- 著者
- 山國 徹 川畑 伊知郎
- 出版者
- 公益社団法人 日本薬理学会
- 雑誌
- 日本薬理学雑誌 (ISSN:00155691)
- 巻号頁・発行日
- vol.145, no.5, pp.229-233, 2015 (Released:2015-05-10)
- 参考文献数
- 29
- 被引用文献数
- 1 2
超高齢化社会を迎えた我が国の高齢者認知症の人口は今や約462万人に上るともいわれ,認知症の克服は喫緊の国家的課題となっている.著者らはアルツハイマー病(Alzheimer’s disease:AD)の克服のため,初期のADの分子的病態に注目してその進行を阻止する活性をもつ天然薬物の探索研究および薬理研究を進めてきた.本稿ではADにおいて臨床研究の取り組みがなされているノビレチン高含有陳皮(N陳皮)の抗認知症作用についてその薬理学的解析結果を解説し,ノビレチン単体に対する「N陳皮の優位性」に関するエビデンスを紹介する.また,認知症の周辺症状の漢方治療薬抑肝散加陳皮半夏について,N陳皮配合処方エキスの抗認知症作用の特徴を簡潔に解説する.本総説では生薬や漢方処方の抗認知症作用に関する薬理学データに基づいてこれらの薬剤のもつ「多成分系薬剤の優位性」を考察したい.
- 著者
- 山國 徹 中島 晶 大泉 康
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.130, no.4, pp.517-520, 2010 (Released:2010-04-01)
- 参考文献数
- 11
- 被引用文献数
- 4 14
Alzheimer's disease (AD) has become a major health burden to society. However, no fundamentally therapeutic drugs for AD have been developed. Increasing evidence suggests that the elevation of β-amyloid (Aβ) peptides in the brain is central to AD pathogenesis. Recently, in the course of our survey of substances having anti-dementia activity from natural resources, we have successfully found nobiletin, a polymethoxylated flavone contained in AURANTII NOBILIS PERICARPIUM which is a component of traditional Chinese medicines. In this review, we describe the beneficial effects of nobiletin on memory impairment and Aβ pathology in a transgenic mouse model introduced human “Swedish” and “London” mutant amyloid precursor protein. We also note the possible molecular mechanism underlying the protective action against Aβ-induced memory impairment provided by our studies using cultured hippocampal neurons. Namely, daily administration of nobiletin for four months rescued the memory impairment in fear conditioning, and decreased hippocampal Aβ deposit in the transgenic mice as analyzed by immunohistochemistry. PKA-dependent signaling and membrane trafficking of AMPA receptor subunit, GluR1, which are known to be required for long-term potentiation (LTP), have been demonstrated to be inhibited by a sublethal concentration of Aβ in cultured hippocampal neurons. Our in vitro studies evidently showed that a sublethal concentration of Aβ actually inhibited glutamate-induced increases in both PKA substrates phosphorylation and GluR1 membrane trafficking in cultured hippocampal neurons, whereas nobiletin reversed the Aβ-induced inhibition of such biochemical processes. The natural compound with these unique actions has thus potential to become a novel drug for fundamental treatment of AD.