In vivo assessment of antidiabetic and antioxidative activity of natural phytochemical isolated from fruit-pulp of Eugenia jambolana in streptozotocin-induced diabetic rats.

OBJECTIVES: Eugenia jambolana (E. jambolana) is well known for its antidiabetic potential. The aim of the present study was to investigate the antidiabetic and antioxidative effect of an active compound (FIIc) isolated from fruit-pulp of E. jambolana in streptozotocin (45 mg/kg body weight)-induced diabetic rats. METHODS: FIIc was isolated from the crude aqueous extract of fruit-pulp by ion-exchange column chromatography and high-performance column chromatography. Detailed UV, NMR, and IR spectra suggested that FIIc is α-hydroxy succinamic acid. FIIc was orally administered to diabetic rats at a dose of 10, 15, and 20 mg/kg body weight (mg/kg bwt.) to determine its effective dose. Thereafter, effective dose was administered to 8 weeks to determine its antidiabetic and antioxidative activity by estimation of glycemic index, lipid profile, key enzymes of carbohydrate metabolism, and oxidative stress parameters. RESULTS: Administration of 15 mg/kg dose daily for 8 weeks led to significant (P < 0.001) fall in fasting blood glucose. Treatment with FIIc (15 mg/kg bwt.) showed significant improvement (P < 0.001) in all the biochemical parameters. DISCUSSION: The results demonstrate that FIIc possesses significant antidiabetic and antioxidative activity.

Ameliorative Effect of Active Principle Isolated from Seeds of Eugenia jambolana on Carbohydrate Metabolism in Experimental Diabetes.

The aim of this study was to evaluate the antidiabetic activity of LH II purified from ethanolic seed extract of Eugenia jambolana in alloxan-induced mild diabetic (MD) and severely diabetic (SD) rabbits. Ethanolic extract upon chromatographic purification yielded partially purified hypoglycemic principle (SIII) which on further purification by sephadex LH 20 yielded pharmacological active compound LH II. Homogeneity of LH II was tested by HPLC. Phytochemical investigation of LH II by various structural spectra showed the presence of saturated fatty acid, Δ(5) lipid and presence of sterol. LH II was administered orally at a dose of 10 mg kg(-1) body weight to MD and SD. LH II resulted, significant fall in FBG at 90 min (21.2% MD: 28.6% SD), 7th day (35.6% MD) and 15th day (59.6% SD). Glycosylated hemoglobin was significantly decreased (50.5%) in SD after 15 days treatment (Tt). Plasma insulin levels were significantly increased (P < .001). In vitro studies with pancreatic islets showed 3-fold increase in insulin levels as compared to untreated animals. LH II also showed extrapancreatic effect by significantly increasing (P < .001) the activity of key enzymes of glycolysis and significantly decreasing (P < .001) the activity of key enzymes of gluconeogenesis. Liver and muscle glycogen content were increased by 36.6 and 30% for MD, and 52 and 47% for SD, respectively. Thus, the present study demonstrates that LH II possesses potent antidiabetic activity and it is effective in both MD and SD rabbits.

Antiatherosclerotic Potential of Active Principle Isolated from Eugenia jambolana in Streptozotocin-Induced Diabetic Rats.

The aim of the present study was to investigate the antiatherosclerotic effect of active principle (FIIc) isolated from aqueous fruit pulp extract of Eugenia jambolana. Crude aqueous extract of E. jambolana was subjected to purification using chromatographic techniques which yielded purified active compound (FIIc). Purity of FIIc was tested by HPLC. Phytochemical investigation of FIIc by NMR, IR, and UV spectra showed that the purified compound is α-hydroxy succinamic acid. The streptozotocin- (STZ-) induced diabetic rats were fed atherosclerotic (Ath) diet containing 1.5 mL olive oil containing 8 mg (3, 20,000 IU) vitamin D(2) and 40 mg cholesterol for 5 consecutive days. The STZ-induced diabetic rats receiving Ath diet were orally administered FIIc at doses of 10, 15, and 20 mg/kg, and results were compared with reference drug, that is, glibenclamide (600 µg/mg) and healthy control. 30-day treatment with FIIc resulted in significant (P < .001) improvement in blood glucose, serum lipid profile, apolipoproteins (Apo A(1) and apoB(100)), and endothelial dysfunction parameters. Histomorphological studies also confirmed biochemical findings. Our results showed that FIIc has protective effect on hyperglycemia-induced atherosclerosis.

Attenuation of renal dysfunction by anti-hyperglycemic compound isolated from fruit pulp of Eugenia jambolana in streptozotocin-induced diabetic rats.

The renal protective effect of an active principle isolated from the aqueous extract of fruit pulp of Eugenia jambolana was investigated in streptozotocin (45 mg/kg body weight)-induced severely diabetic rats (FBG > or = 300 mg/dl). For isolation of active principle, crude aqueous extract of E. jambolana fruit pulp was subjected to purification by ion-exchange column chromatography, which yielded a partially purified compound (FII), which on further purification by rechromatography gave a purified active compound (FIIc). Purity of FIIc was confirmed by high pressure liquid chromatography. Detailed UV, NMR, IR spectra suggested that FIIc is a small aliphatic organic compound having molecular formula C4H7O4N. Oral administration of FIIc to diabetic rats (10, 15 and 20 mg/kg body weight per day for a period of 60 days) produced significant (P<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with FIIc (15 mg/kg body wt.) showed significant (P<0.001) improvement in body weight, blood urea, plasma creatinine levels, urinary volume, urinary sugar and microalbuminuria. Renal hypertrophy, assessed as the ratio of the weight of the two kidneys to total body weight was also significantly (P<0.05) improved after treatment with FIIc. The above results suggest that FIIc possesses significant nephroprotective activity.

Protective role of Cassia auriculata leaf extract on hyperglycemia-induced oxidative stress and its safety evaluation.

Cassia auriculata L. (Caesalpiniaceae) is widely used from the ancient period to treat diabetes mellitus. In the present study, the antioxidant activity of C. auriculata aqueous leaf extract (CLEt) was evaluated in streptozotocin-induced mild diabetic (MD) and severe diabetic (SD) rats. A short-term toxicity assessment was also conducted in healthy rats to examine toxic effects of the extract. Oral administration of CLEt to MD and SD rats (100, 200 and 400 mg/kg body weight per day for a period of 21 days) produced significant fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant reduction in serum levels of thiobarbituric acid reactive substances (TBARS) and oxidized low-density lipoprotein (OxLDL) in both MD and SD rats. The antioxidant defense system was also found to be improved in CLEt-treated (400 mg/kg) MD and SD rats, as revealed by significant increase in activities of erythrocyte's antioxidant enzymes, i.e., superoxide dismutase (SOD) and catalase (CAT) with a concomitant elevation in erythrocyte's reduced glutathione (GSH) content. Moreover, there were no toxic signs in rats treated with high doses of the extract (1000 and 2000 mg/kg body weight per day for 21 days). Blood glucose, hepatic and renal function parameters in these rats were found within normal limits. Phytochemical screening of CLEt revealed the presence of alkaloids, flavonoids, saponins, tannins and cardiac glycosides with antihyperglycemic and antioxidant properties. This study suggests that CLEt possesses potent antioxidant activity along with antihyperglycemic potential, hence protective against diabetic complications.

Antihyperglycemic and hypolipidemic activity of aqueous extract of Cassia auriculata L. leaves in experimental diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia auriculata L. (Caesalpiniaceae) is widely used from ancient period to treat diabetes mellitus. The leaves of Cassia auriculata are having potential in the development of drug for diabetes due to its antihyperglycemic and lipid-lowering activity. AIM OF THE STUDY: The present study was to evaluate antihyperglycemic and hypolipidemic activity of aqueous extract of Cassia auriculata leaves (CLEt) in streptozotocin (STZ)-induced mild diabetic (MD) and severe diabetic (SD) rats. MATERIALS AND METHODS: Male Albino rats were rendered diabetic by STZ (45 mg/kg, intraperitoneally). CLEt was orally administered to MD and SD rats at 100, 200 and 400 mg/kg doses for 1 day to determine antihyperglycemic activity. The 400 mg/kg dose was administered daily for 3 weeks to assess glycemic control and hypolipidemic effect. RESULTS: CLEt showed dose dependant fall in fasting blood glucose (FBG). After 5h of extract administration at 400mg/kg dose, FBG was reduced by 13.9% and 17.4% in MD and SD rats respectively. After 3 weeks treatment, CLEt produced significant reduction in FBG and glycosylated haemoglobin (GHb) in both MD and SD rats. Serum lipid levels were reversed towards normal in extract fed MD and SD rats. CONCLUSIONS: The results demonstrate that CLEt possesses potent antihyperglycemic and hypolipidemic activity in both MD and SD rats.

Antihyperglycemic effect of the fruit-pulp of Eugenia jambolana in experimental diabetes mellitus.

The oral antihyperglycemic effect of the water and ethanolic extracts of the fruit-pulp of Eugenia jambolana (EJ) was investigated in alloxan-induced diabetic with fasting blood glucose between 120 and 250 mg/dl as well as severely diabetic rabbits (fasting blood glucose above 250 mg/dl). Water extract was found to be more effective than the ethanolic extract in reducing fasting blood glucose and improving blood glucose in glucose tolerance test. Chromatographic purification of the water extract yielded not only two hypoglycaemic fractions (F-III more active than F-IV) but indicated the presence of hyperglycemic compounds (F-I and F-II) also in the water extract of Eugenia jambolana fruits. When administered as a single dose of 25 mg/kg of body weight; F-III could reduce fasting blood glucose from 174.0 +/- 4.6 to 137.3 +/- 5.4 mg/dl in diabetic (21% fall) and from 266.0 +/- 5.4 to 202.2 +/- 5.2 mg/dl in severely diabetic rabbits (24% fall). After treatment of diabetic and severely diabetic rabbits daily once with 25mg/kg, body weight with F-III for 7 and 15 days, respectively, there was fall in fasting blood glucose (38% diabetic; 48% severely diabetic) and improvement in blood glucose during glucose tolerance test (48%) in diabetic rabbits. Further, there was increase in the plasma insulin levels in both diabetic (24.4%) and severely diabetic rabbits (26.3%). The in vitro studies with pancreatic islets showed that the insulin release was nearly two and half times more than that in untreated diabetic rabbits. The mechanism of action of FIII fraction appears to be both pancreatic by stimulating release of insulin and extra pancreatic by directly acting on the tissues.