Bioflavonoid ellagic acid inhibits aldose reductase: Implications for prevention of diabetic complications

Accumulation of intracellular sorbitol due to increased aldose reductase (AR or ALR2) activity is one of the pathways implicated in the development of long-term diabetic complications. In the present study, we described the inhibition of ALR2 by ellagic acid (EA), a bioflavonoid present in many dietary sources. EA inhibited ALR2 with an IC50 of 48 nM in a non-competitive manner. Further, EA is relatively more specific towards ALR2 as it did not inhibit aldehyde reductase, a closely related member of AKR family. Molecular docking studies support and substantiate these findings. Further, EA suppressed sorbitol accumulation in human erythrocytes, rat lens and rat retina under high glucose conditions. Finally, physiologic significance of EA was demonstrated in terms of delay of diabetic cataract in rats as a prototype model of diabetic complications. Together, these observations suggest that EA holds a therapeutic promise to prevent or treat complications of diabetes.