A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6-penta-O-galloyl-beta-d-glucopyranose have potent anti-aggregation effects on Alzheimer's amyloid beta proteins in vitro and in vivo

作者：Fujiwara Hironori; Tabuchi Masahiro; Yamaguchi Takuji; Iwasaki Koh; Furukawa Katsutoshi; Sekiguchi Kyoji; Ikarashi Yasushi; Kudo Yukitsuka; Higuchi Makoto; Saido Takaomi C; Maeda Sumihiro; Takashima Akihiko; Hara Masahiko; Yaegashi Nobuo; Kase Yoshio; Arai Hiroyuki^*

来源：Journal of Neurochemistry, 2009, 109(6): 1648-1657.

DOI：10.1111/j.1471-4159.2009.06069.x

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• 6-penta-O-galloyl-beta-d-glucopyranose
• Alzheimer's disease
• amyloid beta protein
• medicinal herb
• Paeonia suffruticosa
• Tg2576 transgenic mice

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.

• 出版日期2009-6