Uncaria rhynchophylla, a Chinese medicinal herb, has potent antiaggregation effects on Alzheimer's β-amyloid proteins

Uncaria rhynchophylla, a Chinese medicinal herb, has potent antiaggregation effects on Alzheimer's β-amyloid proteins
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DOI:
10.1002/jnr.20891
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发表时间:
2006-08-01
影响因子:
4.2
通讯作者:
Arai, Hiroyuki
Arai, Hiroyuki
中科院分区:
医学3区
文献类型:
--
作者:
Fujiwara, Hironori;Iwasaki, Koh;Arai, Hiroyuki

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由于β-淀粉样蛋白(A β)的沉积是阿尔茨海默病(AD)脑的一致病理学标志,因此抑制A β产生、预防A β原纤维形成或使预先形成的A β原纤维不稳定将是治疗AD的有吸引力的治疗策略。我们研究了几种中药中使用的传统中药配方的A β纤维的形成和不稳定的影响,通过使用硫磺素T结合试验,原子力显微镜成像,和电泳。我们的研究表明,这些草药中有几种对A β(1-40)和A β(1-42)的原纤维形成具有浓度依赖性的抑制作用;特别是钩藤抑制A β聚集最强烈。钩藤和其他一些草药提取物也能诱导预先形成的A β(1-40)和A β(1-42)原纤维的显著不稳定。三维HPLC分析表明,这种草药的水提取物含有几种不同的化学成分,包括氧化吲哚和吲哚生物碱,这被认为是神经保护。我们的研究结果表明,钩藤对A β纤维的调节具有显着的抑制作用,我们得出结论,这种草药可能是一种新的治疗药物,以预防和/或治疗AD的潜力。(c)2006 Wiley-Liss,Inc.
Because the deposition of P-amyloid protein (A beta) is a consistent pathological hallmark of Alzheimer's disease (AD) brains, inhibition of A beta generation, prevention of A beta fibril formation or destabilization of preformed A beta fibrils would be attractive therapeutic strategies for the treatment of AD. We examined the effects of several medicinal herbs used in traditional Chinese medical formulae on the formation and destabilization of A beta fibrils by using the thioflavin T binding assay, atomic force microscopic imaging, and electrophoresis. Our study demonstrates that several of these herbs have potent inhibitory effects on fibril formation of both A beta(1-40) and A beta(1-42) in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited A beta aggregation most intensively. Significant destabilization of preformed A beta(1-40) and A beta(1-42) fibrils was also induced by Uncaria rhynchophylla as well as some other herb extracts. Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective. Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of A beta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD. (c) 2006 Wiley-Liss, Inc.