Fujiwara Hironori, Iwasaki Koh, Furukawa Katsutoshi, Seki Takashi, He Mei, Maruyama Masahiro, Tomita Naoki, Kudo Yukitsuka, Higuchi Makoto, Saido Takaomi C, Maeda Sumihiro, Takashima Akihiko, Hara Masahiko, Ohizumi Yasushi, Arai Hiroyuki
Department of Geriatric and Complementary Medicine, Center for Asian Traditional Medicine Research, Tohoku University School of Medicine, Sendai, Japan.
J Neurosci Res. 2006 Aug 1;84(2):427-33. doi: 10.1002/jnr.20891.
Because the deposition of beta-amyloid protein (Abeta) is a consistent pathological hallmark of Alzheimer's disease (AD) brains, inhibition of Abeta generation, prevention of Abeta fibril formation, or destabilization of preformed Abeta 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 Abeta 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 Abeta(1-40) and Abeta(1-42) in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited Abeta aggregation most intensively. Significant destabilization of preformed Abeta(1-40) and Abeta(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 Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.
由于β-淀粉样蛋白(Aβ)的沉积是阿尔茨海默病(AD)大脑一致的病理特征,抑制Aβ生成、防止Aβ纤维形成或使已形成的Aβ纤维不稳定将是治疗AD的有吸引力的治疗策略。我们通过使用硫黄素T结合试验、原子力显微镜成像和电泳,研究了几种用于中医方剂的草药对Aβ纤维形成和不稳定的影响。我们的研究表明,其中几种草药对Aβ(1-40)和Aβ(1-42)的纤维形成具有浓度依赖性的强效抑制作用;特别是,钩藤对Aβ聚集的抑制作用最为强烈。钩藤以及其他一些草药提取物也能使已形成的Aβ(1-40)和Aβ(1-42)纤维显著不稳定。三维高效液相色谱分析表明,这种草药的水提取物含有几种不同的化合物,包括氧化吲哚和吲哚生物碱,它们被认为具有神经保护作用。我们的结果表明,钩藤对Aβ纤维的调节具有显著的抑制作用,我们得出结论,这种草药有可能成为预防和/或治疗AD的新型治疗剂。