Nutrients 2013, 5, 1757-1800; doi:10.3390/nu5051757
Can Scientific Evidence Support Using Bangladeshi Traditional
Medicinal Plants in the Treatment of Diarrhoea? A Review on
Helle Wangensteen 1,*, Line Klarpås 1, Mahiuddin Alamgir 2, Anne B. C. Samuelsen 1
and Karl E. Malterud 1
1 Department of Pharmaceutical Chemistry-Pharmacognosy, School of Pharmacy,
University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway;
E-Mails: firstname.lastname@example.org (L.K.); email@example.com (A.B.C.S.);
2 School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia;
* Author to whom correspondence should be addressed; E-Mail: firstname.lastname@example.org;
Tel.: +47-22-85-65-67; Fax: +47-22-85-44-02.
Received: 13 March 2013; in revised form: 18 April 2013 / Accepted: 22 April 2013 /
Published: 22 May 2013
Abstract: Diarrhoea is a common disease which causes pain and may be deadly, especially
in developing countries. In Bangladesh, diarrhoeal diseases affect thousands of people
every year, and children are especially vulnerable. Bacterial toxins or viral infections are
the most common cause of the disease. The diarrhoea outbreaks are often associated with
flood affected areas with contaminated drinking water and an increased risk of spreading
the water-borne disease. Not surprisingly, plants found in the near surroundings have been
taken into use by the local community as medicine to treat diarrhoeal symptoms. These
plants are cheaper and more easily available than conventional medicine. Our question is:
What is the level of documentation supporting the use of these plants against diarrhoea and
is their consumption safe? Do any of these plants have potential for further exploration? In
this review, we have choosen seven plant species that are used in the treatment of
diarrhoea; Diospyros peregrina, Heritiera littoralis, Ixora coccinea, Pongamia pinnata,
Rhizophora mucronata, Xylocarpus granatum, and Xylocarpus moluccensis. Appearance
and geographical distribution, traditional uses, chemical composition, and biological
studies related to antidiarrhoeal activity will be presented. This review reveals that there is
limited scientific evidence supporting the traditional use of these plants. Most promising
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are the barks from D. peregrina, X. granatum and X. moluccensis which contain tannins
and have shown promising results in antidiarrhoeal mice models. The leaves of P. pinnata
also show potential. We suggest these plants should be exploited further as possible
traditional herbal remedies against diarrhoea including studies on efficacy, optimal dosage
Keywords: diarrhoea; Bangladesh; traditional medicine; mangrove plants; Diospyros
peregrina; Heritiera littoralis; Ixora coccinea; Pongamia pinnata; Rhizophora mucronata;
Xylocarpus granatum; Xylocarpus moluccensis
Diarrhoea is a common and serious disease in almost all tropical countries of the world. Particularly
children are exposed to diarrhoea, and diarrhoea is the principal cause of morbidity and mortality
among children in the developing world . It is proposed that about 17% of all deaths in children up
to 5 years are caused by diarrhoea, corresponding to 1.8 million deaths annually (estimates for
2000–2003). The countries in South-East Asia contribute significantly to this . There has been a
decline in mortality caused by diarrhoea in the last decades, but the morbidity remains high . The
need to provide clean drinking water and hygiene facilities still remains a huge challenge in developing
countries today. Currently, 1.1 billion people lack access to safe water .
The World Health Organization has defined diarrhoea as the passage of three or more loose or
liquid stools per day, or more frequently than normal for the individual. Disturbances in the transport
of electrolytes and water in the intestines give rise to diarrhoea. There are four major mechanisms
responsible for the pathophysiology in electrolyte and water transport: (1) increased luminal
osmolarity; (2) increased electrolyte secretion; (3) decreased electrolyte absorption; and (4) deranged
intestinal motility causing a decreased transit time . Diarrhoea is usually a result of gastrointestinal
infection, which can be caused by a variety of bacterial, viral and parasitic organisms. Infection is
spread through contaminated food or drinking water, or from person to person as a result of poor
personal hygiene. Vibrio cholerae together with enterotoxigenic Escherichia coli, enteropathogenic
E. coli, Shigella spp., Campylobacter jejuni, and rotavirus are the most likely causes of diarrhoea in
Bangladesh [5,6]. Infections with multiple pathogens are common, making the identification of the
causative agent difficult. It may also be that multiple pathogens act synergistically to produce
diarrhoeal symptoms . There are differences in the causes of diarrhoea between patients of different
ages. Enterotoxigenic E. coli was shown to be the commonest cause of diarrhoea in patients below
two years of age, while in older children and adults, cholera was the most common cause of
In order to study antidiarrhoeal effects appropriate models are necessary. The most common method
is to study the inhibitory effect of a test compound in an animal model after induction of diarrhoea.
The inducing agent may be castor oil, magnesium sulphate, prostaglandin E2 or arachidonic acid.
These agents appear to induce diarrhoea by different mechanisms, e.g., castor oil increases peristaltic
activity and alters the permeability of the intestinal mucosa to water and electrolytes, while magnesium
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sulphate is an osmotically active agent . The gastrointestinal transit is often determined by
measuring the transit of a charcoal plug or suspension and the distance traveled by the agent is
expressed as a percentage of the total length of the intestine. In addition to the effect of the test
compounds on the gastrointestinal system, it is of interest to investigate the effect on microorganisms
causing diarrhoea, as well.
Herbal remedies continue to be the only therapeutic possibility for the majority of the global
population. A number of traditional medicinal plants and their constituents from all over the world are
reported as agents used to treat diarrhoea. Dragon’s blood (sap of Croton lechleri) is an example of a
traditional antidiarrhoeal plant utilized in the production of the commercial Dragon’s blood extract
named SP-303™ by Shaman Pharmaceuticals, Inc. . Traditional cocoa preparations have been used
by indigenous people of Central America to treat childhood diarrhoea and other intestinal ailments, as
well . Numerous spices and medicinal plants such as ginger, rhubarb, Galla Chinensis, cardamom,
Moringa oleifera, Anthocephalus cadamba as well as green and black tea have also been used against
diarrhoea, and have been shown to give certain effects in antidiarrhoeal studies [11–17]. The plant
extracts can show antispasmodic effects, delay gastrointestinal transit, suppress gut motility, stimulate
water adsorption or reduce electrolyte secretion . Plant extracts may have an inhibitory effect on the
microorganisms involved in the pathogenesis of diarrhoea, as well. In complex natural products,
synergistic effects may contribute to effective antidiarrhoeal treatment. An herbal preparation
containing Myrtus communi, Aegle marmelos, Punica granatum, Phyllanthus emblica and
Berberis vulgaris was recently reported to be superior to the allopathic drug Furoxone (furazolidone)
in a clinical study of diarrhoea treatment . Proanthocyanidins are major constituents of
Croton lechleri sap . This class of compounds is common in plants used to treat diarrhoea ,
and it has been suggested that the proanthocyanidin-rich SP303 may act by inhibition of fluid
accumulation and chloride secretion .
The inhabitants of Bangladesh are highly affected by diarrhoeal diseases. One important reason is
the annual heavy monsoon rainfall which makes disastrous floods followed by contamination of
drinking water, thereby leading to spreading of water-borne diseases such as cholera. Cyclones and
tsunamis are risk factors for cholera outbreaks, as well. The number of people affected by flooding is
projected to increase as a result of the raising global average temperature, thus leading to an increased
risk of water-borne diseases, e.g., diarrhoea. The risk for diarrhoeal mortality and disease is projected
to increase by a factor of 1.09 until 2030 due to the climate changes . The future need of effective
antidiarrhoeal medications is therefore highly warranted. The plants presented in this review are
growing in the Sundarbans mangrove forest. The Sundarbans is the largest single tract of mangrove
ecosystem in the world, covering about 6000 km2 of Bangladesh and India . There is a worry,
however, that this mangrove forest may be dwindling [24,25]. Mangroves are usually found only in
tropical climates, as consistently warm conditions are necessary for development and survival of this
type of forest. These wetland ecosystems are among the most productive and diverse in the world, and
a wide variety of biologically active natural products have been reported from mangrove forests .
The mangroves play a vital role for the local people . It has been estimated that ca. four million
people depend on the mangroves for their livelihood . Fishery, seafood and honey are important
sources of income; the mangroves also provide raw material for paper, wood and furniture industry.
In addition, there might be a potential for local sales of herbal remedies as an income source.
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Bangladesh is in particular affected by tropical cyclones due to its geographical position, but
mangroves play an important role reducing the impact of the cyclones and accompanying surges .
The aim of this review is to summarize the present knowledge of some traditional medicinal
plants used against diarrhoea in the Sundarbans mangrove forest in Bangladesh and to consider
whether this documentation support the use and safety of these plants. The plants discussed are
Diospyros peregrina, Heritiera littoralis, Ixora coccinea, Pongamia pinnata, Rhizophora mucronata,
Xylocarpus granatum, and Xylocarpus moluccensis (Table 1). These plants all grow in the Sundarbans.
However, the scientific evidence for their antidiarrhoeal effects turns out to be limited for most of the
plants. When we describe each plant, various traditional medicinal usages are given (not only uses
against diarrhoeal related diseases). The chemical composition of each plant part is described in detail.
Concerning the biological activities, we have primarily focused on studies related to antidiarrhoeal
effects or studies dealing with effects on diarrhoea inducing microorganisms. When such studies have
been conducted, the potential toxicity of each plant is described. Potential associations between
observed biological activity and chemical composition in relation to antidiarrhoeal effects are briefly
discussed. The literature sources used in this review are the SciFinder and PubMed databases and
Google searches in the “grey” literature, as well as handbooks, reference works and articles from the
archives of the authors.
Table 1. Traditional antidiarrhoeal plants from Sundarbans mangrove forest.
Diospyros peregrina Gürke
D. biflora Blanco
D. citrifolia Wall. ex A.DC.
D. embryopteris Pers.
D. glutinifera (Roxb.) Wall.
D. glutinosa J.König ex Roxb.
D. malabarica (Desr.) Kostel.
D. siamensis Hochr.
Embryopteris gelatinifera G.Don
E. glutinifera Roxb.
E. glutinifolia Link
E. peregrina Gaertn.
Amygdalus littoralis (Dryand.)
Balanopteris tothila Gaertn.
H. minor Bojer
Pavetta coccinea (L.) Blume
Heritiera littoralis Dryand. Looking-glass
Ixora coccinea L. Jungleflame ixora
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Table 1. Cont.
Pongamia pinnata (L.)
Cytisus pinnatus L.
Dalbergia arborea Willd.
Derris indica (Lam.) Bennet
Galedupa indica Lam.
G. pinnata (L.) Taub.
G. pungum J.G.Gmel.
Millettia pinnata L.
M. novo-guineensis Kaneh. & Hatus.
P. glabra Vent.
P. mitis (L.) Kurz
P. xerocarpa Hassk.
Pterocarpus flavus Lour.
Robinia mitis L.
Indian beech tree
Rhizophora mucronata Lam. Mangium candelarium Rumphius
R. candelaria Wight & Am.
R. longissima Blanco
R. macrorrhiza Griff.
Xylocarpus granatum König X. obovatus A. Juss.
Carapa granatum (Koen.) Alston
Xylocarpus moluccensis M.
True mangrove Rhizophoraceae
Puzzle nut tree
Cannon ball tree
Carapa moluccensis Lam. Meliaceae
2. Traditional Antidiarrhoeal Plants from Bangladesh
2.1. Diospyros peregrina Gürke (Ebenaceae)
Diospyros peregrina (Figure 1) is a medium-sized evergreen tree up to 15 m high. It has
bell-shaped flowers, the fruits are yellow when ripe, round and 4–8 cm in diameter . The tree is
indigenous to Bangladesh and India, and is also found in many other countries of Asia and America.
The Bengali name is “gab”.
Figure 1. Diospyros peregrina (syn. D. malabarica) .
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2.1.1. Traditional Use and Plant Parts Used
The bark is astringent and has traditionally been used against dysentery and intermittent fevers. The
seeds and the oil from the seeds are given as an astringent agent against diarrhoea. The ripe fruit has
been used against biliousness, diseases of the blood, urinary losses, and stones in the urinary tract. The
infusion of fruits is used as gargle in mouth ulcers and sore throats. The juice of the unripe fruit is used
on wounds and ulcers, it has astringent properties, and it has also been used for the treatment of
diabetes. The flowers are believed to be aphrodisiac and good for lumbago. They are also used in
biliousness and diseases of the blood. The flowers and fruits are given to children with
hiccough [28,30,31]. Tannins from D. peregrina are used for dyeing and in the tanning industry .
In Namibia, D. peregrina (unspecified plant parts) is employed against malaria . Interestingly, an
antiplasmodial activity of a stem bark extract of D. peregrina has been reported .
An extract of unripe fruits of the related species D. melanoxylon in milk has been reported to be
used against diarrhoea in Madhya Pradesh, India .
2.1.2. Chemical Composition (Figure 2)
Triterpenoids: lupeol, betulin, betulinic acid, oleanolic acid ;
Sterol: β-sitosterol ;
Long-chain alcohol: myricyl alcohol ;
Triterpenoid: Lupeol .
Sterol: β-sitosterol ;
Flavonoid: leucopelargonidin-3-O-α-L-rhamnopyranoside ;
Aliphatic ketone: nonadecan-7-ol-2-one .
Triterpenoids: betulin, oleanolic acid, peregrinol [40,41];
Sterol: β-sitosterol [40,41].
Triterpenoids: peregrinol, lupeol, betulin, betulinic acid, taraxerone, marsformosanone [32,42,43];
Sterols: β-sitosterol, β-sitosterol-D-glucoside ;
Flavonoids: furano-(2″,3″,7,8)-3′,5′-dimethoxy-5-hydroxyflavone, 3,6-dimethoxy-2-(3′,5′-dime
5-hydroxy-3,6,7-trimethoxyflavone, 4′-O-methylluteolin 7-glucoside, quercetin 3-O-glucosyl
Naphtoquinone: 2,6′-bis-7-methyljuglone ;
Phenolic acid: gallic acid ;
Fats: glycerides of myristic, palmitic, stearic, oleic and palmitoleic acids ;
Tannins, free sugars and proteins [30,32,42–44,46];
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The fruits have been reported to be rich in vitamin C; 229 mg/100 g fresh fruit .
Triterpenoid: betulinic acid .
Figure 2. Triterpenoids from Diospyros peregrina bark and seeds. In the formulas in this
paper, selected substances from the active plant parts are shown. Ubiquitous substances
have been omitted. In most cases, it is unknown which substances are responsible for the
R=COOH: Betulinic acid
The methanol extracts of the bark and the seeds of D. peregrina have been investigated as an
antidiarrhoeal . Mice received bark and seed extracts at oral doses of 250 and 500 mg/kg. Then
diarrhoea was induced by oral administration of 0.5 mL castor oil 45 min after each treatment. Both
the total number of faecal output and the total number of diarrhoeic faeces the next 4 h were
significantly reduced for both dosages of seed and bark extract. In the gastrointestinal motility test
mice received the same dosage as described above, and after 30 min they were fed with 1 ml of a
charcoal suspension. After 30 min the mice were sacrificed in order to measure the intestinal
movement. The results showed that D. peregrina extracts delayed gastrointestinal transit of charcoal
significantly compared to the control. The seed extract showed stronger effect than the bark extract.
Anthelmintic activity of a methanol extract of unripe fruits of D. peregrina has been reported .
The methanol extract of D. peregrina fruits has shown inhibition of the growth of a number of
bacteria . The disc-diffusion and tube dilution methods were employed. E. coli was highly
sensitive against the extract with a MIC value of 10 μg/mL. The extract also inhibited the growth of
V. cholerae (100 μg/mL), different Shigella species (200 μg/mL), Pseudomonas aeruginosa
(200 μg/mL), and Staphylococcus aureus (100 μg/mL). The antibacterial potential of the bark and seed
methanol extracts were evaluated against pathogenic bacteria responsible for causing diarrhoea and
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dysentery by using the antimicrobial disc-diffusion test. The bark extract (600 μg/disc) inhibited the
growth of S. aureus, Shigella dysenteriae, E. coli and P. aeruginosa, whereas the seed extract inhibited
S. aureus, S. dysenteriae and E. coli .
In a series of papers, the antidiabetic and antioxidant effects of D. peregrina fruit extract have been
investigated by Dewanjee et al. [45,53–57]. Inhibition of α-amylase, reduction of glucose uptake and
radical scavenging properties have been suggested as possible mechanisms for the antidiabetic effect.
Hypoglycemic and antihyperglycemic activity of aqueous fruit extract from D. peregrina has been
A bark extract of D. peregrina was found to have antitumour activity against Ehrlich ascites
carcinoma in mice . The gum from the fruits of D. peregrina has recently been suggested to be
useful as a binder in tablet formulation .
Approximate LD50 value of D. peregrina extract (whole plant) in mice was found to be
2.6 g/kg (p.o.) .
The use of bark against diarrhoea may be explained by the tannins present having astringent
properties. The chemical composition of the bark methanol extract tested in the mouse model was not
described, but it is likely to contain tannins, elsewhere reported in D. peregrina bark . This extract
had positive effect on chemically induced diarrhoea on mice and also showed some antibacterial
activity, which are promising results. The seed extract showed even better effects in the mouse model,
but since little is known about chemical composition and toxicity seeds are hard to recommend on a
scientific basis. The methanol extracts of bark and seeds have shown antidiarrhoeal activity in mice
and antibacterial effect against several bacterial species associated with diarrhoeal diseases. In several
studies composition of different plant parts has been investigated, and flavonoids, triterpenoids and
tannins have been reported repeatedly. More studies of the bark and seeds are, however, needed in
order to identify the bioactive compounds. It seems reasonable, though, that the flavonoids and tannins
in the bark and seeds may contribute to the medical effects.
2.2. Heritiera littoralis Dryand (Sterculiaceae)
Heritiera littoralis (dungun, looking-glass mangrove; Figure 3) is an evergreen mangrove tree, up
to 25 m in height and with a buttressed trunk up to 60 cm in diameter. The bark is fissured, dark or
gray. Leaves are 10–20 cm long, and they have a green upper surface and a silvery-white lower
surface. The tree has numerous small bell-shaped, yellowish-green flowers. The fruits are hard and
shining, 4–8 cm long . H. littoralis is distributed from Madagascar and East Africa to Hong Kong,
the Pacific and Australia.
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Figure 3. Heritiera littoralis .
2.2.1. Traditional Use and Plant Parts Used
H. littoralis seed extracts are traditionally used to treat diarrhoea and dysentery . The stems and
leaves have also been used against diarrhoea and dysentery. In addition, they have been used to control
mosquitos and as a piscicide [65–67]. The sap is reported to be a fish poison and arrowhead and
spearhead poison [64,68]. The seeds and leaves are, however, regarded as edible in the Andaman and
Nicobar islands . The tree is used as tooth brushes and chew sticks. The wood is also valuable for
its timber .
2.2.2. Chemical Composition (Figure 4)
Coumarin: isofraxidin ;
Triterpenoids: friedelin, betulinic acid etc. ;
Sterols: β-sitosterol, stigmasterol, sitost-4-en-3-one, ergosterol peroxide, etc. ;
Anthraquinone: physcion [64,71];
Flavonoids: quercitrin, quercetin, kaempferol-3-O-(6″-O-E-p-coumaroyl)-β-D-glucopyranoside,
kaempferol, kaempferitrin, myricetin, eriodictyol, afzelin, astragalin, tribuloside, catechin ;
Lignan: isolariciresinol-3a-O-β-D-glucoside ;
Others: (Z)-3-hexenyl β-D-glucoside, Me [β-D-xylopyranosyl-(1→6)-β-D-glucopyranosyl]-
salicylate, and 2-O-[4′-(3″-hydroxypropyl)-2′,5′-dimethoxyphenyl]-1-O-β-D-glucopyranosyl-
Fatty acids: malvalic, sterculic, palmitic, oleic and linoleic acid .
Sesquiterpenes: heritol, heritonin, heritianin, vallapin, vallapianin [68,76–78];
Triterpenoid: friedelin .
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Figure 4. Fatty acids and phenolic constituents of Heritiera littoralis leaves and seeds.
In a related species, Heritiera fomes, we have found a high content of proanthocyanidins in the
bark . H. fomes is used locally in the Sundarbans against diarrhoea, accordingly to unpublished
field work done by one of the authors of this review (M. Alamgir).
In spite of the often reported antidiarrhoea use of H. littoralis, it appears that no systematic
scientific studies have so far evaluated the antidiarrhoeal effects of the plant. Aqueous leaf and stem
extracts of the plant have shown antibacterial activity against Salmonella paratyphoid, while the
ethanol extract was inactive. Some other bacteria, e.g., S. aureus and P. aeruginosa were also
inhibited . Several triterpenoids and steroids showed anti-inflammatory activity determined as NO
inhibitory effect and anti-PGE2 activity, with ergosterol peroxide being the most active substance .
The toxicity of H. littoralis to land animals has, as far as we know, not been evaluated. The
sesquiterpenes from the roots are toxic to fish [68,77,78].
There are no studies available on the efficacy of H. littoralis against diarrhoea, and toxicity testing
has not been performed. However, since the stems are commonly used for maintaining dental hygiene
and since leaves and seeds are regarded as edible, they can probably be considered as quite safe. Since
no biological studies have been carried out to evaluate the chemical composition of seeds and few
studies on pharmacological properties have been conducted we can only invite the scientific
community to investigate this plant further.
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2.3. Ixora coccinea L. (Rubiaceae)
Ixora coccinea (Jungle geranium, Bengali: Kangan; Figure 5) is a perennial shrub 0.6–0.9 m in
height, widely grown in gardens as an ornamental. The flowers are bright scarlet red, sometimes
yellow, pink or orange-yellow. The bush has small globular fruits which are purple when ripe. The
shrub is native to tropical Asia. However, it is cultivated for ornamental purposes in tropical and
subtropical areas in other continents, as well [28,81].
Figure 5. Ixora coccinea .
2.3.1. Traditional Use and Plant Parts Used
The roots, bark, leaves and flowers are used in traditional medicine in South East Asia from India to
the Philippines [83–86]. The roots of I. coccinea are used to treat hiccoughs, nausea, fever, ulcers,
gonorrhea, and loss of appetite. The flowers of I. coccinea are used against reddened eyes, eruptions,
catarrhal bronchitis, dysentery, and as an anti-inflammatory agent. The leaves have been utilized in the
treatment of diarrhoea. A paste from the root of an unspecified Ixora species is used against diarrhoea
in children . The ethnomedical uses and pharmacology of this plant have been reviewed
2.3.2. Chemical Composition (Figure 6)
Triterpenoid: lupeol [81,89];
Proanthocyanidins: ixoratannin A-2 (a trimeric A-type proanthocyanidin), procyanidin A2,
cinnamtannin B-1 ;
Flavonoids: epicatechin, kaempferol- and quercetin-rhamnosides .
Triterpenoids: ursolic acid, cycloartenol esters, lupeol esters, lupeol, oleanolic acid [84,91];
Sterol: sitosterol ;
Flavonoids: biochanin A, myricetin, quercetin, rutin, daidzein formononetin, monoglycosides of
cyanidin and delphinidin, rutin, kaempferol-3-rutinoside, traces of leucocyanidin glycoside .
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Triterpenoids: lupeol, 3-acetylbetulic acid, betunolic acid, α-amyrin, β-amyrin, ursolic acid,
3-acetylursolic acid, oleanonic acid ;
Sterols: 6β-hydroxystigmast-4-en-3-one, sitosteryl-3-O-β-D-glucoside, β-sitosterol, stigmasterol ;
Flavonoids: kaempferol, kaempferol-7-O-α-rhamnoside, kaempferitrin, luteolin, (−)-epicatechin,
Proanthocyanidin: epicatechin-4β->8, 2β->O->7-ent-epicatechin ;
Coumarins: scopoletin, coumarin, erythro-1′,2′-albiflorin ;
Diterpenoids: 16a-hydro-19-acetoxy-(−)kauran-17-oic acid, 16a-hydro-19-ol-(−)-kauran-17-oic
Quinones: 1,4-dihydroxy-3-methylanthraquinone, tocopherylquinone ;
Peptides: ixorapeptides I and II .
Fatty acids: palmitic, stearic, oleic and linoleic acid ;
Essential oil: (main constituent β-sesquiphellandrene) [81,94].
Figure 6. Triterpene esters and polyphenols from Ixora coccinea.
Cycloartenol 3-palmitate: R= CH3(CH2)14
Cycloartenol 3-myristate: R= CH3(CH2)12
Kaempferol 3-O-α-L-rhamnoside: R1 = H, R2 = rhamnose, R3 = H
Kaempferol 7-O-α-L-rhamnoside: R1 = rhamnose, R2 = H, R3 = H
Kaempferol 3,7-di-α-L-rhamnoside: R1 = R2 = rhamnose, R3 = H
Quercetin 3-O-α-L-rhamnoside: R1 = H, R2 = rhamnose, R3 = OH
Procyanidin A-2 Ixoratannin A-2 Cinnamtannin B-1
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The antidiarrhoeal effect of I. coccinea has been investigated . An aqueous extract of the
flowers showed significant inhibition of castor oil induced diarrhoea in rats as determined by weight
and volume of intestinal content and by gastrointestinal motility.
I. coccinea has been investigated for antimicrobial effects. In a study by Annapurna et al. , ether
and methanol extracts of the leaves were tested against a selection of bacteria and fungi. The ether
extract was found to have higher activity than the methanol extract, and both Gram-negative and
Gram-positive bacteria were inhibited. The activity against fungi was not significant .
Srinivasan et al.  reported that the essential oil from I. coccinea roots exhibited antimicrobial
activity towards Gram-positive and Gram-negative bacteria. Sasidharan  found that an alcoholic
extract of I. coccinea (plant part not specified) was active against S. aureus and E. coli, the aqueous
extract was active against E. coli but not S. aureus, and neither the aqueous nor the alcoholic extract
were active against the fungi Aspergillus niger. Leaf constituents were active against E. coli, S. aureus,
P. aeruginosa and B. subtilis . In these studies the disc-diffusion method was employed. Ethanolic
and aqueous root extracts inhibited bacterial growth of Enterococcus faecalis, E. coli, Salmonella typhi
and several other bacteria (S. aureus, B. pumilus, P. aeruginosa) with MIC values of 12.5–100 μg/mL.
The extracts were, however, inactive against fungi. Interestingly, these extracts were also reported to
have wound-healing properties .
An ethanol extract of I. coccinea roots protected rats from aflatoxin B1-induced liver damage. This
was suggested to be due to the potent antioxidant activity of the extract . Antioxidant activity of
leaf constituents were reported by Idowu et al. . Antioxidant properties (as radical scavenging,
total antioxidant capacity, and xanthine oxidase inhibition) of methanol extracts from flowers, leaves
and stems of I. coccinea were reported . The antioxidant activity seemed to be correlated to the
phenolic content. The antioxidant properties of the methanolic extract of I. coccinea was also believed
to be important for its ability to counteract doxorubicin induced cardiotoxicity in rats .
Haridass et al.  investigated the antioxidant and cytotoxic activity of petroleum ether, ethyl
acetate and methanol extracts of I. coccinea flowers, finding that the ethyl acetate extract was the most
active one. Ixorapeptide I was found to have selective cytotoxicity towards Hep3B liver cancer cells
relative to normal cells . An aqueous extract of the flowers of I. coccinea had antimutagenic
An aqueous extract of the leaves exhibited hypoglycaemic and hypolipidaemic activity in diabetic
rats . A methanolic flower extract had anti-inflammatory and analgesic properties .
The methanol extract of I. coccinea leaves has been reported to be without larvicidal activity
towards Anopheles mosquitoes .
In a mice toxicity test it was found that the petroleum ether extract of I. coccinea root, up to an oral
dose of 1.5 g/kg body weight, did not show any toxic effects . In another study, the active fraction
(AF) (the cytotoxic fraction from a flower hexane extract) up to 400 mg/kg was given i.p. to mice. No
deaths were observed in 24 h . The test animals did not show any changes in general behavior
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during the study. Chronic administration of AF (200 mg/kg i.p.) did not produce any significant
differences in the food or water consumption and body weight of the mice either. However,
Atiq-Ur-Rahman et al.  have reported that a methanolic extract of I. coccinea flowers and
fractions therefrom were cardiotoxic to the perfused guinea pig heart and might lead to heart failure.
Whether this is relevant for in vivo conditions appears unknown.
The leaves of I. coccinea have been used in traditional medicine against diarrhoea. This activity has
recently been documented in animal experiments. Numerous biological activities have been reported
for different parts of the plant, although most of these are in vitro. It would appear that some of these
effects are related to the antioxidant activity of the plant, which again has been suggested to be
correlated to its content of phenolic compounds such as flavonoids and A-type proanthocyanidins.
In this connection, it might be mentioned that A-type proanthocyanidins from cranberries have been
reported to be partly responsible for the putative effects of cranberries against urinary bladder
infections . Investigation of proanthocyanidins from I. coccinea for this condition might
2.4. Pongamia pinnata (L.) Pierre (Fabaceae)
Pongamia pinnata (syn. Pongamia glabra Vent.; Figure 7) is a medium sized tree, 15–25 m in
height, with white, purple and pink flowers growing in clusters and maturing into brown seed pods.
The species is distributed from India to Philippines and the north of Australia. “Karanja” is the local
name used in Bangladesh . The traditional use, chemistry and pharmacology of this tree have been
Figure 7. Pongamia pinnata .
More than a thousand scientific articles, as indexed in the SciFinder database, deal with
Pongamia pinnata and its constituents, and it would be beyond the scope of this article to give a
detailed review of this plant. In recent years, a large number of papers have dealt with P. pinnata as a
source of biofuel. These are not covered in the present paper.
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2.4.1. Traditional Use and Plant Parts Used
P. pinnata has been widely used as a traditional medicinal agent, and both the leaves, bark, flowers,
seeds, and roots are reported to have a healing effect [28,30,114]. The leaves of P. pinnata have been
used against flatulence, dyspepsia and diarrhoea . In Tamil Nadu, India, preparations of the plant
are used against gastric trouble and as a cure for wounds [116,117]. A poultice of the leaves is applied
to ulcers infested with worms. A decoction of the leaves is used for medicated baths and fomentations
in cases of rheumatic pains. The juice from the roots is used for closing fistulous sores and for cleaning
foul ulcers. It is used for cleaning the teeth and strengthening the gums. It is also given internally
mixed with coconut milk and lime water for the cure of gonorrhea. The oil from the seeds is useful in
skin diseases such as herpes and scabies, and in rheumatism . A paste from the seeds has also been
used in rheumatism . The use of the bark or leaves of the plant against fever in humans  and
animals  and against malaria  has been reported. Both the seeds and roots are used as fish
poison. The fresh bark is used internally in the treatment of bleeding piles . In Madhya Pradesh,
India, the plant has been used against burns, but no details are given . It is also reported that the
plant is recommended for the treatment of snake bites and scorpion stings. However, the efficacy of
this treatment has been debated [28,30].
2.4.2. Chemical Composition (Figure 8)
P. pinnata is rich in flavonoids, especially prenylated flavonoids which are common in the
Fabaceae family. A search in the SciFinder database with the keyword “Pongamia pinnata flavonoid”
resulted in 100 hits, and several hundred different chemical constituents are reported in the literature.
To limit the number of chemical constituents listed for this plant, this paragraph will focus on the
chemistry of the leaves, which are the plant parts used for diarrhoeal diseases.
Chromenes: glabrachromene I and II ;
Triterpenoids: cycloart-23-ene-3β,25-diol, friedeline, lupeol, lupenone, betulin [126,127];
Sterol: β-sitosterol [124,126];
Fatty acids: .
Figure 8. Flavonoids, a chromene and a triterpene from Pongamia pinnata leaves.
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Figure 8. Cont.
Glabrachromene I Friedeline
Until now, two studies have investigated the antidiarrhoeal activity of P. pinnata leaves. In the first
study, the methanol leaf extract was given to mice in doses of 3, 7.5 and 15 mg/kg, 30 min before
castor oil administration. The mice were observed the next four hours, and it was found that the onset
time of diarrhoea was significantly increased, and the total number of faeces, the number of wet faeces
and the total weight of wet faeces were significantly reduced when compared to control group .
In a study by Brijesh et al. , the antidiarrhoeal properties of hot water decoction of P. pinnata
leaves were investigated against various virulence parameters of infectious diarrhoea. The decoction
showed no activity against Shigella flexneri, V. cholerae or of different strains of E. coli. The viability
of Giardia lamblia trophozoites and rotavirus were not affected. However, the production of cholera
toxin was significantly reduced when V. cholerae was grown in the presence of the decoction (1%, 5%
and 10%). The production of labile toxin by E. coli was not affected either. Finally, the decoction did
not inhibit the adherence of E. coli to epithelial cells. However, the invasion of both E. coli and
S. flexneri into epithelial cells was significantly reduced after treatment with the leaf decoction.
Antibacterial activity of leaf extracts in vitro has been reported by several groups [130–136]. Most of
these investigations include enteric bacteria such as E. coli, Salmonella typhimurium, S. typhi, and
Enterobacter aerogenes. Interestingly, activity against methicillin-resistant S. aureus was observed by
Ramesh et al. . Antioxidant properties of leaf extracts have been reported [137,138].
Numerous other activities have been reported for extracts and constituents from P. pinnata. A few
examples are: Antidiabetic activity of leaf extract of P. pinnata and of cycloart-23-ene-3β, 25-diol has
been investigated [138–141]. This compound has also been shown to have antioxidant and
antimicrobial properties . The flavonoids pongamol and karanjin from P. pinnata also have been
reported to have antihyperglycemic effect, apparently by regulating the levels of the insulin-sensitive
glucose transporter GLUT4 [143–145]. The methanolic seed extract  and the substance
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karanjin  has been reported to exert a gastroprotective activity in vivo in rats. Anti-dyslipidemic
and antioxidant activities of fruit extracts were investigated by Bhatia et al. .
Anti-insect activity of P. pinnata has been reported repeatedly. Effect against larvae of the
mosquitoes Aedes aegypti and Culex quinquefasciatus has been shown [149–151]. In addition,
oviposition deterrent activity towards these mosquitoes was found by Swathi et al. . A petrol
ether extract of the leaves showed promising activity as a pediculocide aginst head lice, Pediculus
humanus capitis .
A rather unusual preparation of P. pinnata was reported by Shanthi et al. : leaves extracted in
cow urine were reported to be a remedy for bacterial leaf blight in rice paddies.
The ethanol extract of the leaves was administered orally to mice in doses of 3.0–10.125 g/kg .
In the next 24 h no toxic symptoms or mortality were observed. In another study, no toxic effects were
observed in mice after dosages of 250 mg/kg of methanol leaf extract . An ethanolic flavonoid
extract of the leaves was non-toxic in human erythrocytes in vitro , and pongamol, an important
bioactive constituent of the plant, appeared non-toxic towards rats .
The leaves of P. pinnata have been used in the treatment of diarrhoea. The presented studies
indicate a potential antidiarrhoeal effect of the leaves. Until now, only the low-molecular weight
compounds of the leaves have been systematically described, and they comprise a number of
methoxylated furanoflavones. However, the chemistry of the aqueous extract investigated by
Brijesh et al.  has not been studied in detail. The plant leaves seems to have low toxicity. More
studies are needed to clarify the mode of action and to identify the constituents responsible for the
anti-diarrhoeal properties. The flavonoids in the plant might be correlated to this activity, although
numerous other constituents have been described. In sum, this plant appears to be of high interest, both
from a pharmacological and a phytochemical point of view.
2.5. Rhizophora mucronata Lamk. (Rhizophoraceae)
R. mucronata (Figure 9) is an evergreen small tree up to 15 m tall, with small white flowers and
long ovoid-conical fruits. The tree is distributed along muddy shores and tidal creeks in tropical zones
of East- and South Africa, Asia, Northeast Australia and Central America . “Bhora” is the local
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Figure 9. Rhizophora mucronata .
2.5.1. Traditional Use and Plant Parts Used
The bark is known as an astringent, and it has traditionally been used in the treatment of diabetes,
diarrhoea, nausea, haematuria, haemorrhages and angina [28,86]. The bark has been used for
extraction of tannins for the leather industry and for dyeing purposes which also continues today .
The traditional use of several mangrove plants including R. mucronata has recently been
2.5.2. Chemical Composition (Figure 10)
Tannins (hydrolysable) [72,86,159,160];
Triterpenoids: Lupeol, β-sitosterol, adene-5-en-3-ol, 3β-O-(E)-4-methoxycinnamoyl-15α-
Flavonoid: quercetin [161,163];
Phenolic acid: caffeic acid .
Indole: rhizophorine ;
Diterpenoids: gibberelline A3, A5 and A9, phytol [165,166];
Triterpenoids: β-amyrin, α-amyrin, betulin, lupeol, ursolic acid, squalene [86,167];
Sterols: cholesterol, stigmasterol, β-sitosterol,
Fatty acids: [166–168];
Tannins  and catechins (flavonoids)  have been reported, as well.
Triterpenoids: 3β-E-caffeoyltaraxerol, 3β-E-p-coumaroyltaraxerol, 3β-Z-p-coumaroyltaraxerol,
3β-Z-caffeoyltaraxerol, β-taraxerol ;
Sesquiterpenoid: mucronatone ;
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Unripe fruits are rich in tannins, the ripe ones are less so .
Diterpenoids: rhizophorin A–D [172–174];
Sugar alcohol: 1D-1-O-methyl-muco-inositol ;
25S-spirost-5-ene-3β,14α-diol (steroid sapogenin) has been reported, plant part not specified .
Figure 10. Constituents of Rhizophora mucronata bark (above) and leaves (below).
Caffeic acid Quercetin
Antidiarrhoeal and antiinflammatory activity of Rhizophora mucronata bark extracts were
reported by Rohimi and Das . Of the substances isolated, quercetin and caffeic acid appeared to
have highest activity as antidiarrhoeals. In addition, sitosterol, lupeol and adene-5-ene-3-ol were
anti-inflammatory, but did not show antidiarrhoeal effect. Antidiarrhoeal effect was also demonstrated
in a methanol extract of the leaves .
Antiviral activity has been investigated [177–179]. The ethanol bark extract was found to have high
activity against the Newcastle disease, vaccinia, encephalomyocarditis and Semliki Forest viruses.
Also the ethanol flower extract showed good activity, except against the vaccinia virus.
A polysaccharide from the bark protected cells from HIV-induced cytopathogenicity in vitro. Among
73 extracts of marine plants and mangroves, the bark of R. mucronata was the most promising antiviral
agent . Leaf methanol extracts exhibited antibacterial activity towards drug resistant Vibrio spp.
and S. aureus [180–182]. Hexane and chloroform extracts of leaves and roots of R. mucronata showed
strong inhibitory activity towards a series of bacteria and fungi . Ethanol-water extracts of the
bark and flowers showed antiplasmodial activity towards P. falciparum with IC50 values of
62 μg/mL (bark), 92 μg/mL (flowers) [184,185].
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Extracts of R. mucronata showed moderate antioxidant effect determined in the FRAP and DPPH
Honey from the flowers is reported to be poisonous . Scientific toxicity studies have, as far as
we know, not been carried out.
The bark of R. mucronata seems to have widest application in traditional medicine of this plant,
e.g., against diarrhoea. The few studies that have been performed seem to confirm the traditional use.
It appears reasonable that tannins and other polyphenolics in the bark may be involved in the
antidiarrhoeal properties. The antiviral, antibacterial and antifungal tests indicate promising bioactivity
of the bark and leaves. Toxicity studies should also be performed.
2.6. Xylocarpus granatum König (Meliaceae)
Xylocarpus granatum (Figure 11), also known as “dhundul” in Bangladesh, “cannonball tree” or
“puzzle nut tree”, is an evergreen tree with gray bark, up to 15 m in height. The fruits can be up to 25
cm in diameter . X. granatum is distributed in mangrove forests in East Africa, tropical Australia
and Southeast Asia [62,188]. The bark possesses extreme bitterness .
Figure 11. Xylocarpus granatum .
2.6.1. Traditional Use and Plant Parts Used
The astringent bark is used to treat fever, cholera, colic, diarrhoea and other abdominal
affections [28,86,190,191]. To treat diarrhoea, the bark is used traditionally as a water decoction
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prepared overnight . The bark has been used for tanning and for the preparation of dyes of umber
color . The fruits are also used against diarrhoea and externally to soothe inflammation [192,194].
An Indian patent application  describes the use of fruit seed coats of X. granatum for making an
antidiarrhoeal drug. Seed kernels are used in tonics, and the bitter and astringent oily fluid from the
seeds is taken for diarrhoea, dysentery, as an illuminant, and as hair oil .
2.6.2. Chemical Composition (Figure 12)
Flavonoids: catechin, epicatechin ;
Proanthocyanidins: procyanidin B1 (epicatechin (4β → 8) catechin), procyanidin trimer and
pentamer (composed of catechin as the starter and epicatechin as the extender units) [197,198];
Triterpenoids: gedunin, xyloccensins L–V, 6-dehydroxyxylocarpin D (limonoids) [197–203];
Condensed tannins: [72,86,160]. The bark is stated to contain more than 20% tannins .
Triterpenoid: gedunin (limonoid) ;
Tannins: (composition not specified) [160,204].
Sterols: cholesterol, campesterol, stigmasterol, sitosterol, 28-isofucosterol ;
Hydrocarbons and fatty acids ;
Long-chain aliphatic alcohol: triacontanol ;
Flavonoid: kaempferol 3-O-β-D-glucoside ;
Lactone: 3-(1-hydroxyethyl)-4,4-dimethyl-4-butyrolactone .
A large number of limonoids and protolimonoids (triterpenoids) have been described [190,206–223];
Sterols: ergosterol peroxide, β-sitosterol, daucosterol ;
Triterpenoid: hispidol B ;
Coumarin: scopoletin .
Triterpenoids: limonoids and protolimonoids [224–234], butyrospermol fatty acid esters ;
Sterols: daucosterol , β-sitosterol fatty acid esters ;
Peptide: aurantiamide ;
Flavonoid: catechin ;
Sesquiterpenoid: abscisic acid ;
Benzoic acids: 4-hydroxybenzoic acid, ethyl 3,4-dihydroxybenzoate ;
Alkaloids: xylogranatinin , granatoin ;
α-Tocopherol (vitamin E) .
The chemistry of the genus Xylocarpus has been reviewed .
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Figure 12. Catechins and proanthocyanidins (above) and limonoids (below) from
Xylocarpus granatum bark.
Epicatechin (top), catechin (below)
N = 1: Epicatechin(4->8)-catechin
N = 2: Epicatechin(4->8)epicatechin(4->8)catechin
N = 4: Epicatechin(4->8)(epicatechin)3(4->8)catechin
Gedunin Xyloccensin O
To scientifically investigate the antidiarrhoeal effect of X. granatum bark, Rouf et al. 
administered methanol extract of X. granatum bark to diarrhoeal induced mice and studied the effect
on gastrointestinal motility. The results showed a significant dose-dependent reduction in the total
number of faeces in 4 h after administration of 250 and 500 mg/kg methanol extract. The intestinal
transit of charcoal meal after peroral administration of 250 and 500 mg/kg of the extract was
significantly reduced as well.
The methanol extract from X. granatum bark showed antibacterial action against Kocuria
rhizophilia, S. aureus, B. subtilis and P. aeruginosa in the disc-diffusion assay . Growth of E. coli
and C. albicans was not affected.
Ethanol extracts of pericarp and seeds of X. granatum inhibited the growth of the pathogenic
bacterium Acinetobacter baumannii . Extracts of the stem bark made with different solvents
showed activity against Staphylococcus aureus, S. epidermis, E. coli, Shigella boydii and Proteus sp.,
but were inactive towards Shigella dysentery, Salmonella typhi and Enterococci . Xyloccensins
isolated from X. granatum have been tested as antimicrobial agents. In the first study, the limonoid
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gedunin (0.5%–2.0% solutions of gedunin was impregnated into wood blocks) isolated from the stem
was found to exhibit antifungal activity against the wood-rot fungi Polyporus palustris and
P. versicolor . 3-(1-Hydroxyethyl)-4,4-dimethyl-4-butyrolactone showed fungicidal activity
towards powdery mildew . Xyloccensin I, J, O and P were found to have no antimicrobial
effects [190,198], and hexane leaf extracts and and methanol stem extracts of X. granatum were found
inactive or nearly inactive towards a series of fish pathogenic bacteria .
Some of the limonoids have antifeedant effect towards larvae of Mythimna separata .
Gedunin and photogedunin had antifilarial activity towards the human parasite Brugia malayi ,
and a chloroform extract of the fruits of X. granatum showed antimalarial activity against
Plasmodium falciparum . The activity was ascribed to gedunin and xyloccensin-I.
Gedunin and photogedunin from X. granatum had anti-secretory effect and were protective
against peptic ulcer in mice . Gedunin also inhibited the growth of Caco-2 colon cancer cells
in vitro .
It is reported that the plant is used by the Orange-Dyakouns of the Malay-Peninsula to prepare their
poison “ipokrohi” . However, scientific toxicity studies have not been carried out on this plant.
The bark from X. granatum is widely used in tropical Asian countries as an antidiarrhoeal agent,
and the pharmacologic effect of the methanolic bark extract has been demonstrated . The
methanol extract contains high amounts of flavan-3-ols and procyanidins . Proanthocyanidin-rich
plants have a long tradition of use as antidiarrhoeals in folk medicine , and this class of compounds
may contribute to the observed effects. Inhibitory activity towards bacteria involved in gastrointestinal
disease may also be of importance. Chemical studies of X. granatum have also shown a high variety of
tetranortriterpenoids in lipophilic extracts of the seeds, fruits and stem bark. Until now, more than
50 limonoid derivatives have been identified. However, further studies are necessary both to identify
the active antidiarrhoeal compounds and their mode of action. Additionally, controlled clinical studies
are needed to evaluate the effects in humans. Finally, more toxicological data are necessary.
2.7. Xylocarpus moluccensis M. Roem (Meliaceae)
Xylocarpus moluccensis (Figure 13) is a glabrous, medium sized tree that grows in the tropical
mangroves spanning from East-Africa to Philippines, Australia and the Pacific Islands . In
Bangladesh, the tree grows in the north tract, remote from the sea, chiefly in the low lying swampy
locality of the Sundarbans. The local name in Bangladesh is “passur” .
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Figure 13. Xylocarpus moluccensis. Note: this picture is reproduced with permission of
Ron Yeo. Copyright © 2013 Ron Yeo (Ron Yeo@tidechaser.blogspot.com).
2.7.1. Traditional Use and Plant Parts Used
The bark is used as an astringent and a febrifuge, and has been used traditionally in the treatment of
fever, dysentery, diarrhoea and other abdominal troubles . Fruits from X. moluccensis have been
used to cure swellings of the breast and elephantiasis [28,243] and (powdered or as a decoction)
against diarrhoea . An ointment prepared from seed ash, sulphur and coconut oil is used as a cure
for itch .
2.7.2. Chemical Composition (Figure 14)
Flavonoids: catechin, epicatechin ;
Proanthocyanidins: procyanidin B1 (epicatechin (4β → 8) catechin), procyanidin B3 (catechin
(4α → 8) catechin), procyanidin trimer, procyanidin pentamer, procyanidin hexamer, procyanidin
decamer and procyanidin undecamer (non-hydrolyzable tannins) .
Triterpenoids: limonoids [247–249];
Fatty acid: 4-oxo-19-phenylnonadec-5-enoic acid .
Triterpenoids: limonoids ;
Monoterpenoid: (secoiridoid): xylomollin .
Triterpenoids: limonoids [190,247,248,253–261], tirucallane-type triterpenoids ;
Protein, minerals and fatty acids .
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Figure 14. Proanthocyanidins from Xylocarpus moluccensis bark.
N = 5: Epicatechin(4->8)(epicatechin)4(4->8)catechin (procyanidin hexamer)
N = 9: Epicatechin(4->8)(epicatechin)8(4->8)catechin (procyanidin decamer)
N = 10: Epicatechin(4->8)(epicatechin)9(4->8)catechin (procyanidin undecamer)
2.7.3. Bioactivity Studies
In castor oil- and magnesium sulphate-induced diarrhoeal mice the methanol bark extract of
X. moluccensis (250 and 500 mg/kg) reduced the severity of diarrhoea dose-dependently . The
methanol fraction (500 mg/kg) did also reduce the intestinal transit of charcoal meal in mice. In the
same study, the ethyl acetate and residual methanol fractions at 250 mg/kg showed an even stronger
antidiarrhoeal effect while the chloroform soluble fraction was inactive.
The antibacterial effects of the methanol crude extract, the chloroform and ethyl acetate soluble
fractions and the residual methanol fraction have been investigated . The disc-diffusion method
was employed with 500 μg of extract per disc. The methanol crude extract was active against E. coli,
V. cholerae, S. dysenteriae, S. aureus, Staphylococcus epidermis, Staphylococcus pyogenes,
Salmonella typhi, P. aeruginosa and Enterobacter aerogenes. The growth of Shigella boydii,
S. flexneri and Shigella sonnei were not affected. The tested bacteria are associated with diarrhoea
The limonoids of X. moluccensis seeds have been investigated for insecticidal, pesticidal and
anti-feedant effects, with many of them being found active [254,256,258,260,261]. Some of these
applications have been patented [263,264].
7-Deacetylgedunin from X. moluccensis seeds has anti-inflammatory activity , and
7-oxo-deacetoxygedunin inhibits osteoclastogenesis and has been suggested as a possible treatment for
Methanolic extracts of bark and pneumatophores of X. moluccensis had CNS depressant properties,
with the pneumatophore extract showing the highest activity .
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Methanolic and aqueous extracts of X. moluccensis pneumatophores showed cytotoxicity towards
two human cancer cell lines, but were inactive against normal mouse fibroblast cells .
X. moluccensis bark has shown significant antidiarrhoeal effect in mice models. The mode of action
may be exerted by antisecretory mechanisms, by preventing the reabsorption of water and by delaying
the gastrointestinal transit, and by a direct antibacterial activity. The traditional use of bark from
X. moluccensis as an antidiarrhoeal agent can likely be ascribed to its content of flavan-3-ols and
procyanidins which are found in high content in the methanol crude extract and in fractions that are
polar and semipolar. X. moluccensis is rich in lipophilic limonoids. Since the chloroform soluble
fraction was inactive in the antidiarrhoeal test, the lipophilic limonoids probably do not contribute to
the observed biological effect. Recent research has, however, shown a variety of other biological
effects for these compounds. Toxicity studies and controlled clinical studies are warranted to make the
human use of this herbal medicine safer.
3. General Discussion
This review indicates that D. peregrina, I. coccinea, P. pinnata, R. mucronata, X. granatum, and
X. moluccensis may be considered as potential sources of antidiarrhoeal phytomedicines or herbal
drugs. They show promising potential, since their intake may counteract the diarrhoeal gastrointestinal
symptoms in animal models and act against pathogenic microorganisms that cause diarrhoea.
For H. littoralis, less scientific evidence has been obtained at present, in spite of its documented
traditional use in treatment of diarrhoea. However, the scientific literature concerning antidiarrhoeal
effects of most plant remedies is quite limited, and on the basis of the available information we are not
able to recommend one single species for future exploitation as an antidiarrhoeal drug in this area.
Additional investigations are required to elucidate the exact mechanism of action and possible toxic
effects. Properly designed clinical trials of promising herbal medicines should also be performed to
ascertain the optimal dosages, formulation and effects. A common feature of several of the presented
antidiarrhoeal plants is the high content of tannins or proanthocyanidins, which are known from
previous studies to have antidiarrhoeal activities [266–268]. The efficacy of some flavonoids,
e.g., catechins and proanthocyanidins, and proanthocyanidin-rich extracts as antidiarrhoeal agents has
been shown in a number of investigations [21,269–271]. Since proanthocyanidins usually are very
good antioxidants, it is noteworthy that well known inducers of dysentery such as S. dysenteria
toxin  and Entamoeba histolytica lectin  have been reported to increase oxidative stress in
intestinal cells. A similar pro-oxidative effect has been reported for chronic diarrhoea . In
addition, ulcerative colitis has been suggested to be related to neutrophil-dependent oxidative
stress . It is plausible that phenolic compounds are involved in the medical effects of several of
the plants from Bangladesh discussed in this review. In many cases, the bark is the part of the plant
traditionally used to treat diarrhoea, and barks are often good sources of tannins. However, the extracts
showing positive effects should be investigated further by biological activity-guided searching for
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active compounds which may lead to concentrated extract with bioactive compounds, excluding toxic,
unhealthy and undesirable substances.
Every year, thousands of people in Bangladesh and millions worldwide are affected by diarrhoeal
diseases. Especially children are suffering. For the rural people in Bangladesh it is extremely important
to have access to safe and effective medicines to reduce the mortality and morbidity of diarrhoea. In
order to reach that goal, development of local resources such as traditional plant medicines may be a
good solution. An increased focus on phytomedicines with antidiarrhoeal effects may help relieving
the local population from symptoms, disease and death. A local utilization of medicinal plants for the
development and production of herbal medicines and/or phytomedicines may also give the people
involved work and income, securing their private economy. Protection of intellectual property rights
has to be maintained when exploring the plant material in order to produce phytomedicines and herbal
drugs for commercial use, e.g., local production, local sale, simple procedure, income to local
community. It is important to guarantee that appropriate institutions, local communities or other
involved parts get a fair compensation for their knowledge. From an ecological point of view,
sustainable uses of the species have to be guaranteed, as well. It is well known that mangrove forests
are threatened as ecosystems. All over the world mangrove forests disappear due to deforestation,
urbanization, global changes and pollution. Industrialized fishery, shrimp farming and plantations of
rice, coconut and palm oil lead to deforestation, and the result may be that the basis for existence of the
mangrove species disappears [23,65,70].
As previously pointed out, diarrhoea is a major problem among children, and therefore the
development of antidiarrhoeal preparations to children should be a research purpose of high priority.
However, drug pharmacokinetics is different in children than in adults, differing in the adsorption,
distribution, metabolism and excretion of drugs. The children can be even more susceptible to the toxic
and adverse effects of plant products than adults, and even if the medicines are safe for adults, one
should be careful administrating the same agents to children until safety studies have been performed.
Today, limited information is available about the efficacy and safety of herbal medications in children.
Because of these factors, there is an increased risk carrying out clinical studies in children compared to
Natural products may have advantages compared to conventional modern medicines. The complex
content of chemicals may have multiple targets of action and might therefore have several potential
effects against diarrhoeal diseases. The involvement of synergistic effects is likely too, e.g., astringent
and antibacterial effect in combination with decreased intestinal movements. Thus, separating the
individual components of a plant extract may lead to loss of activity, since it is often the unique
combination of chemical compounds that contribute to the desired effect. Natural products also have a
benefit, especially in developing countries, since the costs are much lower compared to modern
pharmaceuticals. The majority of the world’s population (60%–70%) relies solely upon medicinal
plants as treatment for diseases . One important reason is the high costs of drugs produced by the
pharmaceutical industry, but cultural and social factors are also influencing the choice of drug.
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In conclusion, we have found that some of the plants used as antidiarrhoeals in the Sundarbans
contain constituents that make their efficacy in this respect likely. For six of the plants discussed in this
paper (D. peregrina, I. coccinea, P. pinnata, R. mucronata, X. granatum and X. moluccensis),
pharmacological experiments support this conclusion. Clinical studies and tests for toxicity are largely
missing, and such experiments should be carried out in order to have a basis on which plants to
recommend as phytomedicines useful against diarrhoea.
The authors are grateful to Ron Yeo for permission to use his picture of Xylocarpus moluccensis in
this article. For other pictures, Wikimedia Commons is acknowledged.
Conflict of Interest
The authors declare no conflict of interest.
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