Prospecting for Novel Plant-Derived Molecules of Rauvolfia serpentina as Inhibitors of Aldose Reductase, a Potent Drug Target for Diabetes and Its Complications
Under normal conditions, glucose is metabolized to release carbon dioxide along with energy. Under hyperglycemic conditions, AR converts glucose to sorbitol, utilizing cofactor NADPH and consequently reduces glutathione level. Further, sorbitol is converted to fructose by NAD+ -dependent sorbitol dehydrogenase, leading to production of reactive oxygen species. Intracellular accumulation of sorbitol creates a loss of osmotic integrity and cellular damage, while depletion of NADPH and NAD+ cofactors compromises body’s antioxidant defence systems. In addition, high blood levels of fructose may account for increased glycation. These changes result in osmotic and oxidative stresses, ultimately leading to various micro-vascular complications in a number of tissues. Polyol pathway, thus, is involved in various biochemical changes that are relevant to diabetes-induced vascular dysfunction. AR controls the rate-limiting step of polyol pathway, and inhibition of AR provides a possible strategy to prevent complications of chronic diabetes.