Protective effect of Tephrosia purpurea in diabetic cataract through aldose reductase inhibitory activity

Abstract

Purpose: Tephrosia purpurea (T. purpurea) has been reported to prevent cataract formation in senile cataract model as well as proven effective in STZ induced type 1 diabetes. Aldose reductase (AR) is a key enzyme in the intracellular polyol pathway responsible for the development of diabetic cataract. Objective: To investigate the effects of T. purpurea in the light of inhibition of aldose reductase enzyme in polyol pathway. Methods: We studied the effects of alcoholic extract and flavonoid fraction of T. purpurea in streptozotocin (STZ, 45 mg/kg, i.v.)-induced type I diabetic cataract in rats. The animals were divided into five groups as control, control treated with alcoholic and flavonoid fraction, diabetic control and diabetic treated with alcoholic and flavonoid fraction. In-vitro aldose reductase inhibitory activity was also evaluated. Further, molecular docking study was performed with crystal structure of aldose reductase and its known chemical constituents of the plant. Results: The IC50 value of alcoholic extract for aldose reductase inhibition was found to be 209.13 mg/ml, and that of flavonoid fraction was found to be 46.73 mg/ml. Administration of STZ produced significantly abnormal levels of serum glucose, serum insulin, soluble protein and antioxidants in the lens homogenate. Treatment with alcoholic extract and flavonoid fraction of T. purpurea were able to normalize these levels. Some of the active constituents of T. purpurea showed significant interactions with aldose reductase enzyme in molecular docking studies. Conclusions: Our data suggested that both the extracts might be helpful in delaying the development of diabetic cataract due to the presence of rutin and quercetin. This beneficial effect may be due to its significant inhibition of aldose reductase enzyme and anti-oxidant activity.