Amylin Amyloid Inhibition by Flavonoid Baicalein: Key Roles of Its Vicinal Dihydroxyl Groups of the Catechol Moiety

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• 作者：Paul Velander ; Ling Wu ; W. Keith Ray ; Richard F. Helm ; Bin Xu
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：August 9, 2016
• 年：2016
• 卷：55
• 期：31
• 页码：4255-4258
• 全文大小：301K
• 年卷期：0
• ISSN：1520-4995

文摘

Amyloid formation of the 37-residue amylin is involved in the pathogenesis of type 2 diabetes and, potentially, diabetes-induced neurological deficits. Numerous flavonoids exhibit inhibitory effects against amylin amyloidosis, but the mechanisms of inhibition remain unclear. Screening a library of natural compounds uncovered a potent lead compound, the flavone baicalein. Baicalein inhibits amylin amyloid formation and reduces amylin-induced cytotoxicity. Analogue analyses demonstrated, for the first time, key roles of the vicinal hydroxyl groups on the A-ring. We provided mass spectrometric evidence that incubating baicalein and amylin leads to their conjugation, consistent with a Schiff base mechanism.