Therapeutic potential of resveratrol in diabetic complications: In vitro and in vivo studies

Background: Various mechanisms with a complex integrating paradigm have been implicated in diabetic complications. The present study was aimed to evaluate the aldose reductase (AR) and advanced glycation end products (AGEs) inhibitory activity of resveratrol (RSV) and its potential in the treatment of diabetic complications such as cataract and nephropathy. Methods: RSV was studied for its inhibitory activity against rat lens AR (RLAR) and rat kidney AR (RKAR) in vitro along with its ability to inhibit formation of AGEs. Anticataract activity of RSV was demonstrated using sugar induced lens opacity model in isolated cattle lens. Furthermore the involvement of RSV in streptozotocin-induced diabetic nephropathy was investigated by assessing the key markers of kidney function along with the formation of AGEs. The potent AR inhibitor, fidarestat was as a standard. Results: RSV exhibited inhibitory activity against RLAR and RKAR with IC50 values of 4.99 mu g/ml (21.9 mu M) and 5.49 mu g/ml (24.5 mu M), respectively. It also showed a significant inhibition of AGEs formation in vitro. In sugar-induced lens opacity model, RSV displayed a significant protective effect preventing opacification and formation of polyols in cattle lens. RSV significantly improved glycaemic status and renal function in diabetic rats with a significant decrease in the formation of AGEs in the kidneys. Conclusions: The results obtained in this study underline the potential of RSV as a possible therapeutic agent against long-term diabetic complications. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.