Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats
4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid which is a succinamic acid derivative has been synthesized in 3 step reaction with malic acid. Its structure confirmation was done by various techniques like 1H NMR, 13C NMR, & HRMS and is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study, the effect of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid on plasma glucose, serum insulin, serum lipid profile and lipid peroxidation in streptozotocin–nicotinamide induced type 2 diabetic model was investigated. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid was administered orally (20 mg/kg b.w.) to streptozotocin + nicotinamide (STZ + NAD) induced diabetic rats for 28 days. A significant increase in fasting blood glucose levels, HbA1c levels, Serum lipid profile (TG & TC) and in the levels of Malonaldialdehyde (MDA, end product of lipid peroxidation) was observed in STZ +NAD diabetic rats whereas the levels of high density lipoprotein-cholesterol (HDL-C) and serum insulin levels were significantly decreased in STZ + NAD induced diabetic rats The effect of 4-((benzyloxy)amino)-2-hydroxy-4-oxobutanoic acid was compared with glibenclamide, a reference drug. Treatment with 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid and glibenclamide resulted in a significant reduction of fasting blood glucose levels with increase in plasma insulin levels in diabetic treated rats. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid also resulted in a significant improvement in serum lipids and lipid peroxidation products. Our results suggest the potential role of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid in the management of type-2 diabetes mellitus experimental rats.
Keywords: 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid, dyslipidemia, streptozotocin induced diabetes, lipid peroxidation
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