Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro:: implications for the prevention and therapeutics of Alzheimer's disease
Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro:: implications for the prevention and therapeutics of Alzheimer's disease
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DOI：
10.1046/j.1471-4159.2003.01976.x
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发表时间：
2003-10-01
影响因子：
4.7
通讯作者：
Yamada, M
中科院分区：
文献类型：
--
作者：
Ono, K;Yoshiike, Y;Yamada, M
淀粉样β-肽（Abeta）在脑中的脑沉积是阿尔茨海默病（AD）的不变特征。流行病学研究已经证明了葡萄酒消费对AD具有一致的保护作用。在本研究中，我们使用荧光光谱与硫磺素T和电子显微镜检查葡萄酒相关的多酚（杨梅素，桑色素，槲皮素，山奈酚（+）-儿茶素和（-）-表儿茶素）的形成，扩展和β-淀粉样蛋白原纤维（fAbeta）在体外37 degreesC在pH 7.5的不稳定的影响。所有检测的多酚剂量依赖性地抑制来自新鲜Abeta（1 - 40）和Abeta（1 - 42）的fAbeta的形成以及它们的延伸。此外，这些多酚剂量依赖性地使预制的fAbeta不稳定。所检测的分子的总体活性顺序为：杨梅素=桑色素=槲皮素>山奈酚>（+）-儿茶素=（-）-表儿茶素。杨梅苷、桑色素和槲皮素对fAbetas的形成、延伸和去稳定化的有效浓度（EC 50）在0.1-1 μ M的量级。在细胞培养实验中，杨梅素处理的fAbeta的毒性低于完整的fAbeta，如3-[4，5-二甲基噻唑-2-基]-2，5-二苯基四唑溴化物测定所示。虽然这些多酚抑制Abeta形成fAb和使体外预形成的fAbeta不稳定的机制仍不清楚，但多酚可能是开发AD预防和治疗药物的关键分子。
Cerebral deposition of amyloid beta-peptide (Abeta) in the brain is an invariant feature of Alzheimer's disease (AD). A consistent protective effect of wine consumption on AD has been documented by epidemiological studies. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of wine-related polyphenols ( myricetin, morin, quercetin, kaempferol (+)-catechin and (-)- epicatechin) on the formation, extension, and destabilization of beta-amyloid fibrils (fAbeta) at pH 7.5 at 37 degreesC in vitro. All examined polyphenols dose-dependently inhibited formation of fAbeta from fresh Abeta(1 - 40) and Abeta(1 - 42), as well as their extension. Moreover, these polyphenols dose-dependently destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of: myricetin = morin = quercetin > kaempferol > (+)- catechin = ( -)- epicatechin. The effective concentrations (EC50) of myricetin, morin and quercetin for the formation, extension and destabilization of fAbetas were in the order of 0.1-1 muM. In cell culture experiments, myricetin-treated fAbeta were suggested to be less toxic than intact fAbeta, as demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay. Although the mechanisms by which these polyphenols inhibit fAb formation from Abeta, and destabilize pre-formed fAbeta in vitro are still unclear, polyphenols could be a key molecule for the development of preventives and therapeutics for AD.