Fisetin Prevented Amyloid Formation of Insulin and Attenuated Fibril-induced Cytotoxicity

Abstract

Natural polyphenols are major constituents of plant foods and herbs. Numerous reports demonstrated that these compounds inhibited amyloid formation and destabilized the preformed amyloid fibrils. The present study, utilizing bovine insulin as a model peptide, examined the anti-amyloidogenic effects of fisetin (3,7,3',4'-tetrahydroxyflavone). Fluorescent probes, transmission electron microscopy and hemolytic assay were utilized to determine the roles of fisetin on amyloidogenesis of insulin. The results demonstrated that fisetin dose-dependently inhibited amyloid formation of insulin. Moreover, fisetin disaggregated the preformed insulin fibrils and transformed the fibrils into non-amyloid structures. Hemolysis was observed when erythrocytes were co-incubated with insulin fibrils. Fisetin inhibited fibril-induced hemolysis in a dose-dependent manner. Hydrophobic interaction is suggested to be a key driving force in the anti-amyloidogenic and fibril-disaggregating effects of fisetin. The results of the present work suggest that fisetin is an effective anti-amyloidogenic compound and may serve as a lead structure for the design of novel drugs for the treatment of amyloid diseases.