Inhibition of Islet Amyloid Polypeptide Fibrillation by Structurally Diverse Phenolic Compounds and Fibril Disaggregation Potential of Rutin and Quercetin

被引：18
作者：
Abioye, Raliat O. [1 ]
Okagu, Ogadimma D. [1 ]
Udenigwe, Chibuike C. [1 ,2 ]
机构：
[1] Univ Ottawa, Fac Sci, Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada
[2] Univ Ottawa, Fac Hlth Sci, Sch Nutr Sci, Ottawa, ON K1H 8M5, Canada
来源：
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2022年 / 70卷 / 01期
关键词：
islet amyloid polypeptide; fibril formation; phenolic compounds; aggregation; disaggregation; structure-activity relationship; INSULIN; CYTOTOXICITY; AGGREGATION; MECHANISMS; RISK; ACID;
D O I：
10.1021/acs.jafc.1c06918
中图分类号：
S [农业科学];
学科分类号：
09 ;
摘要：
The influence of 12 food-derived phenolic compounds on islet amyloid polypeptide (IAPP) fibrillation was investigated. Results from thioflavin T assay demonstrated that gallic acid, caffeic acid, and rutin and its aglycone, quercetin, inhibited IAPP fibrillation at 1:0.5, 1:1, and 1:2 IAPP-phenolic molar ratios. Circular dichroism and dynamic light scattering at the 1:1 IAPP-phenolic ratio confirmed the inhibition of fibril formation. Rutin and quercetin increased the lag time by 90 and 6%, and the relative alpha-helix content by 63 and 48%, respectively. Gallic acid decreased the elongation rate by 30%, whereas caffeic acid decreased the maximum fluorescence intensity by 65%. Furthermore, fluorescence microscopy and transmission electron microscopy (TEM) showed IAPP fibril morphologies indicative of fibrillation reduction by the compounds. Molecular docking and TEM showed that rutin and quercetin disaggregated preformed IAPP fibrils potentially through fibrillar-monomeric equilibrium shifts. These findings demonstrate important structural features of phenolic compounds for disaggregating IAPP fibrils or inhibiting their formation.
引用
收藏
页码：392 / 402
页数：11
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