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.
| Original language | English |
|---|---|
| Pages (from-to) | 1648-1657 |
| Number of pages | 10 |
| Journal | Journal of Neurochemistry |
| Volume | 109 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2009 Jun |
| Externally published | Yes |
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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
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
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. / 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.
In: Journal of Neurochemistry, Vol. 109, No. 6, 06.2009, p. 1648-1657.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Fujiwara, Hironori
AU - Tabuchi, Masahiro
AU - Yamaguchi, Takuji
AU - Iwasaki, Koh
AU - Furukawa, Katsutoshi
AU - Sekiguchi, Kyoji
AU - Ikarashi, Yasushi
AU - Kudo, Yukitsuka
AU - Higuchi, Makoto
AU - Saido, Takaomi C.
AU - Maeda, Sumihiro
AU - Takashima, Akihiko
AU - Hara, Masahiko
AU - Yaegashi, Nobuo
AU - Kase, Yoshio
AU - Arai, Hiroyuki
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose
KW - Alzheimer's disease
KW - Amyloid β protein
KW - Medicinal herb
KW - Paeonia suffruticosa
KW - Tg2576 transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=65949101254&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65949101254&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2009.06069.x
DO - 10.1111/j.1471-4159.2009.06069.x
M3 - Article
VL - 109
SP - 1648
EP - 1657
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -