Krishna Madhava Prabhu

Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits

The hypoglycaemic and hypolipidemic effect of ethanolic extract obtained from seeds of E. jambolana was investigated in alloxan-induced diabetic rabbits. Hypoglycaemic activity was assessed by reduction in fasting blood glucose (FBG) at 90min and also fall in peak blood glucose during glucose tolerance test (GTT) in sub-diabetic and mild diabetic (MD) rabbits, but in severe diabetic (SD) rabbits by reduction in FBG at 90min. Ethanolic extract (100mg/kg body weight) when given orally to sub-diabetic (AR) for 1 day, MD for 7 days and SD for 15 days showed significant fall in FBG at 90min (12% AR, 18.9% MD and 29% SD) and also produced 16.9% fall in peak blood glucose in AR and 21% in MD rabbits during GTT. When administered daily for 15 days to MD and SD rabbits, significant fall in FBG (41.3% MD, 31.6% SD) and glycosylated haemoglobin (GHb) levels (23.3% MD, 26.6% SD) were observed, while serum insulin level showed significant increase (32.8% MD, 26.9% SD). Liver and muscle glycogen content also increased. The ethanolic extract of seeds also exhibited significant hypolipidemic effect as evident from fall in total serum cholesterol (TC)/high density lipoprotein cholesterol (HDL-c) ratio, serum low density lipoprotein cholesterol (LDL-c) levels and decreased activity of HMG-CoA reductase. The histopathological studies of liver, pancreas and aorta in alcoholic extract treated diabetic groups revealed almost normal appearance.

Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy.

OBJECTIVES Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications including nephropathy. The aim of the present study was to evaluate oxidative stress status in Asian Indian patients of type 2 DM with nephropathy. DESIGN AND METHODS Serum levels of malondialdehyde (MDA) and nitric oxide end products (nitrite and nitrate), activities of erythrocyte superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) content were estimated in controls, patients of type 2 DM without nephropathy (group 1) and with nephropathy (group 2). RESULTS Serum MDA concentration was significantly high in both the groups of diabetic patients as compared to controls, (p < 0.05), with group 2 having a significantly higher value than group 1 (p < 0.05). Significantly elevated serum nitrite levels were found in diabetic patients as compared to controls (p < 0.001), however, no significant difference was found between group 1 and group 2. Moreover, serum nitrate as well as nitrite + nitrate levels were significantly higher in group 2 as compared to controls (p < 0.05). Activity of erythrocyte SOD and CAT was significantly reduced in both groups as compared to controls (p < 0.001) with catalase activity in group 2 being significantly lower than group 1 (p < 0.05). Erythrocyte GSH content was significantly lower in group 2 as compared to controls (p < 0.05) and group 1 (p < 0.05). CONCLUSIONS Results of the present study indicate that oxidative stress is increased and antioxidant defenses are compromised in type 2 DM. These derangements are of a higher magnitude in patients of type 2 DM with nephropathy.

Medicinal plants for treatment of diabetes mellitus

Many plants have been used for the treatment of diabetes mellitus in Indian system of medicine and in other ancient systems of the world. Out of these only a few have been evaluated as per modern system of medicine. From many such plants only extracts have been prepared and their usefulness evaluated in experimental diabetes in animals. In some plants likeAllium cepa, Allium sativum, Ficus bengalensis, Gymnema sylvestre, Pterocarpus marsupium etc. active hypoglycemic principles have been isolated and their mechanism of action studied. Most of them seem to act directly on pancreas (pancreatic effect) and stimulate insulin level in blood. Some have extra pancreatic effect also by acting directly on tissues like liver, muscle etc. and alter favourably the activities of the regulatory enzymes of glycolysis, gluconeogenesis and other pathways. Since the plant products have less side effects, they have the potential as good hypoglycemic drugs. They may also provide clues for the development of new and better oral drugs for diabetes.

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.

Hypolipidemic effect of water extract ofFicus bengalensis in alloxan induced diabetes mellitus in rabbits

Hypolipidemic effect of the water extract of the bark ofFicus bengalensis was investigated in alloxan induced diabetes mellitus in rabbits. Treatment for one month (50 mg/kg body weight/day) brought down the level of total serum cholesterol (TC) in subdiabetic and diabetic rabbits (five in each group) from 82±11 mg% and 118±10.6 mg% to 42.7±3.1 mg% and 51.7±4.7 mg% respectively. Low density lipoprotein cholesterol and very low density lipoprotein cholesterol values came down from 34±10 mg% and 95±24 mg% to 16±3 mg% and 29±4 mg% in subdiabetic and diabetic rabbits. Triacylglycerol level before treatment was 121±21.6 mg% and 416±70 mg% in subdiabetic and diabetic rabbits. Treatment brought it down to 45±5 mg% and 81±27.5 mg%. Glycosylated hemoglobin was brought down from 2.1±0.3% to 1.5±0.1% in subdiabetic group and from 4.28±0.5% to 2±0.3% in diabetic group, indicating that treatment with water extract effectively controlled blood sugar.After treatment with water extract serum lipid values were nearly equal to those in healthy controls (normal) in subdiabetic rabbits, while in diabetic group, the values were only slightly above those of normal.

Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians.

OBJECTIVES The purpose of this study was to explore the association between lipoprotein (a) [Lp(a)] levels, apo(a) isoforms and family history of premature coronary artery disease (CAD) in young Asian Indians. DESIGN AND METHODS 220 patients (age <40 years) with angiographic evidence of CAD and 160 age matched healthy controls were enrolled for the study. Thirty one percent of the patients and 17% of the controls had positive family history (PFH) of premature CAD. Plasma Lp(a) levels were determined by ELISA and apo(a) isoform size was determined using high-resolution immunoblotting method. RESULTS Median plasma Lp(a) levels were 2.5 times higher in patients as compared to controls (30 mg/dL vs 12.7 mg/dL; p<0.05). The patient group having a heterozygous apo(a) isoform pattern showed higher Lp(a) levels as compared to the homozygous group (44.0+/-38.7 vs 28.0+/-26.4 mg/dL; p<0.001). Further low molecular weight apo(a) isoforms (LMW; <22 KIV repeats) were prevalent among CAD patients with PFH as compared to negative family history (62% vs 14%, p<0.05) and this group had the highest Lp(a) levels. Stepwise regression analysis showed that Lp(a) levels and not the apo(a) isoform size, entered the model as significant independent predictors of CAD in young Asian Indians. CONCLUSIONS This study suggests that elevated Lp(a) levels confer genetic predisposition to CAD in young Asian Indians. Thus determination of Lp(a) levels along with other risk factors should be used to assess overall risk for CAD in this ethnic group.

Elucidation of mechanism of action of Cassia auriculata leaf extract for its antidiabetic activity in streptozotocin-induced diabetic rats.

Cassia auriculata traditionally has been used to treat diabetes from ancient times. The objective of the present study was to investigate the mechanism of action for the antidiabetic activity of aqueous leaf extract of C. auriculata (CLEt) in streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) rats. CLEt was orally administered to MD and SD rats at a dose of 400 mg/kg once a day for 15 days. CLEt-treated MD and SD rats showed significant reduction in fasting blood glucose. Assessment of plasma insulin and C-peptide following treatment with CLEt revealed significant elevation in their levels. Administration of CLEt enhanced the activity of hepatic hexokinase and phosphofructokinase and suppressed glucose-6-phosphatase and fructose-1,6-bisphosphatase in both MD and SD rats. A significant rise in glycogen content was also observed in both liver and muscles of CLEt-fed MD and SD rats. Histopathological examination of pancreatic sections revealed increased number of islets and beta-cells in CLEt-treated MD as well as SD rats. The findings of the study suggest that the antidiabetic effect of CLEt could be due to its insulinogenic action. In addition, impaired glucose homeostasis was improved by feeding the extract through amelioration in the carbohydrate metabolic pathways. Thus, the extract may exert an antidiabetic effect through pancreatic as well as extrapancreatic action.

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, Δ5 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.

Hypocholesterolemic effect of water extract of the bark of banyan tree,Ficus bengalensis

The hypocholesterolemic effect of the water extract of the bark ofFicus bengalensis was investigated in 3 groups of rabbits, 5 in each group. Group 1 rabbits served as healthy controls and were fed with groundnut oil 1 ml/kg body wt. (bw) for five weeks. Groups 2 and 3 were made hypercholesterolemic by feeding orally cholesterol suspended in groundnut oil (1 ml/kg bw) at a dose of 100 mg/kg bw/day. Group 2 animals (untreated) continued to get the same amount of cholesterol for another four weeks. Group 3 animals received water extract of the bark (50 mg/kg bw/day) in addition to cholesterol as above. At the end of the 5th week, water extract not only prevented the elevation of serum cholesterol in the treated animals (Group 3) but also brought down its level to 160±14 mg% as compared to untreated animals (Group 2) 290±42 mg%. There was improvement in other parameters of lipid profile namely HDL & LDL+VLDL cholesterol and triacylglycerol.

Antihyperlipidemic Effect of Active Principle Isolated from Seed of Eugenia jambolana on Alloxan-Induced Diabetic Rabbits

Diabetes is accompanied by lipid abnormalities, which contribute significantly to cardiovascular morbidity and mortality in diabetic patients. We previously demonstrated the potent antihyperglycemic activity of the active principle (fraction II from Sephadex LH 20 chromatography [LH II]) isolated from ethanolic seed extract of Eugenia jambolana in diabetic rabbits. In the present study, the efficacy of LH II was evaluated for its hypolipidemic activity in alloxan-induced mildly diabetic (MD) and severely diabetic (SD) rabbits. Phytochemical investigation of LH II by various structural spectra showed the presence of saturated fatty acid, Δ(5) lipid, and sterol. Oral administration of LH II (10 mg/kg of body weight) for 21 days resulted in improved glycemic control in both MD and SD rabbits. After treatment with LH II, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and the total cholesterol/high-density lipoprotein cholesterol ratio were significantly improved. LH II also resulted in significant (P < .001) improvement in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and levels of total lipids and glycogen in both MD and SD rabbits. Thus, the present study demonstrates that LH II possesses potent hypolipidemic activity and efficacy in both MD and SD rabbits.