Inhibition effects of quinones on aldose reductase: Antidiabetic properties

Abstract

Diabetes mellitus is a chronic metabolic disease characterized by abnormal glucose metabolism. Aldose reductase (AR) is the first enzyme in the polyol pathway and converts glucose to sorbitol. It plays a vital role as a glucose reducing agent and is involved in the pathophysiology of diabetic complications. In this study, we purified AR from sheep kidney with a specific activity of 2.00 EU/mg protein and 133.33- fold purification After the purification of the AR enzyme, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed and the molecular weight of the enzyme was found approximately as 38 kDa. The inhibition effects of eight quinones were studied against AR. The quinones were potent inhibitors of AR with K-i values in the range of 0.07-20.04 mu M. Anthraquinone showed the best potential inhibitory effects against AR. All compounds exhibited noncompetitive inhibition against AR. These compounds may be selective inhibitors of this enzyme. AR inhibition is an essential strategy for the attenuation and prevention of diabetic complications.