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Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al www.pharmasm.com 36 PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES A SYSTEMATIC REVIEW ON NATURAL MEDICINE USED FOR THERAPY OF DIABETES MELLITUS OF SOME INDIAN MEDICINAL PLANTS Donga J.J.*, Surani V.S., Sailor G.U., Chauhan S.P., Seth A.K. Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Vadodara-391760 ABSTRACT Diabetes mellitus is one of the world’s major diseases. It currently affects an estimated 143 million people worldwide and the number is growing rapidly. In the India, about 1- 5% population suffer from diabetes or related complication. Plant-based medicinal products have been known since ancient times, and several medicinal plants and their products (active natural principles and crude extracts) have been used to control diabetes in the traditional medicinal systems of many cultures worldwide. Several medicinal plants have found potential use as hypoglycemic in the Indian system of medicines. Several oral hypoglycaemic agents are the primary forms of treatment for diabetes. However, prominent side-effects of such drugs are the main reason for an increasing number of people seeking alternative therapies that may have less severe or no side- effects. In this review, we represent the profile of plants commonly used in India in the treatment of diabetes, reported in literature. A total of 45, 000 plant species have records of a popular use in the treatment of this syndrome in India. The profile presented includes information about scientific name, family, species, methodology used, the degree of hypoglycaemic activity and the active agents. Indian plants which are most effective and the most commonly studied in relation to diabetes and their complications are: Allium cepa, Allium sativum, Aloe vera, Beta vulgaris, Catharanthus roseus, Azadirachta indica, Gymnema sylvestre, Ipomoea batatas, Momordica cymbalaria,Momordica charantia, Ocimum sanctum, Pterocarpus marsupium, Swertia chirayita, Tinospora cordifolia, and Trigonella foenum graecum. All plants have shown varying degree of hypoglycemic and anti-hyperglycemic activity with different mechanism of action. Keywords: - Diabetes mellitus, Hypoglycemic, Family, Anti-hyperglycemic INTRODUCTION Diabetes mellitus is a metabolic disorder in the endocrine system & metabolic disorder causing hyperglycemia. Diabetes affects about 5% of the global population [1] and management of diabetes without any side effects is still a challenge to the medical

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Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 36

PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

A SYSTEMATIC REVIEW ON NATURAL MEDICINE USED FOR

THERAPY OF DIABETES MELLITUS OF SOME INDIAN

MEDICINAL PLANTS

Donga J.J.*, Surani V.S., Sailor G.U., Chauhan S.P., Seth A.K. Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Vadodara-391760

ABSTRACT Diabetes mellitus is one of the world’s major diseases. It currently affects an estimated 143 million people worldwide and the number is growing rapidly. In the India, about 1-5% population suffer from diabetes or related complication. Plant-based medicinal products have been known since ancient times, and several medicinal plants and their products (active natural principles and crude extracts) have been used to control diabetes in the traditional medicinal systems of many cultures worldwide. Several medicinal plants have found potential use as hypoglycemic in the Indian system of medicines. Several oral hypoglycaemic agents are the primary forms of treatment for diabetes. However, prominent side-effects of such drugs are the main reason for an increasing number of people seeking alternative therapies that may have less severe or no side-effects. In this review, we represent the profile of plants commonly used in India in the treatment of diabetes, reported in literature. A total of 45, 000 plant species have records of a popular use in the treatment of this syndrome in India. The profile presented includes information about scientific name, family, species, methodology used, the degree of hypoglycaemic activity and the active agents. Indian plants which are most effective and the most commonly studied in relation to diabetes and their complications are: Allium cepa, Allium sativum, Aloe vera, Beta vulgaris, Catharanthus roseus, Azadirachta indica, Gymnema sylvestre, Ipomoea batatas, Momordica cymbalaria,Momordica charantia, Ocimum sanctum, Pterocarpus marsupium, Swertia chirayita, Tinospora cordifolia, and Trigonella foenum graecum. All plants have shown varying degree of hypoglycemic and anti-hyperglycemic activity with different mechanism of action. Keywords: - Diabetes mellitus, Hypoglycemic, Family, Anti-hyperglycemic

INTRODUCTION

Diabetes mellitus is a metabolic disorder in the endocrine system & metabolic

disorder causing hyperglycemia. Diabetes affects about 5% of the global population[1]

and management of diabetes without any side effects is still a challenge to the medical

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system. [2] In India, the prevalence rate of diabetes is estimated to be 1-5%. Diabetes is

becoming the third “killer” of the health of mankind along with cancer, cardiovascular

and cerebrovascular diseases because of its high prevalence, morbidity and mortality. The

cause of diabetes is a mystery, although both genetic and environmental factors such as

obesity and lack of exercise appear to play a role. Ethnic and racial differences have been

found in heterogeneous populations within the same area. As a rule, incidence is highest

in Scandinavian countries, intermediate in the US, Spain, and Israel, and lowest in Asian

and most Latin American countries. Most researchers believe that, in the presence of a

genetic predisposition, something in the environment triggers the development of

diabetes. With a long course and serious complications often resulting in high death rate,

the treatment of this disorder takes three main forms: (I) Diet and exercise (II) Insulin

replacement therapy and (III) the use of oral hypoglycemic agents. Currently available

synthetic antidiabetic agents like sulfonyl ureas, biguanides, a glucosidase inhibitors etc

besides being expensive produce serious side effects. Further their use is not safe during

pregnancy. Apart from currently available therapy, herbal medicines recommended for

treatment of diabetes throughout the world. Herbal drugs are prescribed widely because

of their effectiveness, less side effects and relatively low cost.[3]

Thus due to an increase in demand by patients to use natural products with

antidiabetic activity, investigations on hypoglycemic agents derived from medicinal

plants have gained popularity in recent years. Laboratories are conducting research on

these medicinal plants in a scientific manner for the development of alternative drugs and

strategies for better management of diabetes. The main aim of present review is to collate

the all available data on Indian medicinal plants with hypoglycemic effect reported in

literature which may be useful to researcher as well as practitioners. This list is best used

only as a preliminary screening of potential antidiabetic plants, not as a definitive or

complete list of hypoglycemic plants.

Mechanism involve in treatment of diabetes

The present treatment of diabetes is focused on controlling and lowering blood

glucose to a normal level. The mechanisms of medicines and the Medicines to lower

blood glucose are:

§ To stimulate cell of pancreatic islet to release insulin;

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§ To resist the hormones which rise blood glucose;

§ To increase the number or rise the appetency and sensitivity of insulin receptor site

to insulin;

§ To decrease the leading-out of glycogen;

§ To enhance the use of glucose in the tissue and organ;

§ To clear away free radicals, resist lipid per oxidation and correct the metabolic

disorder of lipid and protein;

§ To improve microcirculation in the body.

Anti-diabetic medicinal plants undoubtedly have significant effect on the

lowering of blood sugar but their mechanism of action is yet to be elucidated. The first

evidence that the natural products have insulin potentiating activity was reported in 1929

by Glazer and Halpern. There are several mechanisms through which these herbs act to

control the glucose level. They are more or less similar actions to the synthetic drugs. The

mechanism of action of herbal anti-diabetics could be grouped as:

§ Stimulation of insulin secretion (Teucrium polium, Allium sativum, Allium cepa,

Panax ginseng)

§ Inhibition in renal glucose reabsorption (Fraxinus excelsior)

§ Stimulation of glycogenesis and hepatic glycolysis (Momordica charantia)

§ Protective effect on the destruction of the beta-cells (Thea sinensis)

§ Improvement of digestion and reduction of blood sugar and urea (Aegle marmelos)

§ Prevents pathological conversion of starch to glucose (Eugenia jambolina,

Pterocarpus marsupium)

§ Increasing the use of glucose by tissues and effect on adrenergic receptors (Panax

ginseng, Allium sativum, Allium cepa)

§ Potentiates the action of exogenously injected insulin

§ Cortisol lowering activities ( Boerhaavia diffusa, Ocimum sanctum)

Wide range of plant constituents could have different site of action within the

body and herbs exert similar mechanism of action like synthetic oral hypoglycemic

drugs. Many of these herbs may have a direct or an indirect impact on blood glucose

levels, thus interfering with the clinical management of diabetic patients. The above

mentioned plants have been considered for possible hypoglycemic actions and some

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preliminary investigations have been carried out by the researchers. Scientific studies

available on a good number of medicinal plants indicate that promising phytochemicals

can be developed for diabetes too. However, there are numerous other plants which are

mentioned in the indigenous systems of health care but still await scientific inquiry.

There are many grey areas, which need substantial amount of work in the case of herbal

antidiabetics. For a given dose of herbal medicine, its physiological effect will be

governed by the effective tissue concentration of the remedy, which in turn is determined

by pharmacokinetic parameters, absorption, distribution, metabolism and excretion of its

various components. Only knowledge of herbal pharmacokinetics can provide valuable

information to practitioners in prescribing herbs safely and effectively. Much more work

should be done in this direction to make the herbs useful.[4]

Indian medicinal plants with hypoglycemic activity

India has an officially recorded list of 45,000 plant species and a various

estimation of 7500 species of medicinal importance [5]. India has a rich history of using

various potent herbs and herbal components for treating diabetes. Many Indian plants

have been investigated for their beneficial use in different types of diabetes and reported

in numerous scientific journals. This article highlight on the chemo profiles from Indian

biosphere for treating diabetes with major thrust on the dosage and possible mode of

action of the herbal hypoglycemic so far reported. Various Indian medicinal plants of

different families having potent hypoglycemic activity are described in the following

section.

Acanthaceae

Andrographis paniculata

Oral administration of Andrographis paniculata and andrographolide in normal

and streptozotocin induced diabetic rat shows promising antihyperglycemic activity. The

hypoglycemic action of plants may be due to the prevention of glucose absorption from

gut [6,7]. Zhang and Tan shows the antioxidant activity of Andrographis paniculata

extract in diabetic rats, which may be responsible for beneficial effect in the diabetic state

[8].

Anacardiaceae

Mangifera indica

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The antidiabetic activity of Mangifera indica L(Mango) was seen when an extract

of the leaves of M. indica was given to rats 60 min before the glucose. The

hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of

chlorpropamide (200 mg/kg). The hypoglycaemic action of this plant may be due to a

reduction in the intestinal absorption of glucose [9]. However, possibility of other

mechanism can not be excluded. Mangifera indica has also been shown to exert powerful

anti-oxidant activity in vitro [10].

Annonaceae

Annona squamosa

Aqueous leaf extracts of Annona squamosa shows hypoglycemic activity in

Streptozotocin nicotinamide induced diabetic rats [11]. Oral administration of ethanolic

extract (350 mg/kg) produced significant hypoglycemic activity in normal streptozotocin

(STZ)-diabetic rats and alloxanized rabbits [12]. The plant may act by lowers the blood

glucose level.

Apocynaceae

Catharanthus roseus

Oral administration of water-soluble fraction of ethanolic extract of Vinca rosea

leaves (100, 250, 500 and 1000 mg/kg) showed significant dose-dependent reduction in

blood sugar at 4 h by 26.22, 31.39, 35.57 and 33.37%, respectively, in normal rats. In

addition, oral administration of 500 mg/kg 3.5 h before OGTT (10 gm/kg) and 72 h after

STZ administration (50 mg/kg IP) in rats showed significant anti-hyperglycemic effects.

No gross behavioral changes and toxic effect were observed up to 4 gm/kg IP [13].

Arecaceae

Cocos nucifera

The hypoglycaemic effect of neutral detergent fiber from Cocos nucifera L.

(coconut) was tested in rats fed 5%, 15% and 30% glucose. Increase in fiber intake

caused a significant lowering in glycaemia and serum insulin. Moreover, it increases the

fecal excretion of Cu, Cr, Mn, Mg, Zn and Ca. The results suggest the beneficial effect of

inclusion of coconut fiber in the diet [14].

Areca catechu

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Subcutaneous administration of alkaloid fraction of Areca catechu (0.05_/0.5

mg/kg) in alloxanized rabbits (140 mg/kg) showed significant hypoglycemic effect

lasting for 4_/6 h [15].

Asclepiadaceae

Gymnema sylvestre

GS4 (400 mg/kg) extracted from leaves of Gymnema sylvestre R. Br., was

administered to type II diabetic patients for 18-20 months as a supplement to the

conventional oral drugs. During GS4 supplementation, the patients showed a significant

reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins,

and conventional drug dosage could be decreased. Five of the 22 diabetic patients were

able to discontinue their conventional drugs and maintain their blood glucose

homeostasis with GS4 alone. These data suggested that pancreatic beta cells may be

regenerated and/or repaired in type II diabetic patients on GS4 supplementation. This is

supported by the appearance of raised insulin levels in the serum of patients after GS4

supplementation.35 Furthermore, GS4 was administered (400 mg/day) to 27 patients with

insulin-dependent diabetes mellitus (type I). GS4 therapy appears to enhance endogenous

insulin release, possibly by regeneration/revitalisation of the residual beta cells [16].

Water soluble fraction of an alcoholic extract of G. sylvestre leaves on glycogen

content of isolated rat hemidiaphragm was studied in normal and glucose fed

hyperglycaemic rats. In glucose fed rats, the leaf extract lowered the glycogen content of

the tissue and this effect was amplified by insulin [17].

Bombacaceae

Bombax ceiba

In Sprague-Dawley rats, a dose of 500 mg/kg of Shamimin (a C-flavonol

glucoside from Bombax ceiba) produced a significant reduction in glycaemia [18].

Brassicaceae

Brassica juncea

This study demonstrated the effect of Brassica juncea Coss (Leaf Mustard) on

carbohydrate metabolism in rats. It showed significant hypoglycaemic action. There was

increased activity of glycogen synthetase, and a decrease in glycogenolysis and

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gluconeogenesis demonstrated by a decreased activity of glycogen phosphorylase and

gluconeogenic enzymes [19].

Celastaceae

Salacia reticulata

Oral administration of aqueous decoction (1 ml/rat/day) of Salacia reticulata root

bark to over night fasted rats caused 30% reduction in glucose levels at 3 h [20]. Potent

natural a-glycosidase inhibitors such as kotalanol and salacinol isolated from the roots

and stems of the plant exert potent inhibitory activity against sucrase [21].

Salacia oblonga

Aqueous extract of the root bark of Salacia oblonga has shown hypoglycemic

activity [20]. Two biologically active fractions from the petroleum ether extract of the root

bark has been shown to exert hypoglycemic effect of about 60 and 76% potency of an

equal dose of tolbutamide (250 mg/kg) in albino rats [22]. Petroleum ether extract of the

bark of the root has been shown to prevent STZ (65 mg/ kg) induced hyperglycemia and

hypoinsulinemia in rats. The aqueous-methanolic extract of the roots inhibited increase

in serum glucose level in sucrose and maltose loaded rats. The water-soluble and ethyl

acetate soluble portions of the same extract showed inhibitory activities on alpha-

glucosidase and aldose reductase. Further, salacinol and kotalanol with nine other sugar

related component were isolated from the water soluble portion while, a new triterpene,

kotalagenin 16-acetate along with known diterpene and triterpenes isolated from the ethyl

acetate portion were found to be responsible component for the inhibitory activity on

aldolase reductase [23]. In addition, the extract has shown significant anti-oxidant activity

[24].

Chenopodiaceae

Beta vulgaris

Administration of extracts obtained from Beta vulgaris var. Cicla L. (Leaf beet);

(Sugar beet) inhibited the increase in the nonenzymatic glycosylation of skin proteins and

blood glucose. These results demonstrated the ability of this plant in preventing or at least

retarding the development of some diabetic complications [25]. Betavulgarosides I, II, III,

IV oleanolic acid oligoglycosides were isolated together with betavulgarosides VI, VII,

VIII from the roots of B. vulgaris. Betavulgarosides II, III and IV produced

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hypoglycaemic effects that were demonstrated by an oral glucose tolerance test in rats

[26].

Compositae

Artemisia pallens

Oral administration of an extract of the aerial parts of Artemisia pallens Wall.

produced a dose-dependent reduction in glycaemia in alloxan-induced diabetic rats. In

fasted healthy rats, the extract caused moderate hypoglycaemia at a higher dose. Only the

methanol extract was active whereas the water extract was inactive. Authors

hypothesized that the plant extract increased peripheral glucose utilization or inhibited

glucose reabsorption in the proximal tubules [27].

Convolvulaceae

Ipomea batatas

Oral administration of Ipomea batatas L. (white skinned sweet potato) produced a

reduction in hyperinsulinemia in Zucker fatty rats by 23%, 26%, 60% and 50%, 3, 4, 6

and 8 weeks after treatment respectively. These results were comparable to that of

troglitazone, an insulin sensitizer. After 7 weeks of treatment, increase in glycaemia after

glucose load was inhibited by the administration of I. batatas. Moreover, it normalized

lipid metabolism and produced a regranulation of pancreatic islet B-cells after 8 weeks of

treatment [28].

Cucurbitaceae

Citrullus colocynthis

Aqueous extract of Citrullus colocynthis fruit showed dose-dependent increase in

insulin release from isolated islets. Oral administration of aqueous extract (300 mg/kg) in

normal rabbits significantly reduced plasma glucose after 1 h and highly significant

reduction after 2, 3 and 6 h. Glycosidic extract (50 mg/kg) was more effective in

lowering fasting glucose as compared to alkaloidal extract. Graded doses (10, 15 and 20

mg/kg) of saponin also reduced plasma glucose concentration in alloxanized rabbits.

Thus, saponins and glycosidic components levels of the rind of Citrullus colocynthis are

responsible for its hypoglycemic effect [29].

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Coccina indica

The leaves of Coccina indica Wight & Am. (Ivy Gourd) were extracted with 95 %

ethanol. The residue obtained after evaporation of the solvents was suspended in distilled

water. Oral administration of this extract produced a decrease in glycaemia in normal-fed

(21 %) and 48 h fasted rats (24 %). This effect wast due in part to the inhibition of the

key gluconeogenic enzyme glucose-6-phosphatase [30]. Furthermore, the oral

administration of the pectin isolated from the fruit of the C. indica at a dose of 200

mg/100 g BW/day produced a reduction in glycaemia and an increase in liver glycogen.

Glycogen synthetase activity was significantly increased. Incorporation of labeled

glucose into hepatic glycogen was also found to be higher. A significant reduction in

phosphorylase activity was noted in the pectin-administered groups [31].

Momordica charantia

In healthy mice, an aqueous extract obtained from Momordica charantia L.

(Karela); (Balsam Pear) attenuated the glycemic response to both oral and intraperitoneal

glucose, without altering the insulin response. This aqueous extract and the residue after

alkaline chloroform extraction reduced hyperglycemia in diabetic mice after 1 h. It was

concluded that the hypoglycaemia activity activity of orally administered Karela extracts

was independent of intestinal glucose absorption and involved an extrapancreatic

effect.10 The alcoholic extract of the pulp (500 mg/kg), administered to healthy glucose

primed rats depressed plasma glucose levels at 1 h. Tolbutamide (100 mg/kg), under

similar conditions, produced the same effect. This reduction in plasma glucose levels was

not accompanied by increased insulin secretion. In streptozotocin-induced diabetic rats,

it improved the oral glucose tolerance causing significant reduction in plasma glucose.

The M. charantia extract caused a 4-5 fold increase in the rate of glycogen synthesis from

U-14C glucose in the livers of normally fed rats. These data suggest that the mechanism

of action of this plant could partly be attributed to increased glucose utilization by the

liver rather than an insulin secretion effect [32]. Another study showed the effects of oral

feeding of M. charantia fruit juice on the hepatic cytochrome P450 and glutathione S-

transferase drug-metabolizing enzymes in streptozotocininduced diabetic rats. The results

obtained suggest that the changes in hepatic phase I and phase II drug-metabolizing

enzyme activities in the diabetic animals may be associated with altered expression of

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different cytochrome P450 and glutathione S-transferase isozymes. In addition, M.

charantia did not always reverse the effects on drugmetabolizing enzymes in

streptozotocin-induced diabetes [33]. The activity of the juice of M. charantia fruit was

tested on streptozotocin(STZ)-treated RIN cells and isolated islets in vitro. Feeding the

juice of M. charantia fruit produced a reduction in hyperglycaemia in STZ-induced

diabetic mice. It strongly reduced the STZ-induced lipid peroxidation in the pancreas of

mice, RIN and islet cells. Moreover, it reduced the STZ-induced apoptosis in RIN cells

[34].

Momordica cymbalaria

Treatment over 15 days with Momordica cymbalaria Hook fruit powder produced

a significant blood glucose lowering effect in alloxan-induced diabetic rats, but not in

normoglycaemic rats. Moreover, the fruit powder reduced the level of cholesterol and

triglycerides in diabetic rats [35].

Euphorbiaceae

Phyllanthus amarus

Ten human subjects were treated with a preparation of the whole plant,

Phyllanthus amarus Shum. & Thon., for ten days (9 subjects were hypertensive and four

were diabetic). Glycaemia was reduced in the treated group. In a clinical observation, oral

administration of a preparation of the whole plant of P. amarus (syn. Phyllanthus niruri )

(5 gm/day in divided doses) for 10 days to 9 mild hypertensives (4 with DM) reduces

blood glucose (5-50 mg) in diabetic as well as non-diabetic subjects along with

significant reduction in systolic blood pressure No harmful side effects were noted in this

study [36].

Fabaceae

Cajanus cajan

Single doses of unroasted seeds of Cajanus cajan Millsp. (Pigeon pea) (60 % and

80 %) caused a significant reduction in serum glucose levels 1-3 h after oral

admininistration to healthy and alloxanized mice. In contrast, roasted seeds caused a

significant increase in serum glucose levels during the 3 h experimental period. The

authors concluded that roasting of seeds at high temperature for 30 min resulted in the

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total loss of the hypoglycaemic component but not the hyperglycaemic principle present

in the seeds [37].

Securigera securidacea

A new cardenolide (-)-14-methoxyhyrcanoside was isolated from an aqueous

extract of the seeds of Securigera securidacea L together with five new

dihydrobenzofuran derivatives (securigran I to V). Kaempferol and astragalin were also

isolated from the aqueous extract of the flowers of the plant. The total aqueous extract of

these seeds was hypoglycaemic [38].

Mucuna pruriens

Feeding of Mucuna pruriens seed diet (96.5 gm seed powder per 100 gm of the

total constituents) for 1 week to normal albino rat showed 39 and 61% reduction in

fasting blood glucose and cholesterol level, respectively [39]. Administration of powdered

seeds (0.5, 1 and 2 g/kg) significantly decreased the blood glucose levels of normal

rabbits while 1 and 2 g/kg caused a significant fall in alloxandiabetic rabbits.

Hypoglycemic principles of M. pruriens seeds may be both organic and mineral, which

seem to act indirectly by stimulating the release of insulin and/or by a direct insulin-like

action [40].

Flacourtiaceae

Casearia esculenta

Antihyperglycaemic activity of Casearia esculenta Roxb. root extract (300 mg/kg

p.o.) in normal and streptozotocin-induced diabetic rats for 45 days showed blood

glucose lowering activity of aqueous extracts in normal and glucose loaded rats along

with reduction in the increased plasma thiobarbituric acid reactive substance and blood

urea. There was decrease in the activities of glucose-6-phosphatase and fructose-1,6-

bishosphatase and an increase in the activity of liver hexokinase, resulting in potent

hypoglycemic activity. It showed the significant antioxidant activity of aqueous extract

in STZ diabetic rats at doses of 200 and 300 mg/kg for 45 days [41].

Gentianaceae

Swertia chirayita

The effect of swerchirin isolated from hexane fraction of S. chirayita on blood

sugar levels of healthy and streptozotocin-treated rats was studied. Swerchirin (50 mg/kg,

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p.o.) suspended in gum acacia was fed through cannula to healthy and diabetic rats.

Blood glucose levels measured at 0, 1, 3 and 7 h after after treatment showed a very

significant glucose lowering effect of this plant in healthy and mildly diabetic rats [42].

Single oral administration of the crude/impure swerchirin (SWI) isolated from the hexane

fraction of S. chirayita (50 mg/kg) to fed CF rats induced an approximately 60 % fall in

blood glucose by 7 h post-treatment. This was associated with marked depletion of

aldehyde-fuc stained beta-granules and immunostained insulin in the pancreatic islets. In

vitro, glucose uptake and glycogen synthesis by muscle (diaphragm) was enhanced by the

serum of SWI-treated rats. At 100, 10 and 1 μM final concentrations, SWI greatly

enhanced glucose (16.7 mM)-stimulated insulin release from isolated islets. It is therefore

concluded that SWI lowers glycaemia by stimulating insulin release from the islets of

Langerhans [43].

Enicostemma littorale

Whole plant aqueous extract of Enicostemma littorale Blume in alloxan induced

diabetic rats along with reduction of glycosylated heamoglobin and glucose-6-

phosphatase activity in liver [44]. It also shows glucose lowering activity of aqueous

extract (2 g/kg p.o.) daily for 6 weeks in neonatal non insulin-dependent diabetes mellitus

(NIDDM) rats along with a decrease in the elevated cholesterol,triglyceride and

creatinine levels [45].

Gramineae

Hordeum vulgare

In humans the postprandial glycaemic response of Hordeum vulgare L. (Barley)

was studied in a pool of 18 healthy volunteers and 14 patients having non-

insulindependent diabetes mellitus (type II). The glycaemic response to barley was

significantly lower than that to white bread in both groups of subjects. However, the

insulinemic response to barley was significantly lower than that to white bread in healthy

subjects only. In type II diabetic subjects, there was a tendency for the response to barley

to be higher than that to white bread 0.5 h after ingestion. Barley, with a low glycaemic

index (105.2), seems to mobilize insulin in NIDDM subjects. This makes it an especially

suitable cereal for diabetic patients [46].

Lamiaceae

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Ocimum sanctum

Oral administration of an alcoholic extract of leaves of Ocimum sanctum Linn.

(Tulasi) reduced glycaemia in normoglycaemic, glucose-fed hyperglycaemic and

streptozotocin-induced diabetic rats. Furthermore, the extract potentiated the action of

exogenous insulin in healthy rats. The activity of the extract was 91% and 70 % that of

tolbutamide in healthy and diabetic rats, respectively.113 Reduction in fasting blood

glucose was obtained after one month of treatment of healthy and diabetic rats with O.

sanctum leaf powder [47]. Treatment with Ocimum sanctum and Ocimum album Roxb.

(Holy basil)leaves showed a significant decrease in fasting and postprandial blood

glucose levels compared to treatment with placebo leaves. Fasting blood glucose fell by

21.0 mg/dl, and postprandial blood glucose fell by 15.8 mg/dl. The lower values of

glucose represented reductions of 17.6 % and 7.3 % in the levels of fasting and

postprandial blood glucose, respectively. Urine glucose levels showed a similar trend [48].

Salvia lavandifolia

The authors confirmed the hypoglycaemic effect of Salvia lavandifolia Vahl.

reported previously and suggested that this hypoglycaemic effect may arise by several

mechanisms: a). potentiation of insulin release induced by glucose; b) increased

peripheral uptake of glucose; c) decreased intestinal absorption of glucose; d) hyperplasia

of the pancreatic islet beta cells [49]. The antidiabetic activity of the extract of S.

lavandifolia was investigated in streptozotocin-induced diabetic rats. The extract (10 mg

dry residue/kg) induced an increase in the size and number of cells in the islets of

Langerhans. There was also an increase in pancreatic insulin content. A significant

decrease (>40 %) in blood glucose levels was obtained when the extract (10 mg/kg) and

glibenclamide (1mg/kg) were both administered to streptozotocin-induced diabetic rats

[50].

Leguminosea

Caesalpinia bonducella

The aqueous and alcoholic extract of Caesalpinia bonducella seeds exhibited

significant hypoglycemic and anti-hyperglycemic activities in normal and STZ

hyperglycemic rats [51,52]. In healthy rats, both the aqueous and 50 % ethanolic extracts of

Caesalpinia bonducella Fleming seeds exhibited hypoglycaemic activity as early as 4 h

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after administration at a lower dose of 100 mg/kg. The hypoglycaemia produced by the

aqueous extract was of prolonged duration as compared to the ethanolic extract. In

diabetic rats, both extracts produced marked antihyperglycaemic effects from day 5

onwards [53].

Astragalus species

Oral administration of an extract from Astragalus species to normoglycaemic rats

produced a persistent hypoglycaemic effect. Moreover, in alloxanised diabetic rats, this

extract showed hypoglycaemic effects more potent than that of Daonil [54].

Trigonella foenum graecum

Trigonella foenum graecum L. (fenugreek) is among twelve herbs mostly used to

treat diabetes in Saudi Arabia [55]. In insulin-dependent diabetic patients, the fenugreek

diet significantly reduced fasting blood glucose and improved the glucose tolerance test.

There was a 54% reduction in the 24 h urinary glucose excretion. The results showed the

usefulness of fenugreek seeds in the management of diabete [56]. Oral administration of T.

foenum graecum to healthy and alloxan induced diabetic rats (2 and 8 g/kg) produced a

significant fall in blood glucose level (BGL) both in the normal as well as in diabetic rats.

The hypoglycaemic effect was dose related [57]. On the other hand, the aqueous extract of

fenugreek leaf when given to both healthy and alloxan-diabetic rats, produced a

significant reduction in BGL. However, an ethanolic extract of fenugreek leaf produced

no reduction in BGL in77 healthy rats but i.p. administration of 0.8 g/kg of the ethanolic

leaf extract to diabetic rats produced a significant reduction of BGC [58]. The Soluble

Dietary Fibers (SDF) fraction of fenugreek seeds showed no effect on fasting blood

glucose levels of non-diabetic or NIDDM (type II) rats. However, when fed

simultaneously with glucose, it showed an hypoglycaemic effect in type II diabetic rats.

The major constituent of the SDF is galactomannan [59]. More recently, it has been shown

that the disrupted free radical metabolism in diabetic animals may be normalized by

fenugreek seed supplementation in the die [60]. Moreover, fenugreek significantly

decreased the hyperglycaemic peak and the area under the glucose tolerance curve in

hyperglycaemic rabbits [61].

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Medicago sativa

Medicago sativa L. (Lucerne, alfalfa) when supplied in the diet (6.25 % by

weight) and infusion (1g/400 ml) reduced the level of hyperglycaemia in streptozotocin-

induced diabetes [62].

Pterocarpus marsupium

The hypoglycaemic effect was investigated after i. p. administration of marsupsin,

pterosupin and pterostilbene (3 important phenolic constituents of heartwood of

Pterocarpus marsupium). Marsupsin and pterostilbene significantly lowered the

glycaemia of diabetic rats, and the effect was comparable to that of 1,1-

dimethylbiguanide (metformin) [63].

Cassia auriculata

Oral administration of aqueous flower extract of Cassia auriculata L. in

streptozotocin-induced diabetic rats at different doses for 30 days produced a significant

antihyperglycemic activity. [64,65] in addition to pronounced alpha-glucocidase inhibitory

actions resulting in a significant and potent lowering of blood glycemic response [66]. The

aqueous extract also shows antioxidant activity in the brain of streptozotocin diabetic rats

[66,67]. Such activity may be due to suppression of enhanced gluconeogenesis during

diabetes and,enhance utilization of glucose through increased glycolysis [64,65].

Acacia arabica

Hypoglycaemic activity of 94% seed diet of Acacia arabica in normal rats orally

with no blood sugar lowering activity in alloxanized rats at the same dose level. The plant

may acts through release of insulin from pancreatic beta cells, which accounts for the

hypoglycemic activity in normal rabbits (2, 3and 4 mg/kg) administered orally [68,69].

Liliacecae

Allium sativum

S-allyl cysteine sulphoxide (SACS), a sulphur-containing amino acid of Allium

sativum L. (Garlic) that is the precursor of allicin and garlic oil, has been found to show

significant antidiabetic effects in alloxan diabetic rats. Administration of a dose of 200

mg/kg significantly decreased the concentration of serum lipids, blood glucose and

activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate

dehydrogenase and liver glucose-6-phosphatase. It significantly increased liver and

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intestinal HMG CoA reductase activity and liver hexokinase activity [70]. Oral

administration of SACS to alloxan diabetic rats for a month ameliorated the diabetic

conditions of treated rats comparable with rats treated with glibenclamide and insulin [71].

Treatment of alloxan diabetic rats with SACS ameliorated the diabetic condition almost

to the same extent as glibenclamide and insulin. In addition, SACS controlled lipid

peroxidation better than the other two drugs. Furthermore, SACS significantly stimulated

in vitro insulin secretion from beta cells isolated from healthy rats. Hence it can be

surmised that the beneficial effects of SACS could be due to both its antioxidant and its

secretagogue actions. The former effect is predominant and the latter is only secondary

[72].

Allium cepa

Oral administration of Allium cepa L. (Onion)S-methyl cysteine sulphoxide

(SMCS) daily at a dose of 200 mg/kg body weight for a period of 45 days to alloxan

diabetic rats controlled the blood glucose and lipids in serum and tissues and altered the

activities of liver hexokinase, glucose 6-phosphatase and HMG CoA reductase towards

normal values. These effects of SMCS were comparable to those of glibenclamide and

insulin [73]. Oral administration of onion SMCS to alloxan diabetic rats for a month,

ameliorated the diabetic condition similar to rats treated with glibenclamide and insulin.

The effect of feeding a 15 mg % capsaicin diet or 3 % freeze-dried onion powder

containing diet produced a significant reduction in the hyperglycaemic status of diabetic

animals. This study revealed that onion feeding improves the metabolic status in diabetes

probably because of its hypocholesterolemic as well as its hypoglycaemic effect [74].

Aloe barbadensis

Acute oral administration of an exudate of Aloe barbadensis Mill. (Barbados)

leaves (500 mg/kg) produced no reduction in blood glucose level whereas its bitter

principle (5 mg/kg) administered intraperitoneally produced a significant hypoglycaemic

effect that extended over a period of 24 h with maximum hypoglycaemia observed after

8h. In chronic studies, A. barbadensis and its bitter principle produced a maximum effect

after 5 days. It seems that the hypoglycaemic effect of this plant and its bitter principle

may be mediated through stimulating synthesis and/or release of insulin from the beta-

cells of the islets of Langerhans [75]. Moreover, this plant slightly decreased the area

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under glucose tolerance curve compared to control (1.4 %) or tolbutamide (14.3 %) in

healthy rabbits [76].

Malvaceae

Hibiscus rosa-sinesis

Single oral administration of 250-mg/kg ethanol extract of Hibiscus rosa-sinesis

showed mild but significant hypoglycemia at 120 min in glucose loaded rat. Daily

administration of same dose for 7 days showed significant hypoglycemic effect at 30, 90,

120 min after glucose loading in normal rats. The action was similar to tolbutamide and

possibly due to insulin release by stimulation of pancreatic beta cells or an increase of the

glycogen deposition in liver [77].

Melastomaceae

Memecylon umbellatum

Oral administration of alcoholic extract of the leaves of Memecylon umbellatum

(250 mg/kg) caused a significant reduction in the serum glucose levels in normal and

alloxanized rats at 30, 60 and 90 min after administration [78].

Meliaceae

Azadirachta indica

Hydroalcoholic extract of Azadirachta indica showed hypoglycemic and anti-

hyperglycemic effect in normal, glucose fed and STZ diabetic rats [79]. The plant exerts its

pharmacological activity independent of its time of administration i.e. either prior or after

alloxan administration [80]. The plant blocks the action of epinephrine on glucose

metabolism, thus increasing peripheral glucose utilization [81]. It also increased glucose

uptake and glycogen deposition in isolated rat hemidiaphragm [82].

Menispermaceae

Tinospora cordifolia

Oral administration of 400 mg/kg of aqueous extract of TC for 15 weeks of

treatment showed maximum hypoglycemia of 70.37, 48.81 and 0% in mild (plasma sugar

180 mg/dl), moderate (plasma sugar 280 mg/dl) and severe (plasma sugar 400 mg/dl)

diabetic rats, respectively. Hypoglycemic effect depended upon the functional status of

the pancreatic beta cells [83]. Oral administration of the water extract of Tinospora

cordifolia root (2.5, 5 and 7.5 mg/kg) caused a significant reduction in blood glucose,

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brain lipid level, hepatic glucose-6-phosphatase, serum acid phosphatase, alkaline and

lactate dehydrogenase and increase in body weight, total hemoglobin and hepatic

hexokinase in alloxanized diabetic rats (150 mg/kg, IP) [84]. Anti-oxidant [85] and

hypolipidemic activity is described [86].

Moraceae

Ficus bengalensis

The oral administration of the extract obtained from Ficus bengalensis L.

(Banyan) resulted in enhancement of serum insulin levels in normoglycaemic and

diabetic rats. The incubation of isolated islets of Langerhans from healthy as well as from

diabetic animals with this plant extracts resulted in increased insulin secretion. This

extract inhibited insulinase activity from liver and kidney [87]. The antidiabetic effect of a

dimethoxy derivative of perlargonidin 3-O-alpha-L rhamnoside (250 mg/kg, single dose

study and 100 mg/kg/day, long term study) isolated from the bark of F. bengalensis has

been compared with that of glibenclamide (2 mg/kg and 0.5 mg/kg/day respectively) in

moderately diabetic rats. The single dose glycoside treatment decreased fasting blood

glucose by 19 % and improved glucose tolerance by 29 %. After one-month treatment

with the plant, the fasting blood glucose level went down to almost half of the pre-

treatment levels in both the groups and their glucose tolerance improved by 41 % in the

glibenclamide group and by 15 % in the glycoside treated group. Urine sugar decreased

to trace amounts in both groups. In vitro studies showed that insulin secretion by beta-

cells was greater in the presence of the pelargonidin derivative than in the presence of a

leucocyanidin derivative, reported to be a good antidiabetic agent [88]. Glycoside of

leucopelargonidin isolated from the bark of F. bengalensis demonstrated significant

hypoglycaemic, hypolipidemic and serum insulin raising effects in moderately diabetic

rats with close similarities to the effects of a minimal dose of glibenclamide [89].

Dimethoxy ether of Leucopelargonidin-3-O-alpha-L rhamnoside isolated from the bark

of F. bengalensis was used at a dose of 100 mg/kg on oral administration. The

compound showed significant hypoglycaemic and serum insulin raising actions in healthy

and alloxan induced-diabetic dogs during a period of 2h. This compound appears to

stimulate insulin secretion [90]. A leucodelphinidin derivative isolated from the bark of F.

bengalensis L. showed hypoglycaemic action at a dosage of 250 mg/kg when given to

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both healthy and alloxan diabetic rats. Its action was similar to that of an effective dose of

glibenclamide (2 mg/kg) tested under the same conditions. However, after a glucose

load, the plant product was only just significantly active and not as effective as the

sulphonylureas. The efficacy of the plant product as an hypoglycaemic agent adds to the

other therapeutic effects associated with this class of flavonoids [91].

Morus alba

Chronic subcutaneous administration of the extract of the leaves of Morus alba to

rabbits led to degranulation of beta-cells of the Langerhans islets [92]. Single intra-

peritoneal dose of 200 mg/kg of ethanol insoluble fraction of hot water extract of M. alba

leaves exhibited a potent hypoglycemic activity in fasted and non-fasted STZ (150 mg/kg

IV) diabetic mice and the glucose level fell by 24.69/6% and 81.49/7.9%, respectively.

Increase in glucose uptake was postulated as the mechanism of hypoglycemic action [93].

Alkaloids of this plant are known to possess glycosidase inhibitory activity [94]. Anti-

oxidant activity has been described previously [95].

Musaceae

Musa sapientum

Among the plants most used in the treatment of diabetes mellitus Musa sapientum

Kuntze (Banana) significantly decreased the hyperglycaemic peak and the area under the

glucose tolerance curve in hyperglycaemic rabbits [96]. Oral administration of 1.5, 0.2 and

0.25 g/kg body weight of the chloroform extract of the flowers of M. sapientum during a

30-day period caused a decrease in blood glucose l and glycosylated haemoglobin levels

and an increase in total haemoglobin. The extract showed antihyperglycaemic action and

an antioxidant effect. Banana flower was more effective than glibenclamide [97].

Myrtaceae

Eucalyptus globulus

Eucalyptus globulus Labill. (Tasmanian Bleu Gum) when given to streptozotocin-

diabetic mice reduced the level of hyperglycaemia [98]. In contrast, it has been found that

the decrease in hyperglycaemia caused by E. globulus was not significant.41 In another

study, it was demonstrated that E. globulus possesses an antihyperglycaemic action due

to pancreatic and extrapancreatic effects in diabetic mice [99].

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Eugenia jambolana

The hypoglycaemic activity of the extract of jamun pulp from the fruit of Eugenia

jambolana Lam. (Gambol) = Syzigium cumini Skeels (Jamum) was seen after 30 min,

while the seeds of the same fruit required 24 h to produce the same effect. These results

were confirmed in streptozotocin-induced diabetic animals. The oral administration of the

extract resulted in the enhancement of insulinemia in normoglycaemic and diabetic rats.

The incubation of isolated pancreatic islet cells of normal and diabetic animals with this

plant extracts resulted in increased insulin secretion. This extract inhibited insulinase

activity from liver and kidney.159 Oral administration of 2.5 and 5.0 g/kg body weight of

the aqueous extract of the seeds of S. cumini for six weeks in alloxan-diabetic rats

resulted in a significant reduction in blood glucose concentration and an increase in total

haemoglobin, but in the case of 7.5 g/kg body weight, the effect was not significant. It

also resulted in decreased free radical formation in tissues [100].

Nyctagenaceae

Boerhavia diffusa

The Hypoglycemic activity of aqueous leaf extract of Boerhavia diffusa L. at a

dose of 100, 200 and 400 mg/kg in alloxan induced diabetic rats [101]. Aqueous leaf

extract (200 mg/kg p.o., daily for 4 weeks) in normal and alloxan induced diabetic rats

cause increases plasma insulin levels and improves glucose tolerance. The extract showed

antihyperglycemic and significant antioxidant activity [102,103].

Nymphaeaceae

Nelumbo nucifera

A methanol extract of Nelumbo nucifera Gaerth (East Indian Lotus) obtained by

soxhlet extraction from finely pulverized rhizomes was used. The extract (300 mg/kg and

600 mg/kg, orally) caused a decrease in glycaemia in streptozotocin-induced diabetic rats

by 53 % and 55 %, respectively at the end of 12 h [104]. Oral administration of the

ethanolic extract of rhizomes of N. nucifera markedly reduced the glycaemia of healthy,

glucose-fed hyperglycaemic and streptozotocin-induced diabetic rats compared to

control. The extract improved glucose tolerance and potentiated the action of

exogenously injected insulin in normal rats. The extract exhibited activity of 73% and 67

% of that of tolbutamide in normal and diabetic rats, respectively [105].

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Oleaceae

Olea europea

Maximum hypoglycaemic activity of Olea europea L. olive leaf was obtained

from samples collected in the winter months, especially in February. One of the

compounds responsible for this activity was oleuropeoside, which showed activity at a

dose of 16 mg/kg. This compound also demonstrated antidiabetic activity in animals with

alloxaninduced diabetes. The hypoglycaemic activity of this compound may result from

two mechanisms: (a) potentiation of glucose-induced insulin release, and (b) increased

peripheral uptake of glucose [106].

Oxalidaceae

Averrhoa bilimbi

Oral glucose tolerance test (OGTT) in both normoglycaemic and streptozotocin-

induced diabetic rats showed an optimal hypoglycaemic effect at a dose of 125 mg/kg.

Repeated administration (twice a day) of a dose of 125 mg/kg of ethanolic extract

obtained from Averrhoa bilimbi L. (bilimbi)leaves reduced glycaemia in diabetic rats by

50% and blood triglyceride by 130% when compared with vehicle (water) [107].

Biophytum sensitivum

Subdiabetic, mildly diabetic and severely diabetic male rabbits were induced by

alloxan. Assessment of the activity of the extract from Biophytum sensitivum DC leaves

was made by measuring the fall in fasting plasma glucose level and improvement in the

OGTT, following single dose and prolonged administrations. Following a single dose

administration, there was fall in 1 and 2.5 h glucose values by 26 % and 27 %,

respectively in the subdiabetic rabbits, and by 37 % and 38 % in the mildly diabetic

rabbits. Improved OGTT response was also shown in the subdiabetic as well as in the

mildly diabetic rabbits. More significant improvements occurred following one week of

the above treatment. It was concluded that the plant composites had an hypoglycaemic

effect probably due to pancreatic β-cell stimulating action [108].

Punicaceae

Punica gratum

Oral administration of the aqueous-ethanolic (50%, v/v) extract of the flowers of

Punica gratum L. (Gulnar farsi)produced a significant decrease in glycaemia in

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normoglycaemic, glucose-fed hyperglycaemic and alloxan induced diabetic rats. The

maximum effect was found at 400 mg/kg [109].

Rutaceae

Aegle marmelose

Oral administration of aqueous decoction of Aegle marmelose root bark (1 ml/100

gm) showed hypoglycemic effect which was maximum (44%) at 3 h in normal fasted

rats. In addition, the same extract completely prevented peak rise of blood sugar at 1 h in

OGTT. The hypoglycemic activity was reduced upon storage of extract [110]. The leaf

extract of Aegle marmelose (L.) Corea ex Roxb. was found to be as effective as insulin

in the restoration of blood glucose and body weight to normal levels. A. marmelose can

be used as potentiel hypoglycaemic agent [111]. Alloxan-induced diabetic animals were

given insulin injections while another group received A. marmelose leaf extract. The

blood glucose levels in the extract-treated animals was near to that of controls. Blood

urea and serum cholesterol increased significantly in alloxan diabetic rats. Treatment

with the leaf extract decreased the blood urea and serum cholesterol compared to

controls. A similar effect was seen with insulin treatment. Consequently, the active

principle of A. marmelose extract had similar hypoglycaemic effect to that of insulin [112].

Aqueous leaf extract administered orally for 28 days also normalized STZ (45mg/kg

body weight) induced histo-pathological alterations in the pancreatic and kidney tissues

of rats [113].

Murraya koeingii

Oral feeding of Murraya koeingii leaves diet (10% w/w) for 60 days to normal

rats showed hypoglycemic effect associated with increased hepatic glycogen content due

to increased glycogenesis and decreased glycogenolysis and gluconeogenesis [114].

Dietary supplement with curry leaves has been shown to increase lecithin cholesterol acyl

transferase activity activity [115]. Curry leaves powder supplementation (12 g providing

2.5 g fiber) for a period of 1 month in 30 NIDDM patients showed reduction in fasting

and post-prandial blood sugar levels at 15-day period with no significant changes in

serum glycosylated protein levels, glycosylated low density lipoprotein cholesterol

fraction, serum lipids, lipoprotein cholesterol levels, uronic acid and total amino acids

[116].

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Sapotaceae

Bumelia sartorum

An unsaturated triterpene acid isolated from an ethanolic extract of Bumelia

sartorum Mart.root bark produced an hypoglycaemic effect in alloxan-induced diabetic

rats. It increased glucose uptake and glycogen synthesis in isolated rat diaphragm and

plasma insulin levels. It appears that this effect was mediated by an insulin secretaguogue

effect in pancreatic β cells [117].

Scrophulariaceae

Picrorrhiza kurroa

Alcoholic extract of Picrorrhiza kurroa (75 mg extract/kg) reduced serum glucose

that was maximum 2 h after the dose. It also showed antihyperglycemic effect in

alloxanized diabetic rats. Serum glucose decreased by 43 and 60% with 75 and 150

mg/kg of the extracts, respectively. Anti-oxidant activity is also described in the literature

[118].

Scoparia dulcis

Aqueous leaf extract of Scoparia dulcis L (0.15, 0.30 and 0.45 g/kg body weight

for 45 days p.o.) in experimental diabetic rats along with a reduction in glycosylated

haemoglobin and an increase in total haemoglobin [119]. There was reduction in

hemoglobin, thiobarbituric acid reactive substances, hydroperoxides and plasma insulin,

glutathion peroxidase, glutathion S-transferase enhancing activities of aqueous plant

extract (200mg/kg) in the liver of streptozotocin adult diabetic male albino Wistar rats.

The antidiabetic activity may be due to suppresses glucose influx into the polyol pathway

leading to increased activities of antioxidant enzymes and plasma insulin and decreases

activity of sorbitol dehydrogenase [120]. Also potentiates insulin release from Blood

glucose, sorbitol dehydrogenase, glycosylated pancreatic islets [121].

Solanaceae

Withania somnifera

Six mild NIDDM subjects and six mild hypercholesterolemic subjects were

treated with a powder of Withania somnifera (ashvagandha, Dunal, winter cherry) roots

for 30 days. The treatment produced a decrease in blood glucose levels that was

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comparable of that of an oral hypoglycaemic drug. The authors concluded that W.

somnifera could be a potential source of hypoglycaemic agents [122].

Sterculiaceae

Helicteres isora

Ethanolic root extract of Helicteres isora L cause decrease in plasma glucose at

(300 mg/kg, after 9 days of administration) in insulin resistant and diabetic

C57BL/KsJdb/db mice associated with a reductionin plasma triglyceride level may be

acts through insulin-sensitizing activity [123].

Theaceae

Camellia sinensis

The hot water extract of Camellia sinensis L. (black tea) significantly reduced the

blood glucose levels of streptozotocin-induced diabetic in rats. This extract was found to

possess both preventive and curative effects on experimentally produced diabetes in rats.

The study revealed that black tea, like green tea, also possesses antidiabetic activity [124].

Verbenaceae

Lantana camara

Once daily administration of the juice of Lantana camara L. leaves given at

different dose levels (60, 300, 600 and 1500 mg/kg/day) for 14 days in rats resulted in

alterations in various haemato- and biochemical parameters. A strong hypoglycaemic

effect was seen with 1500 mg only [125].

Potential future research challenges

Although many plant species have been validated for their antidiabetic properties

and related complications, a need exists for research in the following areas.

• Identification of phytochemical compound(s) directly associated with hypoglycaemic

and antihyperglycaemic bioactivity of selected plant species

• Extensive, large-population clinical studies for selected species

• Investigation of combination dosages of natural plant products and synthetic drugs to

determine the optimal combination for cost-effective therapies.

• Determination of the long-term side-effects of natural herbal product formulations

individually and in combination with synthetic drugs.

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• Determination of the mechanisms behind hypoglycaemic and antihyperglycaemic

activity for most of the medicinal plant species.

• Assessment of the inter- and intra-specific variation in secondary metabolite

production in response to environmental (soil, climate, etc.) and production (organic

and inorganic fertilisers, agricultural chemicals, etc.) inputs for most species.

• Investigation of the production potential of plant species with clinically proven

antidiabetic properties in diverse environments.

• Development of potentially easy-to-consume food products fortified with extracts of

plant species with clinically proven hypoglycaemic or antihyperglycaemic properties

that can be incorporated into diabetic diets.

CONCLUSION

Diabetes is a disorder of carbohydrate, fat and protein metabolism attributed to

diminished production of insulin or mounting resistance to its action. Herbal treatments

for diabetes have been used in patients with insulin-dependent and non-insulin-dependant

diabetes, diabetic retinopathy, diabetic peripheral neuropathy, etc. Scientific validation of

several Indian plant species has proved the efficacy of the botanicals in reducing the

sugar level. From the reports on their potential effectiveness against diabetes, it is

assumed that the botanicals have a major role to play in the management of diabetes,

which needs further exploration for necessary development of drugs and nutraceuticals

from natural resources. However lack of scientific and experimental evidence about

effective constituents, toxicity, pharmacokinetics, effectiveness and efficacy resulted in

deficiency of belief in effectiveness, quality and safety of herbal medicines. The need for

adequate standards of herbal preparations to ensure quality, safety and efficacy has been

highlighted since the use of herbal medicines and phytotherapies. This requires biological

testing of plant extracts, isolation of bioactive components, as well as toxicological,

pharmacodynamical and, ultimately, clinical studies. For Indian medicinal preparations,

which are made from plant extracts, and often considered to be effective due to a mixture

of active ingredients rather than a single constituent, standardization is difficult,

furthermore, possible to lose active principles. However, the standardization is an

absolute requirement. It is a significant work to isolate active components of Indian

medicinal plants with confirmed hypoglycemic activity, to explain their pharmacological

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mechanism, and lastly, develop normalized Chinese medicinal preparations for anti-

diabetes and it complications.

REFERENCES

1. Chakraborty R and Rajagopalan R: Diabetes and insulin resistance associated

disorders: disease and the therapy. Current Science 2002; 83: 1533-1538

2. Kameswara Rao B, Renuka Sudarshan P, Rajasekhar MD, Nagaraju N, Appa Rao Ch:

Hypoglycemic activity of Terminalia pallida fruit in alloxan induced diabetic rats. J

Ethnopharmacology 2003; 85: 169-172.

3. Venkatesh S, Reddy GD, Reddy BM, Ramesh M, Appa Rao AVN: 2003.

Antihyperglycemic activity of Caralluma attenuata. Fitoterapia 2003; 74: 274-279.

4. Achrekar S, Kaklij GS, Pote MS and Kelkar SM: 1991. Hypoglycemic activity of

Eugenia jambolana and Ficus bengalenesis : mechanism of action. In Vivo 1991; 5

(2): 143-147.

5. Ashis P, Khan ML, Arunachalam A and Arunachalam K: Current Science 2005; 89:

623–634.

6. Borhanuddin M, Shamsuzzoha M and Hussain AH: Hypoglycaemic effects of

Andrographis paniculata Nees on non-diabetic rabbits. Bangladesh Medical

Research Council Bulletin 1994; 20: 24–26.

7. Yu BC, Hung CR, Chen WC and Cheng JT: Antihyperglycemic effect of

andrographolide in streptozotocin-induced diabetic rats. Planta Medica 2003; 69:

1075–1079.

8. Zhang XF and Tan BK: Anti-diabetic property of ethanolic extract ofAndrographis

paniculata in streptozotocin-diabetic rats. Acta Pharmacologica Sinica 2000; 21:

1157–1164.

9. Aderibigbe AO, Emudianughe TS and Lawal BA: Antihyperglycaemic effect of

Mangifera indica in rat. Phytotherapy Research 1999; 13: 504–507.

10. Martinez G, Delgado R, Perez G, Garrido G, Nunez Selles AJ and Leon OS:

Evaluation of the in vitro antioxidant activity of Mangifera indica L. extract.

Phytotherapy Research 2000; 14 (6): 424- 427.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 62

11. Shirwaikar A, Rajendran K, Dinesh Kumar C and Bodla R: Hypoglycemic activity of

aqueous leaf extract of Annona squamosa in streptozotocin-nicotinamide type 2

diabetic rats. J Ethnopharmacology 2004; 91: 171–175.

12. Gupta RK, Kesari AN, Murthy PS, Chandra R, Tandon V and Watal G:

Hypoglycemic and hypoglycemic effect of ethanolic extract of leaves of Annona

squamosa L. in experimental animals. J Ethnopharmacology 2005; 99: 75–81.

13. Chattopadhyay RR, Sarkar SK, Ganguly S, Banerjee RN and Basu TK:

Hypoglycemic and antihyperglycemic effect of leaves of Vincarosea Linn.Indian J

Physiol Pharmacol 1991; 35: 145– 151.

14. Sindurani JA and Rajamohan T: Effects of different levels of coconut fiber on blood

glucose, serum insulin and minerals in rats. Indian J Physiol Pharmacol 2000; 44: 97-

100.

15. Chempakam B: Hypoglycemic activity of arecoline in betel nut Areca catechu L.

Indian J Exp Biol 1993; 31 (5): 474-475.

16. Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha

Shanmugasundaran K and Kizar Ahmath B: Use of Gymnema sylvestre leaf extract in

the control of blood glucose in insulin-dependent diabetes mellitus. J

Ethnopharmacol 1990; 30: 281-294.

17. Chattopadhyay RR: Possible mechanism of antihyperglycemic effect of Gymnema

sylvestre leaf extract, part I. General Pharmacology 1998; 31: 495–496.

18. Saleem R, Ahmad M, Hussain SA, et al: Hypotensive, hypoglycaemic and

toxicological studies on the flavonol C-glycoside shamimin from Bombax ceiba.

Planta Med 1999; 65: 331-334.

19. Khan BA, Abraham A and Leelamna S: Hypoglycaemic action of Murraya Koenigii

(curry leaf) and Brassica juncea (mustard): Mechanism of action. Indian J Biochem

Biophys 1995; 32: 106-108.

20. Karunanayake EH, Welihinda J, Sirimanne SR and Sinnadorai G: Oral hypoglycemic

activity of some medicinal plants of Sri Lanka. J Ethnopharmacology 1984; 11: 223–

231.

21. Yoshikawa M, Murakami T, Yashiro K and Matsuda H: Kotalanol, a potent alpha-

glucosidase inhibitor with thiosugar sulfonium sulfate structure, from hypoglycemic

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 63

Ayurvedic medicine Salacia reticulata. Chem Pharm Bull (Tokyo) 1998; 46: 1339–

1340.

22. Augusti KT, Joseph P and Babu TD: Biologically active principles isolated from

Salacia oblonga wall. Indian J Physiol Pharmacol 1995; 39: 415-417.

23. Matsuda H, Murakami T, Yashiro K, Yamahara J and Yoshikawa M: Hypoglycemic

principles of natural medicines. IV. Aldose reductase and alpha-glucosidase inhibitors

from the roots of Salacia oblonga Wall. (Celastraceae): structure of a new friedelane-

type triterpene, kotalagenin 16-acetate. Chem Pharm Bull (Tokyo) 1999; 47 (12):

1725-1729.

24. Krishnakumar K, Augusti KT and Vijayammal PL: Hypoglycemic and anti-oxidant

activity of Salacia oblonga Wall. extract in streptozotocin-induced diabetic rats.

Indian J Physiol Pharmacol 1999; 43 (4): 510-514.

25. Tunali T, Yarat A, Yanardag R, et al: The effect of Chard (Beta vulgaris L. ver.

Cicla) on the skin of streptozotocin induced diabetic rats. Pharmazie 1998; 53: 638-

640.

26. Yoshikawa M, Murakami T, Kadoya M, et al.Medicinal foodstuffs. III. Sugar beet.

(1): Hypoglycaemic oleanolic acid oligoglycosides, betavulgarosides I, II, III, and IV,

from the root of Beta vulgaris L. (Chenopodiaceae). Chem Pharm Bull (Tokyo) 1996;

44: 1212-1217.

27. Subramoniam A, Pushpangadan P, Rajasekharan S, Evans DA, Latha PG and

Valsaraj R: Effects of Artemisia pallens Wall. on blood glucose levels in normal and

alloxan-induced diabetic rats. J Ethnopharmacology 1996; 50 (1); 13-17.

28. Kusano S and Abe H: Antidiabetic activity of white Skinned potato (Ipomoea batatas

) in obese Zucker fatty rats. Biological and Pharmaceutical Bulletin 2000; 23 (1): 23-

26.

29. Abdel-Hassan IA, Abdel-Barry JA and Tariq Mohammeda S: The Hypoglycemic and

antihyperglycemic effect of Citrullus colocynthis fruit aqueous extract in normal and

alloxan diabetic rabbits. J Ethnopharmacology 2000;71: 325–330.

30. Hossain MZ, Shibib BA and Rahman R: Hypoglycaemic effects of Coccina indica:

inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. Indian J Exp Biol

1992; 30: 418-420.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 64

31. Kumar GP, Sudheesh S and Vijayalakshmi NR: Hypoglycaemic effect of Coccina

indica: Mechanism of action. Planta Med 1993; 59: 330-332.

32. Sarkar S, Pranava M and Marita R: Demonstration of the hypoglycaemic action of

Momordica Charantia in a validated model of diabetes. Pharmacol Res 1996; 33: 1-

4.

33. Raza H, Ahmed I, Lakhani MS, Sharma AK, et al: Effect of bitter melon (Momordica

charantia) fruit juice on the hepatic cytochrome P450-dependent monooxygenase and

glutathione S-transferase in streptozotocin-induced diabetic rats. Biochem Pharmacol

1996; 52: 1639-1642.

34. Sitasawad SL, Shewade Y, and Bhonde R: Role of bittergourd fruit juice in STZ-

induced diabetic state in vivo and in vitro. J Ethnopharmacol 2000; 73: 71-79.

35. Rao BK, Kesavulu MM, Giri R and Appa Rao C: Antidiabetic and hypolipidemic

effects of Momordica cymbalaria Hook. Fruit powder in alloxan-diabetic rats. J

Ethnopharmacol 1999; 67: 103-119.

36. Srividya N and Periwal S: Diuretic, hypotensive and hypoglycemic effect of

Phyllanthus amarus. Indian J Exp Biol 1995; 33 (11): 861-864.

37. Amalraj T and Ignacimuthu S: Evaluation of the hypoglycaemic effect of Cajanus

cajan (seeds) in mice. Indian J Exp Biol 1998; 36: 1032-1033.

38. Ali AA, Mohamed MH, Kamel MS, et al: Studies on Securigera securidacea (L.)

Deg. Et Dprfl. (Fabaceae) seeds, an antidiabetic Egyptian folk medicine. Pharmazie

1998; 53: 710-715.

39. Pant MC, Uddin I, Bhardwaj UR and Tewari RD: Blood sugar and total cholesterol

lowering effect of Glycine soja (Sieb and Zucc.), Mucuna pruriens (D.C.) and

Dolichos biflorus (Linn.) seed diets in normal fasting albino rats. Indian J Med

Res1968; 56 (12): 1808-1812.

40. Akhtar MS, Qureshi AQ and Iqbal J: Antidiabetic evaluation of Mucuna pruriens ,

Linn. seeds. The Journal of Pakistan Medical Association 1990; 40 (7): 147-150.

41. Prakasam A, Sethupathy S and Pugalendi KV: Erythrocyte redox status in

streptozotocin diabetic rats: effect of Casearia esculenta root extract. Pharmazie

2003b; 58 : 920–924.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 65

42. Saxena AM, Bajpai MB and Mukherjee SK: Swerchirin induced blood sugar

lowering of streptozotocin treated hyperglycaemic rats. Indian J Exp Biol 1991; 29:

674-675.

43. Saxena AM, Bajpai MB, Murthy PS and Mukherjee SK: Mechanism of blood sugar

lowering by a Swerchrincontaining hexane fraction (SWI) Swertia chirayita. Indian J

Exp Biol 1993; 31: 178-181.

44. Vijayvargia R, Kumar M and Gupta S: Hypoglycemic effect of aqueous extract of

Enicostemma littorale Blume (chhota chirayata) on alloxan induced diabetes mellitus

in rats. Indian J Exp Biol 2000; 38: 781–784.

45. Murali B, Upadhyaya UM and Goyal RK: Effect of chronic treatment with

Enicostemma littorale in non-insulin-dependent diabetic (NIDDM) rats. J

Ethnopharmacology 2000; 81: 199–204.

46. Shukla K, Narain JP, Puri P, et al: Glycaemic response to maize, bajra and barley.

Indian J Physiol Pharmacol 1991; 35: 249-254.

47. Rai V, Iyer U and Mani UV: Effect of Tulasi (Ocimum sanctum) leaf powder

supplementation on blood sugar levels, serum lipids and tissues lipids in diabetic rats.

Plant Foods Hum Nutr 1997; 50: 9-12.

48. Agrawal P, Rai V and Singh RB: Randomized placebocontrolled, single blind trial of

holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin

Pharmacol Ther 1996; 34: 406-409.

49. Zarzuelo A, Risco S, Gamez MJ, et al: Hypoglycaemic action of Salvia lavandufolia

Vahl. Spp. Oxyodon: a contribution to studies on the mechanism of action. Life Sci

1990; 47: 909-915.

50. Jimenez I. Jimenez J, Gamez J, et al: Effects of Salvia lavandulifolia Vahl ssp

oxyodon extract on pancreatic endocrine tissue in streptozotocin-diabetic rats.

Phytother Res 1995; 9: 536-537.

51. Simon OR, Singh N, Smith K and Smith J: Effect of an aqoues extract of Nichol

(Caesalpinia bounduc) in blood glucose concentration: evidence of an antidiabetic

action presented. Journal of Science Research Council 1987; 6: 25-32.

52. Rao VV, Dwivedi SK and Swarup D: Hypoglycemic effect of Caselpinia bonducella

in rabbits. Fitoterpia 1994; 65: 245-247.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 66

53. Sharma SR, Dwivedi SK and Swarup D: Hypoglycaemic, antihyperglycaemic and

hypolipidemic activities of Caesalpinia bonducella seeds in rats. J Ethnopharmacol

1997; 58: 39-44.

54. Shabana MM, Mirhom YW, Genenah AA, et al: Study into wild Egyptian plants of

potential medicinal activity. Ninth communication : Hypoglycaemic activity of some

selected plants in normal fasting and alloxanised rats. Archiv Fur Exp

Veterinarmedizin 1990; 44: 389-394.

55. Al-Rowais NA: Herbal medicine in the treatment of diabetes mellitus. Saudi Med J

2002; 23: 1327-1331.

56. Sharma RD and Raghuran TC, Raos NS: Effect of fenugreek seeds on blood glucose

and serum lipids in type I diabetes. Eur J Clin Nutr 1990; 44: 301-306.

57. Khosla P, Gupta DD and Nagpal RK: Effect of Trigonella foenum graecum

(Fenugreek) on blood glucose in normal and diabetic rats. Indian J Physiol

Pharmacol 1995; 39: 173-174.

58. Abdel-barry JA, Abdel-Hassan IA and Al-Hakiem MH: Hypoglycaemic and

antihyperglycaemic effects of Trigonella foenum-graecum leaf in normal and alloxan

induced diabetic rats. J Ethnopharmacol 1997; 58: 149-155.

59. Ali L, Azad Khan AK, Hassan Z, et al: Characterization of the hypoglycaemic effects

of Trigonella foenum graecum seed. Planta Med 1995; 61:358-360.

60. Ravikumar P and Anuradha CV: Effect of fenugreek seeds on blood lipid

peroxidation and antioxidants in diabetic rats. Phytother Res 1999; 13: 197-201.

61. Alarcon-Aguilar FJ, Roman-Ramos R, Perez-Gutierrez S, et al: Study of the

antihyperglycaemic effect of plants used as antidiabetics. J Ethnopharmacol 1998;

61: 101-110.

62. Swatson-Flatt SK, Day C, Bailey CJ and Flatt PR: Traditional plant treatments for

diabetes: Studies in normal streptozotocin diabetic mice. Diabetologia 1990; 33: 462-

464.

63. Manickam M, Ramanathan M, Jahromi MA, et al: Antihyperglycaemic activity of

phenolics from Pterocarpus marsupium. J Nat Prod 1997; 60: 609-610.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 67

64. Pari L and Latha M: Effect of Cassia auriculata flowers on blood sugar levels, serum

and tissue lipids in streptozotocin diabetic rats. Singapore Medical Journal 2002; 43:

617-621.

65. Latha M and Pari L: Preventive effects of Cassia auriculata L. flowers on brain lipid

peroxidation in rats treated with streptozotocin. Molecular and Cellular Biochemistry

2003b; 243: 23-28.

66. Abesundara KJ., Matsui T and Matsumoto K: Alpha-glucosidase inhibitory activity of

some Sri Lanka plant extracts, one of which, Cassia auriculata, exerts a strong

antihyperglycemic effect in rats comparable to the therapeutic drug acarbose. Journal

of Agricultural and Food Chemistry 2004; 52: 2541–2545.

67. Latha M and Pari L: Modulatory effect of Scoparia dulcis in oxidative stress-induced

lipid peroxidation in streptozotocin diabetic rats. Journal of Medicinal Food 2003a; 6:

379-386.

68. Singh KN, Chandra V and Barthwal KC: Letter to the editor: hypoglycemic activity

of Acacia arabica, Acacia benthami and Acacia modesta leguminous seed diets in

normal young albino rats. Indian J Physiol Pharmacol 1975; 19 (3): 167-168.

69. Wadood A, Wadood N and Shah SA: Effects of Acacia arabica and Caralluma edulis

on blood glucose levels of normal and alloxan diabetic rabbits. The Journal of

Pakistan Medical Association 1989; 39 (8): 208-212.

70. Sheela CG and Augusti KT: Antidiabetic effects of S-allyl cysteine sulphoxide

isolated from garlic Allium sativum Linn. Indian J Exp Biol 1992; 30: 523-526.

71. Sheela CG, Kumud K and Augusti KT: Antidiabetic effects of onion and garlic

sulfoxide amino acids in rats. Planta Med 1995; 61: 356-357.

72. Augusti KT and Sheela CG: Antiperoxide effect of S-allyl cysteine sulfoxide, an

insulin secretagogue, in diabetic rats. Experientia 1996; 52: 115-120.

73. Kumari K, Mathew BC and Augusti KT: Antidiabetic and hypolipidemic effects of S-

methyl cysteine sulfoxide isolated from Allium cepa Linn. Indian J Biochem Biophys

1995; 32: 49-54.

74. Babu PS and Srinivasan K: Influence of dietary capsaicin and onion on the metabolic

abnormalities associated with streptozotocin induced diabetes mellitus. Mol Cell

Biochem 1997; 175: 49-57.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 68

75. Ajabnoor MA: Effect of aloes on blood glucose levels in normal and alloxan diabetic

mice. J Ethnopharmacol 1990; 28: 215-220.

76. Roman-Ramos R, Alarcon-Aguilar F, Lara-Lemus A and Flores-Saenz JL:

Hypoglycaemic effect of plants used in Mexico as antidiabetics. Arch Med Res 1992;

23: 59-64.

77. Sachdeva A and Khemani LD: A preliminary investigation of the possible

hypoglycemic activity of Hibiscus rosa-sinensis. Biomedicine and Environmental

Science 1999; 12 (3): 222-226.

78. Amalraj T and Ignacimuthu S: Evaluation of the hypoglycemic effect of Memecylon

umbellatum in normal and alloxan diabetic mice. J Ethnopharmacology 1998b; 62

(3): 247-250.

79. Chattopadhyay RR, Chattopadhyay RN, Nandy AK, Poddar G and Maitra SK:

Preliminary report on antihyperglycemic effect of a fraction of fresh leaves of

Azadirachta indica (Beng. Neem). Bulletin of the CalcuttaSchool of Tropical

Medicine 1987a; 35: 29–33.

80. Khosla P, Bhanwra S, Singh J, Seth S and Srivastava RK: A study of hypoglycemic

effects of Azadirachta indica (Neem) in normal and alloxan diabetic rabbits. Indian J

Physiol Pharmacol 2000; 44 (1): 69-74.

81. Chattopadhyay RR: Possible mechanism of antihyperglycemic effect of Azadirachta

indica leaf extract, part IV. General Pharmacology 1996; 27: 431–434.

82. Chattopadhyay RR, Chattopadhyay RN, Nandy AK, Poddar G and Maitra SK: The

effect of fresh leaves of Azadirachta indica on glucose uptake and glycogen content

in the isolated rat hemi diaphragm. Bulletin of the CalcuttaSchool of Tropical

Medicine 1987b; 35: 8–12.

83. Grover JK, Vats V and Rathi SS: Anti-hyperglycemic effect of Eugenia jambolana

and Tinospora cordifolia in experimental diabetes and their effects on key metabolic

enzymes involved in carbohydrate metabolism. J Ethnopharmacology 2000; 73 (3):

461-470.

84. Stanely P, Prince M and Menon VP: Hypoglycemic and other related actions of

Tinospora cordifolia roots in alloxan-induced diabetic rats. J Ethnopharmacology

2000; 70 (1): 9 -15.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 69

85. Prince PS and Menon VP: Antioxidant activity of Tinospora cordifolia roots in

experimental diabetes. J Ethnopharmacology 1999; 65 (3): 277-281.

86. Stanely, Mainzen, Prince P, Menon VP and Gunasekaran G: Hypolipidemic action of

Tinospora cordifolia roots in alloxan diabetic rats. J Ethnopharmacology 1999; 64

(1): 53-57.

87. Achrekar S, Kaklij GS, Pote MS and Kelkar SM: Hypoglycaemic activity of Eugenia

jambolana and Ficus bengalensis : Mechanism of action. In vivo 1991; 5: 143-147.

88. Cherian S, Kumar RV, Augusti KT and Kidwai JR: Antidiabetic effects of glycoside

of pelargonidin isolated from the bark of Ficus bengalensis Linn. Indian J Exp Biol

1992; 29: 380-382.

89. Cherian S and Augusti KT: Antidiabetic effects of glycoside of Leucopelargonidin

isolated from Ficus bengalensis Linn. Indian J Exp Biol 1993; 31: 26-29.

90. Augusti KT, Daniel RS, Cherian S, et al: Effect of leucopelargonin derivative from

Ficus bengalensis Linn. on diabetic dogs. Indian J Med Res 1994; 99: 82-86.

91. Geetha BS, Mathew BC and Augusti KT: Hypoglycaemic effects of leucodelphinidin

derivative isolated from Ficus bengalensis (Linn.). Indian J Physiol Pharmacol 1994;

38: 220-222.

92. Gulubova R and Boiadzhiev TS: Morphological changes in the endocrine pancreas of

the rabbit after the administration of a Morus alba extract. Eksperimentalna meditsina

i morfologiia 1975; 14 (3): 166-171.

93. Chen F, Nakashima N, Kimura I and Kimura M: Hypoglycemic activity and

mechanisms of extracts from mulberry leaves (folium mori) and cortex mori radicis in

streptozotocin-induced diabetic mice. Yakugaku Zasshi 1995; 115 (6): 476-482.

94. Asano N, Oseki K, Tomioka E, Kizu H and Matsui K: Ncontaining sugars from

Morus alba and their glycosidase inhibitory activities. Carbohydrate Research 1994;

259 (2): 243_/255.

95. Ohsugi M, Fan W, Hase K, Xiong Q, Tezuka Y, Komatsu K, Namba T, Saitoh T,

Tazawa K and Kadota S: Activeoxygen scavenging activity of traditional nourishing-

tonic herbal medicines and active constituents of Rhodiola sacra. J

Ethnopharmacology 1999; 67 (1): 111-119.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 70

96. Alarcon-Aguilar FJ, Roman-Ramos R, Perez-Gutierrez S, et al: Study of the

antihyperglycaemic effect of plants used as antidiabetics. J Ethnopharmacol 1998;

61: 101-110

97. Pari L and Umamaheswari J: Antihyperglycaemic activity of Musa sapientum

flowers: effect on lipid peroxidation in alloxan diabetic rats. Phytother Res 2000;

14:136-138.

98. Swatson-Flatt SK, Day C, Bailey CJ, Flatt PR: Traditional plant treatments for

diabetes: Studies in normal streptozotocin diabetic mice. Diabetologia 1990; 33: 462-

464.

99. Gray AM and Flatt PR: Antihyperglycaemic actions of Eucalyptus globulus

(Eucalyptus) are associated with pancreatic and extra-pancreatic effects in mice. J

Nutr 1998; 128: 2319-2323.

100. Prince PS, Menon VP and Pari L: Hypoglycaemic activity of Syzigium cumini

seeds: effect on lipid peroxidation in alloxan diabetic rats. J Ethnopharmacol 1998;

61: 1-7.

101. Chude MA, Orisakwe OE, Monne OJ, Gamaniel KS, Vongtau OH and Obi E:

Hypoglycaemic effect of the aqueous extract of Boerhavia dijfusa leaves. Indian

Journal of Pharmacology 2001; 33: 215-216.

102. Pari L and Amamath Satheesh M: Hypoglycemic activity of Boerhaavia dijfusa L.:

effect on hepatic key enzymes in experimental diabetes. J Ethnopharmacology

2004; 91: 109-113.

103. Satheesh MA and Pari L: Antioxidant effect of Boerhavia diffusa L. in tissues of

alloxan induced diabetic rats. Indian J Exp Biol 2004; 42: 989-992.

104. Mukherjee PK, Pal M, Saha K, Saha BP: Hypoglycaemic activity of Nelumbo

nucifera Gaertn (Fam nymphaeaceae) rhizome (Methanolic extract) in

streptozotocin-induced diabetic rats. Phytother Res 1995; 58: 522-524.

105. Mukherjee PK, Saha K, Pal M, Saha BP: Effect of Nelumbo nucifera rhizome

extract on blood sugar level in rats. J Ethnopharmacol 1997; 58: 207-213.

106. Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J and Osuna I:

Hypoglycaemic activity of olive leaf. Planta Med 1992; 58: 513-515.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 71

107. Pushparaj P, Tan CH and Tan BK: Effects of Averrhoa bilimbi leaf extract on blood

glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol 2000; 72: 69-

76.

108. Puri D and Baral N: Hypoglycaemic effect of Biophytum sensitivum in the alloxan

diabetic rabbits. Indian J Physiol Pharmacol 1998; 42: 401-416.

109. Jafri MA, Aslam M, Javed K, Singh S: Effect of Punica granatum Linn. (flowers)

on blood glucose level in normal and alloxan-induced diabetic rats. J

Ethnopharmacol 2000; 70:309-314

110. Karunanayake EH, Welihinda J, Sirimanne SR and Sinnadorai G: Oral

hypoglycemic activity of some medicinal plants of Sri Lanka. J

Ethnopharmacology 1984; 11 (2): 223-231.

111. Seema PV, Sudha B, Padayatti PS, et al: Kinetic studies of purified malate

deshydrogenase liver of streptozotocin-diabetic rats and the effect of leaf extract of

Aegle marmelose (L.) Correa ex Roxb. Indian J Exp Biol 1996; 34: 600-602.

112. Ponnachan PT, Paulose CS and Panikkar KR: Effect of leaf extract of Aegle

marmelose in diabetic rats. Indian J Exp Biol 1993; 31: 345-347.

113. Das AV, Padayatti PS, Paulose CS: Effect of leaf extract of Aegle marmelose (L.)

Correa ex Roxb. on histological and ultrastructural changes in tissues of

streptozotocin induced diabetic rats. Indian J Exp Biol 1996; 34 (4): 341-345

114. Khan BA, Abraham A and Leelamma S: Hypoglycemic action of Murraya koeingii

(curry leaf) and Brassica juncea (mustard): mechanism of action. Indian Journal of

Biochemistry and Biophysics 1995; 32: 106–108.

115. Khan BA, Abraham A and Leelamma S: Biochemical response in rats to the

addition of curry leaf (Murraya koeingii ) and mustard seeds (Brassica juncea ) to

the diet. Plant Foods and Human Nutrition 1996a; 49 (4): 295-299.

116. Iyer UM and Mani UV: Studies on the effect of curry leaves supplementation

(Murraya koeingii) on lipid profile, glycated proteins and amino acids in non-

insulin-dependent diabetic patients. Plant Foods and Human Nutrition 1990; 40

(4):275-282.

Vol-2, Issue-1, 2011 ISSN: 0976-7908 Donga et al

www.pharmasm.com 72

117. Naik SR, Barbosa Filho JM, Dhuley JN and Deshmukh V: Probable mechanism of

mechanism of hypoglycaemic activity of bassic acid, a natural product isolated

from Bumelia sartorum. J Ethnopharmacol 1991; 33: 37-44.

118. Joy KL and Kuttan R: Anti-diabetic activity of Picrorrhiza kurroa extract. J

Ethnopharmacology 1999; 67 (2): 143-148.

119. Pari L and Venkateswaran S: Hypoglycaemic activity of Scoparia dulcis L. extract

in alloxan induced hyperglycaemic rats. Phytotherapy Research 2002; 16: 662-664.

120. Latha M and Pari L: Effect of an aqueous extract of Scoparia dulcis on blood

glucose, plasma insulin and some polyol pathway enzymes in experimental rat

diabetes. Brazilian Journal of Medical and Biological Research 2004; 37: 577-586.

121. Latha M, Pari L, Sitasawad S and Bhonde R: Insulin-secretagogue activity and

cytoprotective role of the traditional hypoglycemic plant Scoparia dulcis (Sweet

Broomweed). Life Science 2004a ; 75: 2003-2014.

122. Andallu B and Radhika B: Hypoglycaemic, diuretic and hypocholesterolemic effect

of winter cherry (Withania somnifera, Dunal) root. Indian J Exp Biol 2000; 38: 607-

609.

123. Chakrabarti R, Vikramadithyan RK, Mullangi R, Sharma VM, Jagadheshan H, Roo

YN, Sairam P and Rajagopalan R: Hypoglycemic and hypolipidemic activity of

Helicteres isora in animal models. J Ethnopharmacology 2002; 81: 343-349.

124. Gomes A, Vedasiromoni JR, Das M, et al.: Antihyperglycaemic effect of black tea

(Camelia sinensis) in rat. J Ethnopharmacol 1995; 45: 223-226.

125. Garg SK, Shah MA, Garg KM, et al: Antilymphocytic and immunosuppressive

effects of Lantana camara leaves in rats. Indian J Exp Biol 1997; 35: 1315-1318.

For Correspondence: Donga J. J. 16, Gopinath Soc.-3, B/H Magan Nagar-2, Katargam road, Surat-395004, Gujarat. E-mail: [email protected]