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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Authors: | Hironori Fujiwara,Masahiro Tabuchi&dagger ,Takuji Yamaguchi&dagger ,Koh Iwasaki,Katsutoshi Furukawa&Dagger ,Kyoji Sekiguchi&dagger ,Yasushi Ikarashi&dagger ,Yukitsuka Kudo§ ,Makoto Higuchi¶ ,,Takaomi C. Saido,Sumihiro Maeda&dagger &dagger ,Akihiko Takashima&dagger &dagger ,Masahiko Hara&Dagger &Dagger ,Nobuo Yaegashi,Yoshio Kase&dagger , Hiroyuki Arai&Dagger |
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Affiliation: | Center for Asian Traditional Medicine, Tohoku University Graduate School of Medicine, Sendai, Aoba-ku, Japan; TSUMURA Research Laboratories, TSUMURA &Co., Ibaraki, Japan; Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Japan; Innovation of Biomedical Engineering Center, Tohoku University, Aoba-ku, Sendai, Japan; Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan; Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan; Laboratory for Alzheimer's Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan; Local Spatio-Temporal Functions Laboratory, RIKEN Frontier Research System, Wako, Saitama, Japan |
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Abstract: | The deposition of amyloid β (Aβ) protein is a consistent pathological hallmark of Alzheimer's disease (AD) brains; therefore, inhibition of Aβ fibril formation and destabilization of pre-formed Aβ 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 Aβ1–40 and Aβ1–42 but it also destabilized pre-formed Aβ fibrils in a concentration-dependent manner. Memory function was examined using the passive-avoidance task followed by measurement of Aβ burden in the brains of Tg2576 transgenic mice. The herb improved long-term memory impairment in the transgenic mice and inhibited the accumulation of Aβ 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-β- d -glucopyranose (PGG). No obvious adverse/toxic were found following treatment with PGG. As was observed with Paeonia suffruticosa , PGG alone inhibited Aβ fibril formation and destabilized pre-formed Aβ 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 Aβ 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. |
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Keywords: | 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose Alzheimer's disease amyloid β protein medicinal herb Paeonia suffruticosa Tg2576 transgenic mice |
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