Phytochemistry xxx (2016) 1e20

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Phytochemistry
journal homepage: www.elsevier.com/locate/phytochem

Review

Medicinal uses, chemistry and pharmacology of Dillenia species

(Dilleniaceae)
Carla W. Sabandar a, Juriyati Jalil a, *, Norizan Ahmat b, Nor-Ashila Aladdin a
a
Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur,
Malaysia
b
Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia

a r t i c l e i n f o a b s t r a c t

Article history: The genus Dillenia is comprised of about 100 species of evergreen and deciduous trees or shrubs of
Received 18 July 2016 disjunct distribution in the seasonal tropics of Madagascar through South and South East Asia, Malaysia,
Received in revised form North Australia, and Fiji. Species from this genus have been widely used in medicinal folklore to treat
12 November 2016
cancers, wounds, jaundice, fever, cough, diabetes mellitus, and diarrhea as well as hair tonics. The plants
Accepted 17 November 2016
Available online xxx
of the genus also produce edible fruits and are cultivated as ornamental plants. Flavonoids, triterpenoids,
and miscellaneous compounds have been identified in the genus. Their extracts and pure compounds
have been reported for their antimicrobial, anti-inflammatory, cytotoxic, antidiabetes, antioxidant,
Keywords:
Dillenia
antidiarrheal, and antiprotozoal activities. Mucilage from their fruits is used in drug formulations.
Dilleniaceae © 2016 Published by Elsevier Ltd.
Medicinal uses
Phytochemical
Pharmacology

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Medicinal uses of Dillenia species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Chemistry of Dillenia species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Triterpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.3. Miscellaneous compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Pharmacology of Dillenia species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2. Anti-inflammatory and antinociceptive activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.3. Cytotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.4. Antidiabetic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.5. Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.6. Antidiarrheal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.7. Antiprotozoal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Toxicology of Dillenia species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6. Role of Dillenia species in drug formulation and drug delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

* Corresponding author.
E-mail address: juriyatijalil@ukm.edu.my (J. Jalil).

http://dx.doi.org/10.1016/j.phytochem.2016.11.010
0031-9422/© 2016 Published by Elsevier Ltd.

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
2 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20
1. Introduction
The genus Dillenia belongs to the Dilleniaceae family and con-
tains approximately 100 known species (Lim, 2012). According to
The Plant List (2013), as many as 175 scientific plant names from the
genus Dillenia have been recorded with 58 accepted names (low
and medium confidence levels) and 71 names of synonym species.
The name Dillenia is derived from Joannes Jacobus Dillenius, a
British botanist who dedicated his efforts in the field of taxonomy
of this genus (Quattrocchi, 2012). Dillenia species are monoecious
plants which produce attractive flowers and yellow fruits. D. indica
is known for its lemon-flavored fruits that are use to make jellies
and curries. These species are evergreen and deciduous trees or
shrubs of disjunct distribution in the seasonal tropics of
Madagascar through South and South East Asia, North Australia,
and Fiji (Dickison, 1979; Horn, 2007; Kerrigan et al., 2011; Lim,
2012). They grow from sea level to an elevation of about 2000 m.
The plants also grow in forests, and several species show an
adaptation to temporary flooded situations. They are mostly trees
that form large leaves and flowers in few-flowered inflorescences
(Dickison, 1979). Their barks are unique in fine colors of red,
grayish, and reddish brown that are used in furniture making
(Hoogland, 1952). Several species of this genus produce sweetish-
sour and astringent edible fruits (Hoogland, 1952; Jansen et al.,
1992; Kerrigan et al., 2011; Lim, 2012; Saha and Sundriyal, 2012)
and are cultivated as ornamental plants (Hoogland, 1952; Kerrigan
et al., 2011).
Based on our extensive search regarding medicinal uses,
chemical constituents, and biological activities of the species from
the genus Dillenia, only very few species have been described thus
far. Starting from 1962 to the present, 19 species of the genus Dil-
lenia have been reported for their medicinal uses and their
phytochemistry. These 19 species are Dillenia andamanica C.E.Par-
kinson, D. aurea Sm., D. bracteata Wight, D. excelsa (Jack) Martelli ex
Gilg., D. indica L., D. ovata Wall. ex Hook.f. & Thomson, D. papuana
Martelli, D. parviflora Griff., D. pentagyna Roxb., D. philippinensis
Rolfe, D. pulchella (Jack) Gilg., D. reticulata King, D. retusa Thunb.,
D. scabrella (D.Don) Roxb. ex Wall., D. eximia Miq., D. serrata Thunb.,
D. suffruticosa (Griff.) Martelli, D. sumatrana Miq., and D. triquetra
(Rottb.) Gilg. However, out of these, only 7 species have been
evaluated for their biological activities. As part of our search for
natural anti-inflammatory compounds, three triterpenes have been
isolated from D. serrata and they performed pronounced inhibitory
activity on the production of prostaglandin E2, which is known as a
predominant inflammatory mediator (Jalil et al., 2015). This review
describes the current state of their medicinal properties, chemistry,
and pharmacological aspects.
2. Medicinal uses of Dillenia species
Dillenia species have been widely used as medicinal plants by
natives in South and Southeast Asian countries (Lim, 2012),
including India, Nepal, Sri Lanka, Bangladesh, Laos, Thailand, Viet-
nam, Malaysia, Indonesia, Philippines, and Papua New Guinea.
Table 1 lists the known medicinal uses of several Dillenia species.
Almost all parts of Dillenia plants are traditionally utilized for
therapeutic purposes. The fresh and dried materials of different
parts of Dillenia plants are processed as decoction, poultice, juice,
and mucilage for the treatment of diarrhea, wounds, cancer, dia-
betes, fever, cough, rheumatism, urinary problems, skin-related
diseases, and aches as well as hair tonics (Table 1). Different
preparations of D. excelsa, D. ovata, and D. parviflora are tradition-
ally used to cure diarrhea (Burkill, 1966; Srithi et al., 2009;
Quattrocchi, 2012). Skin-related diseases such as leucoderma,
skin itches, skin rash, and eczema can be treated using the leaf,
Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
fruit, and stem bark of D. andamanica, D. indica, D. ovata, and
D. pentagyna (Prasad et al., 2008; Quattrocchi, 2012; Boer et al.,
2012; Bhat et al., 2014). In addition, the stem barks of D. aurea
and D. parviflora, as well as the leaf of D. suffruticosa, in the form of
paste or poultice are applied onto skin to heal wounds (Mat-Salleh
and Latiff, 2002; Quattrocchi, 2012; Junsongduang et al., 2014).
Juice and decoction of the fruit and stem bark, as well as the leaves
of D. indica, D. pentagyna, and D. suffruticosa, are used daily to
alleviate cancerous growth, in particular breast and gastric cancers
(Ahmad and Holdsworth, 1995; Sharma et al., 2001; Prasad et al.,
2008; Rosangkima et al., 2008b; Das et al., 2009; Dubey et al.,
2009). Moreover, fruit juices of D. indica and D. philippinensis are
given orally to cure fever and cough symptoms (Angami et al.,
2006; Macahig et al., 2011; Quattrocchi, 2012). The mixed juice of
fruit and calyx of D. indica and the powdered stem bark of
D. pentagyna are administered daily for the treatment of diabetes
(Dubey et al., 2009; Pavani et al., 2012; Ripunjoy et al., 2013). In
pregnancy, the root of D. indica is often used to cause abortion
(Quattrocchi, 2012), while the stem barks of D. papuana and
D. pentagyna are used to assist body delivery at labor time as well as
to avoid infection after delivery (Nick et al., 1994; Dubey et al.,
2009). Preparations of D. pentagyna and D. suffruticosa in the
form of paste or poultice are applied onto joint areas to alleviate
rheumatism (Quattrocchi, 2012; Hanum and Hamzah, 1999).
Furthermore, the juice and mucilage of D. indica, D. pentagyna and
D. philippinensis fruits are used to treat hair loss as well as to clean
hair and to remove dandruff (Saikia et al., 2006; Macahig et al., 201;
Rahman et al., 2011a). Their sweetish-sour edible fruits are
consumed directly or juiced with sugar as a fresh and healthy drink.
Meanwhile, the bark of the stem and root of some Dillenia plants
are reported as a food poisoning neutralizer (Grosvenor et al.,
1995b; Islam et al., 2014). Such usage suggested that Dillenia
plants might contain chemical constituents with broad biological
activities including antimicrobial, anti-inflammatory, anticancer,
and antidiabetes.
3. Chemistry of Dillenia species
Current investigation of the chemical constituents of Dillenia
species resulted in the isolation of two major classes of compounds
that are flavonoids and triterpenoids. In addition to these classes,
miscellaneous compounds including phytosteroids, a diterpene, a
norisoprene, an ionone, phenolics, an anthraquinone, an alcohol,
and ketones also enrich the diversity of phytochemistry in Dillenia
plants. As many as 74 compounds are included in this review ac-
cording to our search and this fact emerges future research op-
portunities as a noble challenge to discover new chemical
constituents from the genus Dillenia.
3.1. Flavonoids
Flavonoids found in Dillenia species are divided into flavonols
(1e18), dihydroflavonols (19e25), a flavan (26), flavan-3-ols
(27e28), and flavanones (29e32) and a chromane (33) as minor
flavonoids. Most of these flavonoids were isolated from the leaves
of Dillenia plants, but some flavonoids were also reported from the
stem bark. Five flavonoids (5, 16e17, 22, 27, 29 and 33) are reported
as new compounds from Dillenia plants. Two flavonols (1 and 3) are
frequently found in these species. Meanwhile, 4e8 are common
feature methylated flavonols in Dillenia species. Only D. triquetra
and D. bracteata have been reported to produce sulfated flavonols
(9e11). The occurrence of flavonoid sulphates in the Dilleniaceae
family is closely related to the derivatization of O-methylated
aglycones (Gurni et al., 1981). Seven dihydroflavonols (19e25) were
found in D. indica, D. retusa and D. pentagyna and they occurred as
 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 3

Table 1
Medicinal uses of several Dillenia species.

Species Part Form Medicinal use Country or References

region

D. andamanica Leaf Juice Leucoderma North Prasad et al. (2008)

Andaman,
India
D. aurea Fruit e Treatment of loss appetite India Quattrocchi (2012)
Stem bark Paste (powder of stem bark in hot rye oil) Wounds healing India Quattrocchi (2012)
D. excelsa Root Decoction Drink for diarrhea Sarawak, Quattrocchi (2012)
Malaysia
D. indica Fruit Decoction Jaundice Mizoram, Rai and Lalramnghinglova
India (2010), Sharma et al. (2012)
Stomach disorders Mizoram, Lalfakzuala et al. (2007)
India
Juice Flatulence, boils, fever and cough as Bangladesh Islam et al. (2014)
well as to help semen production
Laxative and abdominal pain India Kirtikar and Basu (2003)
Fever Arunachal Khongsai et al. (2011)
Pradesh,
India
Dysentery Assam, India Nath and Choudhury
(2010)
Juice (mixed with sugar) Fever Bangladesh Anisuzzaman et al. (2007)
Pickle Cough, fever and weakness India Angami et al. (2006)
Raw fruit To enhance appetite and weakness India Poonam and Singh (2009)
of the body
Mucilage Skin lice India Quattrocchi (2012)
Clean hair Arunachal Sarmah et al. (2008)
Pradesh,
India
Paste (mixed with Zingiber officinale) Hydrocele India Quattrocchi (2012)
Salted juice Expectorant India Quattrocchi (2012)
Paste (mixed with kernels of Castanopsis indica þ flowers of Blood dysentery India Quattrocchi (2012)
Musa balbisiana)
Juice (mixed with root juice of Mimosa pudica þ few drops of Dysentery Assam, India Das et al. (2008)
honey)
Juice Dysentery Assam, India Kalita and Deb (2004)
Paste (mixed with warm water) Cholera Meghalaya, Hazarika et al. (2016)
India
e Used in flavoring of curries and India Abdille et al. (2005), Kar
production of jam and jelly and Borthakur (2007)
Raw fruit Laxative North Prasad et al. (2008)
Andaman,
India
e Laxative, carminative, bechic, India Khare (2007)
febrifuge, antispasmodic (abdominal
pains)
Raw fruit Constipation and stomachache India Ripunjoy (2013)
Juice (fruit mixed with Tamarindus, Capsicum, and Allium Diabetes India Pavani et al. (2012)
sativum)
Juice (fruit mixed with Emblica officinalis and leaf of Diabetes mellitus (orally for 2e6 India Tag et al. (2012)
Stachytarpheta jamaicensis) days)
Dried fruit Cough Arunachal Khongsai et al. (2011)
Pradesh,
India
Raw fruit Stomachache India Srivastava et al. (2010)
e Hair loss Bangladesh Rahman et al. (2011a)
Flower Extract (100 g) Diabetes mellitus (once a day) India Tarak et al. (2011)
Decoction Amoebic dysentery India Purkayastha et al. (2005)
Fresh flower Dysentery Arunachal Sarmah et al. (2008)
Pradesh,
India
Calyx Half ripened fleshy calyx Stomach disorders India Quattrocchi (2012)
Dried powder (mixed with water) Diabetes India Ripunjoy (2013)
Fleshy calyx (mixed with salt) Stomachache Arunachal Kagyung et al. (2010)
Pradesh,
India
Boiled calyx as vegetable Cough, fever Arunachal Sarmah et al. (2008)
Pradesh,
India
Leaf Decoction Malaria Vietnam Nguyen-Pouplin et al.
(2007)
Paste (mixed with leaf of Cymbopogon flexuosus) Diarrhea of domestic animals India Quattrocchi (2012)
Stem bark Paste (Dry stem bark þ seeds of Sesamum orientale) Apply on blistering boils India Quattrocchi (2012)
Urinary diseases India Quattrocchi (2012)
(continued on next page)

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
4 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20

Table 1 (continued )

Species Part Form Medicinal use Country or References

region

Dry powdered (stem bark þ roots of Abroma

augustum þ stem bark of Terminalia augustum)
Poultice (stem bark þ stem bark of Sterculia villosa, Sores caused by septicaemial Uttar Singh et al. (2002)
S. colorata and Hymenodictyon excelsum þ with mustard oil) infection Pradesh,
India
Decoction Diarrhea, dysentery, and cholera Meghalaya, Hazarika et al. (2016)
India
Juice (mixed with sugar and water) Blood cancer Tripura, Majumdar et al. (2006)
India
Root Decoction (roots þ roots of Ficus auriculata and Urena To discharge blood in urine India Quattrocchi (2012)
lobata)
Decoction (roots þ roots of Glycosmis pentaphylla and Litsea Biliousness India Quattrocchi (2012)
monopetala)
Paste Abortion India Quattrocchi (2012)
Leaf, stem e Astringent India Khare (2007)
bark
Stem bark, Decoction Neutralizer for food poisoning Bangladesh Islam et al. (2014)
root
Fruit, leaf, Juice Cancer and diarrhea Mizoram, Sharma et al. (2001)
stem bark India
Juice Drink for cough, cold, fever and India Quattrocchi (2012)
diarrhea
Fruit, leaf e Cancer Bangladesh Azam et al. (2016)
D. ovata Stem bark Astringent preparation Diarrhea Malaysia Burkill (1966)
Stem bark Decoction, poultice, resin Skin itches, rash and vulnerary Laos Boer et al. (2012)
D. papuana Stem bark e Asthma, chest pains and to help in Papua New Nick et al. (1994)
child delivery Guinea
D. parviflora Stem bark Poultice Wounds healing Thailand Junsongduang et al. (2014)
Decoction Diarrhea Thailand Srithi et al. (2009)
Leaf, stem Decoction Treatment of protein deficiency Thailand Khuankaew et al. (2014)
bark
D. pentagyna Fruit e Dropsy India Nyman et al. (1998)
Mucilage Hairs treatment, dandruff Assam, India Saikia et al. (2006)
Hair tonic Bangladesh Uddin et al. (2012)
Juice (mixed with sugar) Fever, pimples and cough India Quattrocchi (2012)
Juice (mixed with sugar and water) Fever and cough Kerala, India Yesodharan and Sujana
(2007)
e Laxative, carminative, bechic, India Khare (2007)
febrifuge, antispasmodic (abdominal
pains)
Leaf Juice Diarrhea India Quattrocchi (2012)
Raw fresh leaf Put on the head of the pregnant India Quattrocchi (2012)
woman at the labor time
Juice Apply externally to heal wounds Mizoram, Sharma et al. (2001)
India
Poultice Bone fracture, bleeding piles Vindhya, Dubey et al. (2009)
India
Decoction Skin diseases, pain of the body Vindhya, Dubey et al. (2009)
(bathing) India
Powder (5e10 g) Breast cancer Vindhya, Dubey et al. (2009)
India
Stem bark Powder Piles, cuts, sores and insect bites India Quattrocchi (2012)
Fermentation (stem bark þ tubers of Pueraria tuberose and Tonic and anti-helmintic India Quattrocchi (2012)
rice)
Juice Pain and swelling of the body Nepal Ghimire and Bastakoti
(orally) (2009)
Tick bites (Juice)
Jaundice and urinary disorders Ghats, India Patil and Patil (2007)
Decoction Hair tonic Vindhya, Dubey et al. (2009)
India
Decoction Diabetes and stomach ulcer Meghalaya, Hazarika et al. (2016)
India
Powder (5e10 g) diluted in water Diabetes Vindhya, Dubey et al. (2009)
India
Infusion Diarrhea, dysentery, and child Vindhya, Dubey et al. (2009)
delivery India
Paste Rheumatic pains Meghalaya, Hazarika et al. (2016)
India
Decoction (25e50 mL) Tonic for woman after delivery and Vindhya, Dubey et al. (2009)
bathing to check the infection India
e Cancer Assam, India Das et al. (2009)
e Eczema Karnataka, Bhat et al. (2014)
India
Root Decoction (25e50 mL) Body pain Dubey et al. (2009)

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 5

Table 1 (continued )

Species Part Form Medicinal use Country or References

region

Vindhya,
India
Leaf, stem e Astringent India Khare (2007)
bark
Stem bark, Decoction Diarrhea India Quattrocchi (2012)
root Paste Rheumatism India Quattrocchi (2012)
Leaf, stem Decoction Chest pain and cancer Mizoram, Sharma et al. (2001),
bark India Rosangkima et al. (2008a)
Vindhya, Dubey et al. (2009)
India
North Prasad et al. (2008)
Andaman,
India
Latex Poultice Bone fracture Madhya Jain et al. (2011)
Pradesh,
India
e e Gastric cancers, diarrhea and Mizoram, Rosangkima et al. (2008b)
stomach ailments India
Latex Latex mixed with coconut oil Dhobi's itch Karnataka, Parinitha et al. (2004)
India
D. philippinensis Fruit Juice Cough and cleaning hair Philippines Macahig et al. (2011)
Juice Cough and pain in the chest Philippines Quattrocchi (2012)
D. retusa Fruit Poultice Pain of fractures and dislocations Sri Lanka Jayaweera (1980)
D. scabrella Fruit Juice Massage of the breasts India Quattrocchi (2012)
D. serrata Stem bark Decoction Bloody vomiting Sulawesi, Windardi et al. (2006)
Indonesia
D. suffruticosa Fruit e Cancer Sabah, Ahmad and Holdsworth
Malaysia (1995)
Leaf Raw young leaf (mixed with raw young leaf of Melastoma Stomachache Malaysia Quattrocchi (2012)
borneese)
Poultice Wounds healing Malaysia Mat-Salleh and Latiff
(2002)
Poultice Rheumatism Malaysia Hanum and Hamzah
(1999)
D. sumatrana Root Decoction Neutralizer for food poisoning Riau, Grosvenor et al. (1995a)
Indonesia

(): not mentioned.

derivatives of 1, 3, and 8. In addition, flavanone (29) dan flavanones
glycosides (30e32) in Dillenia species were reported from the
leaves and stem bark of D. indica and D. pentagyna (Bate-Smith and
Harborne, 1971; Pavanasasivam and Sultanbawa, 1975b; Tiwari
et al., 1979; Srivastava, 1981). Futhermore, a new chromane eluci-
dated as 3,5,7-trihydroxy-2-(4-hydroxybenzyl)-chroman-4-one
(33) was isolated from D. indica leaves (Kaur et al., 2016). These
compounds are listed in Table 2 and their structures are displayed
in Fig. 1.
Proanthocyanidins (oligomeric flavan-3-ols) were isolated from
an aqueous acetone (30%) extract of fresh fruit of D. indica using
Sephadex LH-20 column chromatography. The yield of isolated
proanthocyanidins was 0.28% of dry fruit (Fu et al., 2015) and
considered higher than proanthocyanidins from functional foods
such as from avocados, berries, kiwi, mangoes, and vegetables (Gu
et al., 2004). High content of proanthocyanidins is known for
contributing an astringent flavor in fruits (Joslyn and Goldstein,
1964). It is suggested that the sweetish-sour flavor of Dillenia
fruits is due to the high content of proanthocyanidins. Bate-Smith
alcoholysis and several spectroscopy techniques reported that the
proanthocyanidins from D. indica fruits were primarily composed
of the cis isomer of predominant B-type procyanidins (catechin and
epicatechin) and minor B-type prodelphinidins (gallocatechin and
epigallocatechin) without A-type interflavan linkage (Fu et al.,
2015).
3.2. Triterpenoids
Dillenia plants contain triterpenes having lupene and oleanene
skeletons. Up to now, only 23 triterpenes have been discovered and
two of them were considered as artifacts. Out of these, ten tri-
terpenes (38, 40, 42e48 and 51) are reported as new compounds.
Most of these triterpenes were isolated from the leaves, stem barks,
and fruits of Dillenia plants.
Lupene-type triterpenes (34e41) are found in D. andamanica,
D. aurea, D. bracteata, D. indica, D. papuana, D. parviflora,
D. pentagyna, D. philippinensis, D. retusa, D. scabrella, D. serrata, and
D. suffruticosa. Investigation of these triterpenes was pioneered by
Bhattacharjee and Chatterjee (1962) as they reported the isolation
of 35 and 37 from D. indica stem bark. The occurrence of 37 in the
stem bark of this species was found to be 0.75%. Pavanasasivam and
Sultanbawa (1974) conducted quantification of 37 in different parts
of five plants of Dilleniaceae; two of them were D. indica and
D. retusa. This report indicated that the amount of 37 in the bark
was greater than in the timber and in the pericarp or the fruit. This
report also concluded that 37 could be used as a chemotaxonomic
marker of the family Dilleniaceae (Pavanasasivam and Sultanbawa,
1974). Kumar et al. (2010) described quantification of 37 in the
crude methanol extract and fractions of D. indica fruits by using
HPLC and found that the fraction ethyl acetate contain high
amounts of 37. Similarly, Jalil et al. (2015) performed a quantifica-
tion of this compound in the crude methanol extracts and fractions
of the root bark and stem bark of D. serrata, and found that the
presence of 37 in the stem bark was greater than in the root bark.
On the other hand, a substantial amount of 37 was found abun-
dantly in the root bark of D. suffruticosa, in a study on anticancer of
this plant (Foo et al., 2015). Additionaly, Gandhi and Mehta (2013)
reported that the content of this compound in stem bark and

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6 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20

Table 2
Flavonoids isolated from several Dillenia species.

Structure Compound Type Species Part References

number

1 Kaempferol Flavonol D. bracteata e Gurni and Kubitzki (1981)

D. excelsea Leaf Bate-Smith and Harborne (1971)
Leaf Bate-Smith and Harborne (1971)
D. eximia Leaf Bate-Smith and Harborne (1971)
D. indica Pericarp, twig, Pavanasasivam and Sultanbawa (1975b)
stem bark
Stem Srivastava and Pande (1981)
D. ovata Leaf Bate-Smith and Harborne (1971)
D. pulchella Leaf Bate-Smith and Harborne (1971)
D. reticulata Leaf Bate-Smith and Harborne (1971)
D. retusa Fruit, twig Pavanasasivam and Sultanbawa (1975b), Gurni and
Kubitzki (1981)
D. suffruticosa Leaf Bate-Smith and Harborne (1971)
Root Tor et al. (2015)
D. triquetra e Gurni and Kubitzki (1981)
2 Myricetin Flavonol D. indica Stem bark Banerji et al. (1975)
D. pulchella Leaf Bate-Smith and Harborne (1971)
3 Quercetin Flavonol D. bracteata e Gurni and Kubitzki (1981)
D. excelsa Leaf Bate-Smith and Harborne (1971)
D. eximia Leaf Bate-Smith and Harborne (1971)
D. indica Leaf Bate-Smith and Harborne (1971), Kumar et al.
(2013)
Stem Srivastava and Pande (1981)
D. ovata Leaf Bate-Smith and Harborne (1971)
D. pulchella Leaf Bate-Smith and Harborne (1971)
D. reticulata Leaf Bate-Smith and Harborne (1971)
D. retusa Fruit, twig, stem Pavanasasivam and Sultanbawa (1975b), Gurni and
bark Kubitzki (1981)
D. suffruticosa Leaf Bate-Smith and Harborne (1971)
D. triquetra e Gurni and Kubitzki (1981)
4 Azaleatin Flavonol D. suffruticosa Leaf Bate-Smith and Harborne (1971)
D. triquetra e Gurni and Kubitzki (1981)
5 Dillenetin Flavonol D. indica Pericarp Pavanasasivam and Sultanbawa (1975a)
Leaf Muhit et al. (2010)
6 Rhamnetin Flavonol D. excelsea Leaf Bate-Smith and Harborne (1971)
D. indica Leaf Bate-Smith and Harborne (1971)
D. suffruticosa Leaf Bate-Smith and Harborne (1971)
7 Isorhamnetin Flavonol D. excelsea Leaf Bate-Smith and Harborne (1971)
D. indica Fruit, twig. stem Pavanasasivam and Sultanbawa (1975b)
bark
Leaf Bate-Smith and Harborne (1971)
D. suffruticosa Leaf Bate-Smith and Harborne (1971)
8 Kaempferide Flavonol D. excelsa Leaf Bate-Smith and Harborne (1971)
D. indica Leaf Bate-Smith and Harborne (1971)
D. suffruticosa Leaf Bate-Smith and Harborne (1971)
Root Tor et al. (2015)
9 Kaempferol-3-O-sulphate Substituted D. triquetra e Gurni and Kubitzki (1981)
flavonol
10 Kaempferol-3,7-disulphate Substituted D. bracteata Leaf Gurni et al. (1981)
flavonol
11 Quercetin-3-O-sulphate Substituted D. triquetra e Gurni and Kubitzki (1981)
flavonol
12 Kaempferol-3-O-glucuronide Substituted D. retusa e Gurni and Kubitzki (1981)
flavonol
13 Quercetin-3-O-galactoside Substituted D. retusa e Gurni and Kubitzki (1981)
flavonol
14 Rhamnetin 3-O-glucoside Substituted D. pentagyna Stem Srivastava (1981)
flavonol
15 Kaempferide 3-O-diglucoside Substituted D. indica Leaf Bate-Smith and Harborne (1971)
flavonol
16 30 ,5-Dihydroxy-40 ,3-dimethoxy flavone-7-O-b-D- Substituted D. indica Stem bark Tiwari and Srivastava (1979)
glucopyranoside flavonol
17 5,7-dihydroxy-4’-methoxyflavone-3-O-b-D- Substituted D. indica Stem bark Tiwari and Srivastava (1979)
glucopyranoside flavonol
18 Tiliroside Substituted D. philippinensis Leaf Macahig et al. (2011)
flavonol
19 (þ)-Dihydroxykaempferol Dihydroflavonol D. indica Twig Pavanasasivam and Sultanbawa (1975b)
D. retusa Stem bark Pavanasasivam and Sultanbawa (1975b)
20 (þ)-Dihydroquercetin Dihydroflavonol D. retusa Twig, stem bark Pavanasasivam and Sultanbawa (1975b)
21 (þ)-30 -Methoxy-dihydroquercetin Dihydroflavonol D. indica Stem bark Pavanasasivam and Sultanbawa (1975b)
22 Dihydroquercetin 5-glucoside Dihydroflavonol D. pentagyna Stem Srivastava (1981)
23 (þ)-Dihydroisorhamnetin Dihydroflavonol D. indica Stem bark Pavanasasivam and Sultanbawa (1975a)

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 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 7

Table 2 (continued )

Structure Compound Type Species Part References

number

24 Dihydrokaempferide Dihydroflavonol D. indica Leaf Bate-Smith and Harborne (1971)

25 Dihydrokaempferide 7-diglucoside Dihydroflavonol D. indica Leaf Bate-Smith and Harborne (1971)
26 4,5,7,30 ,40 -Pentahydroxy flavan-3-O-b-D- Flavan D. indica Stem bark Tiwari and Srivastava (1979)
glucopyranoside
27 Leucocyanidin Flavan-3-ol D. excelsea Leaf Bate-Smith and Harborne (1971)
D. eximia Leaf Bate-Smith and Harborne (1971)
D. indica Leaf Bate-Smith and Harborne (1971)
D. suffruticosa Leaf Bate-Smith and Harborne (1971)
D. pulchella Leaf Bate-Smith and Harborne (1971)
D. reticulata Leaf Bate-Smith and Harborne (1971)
28 Leucodelphinidin Flavan-3-ol D. eximia Leaf Bate-Smith and Harborne (1971)
D. ovata Leaf Bate-Smith and Harborne (1971)
D. pulchella Leaf Bate-Smith and Harborne (1971)
29 Naringenin Flavanone D. indica Stem bark Pavanasasivam and Sultanbawa (1975b)
Leaf Bate-Smith and Harborne (1971)
30 Naringenin 7-galactosyl(1 / 4)glucoside Flavanone D. pentagyna Stem Srivastava (1981)
31 Naringenin 7-diglucoside Flavanone D. indica Leaf Bate-Smith and Harborne (1971)
32 Naringenin-40 -O-[4-O-(b-D-glucopyranosyl)]-b- Flavanone D. pentagyna Stem Tiwari et al. (1979)
D-xylopyranoside
33 3,5,7-Trihydroxy-2-(4-hydroxy-benzyl)- Chromane D. indica Leaf Kaur et al. (2016)
chroman-4-one

(): not mentioned.

leaves of D. indica and D. pentagyna using an HPTLC method. Dan
and Dan (1980) investigated triterpenoids in the leaves of
D. andamanica, D. aurea, D. bracteata, D. indica, D. pentagyna, and
D. retusa and found them to contain 34, 35, and 37. The percentage
of 37 in the leaves of these species was in the range of 0.50e1.35% of
dry weight (Dan and Dan, 1980).
The occurrence of oleanene-type triterpenes (42e57) is re-
ported in D. papuana, D. philippinensis, D. pentagyna, D. serrata and
D. suffruticosa. These oleanene-type triterpenes have carboxylic
functionalities at C-28 or C-30 and oxygen functionalities at C-2 and
C-3 in ring A in the skeleton (Nick et al., 1994, 1995b; Ragasa et al.,
2009; Macahig et al., 2011; Jalil et al., 2015; Foo et al., 2015). The
presence of 2,3-seco-oleanene triterpenes (45, 52e56) in
D. papuana, D. philippinensis, D. serrata and D. suffruticosa is unique,
because most of the natural seco-triterpenes from plants are 3,4-
seco-compounds (Nick et al., 1995b). The occurrence of these seco-
triterpenes is suggested because of an oxidative cleavage of ring A
with oxygen functionalities at C-2 and C-3 in the oleanene skeleton
(Brewis et al., 1970; Nick et al., 1995b). Two seco-triterpenes
(54e55) isolated from D. philippinensis are considered to be arti-
facts, which resulted from the esterification of 53 during the
isolation process (Macahig et al., 2011). Another seco-triterpene,
compound 56 was isolated from the root bark of D. serrata and its
presence in the stem bark was detected using HPLC (Jalil et al.,
2015). Furthermore, 57 was the first oleanene-type reported from
D. pentagyna (Tiwari et al., 1981). These triterpenes are listed in
Table 3 and their structures are displayed in Fig. 2.
3.3. Miscellaneous compounds
In addition to flavonoids and triterpenoids, several compounds
including phytosteroids, a diterpene, a norisoprene, an ionone,
phenolics, an anthraquinone, an alcohol, and ketones have been
reported from Dillenia plants. These compounds were isolated from
the twig, fruit, stem bark, and leaves of the plants. Out of these
compounds, 63 was found as a new pimarane-type diterpene,
isolated from the ethanol extract of the dried powdered stem of
D. pentagyna (Srivastava and Srivastava, 1984). These compounds
are listed in Table 4 and shown in Fig. 3.
Several investigations regarding preliminary identification of
chemical constituents from Dillenia plants have been reported.
Savithramma et al. (2011) performed phytochemicals screening of
D. indica leaves and found the presence of terpenoids and tannins.
Abdille et al. (2005) determined the total phenolic contents (TPC) of
the ethyl acetate, methanol, and aqueous extracts of D. indica fruit
and found them to contain 9.37, 34.14, and 1.41% w/w phenolics,
respectively. Khare (2007) reported the amount of tannins in the
dried sepals, leaves, and bark of D. indica were about 0.37, 9.00 and
10.00%, respectively. Deepa and Jena (2011) also determined total
phenolics in aqueous-acetone extract of the stem bark of D. indica
and found to be 54.17% as tannic acid equivalents. Singh et al. (2012)
performed phytochemical screening of the underutilized fruit of
D. indica and found it to contains polyphenol (152.91 mg gallic acid
equivalents/100 g fresh mass), anthocyanin (41.67 mg cyanidine-3-
glucoside equivalents/100 g fresh mass), carotenoid (42.88 mg/g
fresh mass), tannin (3.86 mg tannic acid equivalents/100 g fresh
mass), and ascorbic acid (108.64 mg ascorbic acid equivalents/100 g
fresh mass). Besides D. indica, phytochemical screening and total
polyphenols determination in D. pentagyna and D. suffruticosa also
have been performed. Smitha et al. (2012) screened the phyto-
chemical constituents of methanol extract of dried powdered stem
bark of D. pentagyna and found the presence of tannins, phenolics,
flavonoids, saponins, and alkaloids. Florence et al. (2014) reported
the presence of alkaloids, coumarins, flavonoids, phenolics, phy-
tosterols, quinones, saponins, sterols, and terpenes in the flower
extracts (aqueous, petroleum ether, chloroform, ethanol, and
acetone) of this plant. Meanwhile, D. suffruticosa roots are reported
to contain saponins, triterpenes, phytosterol, and condensed tan-
nins (Armania et al., 2013a). Seal (2012) reported total phenolics,
total flavonoids, and total flavonols contents in the aqueous-
methanol (20%) extract of D. pentagyna flower were 9.33 mg
gallic acid equivalents, 52.14 mg quercetin equivalents and 6.73 mg
quercetin equivalents for every gram of dry material, respectively.
Meanwhile, total phenolics, total flavonoids, and total flavonols
content in its acetone extract were found to be 2.61 mg gallic acid
equivalents, 2.74 mg quercetin equivalents and 0.19 mg quercetin
equivalents for every gram of dry material, respectively (Seal, 2012).
The content of tannins in D. pentagyna stem bark was found to be
6.00% (Khare, 2007). Armania et al. (2013a) determined total
phenolic content of the aqueous and methanol extracts of the dried
powdered root, fruit, leaves, and flower of D. suffruticosa and found
that the root extract possess the highest amount of phenolics
(282.11 and 503.10 mg gallic acid equivalent/g extract, respectively)
compared to others.

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8 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20

Fig. 1. Flavonoids isolated from Dillenia species.

In addition to miscellaneous compounds, protein and carbohy-
drate have also been reported from fruit and seed of Dillenia plants.
Uppalapati and Rao (1980) investigated amino acids content in
D. indica seeds and detected the presence of aspartic acid, lysine,
arginine, serine, glutamic acid, alanine, proline, tyrosine, cystine,
leucine, and phenylalanine. The ripe fruit of this plant was also
found to contain 99.13 mg crude protein and 103.38 carbohydrates
per 100 g fresh mash (Singh et al., 2012). It also yielded 2.00% of a
polysaccharide arabinogalactan (Srivastava and Pande, 1978). The
polysaccharide content in the fruit of D. indica was used as natural
mucoadhesive for drug formulation (Kuotsu and Bandyopadhyay,
2007; Sharma et al., 2009, 2013; Bal et al., 2012a,b).

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 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 9

Table 3
Triterpenoids isolated from Dillenia species.

Structure Compound Triterpene Species Part References

number type

34 Lupeol Lupene D. indica Stem bark Banerji et al. (1975), Parvin et al. (2009)
Leaf Dan and Dan (1980)
Fruit Sundararamaiah et al. (1976)
D. andamanica Leaf Dan and Dan (1980)
D. aurea Leaf Dan and Dan (1980)
D. bracteata Leaf Dan and Dan (1980)
D. pentagyna Leaf Dan and Dan (1980), Tiwari et al. (1981)
D. retusa Leaf Dan and Dan (1980)
D. scabralla Leaf Dan and Dan (1980)
D. parviflora Fruit Li et al. (2009)
35 Betulin Lupene D. indica Stem bark Bhattacharjee and Chatterjee (1962), Banerji et al. (1975)
Leaf Dan and Dan (1980)
Fruit Sundararamaiah et al. (1976)
D. andamanica Leaf Dan and Dan (1980)
D. aurea Leaf Dan and Dan (1980)
D. bracteata Leaf Dan and Dan (1980)
D. pentagyna Leaf Dan and Dan (1980)
Stem bark Tiwari et al. (1981)
D. retusa Leaf Dan and Dan (1980)
D. scabralla Leaf Dan and Dan (1980)
D. parviflora Fruit Li et al. (2009)
36 Betulinaldehyde Lupene D. indica Stem bark Banerji et al. (1975), Parvin et al. (2009)
D. papuana Leaf, stem Nick et al. (1994)
37 Betulinic acid Lupene D. indica Stem bark Bhattacharjee and Chatterjee (1962), Banerji et al. (1975); Parvin
et al. (2009)
Leaf Dan and Dan (1980), Mukherjee and Badruddoza (1981), Muhit
et al. (2010), Kumar et al. (2013)
Fruit Kumar et al. (2010)
D. andamanica Leaf Dan and Dan (1980)
D. aurea Leaf Dan and Dan (1980)
D. bracteata Leaf Dan and Dan (1980)
D. pentagyna Leaf Dan and Dan (1980)
D. retusa Leaf Dan and Dan (1980)
D. scabralla Leaf Dan and Dan (1980)
D. parviflora Leaf Li et al. (2009)
D. philipphinensis Lefa Ragasa et al. (2009), Macahig et al. (2011)
D. papuana Leaf, stem Nick et al. (1995b)
D. serrata Stem bark, Jalil et al. (2015)
root bark
D. suffruticosa Root Foo et al. (2015)
38 a-L-Rhamnopyranosyl-3b-hydroxy-lup- Lupene D. pentagyna Stem Tiwari et al. (1980)
20(29)-en-28-oic acid
39 Betulonic acid Lupene D. pentagyna Stem bark Tiwari et al. (1981)
40 3b-Hydroxylupane-13b,28-lactone Lupene D. indica Stem bark Banerji et al. (1975)
41 Messagenic acid Lupene D. philippinensis Leaf Macahig et al. (2011)
42 Dillenic acid A Oleanene D. papuana Aerial part Nick et al. (1994)
43 Dillenic acid B Oleanene D. papuana Aerial part Nick et al. (1994)
44 Dillenic acid C Oleanene D. papuana Aearial part Nick et al. (1994)
45 Dillenic acid D Oleanene D. papuana Leaf, stem Nick et al. (1995b)
46 Dillenic acid E Oleanene D. papuana Leaf, stem Nick et al. (1995b)
47 3-Oxoolean-1,12-dien-30-oic acid Oleanene D. papuana Aerial part Nick et al. (1994)
48 3-Oxoolean-12-en-30-oic acid Oleanene D. papuana Leaf, stem Nick et al. (1995b)
D. philippinensis Leaf Ragasa et al. (2009)
D. serrata Root bark Jalil et al. (2015)
49 Katonic acid Oleanene D. suffruticosa Root bark Foo et al. (2015)
50 2a,3b-dihydroxyolean-12-en-28-oic acid Oleanene D. philippinensis Leaf Macahig et al. (2011)
51 3-epi-maslinic acid Oleanene D. suffruticosa Root Tor et al. (2015)
52 2,3-seco-olean-12-ene-2,3,30-trioic acid Oleanene D. philippinensis Leaf Macahig et al. (2011)
53 2,3-seco-olean-12-ene-2,3,28-trioic acid Oleanene D. philippinensis Leaf Macahig et al. (2011)
54 2,3-seco-olean-12-ene-2,3-trioic-28- Oleanene D. philippinensis Leaf Macahig et al. (2011)
methyl ester
55 2,3-seco-olean-12-ene-2,3-trioic-28-butyl Oleanene D. philippinensis Leaf Macahig et al. (2011)
ester
56 Koetjapic acid Oleanene D. serrata Stem bark, Jalil et al. (2015)
root bark
D. suffruticosa Root Foo et al. (2015)
57 Morolic acid Oleanene D. pentagyna Stem bark Tiwari et al. (1981)

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Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
10 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20

Fig. 2. Triterpenoids isolated from Dillenia species.

4. Pharmacology of Dillenia species traditional uses for the therapeutic remedies of microbial infection-
related diseases such as diarrhea, dysentery, septicaemical infec-
4.1. Antimicrobial activity tion and skin-related diseases.

Some of Dillenia species were investigated for antibacterial,
antifungal, and antiviral activities. The extracts and fractions of
D. indica, D. papuana, D. pentagyna, D. suffruticosa, and D. sumatrana
were reported to possess growth inhibition against Gram positive
and negative bacteria (Table 5). However, they were found to
exhibit weak growth inhibition against tested fungi, including
Aspergillus fumigatus, A. niger, Candida albicans, C. arriza, C. crusei,
Penicillium sp., Rhizopus oryzae, Saccharomyces cerevisiae, and Tri-
choderma viride (Nick et al., 1995a; Wiart et al., 2004; Haque et al.,
2008; Apu et al., 2010; Smitha et al., 2012). Seven triterpenoids (37,
42e45 and 47e48) from Dillenia plants were proven to have anti-
microbial action (Nick et al., 1994, 1995b; Ragasa et al., 2009).
Strong growth inhibition against Escherichia coli and Bacillus subtilis
has been shown by 45 that was assayed using the bioautographic
method on TLC plate. Meanwhile, 48 was the most active against
the growth of Micrococcus luteus (Nick et al., 1995b). Similar pro-
nounce growth inhibition of 48 also reported towards E. coli,
Pseudomonas aeruginosa, Staphylococcus aureus, and B. subtilis
(Ragasa et al., 2009). These findings suggested that Dillenia plants
had a potential as antimicrobial agent, which supported their
4.2. Anti-inflammatory and antinociceptive activity
Anti-inflammatory action of Dillenia plants was demonstrated
by D. indica, D. retusa, and D. serrata. Carrageenan-induced paw
edema is reduced by anti-inflammatory activity of the alcoholic
extract of D. indica leaves (Yeshwante et al., 2009b). Non-polar
fractions of this extract reduced the colon weight and macro-
scopic damage in acetic acid-induced colitis mice. The fractions also
inhibited the production of tumor necrosis factor alpha (TNF-a) in
colonic tissue as well as production of myeloperoxidase, which
released from azurophilic granules of neutrophils by inflammatory
stimuli (Somani et al., 2014). However, the glycolic extract and
emulsion of D. indica fruit were not successful to accelerate wound
healing process on skin injuries made in rats (Miglianto et al., 2011).
Methanol extracts and organic fractions of stem bark and root bark
of D. serrata was found to inhibit the production of inflammatory
mediator prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-
induced human whole blood. Three triterpenes (37, 48, and 56)
isolated from D. serrata were significantly inhibited the production
of PGE2. This activity was suggested due to the inhibition of

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 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 11

Table 4
Miscellaneous compounds isolated from Dillenia species.

Structure Compound Type Species Part References

Number

58 b-Sitosterol Phytosteroid D. indica Pericarp, twig, Pavanasasivam and Sultanbawa (1975a,b)

stem bark
Fruit Sundararamaiah et al. (1976)
Leaf Mukherjee and Badruddoza (1981), Muhit et al.
(2010), Kumar et al. (2013)
D. retusa Fruit, twig, stem Pavanasasivam and Sultanbawa (1975a,b)
bark
Leaf Dan and Dan (1980)
D. andamanica Leaf Dan and Dan (1980)
D. aurea Leaf Dan and Dan (1980)
D. bracteata Leaf Dan and Dan (1980)
D.pentagyna Leaf Dan and Dan (1980)
D. scabralla Lefa Dan and Dan (1980)
D. parviflora Fruit Li et al. (2009)
59 Daucosterol Phytosteroid D. suffruticosa Root Tor et al. (2015)
60 Stigmasterol Phytosteroid D. indica Stem bark Parvin et al. (2009)
Leaf Kumar et al. (2013)
61 Stigmasteryl palmitate Phytosteroid D. indica Leaf Kumar et al. (2013)
62 Cycloartenone Phytosteroid D. indica Leaf Mukherjee and Badruddoza (1981)
63 Dipoloic acid Diterpene D. pentagyna Stem Srivastava and Srivastava (1984)
64 (3S,5R, 6R,7E,9S)-megastigman-7-ene-3,5,6,9- Norisoprene D. philippinensis Leaf Macahig et al. (2011)
tetraol-3-O-b-D-glucopyranoside
65 Corchoionoside C 60 -O-sulphate Ionone D. philippinensis Fruit Macahig et al. (2011)
66 Gallic acid Phenolic D. indica Twig Pavanasasivam and Sultanbawa (1975a)
D. retusa Twig Pavanasasivam and Sultanbawa (1975a)
D. parviflora Fruit Li et al. (2009)
D. suffruticosa Root Tor et al. (2015)
67 Ethyl gallate Phenolic D. parviflora Fruit Li et al. (2009)
68 Protocatechuic acid Phenolic D. parviflora Fruit Li et al. (2009)
D. suffruticosa Root Tor et al. (2015)
69 Protocatechuic acid methyl ester Phenolic D. parviflora Fruit Li et al. (2009)
70 Benzyl 6-O-sulfo-b-D-glucopyranoside Phenolic D. philippinensis Fruit Macahig et al. (2011)
71 1,8-Dihydroxy-2-methyl-anthraquinone-3-O-b-D- Anthraquinone D. indica Stem bark Tiwari and Srivastava (1979)
glucopyranoside
72 n-Hentriacontanol Alcohol D. indica Leaf Mukherjee and Badruddoza (1981)
73 n-Heptacosan-7-one Ketone D. indica Leaf Kumar et al. (2013)
74 n-Honatriacontan-18-one Ketone D. indica Leaf Kumar et al. (2013)

cyclooxygenase-2 (COX-2) expression, which is known as an
enzyme involved in biosynthesis of inflammatory mediators (Jalil
et al., 2015). Due to antinociceptive activity, the alcoholic extracts
of leaf and stem bark of D. indica were found to exhibit central and
peripheral analgesia assayed using the hot plate method, tail im-
mersion test, and writhing model in mice induced by acetic acid
(Bose et al., 2010; Yeshwante et al., 2011; Alam et al., 2012). Simi-
larly, the aqueous extract of D. retusa fruit also showed central and
peripheral analgesia due to opioid receptor mechanism in rats
when administered with naloxone hydrochloride (Deraniyagala
et al., 2014).
4.3. Cytotoxicity
The main background of some investigations regarding cyto-
toxic properties of Dillenia plants is because of their therapeutic
remedies to treat cancerous growths by natives of India and
Malaysia (Rosangkima et al., 2008b; Kumar et al., 2010; Armania
et al., 2013a). In vitro cytotoxic activity against carcinoma, lym-
phoma, and leukemia cells was reported using methanol extracts of
D. indica fruit (Kumar et al., 2010), leaves (Akter et al., 2014) and
D. suffruticosa root (Armania et al., 2013a). On the contrary, their
ethanol and aqueous extracts were considered non-cytotoxic to-
wards the cancer cell lines (Nguyen-Pouplin et al., 2007; Armania
et al., 2013a,b). There was a significant correlation between the
present of 37 and cytotoxic activity of extracts and fractions of
Dillenia plants. For example, the ethyl acetate fraction of the
methanol extract of D. indica calyx that contained substantial
amounts of 37 exhibited pronounced cytotoxicity when compared
to the n-butanol fraction (Kumar et al., 2010). Similarly, 37 that
accumulated more in the root part than other parts of D. suffruticosa
showed promising cytotoxic activity (Foo et al., 2015). In addition to
37, eleven compounds (34e35, 41, 49e51, 54e55, 56, and 66e67)
isolated from Dillenia plants were proven to have cytotoxic activity
towards cancer cell lines. Two types of triterpenoids from Dillenia
plants that are lupane (34e35, 37, 41) and oleanane (49e51, 54e55,
56) triterpenoids displayed considerable cytotoxic properties
(Table 6). Futhermore, in vivo cytotoxic activity of Dillenia plants
was shown by D. pentayna assayed towards ascites Dalton's
lymphoma-bearing mice (Rosangkima and Prasad, 2004, 2007a,b,c;
Rosangkima et al., 2008a,b; Prasad et al., 2009). The methanol
extract of the dried powdered stem bark of D. pentagyna was found
to increase survivability of tumor-bearing mice. This activity was
associated with the decrease of glutathione levels in tumor cells
which caused a non-protective cell condition and facilitating tumor
cell death (Rosangkima and Prasad, 2007a,b; Rosangkima et al.,
2008a; Prasad et al., 2009). The treatment caused reduction of
sialic acid content, a tumor marker in the liver, kidney, spleen and
Dalton's lymphoma cells (Rosangkima and Prasad, 2007a), and also
reduced the ascites tumor volume (Rosangkima and Prasad,
2007a,c). In contrast to cytotoxicity towards several cancer cells,
the dichloromethane extract of D. suffruticosa root was cytotoxic
towards normal cells 3T3 F442A (Armania et al., 2013a) and non-
tumorigenic MCF10A (Foo et al., 2014). Nonetheless, these find-
ings provided a great opportunity for development of anticancer
compounds from Dillenia plants.

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
12 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20
Fig. 3. Miscellaneous compounds isolated from Dillenia species.
4.4. Antidiabetic activity
Natives of India have long used Dillenia species, such as D. indica
and D. pentagyna, to treat diabetes. Anti-diabetic activity is per-
formed by the leaf extracts of both species assayed using in vitro
and in vivo models (Table 5). The leaf extract of D. indica was found
to inhibit enzymatic activity of rat intestinal sucrose and maltase
(Jong-Anurakkun et al., 2007), while the leaf extract of D. pentagyna
exhibited an inhibitory effect on a-glucosidase activity (Singha
et al., 2013). Furthermore, the leaf extract of D. indica assayed on
streptozotocin- and alloxan-induced type-1 and type-2 diabetes
rats reduced the blood glucose, hypertriglyceridemia, and hyper-
cholesterolemia levels. Indeed, the extract enhanced the produc-
tion of insulin and high-density lipoprotein cholesterol (Kumar
et al., 2011a,b,c). Additionaly, the extract was found to inhibit
overproduction of liver enzymes in diabetes rats, including aspar-
tate transaminase (AST), alanin transaminase (ALT), and alkaline
phosphatase (ALP) (Kumar et al., 2011b, 2011c). Histology studies
showed that the extract of this plant was able to restore normal
conditions of liver, pancreas, and kidney in the treated rats (Kumar
et al., 2011c). Three compounds (3, 58, and 60) isolated from the
ethyl acetate fraction of this extract were found to reduce the blood
glucose level of type-2 streptozotocin-nicotinamide-induced dia-
betic mice comparable with standard drug glibenclamide (Kumar
et al., 2013). Similar activity was performed by the extract of
D. indica fresh leaves assayed on streptozotocin-induced diabetes
adult male Wistar rats. Investigation of the active constituent of this
extract resulted in isolation of 33, which significantly demonstrated
antidiabetic activity by reducing levels of blood glucose, choles-
terol, and triglycerides. The treatment also increased levels of
Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
insulin and HDL-C, as well as body weight, when compared with
diabetic rats. Histopathological study showed that treatment with
the extract and 33 restored kidney structure abnormality due to
oxidative stress and hyperglycaemic activities in the diabetic rats
(Kaur et al., 2016). These findings supported the traditional use of
D. indica for the treatment of diabetes among natives in India.
4.5. Antioxidant activity
The antioxidant activity of Dillenia plants was showed by
D. indica, D. pentagyna, and D. suffruticosa assayed using several
in vitro and in vivo assays (Table 5). Proanthocyanidins isolated from
D. indica fresh fruit exhibited significant antioxidant activity as
measured by FRAP and ORAC assays with values of 2320 mmol
Fe(II)/g and 1.06  104 mmol Trolox Equivalent/g (Fu et al., 2015).
Compound 33 showed remarkable antioxidant activity, based on
assays on DPPH, hydrogen peroxide, and superoxide radicals as well
as ferric ion. Compound 33 also enhanced production of antioxi-
dant enzymes (SOD and GSH) in streptozotocin-induced diabetic
rats. Meanwhile, thiobarbituric acid reactive substances (TBARS)
level as a marker of lipid peroxidation was significantly reduced
under the treatment as compared to diabetic control rats (Kaur
et al., 2016).
4.6. Antidiarrheal
Antidiarrheal activity of Dillenia plants was showed by D. indica
assayed in castor oil-induced mice. The polar extracts of the leaf
and fruit of D. indica showed prolongation of onset and reduced the
frequency of defecation in the treated mice. The extracts also
 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 13

Table 5
Biological activity of extracts and fractions of Dillenia species.

Species Bioactivity Description Reference

D. indica Antibacterial and Non-polar fractions (chloroform, carbon tetrachloride, and hexane) of the methanol extract of Apu et al. (2010)
antifungal the leaves exhibited bacterial inhibition of B. cereus, B. megaterium, B. subtilis, S. aureus, S. lutea,
E. coli, P. aeruginosa, S. paratyphi, S. typhi, S. boydii, S. dysenteriae, V. mimicus, and
V. parahemolyticus and fungal inhibition of A. niger, C. albicans, and S. cerevisiae with inhibition
zones ranging from 6 to 8 mm at 400 mg/disc as compared to kanamycin (30 mg/disc; 30e40 mm)
Hexane, dichloromethane, and ethyl acetate fractions of the methanol extract of the stem bark Alam et al. (2011)
inhibited the growth of B. cereus, B. subtilis, S. aureus, S. lutea, E. coli, P. aeruginosa, S. paratyphi,
S. typhi, S. dysenteriae, V. mimicus, and V. parahemolyticus with minimum inhibitory
concentration (MIC) ranging from 0.31 to 20.00 mg/mL as compared to kanamycin (30 mg/disc;
22e30 mm) and amoxicillin (10 mg/disc; 14e22 mm). The fractions also inhibited the growth of
A. niger, C. albicans, and S. cerevisiae with zones ranging from 7 to 13 mm as compared to
ketoconazole (50 mg/disc; 19e23 mm)
The aqueous acetone (70%) extract of the fruit and stem bark inhibited the growth of food borne Jaiswal et al. (2014)
pathogens (B. cereus, Yersinia enterocolitica, S. aureus, and E. coli) with MIC ranging from 1.25 to
10.00 mg/mL
Anti-inflammatory The methanol extract of the leaves reduced the carrageenan-induced paw edema at doses of 200 Yeshwante et al. (2009b)
and 400 mg/kg bw as compared to indomethacin (10 mg/kg bw)
The methanol extract of the leaves and its non-polar fractions (hexane and chloroform) assayed Somani et al. (2014)
on acetic acid-induced colitis mice reduced the colon weight and macroscopic damage at doses of
200 and 800 mg/kg bw
Antinociceptive The methanol extract of the leaves assayed on acetic acid-induced writhing mice reduced Bose et al. (2010)
writhing behavior by 48.82% and 55.88% inhibition at doses of 250 and 500 mg/kg bw
comparable to diclofenac (60% at 25 mg/kg bw)
The methanol extract of the leaves measured by hot tail, tail immersion, formalin-induced Yeshwante et al. (2011)
nociception, and acetic acid-induced writhing model on mice showed central and peripheral
analgesia effects at doses of 400 mg/kg bw comparable to pentazocine (15 mg/kg bw) and
indomethacin (20 mg/kg bw) as respective standard drugs
The methanol extract of the stem bark exhibited dose-dependent analgesic activity tested using Alam et al. (2012)
hot plate method, tail immersion test, and acetic acid-induced writhing model in mice at doses of
200 and 400 mg/kg bw comparable to standard drugs nalbuphine (10 mg/kg bw) and diclofenac
Na (10 mg/kg bw)
Immunomodulatory The aqueous methanol extract (70%) of the fruit enhanced 90.72% production of polyclonal Sarker et al. (2012)
immunoglobulin M (IgM) in cultured BALB/c female mice spleen cells at a concentration of
200 mg/mL as compared to lipopolysaccharide (0.1 mg/mL)
Cytotoxic The methanol extract of the dried calyx inhibited the growth of U937, HL60, and K562 cancer cell Kumar et al. (2010)
lines with IC50 of 328.80, 297.69, and 275.40 mg/mL, respectively. AraC and Gleevec were used as
standard drugs
The methanol extract of the leaves inhibited the growth of AGS, MCF-7, and MDA-MB-231 cancer Akter et al. (2014)
cell lines with IC50 values of 1.18, 0.34, and 0.54 mg/mL, respectively as compared to
cycloheximide with IC50 values of 0.0010, 0.061, and 0.0004 mg/mL, respectively
Antimutagenic The 70% aqueous acetone extract of the stem bark exhibited antimutagenic activity against Jaiswal et al. (2014)
sodium azide-induced mutation in Salmonella tester strain (TA-1531)
Enzyme inhibition The 50% aqueous methanol extract of the leaves inhibited the rat intestinal sucrose and maltase Jong-Anurakkun et al. (2007)
activity with percentage inhibition of 40 and 56%, respectively
Antidiabetic The ethyl acetate fraction of the methanol extract of the leaves assayed in vivo on streptozotocin Kumar et al. (2011a)
(STZ)-induced type-1 and type-2 diabetes Wistar rats showed reduction in blood glucose, serum
cholesterol, and triglycerides levels after 21 days at doses of 200 and 400 mg/kg bw. This fraction
also increased the level of high-density lipoprotein cholesterol (HDL-C) in the treated rats
The defatted methanol extract of the leaves assayed in vivo on type-1 diabetes Wistar rats Kumar et al. (2011b,c)
induced by STZ and alloxan decreased blood glucose, hypertriglyceridemia, and
hypercholesterolemia levels as well as increased the production of insulin and HDL-C at doses of
250 and 500 mg/kg bw during 21 days of treatment
The alcohol extract of the fresh leaves assayed in vivo on STZ-induced diabetes adult male Wistar Kaur et al. (2016)
rats reduced levels of blood glucose, cholesterol, and triglycerides at doses of 100, 200 and
400 mg/kg bw for 21 days of treatment comparable to glimepiride (10 mg/kg bw). The extract
significantly increased the body weight, serum insulin and HDL-C level
Anticholinesterase The standardized methanol extract of the fruit inhibited acetylcholinesterase (AchE) and Bhadra et al. (2014)
butyrylcholinesterase (BchE) activity with IC50 values of 67.26 and 122.39 mg/mL, respectively
Antidiarrheal Aqueous and methanol extracts of the leaves prolonged onset and reduced total number of feces Yeshwante et al. (2009a)
in castor oil-induced diarrheal mice after two hours of treatment at doses of 200 and 400 mg/kg
bw
The methanol extract of the leaves decreased 65.28% frequency of defecation and number of total Bose et al. (2010)
stool count in mice induced by castor oil at a dose of 500 mg/kg bw as compared to loperamide
(25 mg/kg bw; 77.22%)
Ethanol extracts of the fruit and leaves decreased the total number of wet feces and also reduced Rahman et al. (2011b)
the motility of gastrointestinal tract in castor oil-induced diarrheal mice at doses of 200 and
400 mg/kg bw comparable to loperamide (5 mg/kg bw)
Antioxidant Methanol, ethyl acetate, and aqueous extracts of the fruit reduced molybdenum (IV) to Abdille et al. (2005)
molybdenum (V) with capacity of 1904.80, 1067.00, and 594.60 mmol/g of extract, respectively as
equivalent to ascorbic acid (AEAC). These extracts also exhibited DPPH radical scavenging activity
in the order of methanol extract > ethyl acetate extract > water extract over the concentration
range of 25e100 mg/mL. The extracts assayed on b-carotene bleaching displayed antioxidant
(continued on next page)

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
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14 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20

Table 5 (continued )

Species Bioactivity Description Reference

activity with BHA equivalent antioxidant capacity (BEAC) of 80.20, 55.50, and 45.50%,
respectively at 100 mg/mL as compared to BHA (97.50%)
The methanol extract, as well as n-hexane, carbon tetrachloride, dichloromethane and aqueous Parvin et al. (2009)
fractions of the stem bark measured by DPPH radical showed free radical scavenging activity
with IC50 values of 4.58, 254.84, 611.59, 162.72, and 84.51 mg/mL, respectively as compared to
ascorbic acid with IC50 value of 2.37 mg/mL
The aqueous acetone extract of the stem bark reduced molybdenum (IV) to molybdenum (V) Deepa and Jena (2011)
with capacity of 3.12 mmol/g of extract at 50 mg/mL as equivalent to ascorbic acid and exhibited
DPPH and superoxide radical scavenging activity causing 90.90% and 31.73% inhibition at 25 and
50 mg/mL as compared to BHA (91.00%) and gallic acid (47.73%), respectively. The extract assayed
using hydroxyl radical-induced deoxyribose damage displayed radical scavenging activity with
percentage inhibition of 53.90e74.66% at 100e500 mg/mL
The ethanol extract of the leaves assayed in vitro by DPPH, hydroxyl, and hydrogen peroxide Shendge et al. (2011)
radicals displayed antioxidant activity with IC50 values of 34.80, 64.40 and 51.00 mg/mL,
respectively comparable with ascorbic acid with IC50 of 24.00, 48.00, and 34.40 mg/mL,
respectively. This extract measured using FRAP assay displayed the reduction of ferric ion as
compared with ascorbic acid
The ethanol extract of the leaves assayed in vivo on doxorubicin-induced rats exhibited the Shendge and Gadge (2012)
restoration of GSH level and cardiac MDA content at doses of 250 and 500 mg/kg bw
The methanol extract of the stem bark reduced the production of ROS in kidney cells of male Alam et al. (2012)
Swiss albino mice with IC50 of 34.72 mg/mL as compared with trolox (IC50 8.66 mg/mL)
Methanol, acetone, and water extracts of the stem bark measured by DPPH radical displayed Singh et al. (2012)
antioxidant activity with IC50 values of 188.08, 177.42, and 163.68 mg/mL of fresh mass,
respectively
The methanol extract of the leaves and its fractions (hexane and chloroform) reduced the level of Somani et al. (2014)
MDA, and enhanced levels of the antioxidant enzymes including CAT, SOD, and GSH in acetic
acid-induced colitis mice at doses of 200 and 800 mg/kg
The alcohol extract of the fresh leaves obtained from sequential extraction with petroleum ether, Kaur et al. (2016)
chloroform, alcohol, and aqueous alcohol (40%) exhibited scavenging activity towards DPPH,
hydrogen peroxide, and superoxide radicals with IC50 of 2.98, 228.69, and 75.09 mg/mL,
respectively and ferric reducing antioxidant power with EC50 of 111 mg/mL. The extract also
enhanced the production of antioxidant enzymes (SOD and GSH) in STZ-induced diabetic rats at
doses of 100, 200, and 400 mg/kg bw after 21 days of treatment comparable with glimepiride at
10 mg/kg bw
Antiprotozoal Cyclohexane fraction of the 80% ethanol extract of the leaves exhibited 53% inhibition against Nguyen-Pouplin et al. (2007)
parasite P. falciparum at a concentration of 10 mg/mL as compared to chloroquione (IC50 of
0.10 mM)
Protoscolicidal The methanol extract of the stem assayed on earthworm Pheretima posthuma exhibited the Chowdhury et al. (2013)
paralysis (194-136 min) and death (237-176 min) of the earthworms at 10e25 mg/mL
comparable to albendazole at 10 mg/mL
Hair treatment The aqueous extract of the seed sap found to protect human hair from keratin degradation after Saikia (2013)
treatment with 10 mg hair/1 mL for 12 h
Acute toxicity The methanol extract the leaves was non-toxic and did not produce any mortality in mice during Kumar et al. (2010)
24 h of treatment with 100e1500 mg/kg bw of extract by intraperitoneal administration
Toxicity Water, chloroform, carbon tetrachloride and n-hexane fractions of methanol extract of the leaves Apu et al. (2010)
showed lethality on brine shrimp as compared with vincristine sulphate
Methanol, dichloromethane, ethyl acetate, and n-hexane fractions of the stem bark exhibited Parvin et al. (2009), Alam et al.
inhibition on brine shrimp, but less lethality compared to the leaves (2011), Chowdhury et al. (2013)
Ameliorative The ethanol extract of the leaves restored the level of myocardial enzymes such as alanine Shendge and Gadge (2012)
transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatine
phosphokinase (CK) on myocardium of doxorubicin-induced rats at doses of 250 and 500 mg/kg
bw
Hepatoprotective The ethanol extract of the leaves reduced the levels of serum glutamic oxaloacetic transaminase Padhya et al. (2008)
(SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, and
lipid peroxidation in the liver of albino rats induced by carbon tetrachloride at a dose of 300 mg/
kg bw
The hexane extract of the seeds reduced the levels of serum enzymes, bilirubin, urea, creatinine, Himakar et al. (2010)
and lipid peroxidation as well as increased levels of superoxide dismutase (SOD), colonic catalase
(CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST),
vitamin C, vitamin E, and protein in carbon tetrachloride-induced rats at doses of 250 and
500 mg/kg bw
Haemolytic activity The aqueous acetone (70%) extract of fruit and stem bark assayed using rat whole blood exhibited Jaiswal et al. (2014)
low inhibition against erythrocytes
D. papuana Antibacterial Petroleum ether, dichloromethane, and methanol extracts of the aerial part inhibited the growth Nick et al. (1995a)
of E. coli, B. subtilis, and M. luteus at 180 mg/plate. These extracts were inactive against fungi
Penicillium oxalicum. Chloramphenicol and miconazole were used as standard antibiotics
Enzyme inhibition Petroleum ether and methanol extracts of the aerial part inhibited the protein kinase (PKC) Nick et al. (1995a)
activity with IC50 of 32 and 12 mg/mL, respectively. Nonetheless, the dichloromethane of this part
was inactive towards PKC (IC50 > 100 mg/mL). All extracts showed 42, 41, and 31% inhibition of
tyrosine-specific PKC of epidermal growth factor receptor (PTK) at 50 mg/mL, respectively
Molluscicidal Petroleum ether, dichloromethane, and methanol extracts of the aerial part exhibited weak Nick et al. (1995a)
mortality on mollusks Biomphalaria glabrata as compared to copper sulphate
Toxicity Petroleum ether and methanol extracts of the aerial parts were toxic towards A. salina Nick et al. (1995a)
D. pentagyna Antibacterial and Petroleum ether and ethyl acetate (Ea) extracts of the sun-dried stem bark inhibited the growth Haque et al. (2008)
antifungal of B. cereus, B. subtilis, B. polymyxa, B. megaterium, S. aures, S. haemolyticus, Shigella soni,

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
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 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 15

Table 5 (continued )

Species Bioactivity Description Reference

S. dysenteriae type-1, S. basic, S. flexneri type-1, S. boydii, P. aeruginosa, Vibrio mimicus and
V. cholera with zones ranging from 10 to 23 mm at 3 mg/disc as compared to ampicilin (10 mg/
disc; 10e35 mm). The Ea extract (3 mg/disc) inhibited the fungi A. fumigates, A. niger, C. albicans,
C. arriza, C. krusei, R. oryzae, S. cerevisiae, and Trichoderma sp. with zones ranging from 10 to
17 mm as compared to griseofulvin (25 mg/disc; 12e18 mm)
The methanol extract of the stem bark inhibited the growth of B. subtilis, B. cereus, S. aureus, Smitha et al. (2012)
E. coli, P. aeruginosa, and Salmonella sp. with zones ranging from 7 to 10 mm at 100 mg/disc as
compared to streptomycin (10 mg/disc; 15e20 mm). The extract also active against fungi T. viride,
Penicillium sp., and A. niger with zones ranging from 6 to 10 mm at 1 mg/disc as compared to
albendazol (10 mg/disc; 10e20 mm)
The aqueous methanol extract and its fractions (chloroform and butanol) of the shade-dried fruit Singha et al. (2013)
and leaves inhibited the growth of S. dysenteriae, V. cholera, and E. coli with zones ranging from
0 to 12 mm at 1e3 mg/mL
Chloroform, ethyl acetate, and butanol fractions of the defatted aqueous methanol extract of the De et al. (2014)
fruit inhibited the growth of municipal sewage microbes with zones of 7e19 mm over
concentration range of 2e3 mg/disc as compared to ciprofloxacin (0.001e0.005 mg/disc; 8
e26 mm)
Antitumor The methanol extract of the stem bark increased the survivability of Dalton's lymphoma-bearing Rosangkima and Prasad (2007a,b)
mice (%ILS~70) at a dose of 20 mg/kg bw per day
Enzyme inhibition The 10% aqueous methanol extract of the leaves inhibited the a-glucosidase activity of about 3 Singha et al. (2013)
e70% inhibition at concentration ranging from 0.25 to 5 mg/mL as compared to positive control
acarbose (47e79%)
Antioxidant Aqueous methanol (20%) and acetone extracts of the fruit assayed using FRAP and DPPH assays Seal (2012)
showed antioxidant activity with capacity of 13.19 and 5.03 mg ascorbic acid equivalent/g of dry
fruit and IC50 of 0.51 and 2.21 mg/dry fruit, respectively as compared to butylated hydroxyl
toluene (BHT)
Chloroform and butanol fractions of the 10% aqueous methanol extract of the fruit scavenged Singha et al. (2013)
DPPH radical with percentage inhibition ranging from 6 to 61% and 12e65% at 0.5e50 mg/mL,
respectively. The 10% aqueous methanol extract of the leaf scavenged DPPH radical with
percentage of 7e67% as compared to ascorbic acid (0.5e50 mg/mL; 35e90%). The extracts and
fractions also significantly inhibited the superoxide radical with percentage inhibition ranging
from 5 to 73% at 1e100 mg/mL comparable to BHA (10e27%)
The methanol extract of the stem bark displayed ferric ion reduction with capacity of 109.91 mg Smitha et al. (2012)
GAE/g
The aqueous methanol (90%) extract of the stem bark measured by DPPH assay demonstrated Smitha et al. (2013)
antioxidant activity with IC50 of 416.90 mg/mL comparable to ascorbic acid (IC50 394.56 mg/mL)
The methanol extract of the stem bark exhibited radical scavenging activity towards DPPH and Zothanpuia et al. (2014)
hydroxyl radical with IC50 of 2.85 and 5.14 mg/mL as compared to BHA with IC50 of 2.23 and
3.31 mg/mL, respectively
Anti-hypertension Aqueous, alcoholic, and acetone extracts of the fruit inhibited the activity of angiotensin- Nyman et al. (1998)
converting enzyme (ACE) with percentage inhibition of 8, 28, and 13% at 0.33 mg/mL
Toxicity The ethyl acetate extract of the stem bark was toxic towards A. salina Haque et al. (2008)
D. retusa Insecticidal The ethanolic extract (95%) of the leaves showed moderate mortality (50e58%) towards Rajapakse and Ratnasekera (2008)
Callosobruchus chinensis and C. maculates at a concentration of 10% after 3 days of treatment
D. serrata Anti-inflammatory Methanol extracts of the stem bark and root bark and their fractions (petroleum ether, ethyl Jalil et al. (2015)
acetate, and methanol) inhibited the production of prostaglandin E2 (PGE2) in lipopolysaccharide
(LPS)-induced human whole blood with percentage inhibition ranging from 64 to 73% at 10 mg/
mL comparable to indomethacin (10 mg/mL; 83.9%)
D. suffruticosa Antibacterial and The leaves extract inhibited the growth of B. cereus, B. subtilis, P. aeruginosa, and C. albicans with Wiart et al. (2004)
antifungal zones ranging from 7 to 9 at 1 mg/disc as compared to gentamycin (10 mg/disc; 18e20 mm for
B. cereus, B. subtilis, P. aeruginosa) and nystatin (20 mg/disc; 11 mm for C. albicans)
Antiviral The aqueous extract of the plant inhibited the replication and nonstructural protein 1 (NS1) Muliawan (2008)
expression of dengue virus type 2 at concentration range of 0.025e0.4 mg/mL
Cytotoxic The methanol extract of the root exhibited significant (p < 0.05) cytotoxicity towards MCF-7, Armania et al. (2013a)
HT29, CaOV3, and HeLa cancer cell lines (IC50 of 99.67, 71.67, 92.33, and 44.00 mg/mL,
respectively) compared with methanol and aqueous extracts of fruit, leaves, and flower parts.
Dichloromethane and ethyl acetate extracts of the root were significantly inhibited the growth of
HeLa and CaOV3 with IC50 of 19.67 and 12.33 mg/mL, respectively
Sub-fractions of the ethyl acetate extract of the root inhibited the growth of MDA-MB-231, MCF- Armania et al. (2013b)
7, CaOV3, HeLa, A549, and 3T3 cancer cell lines with IC50 values range of 11.67e146.67, 9.50
e147.33, 19.0e133.3, 20.33e141.67, 21.00e146.00, and 18.00 mg/mL, respectively. Similarly,
sub-fractions of the dichloromethane extract of the root exhibited cytotoxicity towards the
cancer cell lines with IC50 of 70.00, 34.33, 53.67, 140.70, >150, and 94.67 mg/mL, respectively
The dichloromethane extract of the root inhibited the growth of MCF-7 and MCF10A cancer cell Foo et al. (2014)
lines with IC50 of 15.50 and 10.30 mg/mL, respectively
The ethyl acetate extract of the root inhibited the growth of MCF-7 breast cancer cells with IC50 of Tor et al. (2014)
39.00 mg/mL compared to standard drug tamoxifen with IC50 of 8.00 mg/mL
D. sumatrana Antibacterial The 70% aqueous methanol extract of the leaves inhibited the growth of S. aureus at a dose of Grosvenor et al. (1995b)
23 mg fresh weight as compared to chloramphenicol and tetracycline (1 mg/mL each). This
extract was inactive against E. coli, S. cerevisiae and Fusarium oxysporum.
Antioxidant Methanol and aqueous extracts of the root exhibited significant antioxidant activity on DPPH, Armania et al. (2013a)
ABTS and FRAP assays with capacities of 790.64 and 735.92 mg TEAC/g extract, 339.11 and
294.60 mg TEAC/g extract, and 475.75 and 354.93 mg GEAC/g extract, respectively

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
16
Table 6
Biological activity of compounds isolated from Dillenia species.
No Compound
3 Quercetin
33 3,5,7-Trihydroxy-2-(4-
hydroxy-benzyl)-chroman-4-
one
34 Lupeol
35 Betulin
37 Betulinic acid
41 Messagenic acid
42 Dillenic acid A
43 Dillenic acid B
44 Dillenic acid C
45 Dillenic acid D
46 Dillenic acid E
47 3-Oxoolean-1,12-dien-30-oic
acid
48 3-Oxoolean-12-en-30-oic acid
49 Katonic acid
50 2a,3b-dihydroxyolean-12-en-
28-oic acid
51 3-epi-maslinic acid
54 2,3-seco-olean-12-ene-2,3-
trioic-28-methyl ester
55 2,3-seco-olean-12-ene-2,3-
trioic-28-butyl ester
56 Koetjapic acid
58 b-sitosterol
60 Stigmasterol
66 Gallic acid
Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010
C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20
Bioactivity Description Reference
Anti-diabetic Inhibitory effect towards a-amylase (55.2%) and a-glucosidase (78.2%) at 50 mg/mL. The Kumar et al. (2013)
compound reduced blood glucose level in streptozotocin-nicotinamide-induced diabetic mice
at a dose of 10 mg/kg bw as compared to glibenclamide (10 mg/kg bw)
Anti-diabetic Reduced levels of blood glucose, cholesterol, and triglycerides and enhanced production of Kaur et al. (2016)
insulin and HDL-C of streptozotocin-induced diabetic rats at doses of 5 and 10 mg/kg bw after
21 days of treatment comparable to glimepiride (10 mg/kg bw)
Antioxidant Displayed remarkable antioxidant activity against DPPH, hydrogen peroxide, and superoxide Kaur et al. (2016)
radicals with IC50 of 2.36, 23.61, and 23.49 mg/mL, as well as ferric ion with EC50 of 26.95 mg/
mL. It enhanced the production of antioxidant enzymes (SOD and GSH) and decreased
thiobarbituric acid reactive substances (TBARS) level in streptozotocin-induced diabetic rats
at doses of 5 and 10 mg/kg bw comparable to glimepiride (10 mg/kg bw)
Cytotoxicity Inhibitory effect against K562 cells proliferation (26.1%) at 100 mg/mL Li et al. (2009)
Cytotoxic Inhibitory effect against K562 cells proliferation with IC50 of 30 mg/mL Li et al. (2009)
Antibacterial and Growth inhibition against E. coli, P. aeruginosa, S. aureus and B. subtilis with zone inhibition Ragasa et al. (2009)
antifungal ranging from 11 to 14 mm at 30 mg/disc as compared to chloramphenicol (30 mg/disc, 14
e25 mm). It also inhibited the growth of C. albicans (12 mm) and T. mentagrophytes (13 mm)
comparable to canesten (0.2 g/disc)
Growth inhibition against E. coli, B. subtilis and Micrococcus luteus with MIC >10 mg on TLC Nick et al. (1995b)
plate (MIC of chloramphenicol were 0.04, 0.1 and 0.04 mg, respectively)
Anti- Inhibitory effect on LPS-induced PGE2 production in human whole blood with IC50 of 2.59 mM Jalil et al. (2015)
inflammatory comparable to indomethacin (IC50 0.45 mM)
Cytotoxicity Inhibitory effect against K562 cells proliferation with IC50 of 31 mg/mL Li et al. (2009)
Inhibitory effect against U937, HL60, and K562 cell lines with IC50 of 13.73, 12.84, and Kumar et al. (2010)
15.27 mg/mL, respectively comparable to Ara-C and Gleevec
Enzyme inhibition Inhibitory effect towards a-amylase (47.4%) and a-glucosidase (52.2%) at 50 mg/mL Kumar et al. (2013)
Anticholinesterase Inhibitory effect towards AChE and BChE enzymes with IC50 values of 39.08 and 102.77 mg/mL, Bhadra et al. (2014)
respectively
Cytotoxicity Inhibitory effect against A549 cell lines with IC50 of 48.0 mM as compared to Doxorubicin (IC50 Macahig et al.
0.6 mM) (2011)
Anti-leishmanial Growth inhibition against L. major with IC50 of 67.1 mM as compared to Amphotericin B (IC50 Macahig et al.
7.1 mM) (2011)
Antibacterial Growth inhibition against E. coli, B. subtilis, and M. luteus with MIC of 2.4, 2.4 and 1.0 mg on TLC Nick et al. (1994);
plate, respectively as compared to chloramphenicol (MIC of 0.04, 0.1 and 0.04 mg, respectively) Nick et al. (1995b)
Antibacterial Growth inhibition against E. coli, B. subtilis, and M. luteus with MIC of 1.0, 2.0 and 1.0 mg on TLC Nick et al. (1994);
plate, respectively plate (MIC of chloramphenicol were 0.04, 0.1 and 0.04 mg, respectively) Nick et al. (1995b)
Antibacterial Growth inhibition against E. coli, B. subtilis, and M. luteus with MIC of 5.0, 2.0 and 2.0 mg on TLC Nick et al. (1994);
plate, respectively as compared to chloramphenicol (MIC of 0.04, 0.1 and 0.04 mg, respectively) Nick et al. (1995b)
Antibacterial Growth inhibition against E. coli, B. subtilis, and M. luteus with MIC of 0.5, 0.5 and 1.0 mg on TLC Nick et al. (1995b)
plate, respectively as compared to chloramphenicol (MIC of 0.04, 0.1 and 0.04 mg, respectively)
Antibacterial Growth inhibition against E. coli, B. subtilis, and M. luteus with MIC >10 mg on TLC plate as Nick et al. (1995b)
compared to chloramphenicol (MIC of 0.04, 0.1 and 0.04 mg, respectively)
Antibacterial Growth inhibition against E. coli, B. subtilis and M. luteus with MIC of 1.0 mg on TLC plate as Nick et al. (1994);
compared to chloramphenicol (MIC of 0.04, 0.1 and 0.04 mg, respectively) Nick et al. (1995b)
Antibacterial and Growth inhibition against E. coli, B. subtilis, and M. luteus with MIC of 1.0, 0.8 and 0.8 mg on TLC Nick et al. (1995b)
antifungal plate, respectively as compared to chloramphenicol (MIC of 0.04, 0.1 and 0.04 mg, respectively)
Growth inhibition against E. coli, P. aeruginosa, S. aureus and B. subtilis with zone inhibition Ragasa et al. (2009)
ranging from 13 to 14 mm at 30 mg/disc as compared to chloramphenicol (30 mg/disc, 14
e25 mm). It also inhibited the growth of C. albicans (13 mm) and T. mentagrophytes (13 mm)
comparable to canesten (0.2 g/disc)
Anti- Inhibitory effect on LPS-induced PGE2 production in human whole blood with IC50 of 1.54 mM Jalil et al. (2015)
inflammatory comparable to indomethacin (IC50 0.45 mM)
Cytotoxicity Inhibitory effect against MCF-7 cancer cell lines with IC50 of 39.25 mg/mL Foo et al. (2015)
Cytotoxicity Inhibitory effect against A549 cell lines with IC50 of 25.2 mM as compared to doxorubicin (IC50 Macahig et al.
0.6 mM) (2011)
Anti-leishmanial Growth inhibition against L. major with IC50 of 45.0 mM as compared to amphotericin B (IC50 Macahig et al.
7.1 mM) (2011)
Cytotoxicity Inhibitory effect against MDA-MB-231 cell lines with IC50 of 83.0 mg/mL Tor et al. (2015)
Cytotoxic Inhibitory effect against A549 cell lines with IC50 of 44.6 mM as compared to doxorubicin (IC50 Macahig et al.
0.6 mM) (2011)
Anti-leishmanial Growth inhibition against L. major with IC50 of 46.6 mM as compared to amphotericin B (IC50 Macahig et al.
7.1 mM) (2011)
Cytotoxic Inhibitory effect against A549 cell lines with IC50 of 15.4 mM as compared to doxorubicin (IC50 Macahig et al.
0.6 mM) (2011)
Anti-leishmanial Growth inhibition against L. major with IC50 of 56.7 mM as compared to amphotericin B (IC50 Macahig et al.
7.1 mM) (2011)
Anti- Inhibitory effect on LPS-induced PGE2 production in human whole blood with IC50 of 1.05 mM Jalil et al. (2015)
inflammatory comparable to indomethacin (IC50 0.45 mM)
Anti-diabetic Inhibitory effect towards a-amylase (48.8%) and a-glucosidase (52.5%) at 50 mg/mL. The Kumar et al. (2013)
compound reduced blood glucose level in streptozotocin-nicotinamide-induced diabetic mice
at a dose of 10 mg/kg bw as compared to glibenclamide (10 mg/kg bw)
Anti-diabetic Inhibitory effect towards a-amylase (44.3%) and a-glucosidase (34.2%) at 50 mg/mL. The Kumar et al. (2013)
compound reduced blood glucose level in streptozotocin-nicotinamide-induced diabetic mice
at a dose of 10 mg/kg bw as compared to glibenclamide (10 mg/kg bw)
Cytotoxicity Inhibitory effect against K562 cells proliferation with IC50 of 23 mg/mL Li et al. (2009)
 C.W. Sabandar et al. / Phytochemistry xxx (2016) 1e20 17

Table 6 (continued )

No Compound Bioactivity Description Reference

Inhibitory effect against MCF-7 and MDA-MB-231 cell lines with IC50 of 36.0 and 35.0 mg/mL, Tor et al. (2015)
respectively
Anti-hypoxia Exhibited anti-hypoxia effect with no cytotoxicity on anoxic ECV304 cells at 50 mg/mL Li et al. (2009)
67 Ethyl gallate Cytotoxic Inhibitory effect against K562 cells proliferation with a 31.3% inhibition at 100 mg/mL Li et al. (2009)
Anti-hypoxia Exhibited anti-hypoxia effect with no cytotoxicity on anoxic ECV304 cells at 50 mg/mL Li et al. (2009)
68 Protocatechuic acid Anti-hypoxia Exhibited anti-hypoxia effect with no cytotoxicity on anoxic ECV304 cells at 50 mg/mL Li et al. (2009)

reduced the motility of the gastrointestinal tract assayed using
charcoal meal (Yeshwante et al., 2009a; Bose et al., 2010; Rahman
et al., 2011a,b). The antidiarrheal action of this plant is suggested
due to inhibition of inflammatory mediators release by flavonoids
and tannins (Yeshwante et al., 2009a).
4.7. Antiprotozoal activity
Antiprotozoal activities due to malaria and leismanicidal have
been shown by Dillenia species. Cyclohexane fraction of ethanolic
extract of D. indica leaves has been reported to inhibit the growth of
parasite Plasmodium falciparum (Nguyen-Pouplin et al., 2007).
Macahig et al. (2011) performed antileismanial activity of ten
compounds isolated from D. philippinensis and found that tri-
terpenes 41, 49, and 52e53 inhibited parasite Leishmania major
while the major compound 39 together with 19, 50e51, 54, and 57
were inactive against the parasite.
5. Toxicology of Dillenia species
Aqueous and organic extracts of D. indica, D. papuana, and
D. pentagyna were reported for their toxicity action against Artemia
salina (Table 5). Despite the toxicity reported for Dillenia plants,
some extracts of D.indica were non-toxic (Kumar et al., 2010) and
exhibited ameliorative (Shendge and Gadge, 2012) and hep-
atoprotective (Padhya et al., 2008; Himakar et al., 2010) activities
when assayed using in vivo models. The ethnopharmacological use
of D. indica and D. sumatrana as food poisoning neutralizer
(Grosvenor et al., 1995a; Islam et al., 2014) also indicate that Dillenia
plants are safe and not toxic.
6. Role of Dillenia species in drug formulation and drug
delivery
Mucilage prepared from the seeds of D. indica fruit is known to
contain a natural mucoadhesive hydrophilic polymer, which can be
use in the formulation for drug delivery (Sharma et al., 2009; Bal
et al., 2012a,b). The mucoadhesive strength and viscosity of muci-
lage from D. indica fruit was found to be comparable with synthetic
polymers such as Carbopol 934 (Kuotsu and Bandyopadhyay, 2007;
Bal et al., 2012a) and hydroxyl propyl methyl cellulose (Kuotsu and
Bandyopadhyay, 2007). This natural mucoadhesive has been
investigated in the formulation of nasal gel and buccal tablet of
oxytocin (Kuotsu and Bandyopadhyay, 2007; Metia and
Bandyopadhyay, 2008). Bal et al. (2012b) formulated a mucoadhe-
sive carvedilol microcapsule by using the seed mucilage from
D. indica for encapsulation. They found this microcapsule to be free
flowing and almost spherical in shape. From in vitro release and
in vivo animal studies, it was concluded that this mucilage was
effective for retarding drug release, which can be used in control-
ling the hypertension for a period of 24 h. Similar investigations
have been conducted by Sharma et al. (2010, 2013), which used this
mucilage to encapsulate pantoprazole sodium and metformin hy-
drochloride, respectively. It was found to perform good swelling
properties in the intestinal pH and good mucoadhesivity. The
findings suggested that the mucilage has potency for drugs
encapsulation (Sharma et al., 2013).
Nanoparticles have been used as drug carrier for the treatment
of diseases. Singh et al. (2013) was synthesized colloidal silver
nanoparticles (SNP) by using the aqueous extract of D. indica fruit
petals as reducing agent instead of sodium borohydride. The extract
was found to reduce AgNO3 to silver nanoparticles with stability
more than 6 days (166 h). The study indicated that D. indica might
serve as reducing agent for the green synthesis of silver
nanoparticles.
7. Conclusions
Dillenia species have been used as traditional medicine in many
Asian countries. D. indica and D. pentagyna are two species out of
nineteen species reported in this review that are mostly employed
as traditional medicines by natives. Despite a broad range of me-
dicinal properties of Dillenia species, very few investigations
regarding chemical constituents and pharmacological aspects have
been carried out. Current phytochemical studies of species from the
genus Dillenia showed that flavonoids (flavonols, dihydroflavonols,
a flavan, flavan-3-ols, flavanones, and a chromene) and triterpe-
noids (lupenes and oleanenes) are dominant chemical constituents.
The presence of methylated and sulfated flavonoids, as well as seco-
triterpenoids, from this genus is unique, which probably differ
them from other genus in the family Dilleniaceae. Of the nineteen
species reviewed in this study, only seven species have been
investigated for biological activities, including antimicrobial, anti-
inflammatory, cytotoxic, antidiabetic, antioxidant, antidiarrheal,
antiprotozoal, and miscellaneous bioactivities such as immuno-
modulatory, anti-hypertension, protoscolicidal, insecticidal, and
hair protection activities. In addition, fruit mucilage of D. indica has
promising properties as natural mucoadhesive for drug formula-
tion. Current knowledge of Dillenia plants emerges great lacunae
which requiring more investigation and development. Hence,
further studies are highly needed to discover the potential of these
plants on the phytochemical and pharmacological aspects. Future
studies are also required to evaluate the side effects, safety, and
efficacy of extracts and single compound from Dillenia plants in
order to facilitate their clinical applications as modern medicines
for human health.
Acknowledgments
The authors thank the Universiti Kebangsaan Malaysia for a
research grant (GUP-2012-001) and a UKM Zamalah Research
Scheme Scholarship (2012e2014) for financial support.
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Carla W. Sabandar graduated from Halu Oleo University of
Chemistry Department in Indonesia in 2009. She received
her M.Sc in Pharmaceutical Chemistry from the Universiti
Kebangsaan Malaysia in 2016. Her research interests
include the chemistry and pharmacological aspects of
chemical constituents from Euphorbiaceae, Dilleniaceae,
and Myrtaceae plants.
Juriyati Jalil is an Associate Professor at the Faculty of
Pharmacy, Universiti Kebangsaan Malaysia. She received
her B.Sc (Hons) in Chemistry in 1993, M.Sc in Natural
Products Chemistry in 1997, and Ph.D in Pharmaceutical
Chemistry in 2005 from the Universiti Kebangsaan
Malaysia. She is currently a Coordinator for Drug and
Herbal Research Centre at the Faculty of Pharmacy, Uni-
versiti Kebangsaan Malaysia. Her research interests are in
the structure elucidation of bioactive natural products
from the plants family Guttiferae, Annonaceae, Clusiaceae
(Garcinia), Primulaceae, Dilleniaceae, and Myrtaceae,
especially those with anti-inflammatory activities on
platelet-activating factor (PAF) receptor binding, and pro-
duction of thromboxane B2 (TXB2), and prostaglandin E2
(PGE2). She also is involved in the Malaysian Herbal Mono-
graph development and is an active member of the Malay-
sian Natural Products Society.
Norizan Ahmat is an Associate Professor at the Faculty of
Applied Sciences, Universiti Teknologi MARA Malaysia. She
obtained her degree in Chemistry from the Arkansas State
University, U.S.A in 1989. She received her M.Sc. in
Chemistry in 1995 and Ph.D in Natural Products Chemistry
from the Universiti Kebangsaan Malaysia in 2008. In her
current research, she is interested in the chemistry and
pharmacology of alkaloids, flavonoids and resveratrol
oligomers from plants in Malaysia especially from the
family of Annonaceae, Euphorbiaceae, Dipterocarpaceae,
Gnetaceae, Fabaceae, and Sterculiaceae. Her multidisci-
plinary research includes collaborations with researchers
from Indonesia and Japan. She is a member of the GA
Society for Medicinal Plants and Natural Product Research
and the Malaysian Natural Products Society.
Nor-Ashila Aladdin received her B.Sc (Hons) degree in
Chemistry from the Universiti Malaysia Sarawak in 2010.
She obtained her M.Sc degree in Pharmaceutical Chemis-
try from the Universiti Kebangsaan Malaysia in 2016. Her
current research includes the pharmacognosy, chemistry,
structure elucidation, and pharmacological behaviors of
chemical constituents from species of the family of
Primulaceae.

Please cite this article in press as: Sabandar, C.W., et al., Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae),
Phytochemistry (2016), http://dx.doi.org/10.1016/j.phytochem.2016.11.010