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In vitro and in vivo studies of antidiabetic Indian medicinal plants: A review

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Journal of Herbal Medicine and Toxicology 3 (2) 9-14 (2009)
ISSN : 0973-4643 Original Article

IN VITRO AND IN VIVO STUDIES OF ANTIDIABETIC INDIAN


MEDICINAL PLANTS: A REVIEW

B. Dinesh Kumar*, A. Mitra and M. Manjunatha


School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721 302
*Corresponding author E-mail: dkb@iitkgp.ac.in
Received : 10 May, 2009 Revised : 20 June, 2009 Accepted : 20 July, 2009
ABSTRACT: Many medicinal plants have been used for the treatment of diabetes
mellitus in Indian system of medicine and in other ancient systems of the world.
Medicinal plants are significant source of biological compounds and many of the
currently available biological compounds have been derived directly or indirectly from
them. The major focus of this review is on anti-diabetic activity of medicinal plants
like Achillea ligutica, Aegles marmelos, Andrographis paniculata, Azadirachta indica,
Allium sativum, Bergenia ciliata, Brassica juncea, Commelina communis, Euonymus
alatus, Ficus bengalensis, Gymnema sylvestre, Mangifera indica, Medicago sativa,
Momordica charantia, Murraya koenigii, Pterocarpus marsupium, Syzigium cumini,
Trigonella foenum graecum, Tinospora cripa, Tournefortia haetwegiana (active
constituents and crude extracts). These medicinal plants act on various mechanisms-
either by acting directly on pancreas and stimulate insulin levels in blood or by altering
the activities of regulatory enzymes in different pathways like glycolysis, gluconeogensis
and thus producing effects on tissues like liver, muscle, adipose tissue etc. All medicinal
plants, as specified, have shown different degrees of anti-diabetic activity.
Keywords - Medicinal Plants; Diabetes; hypoglycemic; Animal model; â-cell lines
INTRODUCTION
Diabetes is one of the major diseases for morbidity Treatment to diabetes by western classical medicines
and mortality in worldwide[1]. The different factors is costly[5]. Many herbal therapies have been
leading to increased prevalence of diabetes are recommended for the treatment of diabetes. The
population growth, aging, urbanization, obesity and ethno botanical information reports about 800 plants
physical inactivity. The economic impacts of diabetes that may have anti-diabetic activities[6]. Indian
with its complications and associated diseases are medicinal plants such as Azadirachta indica,
large [2]. According to recent estimates the Gymnema sylvestre, Momordica charantia,
prevalence of diabetes mellitus is 4% worldwide and Murraya koenigii, Mangifera indica, Swertia
that indicates 143 millions persons are affected which chirayita, Syzigium cumini, Trigonella foenum
will increase to 300 million by the year 2025[3]. In graecum have been shown to possess hypoglycemic
urban India, mortality rates are two fold higher in activities[7-14]. Bio-active herbal ingredients are
people with diabetes compared to non-diabetic admixtures of many chemical compounds (alkaloids,
subjects[4]. Three types of diabetes of interest to our glycosides, triterpenes, polysaccharides, and saponins
group are: insulin-dependent diabetes mellitus etc) and some of them have documented anti-diabetic
(IDDM), non-insulin-dependent diabetes mellitus activities[15]. Oral hypoglycemic agents such as
(NIDDM), and malnutrition-related diabetes mellitus biguanides, sulphonylureas and thiozolidinediones are
(MRDM), the later affects young people in poor available along with insulin for the treatment of
tropical countries and is linked to a history of nutritional diabetes. But they have side effects associated with
deficiency. their uses[16]. There is a growing interest in herbal

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Journal of Herbal Medicine & Toxicology

remedies because of their effectiveness, minimal side on insulin secretion by clonal BRIN-BD11 pancreatic
effects in clinical experiences and relatively low costs. B-cells[25].
Herbal drugs or their extracts are prescribed widely,
In vitro studies using α-amylase inhibition assay
even when their biological active compounds are
unknown as they are being traditionally used[17]. Methanolic extract of Achillea ligutica showed higher
Thus, studies with medicinal plants extracts are useful antioxidant activity by using 2, 2-diphenyl-1-
to know their efficacy, mechanism of action and picrylhydrazyl (DPPH) and lipid peroxidation assay.
safety. This article reviews in vitro and in vivo models However, assay for α-amylase inhibition of n-hexane
anti-diabetic activities of crude extracts or active extract from Achillea ligutica showed higher anti-
constituents isolated from some Indian medicinal diabetic activity than its methanolic extract [26]. In
plants. vitro α-amylase inhibitory activities of seven
indigenous medicinal plants of Mauritius( namely coxi
Invitro studies on glucose uptake
lacryma-jobi (Poaceae), Aegle mamelos (Rutaceae),
Kaempferol and quercetin form Euonymus alatus Artocarpus heterophyllus (Moraceae), Vangueria
could significantly improve insulin-stimulated glucose madagascariensis (Rubiaceae), Azadirachta indica
uptake in mature 3T3-L1 adipocytes[18]. Aqueous (Meliaceae), Eriobotrya japonica (Rosaceae) and
extract of Momordica charantia showed significant syzigium cumini (Myrtaceae) were showed that only
cell repairing effects and stimulation of insulin Artocarpus heterophyllus could be useful in lowering
secretion in HIT-T15 Hamster pancreatic â-cells[19]. of blood glucose levels [27]. Ethanolic extract of
Methanolic extract of Aegles marmelos and Andrographis paniculata showed α-glucosidase
Syzygium cumini showed glucose transport activation inhibitory effects in a concentration dependent
in a PI3 kinase-dependent fashion in L6 myotubes[20]. manner. It further showed weak á-amylase inhibitory
Methanol extract of Pterocarpus marsupium showed activity. The results indicated that Andrographis
glucose transport activity in a PPARã mediated PI3 paniculata could be considered as a potential
kinase dependent fashion as well as isoflavone from candidate for the management of type 2 diabetes
Pterocarpus marsupium showed glucose transport mellitus [28].
activity in a PPARã mediated but PI3 kinase
In vitro and in vivo studies using á- glucosidase
independent fashion[21].
inhibition assay
In vitro studies using insulin- secreting cell lines
Isolated compounds such as (-)-3-O-
Alcoholic extract of Gymnema sylvestre (GS4) galloylepicatechcin and (-)-3-O-galloylcatechcin from
produced a dose-related increase in insulin release Bergenia ciliate showed significant anti-diabetic
from a variety of beta cell lines Such as HIT-T15, activity by inhibiting intestinal α-glucosidase and
MIN6 AND RINm5F. Insulin release depends on by porcine pancreatic α-amylase [29]. Methanolic
permeabilization of beta cell plasma membrane and extract of Tournefortia haetwegiana showed anti-
channel-independent ca2+ influx into the beta cells[22]. diabetic activity by inhibiting the intestinal α-
Tinospora cripa extract showed insulinotropic action glucosidase enzyme in diabetic rats [30]. Aqueous
in HIT-T15 cell line due to presence of insulin extract of Commelina communis L. showed α-
secretagogue in the extract which causes an increase glucosidase inhibitory activity in a dose dependent
in cytosolic ca2+ - uptake from extracellular medium manner, in vitro and produced significant anti-
and inhibiting ca2+ - efflux from the cytosol[23]. hyperglycemic activity in diabetic mice due to inhibition
Incubation of glucose-responsive BRIN-BD11 cells of α-glucosidase[31].
with aqueous extract of Medicago sativa (Lucerene)
In vivo Antidiabetic Activity studies in animal
showed dose dependent stimulation of insulin secretion
models
at low glucose concentration. Administration of
Lucerne in the diet (62.5g/kg) and drinking water (2.5 Allium sativum: Lahasun (Hindi)
g/l) reduced the hyperglycaemia in streptozotocin-
Garlic (Allium sativum L., Liliaceae) is a common
diabetic mice[24]. Aqueous extract of Viscum album
spicy flavoring agent used since ancient times. Oral
(mistletoe) had a dose-dependent stimulatory effect

10
B. Dinesh Kumar et al.

administration of garlic ethanolic extract (0.1, 0.25, sylvestre leaves per day decreased insulin
0.5 g/kg of body weight) showed anti-diabetic effect requirements with lowered HbA1c levels in patients
in diabetic rats[32]. In vivo treatment with aqueous suffering from type 2 diabetes[41]. Better glycaemic
garlic extract (100mg/kg/day; intra-peritoneal, for 8 control can be obtained with GS4 (an extract from
weeks) inhibited the development of abnormalities in leaves of Gymnema sylvestre) supplementation in
vascular reactivity induced by diabetes in diabetic Type 2 diabetic patients[42]. Feeding of powdered
rats[33]. Daily Oral administration of 1 ml of either leaves of Gymnema sylvestre to beryllium-exposed
onion or garlic juices/100mg body weight for four week rats tend to decreased blood sugar levels[43].
showed hypoglycemic effects in alloxan diabetic
Mangifera indica: Aam (Hindi)
rats[34].
Mangifera indica (family: Anacardiacea) is used
Azadirachta indica: Neem (Hindi)
medicinally in tropical Africa. aqueous extract of
Neem (Azadirachta indica) is an evergreen tree, Mangifera indica Linn stem bark showed Anti-
cultivated in various parts of the India subcontinent. inflammatory, analgesic, and anti-diabetic activities due
Neem has been extensively used in ayurveda, unani to different chemical constituents, especially the
and homoeopathic medicine and has become a polyphenolics, flavonoids, triterpenoids, mangiferin and
cynosure of modern medicine. Azadirachta indica other chemical compounds present in the plant[44].
leaf extract (200mg/kg) showed reduction of Intra-peritoneal administration of mangiferin isolated
peripheral utilization of glucose and glycogenolytic from Mangifera indica exhibited potent antioxidant
effect due to epinephrine action [35]. It also blocked effects and ameliorates glycosylated haemoglobin
the inhibitory effect of serotonin on insulin secretion levels in diabetic animals[45]. Chronic intra-peritoneal
mediated by glucose [36]. administration of mangiferin (10 and 20mg/kg) once
daily for 28 days showed antidiabetic activity in
Brassica juncea : Rai (Hindi)
diabetic rats[46].
In common terminology, seeds of Brassica juncea
Momordica charantia: Karela (Hindi)
are called as Rai and commonly used spice in various
food items in India. Various strengths (5%, 10%, and Momordica charantia (family, Cucurbitaceae),
15%) of Brassica juncea seed diet were studied in commonly known as karela or bitter melon. It is used
alloxan induced diabetic albino rats. Brassica juncea as a vegetable in the Indian subcontinent. Effects of
diet (10 and 15%) showed significant long term feeding (10 weeks) of Momordica
antihyperglycemic effect in alloxan diabetic rats [37]. charantia fruit extract showed hypoglycemic, strong
Powdered Murraya koeginii leaves (15%) and hypolipidemic properties in streptozotocin induced
Brassica juncea seed (10%) showed only a weak diabetic rats [47]. Water soluble hypoglycemic peptide
anti-hyperglycemic activity in severe hyperglycemic in Momordica charantia L. Var. addreviata Ser.
state in streptozotocin diabetic rats[38]. (MCV) fruit aqueous extract showed hypoglycemic
activity in alloxan induced diabetic mice[48]. Treating
Gymnema sylvestre : Gudmar (Hindi)
alloxan- induced diabetic rats with Momordica
Gymnema sylvestre (family Asclepiadaceae), a charantia and Andrographis paniculata increased
woody climber growing in unkempt tropical forest of Body weight and reduced blood sugar levels. Further
the central and southern parts of India. Ii has been Momordica charantia and Andrographis
used as an adjunct in the treatment of diabetes mellitus paniculata restore the impaired estrous cyclicity in
in ancient India. Water soluble extract of Gymnema alloxan-induced diabetic rat[49].9 Treatment with
sylvestre leaves decreased blood sugar levels by 400mg/day of aqueous extracts of Momordica
regeneration of the pancreatic islets and beta cells in charantia and Eugenia jambolana for 15 days
diabetic rats[39]. Water soluble fraction of alcoholic substantially prevented hyperglycemic and
extract of Gymnema sylvestre leaves decreased the hyperinsulinemia in fructose fed rats[50]. Oral feeding
glycogen content of the tissue in glucose fed rat, but of Momordica charantia fruit juice involved renewal
failed to alter the glycogen content in normal rats[40]. of beta cells in streptozotocin diabetic rats[51].
A dose of 400mg water soluble extract of Gymnema Alcoholic extract of Momordica charantia fruit

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Journal of Herbal Medicine & Toxicology

showed hypoglycemic action due to stimulation of effects of Eugenia jambolanan seed kernel
glycogen synthesis in the liver of streptozotocin- decreased oxidative stress in sterptozotocin diabetic
induced diabetic rats[52]. rats, which inturn may be due to its hypoglycemic
property[62]. Oral administration of aqueous extract
Murraya koenigii: Kurry patta (Hindi)
of syzigium cumini bark showed beneficial effect on
Murraya koenigii (L.) Spreng (family: Rutaceae) is glycoproteins in addition to its anti-diabetic action in
an aromatic pubescent shrub or small tree commonly streptozotocin induced diabetes rats [63].
known as ‘curry patta’ in India. The plants originated
Trigonella foenum graecum (Fenugreek): Methi
in Tarai regions of Uttar Pradesh, India and now
(Hindi)
widely found in all parts of India. The oral
administration of aqueous extract of Murraya The seeds of Trigonella foenum graecum, a
koenigii leaves decreased plasma lipid levels leduminous annual plant belonging to the family
associated with diabetes mellitus[53]. The ethanolic Fabaceae and commonly called fenugreek or methi
extract of Murraya koenigii leaves exhibited anti- are used as a condiment in the Indian sub-continent
hyperglycaemic as well as antioxidant activity in and in Mediterranean countries. Oral administration
experimental rats and it was observed that antioxidant of Trigonella seed powder (5% in the diet) for 21
potential of Murraya koenigii may be responsible days in alloxan-induced diabetic rats showed excellent
for its anti-diabetogenic properties[54]. The ethanolic antidiabetic effects in experimental Type-1 diabetes
leaf extract significantly decreased the level of blood without such complications [64]. Feeding of fenugreek
glucose in experimental diabetic rats [55]. The (Trigonella foenum graecum) seed mucilage and
aqueous extract of Murraya koenigii leaves spent turmeric (curcuma longa) showed anti-diabetic
produced hypoglycemic activity in normal and alloxan actions in streptozotocin induced diabetic rats.
diabetic dogs [56]. Feeding different doses (5, 10 and fenugreek seed mucilage compared with spent
15%) of Murraya koenigii leaves to diabetic rats turmeric was more effective in ameliorating diabetic
showed hypoglycemic effect in mild diabetes [57]. state [65]. The soluble dietary fibre fraction of
Trigonella foenum graecum showed anti-
Syzigium cumini (Eugenia jambolana): Jamun
hyperglycemic effects and it had a tendency to reduce
(Hindi)
platelet aggregation in diabetic rats[66]. Fenugreek
Syzigium cumini, commonly known as ‘jamun’. The (Trigonella foenum graecum) seed powder when
jamnu belongs to the family Myrtaceae. The jamnu included in the daily diet of patients improves glucose
tree which is native to India thrives easily in tropical tolerance, serum insulin levels and also reduced the
climate and is found in many parts of our sub-continent 24 hour excretion of sugar in urine[67].
as well as countries of Asia and Eastern Africa. The
jamnu tree is a large evergreen, grown widely in the CONCLUSION
indogangetic plains and also in the cauvery delta of
Tamilnadu. Ethanolic and water extracts of fruit pulp The ethnopharmacological use of herbal medicine for
of Eugenia jambolana showed less and significant the treatment of diabetes mellitus is developed
anti-hyperglycemic in both mild and severe diabetic potentially as a preliminary point in the development
rabbits respectively [58]. Alcoholic and aqueous of alternative and inexpensive therapies for treating
extracts of syzigium cumini seed decreased tissue the disease. Many valuable drugs have been obtained
damage in diabetic rat brain and the results showed from plants over the years, including digitalis (Digitalis
that Effect of alcoholic extract was better than species), cinchona (cinchona species) and the pacific
aqueous extract [59]. Oral administration of 2.5 and yew (Taxus brevifolia Nutt.) [68]. India is facing
5.0 g/kg body weight of the aqueous extract of diabetic explosion. Many medicinal plants are being
syzigium cumini seed for 6 weeks showed used to treat diabetes since ancient times and have
hypoglycemic activity and antioxidant property [60]. served as an exemplary source of medicine. Herbal
Feeding of Eugenia jambolanan seed powder treatments are in practice both in patients with insulin
(500mg/kg body weight) showed antidiabetic activity dependent and non-insulin-dependent diabetes.
in streptozotocin-induced diabetic rats [61]. Ethanolic Medicinal plants continue to provide valuable anti-

12
B. Dinesh Kumar et al.
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