Hepatoprotective and antioxidant activity of N-Trisaccharide in different experimental rats.

OBJECTIVES: To investigate the hepatoprotective, antioxidant and antihyperlipidemic effect of N-Trisaccharide isolated from Cucumis prophetarum (L.) on different experimental rats. METHODS: N-Trisaccharide (25 and 50 mg/kg.b.w), silymarin (25 mg/kg) and glibenclamide (25 mg/kg) was orally administered once daily for 28 days and toxicity evaluation studies were carried out. Liver damage was assessed by determining DNA damage, serum enzyme activities and hepatic histopathology of carbon tetrachloride (CCl4) induced hepatic injury in rats. Enzymatic and non enzymatic antioxidant levels in liver and kidney were determined and biochemical parameters such as, serum lipid profile, renal function markers were estimated in type 2 diabetic rats. RESULTS: DNA fragmentation analysis revealed the protective effect of N-Trisaccharide on liver DNA damage. Histopathological studies indicated that CCl4-induced liver injury was less severe in N-Trisaccharide (25 and 50mg/kg) treated group. Given at the above doses conferred significant protection against the hepatotoxic actions of CCl4 in rats, reducing serum markers like SGOT, SGPT, ALP, creatinine and urea levels back to near normal (p<0.05) compared to untreated rats. In diabetic rats, N-Trisaccharide treatment significantly reversed abnormal status of enzymatic and non-enzymatic antioxidants levels to near normal. Also, serum lipids such as TG, TC, LDL-C and VLDL-C levels were significantly (p<0.05) reduced compared to diabetic untreated rats. CONCLUSION: Present study results confirm that N-Trisaccharide possesses significant antihyperlipidemic, antioxidant and hepatoprotective properties.

Anti-diabetic effect of a novel N-Trisaccharide isolated from Cucumis prophetarum on streptozotocin-nicotinamide induced type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cucumis prophetarum (L.) is used in traditional Indian medicine for the treatment of inflammation related problems. AIM OF THE STUDY: The present investigation was designed to study the effect of N-Trisaccharide (a new compound isolated from the fruit of C. prophetarum (L.)) on hyperglycemia in streptozotocin (STZ)-nicotinamide (NA) induced type 2 diabetic rats. MATERIALS AND METHODS: Different doses of N-Trisaccharide (25 and 50 mg/kgb.w.) were administered once daily for 28 days to STZ-NA induced diabetic rats. Plasma insulin and glycogen levels were measured. The activities of hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase were measured. Further, histological studies on pancreas were also carried out. RESULTS: The active compound at doses of 25 and 50 mg/kgb.w. given orally for 14 days showed 47.7% and 69.3% antihyperglycemic activity, respectively. Treatment at the same doses for 28 days provided complete protection against STZ-NA challenge (65 and 230 mg/kgb.w., respectively), intraperitoneally. N-Trisaccharide significantly (p≤0.05) increased the plasma insulin and liver glycogen levels in diabetic rats. The altered enzyme activities of carbohydrate metabolism in the liver and kidney of the diabetic rats were significantly (p≤0.05) improved. Additionally, N-Trisaccharide increased glycogen synthase and decreased glycogen phosphorylase activity in diabetic rats. Histological studies confirmed an increase in insulin level is due to stimulation of injured pancreatic ß-cells. CONCLUSION: The results of the study suggested that N-Trisaccharide possesses propitious effect on STZ-NA induced type 2 diabetes, indicating its usefulness in diabetes management.

Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats.

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Its complications such as neuropathy, cardiopathy, nephropathy, and micro and macro vascular diseases are believed to be due to the increase in oxidative stress and decrease in the level of antioxidants. The aim of this study was to determine the antihyperglycemic activity of synthetic Secoisolariciresinol diglucoside (SDG) in streptozotocin (STZ)-induced diabetic rats. The synthetic SDG in a single-dose (20 mg/kg b.w.) two-day study showed dose-dependent reduction in glucose levels with maximum effect of 64.62% at 48 h post drug treatment (p<0.05), which is comparable to that of the standard drug tolbutamide (20 mg/kg b.w.). In a multi-dose fourteen-day study, lower doses of SDG (5 and 10 mg/kg b.w.) exhibited moderate reduction in glucose levels, lipid profile, restoration of antioxidant enzymes and improvement of the insulin and c-peptide levels which shows the regeneration of ß-cell which secretes insulin. Altered levels of lipids and enzymatic antioxidants were also restored by the SDG to the considerable levels in diabetic rats. Results of the present investigation suggest that diabetes is associated with an increase in oxidative stress as shown by increase in serum malondialdehyde (MDA), decreased levels of catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). Also, diabetes is associated with an increase in serum total cholesterol as well as triglycerides levels and decrease in insulin and c-peptide levels. SDG is effective in retarding the development of diabetic complications. We propose that synthetic SDG exerts anti hyperglycemic effect by preventing the liver from peroxidation damage through inhibition of ROS level mediated increased level of enzymatic and non-enzymatic antioxidants. And, also maintaining tissue function which results in improving the sensitivity and response of target cells in STZ-induced diabetic rats to insulin.