Terminalia chebula: A review on its Pleiotropism

Abstract

Herbal drug products have a special place in the world of pharmaceuticals whose popularity is continuously increasing worldwide. Terminalia chebula is a species
of Terminalia, native to India, Nepal, China, Sri Lanka, Malaysia and Vietnam. It is a deciduous tree growing tall with leaves alternate to subopposite in
arrangement and fruit is drupe-like blackish with five longitudinal ridges. A number of chemical constituents have been isolated from the plant extract that
include chebulin, ellagic acid, 2,4-chebulyl-D-glucopyranose, arjunglucoside I, arjungenin, chebulinic acid, gallic acid, ethyl gallate, punicalagin, terflavin A,
terchebin, luteolin and tannic acid. The plant has been reported to possess various pleiotropic effects such as antioxidant, antidiabetic, renoprotective,
hepatoprotective, immunomodulator and prokinetic effect. The review elucidates about various phytochemicals and pleiotropic effects exhibited by the plant.
Moreover, therapeutic effects associated with the plant have been clearly mentioned.
Key words: Herbal, Terminalia chebula, Pleiotropic, Therapeutic

Full text

Journal of Pharmacy Research Vol.4.Issue 9. September 2011
M.U. Khan et al. / Journal of Pharmacy Research 2011,4(9),3037-3039
3037-3039
Review Article
ISSN: 0974-6943 Available online through
www.jpronline.info
*Corresponding author.
Dr. M.U. Khan, PhD.
Associate Professor,
Sri Sai College of Pharmacy,
Badani, Pathankot-145001,
Punjab, India
Tel.:09646806032
E-mail:masihkhan.1980@rediffmail.com
INTRODUCTION
Terminalia chebula: A review on its Pleiotropism
M.U. Khan1*, Ankur Rohilla2, Deepika Bhatt1, Shadan Afrin1,Seema Rohilla2, S.H. Ansari 3
1Sri Sai College of Pharmacy, Badani, Pathankot-145001, Punjab, India
2Department of Pharmaceutical Sciences, Shri Gopi Chand Group of Institutions, Baghpat-250609, UP, India
3Facutly of Pharmacy, Jamia Hamdrd University, Delhi-110062, India
Received on: 19-05-2011; Revised on: 08-06-2011; Accepted on:01-07-2011
ABSTRACT
Herbal drug products have a special place in the world of pharmaceuticals whose popularity is continuously increasing worldwide. Terminalia chebula is a species
of Terminalia, native to India, Nepal, China, Sri Lanka, Malaysia and Vietnam. It is a deciduous tree growing tall with leaves alternate to subopposite in
arrangement and fruit is drupe-like blackish with five longitudinal ridges. A number of chemical constituents have been isolated from the plant extract that
include chebulin, ellagic acid, 2,4-chebulyl-D-glucopyranose, arjunglucoside I, arjungenin, chebulinic acid, gallic acid, ethyl gallate, punicalagin, terflavin A,
terchebin, luteolin and tannic acid. The plant has been reported to possess various pleiotropic effects such as antioxidant, antidiabetic, renoprotective,
hepatoprotective, immunomodulator and prokinetic effect. The review elucidates about various phytochemicals and pleiotropic effects exhibited by the plant.
Moreover, therapeutic effects associated with the plant have been clearly mentioned.
Key words: Herbal, Terminalia chebula, Pleiotropic, Therapeutic
Herbal system of medicines has been the oldest method of treatment since
ancient times because of its rich diversity and fewer side effects.[1,2] In addition,
immense improvements have been observed in modern systems of medicine,
but herbal drugs offer a rich source for health care to prevent the patients
amongst different pathological states.[3,4] Terminalia chebula, commonly known
as Harad related to family combretaceae, is a deciduous tree growing to 30 m
tall, with a trunk up to 1 m diameter. The leaves are alternate to subopposite
in arrangement, oval, 7-18 cm long and 4.5-10 cm broad with a 1-3 cm
petiole. The fruit is drupe-like, 2-4.5 cm long and 1.2-2.5 cm broad, blackish,
with five longitudinal ridges. Terminalia chebula native to southern Asia from
India and Nepal east to southwestern China (Yunnan), and south to Sri Lanka,
Malaysia and Vietnam.[5,6] In central India, where trees are leafless for short
period between April and August and fruiting from November to February;
while in Karnataka, flowering and fruiting occurs from January to September.
Moreover, various pleiotropic effects such as antioxidant, antidiabetic,
renoprotective, hepatoprotective, antianaphylactic, immunomodulator and
prokinetic (Fig. I) have been found to be associated with the plant. [7-10] The
review outlines the various phytochemical constituents exhibited by the plant
extracts. In addition, the pleiotropic pharmacological and therapeutic effects
of the plant have been critically discussed.
Phytochemical Constituents Associated with Terminalia chebula
The phytochemical screening of the plant extract showed the presence of
tannins (10-20%), which on hydrolysis gave chebulic acid and D-galloyl glucose.
Moreover, carbohydrates like glucose and sorbitol (major constituents) and
smaller amount of gentiobiose and traces of arabinose, maltose, rhamnose and
xylose have also been screened. In addition, Terminalia chebula have been
noted to possess about eighteen typical amino acids, some of which are; shikimic
acid, gallic acid, ß-sitosterol, daucosterol, triacontanoic acid, palmitic acid,
luteolin, tannic acid, tri-ethyl eser of chebulic acid and ethyl ester of gallic
acid.[11-13]. Further, the crude extract and the phenolics of Terminalia chebula
retz. fruit has been shown to possess 2,4-chebulyl-beta-D-glucopyranose, a
new natural product; and chebulinic acid, which were tested by ATP assay on
HOS-1 cell line.[14-15]
Pharmacological Literature in Support of Terminalia chebula
Terminalia chebula extract (TCE) have been found to possess various
pharmacological effects, a term referred to as its pleiotropic effects; due to
which the herbal drug is shown to provide a number of therapeutic uses, both
experimentally and clinically. The review obtained from the precedent studies
invole:
Antidiabetic and Renoprotective Effects
The anti-diabetic property of medicinal plants and its relationship with their
antioxidant potential have long been established. The methanolic extract of
Terminalia chebula, Terminalia belerica, Emblica officinalis and their
combination named ‘Triphala’ was found to inhibit lipid peroxide formation
and scavenge hydroxyl and superoxide radicals in the diabetic rats confirminf
their antidiabetic potential.[22]. Moreover, the antidiabetic and renoprotective
Cytoprotective Effect
Saleem et al. evaluated inhibition of cancer cell growth by crude extract and
the phenolics of Terminalia chebula fruit which was tested by ATP assay on
HOS-1 cell line. The results showed chebulinic acid, tannic acid and ellagic acid
as the most growth inhibitory phenolics of TCE fruit.[20] Moreover, the
cytoprotective effect on oxidative stress and inhibitory effect on cellular
aging of Terminalia chebula fruit was evaluated. In the peroxidation model
using t-BuOOH, the TCE showed a notable cytoprotective effect on the HEK-
N/F cells with 60.5 +/- 3.8% at a concentration of 50 microgm/ml. Further,
the life-span of the HEK-N/F cells was elongated by 40% as a result of the
continuous administration of 3 microgm/ml of the TCE when compared to
that of the control. These observations were attributed to the inhibitory
effect of the TCE on age-dependent shortening of the telomere; length shown
by the southern blots of the terminal restriction fragments (TRFs) of DNA
extracted from subculture passages.[21]
Hepatoprotective Effect
The hepatoprotective potential of Terminalia chebula (fruit) in preventing
liver toxicity caused by sub-chronic administration of rifampicin, isoniazid
and pyrazinamide in combination was investigated, which was chemically
characterized on the basis of chebuloside II as a marker against anti-tuberculosis
(anti-TB) drug-induced toxicity. The prominent anti-oxidative and membrane
stabilizing activities of TCE supported its hepatoprotective potential that was
further evidenced by reductions in biochemical observations alongwith the
histopathological studies.[19]
Antioxidant Effect
Terminalia chebula has been noted to be a potent antioxidant due to the
presence of the phenolic compounds present in its extract.[16,17] The aqueous
extract of the fruits of Terminalia chebula showed antioxidant activity as
confirmed by the fact that TCE from plants decreased lipid peroxidation and
plasmid DNA assay significantly.[17] Moreover, the antioxidant effects of aqueous
extract of Terminalia chebula in vivo and in vitro were demonstrated on the
tert-butyl hydroperoxide (t-BHP)-induced oxidative injuries that were observed
in cultured rat primary hepatocytes and rat liver. Treatment and pretreatment
of the hepatocytes with the TCE significantly reversed the t-BHP-induced cell
cytotoxicity and lactate dehydrogenase (LDH) leakage. In addition, TCE
exhibited in vitro ferric-reducing antioxidant activity and 2,2-diphenyl-1-
picryhydrazyl free radical-scavenging activities that further confirmed its
antioxidant potential.[18]

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effects of the chloroform extract of Terminalia chebula Retz. seeds in
streptozotocin-induced diabetic rats was investigated. The chloroform extract
of Terminalia chebula seeds produced dose-dependent reduction in blood glucose
of diabetic rats compared with standard drug glibenclamide in both short-and
long term study.[23]
Immunomodulatory Effect
Hamada et al. evaluated immunosuppressive effects of gallic acid and chebulagic
acid, the active phytoconstituents of TCE, on cytotoxic T lymphocyte (CTL)-
mediated cytotoxicity. It has been noted that gallic acid and chebulagic acid
blocked the CTL- mediated cytotoxicity. Moreover, gallic acid and chebulagic
acid has been shown to inhibit the killing activity of CD8+ CTL clone at IC50
values of 30 microM and 50 microM, respectively. Additionally, the granular
exocytosis in response to anti-CD3 stimulation was also blocked by gallic acid
and chebulagic acid that further evidenced its immunosuppressive effect.[24]
Antimicrobial Effect
Sato et al. evaluated the extraction and purification of effective antimicrobial
constituents of Terminalia chebula retz.against methicillin-resistant
Staphylococcus aureus. The examination of the EtOH extract of the fruiting
bodies of Terminalia chebula retz. showed the isolation of two potent
antimicrobial substances, gallic acid and its ethyl ester, which significantly
reduced the score of methicillin-resistant strains of Staphylococcus aureus
confirming its antimicrobial potential.[25]
Anaphylactic Effect
Inhibitory action of water soluble fraction of Terminalia chebula on systemic
and local anaphylaxis has also been evaluated. The effects of the water soluble
fraction of Terminalia chebula showed the reductiobn and frequency of
anyphylactic shock that further confirmed the fact that it may possess a
strong antianaphylactic action.[26]
Antibacterial Effect
Malekzadeh et al. evaluated the antibacterial activity of black myrobalan
(Terminalia chebula Retz) against Helicobacter pylori. The effect of ether,
alcoholic and water extracts of black myrobalan on Helicobactor pylori were
examined using an agar diffusion method on columbia agar, which showed that
the TCE extracts contain a heat stable agent that was responsible for reduction
in colony formation of the bacteria confirming its antibacterial potential.[27]
Anticaries Effect
The potential of the aqueous extract of Terminalia chebula as an anticaries
agent have also been evaluated. The extract strongly inhibited the growth,
sucrose-induced adherence and glucan-induced aggregation of S. mutans. In
addition, rinsing the mouth with the extract significantly reduced total bacterial
counts and the total streptococcal counts in the saliva samples obtained after
three hours of rinsing, compared with the counts obtained after placebo rinsing
confirming its anticaries effect.[28]
Prokinetic Effect
Proper gastric emptying has been associated with the correct therapeutic
effects shown by the drug therapy and thus, it is essential that the gastric
emptying process remains proper. The oral administration of Terminalia
chebula on gastric emptying has been investigated to confirm its potent
prokinetic effect. Metoclopramide significantly increased the gastric emptying
(76.33 +/- 12.37%; p < 0.01) and atropine inhibited the motility percent
gastric emptying (7.26 +/- 19.76%; p < 0.01). TCE was found to increase the
percent gastric emptying (86.57 +/- 6.65%; p < 0.01), which showed that TCE
may serve as an useful alternative to prokinetic drugs available.[29]
Antiarthritic Effect
The antiarthritic potential of Terminalia chebula has been evaluated in mouse
model of arthritis. The suppression of the onset and progression of collagen-
induced arthritis by chebulagic acid obtained from the immature seeds of
Terminalia chebula confirms its antiarthritic potential with a mechanism
involving suppression of T cell activity. This study examined the effectiveness
of TCE against the onset and progression of collagen-induced arthritis in
mice.[30]
Radiationprotective Effect
Studies have evaluated the radiation protection by Terminalia chebula that
involve certain mechanistic aspects. The administration of TCE (80 mg/kg
body weight, i.p.) prior to whole body irradiation of mice (4 Gy) resulted in a
reduction of peroxidation of membrane lipids in mice liver as well as a decrease
in radiation-induced damage to DNA, as assayed by single-cell gel electrophoresis
(comet assay). In addition, TCE protected the human lymphocytes from
undergoing the gamma radiation-induced damage to DNA exposed in vitro to
2 Gy gamma-radiations. These results suggested the radioprotective ability of
Terminalia chebula.[31,32]
Theraputic Benefits of Terminalia chebula
Based upon the pleiotropic effects exhibited by the plant drug, it has been
noted to offer a number of therapeutic effects. Terminalia chebula has been
used in management of bleeding piles.[33] Moreover, it has been noted to treat
hyperlipidemia as it lowers the level of total lipids content, serum triglycerides
levels, low density lipoprotein (LDL) and very low density lipoprotein (VLDL)
levels.[34]. Studies have revealed its antacid properties that have a therapeutic
role in releving constipation and also show good effects in releving symptoms
of indigestion, belching, nausea and vomiting.[35]. In addition, Terminalia chebula
has been used as a potential therapy in the treatment of candidiasis and other
microbial infections.[36,37] Moreover, Terminalia chebula has been known to
inhibit tyrosinase, the enzyme which is involved in depigmentation of skin
and thus provides sympatomatic rekief in skin allergies and infections.
Terminalia chebula has been reported to protect the epithelial cells against
influenza A virus infection.[38] Furthermore, Terminalia chebula is used to
inhibit immediate hypersensitivity reaction that confirms its role in allergic
conditions.[26,39]. In addition, it is used in people having leprosy, anemia, chronic
intermittent fever, heart disease, diarrhoea, anorexia, cough and excessive
secretion of mucus and a range of other complaints and symptoms.[40,41]
CONCLUSION
Terminalia chebula has long been used since ages because of its rich ethnomedical
significance. A number of phytochemical constituents have been found to be
associated with the plant extract that include mainly the different types of
amino acids like shikimic acid, gallic acid, ß-sitosterol, daucosterol,
triacontanoic acid, palmitic acid, luteolin, tannic acid, tri-ethyl eser of chebulic
acid and ethyl ester of gallic acid. Moreover, numerous pleitropic effects have
been exhibited by the plant including antioxidant, antidiabetic, renoprotective,
hepatoprotective, antianaphylactic, immunomodulator and prokinetic effects.
The pleitropism shown by the plant makes it the choice of herbal drug therapy
in a number of therapeutic uses. However, further investigations on
identification of the active principles and their mechanism of action are
needed to untie the molecular mechanisms involved in these observed effects
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Source of support: Nil, Conflict of interest: None Declared