INTRODUCTION:^{1, 2}

Diabetes is any disorder characterized by excessive urine excretion. The most common form of diabetes is diabetes mellitus, a metabolic disorder in which there is an inability to oxidize carbohydrate due to disturbances in insulin function. Diabetes mellitus is characterized by elevated glucose in the plasma and episodic ketoacidosis. Additional symptoms of diabetes mellitus include excessive thirst, glucosuia, polyuria, lipemia and hunger. If left untreated the disease can lead to fatal ketoacidosis. Other forms of diabetes include diabetes insipidus and brittle diabetes. Diabetes insipidus is the result of a deficiency of antidiuretic hormone. The major symptoms of diabetes insipidus (excessive urine output) results from an inability of the kidneys to reabsorb water. Brittle diabetes is a form that is very difficult to control. It is characterized by unexplained oscillations between “Hypoglycemia and Acidosis”. Criteria, which clinically establish an individual as suffering from diabetes mellitus, include:

1. Having a fasting plasma glucose level in excess of 126mg/dl (7mmol/L). Normal levels should be less than 100mg/dL (<5.6mmol/L).

2. Glucose tolerance test.

Current status of diabetes:^{2, 3}

In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population. Its incidence is increasing rapidly, and it is estimated that by the year 2030, this number will almost double. Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will probably be found by 2030. The increase in incidence of diabetes in developing countries follows the trend of urbanization and lifestyle changes, perhaps most importantly a "Western-style" diet. This has suggested an environmental (i.e., dietary) effect, but there is little understanding of the mechanism(s) at present, though there is much speculation, some of it most compellingly presented. For at least 20 years, diabetes rates in North America have been increasing substantially. In 2008 there were about 24 million people with diabetes in the United States alone, from those 5.7 million people remain undiagnosed. Other 57 million People are estimated to have pre-diabetes.³

Classification of Diabetes Mellitus:⁴

Insulin-Dependent Diabetes Mellitus (IDDM):

Type 1diabetes has been shown to be the result of an autoimmune reaction to antigens of the islet cells of the pancreas. There is a strong association between IDDM and other endocrine auto immunities (e.g. Addison disease). Additionally, there is an increased prevalence of autoimmune disease in family members of IDDM patients.

Non-Insulin-Dependent Diabetes Mellitus (NIDDM):

NIDDM is characterized by a lack of the need for insulin to prevent ketoacidosis. Type 2 diabetes refers to the common form of idiopathic NIDDM. NIDDM is not an autoimmune disorder; however, there is a strong genetic correlation to the susceptibility to NIDDM. The susceptibility genes that predispose one to NIDDM have not been identified in most patients. This is due in part to the heterogeneity of the genes responsible for the susceptibility to NIDDM. Obesity is a major risk factor that predisposes one to NIDDM. Genetic studies in mice and rats have demonstrated a link between genes responsible for obesity and those that cause diabetes mellitus.

Problems Associated With Diabetes:⁵

The most important health impacts of diabetes are the long-term complications it can cause. Most of these long-term complications are related to the adverse effects diabetes has on arteries and nerves. Complications related to artery damage: - Diabetes causes damage to both large and small arteries. This artery damage results in medical Problems that is both common and serious:

• Cardiovascular disease. Diabetics have up to a 400% greater chance of heart attack or stroke. Heart disease and stroke cause about 65% of deaths among people with diabetes. These deaths could be reduced by 30% with improved care to control blood pressure and blood glucose and lipid levels.

• Amputations. About 82,000 people have diabetes-related leg and foot amputations each year. Over 60% of non-traumatic lower limb amputations are diabetes related. Foot care programs that include regular examinations and patient education could prevent up to 85% of these amputations.

• Kidney disease. About 38,000 people with diabetes develop kidney failure each year. Treatment to better control blood pressure and blood glucose levels could reduce diabetes-related kidney failure by about 50%.

• Eye disease and blindness. Each year, 12,000-24,000 people become blind because of diabetic eye disease, including diabetic retinopathy. Diabetes is the leading cause of new cases of blindness among adults 20-74 years old. Screening and care could prevent up to 90% of diabetes-related blindness.

• Sexual Dysfunction. Approximately 70% of all adult males with diabetes currently suffer or will experience sexual dysfunction or impotence.

Other Complications:-

· Flu- and pneumonia-related deaths. Each year, 10,000-30,000 people with diabetes die of complications from flu or pneumonia. They are roughly three times more likely to die of these complications than people without diabetic

· Pregnancy complications. About 18,000 women with pre-existing diabetes deliver babies each year, and an estimated 135,000 expectant mothers are diagnosed with gestational diabetes. These women and their babies have an increased risk for serious complications.

Many of these potential complications can significantly shorten the life of a person with diabetes, and all of them can diminish the quality of life.

Role of Natural Products to Management the Diabetic:

Alkaloids:

1. Aporphin obtained from the aqueous fraction of an alcoholic extract of leaves of Vinca rosea L. Catharanthus roseus (Apocynaceae) Don leads to marked lowering of glycaemia in normal and streptozotocin-induced diabetic rats. This effect was comparable with that of tolbutamide. Three suspension cultures of C. rosea were obtained from three different cell lines (CWS, CW-A and CWS-G). In the production medium, the first cell line produced 0.1 % ajmalicine and the cell extract caused a 71 % decrease in glycaemia in diabetic rats. In contrast, in the growth medium, CWS produced trace amounts of alkaloids and the extract did not show any anti-diabetic activity. The CWA cell line synthesized 0.036 % ajmalicine. The extract had no hypoglycemic effect while in the growth medium the cells produced trace amounts of alkaloids and the extract induced an 86 % decrease in blood sugar⁶

2. Cryptolepine is a natural product isolated from Cryptolepis sanguinolentav (Asclepiadaceae). A series of substituted and hetero substituted cryptolepine analogues have been synthesized. Anti hyperglycemic activity was measured in vitro and in a NIDDM mouse model to generate the first structure bioactivity study of the cryptolepine nucleus. It was shown that cryptolepine, isolated from C. sanguinolenta, significantly lowers glucose when given orally to diabetic mice. The anti hyperglycemic effect of cryptolepine leads to a significant decline in blood glucose concentration, associated with evidence of an enhancement in insulin mediated glucose disposal. Finally, cryptolepine increased glucose uptake by 3T3- L1 cells.⁷

3. Tecomine and Tecostanin study was performed in rabbits subjected to weekly glucose tolerance tests after gastric administration of water, tolbutamide or a preparation of the plant. The results showed that Tecoma stans (Bignoniaceae) significantly decreased the area under glucose tolerance curve, compared to control (17.5%), or tolbutamide (14.3 %).^8,9

4. Ephedrine In a study of desert plants collected from some Egyptian localities, oral administration of an extract obtained from Ephedra elata (Gnetaceae) to normal glycaemic rats produced a persistent hypoglycemic effect when compared to Daonil.⁹

5 .Indole alkaloid the postprandial glycaemic response of Hordeum vulgare (Barley) (Gramineae) was studied in a pool of 18 healthy volunteers and 14 patients having non-insulin dependent diabetes mellitus (type II). The glycaemic response to barley was significantly lower than that to white bread in both groups of subjects. However, the insuline mice 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.¹⁰

6. Ephedrine, obtained from Sida cordifolia (Malvaceae) extracts of the aerial and root parts showed hypoglycemic activity. Moreover, the methanol extract of root was found to possess significant hypoglycemic activity.¹¹

7. Berberine obtained from an aqueous extract of Tinospora Cordifolia (Menispermaceae) roots on oral administration produced a significant decrease in glycaemia and brain lipids in alloxan-induced diabetic rats.¹²

8. Isoquinoline A obtained from methanol extract of Nelumbo nucifera Gaerth (Nymphaeaceae) (East Indian Lotus) obtained by soxhlet extraction from finely pulverized rhizomes was used. The extract (300 mg/kg and600 mg/kg, orally) caused a decrease in glycaemia in streptozotocin-induced diabetic rats by 53 % and 55 %,respectively at the end of 12 h. 173 Oral administration of the ethanolic extract of rhizomes of N. nucifera mark early reduced the glycaemia of healthy, glucose-fed hyperglycemic 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.¹³

9. Carbazole obtained from Murraya koenigii Spreng (Rutaceae). This study demonstrated the Hypoglycaemic increased activity of glycogen synthetase, and decrease in glycogenolysis and gluconeogenesis as shown by decreased activity of glycogen phosphorylase and gluconeogenic enzymes after treatment with M. koenigii.¹⁴

10. Withanolides Six mild NIDDM subjects and six mild hyper cholesterolemic subjects were treated with a powder of Withania somnifera (ashvagandha) (Solanaceae) roots for 30 days. The treatment produced a decrease in blood glucose levels that was comparable of that of normal hypoglycemic drug. The authors concluded that W.somnifera could be a potential source of hypoglycemic agents.¹⁵

11. Hyoscyamine obtained as the extracts of Daucus carota L (Apiaceae) which had been given by oral loading. The extract of Daucus carota L. was prepared by boiling the dried material with water or macerating it with 80 % ethanol. It was shown that the extract improved the glucose tolerance.¹⁶

12. Solasonine obtained from Solanum verbascifolium (Solanaceae) significantly decreased the area under glucose tolerance curve, compared to control (21.1%) and tolbutamide (14.3%).¹⁶

2. Flavonoids:

1. Kaempherol, myricetin obtained from Mangifera indica L (Mango) (Anacardiaceae). The antidiabetic activity of was seen when an extract of the leaves of M. indica was given to rats 60 min before the glucose. The hypoglycemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg). The hypoglycemic action of this plant may be due to a reduction in the intestinal absorption of glucose.¹⁷

2. 2-beta-D-glucopyranosyloxyl-1-hydroxy-6(E)-tidecene-7, 9, 11-triyne (1) and 3- Beta-Dglucopyranosyloxyl-1-hydroxy-6(E)-tetradecene-8, 10, 12-triyne (2). A 3:2 mixture of glucosides (1) and (2) In vivo bioguided fractionation of the aqueous alcohol extract of the aerial part of Bidens pilosa Sch. Bip. Var. Radiata (Asteraceae) using a model of type 2 diabetes (C57 BL/Ks-db/dbmice).¹⁸

3. Flavone (5, 7, 3’-trihydroxy-3, 6, 4’-trimethoxyflavone) intraperitoneal administration of 300 mg/kg of the hexane extract from Brickellia veronicaefolia A. (Asteraceae) to diabetic mice decreased blood glucose levels by 72 %. This extract administered to normal mice reduced blood glucose levels by 40 %. The hypoglycemic effect of this plant extract confirmed its use in traditional medicine for the treatment of diabetes. This flavone produced a significant hyperglycemic action when tested in normal glycaemic and alloxan-induced diabetic mice (CD 1 mice). The doses tested were 10, 20 and 50 mg/kg. The glycaemia was measured 1.5, 3, 4.5 and 24 hours after drug administration.¹⁹

4. The oral administration of the pectin isolated from the fruit of the Coccina indica Wight and Am. (Ivy Gourd) (Cucurbitaceae) at a dose of 200 mg/100gBW/day produced a reduction in glycaemia and an increase in liver glycogen. Glycogen synthetase activity was significantly increased. Incorporation of labeled glucose significant reduction in phosphorylase activity was noted in the pectin-administered groups.²⁰

5. Ginkgetin In humans: An oral glucose tolerance test (OGTT) was undertaken (75g) before and after ingestion of Ginkgobiloba extract (Ginkgoacea) (120 mg/day at bed time) for three months in 20 individuals (14 females and 6 males, ages 21-57).Fasting plasma insulin and C-peptide areas under the curve during the OGTT changed from 136+/- 55 to 162+/- 94micro U/ml/h (p = 0.1232) and 9.67+/- 5.34 to 16.88 +/-5.20 ng/ml/h (p<0.001), respectively. It seems that G. biloba may increase insulin release.²¹

6. Kolaviron, a mixture of C-3/C-8 obtained from Garcinia kola Heckel (Guttifere) Produced significant hypoglycemic effects when administered intraperitoneal to healthy and alloxan diabetic rabbits at a dose of 100mg/kg. The fasting blood glucose in normoglycaemic rabbits was reduced from 115 mg/100 ml to 65 mg/100 ml after 4 h. In alloxan-diabetic rabbits the blood sugar was lowered at 12 h. Kolaviron inhibited rat lens aldose reductase activity with an IC 50 value of 5.4 x 10-6 M.107.²²

7. Apigenin A study was performed using healthy rabbits with intragastric administration of water, tolbutamide or a decoction of the Marrubium vulgare L (Lamiaceae). Before the induction of temporary hyperglycemia by subcutaneous injection of 50 % dextrose solution (4 ml/kg of weight) at 0 and 60min. Tolbutamide and M. vulgare significantly decreased the hyperglycemia as compared to control (water) in healthy rabbits.²³

8. Cycloartemone, cycloartenol, beta-sitosterol the water extract of Artocarpus heterophyllus Lam. (JackFruit) (Moraceae) significantly lowered the fasting blood glucose level and markedly improved glucose tolerance in Sprague-Dawley rats. Moreover, the hypoglycemic activity of this plant was greater than that of tolbutamide. The magnitude of the hypoglycemic effects varied with the dosage used but did not change with storage, even up to 3 days.²⁴

9. Anthocyamines, artocarpine cycloarticarpine the hypoglycemic effects of hot water extracts (WE) from Morus alba L. (Folium mori, Mulberry leaves) or cortex Mori radicis (Moraceae) were tested in fasted and nonfasted streptozotocin-induced diabetic mice at a single dose of200 mg/kg (i.p.). The WE of M. alba exhibited the most potent hypoglycemic effects. The most potent fractions of M. alba and cortex Mori radicis were ethanol-insoluble extracts (A2). These A2 fractions produced a decrease in glycaemia of 24.6 ± 6.0 % and 60.5 ± 9.1% in non fasted streptozotocin-mice, and 81.4 ± 7.9 % and 77.3 ± 5.8 in fasted streptozotocin-mice, respectively. The authors concluded that the increased hypoglycemic action of WE and A2 of M. alba was mediated by an increase in glucose uptake.²⁵

10. Coutareagin Oral intragastric administration of an extract of Hintonia latiflora cortex (Rubiaceae) produced a significant blood glucose lowering effect.²⁶

11. Anthemidime Chamaemelum nobile = Anthemis mobilis Linn. (Compositae) is a 3hydroxy-3-methylglutaric acid (HMG) containing flavonoids, which has been shown to have in vivo hypoglycemic activity comparable to that of free HMG.²⁷

12. Kampherol is a preparation of the whole plant, Phyllanthus amarus Shum. and Thon (Euphorbiaceae) possesses antidiabetic activity.²⁸

13. Queratin is a 50 % methanolic extract (30mg/kg) of Phyllanthus urinaria Linn.

(Euphorbiaceae). A decrease in blood glucose level (BGL) was observed 3 h after oral administration of this extract in streptozotocin induced diabetic rats. The n butanol soluble fraction extract was most effective. In the oral glucose tolerance test, the n-butanol fraction of the tow plants inhibited the initial increase of BGL. The n butanol fraction of P. urinaria did not inhibit the increase of BGL prominently after intraperitoneal glucose load. P. urinaria extract may act via the facilitation of glucose metabolism and/or the inhibition of glucose absorption in the gut like the action of biguanides.²⁹

3 Saponines:

1 Senticosus saponin isolated from the leaves of Acantho panax (Araliaceae) injected to mice (100, 200 mg/kg, i.p.) decreased experimental hyperglycemia induced by injection of adrenaline, glucose and alloxan, without affecting the levels of blood sugar in untreated mice.³⁰

2. Elatosides E was isolated from the root cortex of Araliae lata Seem. (Japanese Angelica) Seem (Araliaceae). It was shown to affect the elevation of plasma glucose levels in an oral sugar tolerance test in rats.³¹

3. Gymnemosides A and B, but also gymnemic acid V as the active principle, effects of the water soluble fraction of an alcoholic extract of Gymnema sylvestre R. Br. (Asclepiadaceae) leaves on glycogen content of isolated rat hemi diaphragm was studied in normal and glucose fed hyperglycemic rats. In glucose fed rats, the leaf extract lowered the glycogen content of the tissue and this effect was amplified by insulin.³²

4. Scoparianosides A, B and C. A methanolic extract of the Japanese fruit Kochia scopariaL. (Chenopodiaceae) was shown to inhibit the increase in serum glucose in glucose-loaded rats. The active principles shown to inhibit glucose and ethanol absorption in rats.³³

4 Glycosides:

1. Betavulgarosides II, III and IV extracts obtained from Beta vulgaris var.Cicla L.

(Leaf beet); (Sugar beet) (Chenopodiaceae) inhibited the increase in the non enzymatic 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 and produce hypoglycemic mice effects that were demonstrated by an oral glucose tolerance test in rats.³⁴

2. Bitter glycoside Treatment over 15 days with Momordica cymbalaria Hook (Cucurbitaceae) fruit powder produced a significant blood glucose lowering effect in alloxan-induced diabetic rats, but not in normal glycaemic rats. Moreover, the fruit powder reduced the level of cholesterol and triglycerides in diabetic rats.³⁵

3. A new cardenolide (-)-14-methoxyhyrcanoside was isolated from an aqueous extract of the seeds of Securigera securidacea L (Fabaceae) 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 hypoglycemic.³⁶

4. Escins-Ia, Ib, IIa,IIb and IIIa were isolated from the seeds of Aesculus hippocastanum L. (Common Horse-Chestnut) (Hippocastanaceae) plant.These compounds showed hypoglycemic activity. Greater hypoglycemic activities were obtained with escins IIa and IIb.³⁷

5. S-allyl cysteine sulphoxide (SACS), a sulphur-containing amino acid of Allium sativum L. (Garlic) ( Liliaceae) 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 intestinal HMG CoA reductase activity and liver hexokinase activity. 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.³⁸

6. Allyl propyl disulphide, allicin, diphenylamine Oral administration of Allium cepa L. (Onion) (Liliaceae) S-methylcysteine 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. 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 a15 mg % capsaicin diet or 3 % freeze-dried onion powder containing diet produced a significant reduction in the hyperglycemic status of diabetic animals. This study revealed that onion feeding improves the metabolic status in diabetes probably because of its hypo cholesterolemic as well as its hypoglycemic effect.³⁹

7. Furanditerpene glycoside. A study showed that the anti hyperglycemic effect of Tinospora crispa (Menispermaceae) was not due to interference with intestinal glucose uptake or uptake of the sugar into peripheral cells. Rather, the anti hyperglycemic effect of T. crispa is probably due to stimulation of insulin release via modulation of intracellular Ca2+ concentration in pancreatic beta-cells.⁴⁰

8. Senegin-II, the main component of Polygala senega (Polygalaceae) when given at2.5 mg/kg, reduced the level of blood glucose in healthy mice 4 h after intraperitoneal administration.⁴¹

10. Christinin-A In healthy rats, treatment of one to four weeks duration with the butanol extract of Zizyphus spina-christi (Christ-Thoron) (Rhamnaceae) leaves produced in significant changes in all studied parameters. However, in streptozotocin-induced diabetic rats, both treatments significantly reduced serum glucose levels, liver phosphorylase and glucose-6-phosphatase activities, and significantly increased the serum pyruvate level and liver glycogen content after 4 weeks of treatment. There was also marked improvement in glucose utilization in diabetic rats in both cases. Serum insulin and pancreatic cAMP levels showed significant increases in diabetic rats treated for a period of 4 weeks with the butanol extract.⁴²

11. Prunin (naringenin 7-O-beta-D-glucoside), a methanolic extract of Prunus davidiana (Rosaceae) Franch stems produced a significant hypoglycemic effect. The authors suggested that the methanolic extract contains one or more hypoglycemic principles including the main flavone glycoside, pruning, which can significantly reduce the level of blood glucose and total lipids in streptozotocin induced diabetic rats.⁴³

5 Terpenoides:

1. 3 hydroxy-3-methylglutaric acid, from the water soluble fraction of Tillandsia usneoides L. (Spanish moss) (Bromeliaceae) shows hypoglycaemic effect in fasting healthy mice.⁴⁴

2. Trans-dehydrocrotonin (t-DCTN), a 19-nor-clerodanediterpene isolated from the bark of Croton cajucara Benth. (Euphorbiaceae) showed a significant hypoglycaemic activity in alloxan induced diabetic rats but not in healthy rats at oral doses of 25 and 50 mg/kg body weight.⁴⁵

3. Colosolic acid and maslinic acid from Lagerstroemia speciosa Pers. (Queen Carpe-Myrtle) (Banaba) (Lythraceae) was the most active on D-glucose uptake by Ehrlich ascites tumor cells. The hypoglycaemic effects of L. speciosa were studied using hereditary diabetic mice (Type II, KK-Ay/TaJcl). A treatment of 5-week duration with different extracts from banaba leaves showed beneficial effects on the level of plasma glucose in non-insulin dependent diabetes mellitus.⁴⁶

6. Volatile Oil:

1 Alfa-pinene, sabinene, alpha-terpinene obtained from dried berries of Juniperus communis Linn. (Cupressaceae) supplied in the diet (6.25 % by weight) and decoction (1g/400 ml) reduced the level of hyperglycemia in streptozotocin induced diabetes. Furthermore, administration of the decoction decreased glycaemia at a dose of 250 mg/kg. Administration of the decoction (125mg/kg of total juniper/kg) to streptozotocin-induced diabetic rats during 24 days also produced blood glucose lowering effects.⁴⁷

2. Delta-linalool obtained from Seeds of Coriandrum sativum L (Coriander) (Apiaceae) when supplied in the diet (6.25 % by weight) and infusion (1 g/400 ml) inplace of drinking, reduced the hyperglycemia during the development of streptozotocin-induced diabetes in mice.⁴⁷

3. Eugenol obtained from Ocimum sanctum and Ocimum album Roxb. (Holy basil) (Lamiaceae) 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 15.8mg/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 glucoselevels showed a similar trend.⁴⁸

4. Cineol obtained from Eucalyptus globulus Labill. (Tasmanian Bleu Gum) (Myrtaceae) when given to streptozotocin-diabetic mice reduced the level of hyperglycaemia. In contrast, it has been found that the decrease in hyperglycemia caused by E. globulus was not significant. In another study, it was demonstrated that E.globulus possesses an anti hyperglycemic action due to pancreatic and extra pancreatic effects in diabetic mice.⁴⁹

7. Tannins:

1. Marsupsin and pterostilbene obtained from heartwood of Pterocarpus marsupium (Leguminosea) significantly lowered the glycaemia of diabetic rats, and the effect was comparable to that of 1,1- dimethylbiguanide(metformin).⁵⁰

2.Polyphenols—(−)-epicatechingallate,(−)epigallocatechine galate, the aflavin monogallate A or B, and or theaflavin digallate obtained from The hot water extract of Camellia sinensis L. (blacktea) (Theaceae) significantly reduced the blood glucose levels ofstreptozotocin-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.⁵¹

8. Xanthones Derivatives:

1. Swerchirin isolated from the hexane fraction of Swertia chirayita Bush-Ham (Gentianaceae) has a very significant blood sugar lowering effect in fasted, fed, glucose loaded, and tolbutamide pre-treated albino rats. The ED50 for 40 %glycaemia lowering in CF male albino rats is 23.1 mg/kg when orally administered.⁵²

2. Bellidifolin obtained from the ethyl acetate soluble fraction of Swertia japonica (Javanica) Blum Bijdr. (Gentianaceae) showed a potent and dose dependent hypoglycemic activity in streptozotocin-induced diabetic rats both in intraperitoneal and administration. Bellidifolin, by both oral and intraperitoneal administration, significantly lowered glucose concentrations in normal and streptozotocin-induced diabetic rats. Bellidifolin also lowered blood triglyceride levels. It also stimulated glucose uptake activity in rat 1-fibroblasts expressing human insulin receptors.⁵³

9. Others:

1. Neobetanin obtained from Opuntia ficus indica Mill. (Indian fig) (Cactaceae) In humans: Oral intake of 500 g of entire broiled, blend broiled, blend crude or blended crude and heated (at 60° C) by eight patients with type II diabetes significantly decreased glycaemia after 120 and 180 min in each group. The major hypoglycemic effect shown ranged from 23.3 ± 4.4 to25.4 ± 14.3 mg/dl below the glucose levels at 0 min. No differences in the hypoglycemic effects were observed between diverse preparations.⁵⁴

2. Lantadenes A, B obtained from Lantana camaraL. (Verbenaceae) leaves given at different dose levels (60, 300, 600 and1500 mg/kg/day) for 14 days in rats resulted in alterations in various hematology and biochemical parameters, a strong hypoglycemic effect was seen with 1500 mg only.⁵⁵

CONCLUSION:

Diabetes is a metabolic disorder which can be considered as a major cause of high economic loss which can in turn impede the development of nations. Moreover, uncontrolled diabetes leads to many chronic complications such as blindness, heart failure, and renal failure. In order to prevent this alarming health problem, the development of research into new hypoglycemic and potentially antidiabetic agents is of great interest. This review paper has presented a list of natural products used in the treatment of diabetes mellitus. The natural product of plants with the most potent hypoglycemic effects include: Alkaloids, flavonoids, Flavones, Pectin, Terpenoides, Saponins, Tannins, Glycosides, Volatile oils, Xanthones derivatives. The most commonly studied family are: Apocynaceae, Asclepiadaceae, Bigoniaceae, Gnetaceae, Gramineae, Malvaceae, Menispermaceae, Nymphaeaceae, Rutaceae, Solanaceae, Apiaceae, Anacardiaceae, Asteraceae, Cucurbitaceae, Ginkgoaceae, Lamiaceae, Moraceae, Rubiaceae, Euphorbiaceae, Chenopodiaceae, Fabaceae, Hippocastanaceae, Liliaceae, Menispermaceae, Myrtaceae, Leguminoseae, Cactaeae, Verbenaceae.. It showed that these products have hypoglycemic effects. Many new bioactive drugs isolated from plants having hypoglycemic effects showed antidiabetic activity equal and sometimes even more potent than known oral hypoglycemic agents such as Daonil, Tolbutamide and Chlorpropamide. However, many other active agents obtained from plants have not been well characterized. More investigations must be carried out to evaluate the mechanism of action of natural products with antidiabetic effect. The toxic effect of these plants should also be elucidated.

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Received on 07.01.2010 Modified on 13.02.2010

Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 650-656