Structure-Activity Relationship Of Dietary Flavonoids As Aldose Reductase Inhibitors

Plant-derived foods provide mankind with plenty of nutrients,minerals and also with secondary metabolite products.Dietary flavonoids as important class of secondary plant products constitute most abundant antioxidants of plant-derived foods.Flavonoids are generally regarded as the most abundant antioxidant of food resources and might contribute to maintain human health such as anticancer,antidiabetics,antibacterial and other pharmacological effects.Aldose reductase is found in many tissues and organs of the body,such as nerves,red blood cells,lenses,retina,etc.Together with NADPH(adenine dinucleotide phosphate)-dependent oxidoreductase,it mediates conversion of glucose to sorbitol,or accumulation of sorbitol,which is the first step and key reductase glucose metabolism.Aldose reductase inhibitors include mainly carboxylic acids,heterocyclic compounds,flavonoids from traditional Chinese medicine.As the only non-drug and low side-effect substance of dietary flavonoids,many scholars have proved that it can be a good inhibitor of aldose reductase.We systematically studied structure-activity relationship of dietary flavonoids as of aldose reductase inhibitors.It is generally believed that dietary polyphenols play an important role in the treatment of diabetic complications as aldose reductase inhibitors.The aim of this study is to study the structure-activity relationship of polyphenols and aldose reductase,to understand how these inhibitors bind to this enzyme and to provide a reasonable basis for the new inhibitors of aldose reductase.Herein,we investigated the inhibitory effects of typical flavonoids with regard to their activity on AR,and summarized the structure – activity relationship.It affected the inhibitory potential against aldose were summarized as follows:(1)The methylation on C5,C3',C4' of flavones remarkably weakened the inhibition;The methylation on C6,C8 of flavones enhanced the inhibition.(2)The hydroxylation on C5,C6,C7 of flavones,notably at positions 5 and6,observably enhanced the inhibition;The hydroxylation on C3' of flavones remarkably weakened the inhibition.(3)The hydrogenation of the C2=C3 double bond of flavones weakened the inhibition.(4)The glycosylation of flavonoids at different positions show different influence on their inhibitory potential.