Metabolism-dependent inhibition of CYP3A4 and CYP2D6 by extracts from 26 herbal medicines
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概要
- 論文の詳細を見る
26種の生薬のシトクロムP450 3A4(CYP3A4)及び2D6(CYP2D6)に対する阻害作用を調べた。生薬エキス粉末から調製されたメタノール可溶性画分をNADPH生成系存在下, ヒト肝ミクロソームとプレインキュベーションした後のCYP3A4の残存活性(erythromycin N-demethylation活性)とCYP2D6の残存活性(dextromethorphan O-demethylation活性)を測定した。その結果, 16種の生薬がCYP3A4活性をプレインキュベーション時間依存的に低下させた。中でも, 呉茱萸によるCYP3A4活性の低下作用が最も顕著であった(30分間プレインキュベーションした後の活性の残存率は22.3%)。次いで, 蘇木, 羌活, 五味子, 牛蒡子, 白止, 大黄が顕著な低下を示した(30分間プレインキュベーションした後の活性の残存率は, それぞれ40.6, 41.2, 53.4, 47.1, 53.4, 59.2%)。これら7種生薬によるCYP3A4活性低下作用は, CYP3A4に対する不可逆的阻害剤であるtroleandomycinによる残存率(49.4%)に匹敵した。CYP2D6活性に対してプレインキュベーション時間依存的な活性の低下を示した生薬は, 5種であった。最もCYP2D6活性の低下作用が大きかった生薬は, 羌活であり, 30分間プレインキュベーションした後の活性の残存率は61.9%であった。以上の結果から, 呉茱萸, 蘇木, 羌活, 五味子, 牛蒡子, 白止, 大黄等の複数の生薬エキス中に, CYP3A4に対するmetabolism-dependent inhibitorが含まれていることが示唆された。
- 和漢医薬学会の論文
- 2004-12-20
著者
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KADOTA Shigetoshi
Institute of Natural Medicine, University of Toyama
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手塚 康弘
富山医科薬科大学和漢薬研究所
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Kadota S
富山大学和漢医薬学総合研究所
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手塚 康弘
富山大学和漢医薬学総合研究所化学応用分野
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IWATA Hiroshi
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University
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HIRATSUKA Akira
The School of Pharmacy, Tokyo University of Pharmacy and Life Science
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WATABE Tadashi
Department of Molecular Toxicology, Nihon Pharmaceutical University
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Kadota Shigetoshi
富山大学和漢医薬学総合研究所 化学応用分野
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Kadota S
Institute Of Natural Medicine University Of Toyama
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Kadota Shigetoshi
インドネシア
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Hiratsuka Akira
東京大学 薬学系研究科医薬品情報学
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Hiratsuka Akira
Department Of Drug Metabolism And Molecular Toxicology Tokyo University Of Pharmacy And Life Science
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Watabe Tadashi
Department Of Drug Metabolism And Molecular Toxicology Tokyo University Of Pharmacy And Life Science
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Watabe T
Institute Of Natural Medicine Toyama Medical And Pharmaceutical University
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門田 重利
Institute Of Natural Medicine University Of Toyama
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Hiratsuka Akira
The School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Kadota Shigetoshi
Institute Of Natural Medicine Toyama Medical And Pharmaceutical University
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Kalauni S
Institute Of Natural Medicine University Of Toyama
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Kadota S
Toyama Medical And Pharamaceutical Univ. Toyama Jpn
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Iwata Hiroshi
Department Of Oral And Maxillofacial Radiology The Nippon Dental University School Of Life Dentistry
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Watabe Tadashi
Department Of Drug Metabolism And Molecular Toxicology School Of Pharmacy Tokyo University Of Pharma
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手塚 康弘
Institute Of Natural Medicine University Of Toyama
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