Inhibition of Islet Amyloid Polypeptide Fibrillation by Structurally Diverse Phenolic Compounds and Fibril Disaggregation Potential of Rutin and Quercetin
Inhibition of Islet Amyloid Polypeptide Fibrillation by Structurally Diverse Phenolic Compounds and Fibril Disaggregation Potential of Rutin and Quercetin
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DOI：
10.1021/acs.jafc.1c06918
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发表时间：
2022-01-12
影响因子：
6.1
通讯作者：
Udenigwe, Chibuike C.
中科院分区：
文献类型：
--
作者：
Abioye, Raliat O.;Okagu, Ogadimma D.;Udenigwe, Chibuike C.
研究了12种食源性酚类化合物对胰岛淀粉样多肽（IAPP）纤颤的影响。硫黄素T试验结果表明，没食子酸、咖啡酸、芦丁及其苷元槲皮素在IAPP-酚物质的摩尔比为1:0.5、1:1和1:2时抑制IAPP纤颤。圆二色性和iapp -酚比为1:1的动态光散射证实了对纤维形成的抑制。芦丁和槲皮素分别使滞后时间增加了90%和6%，相对α -螺旋含量分别增加了63%和48%。没食子酸使延长率降低30%，咖啡酸使最大荧光强度降低65%。此外，荧光显微镜和透射电子显微镜（TEM）显示IAPP纤维形态，表明化合物减少了纤颤。分子对接和透射电镜显示，芦丁和槲皮素可能通过纤维-单体平衡转移分解预形成的IAPP原纤维。这些发现证明了酚类化合物分解或抑制IAPP原纤维形成的重要结构特征。
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.