Natural aldose reductase inhibitors act as potent agonists of PPARγ

Abstract

Background: Diabetes and cancer have been the leading cause of mortality all over the world. Studies on association between diabetes and cancers over a decade indicate a positive relationship between them. Epidemio-logic evidence suggests that people with diabetes are prone to various types of cancers. This work suggests a novel strategy for the treatment of diabetes and cancers. Methods: Extra-precision (XP) docking strategy, was used to predict the binding interactions of partial, full agonists of PPARγ and aldose reductase inhibitors on the PPARγ crystal structures. Binding interactions of PPARγ with the partial agonists, NTzDpa and MEKT76 and the full agonist Rosiglytasone were exploited to identify partial and full agonists of PPARγ among aldose reductase inhibitors. Results: Full and partial agonists of PPARγ inhibit various cancers, by suppressing the factors associated with neovascularisation. Partial agonists of PPARγ are prefered than full agonists like thiazolidinediones, reported to have serious side effects. Aldose reductase inhibitors used to treat diabetic complications, show binding interactions similar to the agonists of PPARγ and could hold a heuristic approach in treating diabetes and cancers. Conclusion: Aldose reductase inhibitors, tetrahydrocurcumin, catechin-5-O-gallate, rutin, (2S)-2’- methoxykurarinone, epalrestat, 8-lavandulylkaempferol depict interactions of partial agonists of PPARγ and could be further studied for their dual role as agonist and antagonist of the proteins PPARγ and Aldose reductase respectively.