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The ethno-medicinal and pharmaceutical attributes of Bryophytes: A review

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DOI: 10.1016/j.phyplu.2022.100255

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 Phytomedicine Plus 2 (2022) 100255

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The ethno-medicinal and pharmaceutical attributes of Bryophytes:

A review
Anustup Bandyopadhyay , Abhijit Dey *
Department of Life Sciences, Presidency University, 86/1, College Street, Kolkata 700073, West Bengal, India

A R T I C L E I N F O A B S T R A C T

Keywords: Background: There are over 24,000 species of bryophytes on the planet, which is a heterogeneous group of
Bryophytes terrestrial plants. Various aboriginal groups around the world use bryophytes as a remedy against a number of
Traditional use ailments. Bryophytes have a huge commercial potential due to their promising biological activities.
Pharmacology
Methods: All popular search engines such as Google scholar, PubMed, ScienceDirect and Scopus were used to
Anticancer
Herbal medicine
retrieve the relevant literature using various search strings related to the topic.
Results: It has been demonstrated that bryophytes contain a number of potentially useful natural products, such
as lipids, phenylpropanoids, polysaccharides, quinones, rare amino acids, terpenoids, and many other specialized
compounds. There have been reports of compounds isolated from bryophytes showing antimicrobial, antiviral,
cytotoxic, neuroprotective, nematocidal and insecticidal effects. Besides, they have demonstrated their effects on
smooth and non-striated muscles and weight loss, as plant growth regulators and allelopathic. In addition to
causing allergies and skin reactions, bryophytes were also reported to cause contact dermatitis. Bryophytes
display a plethora of medicinal properties and may be used to treat hepatic disorders, skin diseases, cardio­
vascular diseases, fever and wound. The phytochemicals isolated from them can be used to produce a range of
novel pharmacologically active compounds.
Conclusions: Future drug development programs will take advantage of phytochemical data-mining methods that
encompass identification, quantification, evaluation, conformational analysis, clinical assessment, monitoring,
bioactivity analysis, and designing new drugs based on these unique bioactive chemicals found in bryophytes.
Taking all of these factors into account, bryophytes are promising sources of herbal remedies and ingredients for
a variety of products.

Introduction (Hallingbäck and Hodgetts, 2000). Approximately 8000 species of

Historically, bryophytes, a group of terrestrial plants that is called by
one name but that is also meant to encompass several groups. They are
typically grouped as liverworts, hornworts, and mosses. A growing body
of evidence suggests that the bryophytes can be divided into three
groups based on morphological, molecular, and phytochemical
evidence.
1 Anthocerotophytes that includes hornworts.
2 Bryophytes comprising mosses, including peat, lantern and haircap
mosses.
3 Marchantiophyta includes both leafy and thalloid liverworts
In total, there are 24,000 species of bryophytes throughout the world
mosses are known, and 6000 species of liverworts as well as 200 species
of hornworts (Marko et al., al.,2001). These plants are believed to be
second in size to angiosperms in terms of land plants. There are 2504
species of bryophytes in India, comprising 17.27% of the world’s spe­
cies. The Indian population of bryophytes numbers 642 species, with
25.6% endemism. The Indian moss fauna comprises 1786 species and
355 genera, Liverworts are classified into 121 genera and 675 species
and a total of 25 species and 6 genera are found in hornworts (Sathish
et al., 2013, MoEF, 2014). India has 133 threatened species listed under
the category of rare species, 78 of which are mosses, 53 of which are
liverworts, and 2 of which are hornworts. There are further 14 species
from different bryophytes groups in India that fall into the endangered
category (Dandotiya., 2011). The bryophytes are unique in their di­
versity, but they share certain common characteristics, such as

* Corresponding author.
E-mail address: abhijit.dbs@presiuniv.ac.in (A. Dey).

https://doi.org/10.1016/j.phyplu.2022.100255
Received 29 December 2021; Received in revised form 24 February 2022; Accepted 9 March 2022
Available online 11 March 2022
2667-0313/© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
A. Bandyopadhyay and A. Dey
predominant haploid green photosynthesizing phase and the omission of
key steps towards lignin synthesis (Weng and Chapple, 2010). Thus,
bryophytes are considered atracheophytes, in contrast with vascular
plants which synthesize lignin as a substance to support their wall.
Because bryophytes act as a buffer system for other plants, they are
crucial for maintaining ecosystems. They are classified as cryptogams
due to their lack of seeds and flowers. The small size of these plants
results in less biomass; therefore, they are less known to most people
(Harris, 2008). All ecosystems contain bryophytes except for salt water
environments, with halophytic bryophytes like Riella sp. occurring in
salt-rich environments. The growth of non-halophytic species such as
Physcomitrella patens (Hedw.) Mitt. was demonstrated in laboratory
conditions for some non-halophytic species with 1.5% salt concentration
(King et al., 2016). Each year, however, new species are discovered and
others are synonymized, so the number of taxa is constantly changing.
Bryophytes have been used as packaging, plugging, and decoration since
ancient times. In addition to being indicator species, bryophytes serve as
erosion control systems and as heavy metals bioindicators. Also, it can
be used as a bioindicator for aquatics, as a radioactivity indicator and
fuel (Saxena and Harinder, 2004; Glime, 2007). Bryophytes have a
number of active constituents demonstrating a variety of activities such
as antimicrobial, antifungal, cytotoxic, antitumor, and insecticidal
properties (Asakawa 2007; Ucuncu et al., 2010) which can also be used
as well in agricultural and medicinal processes (Pant 1998; Saxena and
Harinder, 2004). Vitamins B2 and E, along with related compounds, are
produced by some of these plant species. Therefore, it is thought that
bryophytes possess important properties that could be utilized for the
production of food and drugs. Mosses, however, have been used as
medicines for centuries. In addition to dried and crushed bryophytes, oil
is used to make ointments from which blisters, abrasions, and surface
injuries are said to be healed. Indigenous peoples of North America used
medicinal mosses to treat injuries, swellings, and lesions, including
Bryum, Mnium, and Philonotis species (Ando and Matsuo 1984). Euro­
peans have historically used Marchantia polymorpha as a diuretic. The
extracts of French liverworts were prepared by soaking in white liquor
and then consumed by patients. Chinese prescriptions have documented
the Latin names, the morphological characteristics, distribution spots,
pharmacological activities, effects, and prescription usages of 24 li­
chens, 74 algae, 22 mosses, five liverworts, and 329 ferns (Ding et al.,
1982). There are a number of mosses widely used for medical reasons in
China to treat wounds, bruising, injuries to the outside skin, snakebites,
chronic lung disease, emotional disturbances, broken bones, seizures,
burned skin, urinary tract infections, respiratory infections, and neuro­
logical disorders, besides several different applications (Ding,
1982Asakawa, 1999; Asakawa and Ludwiczuk, 2008). The rpesent re­
view mainly encompasses the ethnomedicinal and pharmacological at­
tributes of bryophytes with notes on their phytochemical variations and
future applications in clinical studies.
Materials and methods
Throughout this review, there is information on general uses,
bioactive compounds, ethnomedical applications, and potential dangers
described in peer-reviewed publications on Bryophytes. Despite the non-
systematic nature of the literature search, the literature review was
comprehensive. Most of the papers we considered were published be­
tween 2005 and 2021. Nonetheless, there were some really valuable
information that were published well before 2005 that we considered. A
variety of search strings related to the topic were used to retrieve the
relevant literature from bibliographic data-bases, including Google
Scholar, PubMed, ScienceDirect, Scopus etc. After scanning the refer­
ences in the retrieved articles, we scanned bryophyte chemistry manuals
such as Asakawa (2007) and Asakawa et al. (2013). The review included
literature that dealt with both bryophytes and ethnomedical properties
in a thorough manner. Reviews with low or unclear validity, papers in
languages other than English, papers that did not have significant
2
Phytomedicine Plus 2 (2022) 100255
findings, unpublished studies, and unoriginal papers were excluded,
while studies with high relevance were critically appraised. We sourced
and/or verified the scientific names of the plants from The Plant List
(www.theplantlist.org). The results of 108 articles and published liter­
ature were collected quantitatively to frame this article.
Ethno-medicinal properties
The "doctrine of signatures" from Paracelsus, is an ancient method of
determining herbal properties based on the similarity of plant parts to
organs in human or animal bodies. In accordance with the above phi­
losophy, liverworts are used to treat liver diseases (Miller and Miller,
1979). The women of ancient times used the oil from Polytrichum
commune, which bears hairy calyptra, on their hair (Glime, 2007).
Traditional Chinese medicine (TCM) uses bryophytes extensively. These
tiny plants were used by different ethnic groups around the world to
treat various aliments on a regular basis. Plagiochasma appendiculatum
was used by Gaddi tribes in Himachal Pradesh, India to heal dermato­
logical infections (Kumar et al., 2000). Targionia hypophylla is used in the
treatment of dermatological disorders by the Irular tribe of Attappady
Valleys in Kerala, since the thallus of the plant is similar to the scabby
appearance of the affected area. Tribal people in South India use Frul­
lania ericoides to treat hair-related ailments due to its long, hair-like
stems (Remesh and Manju, 2009). Inflammation is treated with March­
antia polymorpha. After rinsing the whole thallus under running water, it
is ground into a paste and applied topically. Skin diseases can be treated
with Plagiochasma appendiculata. It is applied externally by making a fine
paste from thoroughly washed thalli. Plant species of Polytrichum is used
for hair growth whcih can be stimulated by applying Polytrichum thallus
powder mixed with oil to the hair. Essentially, it acts as a wound healer,
causing the wound to heal through the application of thallus paste.
Children with ringworms are treated with Riccia sp. Infected children are
given a mixture of jiggery and ground thallus to be used as a ringworm
remedy (Shirshat, 2008). To make ointments for cutaneous problems,
cardiovascular problems, hypertension, injuries, the whole thallus of
Funaria hygrometrica Hedw. is used. The whole thallus of Marchantia
polymorpha is used for pustules, as an ointment for wounds, to treat
fever, as a laxative, to treat diuresis and to treat hypertension. The
thallus of Riccia glauca is used as antipyretics, bowel cleanser, promotes
urination, relieves hypertension, and eases inflammation. Medicinal
uses of Shagnum fembriatm whole thallus encompasses hypertension,
heart problems, antipyretics, among other conditions (Muhammad
et al., 2018). Other ethnomedicinal uses of bryophytes are listed in
Tables 1 and 2.
Bioactive phytochemicals from bryophytes
Researchers around the world have evaluated the biological activity
and phytochemistry of several medicinal bryophyte species. To evaluate
the biological potency of these compounds, in vitro and in vivo assays
have been carried out. In order to identify chemical constituents, a wide
range of separation processes are employed. This includes partitioning
and chromatography, like low-pressure column chromatography, high-
performance liquid chromatography (HPLC) and others. The results
are then analyzed using a combination of UV and NMR techniques to
name a few. Many secondary metabolites have been found to be active in
bryophyte species, mostly belonging to the terpenoids and bibenzyls
(Table 3) Fig. 1. depicts the major pharmacological properties of bryo­
phytes Fig. 2. represents a pie chart presenting the bryophytes reported
against different human diseases Fig. 3
Anticancer properties
In TCM, Polytrichum commune is used to treat a range of illnesses,
from fever, hemorrhoids and severe injuries to respiratory illnesses,
prolapse of the uterus, and blood cancer. Polytrichum juniperum was
A. Bandyopadhyay and A. Dey Phytomedicine Plus 2 (2022) 100255

Table 1 Table 2
Ethno-medicinal properties of Liverworts. Ethno-medicinal properties of Mosses.
Family Species Application References Family Species Application References

Weisnerellaceae Wiesnerella denudate Anti-leukemic Alam. 2012 Thuidiaceae Haplocladium Anti-pyretic Ding, 1982
(Mitt.) Stephani microphyllum
Targioniaceae Targionia hypophylla Dermatological Remesh and (Hedw.) Broth.
L. disorders, Skin Manju. 2009 Sphagnaceae Sphagnum Dermatological Azuelo et al.,
irritation sericeum Mull. disorders 2011
Scapaniaceae Diplophyllum sp. Anti-leukemic Hong, 1980 Hal
Ricciaceae Riccia L. sp. Antimicrobial Shirsat, 2008 Sphagnaceae Sphagnum teres Ocular conditions Ding, 1982,
Radulaceae Radula sp. Blood clotting, Castle, 1967 (Schimp.) Glime, 2007
Virucidal Ångström
Porellaceae Porella sp. Anti-bacterial, Dey and Pottiaceae Hyophila Anti-Cough and cold Lubaina et al.,
Anti-leukemic Mukherjee, attenuata Broth. 2014
2015 Pottiaceae Barbula Myalgia, Anti-pyretic Azuelo et al.,
Plagiochilaceae Plagiochila beddomei Antiflu, Anti- Alam, 2012, unguiculata 2011
Steph. carcinogenic Asakawa, Hedw.
2007 Pottiaceae Barbula indica Dysmenorrhea, Fever Lubaina et al.,
Pelliaceae Pellia endiviifolia Anti-bacterial, Sharma et al., (Hook.) Spreng. occurring at intervals 2014
(Dicks.) Dumort Dermal Disorders 2015 Pottiaceae Weisia viridula Anti-Cough and cold Asakawa,
Pallaviciniaceae Pallavicinia sp. Antimicrobial Azuelo et al., (L.) Hedw. 2007, Pant,
2011 1998
Neotrichocoleaceae Trichocoleopsis Superoxide Asakawa, Polytrichaceae Dawsonia superba Hair care, Anti-cold Azuelo et al.,
sacculate (Mitt.) S. release inhibition 2007 Grev. Anti -fever 2011
Okamura Polytrichaceae Polytrichum Anti -fever, Hepatic Pant, 1998,
Marchantiaceae Marchantia Hepatic disorder Azuelo et al., commune Hedw. disorder, Facilitates Shirsat, 2008;
polymorpha L. 2011, child birth Ding, 1982
Shirsat, 2008 Polytrichaceae Polytrichum Urinary tract infection Glime, 2007
Marchantiaceae Marchantia palmata Blisters and Tag et al., juniperinum
Nees infection 2007 Hedw
Marchantiaceae Marchantia convoluta Gastrointestinal Rao, 2009 Polytrichaceae Pogonatum Purgatives, Anti- Alam, 2012,
Gao et K.C. Zhang irritation macrophyllum inflammatory Azuelo et al.,
Marchantiaceae Marchantia paleacea Hepatic disorder, Sabovljevic Dozy & Molk. 2011
Bertol. Anti-fever et al., 2011, Mniaceae Mnium sp. Wound healing, Burns Asakawa
Azuelo et al., and blisters (2013c), Singh
Lophocoleaceae Hepatostolonophora Anti-leukemic Asakawa et al. (2011)
paucistipula et al., 2013 Mniaceae Mnium Epistaxis Pant 1998,
(Rodwey) J.J. Engel cuspidatum Asakawa, 2007
Lophocoleaceae Chiloscyphus rivularis Anti-leukemic Asakawa Hedw.
(Schrad.) Hazsl. et al., 2013 Mniaceae Plagiomnium Edema Azuelo et al.,
Lophocoleaceae Plicanthus hirtellus (F. Anti-leukemic Asakawa, acutum (Lindb.) 2011
Web.) Schust. 2007, T.J. Kop.
Sabovljevic Meteoriaceae Aerobryum Blisters Lubaina et al.,
et al.2001 lanosum (Mitt.) 2014
Lepidoziaceae Bazzania sp. Anti- Scher et al. Mitt.
carcinogenic, (2004) Hypnaceae Hypnum Anti-bacterial, Veljic’ et al.
Antibacterial cupressiforme Fungicidal (2009)
Lepidoziaceae Lepidozia sp. Anti-platelet, Paliwal et al., Hedw.
Antibacterial 2014 Fontinalaceae Fontinalis Anti-pyretic Chandra et al.,
Jungermaniaceae Jungermannia sp. Neurotrophic Kondoh et al., antipyretica 2016
properties 2005 Hedw.
Jubulaceae Frullania tamarisci Antiseptic Remesh and Fissidentaceae Fissidens nobilis Hair care, Wound Harris, 2008
(L.) Dumort. Manju 2009 Griff. healing
Jubulaceae Jubulaceae ericoides Hair care Remesh and Entodontaceae Entodon Anti-Cold and Cough Lubaina et al.,
(Nees ex Mart.) Mont. Manju, 2009 flavescens 2014
Herbertaceae Herbertus sp. Astringents, Anti- Alam, 2012, (Hook.) A. Jaeger
fungal Azuelo et al., Entodontaceae Entodon myurus Anti-microbial Singh et al.,
2011 (Hook.) Hampe 2011
Dumortieraceae Dumortiera hirsute Anti-bacterial, Azuelo et al., Ditrichaceae Ceratodon Fungicidal Frahm, 2004
(Sw.) Nees Anti-leukemic 2011, purpureus
Madsen and (Hedw.) Brid.
Pates 1952 Dicranaceae Leucobryum Analgesic Asakawa,
Conocephalaceae Conocephalum Antimicrobial Alam, 2012, bowringii Mitt. 2007,
conicum (L.) Dum Ding, 1982 Dicranaceae Oreas martiana Wound healing Lubaina et al.,
Aytoniaceae Plagiochasma Anti-fungal Alam, 2012, (Hoppe and 2014
intermedium Lindenb. Shirsat, 2008 Hornsch.) Brid.
& Gottsche Bryaceae Bryum argenteum Anti-fungal Asakawa, 2007
Aytoniaceae Plagiochasma Used in the Asakawa, Hedw.
appendiculatum treatment of skin 2007 Bryaceae Rhodobryum Cardiovascular Asakawa,
Lehm. disorders roseum (Hedw.) ailments, Emotional 2007, Pant,
Aneuraceae Riccardia sp. Anti-leukemic Alam, 2012, Limpr. disorder 1998; Wu,
Azuelo et al., 1977
2011 Bryaceae Rhodobryum Cardiovascular Wu, 1982,
giganteum ailments, Emotional Asakawa,
(Schwagr.) Paris disorder, Anti-fever, 2007; Pant,
Lowers blood pressure 1998
Bartramiaceae Blisters and infection
(continued on next page)

3
A. Bandyopadhyay and A. Dey Phytomedicine Plus 2 (2022) 100255

Table 2 (continued ) extract contains benzonaphthoxanthenones and bibenzyl derivatives

Family Species Application References that inhibit the progression of RPMI-7951 melanoma and U-251glio­
blastoma multiforme (Zheng et al., 1993). In terms of anti-leukemia
Philonotis fontana Asakawa,
(Hedw.) Brid. 2007,
activity, bryophytes show great promise. Marchantin A, riccardin, per­
Flowers, 1957; rottetin E from Marchantia palacea, Riccardia multifida, and Radula per­
Pant, 1998 rottetii respectively have cytotoxic effects on malignant KB cells
Bartramiaceae Philonotis sp. Blisters, Anti-fever Asakawa, 2007 (Asakawa, 1982). Human epidermoid carcinoma was significantly
Amblystegiaceae Cratoneuron Cardiovascular Asakawa,
reduced by diplophyllin, isolated from the liverwort Diplophyllum abli­
filicinum (Hedw.) ailments 2007, Pant,
Spruce 1998 cans and D. taxifolium (Ohta et al., 1977). Tulipinolide, extracted from
Amblystegiaceae Leptodictyum Anti -fever and urine Pant, 1998 Plagiochila semidecurrens, inhibited the growth of nasal carcinomas.
riparium (Hedw.) infection Plagiochilla fasciculatae has been shown to inhibit P388 cells responsible
Warnst. for leukemia (Asakawa, 1981). Mosses have also been shown to inhibit
Bartramiaceae Plagiopus oederi Depressant Pant, 1998
(Brid.) Limpr.
cancer cell growth (Hallingback and Hodgetts, 2000).
As a result of their biologically active components, liverwort me­
tabolites are potentially valuable as drugs; especially effectives are bis-
found to inhibit the growth of Sarcoma 37 in CAF1 mice (Zhonghua bibenzyls, such as marchantin and isoplagiochin. Similar to paclitaxel,
1999). Polytrichum ohioense has been found to contain ohioensin A, a they interfere with the degradation of microtubules during the division
compound that exhibits cytotoxic effects toward 9PS murine leukemia of cancerous cells. Marchantia polymorpha and M. paleacea sp. diptera,
and MCF-7 mammary carcinoma cells. Polytrichum pallidisetum ethanolic strains that produce marchantin A and its analogues in large quantities,

Table 3
Terpenoids and bibenzyls as major phytochemicals in Bryophytes.
Class Bioactive IUPAC name The species in which they are
compound prevalent

Diterpenoid Sacculatal 1,2-Naphthalenedicarboxaldehyde, 1,4,4a,5,6,7,8,8a-octahydro-5,8a-dimethyl-5-(4-methyl-3- Hypnum plumaeforme,

(C20H30O2) penten-1-yl)-,(1S,4aS,5S,8aS) Anthoceros caucasicus,
Isosacculatal 1,2-Naphthalenedicarboxaldehyde, 1,4,4a,5,6,7,8,8a-octahydro-5,8a-dimethyl-5-(4-methyl-3- Lepidozia reptans
(C20H30O2) penten-1-yl)-, (1S,4aS,5S,8aS)
Clerodane (C20H38) (1S,2R,4aS,5S,8aS)− 1,2,4a,5-Tetramethyl-1-(3-methylpentyl)decahydronaphthalene
Kaurane (C20H34) Kaurane
Labdane (C20H38) (4aR,5S,6S,8aS)− 1,1,4a,6-Tetramethyl-5-[(3R)− 3-methylpentyl]decahydronaphthalene
Spiroclerodane

5,10-seco-clerodane
9,10-seco-clerodane
Infuscane
abeo-labdane

Sacculatane
Sesquiterpenoids β-barbatene (1R,2R,6S,7R)− 1,2,6-Trimethyl-8-methylenetricyclo[5.3.1.02,6]undecane Dumortiera hirsute,
(C15H24) (1S,4S)− 4-Isopropyl-1,6-dimethyl-1,2,3,4-tetrahydronaphthalene Lepidolaena hodgsoniae,
Calamenene 1-methyl-4-[(1R)− 1,2,2 trimethylcyclopentyl]benzene Lepidolaena clavigera
(C15H22) (3aS,6aR,9aR,9bS)− 3,6,9-Tris(methylene)decahydroazuleno[4,5-b]furan-2(3H)-one
Cuparene (C15H22)
Dehydrocostus
lactone (C15H18O2)
a-furanopinguisanol
Furanopinguisanone
Triterpenoids Hopene (C30H50) Hop-17(21)-ene
Hopene II (C30H50) (3R,3aR,5aS,5bR,7aS,11aS,11bR)− 3-Isopropyl-3a,5a,5b,8,8,11a-hexamethyl-
2,3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13-octadecahydro-1H-cyclopenta[a]chrysene
Monoterpenoids b-cyclocitral 2,6,6-Trimethyl-1-cyclohexene-1-carbaldehyde Plagiomnium acutum, Mnium
(C10H16O) (4S)− 4-Isopropenyl-1-methylcyclohexene hornum, Plagiomnium
b-pinene (4S)− 4-Isopropenyl-1-methylcyclohexene undulatum
Limonene (C10H16) 1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one
Camphor (C10H16O)
Bis(bi)benzyls and Isoplagiochin A (7Z)− 14-Oxapentacyclo[21.3.1.12,6.19,13.015,20]nonacosa-1(27),2(29),3,5,7,9 Riccardia multifida
Bibenzyls (C28H22O4) (28),10,12,15,17,19,23,25-tridecaene-3,18,26-triol Marchantia paleacea
Isoplagiochin B (7Z)− 14-Oxapentacyclo[21.3.1.12,6.19,13.015,20]nonacosa-1(27),2(29),3,5,7,9 M.Polymorpha
(C28H22O4) (28),10,12,15,17,19,23,25-tridecaene-3,18,26-triol M.papillata
Marchantin A 2,15-Dioxapentacyclo[22.2.2.13,7.110,14.016,21]triaconta-1(26),3(30),4,6,10 Dumortiera hirsute
(C28H24O5) (29),11,13,16,18,20,24,27-dodecaene-4,5,17-triol
Marchantin E 8-Methoxy-2,15-dioxapentacyclo[22.2.2.13,7.110,14.016,21]triaconta-1(26),3
(C29H26O6) (30),4,6,10(29),11,13,16,18,20,24,27-dodecaene-4,5,17-triol
Pakyonol 4-Methoxy-2,15-dioxapentacyclo[20.2.2.216,19.13,7.110,14]triaconta-1(24),3
(C29H26O4) (30),4,6,10(29),11,13,16,18,22,25,27-dodecaen-17-ol
Perrottetin E 4-[2-(3-Hydroxyphenyl)ethyl]− 2-{4-[2-(3-hydroxyphenyl)ethyl]phenoxy}phenol
(C28H26O4) 3-Methyl-8-(2-phenylethyl)− 2,5-dihydro-1-benzoxepin-6-ol
Radulanin A 5-Methoxy-14-oxapentacyclo[20.2.2.210,13.115,19.02,7]nonacosa-1(24),2,4,6,10,12,15
(C19H20O2) (27),16,18,22,25,28-dodecaene-16,24-diol
Riccardin A 2,14-Dioxapentacyclo[20.2.2.210,13.13,7.115,19]triaconta-1(24),3(30),4,6,10,12,15
(C29H26O4) (27),16,18,22,25,28-dodecaene-4,12-diol
Riccardin B
(C28H24O4)

4
A. Bandyopadhyay and A. Dey
Fig. 1. Pharmacological properties of bryophytes.
are readily cultivable in the field and under greenhouse conditions. In
the kingdom of plants, luteolin is a common glycoside. Among the many
families of plants with luteolin, Bryophyta is known to contain it. These
flavones exhibited antioxidant, analgesic, antibacterial, and anticarci­
nogenic abilities in preclinical studies. Luteolin has been reported to
show anti-cancer effect with its great potential to be a promising
chemotherapeutic agent. Its ability to inhibit angiogenic processes, to
trigger programmed cell death, to prevent the development of cancer in
animal model systems, to suppress in vivo tumor progression and to
improve the cytotoxicity of certain cancer-fighting drugs have deter­
mined its potential as a chemotherapeutic agent. In addition to modi­
fying ROS levels, luteolin also inhibited topoisomerase 1 and 2, reduced
NF-kappa β and AP1 activity, stabilized P53, and inhibited PI3K, STAT3,
IGF1R, and HER2. The cancer-inhibiting and therapeutic properties of
luteolin have been demonstrated recently (López-Lázaro, 2009).In
addition to benzonaphthoxanthenone and ohioenesin H, one study
found the presence of communin A and B from Polytrichum commune. It
has been shown that these compounds were effective against cancer of
the lung, human hepatic carcinoma, and human gastrointestinal cancer
and demonstrated cytotoxic efficacy towards a variety of human cancer
cells, like human breast cancer and human T-cell blood cancer (Fu et al.,
2009)
The antitumor activities of the compounds 8,9-secokauranes, rab­
doumbrosanin, and 8,14-epoxyrabdoumbrosanin, derived from New
5
Phytomedicine Plus 2 (2022) 100255
Zealand Lepidolaena taylorii, were evaluated in an in vivo model system.
Human cervical tumor xenografts in a nude mouse model were strongly
inhibited by marchantin C, from an extract from Asterella angusta (Perry
et al., 1999). Human glioma A172 cells and human cervical adenocar­
cinoma HeLa cells when treated with marchantin C (8 − 16 μM), were
also found to have reduced microtubules in a dose-dependent and
time-dependent manner during the G2/M phase (Shi et al., 2009).
As with the potent known microtubule depolymerizer vincristine, the
same compound decreased tubulin polymerization at 8 − 24 μM. Both its
apoptotic effects in the cell and antitumor activity in vivo suggest that
cytotoxic bis-bibenzyls may play the same role in microtubule depoly­
merization. Marchantin C inhibits microtubules, causing mitotic arrest
in tumor cells and suppressing their growth. In contrast to the classical
microtubule inhibitors such as colchicine, podophyllotoxin, vincristine,
the unique structure of marchantin C, which inhibits microtubule
polymerization like vinblastine or vincristine, may make it a potentially
useful anti-tumor agent for further in vivo testing in more complex anti-
tumor models (Shi et al., 2009).
A high degree of cytotoxicity was observed for all bryophytes in 5-
FU-selected CD24+ colorectal cancer cells and bryophytes decreased
Rhodamin123low cell population in those. Rhodamin123 is a fluorescent
dye that indicates where mitochondria are located in live cells. Rho123
can be used to detect changes in mitochondrial distribution (Johnson
et al., 1980). Rho123 accumulation in stem cells is very low (Suzergoz
A. Bandyopadhyay and A. Dey Phytomedicine Plus 2 (2022) 100255

Fig. 2. Bryophytes reported against different human diseases.

Fig. 3. Some phytoconstituents of bryophytes (from ChemDraw). Sacculatal, Isosacculatal, Clerodane, Kaurane, Labdane, Spiroclerodane, 5,10-seco-clerodane,
β-barbatene, Calamenene, Cuparene, Dehydrocostus lactone, Hopene, Hopene II, b-cyclocitral, b-pinene, Limonene, Camphor, Isoplagiochin A, Isoplagiochin B,
Marchantin A, Pakyonol, Perrottetin E, Radulanin A, Riccardin A, Riccardin B (1–25).

6
A. Bandyopadhyay and A. Dey
et al., 2007) because these cells are metabolically inactive and dormant.
It was determined that Rho123high cell subpopulations can lead to tumor
development and progression (Lu et al., 2013). On the other hand,
Rho123low cells have properties more similar to stem cells. A traditional
Chinese folk medicine, Scutellaria barbata, inhibited the proliferation of
cells, resulting in a higher level of Rho123 retention in HCT-8/5-FU.
However, there is a substantial research gap that uncovers the mecha­
nisms responsible for bryophyte as anti-cancer aganets. This is an
important area of research for understanding molecular cross talks and
druggability of bryophyte-derived molecules.
Neuroprotective activity
The sesquiterpenoids in Mastigophora diclados, mastigophorenes A, B,
and D, displayed neurotrophic effects at 10–5 to 10–7 M concentrations.
They were highly effective in stimulating neurite outgrowth and estab­
lishing networks in primary cultures prepared from embryonic rat brains
(Fukuyama and Asakawa, 1991a). Mastigophorenes A and B, at con­
centrations of 0.1 and 1 μM, were shown to not only enhance neuritic
sprouting but also promoted survival of neurons. It was found that both
compounds were toxic to neurons at concentrations of 10 μM
(Fukuyama et al., 2001). According to these findings, mastigophorenes
may be capable of protecting neurons against the ill effects of harmful
substances like oxygen free radicals. In order to obtain new selective
stimulators of neurotrophic activity from such chemical structures,
other researchers investigated the neurotrophic properties of mastigo­
phorenes. Analogues of mastigophorene were synthesized by Gille and
coworkers (Gille et al., 2000). Dopaminergic neurons in primary cell
culture were affected differently by both compounds. Only one com­
pound significantly stimulated cell growth. At concentrations above 0.5
μM, the number of cells and the quantity of processes decreased. In
addition, another compound stimulated the number of cells and the
morphology of cells. In the range of 0.05 to 1.0 μM, cells were able to
survive 20–30% longer. A slight increase of 12% was observed in the
surface of the cell at 0.5 μM (Gille et al., 2000). In addition,
secoaromadendrane-type sesquiterpenoids are also derived from liver­
worts that show neurotrophic properties. Plagiochilide and plagiochilal
B, both isolated from Plagiochila fruticosa, effectively accelerated neurite
outgrowth and also significantly improved choline acetyl transferase
function in embryonic rat cerebral hemisphere neuronal cell cultures
(Fukuyama and Asakawa, 1991b). H. cupressiforme ethyl acetate extract
inhibited neuroinflammation. In order to achieve this, nitric oxide is
reduced in BV2 microglial cells stimulated with lipopolysaccharide.
Additionally, it shows potent inhibitory activities against tyrosinase and
acetylcholinesterase (AChE). Studies of neuroinflammation using
lipopolysaccharide-induced stimulation of microglia have long been
undertaken, linked to the pathological surveillance of neurodegenera­
tive ailments such as Alzheimer’s disease (AD) and Parkinson’s disease
(PD) (Batista et al., 2019). Different pro-inflammatory cytokines and
neurotoxic mediators are released by activated microglia, including ni­
tric oxide, tumor necrosis factor-alpha, interleukin-1β, interleukin-6,
and reactive oxygen species (ROS) (Zhang et al., 2020). Inflammation
and neuronal damage result from the accumulation of these factors.
Inhibiting overactive and persistent microglial activity may therefore
mitigate neurodegenerative processes. Also, suppressing enzymes that
play a role in the pathogenesis of AD and PD, including AChE and
tyrosinase, offers a promising avenue for treatment (Luni´c et al., 2020).
Inhibition of acetylcholinesterase
Inhibition of AChE led to the isolation of sesquiterpenoids of the ent-
longipinane-type from Marsupella alpina extracts in the presence of
ethanol. In this liverwort species, these active components were present.
Marshupellin A and B were the most active of nine isolated compounds.
Compared to galanthamine with a positive control of 0.004 μg, marsu­
pellin A and B required 0.66 and 0.85 μg, correspondingly, to inhibit
7
Phytomedicine Plus 2 (2022) 100255
AChE, according to the bioautographic TLC assay. Microplate tests
showed that both compounds inhibited AChE (Zhang et al., 2014). The
liverwort Scapania undulata contains a new labdane diterpene, sca­
paundulin C. This compound demonstrated mild AchE inhibitory ac­
tivity with a low inhibiting concentration of 250 ng versus galantamine
as positive control at 10 ng (Kang et al., 2015). Wang and colleagues
proved flavonoid-rich extracts of gametophytes and sporophytes of
Marchantia polymorpha inhibited the activity of AChE (Wang et al.,
2016). AChE was significantly inhibited by the sporophyte extracts.
Flavonoids were found in sporophytes to be ten folds more abundant
than in gametophytes in M. polymorpha (Wang et al., 2016).
Antispasmodic activity
The bisbibenzyl-isoquinoline alkaloids have similar structures to
marchantin-type cyclic bisbibenzyls. Like d-tubocurarine, these sub­
stances comprise a bisbisbenzylether moiety. It is an agent that is used
clinically for skeletal muscle relaxation. The muscle relaxant activity of
marchantin A and its trimethyl ether has surprised researchers. As a
result of not carrying a positively charged nitrogen atom, the mentioned
bisbisbibenzyls have effectiveness which is 3.5 times weaker than those
of d-tubocurarine (Taira et al., 1994). As evidenced by the stereo­
chemical, water-repellent characteristics of marchantin A and cepha­
rathine, as well as by their biological and biochemical actions, both
compounds are likely to possess similar therapeutic effects due to their
affinity for a similar receptor. Marchantin A shows a wide range of ac­
tivity based on its potent calcium binding mechanism (Keseru and
Nogradi, 1995).
Cathepsin L and cathepsin B suppressive properties
There is a correlation between cathepsin L and osteoporosis (Katsu­
numa, 1997) and allergic reactions (Matsunaga et al., 1993). A che­
mopreventive drug for these diseases is being developed by researching
enzyme inhibitors from natural products. There was an inhibitory effect
of both cathepsin L and cathepsin B in the marchantin series. As far as
enzyme inhibitors are concerned, isomarchantin C isolated from
M. polymorpha and Marchantia palmata was the most active inhibitor.
According to Asakawa, infuscaic acid also exhibits the same activity as
isomarchantin C (Asakawa, 2008).Both cathepsins B and L were potently
inhibited by the crude extract of Porella japonica. By fractionating the
crude extract based on biological activity, three new guaianolides were
produced. Among these compounds, 11,13-dehydoporelladiolide
weakly inhibited cathepsin B and cathepsin L (Hashimoto et al., 1998a).
Antiplatelet properties
Using Reboulia hemisphaerica as a source of marchantiaquinone, a
concentration of 100 mg/ml of this compound demonstrated antiplate­
let activity (Wei et al., 1995). Plagiochilal C, isolated from Plagiochila
fruticosa also shows a remarkable antiplatelet property. Antiplatelet ef­
fects of plagiochilal C were significant with arachidonate (100 μM) with
95% inhibition at 50 μg/ml and 45% inhibition at 50 μg/ml. With
collagen (10 μg/ml), 100% blockade at 100 μg/ml level resulted in
aggregate formation in rabbit platelets, which were washed. Compared
with plagiochilal C, isoplagiochilide produced less potent effects (Lin
and Wu, 1996), though both of them were isolated from same source. A
potent antiplatelet effect was observed for both lepidozenolide and (-)−
5beta hydroperoxylepidozenolide extracted from Lepidozia vitrea and
Lepidozia fauriana (Shu et al., 1994).
Antimicrobial and antifungal activities
Bacteriostatic efficacy of sacculatal, isolated from Pellia endiviifolia,
was demonstrated against Streptococcus mutans, responsible for dental
caries with an LD50 of 8 μg/ml (Asakawa et al., 2009). Agar diffusion
A. Bandyopadhyay and A. Dey
tests were performed on sesquiterpenoids isolated from Mastigophora
diclados to determine how they react against a Staphylococcus aureus
strain. Compared to standard antibiotics chloramphenicol and kana­
mycin, these sesquiterpenoids showed weaker activity. Tested com­
pounds included mastigophorene C, a dimeric herbertene-1,2-diol. The
monomer also showed antibacterial activity (13 mm) along with the
compound as a whole (17 mm). Analyses of ether and methanol extracts
from a Tahiti specimen of M. diclados that inhibited the growth of
B. subtilis and S. aureus (MIC 16 μg/mL) (Komala et al., 2010). Both
extracts were fractionated based on their bioactivity to yield (− )-her­
bertene-1,2-diol, (− )-mastigophorene C, and (− )-mastigophorene D,
with MIC values of 2–8 μg/mL, this formulation exhibited moderate
antimicrobial activity against B. subtilis. The antibacterial activity of
marchantin A was evident against Acinetobacter calcoaceticus, Bacillus
cereus, B. megaterium, B. subtilis, Cryptococcus neoformans and Staphylo­
coccus aureus at MIC 6.25 μg/mL, 12.5 μg/mL, 25 μg/mL, 25 μg/mL,
12.5 μg/mL, and 3.13− 25 μg/mL respectively (Asakawa et al., 1990).
Antimicrobial activity was observed for marchantin A isolated from the
Hungarian M. polymorpha which was resistant to Gram-negative bacteria
Pasteurella multocida (MIC 4.5 nM), Pseudomonas aeruginosa (MIC 84.5
nM), Haemophilus influenzae (MIC 72.7 Nm), and Neisseria meningitidis
(MIC 72.7 nM) and against the Gram-positive Staphylococcus aureus
(MIC 6.9 nM), Streptococcus pyogenes (MIC 9.1 nM), and Streptococcus
viridans (MIC 18.1 nM) (Kamory et al., 1995). Asterella angusta ether
extracts had antifungal activity against C. albicans as detected by direct
TLC. The antifungal effects of riccardin D and B, and dihydroptychantol
were observed against C. albicans, showing minimum inhibitory quan­
tity values between 0.25 and 0.8 μg and minimum inhibitory concen­
tration in range of 16− 64 μg/mL (Qu et al., 2007; Jensen et al., 2012). In
this regard, free phenolic hydroxy groups appear to play an important
role, as bis-bibenzyls containing phenolic hydroxy groups exhibited
reduced potency (Scher et al., 2004)
Further ad hoc applications
People make use of synthetic compounds to combat pests, fungi,
rodents and insects that may cause adverse effects to the environment as
well as human health. In addition to this, the widespread use of in­
secticides has led to insects becoming more resistant to the chemicals
(Alyokhin et al., 2008; Whalon et al., 2012). Hence, natural products
that have low toxicity and are environment friendly are needed to
replace the hazardous chemicals that may otherwise alter soil chemistry
and health. In the past few years, bryophytes with insecticidal properties
have become increasingly important. The fatty acids contained in Hyp­
num cupressiforme, Dicranum scoparium, Polytrichastrum formosum,
Homalothecium lutescens and liverwort Conocephalum conicum, are used
for controlling Sitophilus granaries. There have also been reports of the
use of moss extracts of Calymperes afzelii, Thuidium gratum, Bryum cor­
onatum and Barbula lambarenensis for the eradication of maize stem
borer (Ande et al., 2010; Abay et al., 2013). Many studies also demon­
strate that plant extracts work as fumigant (Rajendran and Sriranjini,
2008) and are effective as antifeedants (Susurluk 007). In shallow wa­
ters of lakes, streams and springs a lot of different types of mosses such as
Bryum, Hypum and Fissidens growing with thallophytes are found.
These mosses are high in lime content and help build rocks. Soil con­
servation is made possible by the precipitation of calcium carbonate and
mosses with their associated symbionts. First world countries typically
use hepatics and mosses for the manufacture of natural gas, hydrogen,
ethylene, methanol, etc. The most efficient moss for generating heat,
methane and having rapid regeneration, a low sulfur content and pro­
ducing greater heat value than wood is peat moss (Saxena and Harinder
2004). Bryanites do not have a leaf cuticle, therefore they can gain and
lose water more easily. Other plants are unable to use the tiny amounts
of water that come from fog, mist, and dew that these plants can.
Bryophytes, such as liverworts and mosses, are also useful as environ­
mental indicators, producers of growth-regulating substances like,
8
Phytomedicine Plus 2 (2022) 100255
auxins, gibberellins, cytokinins and ethylene and mosses can also be
used in stuffing (Sabovljevic et al., 2011)
Adverse effects of bryophytes
There are a few Frullania species, such as F. dilatata, F. tamarisci spp.
nisquallensis, Chiloscyphus polyanthos and Schistochila appendiculata that
are capable of causing allergic reaction and skin allergies due to their
sesquiterpene lactone content containing alpha-methylene gamma-lac­
tones. The species of Frullania mentioned above are also medicinally
important and epiphytic on trees. Consequently, they have been iden­
tified as a cause of occupational contact dermatitis in Western Europe
and North America among tree fellers, lumberjacks, and olive harvesters
(Knoche et al., 1969; Mitchell et al., 1970; Mitchell 1986). The allergens
(+)-frullanolide derived from F. dilatata and (-)-frullanolide isolated
from F. tamarisci ssp. tamarisci, results in a severe allergic reaction and
dermal irritation. Marchantia polymorpha and Metzgeria furcata both
cause allergic skin irritation, but their allergens remain unidentified
(Asakawa 1982; Asakawa et al., 2013b). Frullania or lichens growing on
certain tree trunks are sometimes responsible for allergenic contact
dermatitis in Finnish woodcutters. A patient was diagnosed with occu­
pational allergic contact dermatitis caused by lichen, even though he
had not reacted to sesquiterpene lactones from other possible sources
(Aalto-Korte et al., 2005). Additionally, liverwort species contain sec­
ondary metabolites that can alter the activity of the central nervous
system (CNS) as well. Among these are perrottetinene and perrottetineic
acid which are bibenzyl cannabinoids belonging to the tetrahydrocan­
nabinol family. Some Radula species produce volatile extracts that
contain both the compounds. Radula perrottetii was responsible for the
isolation of perrottetinene (PET) (Toyota et al., 1994). Following this
discovery, the compound was also found in R. campanigera, R. chinensis,
R. laximera and R. marginata (Asakawa et al., 2013c). R. marginata is also
capable of producing perrottetineic acid. The structure of perrottetinene
is similar to that of Δ9 -tetrahydrocannabinol (Δ9 -THC) from Cannabis
sativa, however, liverwort contains cyclohexene rings in the cis config­
uration, unlike trans-THC Chicca et al. (2018). have revealed that cis-
and transdiastereoisomers of PET permeate the brain with relative ease.
Consequently, it leads to temperature drops, seizures, an inhibitory ef­
fect on behavior or locomotion and numbing in mice. These effects are
similar to those caused by Δ9 - trans-THC. Trans-PET was more effective
than the cis-PET at releasing partial agonis from the CB1R. There were
unexpected pharmacological differences between the perrottetinene
diastereoisomers and Δ9 -trans-THC. Consequently, it has the potential
to limit its adverse effects and reduce neuroinflammation, because its
basal levels of PGD2 and E2 in the brain are significantly reduced.
cis-PET derived from Radula species might be an appealing drug dis­
covery candidate since it is likely to have fewer side effects than Δ9
-trans-THC naturally occurring in Cannabis sativa also it can reduce
prostaglandin levels (Chicca et al., 2018).
Clinical status
Recent advances in the bryophyte based pharmaceutical field gained
more traction after one of the candidates passed the first clinical trial.
Alpha-galactosidase (aGal) deficiency is responsible for Fabry disease, a
rare form of lysosomal storage disease. Global triacylceramide (Gb3) is
broken down by aGal, a lysosomal enzyme. Gb3 accumulates continu­
ously in the cells of people with Fabry disease due to the absence of aGal.
Patients often experience discomfort, severe skin problems, cardiovas­
cular, kidney, and hepatic complications, and can have organ failure as a
result. In enzyme replacement therapy, a biopharmaceutically produced
substitute is administered intravenously to replace the missing enzyme.
As part of an enzyme replacement therapy, the patients are administered
the enzyme α-galactosidase to treat the Fabry disease. As a leading
biopharmaceutical company developing next-generation bio­
pharmaceuticals for orphan diseases, Greenovation Biotech has built a
A. Bandyopadhyay and A. Dey
proprietary pipeline of drug candidates. A first-of-its-kind moss-made
biopharmaceutical α-galactosidase (moss-aGal) has successfully
completed the phase I clinical trial. It provided proof that “Bryo­
technology” meets current good manufacturing practice standards. As a
result, moss can be used as a more efficient expression system for bio­
pharmaceutical production. Production for straightforward phase II/III
is well underway. (Niederkrüger et al., 2019)
Future prospects
The earliest plants, bryophytes, evolved from aquatic environments
to terrestrial environments, and so lack complex architectures like those
found in modern terrestrial plants. In particular, they lack defense and
growth mechanisms. So, liverworts get their survival and protection
from the environment from the biochemical activities of secondary
metabolites (Chen et al., 2018; Clayton et al., 2018). Currently, many
pharmaceutical laboratories, research institutes, and universities are
conducting studies on the medicinal benefits of bryophytes. Current
studies are investigating how bryophytes can be used for the remedy of
conditions such as liver ailments, dermatological disorders, cardiac
disorders, among others. Hepatic disorders are treated with bryophytes
such as Conocephalum conicum, Marchantia polymorha, Reboulia hemi­
sphaerica and mosses Bryum argenteum, Climacium dendroides, Funaria
hygrometrica, Rhodobryum roseum, Sphagnum spp. and Weissia con­
troversa. A variety of eye diseases are treated using the peat moss species
Sphagnum teres in China. The moss Rhodobryum giganteum and R. roseum
have long been used to treat cardiovascular disorders and nerve prob­
lems in China. Polytrichum commune is effective as analgesic and diuretic
and Haplocaldium microphyllum is beneficial for chest cold, urinary tract
infections, pharyngitis and sore throat. In addition to its ethnomedical
properties, Sphagnum spp. has been used in postoperative dressings
because of its fast absorption.
Future drug development programs will take advantage of phyto­
chemical data-mining methods that encompass identification, quantifi­
cation, evaluation, conformational analysis, clinical assessment,
monitoring, bioactivity analysis, and designing new drugs based on
these unique bioactive bibenzyls found in bryophytes. Assessment of this
potent chemical group is imperative for expanding the sector of herbal
medicines and natural therapies, as well as dietary supplements derived
from natural products. Bryophytes produce chemicals that are often
studied in a laboratory or on animal models on a molecular level, yet
they are rarely studied in the context of interactions between molecules,
drug kinetics or substance stoichiometry and toxicology. Several studies
have shown that bibenzyl compounds from bryophytes have anti-cancer
properties. However, there is a substantial research gap that uncovers
the mechanisms responsible for this anti-cancer properties. It is imper­
ative that all the knowledge gaps be filled before bibenzyls can be rec­
ommended as an effective chemotherapeutic agent or exploited for drug
design. In what applications might bryophyte-derived bibenzyl canna­
binoids be used? Is it possible to stimulate endocannabinoid activity
with these chemicals? How does its particular structure affect this? As
cytotoxic agents, how could bibenzyls function? Are there a good chance
that marchantin-group bibenzyls can be developed into potential ther­
apeutics? These are all issues that need clarifying and demonstrating.
This is an important area of research for understanding molecular cross
talks and structure-activity relationships properly. Apart from this, cis-
PET derived from Radula species might be an appealing drug discov­
ery candidate since it is likely to have fewer side effects than Δ9 -trans-
THC naturally occurring in Cannabis sativa also it can reduce prosta­
glandin levels. Research should be conducted in this area as well. It is
also advisable to carry out more scientific evaluations and validations of
traditional medicines, such as those from Ayurveda and Unani systems.
As traditional practices are evaluated and validated by modern methods,
this new trend opens the door to new drug discovery and contributes to
improved healthcare.
Only liverworts and mosses have been linked to chemistry and
9
Phytomedicine Plus 2 (2022) 100255
ethnopharmacology. Chemicals and proteins are already produced by
bryophytes (Simonsen et al., 2009; Ikram et al., 2015). Aside from the
studies of novel transformation technologies and development of bio­
reactors (King et al., 2016), the application of bryophytes is only starting
to be explored. A range of bryophytes is worth investigating to discover
known and potentially new natural products. A useful biotechnological
tool for acquiring enough plants is in vitro establishment and propaga­
tion of clean material (Rowntree et al., 2011; Sabovljevic et al., 2014),
and optimization strategy for achieving higher levels of certain sec­
ondary metabolites (Sabovljevic et al., 2016).
Conclusion
It is thought that as a result of their small size and lack of nutritional
value to humans, the bryophytes have been neglected chemically since
the beginning of the 20th century. The use of bryophytes as medicinal
plants is widely prevalent in Asia. The focus of this review is on the
synthesis, characterization, and structural evaluation of bioactive sec­
ondary metabolites found in bryophytes, as well as their ethnomedical
properties. Since the 1960s, hundreds of novel compounds that include
many aromatics and terpenoids, have been found in bryophytes. In the
hornwort family, chemistry and ethnopharmacology have not been
correlated. With the modern advent of bryotechnology, these plants can
be cultivated at large scale under controlled conditions to produce their
major secondary metabolites with biomedical and therapeutic signifi­
cance. .
Author agreement
Manuscript title: Ethno-medicinal attributes of Bryophytes: A po­
tential pharmaceutical breakthrough? “. We, the undersigning authors
declare that this manuscript is original, has not been published before
and is not currently being considered for publication elsewhere. We
confirm that the manuscript has been read and approved by all named
authors and that there are no other persons, who satisfied the criteria for
authorship, but are not listed. We further confirm that the order of au­
thors listed in the manuscript has been approved by all of us.
CRediT authorship contribution statement
Anustup Bandyopadhyay: Conceptualization, Writing – original
draft. Abhijit Dey: Conceptualization, Supervision.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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