Advance in Dietary Polyphenols as Aldose Reductases Inhibitors: Structure-Activity Relationship Aspect

Abstract

The dietary polyphenols as aldose reductases inhibitors (ARIs) have attracted great interest among researchers. The aim of this review is to give an overview of the research reports on the structure-activity relationship of dietary polyphenols inhibiting aldose reductases (AR). The molecular structures influence the inhibition of the following: (1) The methylation and methoxylation of the hydroxyl group at C₃, C_3′, and C_4′ of flavonoids decreased or little affected the inhibitory potency. However, the methylation and methoxylation of the hydroxyl group at C₅, C₆, and C₈ significantly enhanced the inhibition. Moreover, the methylation and methoxylation of C₇-OH influence the inhibitory activity depending on the substitutes on rings A and B of flavonoids. (2) The glycosylation on 3-OH of flavonoids significantly increased or little affected the inhibition. However, the glycosylation on 7-OH and 4′-OH of flavonoids significantly decreased the inhibition. (3) The hydroxylation on A-ring of flavones and isoflavones, especially at positions 5 and 7, significantly improved the inhibition and the hydroxylation on C3′ and C4′ of B-ring of flavonoids remarkably enhanced the inhibition; however, the hydroxylation on the ring C of flavones significantly weakened the inhibition. (4) The hydrogenation of the C2˭C3 double bond of flavones reduced the inhibition. (5) The hydrogenation of α=β double bond of stilbenes hardly affected the inhibition and the hydroxylation on C_3′ of stilbenes decreased the inhibition. Moreover, the methylation of the hydroxyl group of stilbenes obviously reduced the activity. (6) The hydroxylation on C₄ of chalcone significantly increased the inhibition and the methylation on C₄ of chalcone remarkably weakened the inhibition.

Keywords:

• Polyphenols
• flavonoids
• aldose reductases inhibitors (ARIs)
• structure-activity relationship

ACKNOWLEDGMENTS

The authors are grateful for financial sponsorship from National Natural Science Fund of China (31301442), Alexander von Humboldt Foundation, and “China-African University 20+20” project financial sponsored by the China Ministry of Education.