Myricetin Prevents Fibrillogenesis of Hen Egg White Lysozyme

【摘要】：Myricetin is a natural flavonol found in many grapes, berries, fruits, vegetables, herbs aswell as other plants. Recent studies have identified potential anti-amyloidogenic activityfor this compound. In this study, the kinetics of amyloid fibril formation by hen egg whitelysozyme(HEWL) and the anti-fibril forming activity of myricetin were investigated. Wedemonstrate that myricetin significantly inhibits the fibrillation of HEWL and the inhibitoryeffect is dose-dependent. Interestingly, the inhibitory effect towards HEWL fibrillation wasstronger than that exerted by the previously characterized fibril-forming inhibitor quercetin,which has high structural similarity with myricetin. Spectrofluorometric and computationalstudies suggest that the mechanism underlying the inhibitory action of myricetin ata molecular level is to reduce the population of partially unfolded HEWL intermediates.This action is achieved by the tight binding of myricetin to the aggregation prone regionof the β-domain of HEWL and linking to the relatively stable α-domain, thus, resulting inthe inhibition of amyloid fibril formation.