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Inhibition of aldose reductase and sorbitol accumulation by dietary rutin

Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2 or AKR1B1) activity has been implicated in the development of various secondary complications of diabetes. Previously we have reported that some common dietary sources such as spices, fruits and vegetables have the potential to inhibit ALR2 under in vitro conditions and in animal models. In this study, we describe the inhibition of ALR2 by rutin, a bioflavonoid present in many dietary sources. Rutin inhibited ALR2 with an IC50 value of 13 μM in an uncompetitive manner, but was a poor inhibitor of closely related members of the aldo–keto reductase (AKR) superfamily, particularly aldehyde reductase (ALR1). Results from molecular docking studies were consistent with the pattern of inhibition of ALR2 by rutin and its specificity. Moreover, rutin was able to suppress sorbitol accumulation in human erythrocytes under high glucose conditions, demonstrating an in vivo potential of rutin to prevent sorbitol accumulation. These results suggest that rutin holds a promise as an agent to prevent or treat diabetic complications.