A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose have potent anti-aggregation effects on Alzheimer's amyloid β proteins in vitro and in vivo
A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose have potent anti-aggregation effects on Alzheimer's amyloid β proteins in vitro and in vivo
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DOI：
10.1111/j.1471-4159.2009.06069.x
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发表时间：
2009-06-01
影响因子：
4.7
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
--
作者：
Fujiwara, Hironori;Tabuchi, Masahiro;Arai, Hiroyuki
淀粉样β蛋白的沉积是阿尔茨海默病(AD)脑内一贯的病理特征，因此，抑制Aβ纤维的形成和预先形成的Aβ纤维的不稳定是开发AD疾病修饰药物的一种有吸引力的治疗和预防策略。本研究表明，牡丹不仅抑制Aβ(1-40)和Aβ(1-42)的纤维形成，而且还以浓度依赖的方式破坏预先形成的Aβ纤维的稳定性。通过被动回避任务检测Tg2576转基因小鼠的记忆功能，然后测量大脑中Aβ负荷。该草药改善了转基因小鼠的长期记忆损伤，并抑制了Aβ在大脑中的积累。三维高效液相色谱分析表明，该草本植物的水提物中含有几种不同的化合物，包括甘油三酯(1，2，3，4，6-penta-O-galloyl-beta-d-glucopyranose，PGG)。治疗后未发现明显的不良反应或毒性反应。正如牡丹中观察到的那样，在体外和体内，单独的PGG抑制Aβ纤维的形成和破坏预先形成的Aβ纤维的稳定。结果表明，牡丹及其活性成分PGG在体内外均有较强的抑制Aβ纤维形成的作用。在开发预防和/或治疗AD的疾病修饰药物方面，PGG可能是一种安全和有前途的先导化合物。
The deposition of amyloid beta (A beta) protein is a consistent pathological hallmark of Alzheimer's disease (AD) brains; therefore, inhibition of A beta fibril formation and destabilization of pre-formed A beta fibrils is an attractive therapeutic and preventive strategy in the development of disease-modifying drugs for AD. This study demonstrated that Paeonia suffruticosa, a traditional medicinal herb, not only inhibited fibril formation of both A beta(1-40) and A beta(1-42) but it also destabilized pre-formed A beta fibrils in a concentration-dependent manner. Memory function was examined using the passive-avoidance task followed by measurement of A beta burden in the brains of Tg2576 transgenic mice. The herb improved long-term memory impairment in the transgenic mice and inhibited the accumulation of A beta in the brain. Three-dimensional HPLC analysis revealed that a water extract of the herb contained several different chemical compounds including 1,2,3,4,6-penta-O-galloyl-beta-d-glucopyranose (PGG). No obvious adverse/toxic were found following treatment with PGG. As was observed with Paeonia suffruticosa, PGG alone inhibited A beta fibril formation and destabilized pre-formed A beta fibrils in vitro and in vivo. Our results suggest that both Paeonia suffruticosa and its active constituent PGG have strong inhibitory effects on formation of A beta fibrils in vitro and in vivo. PGG is likely to be a safe and promising lead compound in the development of disease-modifying drugs to prevent and/or cure AD.