College of Life Science, Shaanxi Normal University, Xi'an 710062, China.
Biochem Biophys Res Commun. 2011 Dec 2;415(4):675-9. doi: 10.1016/j.bbrc.2011.10.135. Epub 2011 Nov 6.
Growing interest and research efforts have recently been focused on elucidating the molecular mechanism of amyloid formation and the screening of effective inhibitors to interrupt amyloid structures. In the present study, the anti-amyloidogenic effects of quercetin were investigated in vitro using bovine insulin as a model protein. The results demonstrated that quercetin dose-dependently inhibited amyloid formation of insulin. Moreover, quercetin destabilized the preformed insulin fibrils and transformed the fibrils into amorphous aggregates. Hemolysis was observed when human erythrocytes were co-incubated with insulin fibrils. Quercetin inhibited fibril-induced hemolysis in a dose-dependent manner. SDS-PAGE showed that insulin fibrils induced the aggregation of cytoskeletal proteins of erythrocyte membranes and that quercetin attenuated this fibril-induced cytoskeletal aggregation. The results of the present work suggest that quercetin may serve as a lead structure for the design of novel anti-amyloidogenic drugs.
最近，人们对阐明淀粉样蛋白形成的分子机制以及筛选有效的抑制剂以打断淀粉样结构的研究兴趣日益浓厚。在本研究中，以牛胰岛素为模型蛋白，在体外研究了槲皮素的抗淀粉样蛋白形成作用。结果表明，槲皮素能剂量依赖性地抑制胰岛素的淀粉样蛋白形成。此外，槲皮素还能使已形成的胰岛素纤维解聚，并将纤维转化为无定形聚集体。当人红细胞与胰岛素纤维共孵育时，会发生溶血。槲皮素能呈剂量依赖性地抑制纤维诱导的溶血。SDS-PAGE 显示，胰岛素纤维诱导红细胞膜骨架蛋白聚集，而槲皮素则能减弱这种纤维诱导的骨架蛋白聚集。本研究结果表明，槲皮素可能成为设计新型抗淀粉样蛋白形成药物的先导结构。
