Ciddi Veeresham, Dodda Dilip
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, AP, India.
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, AP, India.
Pharmacol Rep. 2014 Oct;66(5):799-803. doi: 10.1016/j.pharep.2014.04.006. Epub 2014 Apr 30.
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.
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.
RSV exhibited inhibitory activity against RLAR and RKAR with IC50 values of 4.99 μg/ml (21.9 μM) and 5.49 μg/ml (24.5 μM), 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.
The results obtained in this study underline the potential of RSV as a possible therapeutic agent against long-term diabetic complications.
多种机制以复杂的整合模式参与糖尿病并发症的发生。本研究旨在评估白藜芦醇(RSV)对醛糖还原酶(AR)和晚期糖基化终产物(AGEs)的抑制活性,及其在治疗糖尿病并发症如白内障和肾病方面的潜力。
研究了RSV对大鼠晶状体AR(RLAR)和大鼠肾脏AR(RKAR)的体外抑制活性,以及其抑制AGEs形成的能力。使用糖诱导的离体牛晶状体混浊模型证明了RSV的抗白内障活性。此外,通过评估肾功能的关键标志物以及AGEs的形成,研究了RSV在链脲佐菌素诱导的糖尿病肾病中的作用。强效AR抑制剂非达司他作为对照标准。
RSV对RLAR和RKAR表现出抑制活性,IC50值分别为4.99μg/ml(21.9μM)和5.49μg/ml(24.5μM)。它在体外也显示出对AGEs形成的显著抑制作用。在糖诱导的晶状体混浊模型中,RSV表现出显著的保护作用,可防止牛晶状体混浊和多元醇的形成。RSV显著改善糖尿病大鼠的血糖状态和肾功能,同时肾脏中AGEs的形成显著减少。
本研究获得的结果强调了RSV作为抗长期糖尿病并发症潜在治疗药物的潜力。