Quercetin inhibits amyloid fibrillation of bovine insulin and destabilizes preformed fibrils

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.

► Quercetin dose-dependently inhibited amyloid formation of bovine insulin.
► Quercetin transformed the preformed fibrils into amorphous aggregates.
► Insulin fibrils induced hemolysis and cytoskeletal aggregation of erythrocytes.
► Quercetin attenuated the fibril-induced cytotoxicity.