Neuroprotection by resveratrol in diabetic neuropathy: concepts & mechanisms

Resveratrol is a naturally occurring phytoalexin found in many plants, nuts and fruits and is abundant in grapes and red wine. Resveratrol possesses a wide range of biological activities which include antioxidant, anti-inflammatory, chemoprotective, chemopreventive etc. Resveratrol has been investigated extensively in diabetes and its complications which suggest its anti-diabetic activity and protective effect against various diabetic complications. Neurons are extremely susceptible to oxidant-induced damage which may be due to their high rate of oxygen consumption and low levels of antioxidant defence enzymes. Traditionally, it was thought that the protective actions of resveratrol in diabetic neuropathy are due to its intrinsic radical scavenger properties. However, recently many other associated or separate mechanisms like upregulation of Nrf2, SIRT1 and inhibition of NF-κB, AP-1 have been proposed for its beneficial effect against nerve dysfunction. This present review discusses the neuroprotective effects of resveratrol that have been observed in experimental diabetic neuropathy and possible mechanistic explanations, as these effects may provide directions for the development of newer therapies. Futuristic therapies can be based on either resveratrol or its analogs with better bioavailability, or combining the resveratrol with existing therapies.