IAPP aggregation and cellular toxicity are inhibited by 1,2,3,4,6-penta-O-galloyl-β-D-glucose.
IAPP aggregation and cellular toxicity are inhibited by 1,2,3,4,6-penta-O-galloyl-β-D-glucose.
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DOI：
10.3109/13506129.2012.762761
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Moffet DA
中科院分区：
文献类型：
--
作者：
Bruno E;Pereira C;Roman KP;Takiguchi M;Kao PY;Nogaj LA;Moffet DA
多酚1,2,3,4,6-五- o -没食子酰-β- d -葡萄糖（PGG）已被发现具有许多积极的药理活性，包括抗癌和抗糖尿病。我们对PGG产生这些积极活性的作用方式知之甚少。我们在这里表明，PGG是IAPP（胰岛淀粉样多肽，胰淀素）聚集的有效抑制剂。阻止IAPP的初始聚集事件是减缓甚至可能预防IAPP低聚中间体毒性作用的一种策略。等摩尔比的PGG与IAPP大大降低了IAPP结合硫黄素t的能力。原子力显微镜显示，在有利于形成IAPP聚集体的严格条件下，PGG阻止淀粉样蛋白基纤维的形成。PGG还被发现可以保护PC12大鼠细胞免受毒性IAPP的侵害。将PGG与已知的淀粉样蛋白抑制剂（以及结构上的近亲）进行比较；单宁酸和没食子酸。在每项试验中，PGG在抑制淀粉样蛋白聚集方面都远优于单宁酸和没食子酸。这些结果表明，PGG是一种有效的IAPP淀粉样蛋白聚集抑制剂，是开发淀粉样蛋白抑制疗法的潜在先导分子。
The polyphenol, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. PGG was compared to the known amyloid inhibitors (and structural relatives); tannic acid and gallic acid. In every test, PGG was far superior to tannic and gallic acids at inhibiting amyloid aggregation. These results indicate that PGG is a potent inhibitor of IAPP amyloid aggregation and a potential lead molecule for development of an amyloid inhibiting therapeutic.
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