Clinical Biochemistry & Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, 226026, U.P., India.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
Int J Biol Macromol. 2018 Sep;116:983-992. doi: 10.1016/j.ijbiomac.2018.05.115. Epub 2018 May 18.
Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is greatly influenced by 3-hydroxy-3-methyl-glutaryl Co-A reductase (HMG-R) activity. HMG-R inhibitors, statins, are well known for reducing mortality and morbidity of ASCVD in patients with diabetes due to their pleiotropic effects independent of cholesterol lowering. Due to distinct chemical structures, various statins may play important role in the inhibition of AGEs mediated pathologies. Herein, we evaluated the anti-glycating potential of atorvastatin (AT), rosuvastatin (RT), pitavastatin (PT), fluvastatin (FT), simvastatin (ST) alone as well in combination with ezetimibe (EZ) and tocotrienol (TT) against d-ribose mediated BSA and LDL glycation by various physicochemical approaches. Our data suggested that AT, TT, RT, EZ, EZ-AT, and EZ-RT were able to substantially inhibit the AGEs formation via modulation of hyperchromicity, fluorogenic AGEs, % contribution of α-helix and β-sheets to protein secondary structure, amide-I band stretching, carbonyl and HMF content in Gly-BSA as well as Gly-LDL. On the basis of above findings, we concluded that HMG-R inhibitors and TT, alone or in combination with EZ, may be established as terrific therapeutic agents for the patients suffering from AGEs induced diabetic cum ASCVD complications.
非酶糖基化介导的晚期糖基化终产物（AGEs）的产生导致了糖尿病并发症和动脉粥样硬化性心血管疾病（ASCVD）的发病机制，而这一过程受到 3-羟-3-甲基戊二酰辅酶 A 还原酶（HMG-R）活性的极大影响。HMG-R 抑制剂，即他汀类药物，由于其独立于降胆固醇作用的多效性，在降低糖尿病患者 ASCVD 的死亡率和发病率方面表现出色。由于其独特的化学结构，各种他汀类药物可能在抑制 AGEs 介导的病变方面发挥重要作用。在此，我们评估了阿托伐他汀（AT）、瑞舒伐他汀（RT）、匹伐他汀（PT）、氟伐他汀（FT）、辛伐他汀（ST）单独以及与依折麦布（EZ）和生育三烯酚（TT）联合应用对 d-核糖介导的 BSA 和 LDL 糖基化的体外抗糖化潜力，采用了多种物理化学方法进行评估。我们的数据表明，AT、TT、RT、EZ、EZ-AT 和 EZ-RT 能够通过调节增色效应、荧光 AGEs、α-螺旋和β-折叠对蛋白质二级结构的贡献、酰胺-I 带拉伸、羰基和 HMF 含量，显著抑制 AGEs 的形成，从而抑制 Gly-BSA 和 Gly-LDL。基于上述发现，我们得出结论，HMG-R 抑制剂和 TT，单独或与 EZ 联合使用，可能成为治疗因 AGEs 引起的糖尿病伴 ASCVD 并发症患者的有效治疗药物。
