenan-induced edema in rats [7], whereas methanol extract was active in
cotton-pellet implantation in rats, which was attributed to the high content of
biologically active steroids in the plant, of which withaferin A is the major com-
ponent. This activity was comparable to a dose of 5 mg/kg hydrocortisone sodium
succinate [8]. Begum and Sadique [16, 17] reported a significant protective effect
on adjuvant-induced arthritis in rats and on glycosaminoglycan synthesis in the
granulation tissue of carrageenan-induced air pouch granuloma. The root powder
and its aqueous extract produced significant short-term chondroprotective effect on
damaged human osteoarthritic cartilage matrix in 50% of the patients and caused a
significant and reproducible in vitro inhibition of gelatinase activity of collagenase
type-2 enzyme [124]. Root powder also ameliorated changes in the levels of LPx,
glycoproteins, depleted antioxidant status and bone collagen in adjuvant-induced
arthritis [103], and significantly improved collagen-induced arthritis in rats [51].
Withaferin A increases osteoblast proliferation and differentiation and prevents
bone loss by both inhibition of resorption and stimulation of new bone formation
before the onset of osteoporosis [67, 68].
Aqueous extract treatment of NIDDM rats reduced blood glucose, HbA1c and
insulin, improved glucose tolerance and insulin sensitivity index [12], reversed
alloxan-diabetes induced blood glucose and lipid changes [127], improved antiox-
idant status [76, 128], and corrected dexamethasone and metformin-induced
hypothyroidism [61]. The root extract also increased serum T3 and T4 levels and
hepatic G-6-Pase activity in normal mice of either sex [91, 93]. Root powder and the
extract significantly decrease plasma LPO and increase activity of both SOD and
CAT in normal mice [74, 92], aqueous root extract in dehydration-induced LPO in
rats [31], and glycowithanolides induced a dose-related increase in SOD, CAT and
GPx activity in frontal cortex and striatum of rat brain [19, 23, 115]. Ethanol extract
exerts strong cardioprotective effect in isoprenaline-induced myonecrosis in rats,
augments endogenous antioxidants, maintains myocardial antioxidant status and
1938 Withania somnifera (L.) Dunal

restores most of the altered hemodynamic parameters [54, 83]. A standardized

extract effectively attenuated doxorubicin-cardiotoxicity and oxidative stress-
induced biochemical and histological alterations [56]. Root powder also signifi-
cantly reduced right ventricular pressure and all markers of right ventricular
hypertrophy in monocrotaline-induced pulmonary hypertension in rats, and
improved inflammation, oxidative stress and endothelial dysfunction [62]. Alcohol
extract of defatted seeds increased swimming endurance of mice, and prevented
chemically and stress-induced gastric ulcers in rats, and induced a state of
nonspecifically increased resistance during stress [118].
Combination of paclitaxel with W. somnifera extract exhibits synergistic effects
against B(a)P-induced lung cancer in mice and prevents paclitaxel toxicity [111,
112]. It also reduces side effects of CP and paclitaxel without interfering with their
tumor-reducing effects [133]. Ethanol extract of the whole plant protected mice
from urethane-induced lung adenomas and prevented increase in mortality [119].
Injection of the alcoholic root extract (i.p.) to BALB/c mice bearing Sarcoma-180,
significantly increased delay in tumor growth, and complete regression of tumor at
doses above 400 mg/kg/day [39]. Devi et al. [40] reported 18, 38 and 45% response
of the extract injected into mice bearing tumors, with or without local treatment of
10 Gy gamma radiation or hyperthermia, and the extract increased effect of radi-
ation on tumor regression and the growth delay. Ethanol extract protected against
Dalton’s ascitic lymphoma [29], inhibited 20-MCA-induced fibrosarcoma [32, 98]
and DMBA-induced skin carcinogenesis [36, 90], and increased life span of
tumor-bearing animals. Withaferin A also inhibits growth and increased Ehrlich
ascites carcinoma-free survival; drug treatment before irradiation synergistically
increased survival even in advanced tumors [41, 114], protected against radiation-
induced myelosuppression [48], and reversed paclitaxel-induced neutropenia [55].
The root extract significantly reduces spontaneous estrogen receptor-negative
mammary carcinoma in transgenic female mice [66], and significantly inhibits
the metastatic colony formation of melanoma in lungs, and increases animals
survival [77].
Immunomodulatory activity in myelosuppression induced by various myelosup-
pressive agents [2, 45, 104, 134], protection against L. monocytogenes-induced
toxicity and mortality in mice [125], and enhancement of natural killer cell activity
(NK) in both normal and the tumor-bearing mice have been reported [33]. Methanol
extract significantly increased total WBC count in normal Balb/c mice and reduced
leucopenia induced by sublethal dose of gamma radiation [75]. Urethane-induced
decrease in leucocyte count and lymphocyte percentage are significantly reversed,
and animals treated with W. Somnifera alone increase leucocyte count and lym-
phocyte percentage [119]. W. somnifera extract treatment of BALB/c mice also
shows immunopotentiating and myeloprotective effects by enhancing cytokines
production and stem cell proliferation, increasing levels of IFN-c, IL-2 and GM-CSF,
and lower TNFa level [35, 37]. It also protects against nephrotoxicity caused by
CP [34], gentamicin [61], and bromobenzine [129], and CP-induced hematotoxicity
[38]. However, Rasool and Varalakshmi [102] reported an immunosuppressive effect
of aqueous suspension of the root powder.
Withania somnifera (L.) Dunal 1939

Crude extract and isolated compounds are active against S. aureus [63]; whereas
methanol and hexane extracts of both leaves and roots exhibit potent antibacterial
activity against S. typhimurium and E. coli [14, 89]; also, a significant (50%)
inhibition of malarial parasitemia by the root extract [44]. Alcohol leaf extract is
protective against CCl4-hepatotoxicity [122]; whereas methanol extract signifi-
cantly reduces ulcer index, volume of gastric secretion, free acidity, and total
acidity in experimentally-induced gastric ulcers, especially stress-induced gastric
ulcers; and significantly increases antioxidant defense, and significantly decreases
LPO [18]. Addition of root powder to the diet of hypercholesteremic rats reduced
total plasma lipids, TC and TGs, and significantly increased HDL-C, HMG-CoA
reductase activity and bile acid content [131]. Spermatogenic effects of aqueous
extract in immature rats have been reported [1]; whereas high doses (3 g/kg/d) of
methanol extract caused reversible impairment of libido, sexual vigor, sexual per-
formance, and penile erectile dysfunction in rats; which were attributed to hyper-
prolactinemic, GABAergic, serotonergic or sedative activities of the extract [57].
Clinical Studies: Aqueous extract of roots and leaves is reported to improve
cognitive and psychomotor performance of healthy individuals [96]. Significant
anxiolytic and antistress effects of root extracts and decrease in blood cortisol levels
have been observed in double-blind RCTs in Indian patients [11, 25, 106].
Seventy-five patients with moderate to severe anxiety of more than 6-weeks
duration responded significantly better to naturopathic care, that included ashwa-
gandha extract, than to standardized psychotherapy intervention for overall mental
health, concentration, fatigue, social functioning, vitality and overall quality of life
[30]. In an 8-week clinical study to treat bipolar disorder with ashwagandha, a
significant increase in thyroxine level was noted [49]. Added adjunctively to
standard treatment of twenty-four subjects with ashwagandha extract (500 mg/d)
and twenty-nine control euthymic subjects with DSM-IV bipolar disorder for an
8-week, double-blind RCT, showed significant benefits for 3 cognitive tasks: digit
span backward, Flanker neutral response time, and the social cognition response
rating of the Penn Emotional Acuity Test [27]. Treatment of fifteen Indian schi-
zophrenic patients with an W. somnifera extract for a month significantly reduced
serum TGs and FBG without affecting psychological profile [3].
Stress is an important factor of infertility in normozoospermic individuals.
Treatment with W. somnifera root powder inhibited LPO, improved sperm count and
motility, significantly increased serum testosterone and LH levels in infertile men
and reduced levels of FSH and prolactin [5]. In normozoospermic infertile men with
psychological stress, treatment with root powder for 3-months improved sperm
count by 36% and motility by 13%, compared to 17% and 9%, respectively in
normozoospermic infertile men without psychological stress [79]. The results have
been more outstanding in patients with oligospermia (sperm count <20 million/mL),
where treatment with the root extract (675 mg/d in three doses for 90-days) resulted
in 53% increase in semen volume, 167% increase in sperm count and 57% increase
in sperm motility on day 90 from baseline [9].
1940 Withania somnifera (L.) Dunal

Administration of root powder to six mild NIDDM and six mild hypercholes-
terolemic individuals for 30-days significantly lowered blood glucose, serum TC,
TGs, LDL-C and VLDL-C, and increased urinary volume and sodium excretion
[10]. In a double-blind, randomized placebo-controlled, crossover study, 42 patients
with osteoarthritis received either drug treatment with a herbomineral formulation
containing roots of W. somnifera, stem of Boswellia serrata, rhizomes of Curcuma
longa and a zinc complex (Articulin-F) or a matching placebo for three-months.
The groups were reversed after a 15 days wash-out period. A significant drop in
severity of pain and disability score were observed in the treatment group [123].
However, radiological examination did not show any significant changes in both
groups [71].
Mechanism of Action: GABAergic signaling dysfunction such as in general
anxiety disorders, sleep disturbances, muscle spasms, and seizures are suggested to
be the target of W. sominifera for its pharmacological effects [24]. Methanol extract
inhibited [3H]GABA in vitro binding by 100% at the dose of 1 mg; while binding of
[3H]flunitrazepam to their putative receptor sites was enhanced up to 91% at 100 µg
dose. The authors suggested the presence of a GABA-mimetic substance in the
extract [80]. However, administration of sitoindosides VII–X and withaferin-A,
isolated from aqueous methanol extract, to rats affected preferentially events in the
cortical and basal forebrain cholinergic signal transduction cascade, and increased
cortical muscarinic ACh receptor capacity without affecting GABAA and benzodi-
azepine receptor binding or NMDA and AMPA glutamate receptor subtypes in the
cortical or subcortical regions [110]. Withanolides are generally credited for its
anticancer activity, and withaferin A is the most active of them [132]. Withano-
lide A, withanoside IV, and withanoside VI have also been recommended for
therapeutic use in neurodegenerative diseases [126].
Human A/Es, Allergy and Toxicity: No known A/Es in normal doses.
Animal Toxicity: Administration of root extract, up to a dose of 2,000 mg/kg to
pregnant rats produced no maternal or fetal toxicity, and no changes in body
weight, implantation, fetuses or other malformations [97]. However, Arseculeratne
et al. [15] reported renal toxicity in feeding trials of rats. They also reported absence
of pyrrolizidine alkaloids in the plant.
CYP450 and Potential for Drug-Herb Interactions: Ethanol extract does not
show any significant interaction with CYP450 enzymes (CYP3A4, CYP2D6,
CYP1A2 and CYP 2C9) in human liver microsomes; therefore, little if any chance
of drug-drug interaction with drugs metabolized by these CYP450 enzymes [107,
108]. However, Padmavathi et al. [90] reported that root powder administered in
diet to mice for 2-weeks inhibited phase I and activated phase II and antioxidant
liver enzymes.
Commentary: Most common uses of the root in Ayurveda and Unani systems of
medicine are as adaptogen, to improve cognition and memory, and in male sexual
dysfunctions. Some of the clinical trials have demonstrated these therapeutic effects.
Withania somnifera (L.) Dunal 1941

Even the effect on infertility in men with psychological stress was better than in
infertile men without psychological stress, an indication that antistress effect played
a role in improving the physical parameters of infertility, such as sperm count and
motility. Neverthelss, more RCTs in large numbers and diverse patient populations
are needed to reproduce and validate these benefits.

References
1. Abdel-Magied EM, Abdel-Rahman HA, Harraz FM. The effect of aqueous
extracts of Cynomorium coccineum and Withania somnifera on testicular
development in immature Wistar rats. J Ethnopharmacol. 2001;75:1–4.
2. Agarwal R, Diwanay S, Patki P, Patwardhan B. Studies on immunomod-
ulatory activity of Withania somnifera (ashwagandha) extracts in exper-
imental immune inflammation. J Ethnopharmacol. 1999;67:27–35.
3. Agnihotri AP, Sontakke SD, Thawani VR, Saoji A, Goswami VS. Effects
of Withania somnifera in patients of schizophrenia: a randomized, double-
blind, placebo-controlled pilot trial study. Indian J Pharmacol. 2013;45:
417–8.
4. Ahmad M, Saleem S, Ahmad AS, et al. Neuroprotective effects of
Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats.
Hum Exp Toxicol. 2005;24:137–47.
5. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves
semen quality by regulating reproductive hormone levels and oxidative
stress in seminal plasma of infertile males. Fertil Steril. 2010;94:989–96.
6. Akula KK, Dhir A, Kulkarni SK. Effect of various antiepileptic drugs in a
pentylenetetrazol-induced seizure model in mice. Methods Find Exp Clin
Pharmacol. 2009;31:423–32.
7. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory
activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26:
163–8.
8. Al-Hindawi MK. al-Khafaji SH, Abdul-Nabi MH. Antigranuloma activity
of Iraqi Withania somnifera. J Ethnopharmacol. 1992;37:113–6.
9. Ambiye VR, Langade D, Dongre S, et al. Clinical evaluation of the sper-
matogenic activity of the root extract of ashwagandha (Withania somnifera)
in oligospermic males: a pilot study. Evid Based Complement Alternat
Med. 2013;2013:571420.
10. Andallu B, Radhika B. Hypoglycemic, diuretic and hypocholesterolemic
effect of winter cherry (Withania somnifera, Dunal) root. Indian J Exp
Biol. 2000;38:607–9.
11. Andrade C, Aswath A, Chaturvedi SK, Srinivasa M, Raguram R. A double-
blind, placebo-controlled evaluation of the anxiolytic efficacy of an
ethanolic extract of Withania somnifera. Indian J Psychiatry. 2000;42:
295–301.
1942 Withania somnifera (L.) Dunal

12. Anwer T, Sharma M, Pillai KK, Iqbal M. Effect of Withania somnifera on

insulin sensitivity in noninsulin-dependent diabetes mellitus rats. Basic
Clin Pharmacol Toxicol. 2008;102:498–503.
13. Archana R, Namasivayam A. Antistressor effect of Withania somnifera.
J Ethnopharmacol. 1999;64:91–3.
14. Arora S, Dhillon S, Rani G, Nagpal A. The in vitro antibacterial/synergistic
activities of Withania somnifera extracts. Fitoterapia. 2004;75:385–8.
15. Arseculeratne SN, Gunatilaka AA, Panabokke RG. Studies of medicinal
plants of Sri Lanka. Part 14: toxicity of some traditional medicinal herbs.
J Ethnopharmacol. 1985;13:323–35.
16. Begum VH, Sadique J. Effect of Withania somnifera on glycosaminogly-
can synthesis in carrageenin-induced air pouch granuloma. Biochem Med
Metab Biol. 1987;38:272–7.
17. Begum VH, Sadique J. Long term effect of herbal drug Withania somnifera
on adjuvant induced arthritis in rats. Indian J Exp Biol. 1988;26:877–82.
18. Bhatnagar M, Sisodia SS, Bhatnagar R. Antiulcer and antioxidant activity
of Asparagus racemosus Willd. and Withania somnifera Dunal in rats.
Ann N Y Acad Sci. 2005;1056:261–78.
19. Bhattacharya A, Ghosal S, Bhattacharya SK. Antioxidant effect of Withania
somnifera glycowithanolides in chronic footshock stress-induced pertur-
bations of oxidative free radical scavenging enzymes and lipid peroxidation
in rat frontal cortex and striatum. J Ethnopharmacol. 2001;74:1–6.
20. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-
antidepressant activity of Withania somnifera glycowithanolides: an experi-
mental study. Phytomedicine. 2000;7:463–9.
21. Bhattacharya SK, Bhattacharya D, Sairam K, Ghosal S. Effect of Withania
somnifera glycowithanolides on a rat model of tardive dyskinesia.
Phytomedicine. 2002;9:167–70.
22. Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withania
somnifera: an experimental study using a rat model of chronic stress.
Pharmacol Biochem Behav. 2003;75:547–55.
23. Bhattacharya SK, Satyan KS, Ghosal S. Antioxidant activity of glycowith-
anolides from Withania somnifera. Indian J Exp Biol. 1997;35:236–9.
24. Candelario M, Cuellar E, Reyes-Ruiz JM, et al. Direct evidence for
GABAergic activity of Withania somnifera on mammalian ionotropic
GABAA and GABAq receptors. J Ethnopharmacol. 2015;171:264–72.
25. Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized
double-blind, placebo-controlled study of safety and efficacy of a high-
concentration full-spectrum extract of ashwagandha root in reducing stress
and anxiety in adults. Indian J Psychol Med. 2012;34:255–62.
26. Chaudhary G, Sharma U, Jagannathan NR, Gupta YK. Evaluation of
Withania somnifera in a middle cerebral artery occlusion model of stroke
in rats. Clin Exp Pharmacol Physiol. 2003;30:399–404.
Withania somnifera (L.) Dunal 1943

27. Chengappa KN, Bowie CR, Schlicht PJ, et al. Randomized placebo-
controlled adjunctive study of an extract of Withania somnifera for cogni-
tive dysfunction in bipolar disorder. J Clin Psychiatry. 2013;74:1076–83.
28. Choudhary MI, Yousuf S, Nawaz SA, et al. Cholinesterase inhibiting
withanolides from Withania somnifera. Chem Pharm Bull (Tokyo). 2004;
52:1358–61.
29. Christina AJ, Joseph DG, Packialakshmi M, et al. Anticarcinogenic
activity of Withania somnifera Dunal against Dalton’s ascitic lymphoma.
J Ethnopharmacol. 2004;93:359–61.
30. Cooley K, Szczurko O, Perri D, et al. Naturopathic care for anxiety: a
randomized controlled trial ISRCTN78958974. PLoS ONE. 2009;4:e6628.
31. Das K, Samanta TT, Samanta P, Nandi DK. Effect of extract of Withania
Somnifera on dehydration-induced oxidative stress-related uremia in male
rats. Saudi J Kidney Dis Transpl. 2010;21:75–80.
32. Davis L, Kuttan G. Effect of Withania somnifera on 20-methylcholanthrene
induced fibrosarcoma. J Exp Clin Cancer Res. 2000;19:165–7.
33. Davis L, Kuttan G. Effect of Withania somnifera on cell mediated immune
responses in mice. J Exp Clin Cancer Res. 2002;21:585–90.
34. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-
induced urotoxicity. Cancer Lett. 2000;148:9–17.
35. Davis L, Kuttan G. Effect of Withania somnifera on cytokine production in
normal and cyclophosphamide treated mice. Immunopharmacol Immuno-
toxicol. 1999;21:695–703.
36. Davis L, Kuttan G. Effect of Withania somnifera on DMBA induced
carcinogenesis. J Ethnopharmacol. 2001;75:165–8.
37. Davis L, Kuttan G. Immunomodulatory activity of Withania somnifera.
J Ethnopharmacol. 2000;71:193–200.
38. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced
toxicity by Withania somnifera extract in mice. J Ethnopharmacol. 1998; 62:
209–14.
39. Devi PU, Sharada AC, Solomon FE, Kamath MS. In vivo growth
inhibitory effect of Withania somnifera (ashwagandha) on a transplantable
mouse tumor, Sarcoma 180. Indian J Exp Biol. 1992;30:169–72.
40. Devi PU, Sharada AC, Solomon FE. Antitumor and radiosensitizing effects
of Withania somnifera, ashwagandha) on a transplantable mouse tumor,
Sarcoma-180. Indian J Exp Biol. 1993;31:607–11.
41. Devi PU, Sharada AC, Solomon FE. In vivo growth inhibitory and
radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma.
Cancer Lett. 1995;95:189–93.
42. Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in
rats and frogs. J Ethnopharmacol. 2000;70:57–63.
43. Dhuley JN. Effect of ashwagandha on lipid peroxidation in stress-induced
animals. J Ethnopharmacol. 1998;60:173–8.
44. Dikasso D, Makonnen E, Debella A, et al. Antimalarial activity of Withania
somnifera L. Dunal extracts in mice. Ethiop Med J. 2006;44:279–85.
1944 Withania somnifera (L.) Dunal

45. Diwanay S, Chitre D, Patwardhan B. Immunoprotection by botanical drugs

in cancer chemotherapy. J Ethnopharmacol. 2004;90:49–55.
46. Elsakka ME, Grigorescu E, Stanescu U, et al. New data referring to
chemistry of Withania somnifera species. Rev Med Chir Soc Med Nat Iasi.
1990;94:385–7.
47. Elsakka ME, Pavelescu M, Grigorescu E. Withania somnifera, a plant with a
great therapeutical future. Rev Med Chir Soc Med Nat Iasi. 1989;93:349–50.
48. Ganasoundari A, Zare SM, Devi PU. Modification of bone marrow
radiosensensitivity by medicinal plant extracts. Br J Radiol. 1997;70:599–
602.
49. Gannon JM, Forrest PE, Roy Chengappa KN. Subtle changes in thyroid
indices during a placebo-controlled study of an extract of Withania somni-
fera in persons with bipolar disorder. J Ayurveda Integr Med. 2014; 5:241–5.
50. Grandhi A, Mujumdar AM, Patwardhan B. A comparative pharmacological
investigation of ashwagandha and Ginseng. J Ethnopharmacol. 1994;44:
131–5.
51. Gupta A, Singh S. Evaluation of anti-inflammatory effect of Withania
somnifera root on collagen-induced arthritis in rats. Pharm Biol. 2014;52:
308–20.
52. Gupta GL, Rana AC. Effect of Withania somnifera Dunal in ethanol-
induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol.
2008;46:470–5.
53. Gupta GL, Rana AC. Protective effect of Withania somnifera dunal root
extract against protracted social isolation induced behavior in rats. Indian J
Physiol Pharmacol. 2007;51:345–53.
54. Gupta SK, Mohanty I, Talwar KK, et al. Cardioprotection from ischemia
and reperfusion injury by Withania somnifera: a hemodynamic, biochem-
ical and histopathological assessment. Mol Cell Biochem. 2004;260:39–47.
55. Gupta YK, Sharma SS, Rai K, Katiyar CK. Reversal of paclitaxel induced
neutropenia by Withania somnifera in mice. Indian J Physiol Pharmacol.
2001;45:253–7.
56. Hamza A, Amin A, Daoud S. The protective effect of a purified extract of
Withania somnifera against doxorubicin-induced cardiac toxicity in rats.
Cell Biol Toxicol. 2008;24:63–73.
57. Ilayperuma I, Ratnasooriya WD, Weerasooriya TR. Effect of Withania
somnifera root extract on the sexual behaviour of male rats. Asian J Androl.
2002;4:295–8.
58. Jain S, Shukla SD, Sharma K, Bhatnagar M. Neuroprotective effects of
Withania somnifera Dunn. in hippocampal subregions of female albino rat.
Phytother Res. 2001;15:544–8.
59. Jatwa R, Kar A. Amelioration of metformin-induced hypothyroidism by
Withania somnifera and Bauhinia purpurea extracts in Type 2 diabetic
mice. Phytother Res. 2009;23:1140–5.
Withania somnifera (L.) Dunal 1945

60. Jayaprakasam B, Zhang Y, Seeram NP, Nair MG. Growth inhibition of

human tumor cell lines by withanolides from Withania somnifera leaves.
Life Sci. 2003;74:125–32.
61. Jeyanthi T, Subramanian P. Nephroprotective effect of Withania somnifera:
a dose-dependent study. Ren Fail. 2009;31:814–21.
62. Kaur G, Singh N, Samuel SS, et al. Withania somnifera shows a protective
effect in monocrotaline-induced pulmonary hypertension. Pharm Biol.
2015;53:147–57.
63. Kazmi SU, Ali SN, Jamal SA, Atta-ur-Rahman. New bioactive compounds
of plant origin. Pak J Pharm Sci. 1991;4:113–23.
64. Khan B, Ahmad SF, Bani S, et al. Augmentation and proliferation of T
lymphocytes and Th-1 cytokines by Withania somnifera in stressed mice.
Int Immunopharmacol. 2006;6:1394–403.
65. Khattak S, Saeed-Ur-Rehman, Shah HU, et al. In vitro enzyme inhibition
activities of crude ethanolic extracts derived from medicinal plants of
Pakistan. Nat Prod Res. 2005;19:567–71.
66. Khazal KF, Hill DL, Grubbs CJ. Effect of Withania somnifera root extract
on spontaneous estrogen receptor-negative mammary cancer in MMTV/Neu
mice. Anticancer Res. 2014;34:6327–32.
67. Khedgikar V, Ahmad N, Kushwaha P, et al. Preventive effects of with-
aferin A isolated from the leaves of an Indian medicinal plant Withania
somnifera (L.): comparisons with 17-b-estradiol and alendronate. Nutri-
tion. 2015;31:205–13.
68. Khedgikar V, Kushwaha P, Gautam J, et al. Withaferin A: a proteasomal
inhibitor promotes healing after injury and exerts anabolic effect on
osteoporotic bone. Cell Death Dis. 2013;4:e778.
69. Kirira PG, Rukunga GM, Wanyonyi AW, et al. Antiplasmodial activity
and toxicity of extracts of plants used in traditional malaria therapy in
Meru and Kilifi Districts of Kenya. J Ethnopharmacol. 2006;106:403–7.
70. Kuboyama T, Tohda C, Komatsu K. Effects of ashwagandha (roots of
Withania somnifera) on neurodegenerative diseases. Biol Pharm Bull. 2014;
37:892–7.
71. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a
herbomineral formulation: a double-blind, placebo-controlled, crossover
study. J Ethnopharmacol. 1991;33:91–5.
72. Kulkarni SK, Akula KK, Dhir A. Effect of Withania somnifera Dunal
root extract against pentylenetetrazol seizure threshold in mice: possible
involvement of GABAergic system. Indian J Exp Biol. 2008;46:465–9.
73. Kulkarni SK, Ninan I. Inhibition of morphine tolerance and dependence by
Withania somnifera in mice. J Ethnopharmacol. 1997;57:213–7.
74. Kumar A, Kalonia H. Protective effect of Withania somnifera Dunal on the
behavioral and biochemical alterations in sleep-disturbed mice (Grid over
water suspended method). Indian J Exp Biol. 2007;45:524–8.
75. Kuttan G. Use of Withania somnifera Dunal as an adjuvant during
radiation therapy. Indian J Exp Biol. 1996;34:854–6.
1946 Withania somnifera (L.) Dunal

76. Kyathanahalli CN, Manjunath MJ, Muralidhara. Oral supplementation of

standardized extract of Withania somnifera protects against diabetes-
induced testicular oxidative impairments in prepubertal rats. Protoplasma.
2014;251:1021–9.
77. Leyon PV, Kuttan G. Effect of Withania somnifera on B16F-10 melanoma
induced metastasis in mice. Phytother Res. 2004;18:118–22.
78. Machiah DK, Girish KS, Gowda TV. A glycoprotein from a folk medicinal
plant, Withania somnifera, inhibits hyaluronidase activity of snake venoms.
Comp Biochem Physiol C: Toxicol Pharmacol. 2006;143:158–61.
79. Mahdi AA, Shukla KK, Ahmad MK, et al. Withania somnifera improves
semen quality in stress-related male fertility. Evid Based Complement
Alternat Med. 2011;2011:576962.
80. Mehta AK, Binkley P, Gandhi SS, Ticku MK. Pharmacological effects of
Withania somnifera root extract on GABAA receptor complex. Indian J
Med Res Section A-Infectious Diseases. 1991;94:312–5.
81. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use
of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5:
334–46.
82. Misra L, Mishra P, Pandey A, et al. Withanolides from Withania somnifera
roots. Phytochemistry. 2008;69:1000–4.
83. Mohanty I, Arya DS, Dinda A, et al. Mechanisms of cardioprotective effect
of Withania somnifera in experimentally induced myocardial infarction.
Basic Clin Pharmacol Toxicol. 2004;94:184–90.
84. Muregi FW, Ishih A, Suzuki T, et al. In vivo antimalarial activity of
aqueous extracts from Kenyan medicinal plants and their chloroquine (CQ)
potentiation effects against a blood-induced CQ-resistant rodent parasite in
mice. Phytother Res. 2007;21:337–43.
85. Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root extract
on haloperidol-induced orofacial dyskinesia: possible mechanisms of
action. J Med Food. 2003;6:107–14.
86. Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root extract
on reserpine-induced orofacial dyskinesia and cognitive dysfunction.
Phytother Res. 2006;20:140–6.
87. Nair V, Arjuman A, Gopalakrishna HN, Nandini M. Effect of Withania
somnifera root extract on haloperidol-induced catalepsy in albino mice.
Phytother Res. 2008;22:243–6.
88. Orrù A, Marchese G, Casu G, et al. Withania somnifera root extract
prolongs analgesia and suppresses hyperalgesia in mice treated with
morphine. Phytomedicine. 2014;21:745–52.
89. Owais M, Sharad KS, Shehbaz A, Saleemuddin M. Antibacterial efficacy of
Withania somnifera (ashwagandha) an indigenous medicinal plant against
experimental murine salmonellosis. Phytomedicine. 2005;12:229–35.
90. Padmavathi B, Rath PC, Rao AR, Singh RP. Roots of Withania somnifera
inhibit forestomach and skin carcinogenesis in mice. Evid Based Comple-
ment Alternat Med. 2005;2:99–105.
Withania somnifera (L.) Dunal 1947

91. Panda S, Kar A. Changes in thyroid hormone concentrations after

administration of ashwagandha root extract to adult male mice. J Pharm
Pharmacol. 1998;50:1065–8.
92. Panda S, Kar A. Evidence for free radical scavenging activity of
ashwagandha root powder in mice. Indian J Physiol Pharmacol. 1997;41:
424–6.
93. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the
regulation of circulating thyroid hormone concentrations in female mice.
J Ethnopharmacol. 1999;67:233–9.
94. Parihar MS, Hemnani T. Phenolic antioxidants attenuate hippocampal
neuronal cell damage against kainic acid induced excitotoxicity. J Biosci.
2003;28:121–8.
95. Patil D, Gautam M, Jadhav U, et al. Physicochemical stability and
biological activity of Withania somnifera extract under real-time and
accelerated storage conditions. Planta Med. 2010;76:481–8.
96. Pingali U, Pilli R, Fatima N. Effect of standardized aqueous extract
of Withania somnifera on tests of cognitive and psychomotor performance
in healthy human participants. Pharmacognosy Res. 2014;6:12–8.
97. Prabu PC, Panchapakesan S. Prenatal developmental toxicity evaluation
of Withania somnifera root extract in Wistar rats. Drug Chem Toxicol.
2015;38:50–6.
98. Prakash J, Gupta SK, Kochupillai V, et al. Chemopreventive activity of
Withania somnifera in experimentally induced fibrosarcoma tumours in
Swiss albino mice. Phytother Res. 2001;15:240–4.
99. Raghavan A, Shah ZA. Withania somnifera improves ischemic stroke
outcomes by attenuating PARP1-AIF-mediated caspase-independent apop-
tosis. Mol Neurobiol. 2015;52:1093–105.
100. RajaSankar S, Manivasagam T, Sankar V, et al. Withania somnifera root
extract improves catecholamines and physiological abnormalities seen in a
Parkinson’s disease model mouse. J Ethnopharmacol. 2009;125:369–73.
101. Rajasankar S, Manivasagam T, Surendran S. Ashwagandha leaf extract: a
potential agent in treating oxidative damage and physiological abnormalities
seen in a mouse model of Parkinson’s disease. Neurosci Lett. 2009;454:11–5.
102. Rasool M, Varalakshmi P. Immunomodulatory role of Withania somnifera
root powder on experimental induced inflammation: an in vivo and in vitro
study. Vascul Pharmacol. 2006;44:406–10.
103. Rasool M, Varalakshmi P. Protective effect of Withania somnifera root
powder in relation to lipid peroxidation, antioxidant status, glycoproteins
and bone collagen on adjuvant-induced arthritis in rats. Fundam Clin Phar-
macol. 2007;21:157–64.
104. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six
rasayana herbs used in Ayurvedic medicine. Phytother Res. 1999;13:275–91.
1948 Withania somnifera (L.) Dunal

105. Sankar SR, Manivasagam T, Krishnamurti A, Ramanathan M. The

neuroprotective effect of Withania somnifera root extract in MPTP-
intoxicated mice: an analysis of behavioral and biochemical variables. Cell
Mol Biol Lett. 2007;12:473–81.
106. Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety
disorders, part 2: a review of clinical studies with supporting preclinical
evidence. CNS Drugs. 2013;27:301–19.
107. Savai J, Varghese A, Pandita N, Chintamaneni M. Investigation of
CYP3A4 and CYP2D6 interactions of Withania somnifera and Centella
asiatica in human liver microsomes. Phytother Res. 2015;29:785–90.
108. Savai J, Varghese A, Pandita N, Chintamaneni M. In vitro assessment of
CYP1A2 and 2C9 inhibition potential of Withania somnifera and Centella
asiatica in human liver microsomes. Drug Metabol Personal Ther. 2015;
30:137–41.
109. Scartezzini P, Antognoni F, Conte L, et al. Genetic and phytochemical
difference between some Indian and Italian plants of Withania somnifera
(L.) Dunal. Nat Prod Res. 2007;21:923–32.
110. Schliebs R, Liebmann A, Bhattacharya SK, et al. Systemic administration
of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit
differentially affects cholinergic but not glutamatergic and GABAergic
markers in rat brain. Neurochem Int. 1997;30:181–90.
111. Senthilnathan P, Padmavathi R, Banu SM, Sakthisekaran D. Enhancement
of antitumor effect of paclitaxel in combination with immunomodulatory
Withania somnifera on benzo(a)pyrene induced experimental lung cancer.
Chem Biol Interact. 2006;159:180–5.
112. Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D. Chemother-
apeutic efficacy of paclitaxel in combination with Withania somnifera on
benzo(a)pyrene-induced experimental lung cancer. Cancer Sci. 2006;97:
658–64.
113. Shah PC, Trivedi NA, Bhatt JD, Hemavathi KG. Effect of Withania
somnifera on forced swimming test induced immobility in mice and its
interaction with various drugs. Indian J Physiol Pharmacol. 2006;50:409–
15.
114. Sharada AC, Solomon FE, Devi PU, et al. Antitumor and radiosensitizing
effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo. Acta
Oncol. 1996;35:95–100.
115. Singh A, Naidu PS, Gupta S, Kulkarni SK. Effect of natural and synthetic
antioxidants in a mouse model of chronic fatigue syndrome. J Med Food.
2002;5:211–20.
116. Singh B, Chandan BK, Gupta DK. Adaptogenic activity of a novel
withanolide-free aqueous fraction from the roots of Withania somnifera
Dun. (Part II). Phytother Res. 2003;17:531–6.
117. Singh B, Saxena AK, Chandan BK, et al. Adaptogenic activity of a novel,
withanolide-free aqueous fraction from the roots of Withania somnifera
Dun. Phytother Res. 2001;15:311–8.
Withania somnifera (L.) Dunal 1949

118. Singh N, Nath R, Lata A, et al. Withania somnifera (ashwagandha), a

rejuvenating herbal drug which enhances survival during stress (an
adaptogen). Int J Crude Drug Res. 1982;20:29–35.
119. Singh N, Singh SP, Nath R, et al. Prevention of urethane-induced lung
adenomas by Withania somnifera (L.) Dunal in albino mice. Int J Crude
Drug Res. 1986;24:90–100.
120. Siriwardane AS, Dharmadasa RM, Samarasinghe K. Distribution of with-
aferin A, an anticancer potential agent, in different parts of two varieties of
Withania somnifera (L.) Dunal. grown in Sri Lanka. Pak J Biol Sci. 2013;
16:141–4.
121. Subbaraju GV, Vanisree M, Rao CV, et al. Ashwagandhanolide, a
bioactive dimeric thiowithanolide isolated from the roots of Withania
somnifera. J Nat Prod. 2006;69:1790–2.
122. Sudhir S, Budhiraja RD, Miglani GP, et al. Pharmacological studies on
leaves of Withania somnifera. Planta Med. 1986;1:61–3.
123. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between
chondroprotective and anti-inflammatory effects of Withania somnifera
root and glucosamine sulphate on human osteoarthritic cartilage in vitro.
Phytother Res. 2008;22:1342–8.
124. Sumantran VN, Kulkarni A, Boddul S, et al. Chondroprotective potential
of root extracts of Withania somnifera in osteoarthritis. J Biosci. 2007;32:
299–307.
125. Teixeira ST, Valadares MC, Gonçalves SA, et al. Prophylactic adminis-
tration of Withania somnifera extract increases host resistance in Listeria
monocytogenes infected mice. Int Immunopharmacol. 2006;6:1535–42.
126. Tohda C. Overcoming several neurodegenerative diseases by traditional
medicines: the development of therapeutic medicines and unraveling patho-
physiological mechanisms. Yakugaku Zasshi. 2008;128:1159–67 (Review,
Japanese).
127. Udayakumar R, Kasthurirengan S, Mariashibu TS, et al. Hypoglycaemic
and hypolipidaemic effects of Withania somnifera root and leaf extracts on
alloxan-induced diabetic rats. Int J Mol Sci. 2009;10:2367–82.
128. Udayakumar R, Kasthurirengan S, Vasudevan A, et al. Antioxidant effect
of dietary supplement Withania somnifera L. reduce blood glucose levels
in alloxan-induced diabetic rats. Plant Foods Hum Nutr. 2010;65:91–8.
129. Vedi M, Rasool M, Sabina EP. Protective effect of administration of
Withania somifera against bromobenzene induced nephrotoxicity and
mitochondrial oxidative stress in rats. Ren Fail. 2014;36:1095–103.
130. Vinutha B, Prashanth D, Salma K, et al. Screening of selected Indian
medicinal plants for acetylcholinesterase inhibitory activity. J Ethnophar-
macol. 2007;109:359–63.
131. Visavadiya NP, Narasimhacharya AV. Hypocholesteremic and antioxidant
effects of Withania somnifera (Dunal) in hypercholesteremic rats. Phy-
tomedicine. 2007;14:136–42.
1950 Withania somnifera (L.) Dunal

132. Vyas AR, Singh SV. Molecular targets and mechanisms of cancer preven-
tion and treatment by withaferin a, a naturally occurring steroidal lactone.
AAPS J. 2014;16:1–10 (Review).
133. Winters M. Ancient medicine, modern use: Withania somnifera and its
potential role in integrative oncology. Altern Med Rev. 2006;11:269–77
(Review).
134. Ziauddin M, Phansalkar N, Patki P, et al. Studies on the immunomod-
ulatory effects of ashwagandha. J Ethnopharmacol. 1996;50:69–76.
Wrightia tinctoria R. Br.
(Apocynaceae)

(Syns.: W. laciniata A.DC; W. timorensis Miq.)

Abstract
It is a flowering plant found in India, southeast Asia and Australia. Sometimes, it
is confused with Wrightia antidysenterica (Holarrhena antidysenterica or
Holarrhena pubescens). Unani physicians describe the seeds as carminative,
diuretic, lithotriptic, aphrodisiac and spermatogenic; and used them to disinte-
grate kidney stones, and with other drugs as aphrodisiac and to increase semen
production; leaves are astringent, aphrodisiac, and used for palpitation of heart
and chronic cough. Seeds are also used for the treatment of hypertension and
dyslipidemia in certain South Asian traditional systems of medicine. The plant is
considered preservative and the juice of tender leaves is regarded efficacious in
jaundice. In Siddha system of medicine, it is used for psoriasis and other
skin diseases. Chemical constituents isolated from various parts of the plant
include 3,4-seco-lup-20(29)-en-3-oic acid, lupeol, stigmasterol, campetosterol,
indigotin, indirubin, isatin, tryptanthrin, anthranilate, rutin, triacontanol, wrigh-
tial, cycloartenone, cycloeucalenol, b-amyrin, a-amyrin, b-sitosterol, and 14a-
methylzymosterol. Seed extract is a potent human platelet aggregation inhibitor.
Chlorogenic acid, a phenolic substance isolated from ethanol seed extract has
been identified as the most probable active constituent responsible for platelet
antiaggregation effect. Aqueous methanol seed extract caused a dose-dependent
decrease in arterial pressure in anesthetized rats, and lowered serum TC and TGs
in tyloxapol-induced dyslipidemia, and decreased serum TC and LDL-C,
improved HDL-C, and prevented increase in body weight by decreasing diet
consumption in high-fat diet-induced dyslipidemia in rats.

Keywords





Ankudu Asita-kutaja Dàodiàolàzhú Dyers’ oleander Inderjau-sheereen






Kalakuda Kutaja Lisan-ul-asafir Pala indigo Zaban-e-kunjashk-sheereen

© Springer Nature Switzerland AG 2020 1951

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_198
1952 Wrightia tinctoria R. Br.

Vernaculars: Urd.: Inderjau-sheereen; Hin.: Dudhi, Duhi, Kalakuda, Karayaja,

Kuda, Mitha inderjava; San.: Ambikā, Asita-kutaja, Hayamaraka, Indrayavam
(seeds), Kutaja, Stri-kutaja, Svetakutaja; Beng.: Inderjou; Mal.: Aiyapalai,
Ayyappala, Bhanthappala, Dandappala, Kambippala, Kota-kappala, Neelappala,
Thinnamppala, Vittupala; Mar.: Bhurevadi, GodaIndrajav, Kala kuda, Mitha
inderjav; Tam.: Irumpaalai, Nilapalai, Veppalai, Vetpaalai, Vetpala-verai, Vetpalai
vetpalarisi (seeds); Tel.: Ankid-kodisha, Ankudu, Tedlapala; Ara.: Lisan-ul-asafir;
Chi.: 倒吊蜡烛, Dàodiàolàzhú; Eng.: Dyers’ oleander, Ivorywood, Pala indigo,
Sweet indrajao; Per.: Tukhme-ahare-sheereen, Zaban-e-kunjashk-sheereen; Sin.:
Wal idda.
Description: It is a flowering plant found in India, southeast Asia and Australia.
Sometimes, it is confused with Wrightia antidysenterica (Holarrhena antidysen-
terica or Holarrhena pubescens). Leaves are pale-green, soft, elliptical, lanceolate,
ovate or oblong, acuminate or glabrous; panicles terminal; flowers white, follicles in
pairs, jasmine-like and fragrant. Tube of corolla twice as long as the calyx; bark over
the stem free from red coloring matter and smooth; root bark dark-brown or black,
and here and there marked with warty growths. It is not distinctly sweet, but is free
from bitterness, and tinge the saliva red; seeds greyish-brown, more pointed at the
ends than those of bitter inderjau, and marked with irregularly longitudinal fissures,
some having a tendency to become chanelled; interior is homogeneous, and of a
darkish-red or brick-red color.LXXXI The leaves of this plant turn black when dry,
and afford a kind of indigo called in Mysore Pala Indigo (Figs. 1, 2 and 3).XL

Fig. 1 Wrightia tinctoria, Flowers, J.M. Garg, WikimediaCommons; 3.0 Unported CC BY 3.0,
https://commons.wikimedia.org/wiki/File:Wrightia_tinctoria_in_Hyderabad_W_IMG_7505.jpg;
https://creativecommons.org/licenses/by/3.0/deed.en
Wrightia tinctoria R. Br. 1953

Fig. 2 Wrightia tinctoria, Flower Close up, Vinayaraj, WikimediaCommons; ShareAlike 3.0
Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Wrightia_tinctoria_09.JPG;
https://creativecommons.org/licenses/by-sa/3.0/deed.en

Fig. 3 Wrightia tinctoria, Fruits, Dinesh Valke, Flicker, https://flickr.com/photos/91314344@N00/

2443263514

Actions and Uses: Unani physicians describe the seeds (temperament, hot 2° and
dry 2°) as carminative, diuretic, lithotriptic, aphrodisiac and spermatogenic; and use
them to disintegrate kidney stones, and with other drugs as aphrodisiac and to
increase semen production;LXXVII leaves are astringent, aphrodisiac, and used for
1954 Wrightia tinctoria R. Br.

palpitation of heart and chronic cough.CV Seeds are tonic and used in seminal
weakness; leaves when chewed relieve toothache;LXXXI and the bark is used as a
tonic.XL Ibn-e-Masawaiyh used seeds for hip pain, kidney stones, postsurgery
anuria and as aphrodisiac.LXIX Seeds are also used for the treatment of hypertension
and dyslipidemia in certain South Asian traditional systems of medicine [15]. The
plant is considered preservative and the juice of tender leaves is regarded efficacious
in jaundice. Crushed fresh leaves are filled in decaying tooth cavity to relieve pain.
In Siddha system of medicine, it is used for psoriasis and other skin diseases [16].
In Tamil Nadu, one of the southern states of India, the plant is traditionally used to
treat pain and inflammation by directly applying latex from the leaves on inflam-
mation [8], and for treatment of blisters, mouth ulcers, and on fresh wounds to
promote healing [18]. A proprietary product called “777 oil” is used in the treatment
of psoriasis in the Siddha system of medicine [1].
Phytoconstituents: Chemical constituents isolated from various parts of the
plant include 3,4-seco-lup-20(29)-en-3-oic acid, lupeol, stigmasterol, campetos-
terol, indigotin, indirubin, isatin, tryptanthrin, anthranilate, rutin, triacontanol,
wrightial, cycloartenone, cycloeucalenol, b-amyrin, a-amyrin, b-sitosterol, and
14a-methylzymosterol; and four uncommon sterols, desmosterol, clerosterol,
24-methylene-25-methylcholesterol, and 24-dehydropollinastanol [16]. One of the
major seed storage proteins, Wrightia tinctoria globulin (WTG) has been isolated
from seeds [7]. A thermostable protease, named wrightin, was isolated from the
plant latex that could have applications in food and biotechnology [17].
Pharmacology: Seed extract is a potent human platelet aggregation inhibitor.
Chlorogenic acid, a phenolic substance isolated from ethanol seed extract has been
identified as the most probable active constituent responsible for platelet
antiaggregation effect [2]. Aqueous methanol seed extract caused a dose-dependent
decrease in arterial pressure in anesthetized rats, and lowered serum TC and TGs in
tyloxapol-induced dyslipidemia, and decreased serum TC and LDL-C, improved
HDL-C, and prevented increase in body weight by decreasing diet consumption in
high-fat diet-induced dyslipidemia in rats [15]. An extract of seeds lowered glucose
levels in glucose-challenged Zucker rats without affecting insulin levels [6]. The
latex extract in vitro hydrolyzed blood and plasma clots, was nontoxic and did not
induce any hemorrhagic effect at the dose of 200 lg [12]. Ethyl acetate, acetone and
methanol bark extracts also showed antinociceptive activity in mice, comparable
to ASA [13]. Chloroform leaf extract was active against T. rubrum, E. floccosum,
A. niger and S. brevicaulis; exhibited a maximum protection of 48% against
the cytopathic effect of HIV-1(IIIB) in MT-4 cells [14]. Indirubin isolated from
chloroform leaf extract demonstrated antibacterial activity against S. aureus and
S. epidermidis, and synergistically potentiated activity of ciprofloxacin [11], and
was identified as the major compound responsible for activity against dermato-
phytes such as E. floccosum, T. rubrum, T. tonsurans, T. mentagrophytes and
T. simii, and against nondermatophytes A. niger, C. albicans and Cryptococcus sp
[10]. IC50 value of methanol leaf extract against H1N1 influenza virus was reported
to be 2.25 lg/ml as compared to the IC50 of oseltamivir being 6.44 lg/ml [9].
Wrightia tinctoria R. Br. 1955

Ethanol extract of stem bark inhibited pregnancy in 100% of rats when admin-
istered orally at a dose of 250-mg/kg on days 1–7 or 1–5 post-coitum. Hexane-
soluble, chloroform-soluble, water-soluble and water-insoluble fractions of the
extract showed 100% anti-implantation effect, while n-butanol-soluble fraction
prevented pregnancy in 75% of animals. The active ethanol extract and its fractions
exhibit moderate to potent estrogen-agonistic activity, which might be responsible
for their contraceptive action in this species [5]. Petroleum ether and ethyl acetate
fractions of ethanol and methanol extracts of stem bark also exhibit cytotoxicity to
breast (MCF-7) and cervical adenocarcinoma (HeLa) cells by inducing apoptosis
[3, 4]. Topical application of thermostable serine proteases, isolated from the latex,
possess strong caseinolytic, gelatinolytic and collagenolytic activity, and signifi-
cantly improved excision wound healing rate [18].
Mechanism of Action: Synergistic antibacterial activity potentiation of cipro-
floxacin is suggested to be due to inhibition of the NorA efflux pump [11].
Human A/Es, Allergy and Toxicity: It is suggested to be harmful for stomach.LXXVII
Animal Toxicity: No animal toxicity studies are reported in the literature.
Commentary: There are no clinical studies reported in the published English
journals listed on PubMed. However, two of its traditional therapeutic uses men-
tioned by various authors, i.e. aphrodisiac and disintegration of kidney stones, will
be worth pursuing. Topical application of ‘777 oil’ widely practiced in Siddha for
psoriasis should also be of interest to clinical researchers.

References
1. Alam M, Rukmani B, Joy S, et al. Process and product standardisation of
“77 oil” used for psoriasis in siddha medicine. Anc Sci Life. 1986;6:35–41.
2. Amin RP, Kunaparaju N, Kumar S, et al. Structure elucidation and inhibitory
effects on human platelet aggregation of chlorogenic acid from Wrightia
tinctoria. J Complement Integr Med. 2013;10:1–8.
3. Chaudhary S, Devkar RA, Bhere D, Setty MM, Pai KS. Selective cytotox-
icity and proapoptotic activity of stem bark of Wrightia tinctoria (Roxb.)
R. Br. in cancerous cells. Pharmacogn Mag. 2015;11 Suppl 3:S481–7.
4. Fatima N, Ahmad MK, Ansari JA, et al. Anticancer, antioxidant potential
and profiling of polyphenolic compounds of Wrightia tinctoria Roxb. (R.Br.)
bark. J Adv Pharm Technol Res. 2016;7:159–65.
5. Keshri G, Kumar S, Kulshreshtha DK, et al. Postcoital interceptive activity of
Wrightia tinctoria in Sprague-Dawley rats: a preliminary study. Contracep-
tion. 2008;78:266–70.
6. Kumar S, Kunaparaju N, Zito SW, Barletta MA. Effect of Wrightia tincto-
ria and Parthenocissus quinquefolia on blood glucose and insulin levels in
the Zucker diabetic rat model. J Complement Integr Med. 2011;8. https://
doi.org/10.2202/1553-3840.1538.
1956 Wrightia tinctoria R. Br.

7. Kumar P, Patil DN, Chaudhary A, et al. Purification and biophysical charac-

terization of an 11S globulin from Wrightia tinctoria exhibiting hemagglu-
tinating activity. Protein Pept Lett. 2013;20:499–509.
8. Mahadevan N, Moorthy K, Perumal P, Raju SV. Pharmacognosy of leaves
of Wrightia tinctoria R. Br. Anc Sci Life. 1998;18:78–83.
9. Maria John KM, Enkhtaivan G, Ayyanar M, et al. Screening of ethnic
medicinal plants of South India against influenza (H1N1) and their antioxidant
activity. Saudi J Biol Sci. 2015;22:191–7.
10. Ponnusamy K, Petchiammal C, Mohankumar R, Hopper W. In vitro
antifungal activity of indirubin isolated from a South Indian ethnomedic-
inal plant Wrightia tinctoria R. Br. J Ethnopharmacol. 2010;132:349–54.
11. Ponnusamy K, Ramasamy M, Savarimuthu I, Paulraj MG. Indirubin
potentiates ciprofloxacin activity in the NorA efflux pump of Staphylococ-
cus aureus. Scand J Infect Dis. 2010;42:500–5.
12. Rajesh R, Shivaprasad HV, Gowda CD, et al. Comparative study on plant
latex proteases and their involvement in hemostasis: a special emphasis on
clot inducing and dissolving properties. Planta Med. 2007;73:1061–7.
13. Reddy YS, Venkatesh S, Ravichandran T, et al. Antinociceptive activity of
Wrightia tinctoria bark. Fitoterapia. 2002;73:421–3.
14. Selvam P, Murugesh N, Witvrouw M, et al. Studies of antiviral activity and
cytotoxicity of Wrightia tinctoria and Morinda citrifolia. Indian J Pharm Sci.
2009;71:670–2.
15. Siddiqi HS, Majeed A, Gilani AH. Pharmacological basis for the medicinal
use of Wrightia tinctoria in hypertension and dyslipidemia. J Cardiovasc
Pharmacol. 2014;64:151–63.
16. Srivastava R. A review on phytochemical, pharmacological, and pharma-
cognostical profile of Wrightia tinctoria: adulterant of kurchi. Pharmacogn
Rev. 2014;8:36–44.
17. Tomar R, Kumar R, Jagannadham MV. A stable serine protease, wrightin,
from the latex of the plant Wrightia tinctoria (Roxb.) R. Br.: purification
and biochemical properties. J Agric Food Chem. 2008;56:1479–87.
18. Yariswamy M, Shivaprasad HV, Joshi V, et al. Topical application of serine
proteases from Wrightia tinctoria R. Br. (Apocyanaceae) latex augments
healing of experimentally induced excision wound in mice. J Ethnopharma-
col. 2013;149:377–83.
Zingiber officinale Rosc.
(Zingiberaceae)

(Syns.: Amomum zingiber L.; A. angustifolium Salisb.)

Abstract
Ginger is one of the oldest remedies; Greeks became aware of it probably through
Persian physicians. Dioscorides described it as hot, digestive, gently laxative,
stomachic and having all the properties of pepper; it was an ingredient in collyria
and antidotes to poison. Galen recommended it in all complaints arising from cold
humours. Avicenna and other Arab and Persian physicians followed the Greeks
but expanded its use as an aphrodisiac. It has been used as antiemetic in various
traditional systems of medicine for over 2000 years. Ginger was introduced from
India/China into the Mediterranean region in the 1st Century A.D. In Ayurvedic
texts, it is described as acrid and digestive, useful for the removal of cold humours,
costiveness, nausea, asthma, cough, colic, palpitation of the heart, tympanites,
swellings, and piles. Ginger is one of the three acrids of Hindu physicians, the
other two being black pepper and long pepper. Ginger was one of the most
commonly reported herbs used during early pregnancy among women in the
United States, and 57.8% Norwegian women who reported using herbal remedies
during pregnancy, used most commonly ginger, cranberry, and raspberry leaf.
Ginger is used as a natural galactagogue by breastfeeding Thai women. It is also
reputed in relieving suppressed or retarded menstruation. Chinese describe ginger
(Shengjiang) as pungent and warm; and as a cold-discutient, diaphoretic,
antiemetic, mucolytic, antitussive, detoxicant, and anti-inflammatory. Gingerols
of various chain lengths, with 6-gingerol being the most plentiful, are the most
abundant pungent compounds in fresh rhizomes. Gingerols are thermally labile in
aqueous solution, and form the corresponding shogaols upon dehydration
reactions that imparts the characteristic pungent taste to dried ginger. Both
gingerols and shogaols are responsible for pharmacological activities of ginger. In
a comparative with ibuprofen and placebo crossover study, ginger extract
treatment of Danish patients with osteoarthritis of hip or knee demonstrated a
significant effect compared to placebo before crossover. A three-months ginger

© Springer Nature Switzerland AG 2020 1957

S. Akbar, Handbook of 200 Medicinal Plants,
https://doi.org/10.1007/978-3-030-16807-0_199
1958 Zingiber officinale Rosc.

treatment of Iranian patients suffering from knee osteoarthritis significantly

reduced levels of inflammatory markers, NO and hsCRP, compared to placebo
group.

Keywords




Adrak Gember Gingembre Ginger Ingwer

Jengibre
Katubadra




Mahaushadha Shēng jiāng Zanjabil Zenzero

Vernaculars: Urd. and Hin.: Adrak (fresh), Sonth (dry); San.: Katubadra,
Mahaushadha, Visva-bheshaja; Ben.: Aadaa (plant), Ada (fresh), Sont (dry); Mal.:
Chukka (dry), Inchi (fresh); Mar.: Alen (fresh), Sonth (dry); Tam.: Ingi, Inji
(fresh), Shukku (dry); Tel.: Allam (fresh), Allamu (green ginger), Sonti (dry); Ara.:
Skînzhbîr (Morocco), Zanjabil; Bur.: Gyin; Chi.: Chiang-t’I, Jiang, Gan-jiang
(dried), Kan-chiang, Kan-kiang, Sheng-chiang, Shēng jiāng (fresh); Cze.: Dumbír,
Zázvor, Zázvor kořen; Dan.: Ingefaer; Dut.: Gember, Gewone gember; Eng.:
Ginger; Fin.: Inkivääri; Fre.: Gingembre, Gingembre officinal, Gingembre tradi-
tionnel; Ger.: Inbwer, Ingwer; Gre.: Piperoriza, Tzintzer, Ziggiveris; Hun.:
Gyömbér; Ind.: Aliah, Jahe; Ita.: Pepe Zenzero, Zenzero, Zenzero commun,
Zenzevero; Jap.: Jinjaa, Shôga, Shokyo, Shouga; Kor.: Chinjo, Geon-gang, Jinjeo,
Kon-gang, Saeng gang; Maly.: Halia, Haliya, Haliya merah, Kunyit terus; Nep.:
Aduvaa, Agnimanth, Sutho; Nor.: Ingefær; Per.: Zinjabil; Pol.: Jembier; Por.:
Gengibre, Ingever; Rus.: Imbir’; Sin.: Inguru; Spa.: Anchoas (Mexico), Ginger
común, Jengibre, Kion; Swe.: Ingefära, Ingefoera; Tag.: Fute giya, Giya, Kasumba
giya, Laya, Loya agarisen, Luya; Tha.: Khing, Khing daeng, Khing klaeng; Tur.:
Zencebil, Zencefil, Zentzephil; Vie.: Cây gùng, Gừng, Sinh khương (green ginger).
Description: It is cultivated in all tropical countries. An erect, smooth, small plant
with a stout, cane-like stem 0.9–1.2 m high, rising from thickened rootstock; leaves
with sheathing base, narrowly lanceolate, tip acute, 20–30 cm long. Flowers small,
irregular, yellowish-green, labium purple with yellow spots. The rhizomes are
irregular, ramose, entire or broken pieces; the flat surfaces peeled, fibrous, yel-
lowish in color. Odor is aromatic and the taste is strongly aromatic and pun-
gent.LXXIX Fresh tubers vary in size, flavor and color in different soils. The
pungency of the rhizomes is mainly due to the presence of zingerone and shogaol
and the aroma due to volatile oil (Figs. 1 and 2).
Actions and Uses: Ginger is one of the oldest remedies; Greeks became aware of it
probably through Persian physicians. Dioscorides described it as hot, digestive,
gently laxative, stomachic and having all the properties of pepper; it was an ingre-
dient in collyria and antidotes to poison. Galen recommended it in all complaints
arising from cold humours. Avicenna and other Arab and Persian physicians fol-
lowed the Greeks but expanded its use as an aphrodisiac.XL It has been used as an
antiemetic in various traditional systems of medicine for over 2000 years [229].
Ginger was introduced from India/China into the Mediterranean region in the 1st
Century A.D [314]. In Ayurvedic texts, it is described as acrid and digestive, useful
Zingiber officinale Rosc. 1959

Fig. 1 Zingiber officinale, Plant Illustration, Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen,
WikimediaCommons, https://commons.wikimedia.org/wiki/File:Koeh-146-no_text.jpg

Fig. 2 Zingiber officinale, Ginger Roots, Prof. Akbar, Original

for the removal of cold humours, costiveness, nausea, asthma, cough, colic, palpi-
tation of the heart, tympanites, swellings, and piles. Ginger is one of the three acrids
of Hindu physicians, the other two being black pepper and long pepper. Combined
with other spices and sugar, it is given in dyspepsia and loss of appetite. Juice of
fresh tubers, with or without the juice of garlic, is a favorite remedy for cough and
1960 Zingiber officinale Rosc.

asthma; with lime juice it is used in bilious dyspepsia, and a paste of dry ginger in
warm water is applied to the forehead to relieve headache.XL Unani physicians
regard it (temperament, (fresh) hot 3° and dry 1°; (dried) hot 3° and dry 2°) digestive,
carminative, intellect and memory enhancer, and aphrodisiac; locally, ginger is
rubefacient and anodyne.LXXXI Dried ginger is called sonth and is aromatic, stim-
ulant, stomachic, digestive, carminative, diaphoretic, and sialogogue (when
chewed), produces a sensation of warmth at the epigastrium and expels flatus;
particularly beneficial for indigestion, mild diarrhea and flatulent colic,XXIV,CXXXII
abdominal cramps, anorexia and sexual debility in patients with phlegmatic
temperament,LXXVII and as an adjunct to purgatives to correct their griping prop-
erties.LXXIX It is also used for nausea, vomiting and alcoholic gastritis and is the
top-ranking herbal. Ibn Jazlah considered the Chinese ginger as the best and used it
for headache, to improve sight, for liver and stomach ailments, as an antidote and to
reduce swellings.LIII Ginger was one of the most commonly reported herbs used
during early pregnancy among women in the United States [51], and 334 out of 578
(57.8%) Norwegian women who reported using herbal remedies during pregnancy,
used most commonly ginger, cranberry, and raspberry leaf [107]; in both cases
women had college education and were relatively mature. Ginger is used as a natural
galactagogue by breastfeeding Thai women [232]. It is also reputed in relieving
suppressed or retarded menstruation. The decoction is used by traditional healers of
Algeria for the treatment of cough, flu and allergies [39], and is also reported to
prevent and abort bouts of migraine headache without any side-effects [202]. In the
Philippines, pounded rhizome alone or mixed with oil is used externally as revulsive
(counterirritant) and antirheumatic.CXVII
Chinese describe ginger (Shengjiang) as pungent and warm; and as a cold-
discutient, diaphoretic, antiemetic, mucolytic, antitussive, detoxicant, and anti-
inflammatory. Fresh ginger is used in common cold due to pathogenic “wind-cold”
(characterized by severe intolerance to cold, slight fever, headache, general aches,
nasal congestion, runny nose, and floating and tense pulse), cough and vomiting
caused by pathogenic cold in the stomach.XVIII Ginger is known to remove chills
caused by common cold, and to warm body [111]. In case of vomiting due to
pathogenic cold, ginger can be used singly or in combination with the tuber of
Pinellia ternata. Also, it can be used with the rhizome of Coptis chinensis and the
skinned stem of Phyllostachys nigra, for the treatment of vomiting due to patho-
genic heat in the stomach. With magnolia bark, ginger rhizome is used in many
prescriptions for the treatment of mental disorders [350]. HsuLXVI described it as a
general drug mentioned in The Herbal by Shen Nung, and mainly used for a cold
due to wind-chill, for stridor, for nausea, vomiting, diarrhea, abdominal pain,
rheumatism, and for pain in the spleen. Tongling White Ginger is considered one of
the best varieties in China [81].
Phytoconstituents: Gingerols of various chain lengths, with 6-gingerol being the
most plentiful, are the most abundant pungent compounds in fresh rhizomes [62].
Gingerols are thermally labile in aqueous solution, and form the corresponding
shogaols upon dehydration reactions that imparts the characteristic pungent taste to
Zingiber officinale Rosc. 1961

dried ginger. Both gingerols and shogaols are responsible for pharmacological
activities of ginger. Gingerols exhibit a novel reversible kinetics, undergoing
dehydration-hydration transformations with shogaols [43]. Shogaols, the dehydrated
form of gingerols and mainly present in dried rhizomes [130], are used as important
biomarkers for the quality control of ginger-containing products [279]. Gingerol
content of the African land race are at least 3X higher than the typical commercial
cultivars of ginger [82]. [6]-Gingerol content was significantly higher in samples
from Bourbon, Portland (Jamaica) harvested at 9 months than at 8 months [36].
Concentrations of gingerols are slightly reduced in dried ginger, while the concen-
trations of shogaols are increased [131]. Essential oil, total gingerols and shogaols
decrease on slicing and with increase in drying temperature; ginger rhizomes dried
under sun retain the maximum essential oil and oleoresin content in dried ginger
[120]. Ye et al. [348] chemically analyzed ginger in the different forms used in China.
The analysis showed that the constituents might change under different forms.
Fresh ginger contained 25 constituents while dry ginger showed 22, of which one
was not present in other forms of ginger; ginger roasted with sand in a pan had 23,
two of which were unique to this form; three out of 23 found in ginger roasted with
charcoal were unique to this form of ginger. Jolad and colleagues [130] isolated 51
compounds from fresh Chinese white and Japanese yellow varieties of ginger,
[6]-gingerol being the main constituent; other constituents included gingerols,
paradols, dihydroparadols, acetyl derivatives of gingerols, shogaols, 3-dihydro-
shogaols, gingerdiols, mono- and diacetyl derivatives of gingerdiols, 1-dehydro-
gingerdiones, and diarylheptanoids. One hundred-fifteen compounds were isolated
from Hawaiian white and yellow ginger varieties [131]. Bao and associates [37]
reported b-sitosterol palmitate, isovanillin, glycol monopalmitate, hexacosanoic acid
2,3-dihydroxypropyl ester, maleimide-5-oxime, p-hydroxybenzaldehyde, adenine,
and 1-(omega-ferulyloxyceratyl) glycerols (10a–10f) as new compounds from
Chinese ginger. Three monoacyldigalactosyl-glycerols named gingerglycolipids
A, B and C, and antiulcer components, 6-gingesulfonic acid [351, 352], b-
sesquiphellandrene, b-bisabolene, ar-curcumene and 6-shogaol [343] were isolated
from dried rhizomes from Taiwan. [6]-, [8]-, and [10]-shogaols and [6]-, [8]-, and
[10]-gingerols were identified as the antiemetic principles [143]. [6]-, [8]-, and
[10]-gingerols and 6-gingerdiol also show significant antifungal activities against 13
human pathogens [82]. Gingerols and their derivatives are also excellent in vitro
inhibitors of LPS-induced PGE2 production [130], while 6-shogaol exhibits potent
in vitro cytotoxicity against human tumor cells [153]. 1-Dehydrogingerdione [56],
and several diarylheptanoids [174] have also been isolated. Beta-sesquiphellandrene
was identified as the antirhinoviral sesquiterpene [67], and (E)-8b,17-epoxylabd-
12-ene-15,16-dial inhibited cholesterol biosynthesis in homogenated rat liver [311].
Both cooking and storage significantly affect the antioxidant activity [59].
The rhizomes contain 1–3% volatile oil; major constituent of ginger oil is cur-
cumene [2], but Singh et al. [293] reported geranial (25.9%) as the major com-
ponent in essential oil, and Jeena et al. [122] found a-zingiberene (31%),
ar-curcumene (15.4%) and a-sesquiphellandrene (14.02%) as the major constituents
of Indian ginger oil. The yield of volatile oil from fresh ginger was reported to be
1962 Zingiber officinale Rosc.

0.31 ± 0.08%, and camphene, p-cineole, a-terpineol, zingiberene and pentade-

canoic acid as the major components of volatile oils of both fresh and dried ginger
from Pakistan [75]. The EO from ginger of Ecuadorian origin yielded 71 com-
pounds; a-zingiberene (17.4%), geranial (10.5%), neral (9.1%), camphene (7.8%),
a-farnesene (6.8%) and b-sesquiphellandrene (6.7%), being the main constituents
[106]. Citral, eucalyptol and camphene were the major components of ginger oil
from Thai ginger [184]. Earlier ginger oil was reported to contain sesquiterpene
zingiberene; the terpenes, camphene and phellandrene; also, methyl heptenone,
arnesene, cineol, borneol, geraniol, and linalool. Oleoresin contained aromatic
ketones (zingirone, shogaol) and gingerol.XLVII,CXXXXI The low-boiling con-
stituents from rhizome were identified as heptane, octane, nonane, nonanol,
acetaldehyde, propionaldehyde, butyraldehyde, isovaleraldehyde, acetone, PrOH,
diethyl sulfide, methyl allyl sulfide, methyl and ethyl acetates, a-pinene, camphene,
b-pinene, sabinene, myrcene, limonene, b-phellandrene and 1,8-cineole [134].
Pharmacology: Ginger supplementation in diet of rats for 8-weeks demonstrably
enhanced intestinal lipase, the disaccharidases, sucrase and maltase activities [241],
and pancreatic lipase, amylase, trypsine and chymotrypsine activities [240],
activities of gastric and intestinal mucosal antioxidant enzymes–SOD, CAT, GR,
and GST [252], and increased intestinal microvilli length and perimeter, providing
increased absorptive surface for the bioavailability of food micronutrients [250].
Ginger prevents gastric lesions in rats [139, 329], and 6-gingerol increases bile
secretion as one of its effects on digestive tract [345]. Aqueous extract protected rats
against experimental gastric ulcers, and inhibited H+,K+-ATPase (proton pump)
activity, comparable to lansoprazole [208]. Roasted ginger decoction also prevented
gastric ulcers induced by various noxious agents but the dried ginger was inef-
fective [339], ginger oil was also protective against gastric ulcers in rats [150, 168].
Acetone extract almost completely inhibited HCl/ethanol-induced gastric lesions in
rats, while zingiberene and 6-gingerol were partly protective [342]; the extract also
enhanced gastrointestinal motility [344]. Oral administration of 6-gingerol signifi-
cantly inhibited basal gastric acid secretion in mice [224]. Aqueous ginger extract
was ineffective, while acetone and ethanol extracts were significantly effective
against cisplatin-induced emesis in dogs, but ineffective against apomorphine-
induced emesis [289], and ginger juice and acetone extract reversed cisplatin caused
delay in gastric emptying [288]. 6-Shogaol, however, enhanced carbachol-
accelerated small intestinal transit, and ameliorated BaCl2-induced hyperperistal-
sis of small intestine [102]. Ginger, its aqueous extract and volatile oil were
effective against TNBSA- [109], and acetic acid-induced ulcerative colitis in rats
[73, 262], possibly due to their antioxidant and anti-inflammatory effects. Diet
supplemented with ginger protects against ethanol- [183], and cadmium and
mercury-hepatotoxicity in rats [220], and pretreatment of rats with ethanol extract
protected against CCl4- [198, 235, 349], APAP- [9, 349], bromobenzene- [78], and
atorvastatin-caused hepatotoxicity [103], and ameliorated fructose-induced fatty
liver and hypertriglyceridemia [87], and proinflammatory effect of high-fat diet in
rats [165]. Methanol extract also protects rats against CCl4-hepatotoxicity [28], and
Zingiber officinale Rosc. 1963

6-gingerol protected mice against APAP-hepatotoxicity [270]. However, ginger

extract was ineffective in obstructive jaundice in rats [15]. Hydroalcohol extract was
protective against radiation-induced conditioned taste aversion in rats [99], and
significantly inhibited in vitro growth of C. jejuni [65]. Acetone extract inhibited
5-HT-induced hypothermia and diarrhea; [6]-shogaol was identified mainly
responsible for these activities [111].
Ginger feeding lowered blood glucose, serum TC and ALP and significantly
increased HDL-C in normal rats [4], decreased serum and liver cholesterol in
normal and hypercholesterolemic rats [272], and stimulated conversion of choles-
terol to bile acids by elevating activity of hepatic cholesterol-7 a-hydroxylase [295].
Ginger powder protected against STZ-induced diabetes and oxidative stress [158],
significantly lowered LPO, increased blood GSH content, maintained activities of
antioxidant enzymes: SOD, CAT and GPx [3], protected rats against lindane-
induced oxidative stress [5], and ginger juice also decreased lindane-induced LPO
in rats brain [287]. Dietary ginger consumption (1%) for ten-weeks decreased
serum cholesterol levels in rats [68], and air-dried ginger powder significantly
inhibited development of aortic and coronary atheroma in hypercholesterolemic
rabbits, without significantly lowering blood lipids [323], and in aortae of hyper-
cholesterolemic rats [338]. Oral aqueous extract for 4-weeks to diabetic and insulin
resistant rats reduced FBG and MDA levels, and increased serum insulin level and
enhanced insulin sensitivity [116], significantly decreased kidney glycogen and
increased liver and skeletal muscle glycogen [1]. Aqueous extract feeding of mice
with a high-fat diet for 8-weeks significantly reduced adipose tissue weights [101],
and aqueous extract administered (i.p.) daily for 7-weeks to diabetic rats lowered
serum glucose, cholesterol and triacylglycerol levels, reduced urine proteins, and
prevented weight loss during treatment period [13]. Ginger also effectively pre-
vented the development of diabetic cataract in rats [277], alleviated metabolic
syndrome and elevation of atherogenic indices by increasing insulin level,
enhancing antioxidant defense system and decreasing LPO of diabetic rats [175];
and ginger juice prevented 5-HT-induced hyperglycemia and hypoinsulinemia in
normal rats, and significantly decreased FBG and increased insulin levels of dia-
betic rats [11]. Islam and Choi [118], however, reported that adding freeze-dried
ginger powder to high-fat diet of diabetic rats for four-weeks did not influence body
weight, FBG, HbA1c, liver weight, liver glycogen, and serum lipid profile. Ethanol
extract lowered FBG in diabetic rats [136], attenuated fructose-induced hyperin-
sulinemia and insulin-resistance in rats [328], and increased energy expenditure and
attenuated diet-induced obesity in C57BL/6 J mice [193]. Methanol and ethyl
acetate extracts also significantly reduced body weight, glucose, insulin and lipid
levels in obese mice [90]. Ginger also exhibits very good potential for inhibition of
a-glucosidase and a-amylase [260]. The extract of aerial parts showed hypo-
glycemic and diuretic activities [27].
Ginger powder (5%) with high-fat diet to rats for four-weeks significantly
reduced body weight and lipid profile, and increased HDL-C, without affecting
total bilirubin or pancreatic lipase activity [182]. Aqueous extract inhibits intestinal
absorption of dietary fat by inhibiting its hydrolysis, as it markedly lowers adipose
1964 Zingiber officinale Rosc.

tissue weights in high-fat diet-fed mice [106], ameliorates high-fat diet-induced

hypercholesterolemia in rats [77], paraben-induced liver LPO, and significantly
increases activities of antioxidant enzymes in mice [26]. Ethanol extract lowered
serum and tissue cholesterol, serum TGs, lipoproteins and phospholipids of
hypercholesterolemic rabbits [42], glucose, TC, and TGs, and increased HDL-C of
diabetic rats [41], and protected against development of metabolic syndrome [207],
and downregulated HMG-CoA reductase protein of hyperlipidemic rats [206].
Plasma TGs, TC, VLDL and LDL-C in apolipoprotein E-deficient mice were also
decreased by ethanol extract, while cellular cholesterol biosynthesis rate in peri-
toneal macrophages was reduced [85]. Methanolic extract of dried rhizomes
reduced fructose-induced elevation in lipid levels, body weight, hyperglycemia and
hyperinsulinemia [133]. Ginger reduces intensity of potassium chromate-induced
oxidative stress, anemia, nephrotoxicity, hepatotoxicity, and lipids profile pertur-
bations in rats [159]. Ethanol and polyphenol extracts show potent antioxidant
activity [144, 358], and ethanol extract possesses potent ferric-reducing antioxidant
power [258]; the antioxidant activity is correlated with the phenolic content [257].
Essential oil of dried ginger shows higher antioxidant activity than fresh ginger
EO [75].
Aqueous extract inhibits in vitro platelet aggregation induced by several
aggregation agents and platelet COX products, such as TX and PGF2a, PGE2 and
PGD2 [299, 300, 302]. Gingerols are effective inhibitors of AA-induced human
platelet aggregation [157], and [6]-gingerol and [6]-shogaol exhibit potent
antiplatelet aggregation activity [166]. Pretreatment with ethanol extract protected
against isoproterenol-induced oxidative myocardial injury in rats [19, 21], and
hydroalcohol extract of dried ginger ameliorated changes in heart structure, and
reversed elevated levels of homocysteine and CRP, leptin, cathepsin G, and apoA
and B of diabetic rats [114]. A standardized ginger extract (EV.EXT 33) produced
no significant effect on BP, HR or blood coagulation parameters in rats [332],
whereas, ginger is reported to be a significant ACE inhibitor [261], and [6]-gingerol
is a novel angiotensin II type 1 receptor antagonist [170]. [6]-shogaol (i.v.), though,
caused a rapid fall in BP, bradycardia and apnea in rats by a peripheral action [306].
Crude methanol extract showed potent, positive inotropic effects on isolated left
atria of guinea pig; gingerol was identified as the active principle.
Ginger protects rats’ brain against diabetes-induced damage by reducing
oxidative stress, apoptosis, and inflammation [74], improves antioxidant status
[282], protects against behavioral dysfunction and Alzheimer-like symptoms in rats
[356], improves cognitive performance, memory impairment and antioxidant
markers in cerebral ischemic rats [129, 330]. Ginger also prevents development of
morphine tolerance, and naloxone-induced morphine withdrawal in rats [66], and
ethanol extract potentiated analgesic effect of morphine [280]. Ethanol extract
exhibits significant adaptogenic activity, and reverses changes caused by a variety
of chronic stress models in mice [162]. Incubation with aqueous extract decreases
in vitro iron-induced brain LPO [221], and aqueous methanol (90%) and chloro-
form extracts protect primary neuronal cells from b-amyloid insult [151]. [6]-
Shogaol inhibits spontaneous motor activity, prolongs hexobarbital-induced sleeping
Zingiber officinale Rosc. 1965

time, improves intestinal motility, and exhibits antipyretic, analgesic, and a potent
antitussive effect [304], attenuates apoptotic cell death in rats with spinal cord injury
[161], exhibits significant neuroprotective effects against transient global ischemia
in rats, and inhibits LPS-induced release of NO and the expression of iNOS in
primary microglial cell cultures [97]. Treatment with zingerone prevented
6-OHDA-induced dopamine reduction in mouse striatum; the neuroprotective effect
was mediated mainly by increase in systemic SOD activity [132].
Ginger inhibits COX-1, COX-2, and 5-LOX, suppressing synthesis of both PGs
and LTEs [94], and potently inhibits TX synthetase, raising PGI2 levels, without a
concomitant rise in PGE2 or PGF2a [34]. Oral aqueous extract for four-weeks
significantly lowered serum PGE2 and TXB2 levels, and reduced serum cholesterol
in rats [313]. Ethanol extract exhibits antipyretic, hypoglycemic [190, 222],
anti-inflammatory [190, 222, 256], and analgesic activities and inhibits PG release
from rat peritoneal leucocytes [190]. Oral administration of squeezed ginger juice
to mice augmented TNF-a production in peritoneal cells, but repeated adminis-
tration had opposite effect, increasing serum corticosterone level and producing
anti-inflammatory effect [316]. Hydroalcohol extract (i.p.) effectively reduced rat
paw edema by various noxious stimuli [236], collagen-induced arthritis with
reduction in serum levels of IL-1b, IL-2, IL-6, TNFa, and anti-CII antibodies [84].
Ginger oil also exhibited significant in vivo anti-inflammatory and analgesic
activities and increased antioxidant enzymes levels in the liver after oral adminis-
tration to mice for a month [122], and produced a significant suppression of
M. tuberculosis bacilli-induced paw and joint swelling in rats [286]. [6]-Shogaol
produced anti-inflammatory activity [163, 269, 305] and inhibited platelet aggre-
gation [305], while [10]-gingerol, [8]- and [10]-shogaol in vitro inhibited COX-2
but not COX-1 [320]; however, Nurtjahja-Tjendraputra et al. [219] reported sig-
nificant and better than aspirin in vitro inhibition of AA-induced platelet activation
by [8]-gingerol, [8]-shogaol, and [8]-paradol; [8]-paradol being the most potent
COX-1 inhibitor and antiplatelet aggregation agent. [6]-Gingerol (i.p.) produced
analgesic, anti-inflammatory [354], and hypothermic effects with significant
decrease in metabolic rate [317]. Nongingerol components also contribute to the
antiarthritic effects of gingerols [86], as [6]-shogaol possesses potent antioxidant
and anti-inflammatory properties [70], and is a much stronger inhibitor of AA
release and NO synthesis than [6]-gingerol [276].
Ethanol extract (i.p.) markedly decreases BUN concentrations in normal mice
[191], and orally significantly protects rats against alcohol- [283], diabetes- [259],
lead- [263], gentamicin- [210, 254], cisplatin [10], and doxorubicin-induced
nephrotoxicity [8], increasing levels of renal antioxidant enzymes and reducing
MDA levels. Ginger also exhibits renoprotective effect against I/R injury in rats
[177, 181, 318] and oxidative damage of organs due to cadmium [226]. Con-
sumption of ginger in diet (1%) protected against chemically-induced urothelial
carcinogenesis [113], and significantly inhibited DMH-induced colon carcinogen-
esis in rats [185, 186] and produced hypolipidemic effect [187], but Dias et al. [68]
found no significant effect on DMH-induced colon carcinogenesis in rats. Aqueous
and ethanol extracts suppressed proliferation and colony formation of breast cancer
1966 Zingiber officinale Rosc.

cell lines; the ethanol extract being more effective [76]; exposure of epithelial
ovarian cancer cell lines to ethanol extract profoundly reduced cell growth [265].
Aqueous extract has also been shown to cause apoptosis of human nonsmall lung
epithelium cancer cells and HeLa cells [61]. Hot water extract significantly inhib-
ited development and growth of mammary tumors in SHN virgin mice [204],
whereas oral ethanol extract was active against hepatocarcinogenesis in rats [98,
355], and inhibited growth and progression of PC-3 xenografts by approximately
56% in mice [137]. Significant augmentation of the antiproliferative activity of
ginger extract against prostate cancer cells (PC-3) occurred when the extract was
combined with its constituents (especially, 6-gingerol) [50]. Topical application of
ethanol extract onto the skin of mice significantly inhibited TPA-caused induction
of epidermal ODC, COX, and LOX activities, and highly significantly protected
against DMBA-initiated skin tumor incidence and multiplicity in mice [142].
Topical application of [6]-gingerol also inhibited DMBA-induced and TPA pro-
moted skin papillomas [233], and B[a]P-induced mouse skin tumorigenesis [215].
A number of ginger constituents have shown in vitro anticancer activity, such as
6-shogaol reduced viability of gastric cancer cells [117], human nonsmall cell lung
cancer cells [112], human leukemia HL-60 cells [291]; [6]-gingerol exhibited
considerable cytotoxicity to human epidermoid carcinoma cells [214], rat ascites
hepatoma cells [341], colon cancer cells [52, 125], and produced genotoxicity in
HepG2 cells [347].
Aqueous extract administered to rats for 8-days significantly increased relative
weight of testes, serum testosterone and testicular cholesterol level, and epididymal
a-glucosidase activity, indicating androgenic activity [135]. Both aqueous and
methanol extracts orally administered to diabetic mice for 65 consecutive days
increased fertility index, sex organs weight, serum testosterone level and sperm
motility and count [281]. Pretreatment with ginger restored reproductive functions of
diabetic rats [146], ameliorated aluminium chloride-induced reproductive toxicity
[196], restored lead-induced fall in testosterone levels [266], and busulfan-induced
reproductive damage in male rats [47]. Pretreatment of rats with ethanol extract
significantly restored reproductive function [17], reduced cisplatin-induced sperm
abnormality and enhanced sperm motility, restored MDA and antioxidant enzymes
to control levels [18]. Rat fetuses exposed to ginger tea during gestation were
significantly heavier than controls, especially female fetuses, and had more advanced
skeletal development [335].
Ginger aqueous extract exhibited bactericidal [225], and synergistic or additive
activity with clarithromycin against clinical isolates of H. pylori [218]. Ginger is
potently effective against E. coli [171, 308], and cariogenic bacteria: S. mutans and
S. sanguinis [32]. Commercial ginger paste heated with ground beef at 70 °C for
seven minutes inhibited in vitro growth of E. coli [96]. Hot water extract of fresh
ginger was effective against human RSV [55]. Aqueous, ethanol and methanol
extracts significantly inhibited growth of resistant bacterial strains of S. typhi, Shi-
gella, P. aeruginosa, E. coli, B. subtillis, S. aureus, S. epidermidis and K. pneumo-
niae [95]. Ethanol extract significantly inhibited growth of gentamicin-resistant
clinical isolates of enterococcal strains [264], clinical isolates of S. aureus, S. pyogenes,
Zingiber officinale Rosc. 1967

S. pneumoniae and H. influenzae [12], E. coli [138, 285], S. aureus, Bacillus sp.,
P. aeruginosa, and Proteus sp. [138], and periodontal bacteria, P. gingivalis,
P. endodontalis and P. intermedia [234]. Methanol extract exhibited strong
antioxidant activity [307], and was significantly active against S. aureus [40], 15
strains of H. pylori with an MIC of 25 µg/ml [178, 179], and T. gondii [60]. Aqueous
and ethanol extracts markedly reduced worm burden and egg load in liver and
intestine of S. mansoni-infected mice, and reduced liver fibrosis [16, 197]. The EO
showed modest antibacterial activity against L. monocytogenes, L. innocua and S.
aureus [213], but a significant activity against mycotoxin producing fungi, F.
moniliforme, A. flavus and A. fumigates [212]. Fluconazole-resistant C. albicans, C.
dubliniensis, and Candida nonalbicans were more susceptible to the EO from Brazil
than fluconazole-susceptible yeasts [249]. Essential oil of air-dried rhizomes pos-
sesses potent inhibitory activity against C. albicans, and [6]-shogaol being the most
active constituent, followed by citral and [6]-gingerol [310]; and is virucidal to
clinical isolates of acyclovir-resistant HSV-1 [278] and HSV-2 [156]. However,
successive extracts in petroleum ether, diethyl ether, chloroform, ethyl acetate,
acetone, ethanol and methanol were largely inactive against MDR strains of E. coli,
S. mutans, S. bovis, C. albicans, C. tropicalis, C. glabrata and C. krusie [147]. [6]-
dehydrogingerdione, [10]-gingerol, [6]-shogaol and [6]-gingerol, were effective
against extensively drug-resistant clinical isolates of A. baumannii, and modified
their resistance to tetracycline [327]. [10]-gingerol potentiated in vitro antimicrobial
activity of aminoglycosides against vancomycin-resistant enterococci [205].
Feeding dried ginger to mice stimulated humoral immunity [253], and alcohol
extract also significantly improved humoral immunity of tumor bearing mice [169].
However, ginger volatile oil influences both cell-mediated immune response and
nonspecific proliferation of T lymphocyte in mice [357], and 8-gingerol suppressed
both humoral and cellular immune responses in mice [172]. Aqueous extract
markedly decreases recruitment of eosinophils to the lungs and suppresses Th2
cell-driven response to allergen, and diminishes serum levels of IL-4, IL-5, eotaxin
in the lungs as well as specific IgE titers in mice [6], whereas hydroalcohol extract
reduces serum levels of PGE2 and TXA2 in LPS-induced tracheal hyperreactivity
and lung inflammation in rats [7].
Clinical Studies: A survey of American obstetricians/gynecologists reported
pregnancy-associated N/V (NVP) in 51.4% patients, of which 9.2% had severe and
prolonged N/V, and 2.4% required hospitalization. Most physicians (51.8–59.7%)
recommended their patients to use ginger; women physicians were more likely to
recommend ginger than prescribe an antiemetic [247, 248]. Oral ginger significantly
reduced NVP in Thai and Iranian women [195, 228, 326], and was equally or more
effective than vitamin B6 in reducing episodes of NVP in RCTs [58, 80, 294, 296].
Sixty-seven percent of pregnant Floridian women vomiting during 1st trimester
stopped vomiting by day 6 after using a ginger syrup four times a day [145]. Ginger
administration in four doses of 250 mg daily was significantly effective in
preventing N/V of hyperemesis gravidarum in Danish women [83]. However,
Pongrojpaw et al. [245] reported 500 mg ginger twice daily ineffective in preventing
1968 Zingiber officinale Rosc.

N/V in Thai pregnant women. Pretreatment with ginger also significantly reduced
incidences of postoperative nausea in women who underwent gynecological surgical
procedures, comparable to metoclopramide [46, 209, 238, 244]. A meta- analysis of
controlled RCTs found that a dose of at least 1 g of ginger is more effective in
preventing postoperative N/V than placebo [53]. However, other researchers have
reported no significant postoperative antiemetic effect in such patients [24, 71].
Intake of 2 g ginger or combining it with droperidol did not prevent N/V postdi-
agnostic gynecological laproscopy in Thai women [325]; whereas Apariman et al.
[22] reported significant prevention of N/V in Thai women 6-hours post procedure.
Ginger also protected against antitubercular drugs-induced nausea [79], and lowered
levels of TNF-a, ferritin and MDA [160]. Addition of ginger to standard antiemetic
therapy further reduced severity of chemotherapy-induced nausea in children,
young adults and adults, especially during the 1st 24 h [20, 25, 105, 230, 239, 268,
274]. Zick et al. [359], however, reported no effect of adding ginger to 5-HT3
antagonists and aprepitant on chemotherapy-induced nausea up to a daily dose of
2 g; the reason alleged for this negative report could be that they used a binary
variable (yes or no) instead of grading the severity of nausea, and used ginger
powder extract without masking the odor. Nonetheless, ginger (1 g) started on 1st
day of cisplatin-chemotherapy for 4-days was also not effective in preventing N/V
compared to metoclopramide in Thai gynecological cancer patients [189]. Com-
bining ginger with dexamethasone also did not significantly reduce postoperative
N/V after thyroidectomy [312]. Aromatherapy of children with ginger EO during
perianesthesia period reduced distress [216]. Ginger powder significantly reduced
induced-vertigo in healthy volunteers better than the placebo [93], and significantly
reduced tendency to vomit and cold sweating due to sea sickness in Danish naval
cadets [92]. Powdered ginger was also superior to dimenhydrinate in reducing
motion sickness in 36 men and women with very high susceptibility to motion
sickness [199]. Ginger pretreatment reduced motion-induced nausea, tachygastria,
plasma vasopressin, and prolonged latency for nausea onset, and shortened recovery
time in volunteers with a history of motion sickness [167]. However, effect of ginger
on induced motion sickness [303, 337] and the nystagmus response to it were also
reported comparable to placebo [108]. Supplementation of gastric feed with ginger
extract helped reduce delayed gastric emptying and the incidence of
ventilator-associated pneumonia in hospitalized adult respiratory distress syndrome
patients [284]. However, a dose of 1,200 mg ginger administered to healthy male
volunteers did not significantly affect gallbladder volume or ejection fraction, and
gastric symptoms compared to placebo [63].
Ginger rhizome powder (250 mg) four times daily for three-days, starting from
the onset of menstruation, was as effective as mefenamic acid and ibuprofen in
relieving pain in Iranian students with primary dysmenorrhea [227, 292]. The
intensity and duration of pain was significantly decreased when ginger (500 mg
thrice daily) was started one or two days before the start of periods in Iranian
students with primary dysmenorrhea, but the duration of pain was not significantly
affected when treatment was started with the start of periods [141, 255], and
reduced nausea associated with dysmenorrhea [124]. Ginger powder during first
Zingiber officinale Rosc. 1969

three days of menstruation was also superior to progressive muscle relaxation in

relieving symptoms of dysmenorrhea in 75 Indian nursing students [100]. In an
RCT, ginger treatment, starting seven days before the onset, and continuing for
3-days during menstruation, significantly improved severity of PMS symptoms in
Iranian women [149], and was also highly significantly effective in reducing heavy
menstrual bleeding in high school girls [140]. In an RCT, dried ginger adminis-
tration to Thai women for 7-days postpartum significantly increased milk volume
without affecting prolactin level [232].
In a comparative with ibuprofen and placebo crossover study, ginger extract
treatment of Danish patients with osteoarthritis of hip or knee for 3-weeks
demonstrated a significant effect compared to placebo before crossover [45]. Seven
Danish rheumatic arthritis patients reported relief in pain and associated symptoms
after ginger use [297], and more than three quarters of 46 arthritis Danish patients
and all 10 patients with muscular discomfort experienced relief in pain and swelling
after using ginger from 3 months to 2.5 years [298]. A three-months ginger (1 g/d)
treatment of Iranian patients suffering from knee osteoarthritis significantly reduced
levels of inflammatory markers, NO and hs-CRP, compared to placebo group [200,
203]. A meta-analysis of RCTs showed ginger significantly reducing pain and
disability of osteoarthritis [38]. In an RCT, consumption of 2 g of either raw or
heated ginger for 11 consecutive days, followed by 18 eccentric actions of elbow
flexors to induce pain and inflammation in healthy volunteers, significantly reduced
pain 24 h after eccentric exercise compared to placebo [44]. In an open-label study,
supplementation of diclofenac therapy with ginger powder had synergistic effect on
reducing symptoms of OA of knee [231]. A commercial extract (Zintona EC®) was
significantly superior over placebo in relieving symptoms of gonarthritis in Israeli
patients after 6-months treatment [334]. Intake of both raw and cooked ginger by
healthy volunteers for two weeks did not affect ex vivo TXB2 production by
stimulated platelet [119], though ginger in vitro inhibits COX activity of platelets.
However, serum TXB2 level was significantly decreased in volunteer Danish
women who consumed 5 g of raw ginger daily for 7-days [301]. A pilot random-
ized trial at Emory University of 20 people at increased risk for colorectal cancer
(CRC) showed that 2 g ginger daily for 28-days reduced proliferation in the
normal-appearing colorectal epithelium and increased apoptosis [64], significantly
decreased AA and increased LTB4 versus placebo [360]. Ginger (2 g/d) also sig-
nificantly lowered COX-1 protein expression in patients at increased risk for CRC
but not in those at normal risk for CRC [128]. In healthy volunteers with normal
risk for CRC, ginger showed potential to decrease eicosanoid levels in colonic
mucosa [361].
Townsend and associates [315] of Columbia University Medical Center reported
that as many as 40% of patients with asthma use herbal therapies as adjunct to
standard therapy to manage their asthma symptoms. They found that ginger and its
active constituents, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax airway smooth
muscle, and [8]-gingerol attenuates airway hyperresponsiveness. Acute respiratory
distress syndrome hospitalized patients, fed enteral diet supplemented with gin-
ger, had significantly lower serum levels of IL-1, IL-6, and TNF-a compared with
1970 Zingiber officinale Rosc.

control group, and significantly reduced duration of mechanical ventilation and

length of intensive care unit stay [319].
Daily ginger intake of 3 g in three divided doses for 45-days significantly
reduced TC and TG levels in hyperlipidemic Iranian patients [14]. A two-months
treatment with ginger (2–3 g/d) of Iranian NIDDM patients significantly lowered
levels of blood insulin, LDL-C, TG and HOMA index, without affecting FBG, TC,
HDL-C and HbA1c [180, 201], whereas, ginger intake of 1,600 mg/d by Ira-
nian NIDDM patients for 12-weeks was reported to significantly reduce FBG,
HbA1c, insulin, HOMA, TG, TC, CRP and PGE2 [23, 290]. Another study reported
up to 20% decrease in FBG, compared to baseline values, after 1 g/d ginger for
10-weeks [115], and 2 g/d ginger for 12-weeks significantly reduced FBS, HbA1c,
apolipoprotein B, apolipoprotein B/apolipoprotein A–I and MDA in type 2 DM
Iranian patients [148]. However, eight-weeks intervention with 3 g/d ginger did not
have significant effect on serum FBS, insulin, HbA1c, TC, LDL, TG, HDL [31],
and BP of type 2 diabetic overweight Iranian patients [30]. Ten-weeks intake of
ginger (1 g/d) by peritoneal dialysis patients significantly lowered only serum TG
by up to 15% from baseline and compared to placebo [309]. Addition of 5 g ginger
powder to fatty meal of 100 g butter to healthy volunteers prevented fall in fatty
meal-induced fibrinolytic activity, but rather significantly increased it [322, 324],
and synergistically potentiated antiplatelet activity of nifedipine in healthy volun-
teers and hypertensive patients [353]. A single dose of 2 g dried ginger powder to
eight healthy male volunteers, however, failed to affect bleeding time, platelet count
or platelet aggregation [173]. Ginger administration in a daily dose of 4 g for
3-months to CAD patients also did not affect fibrinolytic activity, fibrinogen level
and platelet aggregation; but a single dose of 10 g significantly reduced platelets
aggregation [48].
A single dose of 20 g ginger in a brunch meal to healthy male Danish adults did
not produce thermogenetic response [91], and a single oral dose of dried gin-
ger powder significantly elevated FFAs, did not significantly affect peripheral and
central thermoregulation but facilitated fat utilization in Japanese adults [194].
However, ten overweight New Yorker men given 2 g ginger powder in a hot water
beverage experienced lower hunger, lower prospective food intake and greater
fullness versus placebo [188]. Phillips et al. [237] reported no effect of ginger on
gastric emptying in healthy adult volunteers; whereas others reported improved
gastroduodenal motility and gastric emptying in healthy volunteers [192, 340], and
prevention of hyperglycemia-induced gastric dysrhythmias, probably by blunting
production of PGs [88]. In Taiwanese patients with functional dyspepsia, a single
dose of 1,200 mg ginger powder significantly increased gastric emptying and antral
contractions without affecting GIT symptoms [110]. The outcome of thirty IBS
patients treated with ginger (1–2 g/d) for 28-days at the University of North
Carolina, Chapel Hill, was comparable to placebo [321].
A standardized ginger extract in doses of 400 and 800 mg once daily for
2-months to healthy middle-aged Thai women demonstrably enhanced cognition
and working memory [271]. After two hours of intake of ginger powder or
sumatriptan by adult Iranian patients, both treatments significantly and similarly
Zingiber officinale Rosc. 1971

reduced severity of migraine headaches in a double-blind, RCT [176]. Marginal

improvement in the CD4 counts and viral load was reported in Nigerian HIV
patients on antiretroviral therapy who also used ginger EO [29]. Backon [35] even
suggested using ginger in the treatment of Kawasaki disease due to its thromboxane
synthetase inhibitory effect.
Mechanism of Action: The gastric ulcers healing effect of ginger extract is mainly
mediated by inhibition of the expression of chemokines and to some extent TNF-a
[155]. Ginger improves TNBSA-induced colitis via modulation of NF-jB activity
and IL-1b signaling pathway [109]. The proinflammatory effect of high-fat diet in
rats is also attenuated, in part, through the NF-jB signaling pathway [165]. [6]-
Gingerol and [10]-gingerol have been identified as mainly responsible for the
cholagogic effect of ginger [345]. [6]-gingerol lowers arsenic induced hyper-
glycemia, and improves impaired insulin signaling by increasing expression levels
of GLUT4, IRS-1, IRS-2, PI3 K, AKT, PPARc signaling molecules in mice [54].
Aqueous extract causes apoptosis of human nonsmall lung epithelium cancer cells
and HeLa cells by directly interacting with cellular microtubules and disrupting
their structure [61]. Ginger also exerts antiangiogenic effect through multiple
interdependent processes, including effects on gene expression, signal processing,
and enzyme activities [346]. Gingerols and diarylhepatanoids were identified as
inhibitors of TX synthetase [154].
Human A/Es, Allergy and Toxicity: Ginger use during first trimester of pregnancy
was reported safe (nonteratogenic) in Canadian women [246, 333]; a commercial
ginger extract (EV.EXT35) was also reported effective as antinauseant and safe in
Australian women [336]. In a large population-based cohort study, 1,020 Norwegian
women who used ginger during pregnancy did not have an increased risk of con-
genital malformations, stillbirth/perinatal deaths, preterm births, or low birth weight
[104]. Reviews of clinical studies found ginger effective and safe to prevent NVP
[49, 69]. As a powerful TX synthetase inhibitor and PGI2 agonist, it may cause potent
effects on bleeding time and on immunological parameters [33]. A case of subacute
thyroiditis in a 34-year Iranian woman was reported after consuming one teaspoon
ginger powder with honey for ten nights [275].
Animal Toxicity: Aqueous extract was nonlethal to rats up to a dose of 5,000 mg/kg
[208]. Aqueous and methanol extracts orally administered up to a dose of
5,000 mg/kg/d to mice for 65 consecutive days were nonlethal [281], and oral
ethanol extract was also nontoxic to hamsters and mice up to a dose of 5,000 mg/kg
[242, 243]. Oral LD50 of roasted ginger decoction was reported as 170.6 g/kg, and
over 250 g/kg of dry ginger decoction [339]. Ginger powder orally administered to
rats of either sex, up to a dose of 2,000 mg/kg for 35-days did not affect hema-
tological and biochemical parameters or any overt organ damage except a slightly
reduced testicular weights at the highest dose [267]. Even ginger oil with zin-
giberene (31.08%) as the main component was harmless to rats up to a dose of
500 mg/kg for 13-weeks [121]. The standardized extract (EV.EXT 33) orally
administered to pregnant rats for 10-days, caused neither maternal nor develop-
mental toxicity to fetuses up to a dose of 1,000 mg/kg [331].
1972 Zingiber officinale Rosc.

CYP450 and Potential for Drug-Herb Interactions: Ginger feeding to rats

stimulated levels of CYP450 and Cytochrome b5 [273]. In human liver micro-
somes, aqueous-ethanol extract inhibited CYP2C19-mediated drug metabolism,
while other CYP isozymes activity were not significantly affected [152]; another
study reported moderate inhibition of CYP2D6 in human liver microsomes [89].
Ginger oil significantly inhibits CYP1A1, CYP1A2, and CYP2B1/2, and increase
levels of phase II carcinogen-metabolizing enzymes uridine 5’-diphospho-
glucuronyl transferase and glutathione-S-transferase in vivo [123]. The pun-
gent components, 6-, 8-, and 10-gingerol potently inhibited CYP2C9, moderately
inhibited CYP2C19 and CYP3A4, and caused weak inhibition of CYP2D6 in a
HepG2 cell line [164]. Ginger juice concurrently administered significantly
decreased oral bioavailability of cyclosporine, but not of intravenously adminis-
tered cyclosporine in rats [57], whereas AUC of oral tacrolimus was significantly
increased [72]. Ginger feeding enhanced absorption of iron, zinc and calcium in rats
[251], and increased lung penetration of ciprofloxacin and isoniazid [211], while
ginger juice significantly increased absorption and T1/2 of metronidazole and
decreased its elimination in rabbits [223]. Administration of ginger preparation at
the recommended dose did not affect pharmacokinetics and pharmacodynamics of
warfarin in healthy individuals [126, 127]. Also, about 40% out of 600 Norwegian
women interviewed used ginger, iron-rich herbs, echinacea and cranberry, and more
than 86% also used conventional drugs during pregnancy with few potential drug
interactions [217].
Commentary: Ginger is one of the most extensively investigated herbs in animal
models for various diseases, and in most cases demonstrated positive beneficial
effects. One can surmise from observation of pharmacological studies that various
extracts provided almost consistent results, with few exceptions. However, its most
common human uses for N/V, GIT symptoms and as analgesic/anti-inflammatory
agent deserve better scrutiny. Despite some outlying negative results most clinical
studies generally validated these traditional uses; still the causes for variations in
clinical outcomes must be delineated. Nevertheless, this unassuming common herb
might hold some more surprises for us, such as its preventive effect on colorectal
cancer or reducing respiratory hyperresponsiveness in bronchial asthma patients.

References
1. Abdulrazaq NB, Cho MM, Win NN, et al. Beneficial effects of ginger
(Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced
diabetic rats. Br J Nutr. 2012;108:1194–201.
2. Agarwal M, Walia S, Dhingra S, Khambay BP. Insect growth inhibition,
antifeedant and antifungal activity of compounds isolated/derived from
Zingiber officinale Roscoe (ginger) rhizomes. Pest Manag Sci. 2001;57:
289–300.
Zingiber officinale Rosc. 1973

3. Ahmed RS, Seth V, Banerjee BD. Influence of dietary ginger (Zingiber

officinales Rosc.) on antioxidant defense system in rat: comparison with
ascorbic acid. Indian J Exp Biol. 2000;38:604–6.
4. Ahmed RS, Sharma SB. Biochemical studies on combined effects of garlic
(Allium sativum Linn.) and ginger (Zingiber officinale Rosc.) in albino rats.
Indian J Exp Biol. 1997;35:841–3.
5. Ahmed RS, Suke SG, Seth V, et al. Protective effects of dietary ginger
(Zingiber officinales Rosc.) on lindane-induced oxidative stress in rats.
Phytother Res. 2008;22:902–6.
6. Ahui ML, Champy P, Ramadan A, et al. Ginger prevents Th2-mediated
immune responses in a mouse model of airway inflammation. Int Immuno-
pharmacol. 2008;8:1626–32.
7. Aimbire F, Penna SC, Rodrigues M, et al. Effect of hydroalcoholic extract
of Zingiber officinalis rhizomes on LPS-induced rat airway hyperreactivity
and lung inflammation. Prostaglandins Leukot Essent Fatty Acids. 2007;77:
129–38.
8. Ajith TA, Aswathy MS, Hema U. Protective effect of Zingiber officinale
Roscoe against anticancer drug doxorubicin-induced acute nephrotoxicity.
Food Chem Toxicol. 2008;46:3178–81.
9. Ajith TA, Hema U, Aswathy MS. Zingiber officinale Roscoe prevents
acetaminophen-induced acute hepatotoxicity by enhancing hepatic antiox-
idant status. Food Chem Toxicol. 2007;45:2267–72.
10. Ajith TA, Nivitha V, Usha S. Zingiber officinale Roscoe alone and in
combination with alpha-tocopherol protect the kidney against cisplatin-
induced acute renal failure. Food Chem Toxicol. 2007;45:921–7.
11. Akhani SP, Vishwakarma SL, Goyal RK. Antidiabetic activity of Zingiber
officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol.
2004;56:101–5.
12. Akoachere JF, Ndip RN, Chenwi EB, et al. Antibacterial effect of Zingiber
officinale and Garcinia kola on respiratory tract pathogens. East Afr
Med J. 2002;79:588–92.
13. Al-Amin ZM, Thomson M, Al-Qattan KK, et al. Antidiabetic and hypolipi-
daemic properties of ginger (Zingiber officinale) in streptozotocin-induced
diabetic rats. Br J Nutr. 2006;96:660–6.
14. Alizadeh-Navaei R, Roozbeh F, Saravi M, et al. Investigation of the effect
of ginger on the lipid levels. A double blind controlled clinical trial. Saudi
Med J. 2008;29:1280–4.
15. Altug E, Sonmez K, Turkyilmaz Z, et al. Effect of ginger extract on liver
damage in experimental obstructive jaundice produced by main bile duct
ligation. Acta Chir Belg. 2013;113:8–13.
16. Aly HF, Mantawy MM. Efficiency of ginger (Zingbar officinale) against
Schistosoma mansoni infection during host-parasite association. Parasitol
Int. 2013;62:380–9.
17. Amin A, Hamza AA, Kambal A, Daoud S. Herbal extracts counteract
cisplatin-mediated cell death in rat testis. Asian J Androl. 2008;10:291–7.
1974 Zingiber officinale Rosc.

18. Amin A, Hamza AA. Effects of roselle and ginger on cisplatin-induced

reproductive toxicity in rats. Asian J Androl. 2006;8:607–12.
19. Amran AZ, Jantan I, Dianita R, Buang F. Protective effects of the stan-
dardized extract of Zingiber officinale on myocardium against isoproterenol-
induced biochemical and histopathological alterations in rats. Pharm Biol.
2015;53:1795–802.
20. Ansari M, Porouhan P, Mohammadianpanah M, et al. Efficacy of ginger in
control of chemotherapy-induced nausea and vomiting in breast cancer
patients receiving doxorubicin-based chemotherapy. Asian Pac J Cancer
Prev. 2016;17:3877–80.
21. Ansari MN, Bhandari U, Pillai KK: Ethanolic Zingiber officinale R. extract
pretreatment alleviates isoproterenol-induced oxidative myocardial necro-
sis in rats. Indian J Exp Biol. 2006;44:892–7.
22. Apariman S, Ratchanon S, Wiriyasirivej B. Effectiveness of ginger for
prevention of nausea and vomiting after gynecological laparoscopy. J Med
Assoc Thai. 2006;89:2003–9.
23. Arablou T, Aryaeian N, Valizadeh M, et al. The effect of ginger
consumption on glycemic status, lipid profile and some inflammatory
markers in patients with type 2 diabetes mellitus. Int J Food Sci Nutr.
2014;65:515–20.
24. Arfeen Z, Owen H, Plummer JL, et al. A double-blind randomized
controlled trial of ginger for the prevention of postoperative nausea and
vomiting. Anaesth Intensive Care. 1995;23:449–52.
25. Arslan M, Ozdemir L. Oral intake of ginger for chemotherapy-induced
nausea and vomiting among women with breast cancer. Clin J Oncol Nurs.
2015;19:E92–7.
26. Asnani VM, Verma RJ. Ameliorative effects of ginger extract on
paraben-induced lipid peroxidation in the liver of mice. Acta Pol Pharm.
2009;66:225–8.
27. Aswal BS, Bhakuni DS, Goel AK, et al. Screening of Indian plants for
biological activity: Part X. Indian J Exp Biol. 1984;22:312–32.
28. Atta AH, Elkoly TA, Mouneir SM, et al. Hepatoprotective effect of
methanol extracts of Zingiber officinale and Cichorium intybus. Indian J
Pharm Sci. 2010;72:564–70.
29. Awodele O, Olayemi SO, Adeyemo TA, et al. Use of complementary
medicine amongst patients on antiretroviral drugs in an HIV treatment
centre in Lagos Nigeria. Curr Drug Saf. 2012;7:120–5.
30. Azimi P, Ghiasvand R, Feizi A, et al. Effect of cinnamon, cardamom,
saffron and ginger consumption on blood pressure and a marker of
endothelial function in patients with type 2 diabetes mellitus: a randomized
controlled clinical trial. Blood Press. 2016;25:133–40.
31. Azimi P, Ghiasvand R, Feizi A, Hariri M, Abbasi B. Effects of cinnamon,
cardamom, saffron, and ginger consumption on markers of glycemic control,
lipid profile, oxidative stress, and inflammation in type 2 diabetes patients.
Rev Diabet Stud. 2014;11:258–66.
Zingiber officinale Rosc. 1975

32. Azizi A, Aghayan S, Zaker S, et al. In vitro effect of Zingiber officinale

extract on growth of Streptococcus mutans and Streptococcus sanguinis.
Int J Dent. 2015;2015:489842.
33. Backon J. Ginger as an antiemetic: possible side effects due to its throm-
boxane synthetase activity. Anaesthesia. 1991;46:705–6.
34. Backon J. Ginger: inhibition of thromboxane synthetase and stimulation of
prostacyclin: relevance for medicine and psychiatry. Med Hypotheses.
1986;20:271–8.
35. Backon J. Implication of thromboxane in the pathogenesis of Kawasaki
disease and a suggestion for using novel thromboxane synthetase inhibitors
in its treatment. Med Hypotheses. 1991;34:230–1.
36. Bailey-Shaw YA, Williams LA, Junor GA, et al. Changes in the contents
of oleoresin and pungent bioactive principles of Jamaican ginger (Zingiber
officinale Roscoe) during maturation. J Agric Food Chem. 2008;56:5564–71.
37. Bao L, Deng A, Li Z, et al. Chemical constituents of rhizomes of Zingiber
officinale. Zhongguo Zhong Yao Za Zhi. 2010;35:598–601 (Article in
Chinese).
38. Bartels EM, Folmer VN, Bliddal H, et al. Efficacy and safety of ginger in
osteoarthritis patients: a meta-analysis of randomized placebo-controlled
trials. Osteoarthritis Cartilage. 2015;23:13–21.
39. Benarba B. Medicinal plants used by traditional healers from South-West
Algeria: an ethnobotanical study. J Intercult Ethnopharmacol. 2016;5:
320–30.
40. Betoni JE, Mantovani RP, Barbosa LN, et al. Synergism between plant
extract and antimicrobial drugs used on Staphylococcus aureus diseases.
Mem Inst Oswaldo Cruz. 2006;101:387–90.
41. Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber
officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol. 2005;97:
227–30.
42. Bhandari U, Sharma JN, Zafar R. The protective action of ethanolic ginger
(Zingiber officinale) extract in cholesterol fed rabbits. J Ethnopharmacol.
1998;61:167–71.
43. Bhattarai S, Tran VH, Duke CC. The stability of gingerol and shogaol in
aqueous solutions. J Pharm Sci. 2001;90:1658–64.
44. Black CD, Herring MP, Hurley DJ, O’Connor PJ. Ginger (Zingiber
officinale) reduces muscle pain caused by eccentric exercise. J Pain. 2010;
11:894–903.
45. Bliddal H, Rosetzsky A, Schlichting P, et al. A randomized, placebo-
controlled, crossover study of ginger extracts and ibuprofen in osteoarthri-
tis. Osteoarthritis Cartilage. 2000;8:9–12.
46. Bone ME, Wilkinson DJ, Young JR, McNeil J, Charlton S. Ginger root—
a new antiemetic. The effect of ginger root on postoperative nausea and
vomiting after major gynaecological surgery. Anaesthesia 1990;45:669–71.
1976 Zingiber officinale Rosc.

47. Bordbar H, Esmaeilpour T, Dehghani F, Panjehshahin MR. Stereological

study of the effect of ginger’s alcoholic extract on the testis in
busulfan-induced infertility in rats. Iran J Reprod Med. 2013;11:467–72.
48. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale
Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids,
blood sugar and platelet aggregation in patients with coronary artery
disease. Prostaglandins Leukot Essent Fatty Acids. 1997;56:379–84.
49. Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Effectiveness and
safety of ginger in the treatment of pregnancy-induced nausea and
vomiting. Obstet Gynecol. 2005;105:849–56.
50. Brahmbhatt M, Gundala SR, Asif G, et al. Ginger phytochemicals exhibit
synergy to inhibit prostate cancer cell proliferation. Nutr Cancer. 2013;65:
263–72.
51. Broussard CS, Louik C, Honein MA, Mitchell AA. National birth defects
prevention study: herbal use before and during pregnancy. Am J Obstet
Gynecol. 2010;202:e1–6.
52. Brown AC, Shah C, Liu J, et al. Ginger’s (Zingiber officinale Roscoe)
inhibition of rat colonic adenocarcinoma cells proliferation and angiogen-
esis in vitro. Phytother Res. 2009;23:640–5.
53. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K,
Leelasettagool C. The efficacy of ginger for the prevention of postoperative
nausea and vomiting: a meta-analysis. Am J Obstet Gynecol. 2006;194:
95–9.
54. Chakraborty D, Mukherjee A, Sikdar S, et al. [6]-Gingerol isolated from
ginger attenuates sodium arsenite induced oxidative stress and plays a
corrective role in improving insulin signaling in mice. Toxicol Lett. 2012;
210:34–43.
55. Chang JS, Wang KC, Yeh CF, et al. Fresh ginger (Zingiber officinale) has
antiviral activity against human respiratory syncytial virus in human
respiratory tract cell lines. J Ethnopharmacol. 2013;145:146–51.
56. Charles R, Garg SN, Kumar S. New gingerdione from the rhizomes of
Zingiber officinale. Fitoterapia. 2000;71:716–8.
57. Chiang HM, Chao PD, Hsiu SL, et al. Ginger significantly decreased the
oral bioavailability of cyclosporine in rats. Am J Chin Med. 2006;34:
845–55.
58. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effec-
tiveness of ginger and vitamin B6 for treatment of nausea and vomiting in
early pregnancy: a randomized double-blind controlled trial. J Med Assoc
Thai. 2007;90:15–20.
59. Chohan M, Forster-Wilkins G, Opara EI. Determination of the antioxidant
capacity of culinary herbs subjected to various cooking and storage processes
using the ABTS(*+) radical cation assay. Plant Foods Hum Nutr. 2008;63:
47–52.
Zingiber officinale Rosc. 1977

60. Choi KM, Gang J, Yun J. Anti-Toxoplasma gondii RH strain activity of

herbal extracts used in traditional medicine. Int J Antimicrob Agents.
2008;32:360–2.
61. Choudhury D, Das A, Bhattacharya A, Chakrabarti G. Aqueous extract
of ginger shows antiproliferative activity through disruption of micro-
tubule network of cancer cells. Food Chem Toxicol. 2010;48:2872–80.
62. Chrubasik S, Pittler MH, Roufogalis BD. Zingiberis rhizoma: a compre-
hensive review on the ginger effect and efficacy profiles. Phytomedicine.
2005;12:684–701.
63. Chuah SK, Wu KL, Tai WC, Changchien CS. The effects of ginger on
gallbladder motility in healthy male humans. J Neurogastroenterol Motil.
2011;17:411–5.
64. Citronberg J, Bostick R, Ahearn T, et al. Effects of ginger supplementation
on cell-cycle biomarkers in the normal-appearing colonic mucosa of
patients at increased risk for colorectal cancer: results from a pilot,
randomized, and controlled trial. Cancer Prev Res (Phila). 2013;6:271–81.
65. Cwikla C, Schmidt K, Matthias A, et al. Investigations into the
antibacterial activities of phytotherapeutics against Helicobacter pylori
and Campylobacter jejuni. Phytother Res. 2010;24:649–56.
66. Darvishzadeh-Mahani F, Esmaeili-Mahani S, Komeili G, et al. Ginger
(Zingiber officinale Roscoe) prevents the development of morphine anal-
gesic tolerance and physical dependence in rats. J Ethnopharmacol. 2012;
141:901–7.
67. Denyer CV, Jackson P, Loakes DM, et al. Isolation of antirhinoviral
sesquiterpenes from ginger (Zingiber officinale). J Nat Prod. 1994;57:
658–62.
68. Dias MC, Spinardi-Barbisan AL, Rodrigues MA, et al. Lack of chemo-
preventive effects of ginger on colon carcinogenesis induced by 1,2-
dimethylhydrazine in rats. Food Chem Toxicol. 2006;44:877–84.
69. Ding M, Leach M, Bradley H. The effectiveness and safety of ginger for
pregnancy-induced nausea and vomiting: a systematic review. Women
Birth. 2013;26:e26–30.
70. Dugasani S, Pichika MR, Nadarajah VD, et al. Comparative antioxidant
and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol
and [6]-shogaol. J Ethnopharmacol. 2010;127:515–20.
71. Eberhart LH, Mayer R, Betz O, et al. Ginger does not prevent
postoperative nausea and vomiting after laparoscopic surgery. Anesth
Analg. 2003;96:995–8.
72. Egashira K, Sasaki H, Higuchi S, Ieiri I. Food-drug interaction of
tacrolimus with pomelo, ginger, and turmeric juice in rats. Drug Metab
Pharmacokinet. 2012;27:242–7.
73. El-Abhar HS, Hammad LN, Gawad HS. Modulating effect of ginger
extract on rats with ulcerative colitis. J Ethnopharmacol. 2008;118:367–72.
74. El-Akabawy G, El-Kholy W. Neuroprotective effect of ginger in the brain
of streptozotocin-induced diabetic rats. Ann Anat. 2014;196:119–28.
1978 Zingiber officinale Rosc.

75. El-Ghorab AH, Nauman M, Anjum FM, et al. A comparative study on

chemical composition and antioxidant activity of ginger (Zingiber offici-
nale) and cumin (Cuminum cyminum). J Agric Food Chem. 2010;58:8231–7.
76. Elkady AI, Abuzinadah OA, Baeshen NA, Rahmy TR. Differential control of
growth, apoptotic activity, and gene expression in human breast cancer cells
by extracts derived from medicinal herbs Zingiber officinale. J Biomed
Biotechnol. 2012;2012:614356.
77. ElRokh el-SM, Yassin NA, El-Shenawy SM, Ibrahim BM. Antihyperc-
holesterolaemic effect of ginger rhizome (Zingiber officinale) in rats. Inflam-
mopharmacology. 2010;18:309–15.
78. El-Sharaky AS, Newairy AA, Kamel MA, Eweda SM. Protective effect of
ginger extract against bromobenzene-induced hepatotoxicity in male rats.
Food Chem Toxicol. 2009;47:1584–90.
79. Emrani Z, Shojaei E, Khalili H. Ginger for prevention of antituberculosis-
induced gastrointestinal adverse reactions including hepatotoxicity: a
randomized pilot clinical trial. Phytother Res. 2016;30:1003–9.
80. Ensiyeh J, Sakineh MA. Comparing ginger and vitamin B6 for the treatment
of nausea and vomiting in pregnancy: a randomised controlled trial.
Midwifery. 2009;25:649–53.
81. Feng T, Su J, Ding ZH, et al. Chemical constituents and their bioactivities of
“Tongling White Ginger” (Zingiber officinale). J Agric Food Chem. 2011;
59:11690–5.
82. Ficker C, Smith ML, Akpagana K, et al. Bioassay-guided isolation and
identification of antifungal compounds from ginger. Phytother Res. 2003;
17:897–902.
83. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of
hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 1991;38:
19–24.
84. Fouda AM, Berika MY. Evaluation of the effect of hydroalcoholic extract
of Zingiber officinale rhizomes in rat collagen-induced arthritis. Basic Clin
Pharmacol Toxicol. 2009;104:262–71.
85. Fuhrman B, Rosenblat M, Hayek T, et al. Ginger extract consumption
reduces plasma cholesterol, inhibits LDL oxidation and attenuates develop-
ment of atherosclerosis in atherosclerotic, apolipoprotein E-deficient mice.
J Nutr. 2000;130:1124–31.
86. Funk JL, Frye JB, Oyarzo JN, Timmermann BN. Comparative effects of
two gingerol-containing Zingiber officinale extracts on experimental
rheumatoid arthritis (perpendicular). J Nat Prod. 2009;72:403–7.
87. Gao H, Guan T, Li C, et al. Treatment with ginger ameliorates
fructose-induced fatty liver and hypertriglyceridemia in rats: modulation
of the hepatic carbohydrate response element-binding protein-mediated
pathway. Evid Based Complement Alternat Med. 2012;2012:570948.
Zingiber officinale Rosc. 1979

88. Gonlachanvit S, Chen YH, Hasler WL, Sun WM, Owyang C. Ginger
reduces hyperglycemia-evoked gastric dysrhythmias in healthy humans:
possible role of endogenous prostaglandins. J Pharmacol Exp Ther. 2003;
307:1098–103.
89. Gorman GS, Coward L, Darby A, Rasberry B. Effects of herbal
supplements on the bioactivation of chemotherapeutic agents. J Pharm
Pharmacol. 2013;65:1014–25.
90. Goyal RK, Kadnur SV. Beneficial effects of Zingiber officinale on gold-
thioglucose induced obesity. Fitoterapia. 2006;77:160–3.
91. Gregersen NT, Belza A, Jensen MG, et al. Acute effects of mustard,
horseradish, black pepper and ginger on energy expenditure, appetite,
ad libitum energy intake and energy balance in human subjects. Br J Nutr.
2013;109:556–63.
92. Grøntved A, Brask T, Kambskard J, Hentzer E. Ginger root against
seasickness. A controlled trial on the open sea. Acta Otolaryngol. 1988;
105:45–9.
93. Grøntved A, Hentzer E. Vertigo-reducing effect of ginger root. A controlled
clinical study. ORL J Otorhinolaryngol Relat Spec. 1986;48:282–6.
94. Grzanna R, Lindmark L, Frondoza CG. Ginger—an herbal medicinal
product with broad anti-inflammatory actions. J Med Food. 2005;8:125–32.
95. Gull I, Saeed M, Shaukat H, et al. Inhibitory effect of Allium sativum
and Zingiber officinale extracts on clinically important drug resistant
pathogenic bacteria. Ann Clin Microbiol Antimicrob. 2012;11:8.
96. Gupta S, Ravishankar S. A comparison of the antimicrobial activity of
garlic, ginger, carrot, and turmeric pastes against Escherichia coli O157:
H7 in laboratory buffer and ground beef. Foodborne Pathog Dis. 2005;2:
330–40.
97. Ha SK, Moon E, Ju MS, et al. 6-Shogaol, a ginger product, modulates
neuroinflammation: a new approach to neuroprotection. Neuropharmacol-
ogy. 2012;63:211–23.
98. Habib SH, Makpol S, Abdul Hamid NA, et al. Ginger extract (Zingiber
officinale) has anticancer and anti-inflammatory effects on ethionine-
induced hepatoma in rats. Clinics (Sao Paulo). 2008;63:807–13.
99. Haksar A, Sharma A, Chawla R, et al. Zingiber officinale exhibits behavioral
radioprotection against radiation-induced CTA in a gender-specific manner.
Pharmacol Biochem Behav. 2006;84:179–88.
100. Halder A. Effect of progressive muscle relaxation versus intake of gin-
ger powder on dysmenorrhoea amongst the nursing students in Pune.
Nurs J India. 2012;103:152–6.
101. Han LK, Gong XJ, Kawano S, et al. Antiobesity actions of Zingiber
officinale Roscoe. Yakugaku Zasshi 2005;125:213–7 (Article in Japanese).
102. Hashimoto K, Satoh K, Murata P, et al. Component of Zingiber
officinale that improves the enhancement of small intestinal transport.
Planta Med. 2002;68:936–9.
1980 Zingiber officinale Rosc.

103. Heeba GH, Abd-Elghany MI. Effect of combined administration of gin-

ger (Zingiber officinale Roscoe) and atorvastatin on the liver of rats.
Phytomedicine. 2010;17:1076–81.
104. Heitmann K, Nordeng H, Holst L. Safety of ginger use in pregnancy:
results from a large population-based cohort study. Eur J Clin Pharmacol.
2013;69:269–77.
105. Hickok JT, Roscoe JA, Morrow GR, Ryan JL. A phase II/III randomized,
placebo-controlled, double-blind clinical trial of ginger (Zingiber offici-
nale) for nausea caused by chemotherapy for cancer: a currently accruing
URCC CCOP cancer control study. Support Cancer Ther. 2007;4:247–50.
106. Höferl M, Stoilova I, Wanner J, et al. Composition and comprehensive
antioxidant activity of ginger (Zingiber officinale) essential oil from
Ecuador. Nat Prod Commun. 2015;10:1085–90.
107. Holst L, Wright D, Haavik S, Nordeng H. The use and the user of herbal
remedies during pregnancy. J Altern Complement Med. 2009;15:787–92.
108. Holtmann S, Clarke AH, Scherer H, Höhn M. The antimotion sickness
mechanism of ginger. A comparative study with placebo and dimenhy-
drinate. Acta Otolaryngol. 1989;108:168–74.
109. Hsiang CY, Lo HY, Huang HC, et al. Ginger extract and zingerone
ameliorated trinitrobenzene sulphonic acid-induced colitis in mice via
modulation of nuclear factor-jB activity and interleukin-1b signalling
pathway. Food Chem. 2013;136:170–7.
110. Hu ML, Rayner CK, Wu KL, et al. Effect of ginger on gastric motility and
symptoms of functional dyspepsia. World J Gastroenterol. 2011;17:105–10.
111. Huang Q, Matsuda H, Sakai K, et al. The effect of ginger on serotonin
induced hypothermia and diarrhea. Yakugaku Zasshi. 1990;110:936–42
(Article in Japanese).
112. Hung JY, Hsu YL, Li CT, et al. 6-Shogaol, an active constituent of dietary
ginger, induces autophagy by inhibiting the AKT/mTOR pathway in
human nonsmall cell lung cancer A549 cells. J Agric Food Chem. 2009;
57:9809–16.
113. Ihlaseh SM, de Oliveira ML, Teràn E, et al. Chemopreventive property of
dietary ginger in rat urinary bladder chemical carcinogenesis. World J
Urol. 2006;24:591–6.
114. Ilkhanizadeh B, Shirpoor A, Khadem Ansari MH, Nemati S, Rasmi Y.
Protective effects of ginger (Zingiber officinale) extract against diabetes-
induced heart abnormality in rats. Diabetes Metab J. 2016;40:46–53.
115. Imani H, Tabibi H, Najafi I, et al. Effects of ginger on serum glucose,
advanced glycation end products, and inflammation in peritoneal dialysis
patients. Nutrition. 2015;31:703–7.
116. Iranloye BO, Arikawe AP, Rotimi G, Sogbade AO. Antidiabetic and
antioxidant effects of Zingiber officinale on alloxan-induced and insulin-
resistant diabetic male rats. Niger J Physiol Sci. 2011;26:89–96.
Zingiber officinale Rosc. 1981

117. Ishiguro K, Ando T, Maeda O, et al. Ginger ingredients reduce viability of

gastric cancer cells via distinct mechanisms. Biochem Biophys Res
Commun. 2007;362:218–23.
118. Islam MS, Choi H. Comparative effects of dietary ginger (Zingiber
officinale) and garlic (Allium sativum) investigated in a type 2 diabetes
model of rats. J Med Food. 2008;11:152–9.
119. Janssen PL, Meyboom S, van Staveren WA, de Vegt F, Katan MB.
Consumption of ginger (Zingiber officinale Roscoe) does not affect ex vivo
platelet thromboxane production in humans. Eur J Clin Nutr. 1996;50:
772–4.
120. Jayashree E, Visvanathan R, John Zachariah T. Quality of dry gin-
ger (Zingiber officinale) by different drying methods. J Food Sci Technol.
2014;51:3190–8.
121. Jeena K, Liju VB, Kuttan R. A preliminary 13-week oral toxicity study
of ginger oil in male and female Wistar rats. Int J Toxicol. 2011;30:662–70.
122. Jeena K, Liju VB, Kuttan R. Antioxidant, anti-inflammatory and
antinociceptive activities of essential oil from ginger. Indian J Physiol
Pharmacol. 2013;57:51–62.
123. Jeena K, Liju VB, Viswanathan R, Kuttan R. Antimutagenic potential and
modulation of carcinogen-metabolizing enzymes by ginger essential oil.
Phytother Res. 2014;28:849–55.
124. Jenabi E. The effect of ginger for relieving of primary dysmenorrhoea.
J Pak Med Assoc. 2013;63:8–10.
125. Jeong CH, Bode AM, Pugliese A, et al. [6]-Gingerol suppresses colon
cancer growth by targeting leukotriene A4 hydrolase. Cancer Res. 2009;69:
5584–91.
126. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal
medicines on warfarin response in healthy subjects: a population pharmaco-
kinetic-pharmacodynamic modeling approach. J Clin Pharmacol. 2006;46:
1370–8.
127. Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on
the pharmacokinetics and pharmacodynamics of warfarin in healthy
subjects. Br J Clin Pharmacol. 2005;59:425–32.
128. Jiang Y, Turgeon DK, Wright BD, et al. Effect of ginger root on
cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expres-
sion in colonic mucosa of humans at normal and increased risk for
colorectal cancer. Eur J Cancer Prev. 2013;22:455–60.
129. Jittiwat J, Wattanathorn J. Ginger pharmacopuncture improves cognitive
impairment and oxidative stress following cerebral ischemia. J Acupunct
Meridian Stud. 2012;5:295–300.
130. Jolad SD, Lantz RC, Solyom AM, et al. Fresh organically grown ginger
(Zingiber officinale): composition and effects on LPS-induced PGE2
production. Phytochemistry. 2004;65:1937–54.
131. Jolad SD, Lantz RC, Chen GJ, et al. Commercially processed dry gin-
ger (Zingiber officinale): composition and effects on LPS-stimulated PGE2
production. Phytochemistry. 2005;66:1614–35.
1982 Zingiber officinale Rosc.

132. Kabuto H, Nishizawa M, Tada M, et al. Zingerone [4-(4-hydroxy-3-

methoxyphenyl)-2-butanone] prevents 6-hydroxydopamine-induced dopa-
mine depression in mouse striatum and increases superoxide scavenging
activity in serum. Neurochem Res. 2005;30:325–32.
133. Kadnur SV, Goyal RK. Beneficial effects of Zingiber officinale Roscoe on
fructose induced hyperlipidemia and hyperinsulinemia in rats. Indian J Exp
Biol. 2005;43:1161–4.
134. Kami T, Nakayama M, Hayashi S. Volatile constituents of Zingiber
officinale. Phytochemistry. 1972;11:3377–81.
135. Kamtchouing P, Mbongue Fandio GY, Dimo T, Jatsa HB. Evaluation of
androgenic activity of Zingiber officinale and Pentadiplandra brazzeana in
male rats. Asian J Androl. 2002;4:299–301.
136. Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation of
hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic
rats. J Ethnopharmacol. 2003;84:105–8.
137. Karna P, Chagani S, Gundala SR, et al. Benefits of whole ginger extract in
prostate cancer. Br J Nutr. 2012;107:473–84.
138. Karuppiah P, Rajaram S. Antibacterial effect of Allium sativum cloves
and Zingiber officinale rhizomes against multiple-drug resistant clinical
pathogens. Asian Pac J Trop Biomed. 2012;2:597–601.
139. Kasahara Y, Saito E, Hikino H. Pharmacological action of Pinellia tubers
and Zingiber rhizomes. Shoyakugaku Zasshi. 1983;37:73–83.
140. Kashefi F, Khajehei M, Alavinia M, Golmakani E, Asili J. Effect of gin-
ger (Zingiber officinale) on heavy menstrual bleeding: a placebo-controlled,
randomized clinical trial. Phytother Res. 2015;29:114–9.
141. Kashefi F, Khajehei M, Tabatabaeichehr M, Alavinia M, Asili J. Compar-
ison of the effect of ginger and zinc sulfate on primary dysmenorrhea: a
placebo-controlled randomized trial. Pain Manag Nurs. 2014;15:826–33.
142. Katiyar SK, Agarwal R, Mukhtar H. Inhibition of tumor promotion in
SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome.
Cancer Res. 1996;56:1023–30.
143. Kawai T, Kinoshita K, Koyama K, Takahashi K. Antiemetic principles of
Magnolia obovata bark and Zingiber officinale rhizome. Planta Med. 1994;
60:17–20.
144. Kazeem M, Akanji M, Hafizur RM, Choudhary M. Antiglycation,
antioxidant and toxicological potential of polyphenol extracts of alligator
pepper, ginger and nutmeg from Nigeria. Asian Pac J Trop Biomed. 2012;
2:727–32.
145. Keating A, Chez RA. Ginger syrup as an antiemetic in early pregnancy.
Altern Ther Health Med. 2002;8:89–91.
146. Khaki A, Khaki AA, Hajhosseini L, Golzar FS, Ainehchi N. The antioxidant
effects of ginger and cinnamon on spermatogenesis dysfunction of diabetes
rats. Afr J Tradit Complement Altern Med. 2014;11:1–8.
Zingiber officinale Rosc. 1983

147. Khan R, Zakir M, Afaq SH, et al. Activity of solvent extracts of Prosopis
spicigera, Zingiber officinale and Trachyspermum ammi against multidrug
resistant bacterial and fungal strains. J Infect Dev Ctries. 2010;4:292–300.
148. Khandouzi N, Shidfar F, Rajab A, et al. The effects of ginger on fasting
blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein a-I and
malondialdehyde in type 2 diabetic patients. Iran J Pharm Res. 2015;14:
131–40.
149. Khayat S, Kheirkhah M, Behboodi Moghadam Z, et al. Effect of treatment
with ginger on the severity of premenstrual syndrome symptoms. ISRN
Obstet Gynecol. 2014;2014:792708.
150. Khushtar M, Kumar V, Javed K, Bhandari U. Protective effect of gin-
ger oil on aspirin and pylorus ligation-induced gastric ulcer model in rats.
Indian J Pharm Sci. 2009;71:554–8.
151. Kim DS, Kim JY, Han YS. Alzheimer’s disease drug discovery from
herbs: neuroprotectivity from beta-amyloid (1-42) insult. J Altern Com-
plement Med. 2007;13:333–40.
152. Kim IS, Kim SY, Yoo HH. Effects of an aqueous-ethanolic extract of ginger
on cytochrome P450 enzyme-mediated drug metabolism. Pharmazie. 2012;
67:1007–9.
153. Kim JS, Lee SI, Park HW, et al. Cytotoxic components from the dried
rhizomes of Zingiber officinale Roscoe. Arch Pharm Res. 2008;31:415–8.
154. Kiuchi F, Iwakami S, Shibuya M, et al. Inhibition of prostaglandin and
leukotriene biosynthesis by gingerols and diarylheptanoids. Chem Pharm
Bull (Tokyo). 1992;40:387–91.
155. Ko JK, Leung CC. Ginger extract and polaprezinc exert gastroprotective
actions by antioxidant and growth factor modulating effects in rats.
J Gastroenterol Hepatol. 2010;25:1861–8.
156. Koch C, Reichling J, Schneele J, Schnitzler P. Inhibitory effect of essential
oils against herpes simplex virus type 2. Phytomedicine. 2008;15:71–8.
157. Koo KL, Ammit AJ, Tran VH, et al. Gingerols and related analogues
inhibit arachidonic acid-induced human platelet serotonin release and
aggregation. Thromb Res. 2001;103:387–97.
158. Kota N, Panpatil VV, Kaleb R, et al. Dose-dependent effect in the
inhibition of oxidative stress and anticlastogenic potential of ginger in
STZ induced diabetic rats. Food Chem. 2012;135:2954–9.
159. Krim M, Messaadia A, Maidi I, et al. Protective effect of ginger against
toxicity induced by chromate in rats. Ann Biol Clin (Paris). 2013;71:165–73.
160. Kulkarni RA, Deshpande AR. Anti-inflammatory and antioxidant effect
of ginger in tuberculosis. J Complement Integr Med. 2016;13:201–6.
161. Kyung KS, Gon JH, Geun KY, et al. 6-Shogaol, a natural product, reduces
cell death and restores motor function in rat spinal cord injury. Eur J
Neurosci. 2006;24:1042–52.
162. Lakshmi BV, Sudhakar M. Attenuation of acute and chronic restraint
stress-induced perturbations in experimental animals by Zingiber officinale
Roscoe. Food Chem Toxicol. 2010;48:530–5.
1984 Zingiber officinale Rosc.

163. Levy AS, Simon O, Shelly J, Gardener M. 6-Shogaol reduced chronic

inflammatory response in the knees of rats treated with complete Freund’s
adjuvant. BMC Pharmacol. 2006;6:12.
164. Li M, Chen PZ, Yue QX, et al. Pungent ginger components modulates
human cytochrome P450 enzymes in vitro. Acta Pharmacol Sin. 2013;34:
1237–42.
165. Li XH, McGrath KC, Nammi S, et al. Attenuation of liver proinflammatory
responses by Zingiber officinale via inhibition of NF-kappa B activation in
high-fat diet-fed rats. Basic Clin Pharmacol Toxicol. 2012;110:238–44.
166. Liao YR, Leu YL, Chan YY, et al. Antiplatelet aggregation and vasorelaxing
effects of the constituents of the rhizomes of Zingiber officinale. Molecules.
2012;17:8928–37.
167. Lien HC, Sun WM, Chen YH, et al. Effects of ginger on motion sickness
and gastric slow-wave dysrhythmias induced by circular vection. Am J
Physiol Gastrointest Liver Physiol. 2003;284:G481–9.
168. Liju VB, Jeena K, Kuttan R. Gastroprotective activity of essential oils from
turmeric and ginger. J Basic Clin Physiol Pharmacol. 2015;26:95–103.
169. Liu H, Zhu Y: Effect of alcohol extract of Zingiber officinale Rose on
immunologic function of mice with tumor. Wei Sheng Yan Jiu. 2002;31:
208–9 (Article in Chinese).
170. Liu Q, Liu J, Guo H, et al. [6]-gingerol: a novel AT1 antagonist for the
treatment of cardiovascular disease. Planta Med. 2013;79:322–6.
171. Lu CL, Zhao HY, Jiang JG. Evaluation of multiactivities of 14 edible
species from Zingiberaceae. Int J Food Sci Nutr. 2013;64:28–35.
172. Lu J, Guan S, Shen X, et al. Immunosuppressive activity of 8-gingerol on
immune responses in mice. Molecules. 2011;16:2636–45.
173. Lumb AB. Effect of dried ginger on human platelet function. Thromb
Haemost. 1994;71:110–1.
174. Ma J, Jin X, Yang L, Liu ZL. Diarylheptanoids from the rhizomes of
Zingiber officinale. Phytochemistry. 2004;65:1137–43.
175. Madkor HR, Mansour SW, Ramadan G. Modulatory effects of garlic, gin-
ger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and
oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr.
2011;105:1210–7.
176. Maghbooli M, Golipour F, Moghimi Esfandabadi A, Yousefi M. Com-
parison between the efficacy of ginger and sumatriptan in the ablative
treatment of the common migraine. Phytother Res. 2014;28:412–5.
177. Maghsoudi S, Gol A, Dabiri S, Javadi A. Preventive effect of ginger (Zin-
giber officinale) pretreatment on renal ischemia-reperfusion in rats. Eur
Surg Res. 2011;46:45–51.
178. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helico-
bacter pylori to botanical extracts used traditionally for the treatment of
gastrointestinal disorders. Phytother Res. 2005;19:988–91.
Zingiber officinale Rosc. 1985

179. Mahady GB, Pendland SL, Yun GS, et al. Ginger (Zingiber officinale
Roscoe) and the gingerols inhibit the growth of Cag A + strains of Helico-
bacter pylori. Anticancer Res. 2003;23:3699–702.
180. Mahluji S, Attari VE, Mobasseri M, et al. Effects of ginger (Zingiber
officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2
diabetic patients. Int J Food Sci Nutr. 2013;64:682–6.
181. Mahmoud MF, Diaai AA, Ahmed F. Evaluation of the efficacy of ginger,
Arabic gum, and Boswellia in acute and chronic renal failure. Ren Fail.
2012;34:73–82.
182. Mahmoud RH, Elnour WA. Comparative evaluation of the efficacy
of ginger and orlistat on obesity management, pancreatic lipase and liver
peroxisomal catalase enzyme in male albino rats. Eur Rev Med Pharmacol
Sci. 2013;17:75–83.
183. Mallikarjuna K, Sahitya Chetan P, Sathyavelu Reddy K, Rajendra W.
Ethanol toxicity: rehabilitation of hepatic antioxidant defense system with
dietary ginger. Fitoterapia. 2008;79:174–8.
184. Mangprayool T, Kupittayanant S, Chudapongse N. Participation of citral
in the bronchodilatory effect of ginger oil and possible mechanism of
action. Fitoterapia. 2013;89C:68–73.
185. Manju V, Nalini N. Chemopreventive efficacy of ginger, a naturally
occurring anticarcinogen during the initiation, post-initiation stages of 1,2
dimethylhydrazine-induced colon cancer. Clin Chim Acta. 2005;358:60–7.
186. Manju V, Nalini N. Effect of ginger on bacterial enzymes in 1,2-dimethyl-
hydrazine induced experimental colon carcinogenesis. Eur J Cancer Prev.
2006;15:377–83.
187. Manju V, Viswanathan P, Nalini N. Hypolipidemic effect of ginger in
1,2-dimethylhydrazine-induced experimental colon carcinogenesis. Toxi-
col Mech Methods. 2006;16:461–72.
188. Mansour MS, Ni YM, Roberts AL, et al. Ginger consumption enhances
the thermic effect of food and promotes feelings of satiety without affecting
metabolic and hormonal parameters in overweight men: a pilot study.
Metabolism. 2012;61:1347–52.
189. Manusirivithaya S, Sripramote M, Tangjitgamol S, et al. Antiemetic effect
of ginger in gynecologic oncology patients receiving cisplatin. Int J Gynecol
Cancer. 2004;14:1063–9.
190. Mascolo N, Jain R, Jain SC, Capasso F. Ethnopharmacologic investigation
of ginger (Zingiber officinale). J Ethnopharmacol. 1989;27:129–40.
191. Mehrdad M, Messripour M, Ghobadipour M. The effect of ginger extract
on blood urea nitrogen and creatinine in mice. Pak J Biol Sci. 2007;10:
2968–71.
192. Micklefield GH, Redeker Y, Meister V, et al. Effects of ginger on gastro-
duodenal motility. Int J Clin Pharmacol Ther. 1999;37:341–6.
1986 Zingiber officinale Rosc.

193. Misawa K, Hashizume K, Yamamoto M, et al. Ginger extract prevents high-

fat diet-induced obesity in mice via activation of the peroxisome proliferator-
activated receptor d pathway. J Nutr Biochem. 2015;26:1058–67.
194. Miyamoto M, Matsuzaki K, Katakura M, et al. Oral intake of encapsulated
dried ginger root powder hardly affects human thermoregulatory function,
but appears to facilitate fat utilization. Int J Biometeorol. 2015;59:1461–74.
195. Mohammadbeigi R, Shahgeibi S, Soufizadeh N, Rezaiie M, Farhadifar F.
Comparing the effects of ginger and metoclopramide on the treatment of
pregnancy nausea. Pak J Biol Sci. 2011;14:817–20.
196. Moselhy WA, Helmy NA, Abdel-Halim BR, et al. Role of ginger against
the reproductive toxicity of aluminium chloride in albino male rats. Reprod
Domest Anim. 2012;47:335–43.
197. Mostafa OM, Eid RA, Adly MA. Antischistosomal activity of ginger
(Zingiber officinale) against Schistosoma mansoni harbored in C57 mice.
Parasitol Res. 2011;109:395–403.
198. Motawi TK, Hamed MA, Shabana MH, et al. Zingiber officinale acts as a
nutraceutical agent against liver fibrosis. Nutr Metab (Lond). 2011;8:40.
199. Mowrey DB, Clayson DE. Motion sickness, ginger and psychophysics.
Lancet (England). 1982;1:655–7.
200. Mozaffari-Khosravi H, Naderi Z, Dehghan A, Nadjarzadeh A, Fallah
Huseini H. Effect of ginger supplementation on proinflammatory cytokines
in older patients with osteoarthritis: outcomes of a randomized controlled
clinical trial. J Nutr Gerontol Geriatr. 2016;35:209–18.
201. Mozaffari-Khosravi H, Talaei B, Jalali BA, Najarzadeh A, Mozayan MR.
The effect of ginger powder supplementation on insulin resistance and
glycemic indices in patients with type 2 diabetes: a randomized, double-
blind, placebo-controlled trial. Complement Ther Med. 2014;22:9–16.
202. Mustafa T, Srivastava KC. Ginger (Zingiber officinale) in migraine head-
ache. J Ethnopharmacol. 1990;29:267–73.
203. Naderi Z, Mozaffari-Khosravi H, Dehghan A, Nadjarzadeh A, Huseini HF.
Effect of ginger powder supplementation on nitric oxide and C-reactive
protein in elderly knee osteoarthritis patients: a 12-week double-blind
randomized placebo-controlled clinical trial. J Tradit Complement Med.
2015;6:199–203.
204. Nagasawa H, Watanabe K, Inatomi H. Effects of bitter melon (Momordica
charantia L.) or ginger rhizome (Zingiber offifinale Rosc.) on spontaneous
mammary tumorigenesis in SHN mice. Am J Chin Med. 2002;30:195–205.
205. Nagoshi C, Shiota S, Kuroda T, et al. Synergistic effect of [10]-gingerol
and aminoglycosides against vancomycin-resistant enterococci (VRE).
Biol Pharm Bull. 2006;29:443–7.
206. Nammi S, Kim MS, Gavande NS, et al. Regulation of low-density
lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme a reductase
expression by Zingiber officinale in the liver of high-fat diet-fed rats. Basic
Clin Pharmacol Toxicol. 2010;106:389–95.
Zingiber officinale Rosc. 1987

207. Nammi S, Sreemantula S, Roufogalis BD. Protective effects of ethanolic

extract of Zingiber officinale rhizome on the development of metabolic
syndrome in high-fat diet-fed rats. Basic Clin Pharmacol Toxicol. 2009;
104:366–73.
208. Nanjundaiah SM, Annaiah HN, M Dharmesh S. Gastroprotective effect of
ginger rhizome (Zingiber officinale) extract: role of gallic acid and
cinnamic acid in H+, K+-ATPase/H. pylori inhibition and antioxidative
mechanism. Evid Based Complement Alternat Med. 2011:249487.
209. Nanthakomon T, Pongrojpaw D. The efficacy of ginger in prevention of
postoperative nausea and vomiting after major gynecologic surgery. J Med
Assoc Thai. 2006;89 Suppl 4:S130–6.
210. Nasri H, Nematbakhsh M, Ghobadi S, et al. Preventive and curative effects
of ginger extract against histopathologic changes of gentamicin-induced
tubular toxicity in rats. Int J Prev Med. 2013;4:316–21.
211. Nduka SO, Okonta MJ, Esimone CO. Effects of Zingiber officinale on the
plasma pharmacokinetics and lung penetrations of ciprofloxacin and
isoniazid. Am J Ther. 2013;20:507–13.
212. Nguefack J, Leth V, Amvam Zollo PH, Mathur SB. Evaluation of five
essential oils from aromatic plants of Cameroon for controlling food
spoilage and mycotoxin producing fungi. Int J Food Microbiol. 2004;94:
329–34.
213. Nguefack J, Budde BB, Jakobsen M. Five essential oils from aromatic plants
of Cameroon: their antibacterial activity and ability to permeabilize the
cytoplasmic membrane of Listeria innocua examined by flow cytometry.
Lett Appl Microbiol. 2004;39:395–400.
214. Nigam N, Bhui K, Prasad S, et al. [6]-Gingerol induces reactive oxygen
species regulated mitochondrial cell death pathway in human epidermoid
carcinoma A431 cells. Chem Biol Interact. 2009;181:77–84.
215. Nigam N, George J, Srivastava S, et al. Induction of apoptosis by [6]-
gingerol associated with the modulation of p53 and involvement of
mitochondrial signaling pathway in B[a]P-induced mouse skin tumorige-
nesis. Cancer Chemother Pharmacol. 2010;65:687–96.
216. Nord D, Belew J. Effectiveness of the essential oils lavender and ginger in
promoting children’s comfort in a perianesthesia setting. J Perianesth Nurs.
2009;24:307–12.
217. Nordeng H, Bayne K, Havnen GC, Paulsen BS. Use of herbal drugs during
pregnancy among 600 Norwegian women in relation to concurrent use of
conventional drugs and pregnancy outcome. Complement Ther Clin Pract.
2011;17:147–51.
218. Nostro A, Cellini L, Di Bartolomeo S, et al. Effects of combining extracts
(from propolis or Zingiber officinale) with clarithromycin on Helicobacter
pylori. Phytother Res. 2006;20:187–90.
219. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, et al. Effective
antiplatelet and COX-1 enzyme inhibitors from pungent constituents of
ginger. Thromb Res. 2003;111:259–65.
1988 Zingiber officinale Rosc.

220. Nwokocha CR, Owu DU, Nwokocha MI, et al. Comparative study on the
hepatoprotection to heavy metals of Zingiber officinale. Pharmacognosy
Res. 2012;4:208–13.
221. Oboh G, Akinyemi AJ, Ademiluyi AO: Antioxidant and inhibitory effect
of red ginger (Zingiber officinale var. Rubra) and white ginger (Zingiber
officinale Roscoe) on Fe(2+) induced lipid peroxidation in rat brain in vitro.
Exp Toxicol Pathol. 2012;64:31–6.
222. Ojewole JA. Analgesic, anti-inflammatory and hypoglycaemic effects of
ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in
mice and rats. Phytother Res. 2006;20:764–72.
223. Okonta JM, Uboh M, Obonga WO. Herb-drug interaction: a case study of
effect of ginger on the pharmacokinetic of metronidazole in rabbit. Indian J
Pharm Sci. 2008;70:230–2.
224. Okumi H, Tashima K, Matsumoto K, et al. Dietary agonists of TRPV1
inhibit gastric acid secretion in mice. Planta Med. 2012;78:1801–6.
225. O’Mahony R, Al-Khtheeri H, Weerasekera D, et al. Bactericidal and
antiadhesive properties of culinary and medicinal plants against Heli-
cobacter pylori. World J Gastroenterol. 2005;11:7499–507.
226. Onwuka FC, Erhabor O, Eteng MU, Umoh IB. Protective effects
of ginger toward cadmium-induced testes and kidney lipid peroxidation
and hematological impairment in albino rats. J Med Food. 2011;14:817–21.
227. Ozgoli G, Goli M, Moattar F. Comparison of effects of ginger, mefenamic
acid, and ibuprofen on pain in women with primary dysmenorrhea.
J Altern Complement Med. 2009;15:129–32.
228. Ozgoli G, Goli M, Simbar M. Effects of ginger capsules on pregnancy,
nausea, and vomiting. J Altern Complement Med. 2009;15:243–6.
229. Palatty PL, Haniadka R, Valder B, Arora R, Baliga MS. Ginger in the
prevention of nausea and vomiting: a review. Crit Rev Food Sci Nutr.
2013;53:659–69.
230. Panahi Y, Saadat A, Sahebkar A, et al. Effect of ginger on acute and
delayed chemotherapy-induced nausea and vomiting: a pilot, randomized,
open-label clinical trial. Integr Cancer Ther. 2012;11:204–11.
231. Paramdeep G. Efficacy and tolerability of ginger (Zingiber officinale) in
patients of osteoarthritis of knee. Indian J Physiol Pharmacol. 2013;57:
177–83.
232. Paritakul P, Ruangrongmorakot K, Laosooksathit W, Suksamarnwong M,
Puapornpong P: The effect of ginger on breast milk volume in the early
postpartum period: A randomized, double-blind controlled trial. Breastfeed
Med. 2016;361–5.
233. Park KK, Chun KS, Lee JM, et al. Inhibitory effects of [6]-gingerol, a
major pungent principle of ginger, on phorbol ester-induced inflammation,
epidermal ornithine decarboxylase activity and skin tumor promotion in
ICR mice. Cancer Lett. 1998;129:139–44.
Zingiber officinale Rosc. 1989

234. Park M, Bae J, Lee DS. Antibacterial activity of [10]-gingerol and [12]-
gingerol isolated from ginger rhizome against periodontal bacteria.
Phytother Res. 2008;22:1446–9.
235. Patrick-Iwuanyanwu KC, Wegwu MO, Ayalogu EO. Prevention of
CCl4-induced liver damage by ginger, garlic and vitamin E. Pak J Biol
Sci. 2007;10:617–21.
236. Penna SC, Medeiros MV, Aimbire FS, et al. Anti-inflammatory effect of
the hydralcoholic extract of Zingiber officinale rhizomes on rat paw and
skin edema. Phytomedicine. 2003;10:381–5.
237. Phillips S, Hutchinson S, Ruggier R. Zingiber officinale does not affect
gastric emptying rate. A randomised, placebo-controlled, crossover trial.
Anaesthesia 1993;48:393–5.
238. Phillips S, Ruggier R, Hutchinson SE. Zingiber officinale (ginger)—an
antiemetic for day case surgery. Anaesthesia. 1993;48:715–7.
239. Pillai AK, Sharma KK, Gupta YK, Bakhshi S. Antiemetic effect of ginger
powder versus placebo as an add-on therapy in children and young adults
receiving high emetogenic chemotherapy. Pediatr Blood Cancer. 2011;56:
234–8.
240. Platel K, Srinivasan K. Influence of dietary spices and their active
principles on pancreatic digestive enzymes in albino rats. Nahrung. 2000;
44:42–6.
241. Platel K, Srinivasan K. Influence of dietary spices or their active principles
on digestive enzymes of small intestinal mucosa in rats. Int J Food Sci
Nutr. 1996;47:55–9.
242. Plengsuriyakarn T, Viyanant V, Eursitthichai V, et al. Anticancer activities
against cholangiocarcinoma, toxicity and pharmacological activities of Thai
medicinal plants in animal models. BMC Complement Altern Med. 2012;
12:23.
243. Plengsuriyakarn T, Viyanant V, Eursitthichai V, et al. Cytotoxicity, toxicity,
and anticancer activity of Zingiber officinale Roscoe against cholangiocar-
cinoma. Asian Pac J Cancer Prev. 2012;13:4597–606.
244. Pongrojpaw D, Chiamchanya C. The efficacy of ginger in prevention of
postoperative nausea and vomiting after outpatient gynecological laparo-
scopy. J Med Assoc Thai. 2003;86:244–50.
245. Pongrojpaw D, Somprasit C, Chanthasenanont A. A randomized compar-
ison of ginger and dimenhydrinate in the treatment of nausea and vomiting
in pregnancy. J Med Assoc Thai. 2007;90:1703–9.
246. Portnoi G, Chng LA, Karimi-Tabesh L, et al. Prospective comparative
study of the safety and effectiveness of ginger for the treatment of nausea
and vomiting in pregnancy. Am J Obstet Gynecol. 2003;189:1374–7.
247. Power ML, Holzman GB, Schulkin J. A survey on the management of
nausea and vomiting in pregnancy by obstetrician/gynecologists. Prim
Care Update Ob Gyns. 2001;8:69–72.
248. Power ML, Milligan LA, Schulkin J. Managing nausea and vomiting of
pregnancy: a survey of obstetrician-gynecologists. J Reprod Med. 2007;52:
922–8.
1990 Zingiber officinale Rosc.

249. Pozzatti P, Scheid LA, Spader TB, et al. In vitro activity of essential oils
extracted from plants used as spices against fluconazole-resistant and
fluconazole-susceptible Candida spp. Can J Microbiol. 2008;54:950–6.
250. Prakash UN, Srinivasan K: Beneficial influence of dietary spices on the
ultrastructure and fluidity of the intestinal brush border in rats. Br J Nutr.
2010;1–9.
251. Prakash UN, Srinivasan K. Enhanced intestinal uptake of iron, zinc and
calcium in rats fed pungent spice principles—piperine, capsaicin and
ginger (Zingiber officinale). J Trace Elem Med Biol. 2013;27:184–90.
252. Prakash UN, Srinivasan K. Gastrointestinal protective effect of dietary
spices during ethanol-induced oxidant stress in experimental rats. Appl
Physiol Nutr Metab. 2010;35:134–41.
253. Puri A, Sahai R, Singh KL, et al. Immunostimulant activity of dry fruits
and plant materials used in indian traditional medical system for mothers
after child birth and invalids. J Ethnopharmacol. 2000;71:89–92.
254. Rafieian-Kopaei M, Nasri H. The ameliorative effect of Zingiber offici-
nale in diabetic nephropathy. Iran Red Crescent Med J. 2014;16:e11324.
255. Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M. Effect
of Zingiber officinale R. rhizomes (ginger) on pain relief in primary
dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med.
2012;12:92.
256. Ramadan G, Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and
antioxidant properties of Curcuma longa (turmeric) versus Zingiber
officinale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation.
2011;34:291–301.
257. Ramkissoon J, Mahomoodally M, Ahmed N, Subratty A. Antioxidant and
antiglycation activities correlates with phenolic composition of tropical
medicinal herbs. Asian Pac J Trop Med. 2013;6:561–9.
258. Ramkissoon JS, Mahomoodally MF, Ahmed N, Subratty AH. Relationship
between total phenolic content, antioxidant potential, and antiglycation
abilities of common culinary herbs and spices. J Med Food. 2012;15:
1116–23.
259. Ramudu SK, Korivi M, Kesireddy N, et al. Nephroprotective effects of
a ginger extract on cytosolic and mitochondrial enzymes against strepto-
zotocin (STZ)-induced diabetic complications in rats. Chin J Physiol.
2011;54:79–86.
260. Rani MP, Padmakumari KP, Sankarikutty B, et al. Inhibitory potential of
ginger extracts against enzymes linked to type 2 diabetes, inflammation
and induced oxidative stress. Int J Food Sci Nutr. 2011;62:106–10.
261. Ranilla LG, Kwon YI, Apostolidis E, Shetty K. Phenolic compounds,
antioxidant activity and in vitro inhibitory potential against key enzymes
relevant for hyperglycemia and hypertension of commonly used medicinal
plants, herbs and spices in Latin America. Bioresour Technol. 2010;101:
4676–89.
Zingiber officinale Rosc. 1991

262. Rashidian A, Mehrzadi S, Ghannadi AR, et al. Protective effect of ginger

volatile oil against acetic acid-induced colitis in rats: a light microscopic
evaluation. J Integr Med. 2014;12:115–20.
263. Reddy YA, Chalamaiah M, Ramesh B, Balaji G, Indira P. Ameliorating
activity of ginger (Zingiber officinale) extract against lead induced renal
toxicity in male rats. J Food Sci Technol. 2014;51:908–14.
264. Revati S, Bipin C, Chitra PB, Minakshi B. In vitro antibacterial activity of
seven Indian spices against high level gentamicin resistant strains of
enterococci. Arch Med Sci. 2015;11:863–8.
265. Rhode J, Fogoros S, Zick S, et al. Ginger inhibits cell growth and
modulates angiogenic factors in ovarian cancer cells. BMC Complement
Altern Med. 2007;7:44.
266. Riaz F, Khan UA, Ayub M, Shaukat S. Protective role of ginger on lead
induced derangement in plasma testosterone and luteinizing hormone
levels of male Sprague Dawley rats. J Ayub Med Coll Abbottabad.
2011;23:24–7.
267. Rong X, Peng G, Suzuki T, et al. A 35-day gavage safety assessment of
ginger in rats. Regul Toxicol Pharmacol. 2009;54:118–23.
268. Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale)
reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576
patients. Support Care Cancer. 2012;20:1479–89.
269. Sabina EP, Rasool M, Mathew L, et al. 6-Shogaol inhibits monosodium
urate crystal-induced inflammation—an in vivo and in vitro study. Food
Chem Toxicol. 2010;48:229–35.
270. Sabina EP, Pragasam SJ, Kumar S, Rasool M. 6-Gingerol, an active
ingredient of ginger, protects acetaminophen-induced hepatotoxicity in
mice. Zhong Xi Yi Jie He Xue Bao. 2011;9:1264–9.
271. Saenghong N, Wattanathorn J, Muchimapura S, et al. Zingiber offici-
nale improves cognitive function of the middle-aged healthy women. Evid
Based Complement Alternat Med. 2012;2012:383062.
272. Sambaiah K, Srinivasan K. Effect of cumin, cinnamon, ginger, mustard and
tamarind in induced hypercholesterolemic rats. Nahrung. 1991;35:47–51.
273. Sambaiah K, Srinivasan K. Influence of spices and spice principles on
hepatic mixed function oxygenase system in rats. Indian J Biochem
Biophys. 1989;26:254–8.
274. Sanaati F, Najafi S, Kashaninia Z, Sadeghi M. Effect of ginger and
chamomile on nausea and vomiting caused by chemotherapy in Iranian
women with breast cancer. Asian Pac J Cancer Prev. 2016;17:4125–9.
275. Sanavi S, Afshar R. Subacute thyroiditis following ginger (Zingiber
officinale) consumption. Int J Ayurveda Res. 2010;1:47–8.
276. Sang S, Hong J, Wu H, et al. Increased growth inhibitory effects on human
cancer cells and anti-inflammatory potency of shogaols from Zingiber
officinale relative to gingerols. J Agric Food Chem. 2009;57:10645–50.
277. Saraswat M, Suryanarayana P, Reddy PY, et al. Antiglycating potential of
Zingiber officinalis and delay of diabetic cataract in rats. Mol Vis. 2010;
16:1525–37.
1992 Zingiber officinale Rosc.

278. Schnitzler P, Koch C, Reichling J. Susceptibility of drug-resistant clinical

herpes simplex virus type 1 strains to essential oils of ginger, thyme, hyssop,
and sandalwood. Antimicrob Agents Chemother. 2007;51:1859–62.
279. Semwal RB, Semwal DK, Combrinck S, Viljoen AM. Gingerols and
shogaols: Important nutraceutical principles from ginger. Phytochemistry.
2015;117:554–68.
280. Sepahvand R, Esmaeili-Mahani S, Arzi A, et al. Ginger (Zingiber officinale
Roscoe) elicits antinociceptive properties and potentiates morphine-
induced analgesia in the rat radiant heat tail-flick test. J Med Food.
2010;13:1397–401.
281. Shalaby MA, Hamowieh AR. Safety and efficacy of Zingiber officinale
roots on fertility of male diabetic rats. Food Chem Toxicol. 2010;48:2920–4.
282. Shanmugam KR, Mallikarjuna K, Kesireddy N, Sathyavelu Reddy K.
Neuroprotective effect of ginger on antioxidant enzymes in streptozotocin-
induced diabetic rats. Food Chem Toxicol. 2011;49:893–7.
283. Shanmugam KR, Ramakrishna CH, Mallikarjuna K, Reddy KS. Protective
effect of ginger against alcohol-induced renal damage and antioxidant
enzymes in male albino rats. Indian J Exp Biol. 2010;48:143–9.
284. Shariatpanahi ZV, Taleban FA, Mokhtari M, Shahbazi S. Ginger extract
reduces delayed gastric emptying and nosocomial pneumonia in adult
respiratory distress syndrome patients hospitalized in an intensive care
unit. J Crit Care. 2010;25:647–50.
285. Sharma A, Chandraker S, Patel VK, Ramteke P. Antibacterial activity of
medicinal plants against pathogens causing complicated urinary tract infec-
tions. Indian J Pharm Sci. 2009;71:136–9.
286. Sharma JN, Srivastava KC, Gan EK. Suppressive effects of eugenol
and ginger oil on arthritic rats. Pharmacology. 1994;49:314–8.
287. Sharma P, Singh R. Dichlorvos and lindane induced oxidative stress in rat
brain: Protective effects of ginger. Pharmacognosy Res. 2012;4:27–32.
288. Sharma SS, Gupta YK. Reversal of cisplatin-induced delay in gastric
emptying in rats by ginger (Zingiber officinale). J Ethnopharmacol. 1998; 62:
49–55.
289. Sharma SS, Kochupillai V, Gupta SK, et al. Antiemetic efficacy of ginger
(Zingiber officinale) against cisplatin-induced emesis in dogs. J Ethnophar-
macol. 1997;57:93–6.
290. Shidfar F, Rajab A, Rahideh T, et al. The effect of ginger (Zingiber officinale)
on glycemic markers in patients with type 2 diabetes. J Complement Integr
Med. 2015;12:165–70.
291. Shieh PC, Chen YO, Kuo DH, et al. Induction of apoptosis by [8]-shogaol
via reactive oxygen species generation, glutathione depletion, and caspase
activation in human leukemia cells. J Agric Food Chem. 2010;24:3847–54.
292. Shirvani MA, Motahari-Tabari N, Alipour A. The effect of mefenamic acid
and ginger on pain relief in primary dysmenorrhea: a randomized clinical
trial. Arch Gynecol Obstet. 2015;291:1277–81.
Zingiber officinale Rosc. 1993

293. Singh G, Kapoor IP, Singh P, et al. Chemistry, antioxidant and

antimicrobial investigations on essential oil and oleoresins of Zingiber
officinale. Food Chem Toxicol. 2008;46:3295–302.
294. Smith C, Crowther C, Willson K, Hotham N, McMillian V. A randomized
controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet
Gynecol. 2004;103:639–45.
295. Srinivasan K, Sambaiah K. The effect of spices on cholesterol 7 alpha-
hydroxylase activity and on serum and hepatic cholesterol levels in the rat.
Int J Vitam Nutr Res. 1991;61:364–9.
296. Sripramote M, Lekhyananda N. A randomized comparison of ginger and
vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med
Assoc Thai. 2003;86:846–53.
297. Srivastava KC, Mustafa T. Ginger (Zingiber officinale) and rheumatic
disorders. Med Hypotheses. 1989;29:25–8.
298. Srivastava KC, Mustafa T. Ginger (Zingiber officinale) in rheumatism and
musculoskeletal disorders. Med Hypotheses. 1992;39:342–8.
299. Srivastava KC. Aqueous extracts of onion, garlic and ginger inhibit platelet
aggregation and alter arachidonic acid metabolism. Biomed Biochim Acta.
1984;43:S335–46.
300. Srivastava KC. Effect of aqueous extracts of onion, garlic and ginger on
platelet aggregation and metabolism of arachidonic acid in the blood
vascular system: in vitro study. Prostagland Leukotr Med. 1984;13:227–35.
301. Srivastava KC. Effect of onion and ginger consumption on platelet
thromboxane production in humans. Prostagland Leukotr Essent Fatty
Acids. 1989;35:183–5.
302. Srivastava KC. Isolation and effects of some ginger components of platelet
aggregation and eicosanoid biosynthesis. Prostaglandins Leukot Med. 1986;
25:187–98.
303. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of ginger on motion
sickness susceptibility and gastric function. Pharmacology. 1991;42:111–20.
304. Suekawa M, Ishige A, Yuasa K, et al. Pharmacological studies on ginger.
I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-
shogaol. J Pharmacobiodyn. 1984;7:836–48.
305. Suekawa M, Sone H, Sakakibara I, et al. Pharmacological studies on gin-
ger. V. Pharmacological comparison between (6)-shogaol and capsaicin.
Nihon Yakurigaku Zasshi. 1986;88:339–47 (Japanese).
306. Suekawa M, Yuasa K, Isono M, et al. Pharmacological studies on ginger.
IV. Effect of (6)-shogaol on the arachidonic cascade. Nihon Yakurigaku
Zasshi 1986;88:263–9 (Japanese).
307. Sultana S, Ripa FA, Hamid K. Comparative antioxidant activity study of
some commonly used spices in Bangladesh. Pak J Biol Sci. 2010;13:340–3.
308. Sutherland J, Miles M, Hedderley D, et al. In vitro effects of food extracts
on selected probiotic and pathogenic bacteria. Int J Food Sci Nutr. 2009;
60:717–27.
1994 Zingiber officinale Rosc.

309. Tabibi H, Imani H, Atabak S, et al. Effects of ginger on serum lipids and
lipoproteins in peritoneal dialysis patients: a randomized controlled trial.
Perit Dial Int. 2016;36:140–5.
310. Takahashi M, Inouye S, Abe S. Anti-Candida and radical scavenging
activities of essential oils and oleoresins of Zingiber officinale Roscoe and
essential oils of other plants belonging to the family Zingiberaceae. Drug
Discov Ther. 2011;5:238–45.
311. Tanabe M, Chen YD, Saito K, Kano Y. Cholesterol biosynthesis inhibitory
component from Zingiber officinale Roscoe. Chem Pharm Bull (Tokyo).
1993;41:710–3.
312. Tavlan A, Tuncer S, Erol A, et al. Prevention of postoperative nausea and
vomiting after thyroidectomy: combined antiemetic treatment with dexam-
ethasone and ginger versus dexamethasone alone. Clin Drug Investig.
2006;26:209–14.
313. Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger
(Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrom-
botic agent. Prostaglandins Leukot Essent Fatty Acids. 2002;67:475–8.
314. Touwaide A, Appetiti E. Knowledge of Eastern materia medica (Indian
and Chinese) in premodern Mediterranean medical traditions: a study in
comparative historical ethnopharmacology. J Ethnopharmacol. 2013;148:
361–78.
315. Townsend EA, Siviski ME, Zhang Y, et al. Effects of ginger and its
constituents on airway smooth muscle relaxation and calcium regulation.
Am J Respir Cell Mol Biol. 2013;48:157–63.
316. Ueda H, Ippoushi K, Takeuchi A. Repeated oral administration of a
squeezed ginger (Zingiber officinale) extract augmented the serum corti-
costerone level and had anti-inflammatory properties. Biosci Biotechnol
Biochem. 2010;74:2248–52.
317. Ueki S, Miyoshi M, Shido O, et al. Systemic administration of [6]-
gingerol, a pungent constituent of ginger, induces hypothermia in rats via
an inhibitory effect on metabolic rate. Eur J Pharmacol. 2008;584:87–92.
318. Uz E, Karatas OF, Mete E, et al. The effect of dietary ginger (Zingiber
officinalis Rosc.) on renal ischemia/reperfusion injury in rat kidneys. Ren
Fail. 2009;31:251–60.
319. Vahdat Shariatpanahi Z, Mokhtari M, Taleban FA, et al. Effect of enteral
feeding with ginger extract in acute respiratory distress syndrome. J Crit
Care. 2013;28:e1–6.
320. van Breemen RB, Tao Y, Li W. Cyclooxygenase-2 inhibitors in ginger
(Zingiber officinale). Fitoterapia. 2011;82:38–43.
321. van Tilburg MA, Palsson OS, Ringel Y, Whitehead WE. Is ginger effective
for the treatment of irritable bowel syndrome? A double blind randomized
controlled pilot trial. Complement Ther Med. 2014;22:17–20.
322. Verma SK, Bordia A. Ginger, fat and fibrinolysis. Indian J Med Sci.
2001;55:83–6.
Zingiber officinale Rosc. 1995

323. Verma SK, Singh M, Jain P, Bordia A. Protective effect of ginger, Zingiber
officinale Rosc. on experimental atherosclerosis in rabbits. Indian J Exp
Biol. 2004;42:736–8.
324. Verma SK, Singh J, Khamesra R, Bordia A. Effect of ginger on platelet
aggregation in man. Indian J Med Res. 1993;98:240–2.
325. Visalyaputra S, Petchpaisit N, Somcharoen K, Choavaratana R. The
efficacy of ginger root in the prevention of postoperative nausea and
vomiting after outpatient gynaecological laparoscopy. Anaesthesia. 1998;
53:506–10.
326. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting
in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet
Gynecol. 2001;97:577–82.
327. Wang HM, Chen CY, Chen HA, et al. Zingiber officinale (ginger)
compounds have tetracycline-resistance modifying effects against clinical
extensively drug-resistant Acinetobacter baumannii. Phytother Res. 2010;
24:1825–30.
328. Wang J, Gao H, Ke D, et al. Improvement of liquid fructose-induced adipose
tissue insulin resistance by ginger treatment in rats is associated with
suppression of adipose macrophage-related proinflammatory cytokines.
Evid Based Complement Alternat Med. 2013;2013:590376.
329. Watanabe K, Watanabe Y, Goto Y. Effects of Chinese crude drug
prescriptions on experimental peptic ulcers in laboratory animals. Proc
Symp on Wakanyaku. 1975;9:51–7.
330. Wattanathorn J, Jittiwat J, Tongun T, et al. Zingiber officinale mitigates
brain damage and improves memory impairment in focal cerebral ischemic
rat. Evid Based Complement Alternat Med. 2011;2011:429505.
331. Weidner MS, Sigwart K. Investigation of the teratogenic potential of a
Zingiber officinale extract in the rat. Reprod Toxicol. 2001;15:75–80.
332. Weidner MS, Sigwart K. The safety of a ginger extract in the rat.
J Ethnopharmacol. 2000;73:513–20.
333. Westfall RE. Use of antiemetic herbs in pregnancy: women’s choices, and
the question of safety and efficacy. Complement Ther Nurs Midwifery.
2004;10:30–6.
334. Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger
extract) on symptomatic gonarthritis. Osteoarthritis Cartilage. 2003;11:
783–9.
335. Wilkinson JM. Effect of ginger tea on the fetal development of Sprague-
Dawley rats. Reprod Toxicol. 2000;14:507–12.
336. Willetts KE, Ekangaki A, Eden JA. Effect of a ginger extract on pregnancy-
induced nausea: a randomised controlled trial. Aust N Z J Obstet Gynaecol.
2003;43:139–44.
337. Wood CD, Manno JE, Wood MJ, Manno BR, Mims ME. Comparison of
efficacy of ginger with various antimotion sickness drugs. Clin Res Pr
Drug Regul Aff. 1988;6:129–36.
1996 Zingiber officinale Rosc.

338. Wu CX, Wei XB, Ding H, et al. Protective effect of effective parts of
Zingiber Offecinal on vascular endothelium of the experimental hyper-
lipidemic rats. Zhong Yao Cai. 2006;29:810–3 (Chinese).
339. Wu H, Ye D, Bai Y, Zhao Y. Effect of dry ginger and roasted ginger on
experimental gastric ulcers in rats. Zhongguo Zhong Yao Za Zhi. 1990;15:
278–80, 317–8 (Chinese).
340. Wu KL, Rayner CK, Chuah SK, et al. Effects of ginger on gastric
emptying and motility in healthy humans. Eur J Gastroenterol Hepatol.
2008;20:436–40.
341. Yagihashi S, Miura Y, Yagasaki K. Inhibitory effect of gingerol on the
proliferation and invasion of hepatoma cells in culture. Cytotechnology.
2008;57:129–36.
342. Yamahara J, Mochizuki M, Qi Rong H, et al. The antiulcer effect in rats of
ginger constituents. J Ethnopharmacol. 1988;23:299–304.
343. Yamahara J, Hatakeyama S, Taniguchi K, et al. Stomachic principles
in ginger. II. Pungent and antiulcer effects of low polar constituents
isolated from ginger, the dried rhizoma of Zingiber officinale Roscoe
cultivated in Taiwan. The absolute stereostructure of a new diarylhep-
tanoid. Yakugaku Zasshi. 1992;112:645–55 (Japanese).
344. Yamahara J, Huang QR, Li YH, et al. Gastrointestinal motility enhancing
effect of ginger and its active constituents. Chem Pharm Bull (Tokyo).
1990;38:430–1.
345. Yamahara J, Miki K, Chisaka T, et al. Cholagogic effect of ginger and its
active constituents. J Ethnopharmacol. 1985;13:217–25.
346. Yance DR Jr, Sagar SM. Targeting angiogenesis with integrative cancer
therapies. Integr Cancer Ther. 2006;5:9–29.
347. Yang G, Zhong L, Jiang L, et al. Genotoxic effect of 6-gingerol on human
hepatoma G2 cells. Chem Biol Interact. 2010;185:12–7.
348. Ye DJ, Ding AW, Guo R. A research on the constituents of ginger in
various preparations. Zhongguo Zhong Yao Za Zhi. 1989;14:278–80, 318
(Chinese).
349. Yemitan OK, Izegbu MC. Protective effects of Zingiber officinale
(Zingiberaceae) against carbon tetrachloride and acetaminophen-induced
hepatotoxicity in rats. Phytother Res. 2006;20:997–1002.
350. Yi LT, Xu Q, Li YC, et al. Antidepressant-like synergism of extracts from
magnolia bark and ginger rhizome alone and in combination in mice. Prog
Neuropsychopharmacol Biol Psychiatry. 2009;33:616–24.
351. Yoshikawa M, Hatakeyama S, Taniguchi K, et al. 6-Gingesulfonic acid, a
new antiulcer principle, and gingerglycolipids A, B, and C, three new
monoacyldigalactosylglycerols, from zingiberis rhizoma originating in
Taiwan. Chem Pharm Bull (Tokyo). 1992;40:2239–41.
352. Yoshikawa M, Yamaguchi S, Kunimi K, et al. Stomachic principles
in ginger. III. An antiulcer principle, 6-gingesulfonic acid, and three
monoacyldigalactosylglycerols, gingerglyco-lipids A, B, and C, from
Zingiberis Rhizoma originating in Taiwan. Chem Pharm Bull (Tokyo).
1994;42:1226–30.
Zingiber officinale Rosc. 1997

353. Young HY, Liao JC, Chang YS, et al. Synergistic effect of ginger and
nifedipine on human platelet aggregation: a study in hypertensive patients
and normal volunteers. Am J Chin Med. 2006;34:545–51.
354. Young HY, Luo YL, Cheng HY, et al. Analgesic and anti-inflammatory
activities of [6]-gingerol. J Ethnopharmacol. 2005;96:207–10.
355. Yusof YA, Ahmad N, Das S, et al. Chemopreventive efficacy of ginger
(zingiber officinale) in ethionine induced rat hepatocarcinogenesis. Afr J
Tradit Complement Altern Med. 2008;6:87–93.
356. Zeng GF, Zhang ZY, Lu L, et al. Protective effects of ginger root extract
on Alzheimer disease-induced behavioral dysfunction in rats. Rejuvenation
Res. 2013;16:124–33.
357. Zhou HL, Deng YM, Xie QM. The modulatory effects of the volatile oil
of ginger on the cellular immune response in vitro and in vivo in mice.
J Ethnopharmacol. 2006;105:301–5.
358. Zhou Y, Xu R. Antioxidative effect of Chinese drugs. Zhongguo Zhong
Yao Za Zhi. 1992;17:368–9 (Chinese).
359. Zick SM, Ruffin MT, Lee J, et al. Phase II trial of encapsulated ginger as a
treatment for chemotherapy